Science, Faculty of
Chemistry, Department of
DSpace
UBCV
Carta, Veronica
Doctor of Philosophy - PhD
University of British Columbia
Two main projects are presented in this thesis. In the first project we used ligand exchange to influence the reactivity of an unstrained palladium-containing metallomacrocycle toward ring-opening metathesis polymerization (ROMP) reaction. The ligand-exchange rate on the palladium center between acetonitrile and six different ligands was investigated for an NNN pincer bis(amido)pyridine metallomacrocycle and compared with its corresponding open form. Kinetic studies showed that the small size of the macrocycle cavity impedes ligand exchange. We then used a bulky ligand (2,6-lutidine) to provide steric hindrance, blocking ring-closing and favouring ROMP of the NNN pincer bis(amido)pyridine metallomacrocycle. The second project involves the synthesis and characterization of several Pt²âº, Pt³âº, and Ptâ´âº phenylpyridine complexes. We first used a bidentate functionalized phenylpyridine ligand, then two flexible tetradentate ligands featuring an ethylene glycol chain, and finally two preorganized tetradentate ligands, one of which contained a full crown ether functionality. The presence of the crown ether functionality makes these compounds attractive for host-guest chemistry applications. The synthetic challenges related to obtaining biscyclometalated platinum monomeric complexes with phenylpyridine-containing ligands were addressed by using different approaches: high dilution, cation coordination, and ligand preorganization. Some of the complexes prepared appear to be promising for cation recognition and for the formation of supramolecular assemblies such as rotaxanes and pseudorotaxanes.
SUPRAMOLECULAR CHEMISTRY OF PALLADIUM AND PLATINUM-CONTAINING MACROCYCLES: FROM RING-EXPANSION TO HOST-GUEST COMPLEXES by Veronica Carta MSc., Sapienza Università di Roma, 2012 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (CHEMISTRY) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) October 2018 © Veronica Carta, 2018 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the dissertation entitled: Supramolecular chemistry of palladium and platinum-containing macrocycles: from ring-expansion to host-guest complexes submitted by Veronica Carta in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Chemistry Examining Committee: Mark MacLachlan Supervisor Michael Fryzuk Supervisory Committee Member Supervisory Committee Member Jennifer Love University Examiner Alexander Wang University Examiner Additional Supervisory Committee Members: Russ Algar Supervisory Committee Member Parisa Mehrkhodavandi Supervisory Committee Member !iii Abstract Two main projects are presented in this thesis. In the first project we used ligand exchange to influence the reactivity of an unstrained palladium-containing metallomacrocycle toward ring-opening metathesis polymerization (ROMP) reaction. The ligand-exchange rate on the palladium center between acetonitrile and six different ligands was investigated for an NNN pincer bis(amido)pyridine metallomacrocycle and compared with its corresponding open form. Kinetic studies showed that the small size of the macrocycle cavity impedes ligand exchange. We then used a bulky ligand (2,6-lutidine) to provide steric hindrance, blocking ring-closing and favouring ROMP of the NNN pincer bis(amido)pyridine metallomacrocycle. The second project involves the synthesis and characterization of several Pt2+, Pt3+, and Pt4+ phenylpyridine complexes. We first used a bidentate functionalized phenylpyridine ligand, then two flexible tetradentate ligands featuring an ethylene glycol chain, and finally two preorganized tetradentate ligands, one of which contained a full crown ether functionality. The presence of the crown ether functionality makes these compounds attractive for host-guest chemistry applications. The synthetic challenges related to obtaining biscyclometalated platinum monomeric complexes with phenylpyridine-containing ligands were addressed by using different approaches: high dilution, cation coordination, and ligand preorganization. Some of the complexes prepared appear to be promising for cation recognition and for the formation of supramolecular assemblies such as rotaxanes and pseudorotaxanes. iv Lay Summary Macrocycles are large molecular rings that can often host molecules, atoms, or ions inside their cavity. Two main types of metal-containing macrocycles are discussed in this thesis. In the first type of macrocycle a palladium atom is coordinated inside the cavity. The reactivity of this macrocycle depends on the interaction between the palladium atom and other large molecules inside the cavity. Depending on the interacting molecule, the cyclic structure can be opened and ring-expanded. In the second type of macrocycle a platinum atom is part of the cyclic structure and the cavity generated is able to host ions or molecules. In this thesis, we present the preparation of several platinum-containing macrocycles and their change in properties when a molecule is hosted inside their cavity. v Preface All the work presented in this thesis was carried out under the supervision of Prof. Mark J. MacLachlan. Chapter 2 involved the collaboration with Dr. S. Hessam M. Mehr, who performed calculations. The DLS and 1H DOSY NMR experiments presented in Chapter 3 were carried out in collaboration with Dr. Miguel A. Soto. Some of the synthesis and characterization presented in Chapter 4 were performed by Dr. Miguel A. Soto, Nathanya Platt, Ryan Andrews, Maria Cano, and Ingrid Suzana. Chapter 2: A version of this chapter has been previously published as: Veronica Carta, S. Hessam M. Mehr, Mark J. MacLachlan, âControlling ligand exchange through macrocyclizationâ Inorg. Chem., 2018, 57, 3243-3253. Dr. S. Hessam M. Mehr performed all the calculations. I performed all other experiments reported in Chapter 2. Chapter 3: Portions of this chapter will be submitted for publication: Veronica Carta, Miguel A. Soto, Francesco Lelj, Mark J. MacLachlan, âLigand-modulated ring-expansionâ, 2018. The DLS experiments and the 1H DOSY NMR spectra were collected in collaboration with Dr. Miguel A. Soto. All the calculations were carried out by Prof. Francesco Lelj. I performed all other experiments reported in Chapter 3. Chapter 4: Compounds Pt(7-Ac)2Cl, Pt(7-Ac)(dmso) and Pt(7)(dmso) were synthesized and characterized by Nathanya Platt. Compounds Pt-9-Cl, Pt(III)-16-Cl, Pt(IV)-16-Cl2, and Pt(II)-19 were synthesized by Dr. Miguel A. Soto. Compounds 19 and Pt(II)-16 were synthesized by Ryan J. Andrews. Compound Pt(IV)-19-Cl2 were synthesized by Maria Cano. Purification and NMR spectroscopic characterization of compound Pt(IV)-11-Cl2 were performed by Ingrid vi Suzana. I performed all other experiments reported in Chapter 4. vii Table of Contents Abstract .................................................................................................................................... iii!Lay Summary ........................................................................................................................... iv!Preface ....................................................................................................................................... v!Table of Contents .................................................................................................................... vii!List of Tables ............................................................................................................................ xi!List of Figures ......................................................................................................................... xii!List of Schemes ........................................................................................................................ xx!List of Symbols and Abbreviations ...................................................................................... xxii!Acknowledgements .............................................................................................................. xxvi!Dedication .......................................................................................................................... xxviii!Chapter 1:! Introduction ....................................................................................................... 1!1.1.! Coordination chemistry ............................................................................................... 1!1.2.! Supramolecular chemistry ........................................................................................... 2!1.2.1! Key supramolecular interactions .......................................................................... 2!1.2.1.1! Van der Waals forces ....................................................................................... 2!1.2.1.2! Hydrogen bonding ........................................................................................... 3!1.2.1.3! Metal coordination ........................................................................................... 3!1.3.! Metals in supramolecular chemistry ............................................................................. 4!1.4.! Macrocycles ................................................................................................................ 7!1.4.1! Shape-persistent macrocycles............................................................................... 8!1.4.2! Metal-containing macrocycles ........................................................................... 10!viii 1.4.2.1! Head-to-tail metallomacrocycles .................................................................... 11!1.4.2.2! Metals coordinated inside the macrocycle ...................................................... 15!(a)! Crown ethers, cryptands and spherands .......................................................... 15!(b)! Porphyrins and calixarenes ............................................................................. 16!1.5.! Pincer ligands ............................................................................................................ 18!1.6.! Metal-containing polymers ........................................................................................ 24!1.6.1! Ring-opening metathesis polymerization............................................................ 28!1.7.! Goals and scope ......................................................................................................... 32!Chapter 2:! Controlling the ligand exchange through macrocyclization........................... 36!2.1.! Introduction ............................................................................................................... 36!2.2.! Results and discussion ............................................................................................... 37!2.2.1! Metallomacrocycle 3: synthesis and behavior in solution ................................... 37!2.2.2! Model compound for ligand exchange ............................................................... 42!2.2.3! Ligand exchange studies: triphenylphosphine, pyridine, DMAP ......................... 44!2.2.4! Ligand exchange studies: quinoline, acridine and 2,6-lutidine ............................ 50!2.2.5! Binding constants determination ........................................................................ 55!2.3.! Conclusions ............................................................................................................... 56!2.4.! Experimental section ................................................................................................. 57!Chapter 3:! Ligand exchange driven ROMP ...................................................................... 72!3.1.! Introduction ............................................................................................................... 72!3.2.! Results and discussion ............................................................................................... 74!3.2.1! Control experiments on compounds 2 and 3 ....................................................... 76!3.2.2! Experiment on compound 3-PPh3....................................................................... 80!ix 3.2.3! Experiment on compound 3-lut .......................................................................... 87!3.2.3.1! Characterization of compound 3-lut-prec ....................................................... 91!3.2.3.2! Characterization of compound 6 ..................................................................... 94!3.3.! Conclusions ............................................................................................................... 97!3.4.! Experimental section ................................................................................................. 98!Chapter 4:! Pt complexes with crown ether functionality ................................................ 104!4.1.! Introduction ............................................................................................................. 104!4.2.! Results and discussion ............................................................................................. 107!4.2.1! Initial strategy for the synthesis of cis-Pt(II)-9 ................................................. 107!4.2.2! Flexible ligand ................................................................................................. 110!4.2.2.1! Host-guest properties of Pt(II)-9-Cl, Pt(II)-11-Cl, Pt(IV)-9-Cl2 and Pt(IV)-11-Cl2............................................................................................................... 119!4.2.3! Synthesis of a preorganized tetradentate ligand ................................................ 126!4.3.! Conclusions ............................................................................................................. 137!4.4.! Experimental section ............................................................................................... 138!Chapter 5:! Conclusion and future directions .................................................................. 160!5.1.! Conclusions ............................................................................................................. 160!5.2.! Reflection ................................................................................................................ 163!5.3.! Future directions ...................................................................................................... 164!Bibliography .......................................................................................................................... 167!Appendices ............................................................................................................................ 184!Appendix A: 1H NMR spectroscopy data (1D and 2D) for Chapter 2. ................................. 184!Appendix B: 1H NMR and 13C NMR spectroscopy data (1D and 2D) for Chapter 3. ........... 195!x Appendix C: Supplementary information for Chapter 4. ...................................................... 199! xi List of Tables Table 2.1 Free energies of activation for ligand rotation, ÎGâ¡rot, in kJ/mol and kcal/mol, for 3-pyr and 3-DMAP, obtained from ab initio techniques and from VT NMR dataa, using either the Eyring equation or the coalescence temperature. ....................................................................... 49!Table 2.2 Equilibrium constants ................................................................................................ 55!Table 2.3. Summary of crystallographic data for compound 5, 5-pyr, 5-PPh3, 5-quin, 5-acr and 5-lut. ......................................................................................................................................... 68!Table 2.4. Summary of crystallographic data for compound 2, 3, 3*, 3-quin and 3-acr. ............. 70!Table 3.1 Summary of geometry optimization calculations results by DFT (wB97xd) in DCM. 86!Table 3.2 Summary of crystallographic data for compounds 3-lut, 3-PPh3, 3-PPh3-trans and 6. ............................................................................................................................................... 101!Table 3.3 Summary of the energy minima obtained by geometry optimization calculations. .... 103!Table 4.1 Summary of crystallographic data for compounds Pt(7-Ac)2Cl and Pt(7-Ac)(dmso)Cl. ............................................................................................................................................... 155!Table 4.2 Summary of crystallographic data for compounds Pt(II)-9-Cl, Pt(II)-11-Cl and Pt(IV)-11-Cl2. ......................................................................................................................... 156!Table 4.3 Summary of crystallographic data for compounds Pt(II)-16, Pt(III)-16 and Pt(IV)-16. ............................................................................................................................................... 157!Table 4.4 Summary of crystallographic data for compounds 9 and 19. .................................... 158!Table 4.5 Summary of crystallographic data for compounds Pt(II)-19 and Pt(IV)-19-Cl2. ....... 159! xii List of Figures Figure 1.1 (a) Three hydrogen bonds between the base pair guanine - cytosine in DNA; (b) A molecule of caffeine. The nitrogen and oxygen atoms responsible for hydrogen bonding are represented in blue and red. ......................................................................................................... 3!Figure 1.2 Schematic representation of: (a) catenane and (b) trefoil knot. .................................... 5!Figure 1.3 Template-directed synthesis of a catenane (a) and a trefoil knot (b). Metals are represented by the red circles. ..................................................................................................... 6!Figure 1.4 A representation of MOF-5. The yellow sphere represents the porous cavity inside the MOF. Zinc atoms are located at the corner of the cube. Reproduced with permission from Yaghi et al.32 Copyright 2007 American Chemical Society.................................................................... 7!Figure 1.5 α, β and γ cyclodextrins composed of 6, 7 or 8 glucose monomers, respectively. ........ 8!Figure 1.6 Arylene ethynylene shape persistent macrocycle synthesized by Moore et al.49 .......... 9!Figure 1.7 Structure of: (a) a Schiff-base macrocycle;51 (b) a campestarene molecule.55 ............ 10!Figure 1.8 Platinum head-to-tail macrocycles: (a) Pt4 macrocycle made by Wang;56 (b) Pt4 and (c) Pt3 macrocycles developed by MacLachlan and coworkers.57,58 ........................................... 12!Figure 1.9 Chemical structure of a (a) tetrameric and (b) hexameric head-to-tail palladium-macrocycles and single crystal X-ray structures for (c) the tetramer and (d) the hexamer. 59,60 ... 13!Figure 1.10 Head-to-tail copper macrocycles: (a) tetramer and (b) hexamer.61........................... 14!Figure 1.11 Head-to-tail manganese macrocycle.62 .................................................................... 14!Figure 1.12 Structures of: (a) 15-crown-5; (b) cryptand [2.2.2]; (c) spherands. .......................... 16!Figure 1.13 (a) Structure of porphyrin; (b) 12-porphyrin figure of eight complex. Reproduced and adapted with permission from74. Copyright 2014 John Wiley and Sons. ............................. 17!xiii Figure 1.14 Structures of: (a) calix[4]arene in a âconeâ conformation; (b) calix[4]arene with bulky substituents coordinated to sodium. ................................................................................. 18!Figure 1.15 Schematic representation of a pincer ligand. ........................................................... 19!Figure 1.16 Bis(amido)pyridine complex. ................................................................................. 19!Figure 1.17 Molecular walker designed by Leigh et al. Reproduced and adapted with permission from Leigh et al.87 Copyright 2014 American Chemical Society. .............................................. 23!Figure 1.18 Schematic representation of Type I and Type II polymers. ..................................... 25!Figure 1.19 Structure of (a) poly(vinyl ferrocene) and (b) polyferrocenylene, and (c) polyferrocenylsilane.98â100 ......................................................................................................... 26!Figure 1.20 Structure of ruthenium containing polymers: (a) Type I; (b) Type II.103,104 ............. 27!Figure 1.21 Mixed-metal polymers: (a) zinc and platinum; (b) iridium and platinum.105,106 ....... 27!Figure 1.22 Structure of Pt-[NCN] pincer metallopolymer developed by the Holliday group.108 28!Figure 1.23 (a) Ring-opening metathesis polymerization intermediate and mechanism; (b) structures of 1st, 2nd and 3rd generation Grubbs catalysts; (c) structures of Hoveyda Grubbs and Schrock catalysts. ..................................................................................................................... 30!Figure 1.24 Schematic representation of the approach used to polymerize an unstrained metal-containing macrocycle (represented in blue) using ligand coordination (ligand is represented in pink). ........................................................................................................................................ 32!Figure 1.25 Structures of: (a) macrocycle 3; (b) model compound 5 and (c) ligands that were exchanged with acetonitrile. ...................................................................................................... 34!Figure 1.26 Structures of some the targeted Pt2+ complexes with crown ether functionality. (a) Flexible ligand with communication between Pt and the crown ether cavity; (b) pre-organized ligand. ....................................................................................................................................... 35!xiv Figure 1.27 Structure of the platinum complexes synthesized: (a) Pt2+; (b) Pt3+ and (c) Pt4+....... 35!Figure 2.1 (a) NNN pincer metallomacrocycle of Pd2+. An acetonitrile molecule occupies the fourth palladium coordination site. (b) NNN pincer complex of Pd2+. This complex represents the open form of the metallomacrocycle. ................................................................................... 37!Figure 2.2 Solid-state structure of compound 2 as determined by SCXRD. (a) front view, (b) side view. ......................................................................................................................................... 39!Figure 2.3 Solid-state structure of compound 3 as determined by SCXRD. (a) front view, (b) side view, (c) top view. .................................................................................................................... 40!Figure 2.4 (a) Solid-state molecular structure of compound 3* as determined by SCXRD. Compound 3* is a macrocycle of macrocycles, where each monomer is bridged by a carbonyl group to the next palladium atom, forming a cyclic tetramer. (b) Spacefilling model (based on van der Waals radii) for compound 3*. The colour of the atoms indicates the atomic displacement parameters: blue if they are small, red if they are high. ........................................ 42!Figure 2.5 Solid-state molecular structure of compound 5 as determined by SCXRD. (a) Front view and (b) side view. ............................................................................................................. 44!Figure 2.6 Compounds used to investigate the ligand exchange: pyridine, triphenylphosphine, 4-dimethylaminopyridine (DMAP), quinoline, acridine, 2,6-lutidine. ........................................ 45!Figure 2.7 Solid-state molecular structures of (a) compound 5-pyr and (b,c) compound 5-PPh3 as determined by SCXRD. ............................................................................................................ 45!Figure 2.8 (a) Structure of DMAP, indicating the protons on the pyridyl ring. (b) High-temperature 1H NMR studies for compound 3-DMAP. (c) High-temperature 1H NMR studies for compound 3-pyr. C2D2Cl4 is represented with the symbol *. The peaks corresponding to the ortho and meta positions become sharper as the temperature increases, generating two xv distinct signals. The signals in blue correspond to the ortho protons, whereas the red peaks are generated by the protons in meta position. ................................................................................. 47!Figure 2.9 (a) Structure of pyridine, indicating the protons on the pyridyl ring. (b) Low-temperature 1H NMR studies for compound 3-DMAP. (c) Low-temperature 1H NMR studies for compound 3-pyr. CD2Cl2 is represented with the symbol *. The peaks corresponding to the ortho and meta positions become sharper as the temperature decreases, generating four distinct signals. The signals in orange correspond to the hydrogen atoms pointing inside of the cavity, which are significantly shielded by the macrocycleâs phenyl groups, whereas the green peaks are the hydrogen pointing away from the cavity. ............................................................. 48!Figure 2.10 Solid-state structure of compound 3-quin as determined by SCXRD. (a) Front view, (b) side view, and (c) top view. ................................................................................................. 50!Figure 2.11 Ligand exchange kinetic study on compound 5, performed with acridine (blue circles) and 2,6-lutidine (orange triangles). 1/X corresponds to the inverse of the concentration of compound 5. The initial concentration of both 5 and the additional ligand were 0.013 M. ......... 51!Figure 2.12 Solid-state molecular structure of (a) 5-quin, (b) 5-acr, and (c) 5-lut as determined by SCXRD. ................................................................................................................................... 52!Figure 2.13 Ligand exchange kinetic study on compound 3, performed with: (a) quinoline (red diamonds); (b) acridine (blue circles); and (c) 2,6-lutidine (orange triangles). (d) comparison between the exchange with 2,6-lutidine and acridine. 1/X corresponds to the inverse of the concentration of compound 3. The concentration of the solutions is 0.013 M and the ratio between compound 3 and the additional ligand is 1:1. ............................................................... 53!Figure 2.14 Solid-state structure of compound 3-acr as determined by SCXRD. (a) Front view, (b) side view, and (c) top view. ................................................................................................. 54!xvi Figure 2.15 Dimers formed by 3-acr due to stacking between two acridineâs phenyl rings. The distance between two phenyl rings is 3.6 Ã . .............................................................................. 54!Figure 3.1 Schematic representation of the approach used to polymerize an unstrained metal-containing macrocycle (represented in blue) using ligand coordination (ligand is represented in pink)................................................................................................................... 73!Figure 3.2 (a) Palladium-containing macrocycles used for ring-expansion and polymerization reactions. (b) Second generation Grubbs catalyst....................................................................... 75!Figure 3.3 Stacked 1H NMR (400 MHz, CDCl3) spectra of: (a) pure compound 2; (b) polymerization reaction crude product. The peaks marked in blue correspond to the trans isomer of compound 2. Residual solvents peaks are indicated with *. ................................................... 77!Figure 3.4 1H DOSY NMR (400 MHz, CDCl3) experiment on compound 2. ............................. 78!Figure 3.5 1H NMR (400 MHz, CDCl3) spectra of: (a) pure compound 3; (b) precipitate obtained from the polymerization reaction; (c) crude filtrate. The spectrum of the precipitate completely overlaps with the starting material 3. The crude filtrate is mostly compound 3, but some other side product (blue circles) is present. Residual solvents peaks are indicated with *. ................... 79!Figure 3.6 1H DOSY NMR (400 MHz, CDCl3) experiment on compound 3. ............................. 80!Figure 3.7 1H NMR (400 MHz, CD2Cl2) of compounds: (a) 3-PPh3; (b) crude reaction mixture. Residual solvent peaks are indicated with *. .............................................................................. 81!Figure 3.8 Polymerization reaction on 3-PPh3 monitored by 1H NMR spectroscopy (400 MHz, THF-d8, 50 °C). Residual solvent peaks are indicated with *. .................................................... 82!Figure 3.9 SCXRD structure of compound 3-PPh3-trans: (a) side view; (b) front view (PPh3 in white to show the trans stereochemistry of the alkene). ............................................................. 83!xvii Figure 3.10 SCXRD structure of compound 3-PPh3 (a) side view; (b) front view (PPh3 in white to show the cis stereochemistry of the alkene). .......................................................................... 84!Figure 3.11 Initial geometries (bottom view) used for the geometry optimization calculations performed on 3-PPh3 and 3-PPh3-trans. Analogous geometries were used for compounds 3 and 3-trans. (a) 3-PPh3 cis geometry obtained from the crystal structure of 3-PPh3. (b) 3-PPh3 cis2 geometry obtained from the crystal structure of compound 3, substituting the acetonitrile ligand with PPh3. (c) 3-PPh3-trans geometry obtained from the crystal structure of compound 3-PPh3-trans. ............................................................................................................................. 85!Figure 3.12 Polymerization reaction on 3-lut monitored by 1H NMR (400 MHz, THF-d8, 50 °C) in the spectral region from 4.30 to 6.50 ppm. ............................................................................ 88!Figure 3.13 1H NMR (400 MHz, CDCl3) of compounds: (a) 3-lut; (b) 3-lut-prec; (c) 6. Residual solvent peaks are indicated with *. ............................................................................................ 89!Figure 3.14 Reaction monitored by DLS. Hydrodynamic radius (RH) distribution measured at selected reaction times: (a) t = 0 min (one peak with RH = 128 nm); (b) t = 1 h 55 min (two peaks with RH = 134 and 413 nm); (c) t = 2 h 8 min (two peaks with RH = 126 and 620 nm); (d) t= 2 h 15 min (two peaks with RH = 127 and 848 nm).......................................................................... 91!Figure 3.15 1H DOSY NMR (400 MHz, CDCl3) experiment on the polymerization crude reaction mixture performed on compound 3-lut. The presence of at least two different species can be noted. The red line corresponds to 6 and the blue line to 3-lut-prec. Some regions of the spectrum (black box in the full 2D spectrum) are magnified and reported in the top image to show more clearly the difference between the two species. ....................................................... 93!Figure 3.16 1H DOSY NMR (400 MHz, CDCl3,) of compounds (a) 3-lut and (b) 6. Residual solvent peaks are indicated with *. ............................................................................................ 95!xviii Figure 3.17 SCXRD structure of: (a) compound 3-lut; (b) compound 6. .................................... 97!Figure 4.1 Examples reported in literature of platinum(II) complexes that contain crown ether functionality reported by (a) Ji et al.192 and (b) Yam et al.193 ................................................... 106!Figure 4.2 Two target complexes discussed in this chapter: (a) cis-Pt(II)-9 and (b) Pt(II)-19. .. 107!Figure 4.3 Reaction plan for the synthesis of cis-Pt(II)-9. ........................................................ 107!Figure 4.4 SCXRD structures for the compounds (a) Pt(7-Ac)2Cl and (b) Pt(7-Ac)(dmso)Cl... 110!Figure 4.5 Two of the possible products with different stereochemistry that could be obtained from the reaction of 9 with Pt2+. .............................................................................................. 112!Figure 4.6 Portions of the 1H NMR (400 MHz, CDCl3) spectra of the crude product from the reaction between compound 9 and K2PtCl4 in AcOH at different concentrations: (a) 16 mM and (b) 4 mM. The broad peaks corresponding to the oligomers are indicated in red, and the sharp peaks corresponding to Pt(II)-9-Cl are indicated in blue. Full spectra shown in Figure C-15. .. 112!Figure 4.7 Reaction scheme and 1H NMR spectrum (400 MHz, CDCl3) of compound Pt(II)-9-Cl. Residual solvent peak is indicated with *. ............................................................................... 114!Figure 4.8 SCXRD structures of compounds (a) Pt(II)-9-Cl and (b) Pt(II)-11-Cl. .................... 115!Figure 4.9 Reaction scheme and 1H NMR (400 MHz, CDCl3) of compound Pt(IV)-9-Cl2. Residual solvent peak is indicated with *. ............................................................................... 117!Figure 4.10 SCXRD structure of compound Pt(IV)-11-Cl2, with a CH3CN molecule coordinating inside the cavity. ..................................................................................................................... 118!Figure 4.11 Schematic representation of cation templation on ligands 9 and 11 with (a) Na+, K+, and (b) Cs+. ............................................................................................................................. 119!Figure 4.12 Stacked 1H NMR (400 MHz, CD2Cl2) spectra of Pt(II)-9-Cl, Pt(II)-9-Cl + 1eq KBF4 and Pt(II)-9-Cl + 1eq NaBF4. Residual solvent peak is indicated with *. ................................. 120!xix Figure 4.13 UV-Vis spectra of compounds Pt(II)-9-Cl (CH3CN, 25 µM) and compound Pt(II)-9-Cl (CH3CN, 250 µM) after the addition of NaBF4 or KBF4 (5 and 20 equiv). ............. 121!Figure 4.14 Molecular structure of (a) dibenzylammonium hexafluorophosphate, (b) N,Nâ-dimethyl-4,4â-bipyridinium hexafluorophosphate, and (c) 1,2-bis(4,4â-bipyridinium)ethane hexafluorophosphate. .............................................................................................................. 122!Figure 4.15 Portion of 1H NMR (400 MHz, 1:1 CDCl3/CD3CN) spectra of (a) Pt(IV)-11-Cl2 and (b) Pt(IV)-11-Cl2 + dibenzylammonium hexafluorophosphate. Full spectra reported in Figure C-20. .......................................................................................................................................... 124!Figure 4.16 Stacked 1H NMR (400 MHz, DMSO-d6) spectra of (a) compound 16, (b) Pt(II)-16 and (c) Pt(IV)-16-Cl2. ............................................................................................................. 129!Figure 4.17 SCXRD structures for compounds (a) Pt(II)-16, (b) Pt(III)-16-Cl and (c) Pt(IV)-16-Cl2. ......................................................................................................................... 130!Figure 4.18 (a) UV-Vis spectrum in DCM 35 µM (b) Emission spectrum in DCM (4 µM, λexc: 370 nm). ................................................................................................................................. 131!Figure 4.19 SCXRD structures for compounds (a) 9, and (b) 19. ............................................. 133!Figure 4.20 Stacked 1H NMR (400 MHz, CD2Cl2) spectra of (a) compound 19, (b) Pt(II)-19, and (c) Pt(IV)-19-Cl2. Residual solvent peaks are indicated with *. ............................................... 135!Figure 4.21 SCXRD structures of compound Pt(IV)-19-Cl2 (a) top view, and (b) side view. ... 136!Figure 4.22 SCXRD structures of compound Pt(II)-19 (a) top view, and (b) side view. ........... 137!Figure 5.1 Structures of: (a) macrocycle 3; (b) model compound 5 and (c) ligands that were exchanged with acetonitrile. .................................................................................................... 162!Figure 5.2 Biscyclometalated platinum complex with full 21-crown-7 ether functionality. ...... 166! xx List of Schemes Scheme 1.1 Palladium-templated synthesis of a rotaxane.85 ....................................................... 20!Scheme 1.2 Synthetic scheme for the [3+3] and [2+2] macrocycles reported by Nitschke et al.84 ................................................................................................................................................. 21!Scheme 1.3 Operation of a palladium-complexed molecular shuttle.88 ....................................... 22!Scheme 1.4 Reaction scheme for the polymerization of vinyl ferrocene as reported by Arimoto et Al.98 .......................................................................................................................................... 24!Scheme 1.5 ROMP reaction to form poly(ferrocenylenedivinylene).113 ..................................... 31!Scheme 1.6 Reaction scheme for ROMP reaction on compound 3, in the presence of a bulky ligand L. ................................................................................................................................... 33!Scheme 2.1 Synthesis of metallomacrocycle 3. ......................................................................... 39!Scheme 2.2 Synthesis of open complex 5. ................................................................................. 43!Scheme 3.1 Reaction scheme for the polymerization reactions (L = generic bulky ligand). ....... 76!Scheme 3.2 Reaction scheme for the ring-opening on compound 3-lut that lead to the formation of compound 6. ......................................................................................................................... 96!Scheme 4.1 Reaction scheme for the synthesis of 7-Ac and the three products obtained by cyclometalation reaction with Pt2+: Pt(7-Ac)2Cl, Pt(7-Ac)(dmso)Cl, and Pt(7)dmsoCl. ........... 109!Scheme 4.2 (a) Reaction scheme for the synthesis of compound 8 and 9. (b) Structures of compounds 10 and 11. ............................................................................................................ 111!Scheme 4.3 Reaction scheme for the synthesis of compound 16. ............................................. 127!Scheme 4.4 Reaction scheme for the cyclometalation reaction of compound 16 with Pt2+. ...... 128!Scheme 4.5 Reaction scheme for the synthesis of compound 19. ............................................. 132!Scheme 4.6 Reaction scheme for the synthesis of compounds Pt(II)-19, and Pt(IV)-19-Cl2. .... 134!xxi Scheme 5.1 Proposed scheme to make a new macrocycle that would generate more soluble polymers. ................................................................................................................................ 165! xxii List of Symbols and Abbreviations δ chemical shift Î gradient λ wavelength Ï-Ï* ligand-based transition Ã Ã ngstrom AcOH acetic acid CD cyclodextrin CDCl3 deuterated chloroform CD2Cl2 deuterated dichloromethane COSY correlation spectroscopy CV cyclic voltammetry d day D diffusion coefficient d-d metal-based transition DCM dichloromethane DFT density functional theory DLS dynamic light scattering DMAP dimethylaminopyridine DMF dimethylformamide DMSO dimethylsulfoxide DMSO-d6 deuterated dimethylsulfoxide xxiii DNA deoxyribonucleic acid DOSY diffusion ordered spectroscopy ECP energy consistent pseudopotential ED-ROMP entropically-driven ring opening metathesis polymerization en ethylenediamine equiv equivalent(s) ESI-MS electrospray ionization mass spectroscopy Et3N triethylamine F structure factor GPC gel permeation chromatography h hours HOMO highest occupied molecular orbital HRESI-MS high resolution electrospray ionization mass spectrometry HSQC heteronuclear single-quantum correlation spectroscopy IR infrared IUPAC international union of pure and applied chemistry LC ligand-centered LMCT ligand-to-metal charge transfer LRMS low resolution mass spectrometry LUMO lowest unoccupied molecular orbital MeOH methanol MHz megahertz xxiv min minute(s) MLCT metal-to-ligand charge transfer MLLâCT metal-ligand-to-ligand charge transfer mM millimolar mol mole MOF metal organic framework mol% mole percent MS mass spectrometry n-Bu4NBr tert-butylammonium bromide NOESY nuclear Overhauser effect spectroscopy NMR nuclear magnetic resonance nm nanometers NPA N-(2â-pyridyl)-7-azaindole OLED organic light-emitting diode p para PPh3 triphenylphosphine ppm parts per million RCM ring closing metathesis Rf retention factor ROMP ring opening metathesis polymerization RT room temperature SCXRD single crystal X-ray diffraction xxv TEM transmission electron microscopy THF tetrahydrofuran UV-Vis ultraviolet-visible VT variable temperature wt% weight percent ZPE zero-point energy xxvi Acknowledgements I am deeply thankful to Prof. Mark MacLachlan for his supervision and guidance during these years. His enthusiasm and passion for research combined with his scientific rigor and chemistry knowledge have been of great inspiration. I am very grateful for the encouragement he gave me to pursue my career goals. I am sincerely grateful to Dr. Brian Patrick and Dr. Anita Lam for the training and help they gave me in structural chemistry, for supporting and encouraging my desire to learn X-ray techniques and my long-term aspiration to become a crystallographer. I also had the pleasure to work in a friendly, kind, fun, knowledgeable and collaborative research group. I am thankful to all the MacLachlan group members, past and present, for the very pleasant time we shared, from the short coffee breaks during the week to the time spent socializing outside the lab, at conferences, at IDW, or on the mountains. I am also deeply thankful for the training I received from my senior colleagues when I joined the lab and for the practical help I kept receiving from everyone throughout my PhD. A very special thank goes to my collaborator and friend Dr. Miguel Soto, for the incredible input he gave to our research, with thoughtful discussions, new ideas and practical help. Collaborating with him has been a valuable and fun learning experience, and he represents for me an example to follow. I also want to thank Miguel for the help he gave me with DLS measurements, 1H DOSY NMR spectroscopy and for the critical contribution he gave to our platinum chemistry. I am grateful to my dear friends Dr. Nicholas White, for training me in single crystal X-ray diffraction and contributing to my research with his creative ideas, and Dr. Hessam Mehr for welcoming me when I joined the lab in 2012. During these past six years, Hessam has always been the friend I would talk to if I had questions regarding NMR techniques or theoretical chemistry. I am thankful to prof. Francesco Lelj, for the contribution he gave to our research by performing computational calculations. I also had the pleasure of supervising two brilliant undergraduate students: Nathanya Plat and Ryan Andrews. The time spent working together represented an incredibly valuable experience for me. Their passion and enthusiasm for chemistry helped me to stay motivated during difficult times of my PhD experience. I also want to thank Maria Cano and Ingrid Suzana for the contribution given to our platinum chemistry under Miguel A. Sotoâs supervision. A huge thank goes to all the people that dedicated time to proof read my thesis. In particular, I want to thank my colleague and friend Dr. Charlotte Boott, who invested a good amount of time in reading Chapters 1, 2, and 3 and gave me very thoughtful advice. I am also grateful for the feedback I received from Dr. Andrea Terpstra, Dr. Nicholas White, Dr. Miguel Soto, Lev Lewis and Chris Walters. A big thank goes to Andy Tran, for teaching me how to use the software BLENDER to make 3D graphics. I am also grateful to the readers from my supervisory committee, Prof. Michael Fryzuk and Prof. Russ Algar, for the helpful and quick feedback they gave me on my thesis. xxvii Sharing the lab space with the Wolf group has been a joy. Our two research labs shared numerous experiences, great conversations during lunchbreaks, beautiful days at the beach, barbeques, nights at the bar, and of course, the traditional MacLachlan/Wolf annual ski trip. I felt like being part of a big family. The feeling of belonging to a community helped me to stay happy and healthy even during the most demotivating moments of my PhD. I owe much gratitude to my parents for their unconditional support. It is hard to be so far from each other, especially during difficult times, but they always trusted that I will make the right choices for my future. I am thankful to my mother, Serenella Silvestrini, for teaching me discipline and will power. As an incredible working mother, she has always been a great example to follow. I am thankful to my father, Giuseppe Carta, for the quality time we spend together and for passing on to me his endless curiosity. My dearest friends Chris Brown, Janet Ochola, Guillaume Beaulieu-Houle, Andrea Terpstra, Debbie Le, Amber Shukaliak, Rosanne Persaud, Marta Moreno, Guadalupe Jaraquemada, Mathieu Lepage, Sandra Irmish, Peter Rahfeld, Mohammad Chaudhry and Francesco DâAcierno have been of incredible support, making every day inside and outside the lab better, particularly during this final year. I will always remember the fun moments we experienced together. I also want to thank my dear friend Andy Tran for the relaxing time we spent playing music together. It was the best break from thesis writing. I am also grateful to my kind roommates Katie Taylor, Amber Donelly, and Michael Salloum for all the encouragement (and also for the good food) they gave me while I was writing my thesis. Finally, I want to thank those friends that gave me support from Europe: Susan Vickers, Charlotte Koshnick, Micol Mattei, Letizia Angelini, Maria Cardellini, Alice Angeletti and Cristiana Mattei. There is no geographical distance that will ever make me feel far from any of them. xxviii Dedication To my parents 1 Chapter 1:! Introduction 1.1.! Coordination chemistry In 1798, the French chemist B.M. Tassaert discovered that dissolving cobalt(II) chloride (CoCl2) in aqueous ammonia produced a brown coloured solution, in contrast to the purple colour of an aqueous CoCl2 solution. This observation remained unexplained for about five decades, until M.E. Frémy showed in 1852 that aqueous CoCl2 oxidized in the air forming orange crystals with formula CoCl3 ! 6 NH3, now conventionally written as [Co(NH3)6]Cl3. The interesting aspect of this discovery was that two stable compounds, CoCl2 and ammonia, both with full valence shells, could combine together to form a new compound that exhibits different properties than the constituent parts.1,2 About a century after Tassaertâs initial discovery, Werner developed a theory to explain the bonding in [Co(NH3)6]Cl3. The theory defines a new type of bond, which he termed a coordination bond. Werner theorized that there are two types of valency that metals tend to satisfy: an oxidation valency and a coordination valency. The oxidation valency is defined as the charge on the metal center, whereas, the coordination valency refers to the fixed positions in space occupied by the molecules that surround the metal center (otherwise known as ligands). In the case of [Co(NH3)6]Cl3 it is the coordination valency of the cobalt that allows the CoCl2 to combine with the ammonia. In addition, Werner was able to separate two enantiomeric crystals of [Co(en)2(NH3)X]2+ (X = Cl, Br, en = ethylene diamine), demonstrating for the first time the existence of chirality in atoms other than carbon. The significance of this discovery resulted in Werner being awarded the Nobel Prize for chemistry in 1913.3 Based on the foundation of Wernerâs theory, the field of coordination chemistry has expanded to a plethora of coordination complexes both naturally- and synthetically-derived. These 2 complexes contain a wide range of ligands from simple ones such as ammonia and water, to ligands that can form multiple coordination bonds with the metal center, called chelators, such as crown ethers or cryptands. 1.2.! Supramolecular chemistry The coordination bond belongs to a wider class of interactions, called supramolecular interactions. Coined by Lehn in 1978, supramolecular chemistry was defined as the chemistry beyond the discrete molecule.4 This new and growing field of chemistry includes interactions that go beyond the covalent bond, such as hydrogen bonding, Ï-Ï stacking, coordination bonds, hydrophobic forces, electrostatic effects and van der Waals forces. Most of these interactions are weaker (0.05 â 40 kJ/mol) than a covalent bond (150 â 1100 kJ/mol)5, but when combined together can generate a stronger collective interaction that can result in the autonomous organization of simple components into complex architectures, a process termed self-assembly. These non-covalent interactions are reversible, favouring formation of the thermodynamic product. Supramolecular chemistry utilizes these intermolecular interactions to generate more complex systems. 1.2.1! Key supramolecular interactions 1.2.1.1!Van der Waals forces The van der Waals forces are one of the weakest types of intermolecular interactions. They are short-range, electrostatic interactions between uncharged molecules, arising from the presence of permanent or transient dipole moments (0.05 â 40 kJ/mol).5 Despite being a weak interaction, when many van der Waals forces are combined they can produce a strong collective result. For example, in nature, this can be observed in geckos, who rely on these types of forces between the nanostructures in their feet and a surface, allowing the gecko to run up a wall without falling.6 3 1.2.1.2!Hydrogen bonding Hydrogen bonding is a strong intermolecular interaction between a positively polarized hydrogen atom and a very electronegative atom, such as N, O and F. Hydrogen bonding is responsible for the double helix structure of DNA, where base pairs on different strands interact with each other through hydrogen bonding, causing two separate DNA strands to self-assemble into a double helix (Figure 1.1a). Hydrogen bonding also affects the solubility of molecules. For example, caffeine has six sites that can hydrogen bond with water, two oxygen and four nitrogen atoms, making the molecule water-soluble (Figure 1.1b). Figure 1.1 (a) Three hydrogen bonds between the base pair guanine - cytosine in DNA; (b) A molecule of caffeine. The nitrogen and oxygen atoms responsible for hydrogen bonding are represented in blue and red. 1.2.1.3!Metal coordination Metal coordination is ubiquitous in nature and it has been extensively utilized in chemistry. The formation of the coordination bond is reversible, allowing for structural reorganization, thus favouring the formation of thermodynamic products. It is also significantly stronger than van der Waals forces and hydrogen bonding, which results in the formation of very stable systems. 4 Coordination complexes have been used in numerous applications including remediation,7 bioimaging,8â11 radiopharmaceuticals8,12,13 and catalysis.14â16 For example, environmental remediation commonly uses chelators that can surround a metal atom in order to separate it from its surrounding. This property allows chemists to remove a pollutant, such as heavy metals, from a contaminated system, for example polluted water.7 Furthermore, coordination compounds can absorb visible light and therefore have been employed in solar cells17â21 or OLEDs.22â24 The inherent color of the complexes is due to the existence of a small difference in energy between the highest occupied molecular orbital (HOMO), which usually is located on the metal, and the lowest unoccupied molecular orbital (LUMO), which is often a ligand anti-bonding orbital. The smaller this gap, the wider the fraction of solar radiation that a material can absorb. In biological systems, zinc-based complexes are particularly common. One significant biological zinc coordination complex is a protein structural motif termed a zinc finger, which involves the interactions between zinc ions and segments of protein to stabilize protein folds.25,26 Another metal that interacts with proteins is copper. For example, plastocyanin and azurin are types of small proteins that bind to one copper atom and are prevalent in bacteria and plants.27 1.3.! Metals in supramolecular chemistry In the past thirty years the field of supramolecular chemistry has been rapidly expanding, from its first applications in host-guest chemistry and receptor systems, through its use in template-directed synthesis, to the most recent discoveries in molecular machinery. The Nobel Prize for chemistry in 2016, conferred to Fraser Stoddart, Jean-Pierre Sauvage and Ben Feringa for âthe design and synthesis of molecular machinesâ, demonstrates the recent growth and importance of this new field of chemistry.28 5 Particularly exploited in supramolecular chemistry are transition metals. The relative strength of the coordination bond compared to other types of supramolecular interactions allowed the design of various metal-containing supramolecular structures, such as metal-organic frameworks (MOFs) and coordination polymers.29â32 One of the most notable roles for metals in supramolecular chemistry is their use as templates to direct the synthesis of more complex architectures, such as catenanes and molecular knots. A catenane is defined as a molecule where two or more rings are interlocked without being chemically bound (Figure 1.2a).33,34 In chemistry, a knot is an interlocked molecule that is arranged into a closed loop.35 Knots are classified by the minimum number of crossings, which are the points where a string passes over or under another. For example, a trefoil knot is a single strand that intersects three times (Figure 1.2b). Figure 1.2 Schematic representation of: (a) catenane and (b) trefoil knot. In the catenane formation (Figure 1.3a), a transition metal (represented by the red circle) is used to bring together different strands that are successively ring closed. The central metal is then removed leaving two interlocked molecules. This approach has been used to synthesize several catenanes, from the simplest form where two rings are interlocked,36,37,38 to a star of David shaped catenane.39 Similarly, the use of metal templation has enabled the synthesis of molecular knots. a b6 The first molecular trefoil knot was prepared by Sauvage using two copper (II) ions to bring together two strands that were successively linked.40 The copper ions were then removed to form one continuous strand that crossed itself three times (Figure 1.3b). Figure 1.3 Template-directed synthesis of a catenane (a) and a trefoil knot (b). Metals are represented by the red circles. Coordination chemistry has also been employed in the formation of metal-containing polymers and MOFs. Coordination polymers are polymeric chains held together by the complexation of metal ions with polydentate ligands.29 They can extend in one, two or three dimensions, forming an alternating network of ligands and metals. In MOFs, the alternation between metals and ligands generates a porous, three-dimensional structure.30 For example, MOF-5 (Figure 1.4) is a highly porous MOF with a simple cubic topology, where 1,4-benzenedicarboxylate ligands bridge [Zn4O]6+ clusters.31 2" +"+"2"$"a" b"$"2"+"2"7 Figure 1.4 A representation of MOF-5. The yellow sphere represents the porous cavity inside the MOF. Zinc atoms are located at the corner of the cube. Reproduced with permission from Yaghi et al.32 Copyright 2007 American Chemical Society. 1.4.! Macrocycles Supramolecular chemistry often involves the synthesis and use of macrocycles. A macrocycle is a molecule that presents a large cyclic structure. The IUPAC definition of macrocycle is a âcyclic macromolecule or a macromolecular cyclic portion of a moleculeâ.41 This definition is broad and includes highly differentiated macrocycles in terms of the number of atoms that constitute them, their size, and the type of functionalities that can be present. They often contain heteroatoms or functional groups that allow them to interact with other molecules or to coordinate to metal ions. The IUPAC definition itself specifies that the term is often used for cyclic molecules of a relatively low mass that would not be considered macromolecules.41 Some macrocycles are relevant for their supramolecular interactions with organic molecules. Cyclodextrins are an important example of this class of macrocycles. They are cyclic oligosaccharides formed from the reaction of starch with the enzyme cyclodextril glycosil transferase.42 They can be classified as α, β or γ cyclodextrins based on the number of D-glucose 8 monomers that they contain (6, 7 or 8 respectively) as represented in Figure 1.5.43 Their structure is a cut-cone with a small and a big opening. The hydroxyl groups of the glucose are located at the openings, making them hydrophilic, whilst the space inside the cavity is hydrophobic. Due to its amphiphilic nature, cyclodextrin (CD) is a water-soluble macrocycle that can sequester hydrophobic molecules in its cavity, enhancing their solubility. In medicinal chemistry, CDs are studied as drug delivery systems, since they can bind biologically active compounds that can then be released under specific conditions.44 Their non-toxicity makes them suitable as additives in the food industry.45,46 Furthermore, CDs can be used for environmental applications to sequester pollutants such as trichloroethane and heavy metals.47 Figure 1.5 α, β and γ cyclodextrins composed of 6, 7 or 8 glucose monomers, respectively. 1.4.1! Shape-persistent macrocycles When a macrocycle presents a rigid structure it is classified as a shape-persistent macrocycle.48 The pre-organization of the structure improves the binding affinity and the selectivity of the macrocycle for specific guests. An important example of a shape-persistent macrocycle was effectively synthesized by Moore et al. in 2005 using an efficient one-pot 9 synthetic procedure.49 This macrocycle (Figure 1.6) contains six aryl groups bridged by rigid ethynylene linkers. Figure 1.6 Arylene ethynylene shape persistent macrocycle synthesized by Moore et al.49 The extended conjugated system present in Mooreâs compound has been inspirational for the subsequent design of more macrocycles, where the Ï electrons are used to self-assemble several of them into nanotubes, through Ï-Ï stacking.50 In addition, designing shape-persistent macrocycles with different functionalities, both in the ring and inside the cavity, allows improving their solubility and binding affinity toward specific cations. One class of shape-persistent macrocycles with an extended conjugated system are Schiff-base macrocycles. Schiff-base macrocycles are synthesized by reaction of 3,6-diformylcatechol and o-phenylenediamine. The âOH substituents on the catechol can hydrogen-bond to the imine nitrogen atoms, stabilizing the macrocyle (Figure 1.7a).51 The MacLachlan group has been studying shape-persistent Schiff-base macrocycles over the past decade, improving their solubility by adding long alkoxy chains to the rigid aromatic groups52, and changing the dimension and the shape of the cavity.53 In 2010 Guieu and coworkers reported the synthesis of a new 5-fold symmetric Schiff-base macrocycle, named RRRRRRR = CO2(-CH2CH2O)3CH310 campestarene.54 Since then we have focused on improving the solubility and the stability of campestarenes through modification of the tert-butyl terminal group and then studying their tautomerization behavior (Figure 1.7b).55 Figure 1.7 Structure of: (a) a Schiff-base macrocycle;51 (b) a campestarene molecule.55 1.4.2! Metal-containing macrocycles As previously mentioned, coordination to a metal can strongly affect the properties of a compound. For example, the optical properties of a macrocycle may dramatically change when a metal is coordinated inside the cavity, leading to compounds that can be used as chromophores in solar cells or in OLEDs. For this reason, macrocycles often present functionalities that allow for coordination of specific cations. In this thesis, metallomacrocycles are divided into two categories: head-to-tail metallomacrocycles and macrocycles coordinating to a metal inside the cavity. In the first case the metal ions are required for ring closure, and can direct the self-assembly of several ligands into a cyclic structure. In this case, removal of the metal would break the macrocycle ring. In the second 11 case, the metal sits inside the macrocyclic cavity, and can be removed without affecting the macrocycle stability. 1.4.2.1!Head-to-tail metallomacrocycles As mentioned previously, coordination chemistry with metal ions can promote the formation of a macrocyclic structure. We refer to this type of macrocycle as metal-containing head-to-tail macrocycles and several examples of them have been reported in the literature.56â62 Head-to-tail macrocycles often contain platinum since it forms inert and stable complexes. The addition of platinum can promote the formation of stacked structures, helping to self-assemble several macrocycles into nanotubes. In 2007, Wang and coworkers discovered that the chelating ligand N-(2â-pyridyl)-7-azaindole (NPA), can cyclometalate on a Pt2+ center, directing intramolecular C-H activation and forming a Pt4 head-to-tail macrocycle (Figure 1.8a).56 In 2010, the MacLachlan group reported a 4-fold Pt4 head-to-tail macrocycle that exploited Ï-stacking interactions to form tubular structures (Figure 1.8b).57 The channels formed by these 1D columnar aggregates were relatively small (diameter 2.4 nm, according to computational calculations). Attempts to increase the size of the channels by using a longer organic linker resulted in the formation of Pt3 macrocycles (Figure 1.8c), which demonstrated enhanced stacking properties compared to the corresponding Pt4 macrocycles, forming longer tubes detectable by transmission electron microscopy (TEM).58 12 Figure 1.8 Platinum head-to-tail macrocycles: (a) Pt4 macrocycle made by Wang;56 (b) Pt4 and (c) Pt3 macrocycles developed by MacLachlan and coworkers.57,58 Platinum is not the only metal that can be used to prepare head-to-tail macrocycles. Other metals such as palladium, copper and manganese have also been employed. Like platinum, Pd2+ exhibits a square-planar geometry and is able to self-assemble into macrocyclic structures. It has been reported that when Pd2+ is coordinated to bis(amido)pyridine tridentate ligands, it can induce the self-assembly of 4-fold or 6-fold symmetric macrocycles, depending on the substituents on the ligand and on the rigidity of the structure. In these structures, each palladium atom coordinates to the tridentate ligand while the fourth coordination site is occupied by the amidic oxygen of the next unit (Figure 1.9).59,60 a c b NONOPtNONOPtNONOPtRRRNONOPtONOPtONOPtNONO Pt NNRRRRN NNPtNNNPtNNNPtNNNPtH3CCH3CH3H3C13 Figure 1.9 Chemical structure of a (a) tetrameric and (b) hexameric head-to-tail palladium-macrocycles and single crystal X-ray structures for (c) the tetramer and (d) the hexamer. 59,60 Cu2+ also may take square-planar geometry and it has been reported to produce 4-fold or 6-fold metallomacrocycles when reacted with N-(2-methylimidazol-4-ylmethylidene)-2-aminoethylpyridine and N-(2-phenylimidazol-4-ylmethylidene)-2-aminoethylpyridine), respectively (Figure 1.10).61 a b c d 14 Figure 1.10 Head-to-tail copper macrocycles: (a) tetramer and (b) hexamer.61 It is also possible to form head-to-tail metallomacrocycles with metals that cannot adopt a square-planar geometry. For example, Berggren and coworkers reported the synthesis of a tetranuclear Mn2+ metallomacrocycle, in which the manganese has an octahedral geometry (Figure 1.11).62 Figure 1.11 Head-to-tail manganese macrocycle.62 MnNONNNROMnNONNNROMnNONNN ROMnN ON NNRO15 1.4.2.2!Metals coordinated inside the macrocycle The second type of metal-containing macrocycles discussed in this thesis are macrocycles that have high affinity for Group I cations, hosting them inside their cavity. The high affinity is due to the macrocyclic effect, which is a combination of two effects: pre-organization and chelation. Pre-organization favours coordination because the molecule does not need to rearrange to bind to a cation and, as a consequence, there is not a significant decrease in the entropy of the system. The chelate effect is the enhanced affinity that multidentate ligands have towards cations when compared to monodentate ligands. When an n-dentate ligand coordinates to a cation, it displaces n monodentate ligands, increasing the number of molecules in solution and therefore the entropy of the system. Macrocycles that coordinate a metal inside their cavity are numerous both in nature and synthetically prepared. Applications range from light-harvesting, environmental chemistry and medicinal chemistry. Some of the most well-known examples are discussed in the following sections. (a)! Crown ethers, cryptands and spherands Crown ethers, cryptands and spherands were the first examples of macrocycles to be synthesized. Discovered in 1967 by Charles Pedersen, crown ethers are a class of macrocycles that have high affinities to coordinate cations.63,64 They are comprised of several ether groups organized into a cyclic structure (Figure 1.12a). The cavity formed can have different sizes depending on the number of oxygen atoms in the crown ether, allowing for selective coordination of different types of cations. In 1969, a three-dimensional analogue of a crown ether, known as a cryptand, was developed by Jean-Marie Lehn et al. (Figure 1.12b).65 Cryptands are formed around 16 cations to produce a cage-like structure that encapsulates the cation. For this reason, cryptands are size-selective and can form stronger host-guest complexes than crown ethers.66 Crown ethers and cryptands are also flexible structures that can rearrange upon cation coordination. Donald Cram and his research group foresaw that a rigid pre-organized crown ether structure could increase the binding affinity toward cations. They developed a new class of compounds, called spherands, that have rigid structures and maintain their shapes even in the absence of the metal ion (Figure 1.12c).67 Their rigidity makes them exceptional ligands that are highly selective to specific metal ions.68 Pederson, Lehn and Cram were awarded the Nobel Prize in 1987 for their âdevelopment and use of molecules with structure-specific interactions of high selectivity".69 Figure 1.12 Structures of: (a) 15-crown-5; (b) cryptand [2.2.2]; (c) spherands. (b)! Porphyrins and calixarenes After the pioneering work of Pederson, Lehn and Cram, the field of supramolecular chemistry rapidly expanded and many macrocycles were developed and studied for host-guest chemistry. An important example from nature is the porphyrin molecule. This shape-persistent macrocycle contains four pyrrole units interconnected by methine bridges. Porphyrins can coordinate different metals where each type of metal can confer unique properties to the entire O OOOO NO ONO OO OOO OO OOa c b 17 molecule. For example, hemoglobin contains an iron-coordinating porphyrin that is key for oxygen transportation in blood. In plants, porphyrin derivatives coordinate to magnesium, producing chlorophyll, which is an important component for enabling the plant to absorb sunlight and perform photosynthesis.70 The versatility of this shape-persistent macrocycle and the strong optical properties resulting from Ï-conjugation have inspired synthetic chemists. Porphyrins have been used to design efficient chromophores in dye sensitized-solar cells.17 Zinc-containing porphyrins have been used as a building unit to form bigger macrocycles71,72,73 and complex supramolecular structures, like a 12-porphyrin figure-of-eight complex and a 12-porphyrin nanoring that were produced via templated synthesis74, exploiting the ability of zinc to form pentacoordinated species. Figure 1.13 (a) Structure of porphyrin; (b) 12-porphyrin figure of eight complex. Reproduced and adapted with permission from74. Copyright 2014 John Wiley and Sons. Calixarenes are another type of macrocycle able to host metal ions in their cavity. Named after the word chalices because their shape resembles a cone, they are made of several phenol groups bridged by methylenes (Figure 1.14).75 Calixarenes are flexible structures and, depending on the relative orientation of the phenyl groups, they can adopt different conformations. Addition 18 of bulky groups at the hydroxyl groups allows the locking of the calixarene in one of its conformers. The inside of the cavity is hydrophobic and can bind small molecules or ions.76 Figure 1.14 Structures of: (a) calix[4]arene in a âconeâ conformation; (b) calix[4]arene with bulky substituents coordinated to sodium. 1.5.! Pincer ligands Pincer ligands are a class of chelating compounds that closely surround a metal center through three coordination sites. First developed in the 1970s, pincer ligands initially contained an anionic carbon, with two pendent neutral donors (generally phosphines).77 Since then, many derivations of this structure have been synthesized: the anionic carbon can be replaced by a heteroatom, changing the total charge of the ligand and allowing coordination of metals with different oxidation states.78 For this reason the definition of pincer ligand is somewhat loose but the unifying concept is that they involve three donor atoms that surround a metal center in its meridional plane reducing any kinetic possibility for the metal ion to escape (Figure 1.15).79 This confers high stability to the complex while still leaving the flexibility of an additional coordination site, which is usually occupied by a solvent molecule or a different ligand. 19 Figure 1.15 Schematic representation of a pincer ligand. Although different types of pincer ligands have been exploited in supramolecular chemistry, relevant to this thesis are the tridentate planar bis(amido)pyridine ligands (Figure 1.16).80â83 They are typically used to coordinate square-planar metals like palladium(II) and platinum(II), and it is possible to modify their structures and bridge their extremities together forming macrocycles of different sizes. These types of macrocycles have been used in supramolecular chemistry for the synthesis of interlocked structures such as catenanes84,85, for making rotaxanes84,86, and for molecular machines and shuttles.87,88 Figure 1.16 Bis(amido)pyridine complex. Coordination of palladium to pincer-type ligands can also template the formation of rotaxanes. A rotaxane is a type of structure where a macrocycle forms a ring around a thread of atoms and is locked into position, despite not being chemically bonded to it, preventing the thread of atoms from escaping the macrocycle. This is usually achieved by designing threads of atoms with bulky groups at the extremities and monodentate donor atoms in the central part of the thread. Scheme 1.1 shows one important example of how a palladium-pincer complex can be used in the synthesis of a rotaxane. First, the palladium atom coordinates to a tridentate planar ND M DM = MetalO OD = DonorNN M N M = MetalO ORR20 bis(amido)pyridine ligand functionalized with olefin terminal groups and to a substituted pyridine with very bulky groups in the 2 and 6 position. Then, the bis-olefin-terminated tridentate ligand can be closed by ring closing metathesis (RCM). Subsequent removal of the palladium atom produces a rotaxane.89â91 If the thread of atoms, instead of bulky substituents, has two terminal olefins, then a RCM reaction can be performed on both ligands, forming two interlocked rings. After removal of palladium the resulting structure would be a catenane composed of two interlocked macrocycles not chemically bonded to each other. Scheme 1.1 Palladium-templated synthesis of a rotaxane.85 Palladium coordination can also direct the self-assembly of different fragments to form a macrocycle.84 In 2014, the Nitschke group reported the synthesis of a [3+3] macrocycle by a one pot reaction of 4,4â-oxydianiline with [Pd(MeCN)4](BF4)2 and 2,6-diformylpyridine in 1:1:1 ratio. Similarly, using the bulkier bis(3-aminophenyl)sulfone as a linker instead of the 4,4â-oxydianiline, a [2+2] macrocycle could be prepared (Scheme 1.2). In these macrocycles the Pd atoms are coordinated to a pincer ligand and to a molecule of acetonitrile. 21 Scheme 1.2 Synthetic scheme for the [3+3] and [2+2] macrocycles reported by Nitschke et al.84 In 2007, Leigh and coworkers reported an example of a palladium containing macrocycle that can translocate between a dimethylaminopyridine (DMAP) residue and a pyridine residue, both present on the same thread of atoms, using reversible protonation and changing the 22 temperature conditions88 (Scheme 1.3). DMAP is more nucleophilic than pyridine and at neutral pH the palladium coordinates preferentially to DMAP, and the palladium containing bis(amido)pyridine macrocycle forms a ring around the DMAP residue. After acidification and stirring of the compound for 16 h at 383 K in DMF, the ring shifts to the pyridine residue, while the DMAP residue is protonated. The ring shifts back to the DMAP residue after deprotonation of DMAP, stirring at 383 K in DMF for 1.5 h. This is an example of a molecular shuttle, a type of supramolecular machine where a molecule can be shuttled between different locations. Scheme 1.3 Operation of a palladium-complexed molecular shuttle.88 The ability of palladium-pincer complexes to switch between pyridine and DMAP depending on the pH conditions has been also used for designing a system defined as a âmolecular walkerâ.87 In this system, a molecular biped switches between two positions on a track, which is a thread of atoms. Only one foot of the molecular biped is labilized at a time insuring that the molecule is always attached to the thread by the other foot. The Leigh group designed a system 23 that employed a platinum(II) complex on one foot, and a palladium(II) complex on the other foot (Figure 1.17). Both metals are coordinating to residues on the same thread of atoms. Changing the conditions of pH and temperature allows the palladium(II) foot to switch between a DMAP residue and a pyridine residue, both present in the same track, while the platinum(II) foot remains kinetically locked. Figure 1.17 Molecular walker designed by Leigh et al. Reproduced and adapted with permission from Leigh et al.87 Copyright 2014 American Chemical Society. 24 1.6.! Metal-containing polymers Coordination bonds play an important role not only in macrocycles, but also in higher molecular weight structures such as polymers. If the monomers have two binding sites to connect with each other, then the polymer generated will be a one-dimensional chain. These types of materials are usually flexible, resistant to corrosion, and they easily form films.92 In metallopolymers, the original characteristics of a polymeric chain are combined with the specific properties of the metal used. Therefore, the incorporation of a metal into a polymer allows tuning its chemical and physical properties, while still maintaining the polymerâs ability to form films.93 For example, incorporating a metal complex with strong absorption in the visible region into a conjugated polymer enhances its photosensitivity. When the metal complex moieties are excited by light irradiation, the conjugated polymeric main chain can transport the excitons formed.94 For this reason some of the applications of metal-containing polymers include photovoltaics and optics.95â97 In 1955 the Arimoto group prepared the first metal-containing polymer, poly(vinyl ferrocene).98 Produced by radical polymerization of vinyl ferrocene, it has a long alkyl chain as the backcone, and the ferrocene moieties are attached to it as pendant groups (Scheme 1.4). Scheme 1.4 Reaction scheme for the polymerization of vinyl ferrocene as reported by Arimoto et Al.98 25 Metal-containing polymers can be classified in different ways, depending on the nature of the polymeric chain (conjugated or not, linear or branched) and on the type of interaction between the metal and the backbone (chemical bond or physical interaction). In this section, the focus is on metallopolymers in which a metal is chemically coordinated to a linear main chain (Figure 1.18). In this case two types of structures are possible. In type I, the polymer molecule coordinates to the metals either through binding sites on the backbone or on side chains, so that removal of the metal does not break the polymeric chain. Arimotoâs ferrocene polymer belongs to type I. In type II the metals are part of the backbone, bridging together different fragments. In this case the metal coordination is integral to the polymeric structure since its removal would destroy the polymer. Type II polymers are also sometimes referred to as one-dimensional coordination polymers. Figure 1.18 Schematic representation of Type I and Type II polymers. As previously mentioned, Arimotoâs poly(vinyl ferrocene) is a type I polymer; but ferrocene has been used to produce type II polymers as well. For example, polyferrocenylene is a polymer constituted only by ferrocenylene units, developed in 1967 by Neuse and Crossland.99 26 Polyferrocenylsilane is an example of a well-characterized, soluble metallopolymer.100 A comparison between the structure of poly(vinyl ferrocene), polyferrocenylene and polyferrocenylsilane is shown in Figure 1.19. Figure 1.19 Structure of (a) poly(vinyl ferrocene) and (b) polyferrocenylene, and (c) polyferrocenylsilane.98â100 Ruthenium complexes present unique redox and photophysical properties and they have been widely used to prepare metallopolymers for a variety of applications, from sensing to solar energy conversion.101,102 Some ruthenium containing polymers have shown to be able to act as light emitters, like the compound shown in Figure 1.20a, where the ruthenium complex is part of a conjugated backbone constituted by poly(phenylene vinylene) and aromatic oxadiazole units.103 The polymer shown in Figure 1.20b has a similar backbone, but the conjugation is interrupted by the presence of ruthenium atoms in the main chain. This material has shown to be a promising photosensitizer in photovoltaic devices.104 27 Figure 1.20 Structure of ruthenium containing polymers: (a) Type I; (b) Type II.103,104 Metallopolymers can also include more than one type of metal (Figure 1.21). For example, zinc-coordinated porphyrin complexes have been introduced in a platinum acetylide polymer.105 Cyclometalated iridium complexes bearing bifunctional pendant acetylene groups can also be combined with platinum to generate phosphorescent polymers of dual metal centers.106 Figure 1.21 Mixed-metal polymers: (a) zinc and platinum; (b) iridium and platinum.105,106 28 The pincer ligand scaffold discussed in the previous section has also been employed to build metallopolymers.107,108 For example, the Holliday group developed a conductive platinum-[NCN] pincer metallopolymer (Figure 1.22) containing a conjugated backbone of thiophene units. Figure 1.22 Structure of Pt-[NCN] pincer metallopolymer developed by the Holliday group.108 1.6.1! Ring-opening metathesis polymerization Ring-opening metathesis polymerization (ROMP) was first reported by Grubbs et al. in 1992.109 This polymerization reaction involves the addition of the Grubbs catalyst (a ruthenium-carbene complex) to a strained cyclic molecule, for example norbornene (Figure 1.23a). The strained double bond of the norbornene interacts with the Grubbs catalyst (Figure 1.23b) to form a cyclic intermediate species that rearranges into an open form. This open form can react with a new monomer and extend the chain to form a high molecular weight polymer. The driving force of most ROMP reactions is the release of ring strain in the monomer. If the ring is not strained enough, then the cyclic intermediate, if formed, would rearrange into a closed form rather than reorganizing into an open form and the equilibrium would be shifted toward the starting materials. ROMP reactions are examples of living polymerization: the chain is not able to terminate itself and the reaction proceeds until all the monomers are consumed. It can also produce intra-chain reactions. For this reason, ROMP reactions need to be quenched. Living polymerizations are characterized by initiation rates higher than propagation rates. This means that all the active species SSSSN NPtnCl29 form fast and they start propagating at the same moment with the same rate. This allows formation of several chains with approximately the same number of monomers and the same molecular weight, thus giving a narrow molecular weight distribution. Also, through selection of the monomer-to-initiator ratio, the molecular weight of the polymer can be controlled. There are numerous catalysts that can be used in ROMP (Figure 1.23b and Figure 1.23c). Since the development of the first generation Grubbs catalyst in 1992, several other catalysts have been synthetized and used.110 The second and third generation Grubbs catalysts are ruthenium-carbene complexes derived from the first generation one. They present improved air- and moisture-stability and higher activity then the first generation catalysts. The Hoveyda-Grubbs catalysts constitute another class of ruthenium-carbene catalysts with improved stability, but they present slower initiation rates. Ruthenium is not the only transition metal employed in ROMP reactions. Molybdenum and tungsten catalysts developed by Schrock have also been widely used.111 30 Figure 1.23 (a) Ring-opening metathesis polymerization intermediate and mechanism; (b) structures of 1st, 2nd and 3rd generation Grubbs catalysts; (c) structures of Hoveyda Grubbs and Schrock catalysts. ROMP has been a valuable tool for the synthesis of many polymeric materials and metallopolymers.112 For example norbornene can be functionalized with a metal-containing group, like ferrocene or a platinum cyclometalated complex, and polymerized. The product would be a Type I polymer with the metals in the side chains. ROMP has also been used to polymerize strained metallated cyclic monomers, forming Type II polymers with the metal in the backbone, like poly(ferrocenylenedivinylene) (Scheme 1.5).113 31 Scheme 1.5 ROMP reaction to form poly(ferrocenylenedivinylene).113 ROMP reactions on unstrained substrates have been rarely reported. High concentrations and moderate temperatures (40â50 °C) seem to be key to successfully polymerize an unstrained substrate. It has been reported that several unstrained macrocyclic esters with up to 34 ring atoms can be polymerized by preparing a solution of the monomer (40-50% w/v) and stirring the solution to evaporation. The gradual increase of concentration provides the polymerization driving force.114 In the case when the macrocycle is unstrained, there is no significant difference in enthalpy between the macrocycle and the polymer. Thus the ÎHÂ° of the polymerization is close to zero. As a consequence, ÎGÂ° = âTÎSÂ°. For the ÎGÂ° to be negative, the ÎSÂ° needs to be positive. This type of ROMP reaction is entropically-driven and it is usually referred to as ED-ROMP.115 There are two types of entropies that influence this reaction, conformational and translational entropies (ÎSÂ° = ÎSÂ°conf + ÎSÂ°trans). Conformational entropy increases during a polymerization reaction: ÎSÂ°conf = SÂ°Pconf â SÂ°Rconf > 0 (SÂ°Pconf and SÂ°Rconf are the conformational energies of products and reagents, respectively). Translational entropy is a function of the concentration, and decreases as the concentration increases. The translational entropy variation during a polymerization reaction is ÎSÂ°trans = SÂ°Ptrans â SÂ°Rtrans. At high concentration the translational energy of the macrocycle (SÂ°Rtrans) is very small and as a consequence the ÎSÂ° of the reaction is positive, giving a negative ÎGÂ° and favouring the reaction.115 ED-ROMP has been used to successfully polymerize cyclic 32 bile acids of 38-units and 25-units,116 but besides sporadic cases, examples of polymers obtained with a ROMP reaction on unstrained substrates are particularly limited.117â119 1.7.! Goals and scope The main goal of this thesis was to demonstrate a new form of supramolecular polymerization that would allow for the polymerization of unstrained metal-containing monomers. The concept is simple: if during a reversible ROMP reaction the ring-closing step becomes irreversible through a supramolecular transformation, then the polymerization will proceed. Although we envision using various supramolecular interactions, including hydrogen-bonding, for this, I set out to investigate coordination chemistry to facilitate the polymerization (Figure 1.24). The idea is that coordination of a bulky ligand to a metal center in an unstrained metallomacrocycle would provide steric hindrance, blocking ring-closing and favouring polymerization upon interaction with a Grubbs catalyst. Figure 1.24 Schematic representation of the approach used to polymerize an unstrained metal-containing macrocycle (represented in blue) using ligand coordination (ligand is represented in pink). Supramolecular""transformation:"Interaction"with"bulky"ligand"L"Unstrained"Metal$containing"macrocycle"Stabilization"of"the"open"form:""ring$closing"step"becomes"irreversible"Grubbs"L"L"L"Pd"Pd"Pd"33 The first approach was to use a palladium pincer complex as the monomer (compound 3, Scheme 1.6). Macrocycle 3 is not strained, since substituents are oriented out of the plane of the pyridine and metal to accommodate the acetonitrile guest. It was anticipated that, if the acetonitrile molecule on compound 3 is exchanged with a bulky ligand and a Grubbs catalyst is added to the reaction, the opened, unstrained intermediate of the ROMP reaction should be stabilized. As a consequence, the polymerization reaction should proceed. Scheme 1.6 Reaction scheme for ROMP reaction on compound 3, in the presence of a bulky ligand L. Chapter 2 covers the synthesis of macrocycle 3 and the ligand exchange studies between acetonitrile and six bulkier ligands. Ligand exchange kinetic studies were performed in order to find the most suitable ligand for the ROMP reaction on macrocycle 3, and a model complex corresponding to the open form of the macrocycle, compound 5, was prepared (Figure 1.25). This study shows that macrocyclization is a way to control ligand exchange on the palladium atom. NO ONNO OPdNNO ONNO OPdLnROMP, LL = Generic Bulky Ligand334 Figure 1.25 Structures of: (a) macrocycle 3; (b) model compound 5 and (c) ligands that were exchanged with acetonitrile. Chapter 3 covers the polymerization attempts on macrocycle 3 by ligand-exchange-driven ROMP reaction and the formation of dual-metal centered macrocyclic dimers. Another goal of this thesis is the formation of cyclometalated platinum complexes with crown ether functionality (Figure 1.26). Two types of systems were designed: a complex formed with a flexible ligand, where the platinum is in direct communication with the crown ether cavity; and a pre-organized ligand, where this communication is interrupted. It was anticipated that the crown-ether cavity of these complexes could be used for the formation of redox-active rotaxanes and pseudo-rotaxanes. Several platinum complexes where prepared containing 18-crown-6 and 15-crown-5. NO ONNO OPdNNO ONN PdNNPN NNNN35a bc35 Figure 1.26 Structures of some the targeted Pt2+ complexes with crown ether functionality. (a) Flexible ligand with communication between Pt and the crown ether cavity; (b) pre-organized ligand. Chapter 4 discusses the synthesis and characterization of platinum complexes with flexible bis(2-phenylpyridine) ligands containing a 18-crown-6 and 15-crown-5 functionalities. The synthesis of these complexes is challenging due to the flexibility of the ligand. Therefore, several synthetic strategies are discussed, as well as the interaction of the platinum complexes with different axial molecules. In addition, chapter 4 discusses the synthesis of pre-organized ligands, and their coordination with platinum, leading to complexes with different oxidation states: Pt2+, Pt4+ and an unexpected Pt3+ complex (Figure 1.27). Figure 1.27 Structure of the platinum complexes synthesized: (a) Pt2+; (b) Pt3+ and (c) Pt4+. 36 Chapter 2:! Controlling the ligand exchange through macrocyclization 2.1.! Introduction Pincer ligands are a class of chelating compounds that bind strongly to a metal through three coordination sites.78,120â124 The tridentate ligand confers high stability to the complex but potentially still leaves a vacant coordination site on a square-planar metal complex. Pincer complexes have attracted enormous attention for catalysis, sensing, and other applications.125â128 Tridentate planar bis(amido)pyridine ligands are pincer ligands that have been widely exploited in supramolecular chemistry.80â83 Their ability to coordinate with metals like palladium(II) and platinum(II) that prefer square-planar geometry, and the potential to modify their structures make them suitable for forming catenanes,84,85 rotaxanes,84,86 and molecular machines.87,88 Ligand exchange on the fourth coordination site of the metal center is also important for several other applications such as designing receptor systems, catalysts129 and drugs. It has been previously reported that bis(amido)pyridine ligands with bulky side groups can be employed to control the ligand exchange on the fourth coordination site of palladium. For instance, the incorporation of larger aromatic rings on the pincer backbone results in a NNN pincer complex of Pd2+ that has enhanced binding between 2-chloroethyl ethyl sulfide and the palladium.130 Bulky ligands have shown to affect the reactivity of transition metal pincer complexes,131 and ligand exchange on the fourth coordination site of the palladium in pincer complex becomes slower with an increase of the steric hindrance near the metal center.132 This is related to the ligand-exchange mechanism on the palladium center, which is usually associative and is therefore impeded by steric bulk around the metal center. In catalysis, this concept has been used to convert palladium(II) complexes from olefin oligomerization catalysts to polymerization catalysts.133 37 In this chapter we investigate control of ligand exchange on a palladium pincer complex by using a supramolecular approach. A tridentate macrocyclic ligand with a NNN pincer bis(amido)pyridine functionality has been prepared (Figure 2.1a). The macrocycle coordinates to a palladium ion to give a rigid pincer complex with a small cavity; an acetonitrile molecule occupies the palladium atomâs fourth coordination site. The small size of the cavity provides steric hindrance and impedes the ligand exchange between acetonitrile and other bulky ligands. Ligand exchange studies were performed with several ligands and the rate of exchange on the new metallomacrocycle was compared with the rate of exchange for its corresponding open form (Figure 2.1b). Figure 2.1 (a) NNN pincer metallomacrocycle of Pd2+. An acetonitrile molecule occupies the fourth palladium coordination site. (b) NNN pincer complex of Pd2+. This complex represents the open form of the metallomacrocycle. 2.2.! Results and discussion 2.2.1! Metallomacrocycle 3: synthesis and behavior in solution The NNN pincer bis(amido)pyridine macrocycle 2 was prepared by the route shown in Scheme 2.1. The ring-closing (final) step proceeded in 71% yield when high dilution conditions were used (2.5 mM). Notably, the macrocycle has C2v symmetry by 1H NMR spectroscopy and the 38 components of the macrocycle are fluxional. A crystal structure of compound 2 is reported in Figure 2.2. The macrocycle is expected to be flexible in solution despite the bridge between the aryl groups. Metallation of macrocycle 2 with Pd(OAc)2 at 50 °C afforded a yellow metallomacrocycle 3 in 54% yield. The new compounds were characterized by 1H and 13C NMR spectroscopy and high-resolution electrospray ionization mass spectrometry (HRESI-MS). The 1H NMR signals (in CDCl3) corresponding to the amidic hydrogen (7.62 ppm) disappeared upon coordination to palladium(II) and a new peak corresponding to the coordinated acetonitrile appeared at 1.50 ppm (excess free acetonitrile is observed at 2.02 ppm). Notably, the methylene hydrogen atoms present in macrocycle 2 became diastereotopic upon Pd2+ coordination, indicating reduction of the C2v symmetry to Cs symmetry. This shows that on the time scale of the NMR experiment, the ring in compound 3 is unable to skip past the acetonitrile molecule coordinated to the metal center, and the conformation is blocked on one side with respect to the palladiumâacetonitrile bond. A 1H-1H COSY NMR experiment was used to correctly assign the chemical shift of each hydrogen atom in complex 3 (Figure A-1). A single crystal of 3 suitable for single crystal X-ray diffraction (SCXRD) was obtained from slow evaporation of a solution of 3 in 1:1 acetonitrile/dichloromethane (DCM). The crystal structure (Figure 2.3) confirmed that the palladium ion has square-planar geometry where it is coordinated to the pyridine, two amido nitrogen atoms, and acetonitrile. The metallomacrocycleâs cavity is small - the distance between the two aromatic rings is 5.802 Ã - but the system is not strained, since substituents are oriented out of the plane of the pyridine and metal to accommodate the acetonitrile guest (Figure 2.3b). This geometry is consistent with the solution 1H NMR data, which showed that the methylene protons are diastereotopic (Figure A-2). 39 Figure 2.2 Solid-state structure of compound 2 as determined by SCXRD. (a) front view, (b) side view. NONHOHNO ONONONPdNO ONONHOHNOH OHNO OCl ClOHNH2+ 1)"Et3N,"THF $78"°C,"N2 50"°C" 2"h N2 Pd(OAc)2 CH3CN 1)"K2CO3,"2$butanone," "reflux,"30"min 2)"cis$1,4$dichlorobutene, """""reflux,"120"h 3 2 1 2)"8"h,"RT 61% 71% 54% 2 Scheme 2.1 Synthesis of metallomacrocycle 3. 40 Figure 2.3 Solid-state structure of compound 3 as determined by SCXRD. (a) front view, (b) side view, (c) top view. It has been previously reported that some palladium bis(amido)pyridine complexes are present in an equilibrium between a monomeric form and a cyclic hexameric or tetrameric form.59,60,134 This equilibrium is facilitated by the lability of the acetonitrile molecule coordinated to the palladium, which in solution exchanges with another bis(amido)pyridine complex that coordinates through its oxygen atom to form a cyclic structure. The addition of ligands that bind the metal center can strongly disrupt this equilibrium, shifting it toward the monomeric form. We anticipated that the macrocyclic structure of 3 would inhibit aggregation and thereby stabilize the monomeric form of the compound. However, through a variable-temperature (VT) 1H NMR spectroscopy experiment (Figure A-3), we found that when metallomacrocycle 3 is heated in chloroform, it partially converts into a new compound (3*). The species 3* is stable and does not revert to the monomeric form upon cooling of the sample to room temperature. 1H NMR spectroscopy indicates that the new product is structurally similar to the monomer, but does not 41 contain acetonitrile. In addition, the peaks corresponding to the pyridine protons become asymmetric (Figure A-4). Our data suggests that compound 3 ejects acetonitrile to form oligomer 3*. A single crystal of compound 3* was grown by vapour diffusion of cyclohexane into a solution of 3* in dichloroethane. Figure 2.4a shows the crystal structure of this aggregate; it is a cyclic tetramer where each monomer is bridged to the next palladium atom through a carbonyl group. As shown in the spacefilling model in Figure 2.4b, the cavity inside compound 3* is quite small, with the Pd1âPd3 distance being 7.878(4) Ã and the Pd2âPd4 distance being 7.095(3) Ã . Figure 2.4b also shows the atomic displacement parameters for compound 3*. It is noticeable that the structure has substantial disorder located in two of the bridging chains and on some phenyl rings. Restraints on the bond lengths and angles worked well enough to model the phenyl rings, while for the bridging chains it was necessary to split the electron density in two parts and fix the total occupancy to 1. Despite the complexity of the structure and the weak diffraction of the crystal, the Rint was brought down to 15.3%. The structure is reliable enough to conclude that the aggregate formed is a tetrameric macrocycle of macrocycles. 42 Figure 2.4 (a) Solid-state molecular structure of compound 3* as determined by SCXRD. Compound 3* is a macrocycle of macrocycles, where each monomer is bridged by a carbonyl group to the next palladium atom, forming a cyclic tetramer. (b) Spacefilling model (based on van der Waals radii) for compound 3*. The colour of the atoms indicates the atomic displacement parameters: blue if they are small, red if they are high. 2.2.2! Model compound for ligand exchange In order to explore the exchange of ligands at palladium in metallomacrocycle 3, we first prepared a model complex, 5, as shown in Scheme 2.2. In this complex, the phenyl rings are not tethered together and they are instead free to move far apart from each other. Compound 5 was characterized by 1H NMR and 13C NMR spectroscopy, HRESI-MS, elemental analysis and SCXRD. Comparing the 1H NMR data with compound 3 shows that for compound 5 the methylene protons are not diastereotopic. These data are consistent with average C2v symmetry in solution. The 1H NMR spectrum of compound 5 in CD2Cl2 (Figure A-5) also shows some broad peaks that are not present if the spectrum is collected in a coordinating solvent such as dimethyl sulfoxide 43 (DMSO). In DMSO (Figure A-6), the peak corresponding to coordinated acetonitrile (1.80 ppm in CD2Cl2) is not present either. This suggests that DMSO exchanges with acetonitrile, shifting the equilibrium toward a monomeric complex, while in chloroform some oligomer is formed. As with compound 3, heating compound 5 in chloroform for 48 h at reflux produces a new species 5*, which is likely to be some higher order aggregate of compound 5 where the acetonitrile molecule is not coordinating, similar to the cyclic tetramer 3*. (Unlike in the case of 3*, we have not been able to isolate and purify 5*, but it behaves similarly to 3* leading us to postulate that it is also an aggregate.) A single crystal of 5 was produced from vapour diffusion of pentane into a solution of 5 in 1:1 chloroform/acetonitrile. The SCXRD structure of compound 5 is shown in Figure 2.5. The phenyl groups are both on one side with respect the palladium coordination plane, but they are able to skip past the acetonitrile molecule in solution, as supported by the 1H NMR data (Figure A-6). This is consistent with the crystal structure of 5 recently obtained by Jerome et al. which presents the same unit cell.135 NO OCl ClNH2 NONHOHNNONONPdN1)"Et3N,"THF,""""""0"°C,"N2, 2)"RT,"8"h 4 5 +"2 Pd(OAc)2,"CH3CN RT,"8h,"N2 79"% 40"% Scheme 2.2 Synthesis of open complex 5. 44 Figure 2.5 Solid-state molecular structure of compound 5 as determined by SCXRD. (a) Front view and (b) side view. 2.2.3! Ligand exchange studies: triphenylphosphine, pyridine, DMAP The ligands selected to investigate the exchange with acetonitrile on the palladium atom are shown in Figure 2.6. Triphenylphosphine (PPh3), pyridine and 4-dimethylaminopyridine (DMAP) exchange quickly with acetonitrile both in the metallomacrocycle 3 and in the open complex 5. Following the ligand exchange by 1H NMR spectroscopy, the disappearance of peaks corresponding to higher order aggregates (3* and 5*) is notable. The equilibrium shifts toward the monomeric form as the ligand exchange completes. The metallomacrocycle exchange products were characterized by 1H NMR, 13C NMR, ESI-MS, elemental analysis and SCXRD. The molecular structures of compounds 5-pyr and 5-PPh3 are shown in Figure 2.7. Attempts to grow single crystals of compound 5-DMAP suitable for SCXRD were unsuccessful. 45 Figure 2.6 Compounds used to investigate the ligand exchange: pyridine, triphenylphosphine, 4-dimethylaminopyridine (DMAP), quinoline, acridine, 2,6-lutidine. Figure 2.7 Solid-state molecular structures of (a) compound 5-pyr and (b,c) compound 5-PPh3 as determined by SCXRD. From the crystal structures of compounds 5-pyr and 5-PPh3, it is clear that the two phenyl rings of the pincer ligands do not move very far from each other upon coordination of pyridine or triphenylphosphine. We anticipated that these ligands, which are substantially bulkier than acetonitrile, would lead to a large splaying of the phenyl rings. In fact, 5-pyr has nearly perfect square-planar geometry at the Pd2+ center, and the triphenylphosphine complex 5-PPh3 shows only 46 a small distortion from square-planar (the torsion angle between the NNN-Pd plane and the phosphorus atom is 15.78°). This is in agreement with the crystal structure published by Jerome et al. for compounds 5-PPh3, which presents the same torsion angle and crystallizes in the same unit cell.135 Jerome et al. synthesized compounds 5 and 5-PPh3 and similar palladium complexes with substituents in the ortho positions and studied their applicability as catalysts in the Suzuki-Miyaura cross-coupling reaction. For pyridine, DMAP and triphenylphosphine, the bridging chain on compound 3 doesnât provide enough steric bulk to significantly slow the exchange process. In spite of this, NMR studies show that the bridging chain provides enough steric hindrance to affect the rotation of pyridine and DMAP around the NâPd bond. Specifically, Ho1 and Hm1 (Figure 2.8a) experience large differences in chemical shift as a result of the ring current from Ho2 and Hm2, which, combined with the intermediate rate of ligand rotation at room temperature, makes them completely invisible in the room temperature 1H NMR spectra of compound 3-pyr and 3-DMAP. That said, the ortho and meta resonances can be detected at 115 °C, where the rotation of pyridine and DMAP is fast enough for the resonances to become equivalent (Figure 2.8). High temperature 1H-1H-COSY and NOESY NMR experiments confirmed the correct assignment of the spectra (Figures A-7, A-8 and A-9). At low temperature, on the other hand, ligand rotation slows down to the point where four distinct 1H resonances emerge (Figure 2.9). The chemical shift difference is especially dramatic between Ho1 and Ho2 (3.30 ppm for 3-DMAP, 3.55 ppm for 3-pyr), given Ho1âs position in the diamagnetic ring current. Low temperature 1H-1H-COSY and HSQC NMR experiments confirmed the assignment of these protons (Figures A-10, A-11 and A-12). 47 Figure 2.8 (a) Structure of DMAP, indicating the protons on the pyridyl ring. (b) High-temperature 1H NMR studies for compound 3-DMAP. (c) High-temperature 1H NMR studies for compound 3-pyr. C2D2Cl4 is represented with the symbol *. The peaks corresponding to the ortho and meta positions become sharper as the temperature increases, generating two distinct signals. The signals in blue correspond to the ortho protons, whereas the red peaks are generated by the protons in meta position. 48 Figure 2.9 (a) Structure of pyridine, indicating the protons on the pyridyl ring. (b) Low-temperature 1H NMR studies for compound 3-DMAP. (c) Low-temperature 1H NMR studies for compound 3-pyr. CD2Cl2 is represented with the symbol *. The peaks corresponding to the ortho and meta positions become sharper as the temperature decreases, generating four distinct signals. The signals in orange correspond to the hydrogen atoms pointing inside of the cavity, which are significantly shielded by the macrocycleâs phenyl groups, whereas the green peaks are the hydrogen pointing away from the cavity. 49 The free energies of activation for ligand rotation, ÎGâ¡rot, for compounds 3-pyr and 3-DMAP are reported in Table 2.1. Experimental values of ÎGâ¡rot were calculated using two different methods: the Eyring plot or through determination of the coalescence temperature, Tc.136,137 ÎGâ¡rot can also be calculated by ab initio methods, obtaining the initial coordinates from the crystal structure of 3-quin, which was modified by changing the quinoline ligand to pyridine, with the assumption that doing so does not significantly perturb the overall geometry of the molecule. Table 2.1 Free energies of activation for ligand rotation, ÎGâ¡rot, in kJ/mol and kcal/mol, for 3-pyr and 3-DMAP, obtained from ab initio techniques and from VT NMR dataa, using either the Eyring equation or the coalescence temperature. computational calculationsb from Tc from the Eyring plot ÎGâ¡rot 3-pyr 3-pyr 3-DMAP 3-pyr 3-DMAP kJ/mol 46.5 52 48 54 50 kcal/mol 11.1 12 12 13 12 aThe rotation rate constants at different temperatures (used to obtain the ÎGâ¡rot) were calculated using approximations of the Bloch equation. The uncertainties associated with these values are estimated to be about ±10-15%.136 bThe B3LYP hybrid functional was used in conjunction with the 6-31+G(d,p) basis set. The LANL2DZ basis set and LANL2 core potential were used in the case of platinum. All calculations were carried out using the Gaussian 09 (rev. D.01)138 suite of ab initio codes. The solvent and dispersion effects were ignored. Calculations were performed at the coalescence temperature (for 3-pyr Tc = 304 K). 50 2.2.4! Ligand exchange studies: quinoline, acridine and 2,6-lutidine We next investigated bulkier ligands (quinoline, acridine and 2,6-lutidine) that we expected to show marked differences in exchange rate between the open complex and the strapped metallomacrocycle. When quinoline was added to the open complex compound 5, the coordinated acetonitrile was rapidly exchanged for quinoline, similar to the behavior observed with pyridine. When quinoline was added to compound 3, however, exchange was much slower and completed in 55 min. The crystal structure of compound 3-quin shows that quinoline coordinates with the phenyl group pointing away from the cavity in order to reduce any steric strain (Figure 2.10). Using the atomic coordinates obtained from SCXRD data for 3-quin, we calculated the size of the metallomacrocycle cavity with the software POVME2.139 This calculation indicates that the cavity is quite small (26.5 Ã 3) compared with the volume of quinoline, acridine and 2,6-lutidine reported in literature: 123 Ã 3, 166 Ã 3 and 113 Ã 3, respectively.140,141 Figure 2.10 Solid-state structure of compound 3-quin as determined by SCXRD. (a) Front view, (b) side view, and (c) top view. Acridine and 2,6-lutidine exchange slowly with the acetonitrile in both compounds 3 and 5. It is possible to follow the exchange process by 1H NMR spectroscopy. Figure 2.11 shows the 51 kinetic studies performed on compound 5 during the exchange of acetonitrile with acridine and 2,6-lutidine. The ligand exchange with acridine reaches completion after 28 minutes, while the ligand exchange with the more sterically hindered 2,6-lutidine is complete after 40 minutes under the same conditions. This difference is probably due to the presence of the two methyl groups on the lutidine. Ligand exchange obeys a second-order kinetic rate law characteristic of an associative reaction mechanism, where both the acetonitrile and the new ligand take part in the transition state. Figure 2.11 Ligand exchange kinetic study on compound 5, performed with acridine (blue circles) and 2,6-lutidine (orange triangles). 1/X corresponds to the inverse of the concentration of compound 5. The initial concentration of both 5 and the additional ligand were 0.013 M. The solid-state molecular structures of the exchanged products of compound 5 are shown in Figure 2.12. For these complexes, the metal center is nearly perfectly square-planar and the phenyl rings are not significantly splayed apart. This possibly indicates that the open complex can easily accommodate the new ligands even if the kinetic studies reveal that this exchange is slow. 52 In all the complexes shown in Figure 2.12, the pincer ligandâs phenyl rings point toward opposite sides of the palladiumâpyridine plane. For compound 5-acr, the distance between the aryl rings of the pincer ligand and the coordinated acridine is 3.6 Ã , indicating a weak intermolecular interaction. In compound 5-lut, the distance between the methyl hydrogens of the 2,6-lutidine and the pincer ligandâs aromatic rings is 3.0 Ã , suggesting a CHâÏ interaction. Regarding 5-quin, one of the pincer ligandâs phenyl moieties stacks with one aromatic ring (the distance between them is 3.7 Ã ), while there is no stacking for the other phenyl moiety. Figure 2.12 Solid-state molecular structure of (a) 5-quin, (b) 5-acr, and (c) 5-lut as determined by SCXRD. Figure 2.13 shows the kinetic study of ligand exchange in metallomacrocycle 3 with quinoline, acridine and 2,6-lutidine. The 1H NMR data fit to a second-order kinetic rate law for compound 3, at least for conversion of <50%. For quinoline substitution, ligand exchange on compound 3 is 90% complete in 55 minutes. The reaction with acridine was monitored for about 8 h, after which it reached 70% completion. On the other hand, the exchange between acetonitrile and 2,6-lutidine on compound 3 was monitored for 10 h, after which the reaction was only 50% complete. Assuming that second-order kinetics holds, extrapolation from a linear fit shows that the time to reach 90% conversions would be 23 and 80 h for acridine and 2,6-lutidine, respectively. 53 The exchange process is significantly slower for 2,6-lutidine than for the other two ligands, an effect attributed to the steric bulk given by the methyl groups. From the crystal structure of 3-acr, Figure 2.14, it is possible to see that the phenyl moieties bend to an almost 90° angle in order to accommodate the acridine molecule. Differently from 5-acr, the acridine molecule does not stack with the phenyl moieties of the pincer ligand. Instead, in the crystal packing two acridine molecules interact through ÏâÏ stacking (distance between phenyl rings: 3.6 Ã ) forming dimers (Figure 2.15). Figure 2.13 Ligand exchange kinetic study on compound 3, performed with: (a) quinoline (red diamonds); (b) acridine (blue circles); and (c) 2,6-lutidine (orange triangles). (d) comparison between the exchange with 2,6-lutidine and acridine. 1/X corresponds to the inverse of the concentration of compound 3. The concentration of the solutions is 0.013 M and the ratio between compound 3 and the additional ligand is 1:1. 54 Figure 2.14 Solid-state structure of compound 3-acr as determined by SCXRD. (a) Front view, (b) side view, and (c) top view. Figure 2.15 Dimers formed by 3-acr due to stacking between two acridineâs phenyl rings. The distance between two phenyl rings is 3.6 Ã . Therefore, our results clearly show that the ligand exchange on compounds 3 and 5 are dramatically different; the rate of ligand exchange on 5 was 50â120 times faster than on 3. Even though the tethering group is far from the metal center, forming the metallomacrocycle substantially affects the sterics near the metal center and thus affects the kinetics of ligand 55 exchange. This can be explained by the formation of a transition state where both the acetonitrile, that is leaving, and the new ligand, that is coordinating, are participating. We think that the small cavity in compound 3 allows the formation of a 5-coordinate transition state. This is because the cavity does not surround the ligands in the plane of the pincer ligand but bends away to accommodate bulky guests at the metal center. This can be noted in the crystal structures of 3, 3-quin, and 3-acr, where the ligands do not sit inside the cavity, and the phenyl groups bend up to almost a 90° angle. The kinetic studies show that the reaction follows a second-order rate law, in agreement with an associative mechanism with two separate molecules participating in the transition state. The small size of the cavity, estimated to be 26.5 Ã 3, provides steric hindrance, which slows ligand exchange on the palladium. 2.2.5! Binding constants determination A measure of the steric bulk increase of the ligands, going from the smaller pyridine to the bulkier 2,6-lutidine, can be given by calculating the equilibrium constants for the exchange of pyridine with quinoline, acridine and 2,6-lutidine in both compounds 3-pyr and 5-pyr. The concentration of each species at equilibrium was calculated by integrating a corresponding 1H NMR peak and each measurement was repeated three times. The values obtained are reported in Table 2.2. Table 2.2 Equilibrium constants compound Keq(pyrâquin)a Keq(pyrâacr)a Keq(pyrâlut)a 3 0.79(±0.07)b no exchange no exchange 5 0.95(±0.07) 0.14(±0.02) 0.016(±0.003) a Keq is the equilibrium constant for the reaction: 3-pyr + X 3-X + pyr. X = quin, acr, lut. b Standard deviation calculated from the three measurements performed. 56 Out of the three ligands studied, quinoline is the only ligand able to exchange with pyridine, but the equilibrium remains slightly shifted toward 3-pyr. Acridine and 2,6-lutidine are probably too bulky and no exchange was observed. In the more flexible complex 5-pyr, all the three ligands can exchange, but there is a noticeable decrease in the equilibrium constants values as the bulk of the ligands increases. The constant is close to 1 only for the equilibrium between 5-quin and 5-pyr, while for acridine and lutidine the equilibrium is strongly shifted toward 5-pyr. 2.3.! Conclusions A novel NNN pincer macrocyclic palladium complex and its corresponding open form have been synthesized. Palladium forms a square-planar complex when coordinated with the NNN pincer macrocycle and an acetonitrile molecule. The lability of the acetonitrile molecule produces an equilibrium between the metallomacrocycle and higher-order aggregates; a tetrameric macrocycle of metallomacrocycles was isolated and structurally characterized by SCXRD. Ligand exchange on the palladium between acetonitrile and six different ligands has been investigated for both the macrocycle and the corresponding open complex. For ligands with little steric bulk, the exchange is rapid and there is no significant difference between the metallomacrocycle and the open complex. When the ligands have more steric bulk, the exchange is substantially slower and, significantly, the ligands exchange much faster on the open complex than on the metallomacrocycle. Kinetic studies also revealed that the ligand exchange reaction proceeds through an associative mechanism. As a consequence, more steric crowding around a metal center inhibits the ligand exchange process. Our results demonstrate that forming a macrocycle is a way to control the rate of ligand exchange at a metal center. We are now exploiting this phenomenon to further control the supramolecular chemistry of metallomacrocycles. 57 2.4.! Experimental section Materials and equipment. Solvents and starting materials were used as received from the supplier. CDCl3, C2D2Cl4 and THF-d8 were purchased from Cambridge Isotope Laboratories. (CD3)2SO and CD2Cl2 were purchased from Sigma Aldrich. All the reactions were performed under N2, with the exception of compound 2 synthesis. Dry solvents were obtained from INERT column solvent purification system. Single crystal X-ray diffraction data (SCXRD) raw data were collected on a Bruker APEX DUO diffractometer. Nuclear magnetic resonance (NMR) spectra were recorded on Bruker AV-400 and AV-300 spectrometers. Variable-temperature 1H NMR spectra were collected on a Bruker AV-400 inverse probe spectrometer and were calibrated to the residual protonated solvents at δ 6.00 and 5.32 for C2D2Cl4, and CD2Cl2, respectively. The concentration of the solutions was 0.06 M. High resolution electrospray ionization mass spectra (HRMS) were obtained on a Micromass LCT time-of-flight (TOF) mass spectrometer equipped with an electrospray ion source. UVâVis data were collected with a Cary 5000 UVâVisâNIR Spectrometer using a 1 cm pathlength quartz cuvette. The compounds analyzed were dissolved in DCM and the spectra were collected in a range of concentrations (from 5 µM to 50 µM). Compound 1 was prepared according to a reported procedure, slightly modified.88 A suspension of 4-hydroxybenzylamine (664 mg, 5.39 mmol) in 20 mL of dry THF was cooled to â78 °C. Triethylamine (0.75 mL, 5.39 mmol) was added to the suspension. A solution of 2,6-pyridinedicarbonyl dichloride (500 mg, 2.45 mmol) in 20 mL of dry THF was added dropwise over 2 h, while keeping the reaction flask at â78 °C. The cooling bath was removed, and the solution was stirred overnight at room temperature. The reaction mixture was then filtered, and the filtrate was concentrated by evaporation under reduced pressure to give 560 mg (1.48 mmol) of 1 as an off-white solid. Yield: 61%. 58 NMR data were consistent with those previously reported.88 Compound 2. Compound 1 (347 mg, 0.99 mmol), K2CO3 (1.37 g, 9.92 mmol) and cis-1,4-dichloro-2-butene (0.10 mL, 1.09 mmol) were heated at reflux in acetonitrile (400 mL) for 120 h. The solution was cooled and filtered in order to remove the K2CO3. The solvent was removed by rotary evaporation to give 300 mg (0.70 mmol) of off-white pure solid. Yield: 71%. Crystals suitable for SCXRD analysis were grown by slow evaporation of a solution of 2 in chloroform. Data for 2. 1H NMR (400 MHz, CDCl3): δ 8.38 (d, 2H, J = 7.61 Hz), 8.08 (t, 1H, J = 7.61 Hz), 7.62 (br m, 2H), 7.18 (d, 4H, J = 8.25 Hz), 6.84 (d, 4H, J = 8.25 Hz), 5.90 (t, 2H, J = 3.17 Hz), 4.77 (d, 4H, J = 3.81 Hz), 4.57 (d, 4H, J = 5.08 Hz). 13C NMR (75 MHz, CDCl3): δ 162.9, 158.0, 148.6, 139.3, 129.4, 129.3, 128.7, 124.9, 115.3, 64.8, 43,3. HRMS (ESI/TOF-Q). Calcd for C25H24N3O4 [2 + H+]: m/z 430.1767. Found: m/z 430.1765. UVâVis [CH2Cl2; λmax, nm (εmax, M-1 cm-1]: 229 (4.8 Ã 104), 276 (1.5 Ã 104). Compound 3. A solution of compound 2 (77 mg, 0.18 mmol) and Pd(OAc)2 (41 mg, 0.18 mmol) in 5 mL of acetonitrile was heated at 50 °C for 2 h, after which the reaction was stirred at room temperature overnight. The product formed as a yellow precipitate. The solution was concentrated to 2.5 mL, and the yellow precipitate was isolated by filtration. The filtrate was left evaporating to give a second batch of product. Yield: 56 mg (0.10 mmol, 54%). Crystals suitable for SCXRD analysis were grown by slow evaporation of a solution of 3 in 1:1 acetonitrile/ethanol. Data for 3. 1H NMR (400 MHz, CDCl3): δ 8.12 (t, 1H, J = 7.61 Hz), 7.84 (d, 2H, J = 7.61 Hz), 7.26 (d, 4H, J = 8.22 Hz), 6.84 (d, 4H, J = 8.68 Hz), 5.75 (br m, 2H), 5.50 (d, 2H, J = 16.50 Hz), 4.93 (dd, 2H, J1 = 14.16 Hz, J2 = 3.88 Hz), 4.62 (d, 2H, J = 13.96 Hz), 3.68 (d, 2H, J = 15.86 Hz), 1.49 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 170.2, 156.7, 153.5, 141.0, 135.3, 128.9, 128.3, 125.0, 115.7, 71.8, 66.1, 64.3, 48.2. HRMS (ESI/TOF-Q). Calcd for C25H22N3O4104Pd [3 â CH3CN 59 + H+]: m/z 532.0641. Found: m/z 532.0646. UVâVis [CH2Cl2; λmax, nm (εmax, M-1 cm-1)]: 229 (3.7 Ã 104), 275 (1.5 Ã 104, 1 shoulder). Compound 3*. Compound 3 (14 mg, 0.02 mmol) was heated in boiling ethanol (5 mL) until the solvent evaporated, yielding a yellow powder that was pure 3* by 1H NMR spectroscopy. Yield: 12 mg (0.01 mmol, 98%). Crystals suitable for SCXRD analysis were grown by vapour diffusion of pentane into a solution of 3* in dichloroethane. Data for 3*. 1H NMR (300 MHz, CD2Cl2): δ 7.72 (m, 2H), 7.36 (m, 1H), 7.34 (d, 2H, J = 8.68 Hz), 7.23 (d, 2H, J = 8.68 Hz), 6.94 (d, 2H, J = 8.68 Hz), 6.52 (d, 2H, J = 8.68 Hz), 5.86 (br m, 2H), 5.77 (dd, 1H, J1 = 7.61 Hz; J2 = 1.27 Hz), 4.98 (m, 3H), 4.76 (d, 1H, J = 15.30 Hz), 4.64 (d, 1H, J = 15.08 Hz), 4.14 (d, 1H, J = 14.85 Hz), 3.41 (d, 1H, J = 15.76 Hz). 13C NMR (100 MHz, CD2Cl2): δ 171.0, 170.3, 158.3, 157.2, 154.2, 152.6, 140.4, 135.2, 131.9, 130.0, 129.2, 128.4, 128.3, 126.6, 126.0, 116.5, 115.9, 66.4, 66.3, 49.4, 46.9. Compound 4. 2,6-Pyridinedicarbonyl dichloride (300 mg, 1.47 mmol) was dissolved in 5 mL of THF, and the solution was cooled to 0 °C. Triethylamine (1.13 mL, 8.08 mmol) was added dropwise, followed by benzylamine (0.35 mL, 3.23 mmol), still dropwise. The solution was stirred at 0 °C for 30 min, then at room temperature overnight. The solution was concentrated by rotary evaporation, extracted with DCM and water (3 x 30 mL), dried over Na2SO4, and evaporated to give 400 mg (1.16 mmol) of a white crystalline solid that was pure by 1H NMR spectroscopy. Yield: 79%. Data for 4. 1H NMR (400 MHz, CD2Cl2): δ 8.35 (d, 2H, J = 7.61 Hz), 8.17 (br t, 2H), 8.04 (t, 1H, 7.61 Hz), 7.30 (m, 10 h), 4.62 (d, 4H, 6.34 Hz). 13C NMR (75 MHz, CD2Cl2): δ 164.0, 149.5, 139.6, 139.0, 129.1, 128.1, 127.9, 125.6, 43.8. HRMS (ESI/TOF-Q). Calcd for C21H20N3O2 [4 + H+]: m/z 346.1556. Found: m/z 346.1563. Elem anal. Calcd for C21H19N3O2: C, 73.03; H, 5.54; 60 N, 12.17. Found: C, 73.11; H, 5.63; N, 12.13. UVâVis [CH2Cl2; λmax, nm (εmax, M-1 cm-1)]: 229 (2.2 Ã 104, 1 shoulder). Compound 5. Compound 4 (97 mg, 0.28 mmol) was stirred with Pd(OAc)2 (63 mg, 0.28 mmol) in 10 mL of acetonitrile at room temperature overnight.142 The precipitate was filtered, washed with cold acetonitrile, and recrystallized from a 1:1 mixture of chloroform and acetonitrile to give 55 mg (0.11 mmol) of yellow crystals. Yield: 40%. Crystals suitable for SCXRD analysis were grown by vapour diffusion of pentane into a solution of 5 in 1:1 acetonitrile/chloroform. Data for 5. 1H NMR (400 MHz, (CD3)2SO): δ 8.23 (t, 1H, J = 7.61 Hz), 7.65 (d, 2H, J = 7.61 Hz), 7.36 (d, 4H, J = 7.61 Hz), 7.29 (m, 4H), 7.18 (t, 2H, J = 6.98 Hz), 4.30 (s, 4H), 2.07 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 170.7, 153.2, 142.0, 141.3, 128.7, 128.3, 127.3, 126.5, 124.0, 50.1, 1.9. HRMS (ESI/TOF-Q). Calcd for C21H18N3O2104Pd [5 â CH3CN + H+]: m/z 448.0439. Found: m/z 448.0435. Elem anal. Calcd for C23H20N4O2Pd: C, 56.24; H, 4.11; N, 11.41. Found: C, 55.52; H, 4.12; N, 10.97. UVâVis [CH2Cl2; λmax, nm (εmax, M-1 cm-1)]: 229 (2.4 Ã 104, 1 shoulder). Compound 5-PPh3. Compound 5 (30 mg, 0.06 mmol) and triphenylphosphine (16 mg, 0.06 mmol) were dissolved in 3 mL of chloroform, and the resulting solution was stirred for 8 h at room temperature. The solution was evaporated to give yellow crystals. Yield: 38 mg (0.05 mmol, 90%). Crystals suitable for SCXRD analysis were grown by vapour diffusion of diethyl ether into a solution of 5-PPh3 in 1:1 acetonitrile/chloroform. Data for 5-PPh3. 1H NMR (400 MHz, CD2Cl2): δ 8.16 (t, 1H, J = 7.61 Hz), 7.88 (d, 2H, J = 7.61 Hz), 7.41 (m, 9H), 7.21 (m, 6H), 7.04 (m, 6H), 6.76 (m, 4H), 3.79 (s, 4H). 13C NMR (75 MHz, CDCl3): δ 173.6, 151.3, 142.1, 141.4, 133.5 (d, J = 11.49 Hz), 131.9 (d, J = 2.30 Hz), 129.3 (d, J = 11.49 Hz), 128.3, 128.1, 126.7, 126.2, 125.4 (d, J = 2.30 Hz), 50.9. HRMS (ESI/TOF-Q). Calcd for C39H33N3O2P104Pd [5-PPh3 + H+]: m/z 710.1351. Found: m/z 710.1354. Elem anal. Calcd 61 for C39H32N3O2P104Pd: C, 65.78; H, 4.49; N, 5.90. Found: C, 64.32; H, 4.39; N, 5.75. UVâVis [CH2Cl2; λmax, nm (εmax, M-1 cm-1)]: 228 (1.1 Ã 105, 2 shoulders). Compound 5-pyr. Compound 5 (30 mg, 0.06 mmol) and pyridine (5.0 µL, 0.06 mmol) were dissolved in 3 mL of chloroform, and the resulting solution was stirred for 30 min. The solution was evaporated to give a yellow solid, which was washed with hexanes. Yield: 30 mg (0.06 mmol, 95%). Crystals suitable for SCXRD analysis were grown by vapour diffusion of diethyl ether into a solution of 5-pyr in 1:1 acetonitrile/chloroform. Data for 5-pyr. 1H NMR (400 MHz, CD2Cl2): δ 8.11 (t, 1H, J = 7.61 Hz), 7.92 (m, 2H), 7.80 (d, 2H, J = 7.61 Hz), 7.26 (m, 1H), 7.06 (m, 6H), 6.97 (m, 2H), 6.81 (m, 4H), 4.19 (s, 4H). 13C NMR (100 MHz, CD2Cl2): δ 171.3, 153.4, 151.7, 141.8, 141.2, 138.7, 128.5, 127.2, 126.5, 125.7, 125.0, 49.1. HRMS (ESI/TOF-Q). Calcd for C26H23N4O2104Pd [5-pyr + H+]: m/z 527.0826. Found: m/z 527.0824. Elem anal. Calcd for C26H22N4O2Pd: C, 59.04; H, 4.19; N, 10.59; Found: C, 58.76; H, 4.04; N, 10.33. UVâVis [CH2Cl2; λmax, nm (εmax, M-1 cm-1)]: 228 (4.1 Ã 104, 2 shoulders). Compound 5-DMAP. Compound 5 (30 mg, 0.06 mmol) and dimethylaminopyridine (7 mg, 0.06 mmol) were dissolved in 3 mL of chloroform, and the resulting solution was stirred for 30 min. The solution was evaporated to give a yellow oil. The oil was recrystallized by slow evaporation from acetone and washed with hexanes to give a yellow solid. Yield: 16 mg (0.03 mmol, 47%). Data for 5-DMAP. 1H NMR (400 MHz, CD2Cl2): δ 8.06 (t, 1H, J = 7.61 Hz), 7.74 (d, 2H, J = 8.25 Hz), 7.52 (d, 2H, J = 7.61 Hz), 7.10 (m, 6H), 6.95 (d, 4H, J = 7.61 Hz), 6.16 (d, 2H, J = 7.61 Hz), 4.19 (s, 4H), 2.99 (s, 6H). 13C NMR (75 MHz, CD2Cl2): δ 171.4, 154.9, 153.6, 150.2, 142.2, 140.9, 128.4, 127.5, 126.4, 124.7, 107.9, 49.3, 39.6. HRMS (ESI/TOF-Q). Calcd for 62 C28H28N5O2104Pd [5-DMAP + H+]: m/z 570.1283. Found: m/z 570.1276. UVâVis [CH2Cl2; λmax, nm (εmax, M-1 cm-1)]: 228 (1.6 Ã 105), 275 (1.8 Ã 105,1 shoulder). Compound 5-quin. Compound 5 (30 mg, 0.06 mmol) and quinoline (7.0 µL, 0.06 mmol) were dissolved in 3 mL of chloroform and stirred for 30 min. The solution was evaporated to give a yellow solid that was recrystallized from a mixture of DCM and hexanes. Yield: 19 mg (0.03 mmol, 56%). Crystals suitable for SCXRD analysis were grown by vapour diffusion of hexanes into a solution of 5-quin in chloroform. Data for 5-quin. 1H NMR (400 MHz, CD2Cl2): δ 8.97 (d, 1H, J = 8.25 Hz), 8.18 (m, 3H), 7.84 (d, 2H, J = 8.25 Hz), 7.81 (d, 1H, J = 7.61 Hz), 7.62 (m, 2H), 6.97 (m, 1H), 6.84 (m, 6H), 6.47 (d, 4H, J = 8.25 Hz), 4.28 (d, 2H, J = 15.23 Hz), 3.72 (d, 2H, J = 15.23 Hz). 13C NMR (75 MHz, CD2Cl2): δ 171.2, 153.6, 153.4, 146.2, 141.4, 141.2, 139.2, 131.8, 129.1, 128.4, 128.35, 128.31, 128.0, 126.7, 126.1, 124.9, 121.7, 49.1. HRMS (ESI/TOF-Q). Calcd for C30H25N4O2104Pd [5-quin + H+]: m/z 577.1018. Found: m/z 577.1021. UVâVis [CH2Cl2; λmax, nm (εmax, M-1 cm-1)]: 230 (9.1 Ã 104), 309 (2.1 Ã 104). Compound 5-acr. Compound 5 (30 mg, 0.06 mmol) and acridine (11 mg, 0.06 mmol) were dissolved in 3 mL of chloroform, and the resulting solution was stirred for 1 h. The solution was evaporated to give a yellow solid that was recrystallized from a mixture of DCM and hexanes. Yield: 20 mg (0.03 mmol, 54%). Crystals suitable for SCXRD analysis were grown by vapour diffusion of hexanes into a solution of 5-acr in chloroform. Data for 5-acr. 1H NMR (400 MHz, CD2Cl2): δ 9.29 (d, 2H, J = 8.88 Hz), 8.90 (s, 1H), 8.19 (t, 1H, J = 7.61 Hz), 7.97 (d, 2H, J = 8.88 Hz), 7.88 (d, 2H, J = 7.61 Hz), 7.67 (m, 2H), 7.54 (t, 2H, J = 7.61 Hz), 6.49 (m, 6H), 6.06 (d, 2H, J = 6.98 Hz), 3.80 (s, 4H). 13C NMR (75 MHz, CDCl3): δ 171.5, 153.7, 148.4, 141.2, 141.1, 141.0, 133.3, 128.5, 127.8, 126.7, 125.1, 49.3. HRMS 63 (ESI/TOF-Q). Calcd for C34H27N4O2104Pd [5-acr + H+]: m/z 627.1174. Found: m/z 627.1180. UVâVis [CH2Cl2; λmax, nm (εmax, M-1 cm-1)]: 228 (4.9 Ã 104), 257 (1.3 Ã 105). Compound 5-lut. Compound 5 (30 mg, 0.06 mmol) and 2,6-lutidine (7.0 µL, 0.06 mmol) were dissolved in 3 mL of chloroform, and the resulting solution was stirred for 8 h. The solution was evaporated to give a yellow solid that was washed with hexanes. Yield: 32 mg (0.06 mmol, 97%). Crystals suitable for SCXRD analysis were grown by vapour diffusion of diethyl ether into a solution of 5-lut in 1:1 acetonitrile/chloroform. Data for 5-lut. 1H NMR (400 MHz, CD2Cl2): δ 8.11 (t, 1H, J = 7.61 Hz), 7.80 (d, 2H, J = 8.25 Hz), 7.64 (t, 1H, J = 8.25 Hz), 7.10 (t, 2H, J = 6.98 Hz), 7.03 (t, 4H, J = 7.61 Hz), 6.95 (d, 2H, J = 7.61 Hz), 6.59 (d, 4H, J = 6.98 Hz), 4.03 (s, 4H), 2.41 (s, 6H). 13C NMR (75 MHz, CD2Cl2): δ 171.5, 160.7, 153.4, 141.8, 141.2, 139.5, 128.6, 127.9, 126.9, 125.1, 123.4, 49.7, 25.8. HRMS (ESI/TOF-Q). Calcd for C28H27N4O2104Pd [5-lut + H+]: m/z 555.1174. Found: m/z 555.1176. Elem anal. Calcd for C26H22N4O2Pd: C, 60.38; H, 4.71; N, 10.06. Found: C, 59.83; H, 4.62; N, 9.75. UVâVis [CH2Cl2; λmax, nm (εmax, M-1 cm-1)]: 229 (5.7 Ã 104, 1 shoulder), 314 (1.1 Ã 104). Compound 3-PPh3. Compound 3 (33 mg, 0.06 mmol) and triphenylphosphine (15 mg, 0.06 mmol) were dissolved in 5 mL of DCM, and the resulting solution was stirred for 24 h. The solution was concentrated under reduced pressure and purified by flash chromatography with an alumina column [eluent, 1% methanol (MeOH) in DCM, Rf = 0.22] to give the product as a yellow solid. Yield: 42 mg (0.01 mmol, 92%). Data for 3-PPh3. 1H NMR (400 MHz, CD2Cl2): δ 8.22 (t, 1H, J = 7.61 Hz), 7.96 (d, 2H, J = 6.61 Hz), 7.40 (t, 3H, J = 6.34 Hz), 7.23 (t, 6H, J = 7.61 Hz), 7.06 (m, 6H), 6.82 (d, 4H, J = 8.88 Hz), 6.71 (d, 4H, J = 8.88 Hz) 5.81 (d, 2H, J = 5.71 Hz), 5.02 (m, 4H), 4.60 (d, 2H, J = 14.59 Hz), 2.54 (d, 2H, J = 15.86 Hz). 13C NMR (100 MHz, CD2Cl2): δ 173.6, 157.0, 152.2, 141.9, 134.6, 64 134.5 (d, J = 2.20 Hz), 132.5 (d, J = 9.54 Hz), 131.7 (d, J = 2.20 Hz), 130.4, 129.3 (d, J = 10.27 Hz), 127.6, 125.6, 116.1, 65.5, 48.3. HRMS (ESI/TOF-Q). Calcd for C43H37N3O4P104Pd [3-PPh3 + H+]: m/z 795.1562. Found: 794.1556. UVâVis [CH2Cl2; λmax, nm (εmax, M-1 cm-1)]: 232 (7.7 Ã 104, 2 shoulders). Compound 3-pyr. Compound 3 (33 mg, 0.06 mmol) and pyridine (4.7 µL, 0.06 mmol) were dissolved in 5 mL of DCM, and the resulting solution was stirred overnight. The solution was concentrated under reduced pressure and washed with hexanes (5 mL x 3) to give the product as yellow oil. Yield: 27 mg (0.04 mmol, 77%). Data for 3-pyr. 1H NMR (400 MHz, C2D2Cl4, 113 °C): δ 8.14 (t, 1H, J = 8.05 Hz), 7.89 (d, 2H, J = 7.68 Hz), 7.55 (t, 1H, J = 7.68 Hz), 7.16 (br, 1H), 6.95 (d, 4H, J = 8.42 Hz), 6.87 (d, 2H, J = 6.95 Hz), 6.83 (d, 4H, J = 8.78 Hz), 5.91 (t, 2H, J = 1.83 Hz), 5.43 (d, 2H, J = 15.73 Hz), 4.94 (dd, 2H, J1 = 13.90 Hz, J2 = 4.03 Hz), 4.68 (d, 2H, J = 13.54 Hz), 3.06 (d, 2H, J = 15.73 Hz). 13C NMR (100 MHz, CD2Cl2): δ 171.1, 157.5, 153.8, 141.2, 137.8, 135.8, 130.3, 128.3, 125.1, 124.9, 118.0, 67.5, 47.5. HRMS (ESI/TOF-Q). Calcd for C30H27N4O4105Pd [3-pyr + H+]: m/z 612.1083. Found: m/z 612.1091. UVâVis [CH2Cl2; λmax, nm (εmax, M-1 cm-1)]: 231 (1.7 Ã 104, 2 shoulders). Compound 3-DMAP. Compound 3 (30 mg, 0.05 mmol) and DMAP (6 mg, 0.05 mmol) were dissolved in 5 mL of chloroform, and the resulting solution was stirred for 2 h. The solution was concentrated under reduced pressure and purified by flash chromatography with an alumina column (eluent, 2% MeOH in DCM, Rf = 0.35) to give the product as yellow oil. Yield: 18 mg (0.03 mmol, 54%). Data for 3-DMAP. 1H NMR (400 MHz, C2D2Cl4, 113 °C): δ 8.11 (t, 1H, J = 7.92 Hz), 7.87 (d, 2H, J = 7.61 Hz), 7.03 (d, 4H, J = 8.53 Hz), 6.83 (d, 4H, J = 8.53 Hz), 6.67 (d, 2H, J = 65 5.79 Hz), 5.95 (d, 2H, J = 7.01 Hz), 5.88 (t, 2H, J = 2.44 Hz), 5.42 (d, 2H, J = 15.53 Hz), 4.94 (dd, 2H, J1 = 13.71 Hz, J2 = 4.26 Hz), 4.68 (d, 2H, J = 13.10 Hz), 3.16 (d, 2H, J = 15.53 Hz). 13C NMR (100 MHz, CD2Cl2): δ 171.1, 157.4, 154.1, 154.0, 140.9, 136.1, 130.3, 128.3, 124.9, 117.9, 107.0, 67.5, 47.4, 39.4. HRMS (ESI/TOF-Q). Calcd for C32H32N5O4104Pd [3-DMAP + H+]: m/z 654.1495. Found: m/z 654.1505. UVâVis [CH2Cl2; λmax, nm (εmax, M-1 cm-1)]: 230 (6.2 Ã 104), 275 (6.6 Ã 104, 1 shoulder). Compound 3-quin. A solution of compound 3 (32 mg, 0.06 mmol) and quinoline (6.8 µL, 0.06 mmol) was stirred in 5 mL of DCM for 4 d. The solvent was evaporated under reduced pressure to give a yellow solid that was purified by flash chromatography on alumina (eluent, 1% MeOH in DCM, Rf = 0.22). The product is a yellow solid. Yield: 28 mg (0.04 mmol, 75%). Crystals suitable for SCXRD analysis were grown by slow evaporation of a solution of 3-quin in DCM. Data for 3-quin. 1H NMR (400 MHz, CD2Cl2): δ 9.63 (d, 1H, J = 8.88 Hz), 8.20 (t, 1H, J = 7.61 Hz), 8.00 (d, 1H, J = 8.25 Hz), 7.89 (m, 4H), 7.69 (t, 1H, J = 6.98 Hz), 6.79 (m, 8H), 6.38 (dd, 1H, J1 = 8.25 Hz, J2 = 5.08 Hz), 5.92 (m, 2H), 5.78 (dd, 1H, J1 = 5.08 Hz, j2 = 1.27 Hz), 5.18 (d, 2H, J = 15.23 Hz) 4.95 (dd, 2H, J1 = 13.32 Hz, J2 = 5.08 Hz), 4.67 (d, 2H, J = 14.59 Hz), 2.67 (d, 2H, J = 15.86 Hz), 2.99 (s, 6H).13C NMR (100 MHz, CD2Cl2): δ 171.2, 157.7, 155.0, 153.9, 146.0, 141.3, 137.9, 136.1, 132.0, 130.4, 129.1, 128.9. 128.4, 128.3, 128.1, 125.2, 121.6, 118.1, 67.7, 47.6. HRMS (ESI/TOF-Q). Calcd for C34H29N4O4104Pd [3-quin + H+]: m/z 661.1229. Found: m/z 661.1250. UVâVis [CH2Cl2; λmax, nm (εmax, M-1 cm-1)]: 230 (1.5 Ã 105, 2 shoulders). Compound 3-acr. A solution of compound 3 (33 mg, 0.06 mmol) and acridine (10 mg, 0.06 mmol) was stirred in 5 mL of chloroform overnight, after which the solvent was evaporated under reduced pressure to give a yellow solid. The compound was purified by flash chromatography using alumina. The initial eluent was DCM. When all the acridine was removed 66 the eluent was changed to 2% methanol in DCM (Rf = 0.36). Yield 39 mg (0.05 mmol, 95%). Crystals suitable for SCXRD analysis were grown by slow evaporation of a solution of 3-acr in DCM in an NMR tube. Data for 3-acr. 1H NMR (400 MHz, CD2Cl2): δ 10. 35 (d, 1H, J = 10.15 Hz), 8.97 (s, 1H), 8.26 (t, 1H, J = 8.25 Hz), 8.12 (d, 1H, J = 7.61 Hz), 8.03 (td, 1H, J1= 8.25 Hz, J2 = 1.27 Hz), 7.95 (d, 2H, J = 7.61 Hz), 7.83 (d, 1H, J = 8.88 Hz), 7.70 (td, 1H, J1 = 8.25 Hz, J2 = 1.27 Hz), 7.17 (t, 1H, J = 6.98 Hz), 6.74 (d, 1H, J = 9.52 Hz), 6.66 (d, 4H, J = 8.88 Hz), 6.57 (d, 4H, J = 8.25 Hz), 6.45 (td, 1H, J1 = 8.25 Hz, J2 = 1.27 Hz), 5.59 (d, 2H, J = 7.61 Hz), 5.13 (dd, 2H, J1 = 8.25 Hz, J2 = 1.90 Hz), 4.91 (d, 2H, J = 15.23 Hz), 4.65 (d, 2H, J = 13.32 Hz), 2.29 (d, 2H, J = 15.23 Hz). 13C NMR (100 MHz, CD2Cl2): δ 171.9, 158.3, 153.9, 149.2, 148.2, 141.4, 141.2, 134.9, 133.5, 131.9, 130.4, 129.5, 128.8, 128.2, 128.0, 127.7, 127.3, 127.0, 126.7, 126.0, 125.5, 117.1, 66.8, 48.1. HRMS (ESI/TOF-Q). Calcd for C38H31N4O4104Pd [3-acr + H+]: m/z 711.1386; Found: m/z 711.1378. UVâVis [CH2Cl2; λmax, nm (εmax, M-1 cm-1)]: 230 (1.1 Ã 105), 253 (1.8 Ã 105), 257(1.8 Ã 105), 360 (2.6 Ã 104). Compound 3-lut. A solution of compound 3 (30 mg, 0.05 mmol) and 2,6-lutidine (6.0 µL, 0.05 mmol) was stirred in 3 mL of chloroform for 24 h, after which the solvent was evaporated under reduced pressure to give a yellow solid that was washed with hexanes (5 mL x 3). Yield: 25 mg (0.04 mmol, 75%). Data for 3-lut. 1H NMR (400 MHz, CD2Cl2): δ 8.14 (t, 1H, J = 8.25 Hz), 7.83 (d, 2H, J = 7.61 Hz), 7.59 (t, 1H, J = 7.61 Hz), 7.15 (d, 1H, J = 7.61 Hz), 6.82 (d, 4H, J = 8.88 Hz), 6.72 (d, 4H, J = 8.25 Hz), 6.62 (d, 1H, J = 7.61 Hz), 5.70 (m, 2H), 5.25 (d, 2H, J = 15.23 Hz), 4.57 (m, 4H), 3.27 (s, 3H), 2.62 (d, 2H, J = 14.59 Hz), 0.32 (s, 3H). 13C NMR (100 MHz, CD2Cl2): δ 171.8, 163.6, 159.5, 158.9, 153.5, 141.2, 139.3, 137.3, 130.7, 129.4, 125.3, 123.0, 122.8, 121.2, 70.5, 67 48.5, 26.8, 23.5. HRMS (ESI/TOF-Q). Calcd for C32H31N4O4104Pd [3-lut + H+]: m/z 639.1386. Found: m/z 639.1375. UVâVis [CH2Cl2; λmax, nm (εmax, M-1 cm-1)]: 230 (3.5 Ã 104), 272 (1.5 Ã 104, 1 shoulder). Single-crystal X-ray diffraction. SCXRD raw data were collected on a Bruker APEX DUO diffractometer using graphite-monochromated Mo Kα radiation (λ = 0.71073) at 90 K, and processed using APEX2.143 Data were collected to a resolution of 0.77 Ã , with the exception of 5-acr (0.65 Ã ) and 5-lut (0.59 Ã ). Compound 3â structure was solved using SHELXS 86,144 and compound 5-lutâs structure was solved using SIR 92.145 All the other structures were solved using SUPERFLIP146 and refined using full-matrix least-squares on F2 within the CRYSTALS147 suite. Hydrogen atoms were initially refined with restraints on bond lengths and angles, after which the positions were used as the basis for a riding model.148 All non-hydrogen atoms were refined anisotropically. In case of strongly disordered solvent molecules PLATON/SQUEEZE149 was used. A summary of the crystallographic data is reported in Table 2.3 and Table 2.4. 68 Table 2.3. Summary of crystallographic data for compound 5, 5-pyr, 5-PPh3, 5-quin, 5-acr and 5-lut. Compound 5 5-pyr 5-PPh3 5-quin 5-acr 5-lut Chemical formula 2(C23H20N4 O2Pd), H2O C26H22N4 O2Pd C39H32N3O2PPd 2(C30H23N4 O2Pd), 2(C30H24N4O2Pd), H2O C34H26N4O2Pd, 0.089(CHCl3), 0.911(C2H3N) C28H26N4O2Pd Formula weight 999.68 528.88 712.08 2331.71 677.00 556.94 a (Ã ) 14.3825(19) 25.4603(15) 9.2672(5) 12.674(4) 14.730(3) 8.9411(15) b (Ã ) 46.210(7) 25.4603(15) 9.7906(5) 14.551(4) 11.218(2) 16.237(3) c (Ã ) 12.4515(17) 14.1760(9) 18.6931(10) 16.437(4) 18.101(4) 16.329(3) ! (°) 90 90 98.2124(11) 115.679(4) 90 90 β (°) 90 90 96.8657(11) 99.791(4) 98.814(4) 90 γ (°) 90 90 105.7061(10) 100.050(4) 90 90 Unit cell volume (Ã 3) 8276(2) 9189.3(10) 1593.55(15) 2584.7(12) 2955.7(10) 2370.6(7) Temperature (K) 90 90 90 90 90 90 Crystal system orthorhombic tetragonal triclinic triclinic monoclinic orthorhombic Space group F d d 2 I 41/a P -1 P -1 P 21/n P212121 Z 8 16 2 1 4 4 69 Compound 5 5-pyr 5-PPh3 5-quin 5-acr 5-lut Absorption coefficient (µ/mm-1) 0.927 0.839 0.673 0.754 0.695 0.817 Total number of reflections 22394 33698 17510 24103 50237 33605 Unique reflections 4798 5284 7245 11716 11267 5495 Final R1 values (I > 2"(I)) 0.0317 0.0247 0.0200 0.0888 0.0418 0.0188 Final wR(F2) values (all data) 0.0420 0.0590 0.0495 0.2440 0.1064 0.0449 70 Table 2.4. Summary of crystallographic data for compound 2, 3, 3*, 3-quin and 3-acr. Compound 2 3 3* 3-quin 3-acr Chemical formula 2(C25H23N3O4) 2(C27H24N4O4Pd), H2O C100H84N12O16Pd4, 0.5(C2H4Cl2), H2O C34H28N4O4Pd, 2(CCl2H2), H2O C38H30N4O4Pd CH2Cl2 Formula weight 858.95 1167.82 2202.94 850.90 798.01 a (Ã ) 19.7331(15) 9.5722(18) 24.806(7) 9.7749(5) 12.7549(11) b (Ã ) 11.1407(8) 9.2696(17) 13.731(4) 12.9004(8) 9.9880(9) c (Ã ) 9.6584(7) 27.630(5) 29.422(11) 15.7518(10) 26.800(2) ! (°) 90 90 90 70.3583(15) 90 β (°) 100.1979(18) 99.893(4) 114.929(6) 73.8200(14) 95.8221(17) γ (°) 90 90 90 87.0480(15) 90 Unit cell volume (Ã 3) 2089.8(3) 2415.2(8) 9088(5) 1794.68(19) 3396.6(5) Temperature (K) 90 90 90 90 90 Crystal system monoclinic monoclinic monoclinic triclinic monoclinic Space group P21/c P21/c P 2/c P-1 P 21/c 71 Compound 2 3 3* 3-quin 3-acr Z 2 2 4 2 4 Absorption coefficient (µ/mm-1) 0.094 0.813 0.886 0.863 0.753 Total number of reflections 14008 5817 59101 33129 36930 Unique reflections 6690 5817 9591 14192 7799 Final R1 values (I > 2"(I)) 0.0649 0.0419 0.1301 0.0411 0.0308 Final wR(F2) values (all data) 0.1666 0.0614 0.2890 0.1037 0.0749 72 Chapter 3:! Ligand exchange driven ROMP 3.1.! Introduction As discussed in chapter 1, ring-opening metathesis polymerization (ROMP) reactions have been widely used for the polymerization of strained monomers.109,112 The fast initiation rates and the low polydispersity of the products make ROMP reactions a valuable tool for the synthesis of diverse polymeric materials and metallopolymers. Metallopolymers can be formed by ROMP of a strained molecule, such as norbornene, that is functionalized with a metal-containing group (e.g., ferrocene).150â153 However strained metallated cyclic monomers can also be polymerized by ROMP, forming metallopolymers with the metal in the backbone; polymers prepared in this way include poly(ferrocenylenedivinylene) and poly(ferrocenylenebutenylene).113 The driving force for the majority of ROMP reactions is the release of ring strain in the monomer, with reports of metathesis polymerizations performed on unstrained substrates being exceedingly rare.117â119 The reason behind the lack of unstrained monomers being employed in ROMP has to do with the metathesis reaction mechanism. Metathesis reactions involve activation of the olefin bond, however, the reverse reaction, which reforms the ring-closed olefin and releases the polymerization catalyst, can also occur. In fact, the reverse reaction is the basis of ring-closing metathesis (RCM) where unstrained rings are produced with an olefin metathesis catalyst.154,155 RCM is usually not stereospecific and, therefore, if the terminal alkenes have different substituent groups, both the E and Z isomers can be formed.156,157 Their ratio depends on the catalyst used and on the strain of the macrocycle formed.158,159 ROMP on unstrained substrates is usually referred to as entropically driven ROMP (ED-ROMP).115 It has been performed on macrocyclic esters with up to 34 ring atoms114 and cyclic bile acids of 38-units and 25-units.116 These reactions require high concentrations (0.1â1 M). 73 In this chapter, we demonstrate a new concept for supramolecular polymerization and show how it can be used to ring-expand an unstrained metal-containing macrocycle. Through a supramolecular interaction (ligand binding) with the ring-opened form of the unstrained monomer, we prevent ring-closure and make the ring-opening step irreversible (Figure 3.1). This new concept of using supramolecular interactions with a polymer to prevent the ring-closing step offers an intriguing driving force for polymerization and ring-expansion. Some of the palladium-containing macrocycles presented in Chapter 2 will be used for the ring-expansion and polymerization reactions. Ligand exchange between acetonitrile and bulkier ligands (e.g. PPh3 and 2,6-lutidine) on the palladium will be employed as driving force. Figure 3.1 Schematic representation of the approach used to polymerize an unstrained metal-containing macrocycle (represented in blue) using ligand coordination (ligand is represented in pink). In Chapter 2 it was discussed how the cavity in these complexes does not surround the ligands in the same plane as the pincer ligand but bends away to accommodate bulky guests at the metal center. In addition, ligand exchange studies demonstrated that macrocyclization is a way to Supramolecular++transformation:+Interaction+with+bulky+ligand+L+Unstrained+Metal=containing+macrocycle+Stabilization+of+the+open+form:++ring=closing+step+becomes+irreversible+Grubbs+L+L+L+Pd+Pd+Pd+74 control the exchange rate between acetonitrile and bulky ligands, in the cases where the ligandâs bulky groups are close to the metal center.160 As a consequence, the exchange of small ligands, like pyridine, with acetonitrile is not affected by the cavity; this is also true for the exchange of ligands that have bulky groups far from the metal center, such as PPh3. These complexes are expected to ring-close, and here we show that ring-closing is stereospecific when PPh3 is employed. In the contrast, the exchange of ligands like 2,6-lutidine, with two methyl groups in ortho position, is strongly impeded by the macrocycle and ring-closing is anticipated to be prevented. 3.2.! Results and discussion The macrocycles used for the ring-expansion and polymerization reactions are reported in Figure 3.2a. Compound 2 does not coordinate to palladium and compound 3 contains acetonitrile coordinated to palladium. These two macrocycles are not strained and are not expected to ring-expand or to form polymers and therefore, they were used in control reactions. The other two macrocyclic complexes studied (3-PPh3, 3-lut) contain two ligands of different sizes. PPh3 is a large ligand compared to the estimated size of the macrocyclic cavity (26.5 Ã 3)160, but the bulky phenyl groups are far from the metal center. 2,6-Lutidine is a smaller ligand but the bulky methyl groups are located close to the palladium center. 75 Figure 3.2 (a) Palladium-containing macrocycles used for ring-expansion and polymerization reactions. (b) Second generation Grubbs catalyst. The reactions reported in this chapter were all performed by adding 5 mol% of second generation Grubbs catalyst (Figure 3.2b) to 12 mM solutions of the monomer in dry THF at 55 °C. All the reactions were stirred for 2 h under N2 atmosphere and then quenched with ethyl vinyl ether (Scheme 3.1). Other types of catalysts were used for some of the reactions (third generation Grubbs catalyst and second generation Hoveyda-Grubbs) but no significant difference was observed when compared to the second generation Grubbs catalyst. Therefore, the systematic study described in this chapter was performed with the second generation Grubbs catalyst. 76 Scheme 3.1 Reaction scheme for the polymerization reactions (L = generic bulky ligand). 3.2.1! Control experiments on compounds 2 and 3 As anticipated, the reaction of compound 2 with Grubbs catalyst gave back compound 2 as the main product (yield: 70%). However, the 1H NMR spectrum of the crude reaction mixture (Figure 3.3b) reveals the presence of another set of peaks (represented by the blue circles), with a down field vinyl proton. A 1H DOSY NMR experiment was performed on the crude product to investigate whether the new set of peaks corresponded to the trans isomer of compound 2, which would form if the macrocycle ring-opens and closes back again, or a higher molecular weight compound. The 1H DOSY NMR experiment showed that the two species have the same diffusion coefficient (7.9 Ã 10-6 cm2/s), and are therefore the same size (Figure 3.4). It can be concluded that compound 2 ring-opens and closes again, forming some of the trans isomer during the reaction (with the vinyl peak shifted downfield), and the ratio between cis and trans, calculated from the vinyl peakâs integrals is ca. 2:1. 77 Figure 3.3 Stacked 1H NMR (400 MHz, CDCl3) spectra of: (a) pure compound 2; (b) polymerization reaction crude product. The peaks marked in blue correspond to the trans isomer of compound 2. Residual solvents peaks are indicated with *. 78 Figure 3.4 1H DOSY NMR (400 MHz, CDCl3) experiment on compound 2. The reaction of compound 3 with Grubbs catalyst afforded the starting material 3 as a precipitate (58%) that was filtered and washed with hexanes. Characterization of the filtrate solution by 1H NMR showed that it contains mainly compound 3, together with a new set of peaks (Figure 3.5c). Characterization of the crude filtrate by 1H DOSY NMR experiment showed that once again, all the species present have the same diffusion coefficient (1.4 Ã 10-5 cm2/s), so the same size (Figure 3.6). Therefore it can be concluded that the new compound detected is the trans isomer of compound 3. 79 Both the control experiments showed that, in the absence of a bulky ligand, the ring-closing step could not be prevented, and the product was a mixture of cis and trans isomers. This was what is expected when two terminal alkenes are reacted to form unstrained macrocycles by RCM, using the second generation Grubbs catalyst. Figure 3.5 1H NMR (400 MHz, CDCl3) spectra of: (a) pure compound 3; (b) precipitate obtained from the polymerization reaction; (c) crude filtrate. The spectrum of the precipitate completely overlaps with the starting material 3. The crude filtrate is mostly compound 3, but some other side product (blue circles) is present. Residual solvents peaks are indicated with *. 80 Figure 3.6 1H DOSY NMR (400 MHz, CDCl3) experiment on compound 3. 3.2.2! Experiment on compound 3-PPh3 When compound 3-PPh3 was reacted with the second-Grubbs catalyst, no broad peaks (usually indication of high molecular weight species) appeared in the 1H NMR spectrum. However, the 1H NMR spectrum of the crude product was significantly different to that of the starting material (Figure 3.7). The PPh3 phenyl peaks (6.96, 7.22 and 7.43 ppm) were broader and the vinyl peak was shifted downfield (from 5.81 to 5.98 ppm). Additionally no trace of starting material was detected. 81 Figure 3.7 1H NMR (400 MHz, CD2Cl2) of compounds: (a) 3-PPh3; (b) crude reaction mixture. Residual solvent peaks are indicated with *. To investigate the formation of this new compound, we performed the reaction in an NMR tube with a J Young valve in deuterated THF and tracked it by 1H NMR spectroscopy at 50 °C. Already, after 5 min from the addition of the Grubbs catalyst, all of the starting material had reacted (Figure 3.8). The vinyl peak at 5.79 ppm for 3-PPh3 disappeared and a new vinyl peak appeared at 6.00 ppm. The aromatic region also changed significantly, with the PPh3 proton signals appearing broader and the pincer ligandâs phenyl protons shifted upfield. The reaction was monitored for 2.5 h but no further significant changes were observed. Most of the peaks in the 1H NMR remained sharp, indicating that no high molecular weight species were formed. 82 Figure 3.8 Polymerization reaction on 3-PPh3 monitored by 1H NMR spectroscopy (400 MHz, THF-d8, 50 °C). Residual solvent peaks are indicated with *. The crude reaction mixture was washed with hexanes and a single crystal was grown by vapour diffusion of hexanes into a DCM solution of the product. The crystal structure revealed that the reaction product was the trans isomer of the palladium-containing metallomacrocycle (Figure 3.9). This result proved that compound 3-PPh3 was successfully ring-opened, but subsequently closed back and formed exclusively the trans isomer. In contrast, compounds 2 and 3 produced a mixture of cis and trans isomers when ring-closed. This showed that exchange with PPh3 can be used in RCM to control the stereochemistry of the products and to convert a cis macrocyclic alkene entirely into a trans macrocyclic alkene. The stereospecificity of this reaction is due to the bulky PPh3 groups, which direct ring-closure exclusively toward the formation of the trans alkene. 83 Figure 3.9 SCXRD structure of compound 3-PPh3-trans: (a) side view; (b) front view (PPh3 in white to show the trans stereochemistry of the alkene). A single crystal of compound 3-PPh3 (cis stereochemistry) was grown by vapour diffusion of hexane into a dichloromethane solution of 3-PPh3. Figure 3.10 shows the molecular structure obtained, that can be compared with the one obtained for 3-PPh3-trans (Figure 3.9) It can be noted that there is almost no difference between the cis and trans isomers, as in both structures the PPh3 bends out of the square planar palladium-pincer ligand plane by a 13° angle. The bridging chain bends to 111° and 112° angles for the cis and for the trans isomer, respectively. The similarity between the two crystal structures suggests that the strain generated by the presence of the PPh3 in the macrocycle cavity is comparable for the two complexes. 84 Figure 3.10 SCXRD structure of compound 3-PPh3 (a) side view; (b) front view (PPh3 in white to show the cis stereochemistry of the alkene). Compounds 3 and 3-PPh3, both cis stereoisomers, showed a different reactivity with the second generation Grubbs catalyst. Compound 3 produced a mixture of cis and trans isomers, while compound 3-PPh3 converted entirely into the trans isomer, 3-PPh3-trans. However, the similarity between 3-PPh3 and 3-PPh3-transâs crystal structures suggests a not significant strain difference between the two complexes. In order to elucidate the causes of the difference in reactivity between 3 and 3-PPh3, geometry optimization calculations were performed on both the complexes with acetonitrile (3 and 3-trans) and with PPh3 (3-PPh3 and 3-Ph3-trans) and the relative thermodynamic stabilities of the cis and trans isomers were calculated. The crystal structures obtained for compounds 3-PPh3, 3 and 3-PPh3-trans provided the initial coordinates for the geometry optimization calculations (Figure 3.11). Regarding the cis stereochemistry, two different isomers are possible: the cis isomer obtained from compound 3-PPh3âs crystal structure, a b85 in which the vinyl hydrogen atoms are pointing inside the cavity (Figure 3.11a) and the cis2 obtained from compound 3 (Figure 3.11b), with the vinyl hydrogen atoms pointing outside the cavity. Both isomers were used as starting geometries for the calculations performed on both compounds 3-PPh3 and 3, substituting the PPh3 with acetonitrile for cis and the acetonitrile with PPh3 for cis2. Regarding the trans isomer, the crystal structure obtained for 3-PPh3-trans provided the initial coordinates for the geometry optimization on both complexes 3-PPh3-trans and 3-trans (Figure 3.11c). For compound 3-trans an acetonitrile molecule substituted the PPh3 molecule. Figure 3.11 Initial geometries (bottom view) used for the geometry optimization calculations performed on 3-PPh3 and 3-PPh3-trans. Analogous geometries were used for compounds 3 and 3-trans. (a) 3-PPh3 cis geometry obtained from the crystal structure of 3-PPh3. (b) 3-PPh3 cis2 geometry obtained from the crystal structure of compound 3, substituting the acetonitrile ligand with PPh3. (c) 3-PPh3-trans geometry obtained from the crystal structure of compound 3-PPh3-trans. 86 The energy differences obtained by geometry optimization DFT calculations with wB97xd functional in DCM are reported in Table 3.1. For compound 3 the cis2 isomer is more stable than the cis by 0.00180218 hartree (1.1 kcal/mol). For compound 3-PPh3 the difference in energy between cis and cis2 is very small (0.2 kcal/mol). Both cis and cis2 isomers are less stable than the trans isomer by 2.7 kcal/mol for 3 and 4.8 kcal/mol for 3-PPh3. The energy differences calculated using other functionals (M06 vs. wB97xD) are not significantly different, as well as the results obtained in CH3CN for compound 3. Further description of the computational calculationsâ methods and results is reported in the experimental section. Table 3.1 Summary of geometry optimization calculations results by DFT (wB97xd) in DCM. Compound (stereoisomer) Energya (Hartree) ÎE (Ecis - Etrans) (Hartree) ÎE (Ecis - Etrans) (kcal/mol) 3 (cis2) -1690.29745916 0.00436452 2.7 3 (cis) -1690.29565698 0.00616670 3.9 3 (trans) -1690.30182368 3-PPh3 (cis2) -2593.66165985 0.00798870 5.0 3-PPh3 (cis) -2593.66191861 0.00772994 4.8 (4.5)b 3-PPh3 (trans) -2593.66964855 aThe wB97xd functional was used in conjunction with the 6-31g(d)161 basis set. For the palladium atom, fully relativistic ECP (energy consistent pseudopotential) with small core and cc-pDZP162 basis set were used. All calculations were carried out using the Gaussian 19 (rev. B.01)163 suite. b Calculations including the harmonic zero-point energy (ZPE) corrections. 87 The large energy difference between 3-PPh3-trans and 3-PPh3 (4.8 kcal/mol) proves that the trans isomer is significantly more stable than the cis isomer, suggesting that after interaction with the Grubbs catalyst, the cyclic intermediate would rearrange exclusively to the more stable isomer, 3-PPh3-trans. However, calculations on compound 3-trans show that it is more stable than 3 by 2.7 kcal/mol. This difference in energy is smaller than the one obtained for 3-PPh3, but not negligible. The reaction of Grubbs catalyst with compound 3, however, produced a mixture of cis/trans (84:16 from the respective 1H NMR peaks integration) isomers. This suggests that the relative thermodynamic stability of the two possible reaction products is not the only factor that determines the reaction outcome.164 The PPh3 influences the squared cyclic intermediate rearrangement and favours the trans orientation, while the CH3CN is not bulky enough to have a significant impact. 3.2.3! Experiment on compound 3-lut Among the ligands discussed in Chapter 2, 2,6-lutidine had the slowest exchange with acetonitrile, therefore we expected compound 3-lut to be the most reactive toward ROMP. The reaction of 3-lut with the second generation Grubbs catalyst in THF was monitored by 1H NMR spectroscopy and dynamic light scattering (DLS). Figure 3.12 shows the reaction monitored by 1H NMR in the 4.30â6.50 ppm spectral region, which is the one that undergoes the biggest changes. The full monitored reaction is reported in Appendix B (Figure B-1). Already after 5 min from the addition of the Grubbs catalyst no 3-lut was detected, as the vinyl peak at 5.72 ppm disappeared and a new vinyl peak appeared downfield at 6.01 ppm, suggesting the formation of a new compound. This is consistent with what was previously observed for 3-PPh3. A new sharp peak also appeared at 4.42 ppm. As the reaction proceeded the 1H NMR signals became broader. After 30 min the vinyl peak at 6.01 ppm was 88 significantly reduced and two new peaks appeared: a broad peak at 6.39 ppm and a sharp peak at 6.33 ppm. The sharp peak at 4.42 ppm was also significantly reduced. This suggests that an intermediate was formed during the reaction and was then consumed, leading to the formation of two main products. After 1 h and 40 min, no signal at 6.01 and 4.42 ppm was detected, and no changes in the 1H NMR spectrum were observed after that. Figure 3.12 Polymerization reaction on 3-lut monitored by 1H NMR (400 MHz, THF-d8, 50 °C) in the spectral region from 4.30 to 6.50 ppm. The reaction was quenched after 2 h and two main products were isolated from the crude reaction mixture: a scarcely soluble precipitate that presented broad 1H NMR peaks, 3-lut-prec (38% yield), and a compound that presented sharp signals, 6 (20% yield), as shown on Figure 3.13. The 1H NMR spectra of both products show one singlet peak corresponding to the 2,6-lutidineâs methyl groups: at 2.47 ppm for 3-lut-prec and at 2.35 ppm for 6. This indicates free rotation of 2,6-lutidine along the PdâN axis. In the starting material 3-lut the rotation of 2,6-lutidine is blocked by the metallomacrocycleâs bridging chain and the methyl groups appear at two different chemical 89 shifts. One methyl group points inside the macrocyclic cavity and is deshielded by the phenylsâ ring currents at 0.32 ppm, while the other methyl group points far from the cavity and the 1H NMR signal appears at 3.27 ppm. When compound 3-lut ring-opens, the two methyl signals coalesce into one peak. The scarce solubility of 3-lut-prec and the broadness of both its 1H and 13C NMRs (Figure B-2) suggest that it could be a high molecular weight species. Figure 3.13 1H NMR (400 MHz, CDCl3) of compounds: (a) 3-lut; (b) 3-lut-prec; (c) 6. Residual solvent peaks are indicated with *. Since NMR data suggests that one of the compounds isolated, 3-lut-prec, is likely to be a high molecular weight product, DLS was used to monitor the formation of molecules with a bigger 90 hydrodynamic radius (RH) than the starting material. A DLS experiment was first performed on a 12 mM solution of pure 3-lut in THF at 50 °C. No particles were observed for this compound within the detection limits of the instrument (0.3â10,000 nm). The second generation Grubbs catalyst was then added and data were collected every 5 min. Immediately after the addition of the Grubbs catalyst, a monomodal distribution was observed (Figure 3.14a). The RH measured for this new species was 128 nm (Figure 3.14b). After 1 h and 55 min a new species was detected (Figure 3.14c), with RH of 413 nm, which continued to increase in size until it reached its maximum RH of 848 nm after 2 h and 15 minutes (Figure 3.14d). The distribution was bimodal, indicating that two main components with a bigger RH than the starting material were present. This result is consistent with the fact that two reaction products were isolated from the crude reaction mixture. The scarcely soluble product that presented broad 1H NMR signals, 3-lut-prec, probably corresponds to the highest RH (848 nm) observed in the DLS, while the soluble product that generates sharp 1H NMR signals, 6, could correspond to the component with lower RH (128 nm). 91 Figure 3.14 Reaction monitored by DLS. Hydrodynamic radius (RH) distribution measured at selected reaction times: (a) t = 0 min (one peak with RH = 128 nm); (b) t = 1 h 55 min (two peaks with RH = 134 and 413 nm); (c) t = 2 h 8 min (two peaks with RH = 126 and 620 nm); (d) t= 2 h 15 min (two peaks with RH = 127 and 848 nm). 3.2.3.1!Characterization of compound 3-lut-prec The low solubility of 3-lut-prec made its complete characterization challenging. The compound is slightly soluble in chloroform, which allowed carrying out a 1H DOSY NMR experiment (Figure B-3). 1H DOSY NMR experiments were also carried out on the reaction starting material, 3-lut (Figure B-4), on the pure soluble product, compound 6 (Figure B-5), and on the reaction crude (Figure 3.15). The diffusion coefficient for 3-lut-prec measured on the pure solution is 3.0 Ã 10-6 cm2/s, about 5 units smaller than pure compound 6 (7.7 Ã 10-6 cm2/s) and 7 units smaller than 3-lut (9.8 Ã 10-6 cm2/s). It can be concluded that the molecular size of 3-lut-92 prec is bigger than the one of 3-lut or 6. 1H DOSY NMR performed on the crude reaction mixture (Figure 3.15) also shows the formation of two species with different molecular size: 3-lut-prec with diffusion coefficient 4.3 Ã 10-6 cm2/s (blue line), and 6 with diffusion coefficient 5.1 Ã 10-6 cm2/s (red line). 93 Figure 3.15 1H DOSY NMR (400 MHz, CDCl3) experiment on the polymerization crude reaction mixture performed on compound 3-lut. The presence of at least two different species can be noted. The red line corresponds to 6 and the blue line to 3-lut-prec. Some regions of the spectrum (black box in the full 2D spectrum) are magnified and reported in the top image to show more clearly the difference between the two species. 94 The low solubility of 3-lut-prec, the DLS experiment, the 1H DOSY NMR and the broadness of the 1H and 13C NMR spectra suggest that this compound is composed by a distribution of oligomers. GPC in THF was attempted on 3-lut-prec but unsuccessfully, due to its poor solubility in THF. 3.2.3.2!Characterization of compound 6 Compound 6 was characterized by NMR techniques, HRMS and SCXRD. Figure 3.16 shows the 1H DOSY NMR experiments performed on compounds 6 and 3-lut side by side. The diffusion coefficients obtained (7.7 Ã 10-6 cm2/s for 6 and 9.8 Ã 10-6 cm2/s for 3-lut) are comparable within each other but the one corresponding for 3-lut is slightly higher. This suggests that the mass of compound 6 is higher than the one of the starting material. This result is confirmed by high-resolution mass spectrometry (HRMS), by which a compound with m/z = 1278.2686 was detected. This mass corresponds to twice the mass of the starting material 3-lut, suggesting that the product could be a dimer of 3-lut. 95 Figure 3.16 1H DOSY NMR (400 MHz, CDCl3,) of compounds (a) 3-lut and (b) 6. Residual solvent peaks are indicated with *. The HRMS results obtained, as well as the 1H DOSY NMR spectrum and the fact that the 1D 1H NMR spectrum of compound 6 did not show the typical end groups associated with Grubbs metathesis, led us to the conclusion that compound 6 is a ring-expanded metallomacrocycle (Scheme 3.2). This conclusion was confirmed by SCXRD data (Figure 3.17). 96 Scheme 3.2 Reaction scheme for the ring-opening on compound 3-lut that lead to the formation of compound 6. A single crystal of 6 was grown by vapour diffusion of THF into a DCM solution. From the crystal structure (Figure 3.17b), it can be noted that the vinyl groups have a trans stereochemistry, whereas the vinyl group in the starting material 3-lut had cis stereochemistry. This change in stereochemistry proved that the double bond ring-opened and closed during the reaction. Furthermore, the distance between the two palladium atoms is 15.8 Ã and between the two vinyl groups 3.3 Ã . The 1H NMR spectrum shows that the macrocycle cavity is big enough to allow 2,6-lutidine rotation around the PdâN axes in solution since the methyl protons coalesce into one peak. However, in both 3-lut and 6 crystal structures, 2,6-lutidine crystalizes with one methyl group pointing inside the cavity and one in the opposite side. The distance between the methyl group and the macrocycle phenyl moiety is 3.2 Ã for 3-lut and 3.5 Ã for 6, suggesting a CHâÏ interaction.165,166 97 Figure 3.17 SCXRD structure of: (a) compound 3-lut; (b) compound 6. No ring-expanded macrocycles were detected when the reaction was performed on compounds 2, 3 and 3-PPh3, but only monomeric species. Only when 2,6-lutidine is used, a dimeric product is formed. This demonstrates that the 2,6-lutidine ligand bulk contributes to the formation of the macrocyclic dimer, preventing ring-closing after reaction with the Grubbs catalyst. 3.3.! Conclusions In summary, these results demonstrated that a supramolecular modification such as ligand coordination can modulate ring-expansion of an unstrained palladium-containing pincer macrocycle. Coordination of a bulky ligand, such as 2,6-lutidine in compound 3-lut, disfavors ring-closing, allowing ring-expansion. The main product of the reaction with the second generation Grubbs catalyst is a metal-containing macrocyclic dimer, but the formation of higher order macrocycles or oligomers cannot be excluded. In the presence of less bulky ligands, such as acetonitrile, or in macrocycle 2, ring-closing occurs, producing a mixture of trans and cis isomers. a+ b+98 This demonstrated that the ring-expansion is caused by the 2,6-lutidine steric bulk. In addition, reaction of 3-PPh3 with the second generation Grubbs catalyst showed that ligand exchange can be used to control the stereospecificity of ring-closing reactions. Compound 3-PPh3 does not ring-expand but converts entirely into the trans isomer. This new concept of using supramolecular interactions to prevent the ring-closing step or to control its stereoselectivity offers an intriguing tool toward new polymerization and ring-expansion reactions. 3.4.! Experimental section Materials and equipment. Solvents and starting materials were used as received from the supplier. CDCl3 and THF-d8 were purchased from Cambridge Isotope Laboratories. All the reactions were performed under N2 and dry solvents were obtained from INERT column solvent purification system. Single crystal X-ray diffraction data (SCXRD) raw data were collected on a Bruker APEX DUO and on a Bruker APEX X8 diffractometers. Nuclear magnetic resonance (NMR) spectra were recorded on Bruker AV-400 and AV-300 spectrometers. 1H DOSY NMR spectra were collected on a Bruker AV-400 inverse probe spectrometer and were calibrated to the residual protonated solvents at δ 7.27 for CDCl3. The concentration of the solutions was 5 mM. High resolution electrospray ionization mass spectra (HRMS) were obtained on a Micromass LCT time-of-flight (TOF) mass spectrometer equipped with an electrospray ion source. DLS data were collected on a Brookhaven NanoBrook Omni instrument. Polymerization reaction on compound 2. Compound 2 (80 mg, 0.19 mmol) and second generation Grubbs catalyst (7.6 mg, 0.0095 mmol) were stirred in 16 mL of dry THF at 55 ËC for 2 h under N2 atmosphere. The reaction was cooled to room temperature, quenched with ethyl vinyl ether and concentrated under vacuum. The resulting solid was washed with hexanes (3 Ã 10 mL) 99 to give 83 mg of a brown powder. Characterization of the brown powder showed that it was 2:1 a mixture of compound 2 and another compound, likely the trans isomer of compound 2. Polymerization reaction on compound 3. Compound 3 (79 mg, 0.14 mmol) and second generation Grubbs catalyst (5.8 mg, 0.007 mmol) were stirred in 12 mL of dry THF at 55 ËC for 2 h under N2 atmosphere. The reaction was cooled to room temperature and quenched with ethyl vinyl ether. The precipitate formed was filtered and washed with THF (3 Ã 10 mL) and hexanes (3 Ã 10 mL) to give compound 3 as a yellow solid. Yield: 43 mg (0.07 mmol, 54 %). The filtrate was concentrated under vacuum and washed with hexanes. Polymerization reaction on compound 3-PPh3. Compound 3-PPh3 (67 mg, 0.09 mmol) and second generation Grubbs catalyst (3.6 mg, 0.004 mmol) were stirred in 7 mL of dry THF at 55 ËC for 2 h under N2 atmosphere. The reaction was cooled to room temperature, quenched with ethyl vinyl ether and concentrated under vacuum. The resulting solid was washed with hexanes (3 Ã 10 mL) to give 3-PPh3-trans as an orange powder. Yield: 65 mg (0.08 mmol, 97%). A single crystal suitable for X-ray analysis was grown by vapour diffusion of hexanes into a DCM solution of 3-PPh3-trans. Data for 3-PPh3-trans. 1H NMR (400 MHz, CDCl3): δ 8.25 (t, 1H, J = 7.6 Hz), 8.07 (d, 2H, J = 7.9 Hz), 7.43 (br, 4H), 7.22 (br, 6H), 6.97 (br, 6H), 6.61 (m, 8H), 5.99 (br, 2H), 5.14 (dd, 2H, J = 16.2 and 4.0 Hz), 4.84 (d, 2H, J = 14.0 Hz), 4.65 (d, 2H, J = 17.1 Hz), 2.60 (d, 2H, J = 15.9 Hz). 13C NMR (75 MHz, CDCl3): δ 173.2, 156.5, 151.9, 141.4, 134.3, 134.2 (d, J = 11.5 Hz), 132.7, 131.4 (d, J = 2.3 Hz), 128.8 (d, J = 10.3 Hz), 128.7, 127.0, 125.5 (d, J = 2.3 Hz), 114.7, 67.6, 48.2. HRMS (ESI/TOF-Q). Calcd for C45H37N3O4P104Pd [3-PPh3-trans + H+]: 796.1562 m/z. Found: 796.1551 m/z. 100 Polymerization reaction on compound 3-lut. Compound 3-lut (125 mg, 0.19 mmol) and second generation Grubbs catalyst (8.1 mg, 0.0095 mmol) were stirred in 16 mL of dry THF at 55 ËC for 2 h under N2 atmosphere. The reaction was cooled to room temperature and quenched with ethyl vinyl ether. The precipitate formed (3-lut- prec) was filtered and washed with THF (3 Ã 10 mL) and hexanes (3 Ã 10 mL) to give 48 mg of a grey solid. The filtrate was concentrated under vacuum and purified by column chromatography with an alumina column [eluent, gradient 0-10% MeOH in DCM; [Rf (3% MeOH in DCM) = 0.38] to give 6 as a yellow solid that was recrystallized from DCM/THF. Yield: 25 mg (0.02 mmol, 20%). A single crystal suitable for X-ray analysis was grown by vapour diffusion of THF into a DCM solution of 6. Data for 6. 1H NMR (400 MHz, CDCl3): δ 8.12 (t, 1H, J = 7.9 Hz), 7.87 (d, 2H, J = 7.9 Hz), 7.65 (m, 1H,), 6.97 (d, 1H, J = 7.6 Hz), 6.56 (m, 4H), 6.52 (m, 4H), 6.11 (m, 2H), 4.46 (s, 4H), 4.05 (s, 4H), 2.35 (m, 6H). 13C NMR (100 MHz, CDCl3): δ 171.3, 160.8, 157.6, 153.0, 140.7, 138.7, 134.0, 128.9, 128.2, 124.9, 122.9, 114.3, 68.0, 49.5, 25.6. HRMS (ESI/TOF-Q). Calcd for C64H61N8O8104Pd105Pd [6 + H+]: 1278.2703 m/z. Found: 1278.2686 m/z. Data for 3-lut-prec. 1H NMR (400 MHz, CDCl3): δ 8.09 (br, 1H), 7.85 (br, 2H), 7.65 (br, 1H), 6.99 (d, 2H, J = 7.0 Hz), 6.57 (d, 4H, J = 7.7 Hz), 6.49 (d, 4H, J = 7.7 Hz), 6.03 (br, 2H), 4.49 (br, 4H), 4.00 (br, 4H), 2.47 (br, 4H). 13C NMR (100 MHz, CDCl3): δ 171.2, 160.4, 157.3, 153.0, 140.7, 139.0, 133.8, 128.7, 128.5, 124.9, 122.9, 114.4, 67.9, 48.9, 29.8, 25.7. Single-crystal X-ray diffraction. SCXRD raw data were collected on a Bruker APEX DUO diffractometer at 90 K for 3-lut and on a Bruker APEX X8 diffractometer at 100 K for 3-PPh3, 3-PPh3-trans and 6. Graphite monochromated MoKα radiation (λ = 0.71073) was used and data were collected to a resolution of 0.77 Ã . The data elaboration was performed with the software APEX2143 for 3-lut and APEX3167 for 3-PPh3-trans and 6. The structures were solved using 101 SUPERFLIP146 and refined using full-matrix least-squares on F2 within the CRYSTALS147 suite. Hydrogen atoms were initially refined with restraints on bond lengths and angles, after which the positions were used as the basis for a riding model.148 All non-hydrogen atoms were refined anisotropically. A summary of the crystallographic data is reported in Table 3.2. Table 3.2 Summary of crystallographic data for compounds 3-lut, 3-PPh3, 3-PPh3-trans and 6. Compound 3-lut 3-PPh3 3-PPh3-trans 6 Chemical formula C32H30N4O4Pd, C4H8O C43H36N3O4PPd, CH2Cl2 C43H36N3O4PPd C32H30N4O4Pd, 1.72(CHCl3), 1.28(C4H8O) Formula weight 713.12 881.08 796.15 938.19 a (Ã ) 16.706(4) 9.3671(3) 16.390(2) 11.9782(10) b (Ã ) 10.745(2) 13.0934(4) 10.3462(15) 15.6397(12) c (Ã ) 17.859(4) 34.4590(11) 20.704(3) 21.9976(17) ! (°) 90 90 90 90 β (°) 102.827(5) 90 94.732(5) 94.145(4) γ (°) 90 90 90 90 Unit cell volume (Ã 3) 3125.8(12) 4226.3(2) 3498.9(9) 4110.2(6) Temperature (K) 90 100 100 100 Crystal system monoclinic orthorhombic monoclinic monoclinic Space group P 21/c P 21 21 21 P 21/c P 21/c Z 4 4 4 4 102 Compound 3-lut 3-PPh3 3-PPh3-trans 6 Absorption coefficient (µ/mm-1) 0.645 0.648 0.626 0.835 Total number of reflections 30358 24968 78565 87723 Unique reflections 7166 9689 14057 9433 Final R1 values (I > 2"(I)) 0.0290 0.0393 0.0316 0.0416 Final wR(F2) values (all data) 0.0742 0.0904 0.0851 0.1001 Computational calculations. Geometries were computed at different levels of theory ranging from meta-GGA (wB97xd168,169 and M06170) to double hybrid functional171 with empirical dispersion corrections172â174. The basis set used for all non-metal atoms was 6-31G(d).161 For the palladium atom, a fully relativistic ECP (energy consistent pseudopotential) with small core was used, coupled with the cc-pDZP162 basis set retrieved from University of Köln (Germany) web site.175 SCXRD geometries, if available, were used as input guesses. All the bond distances involving hydrogen atoms were increased to 1.07 Ã . The starting conformation of PPh3 in the cis2 isomer was generated from the trans optimized geometry. All calculations were carried out using the Gaussian 19 (rev. B.01)163 suite on Compute Canada Facilities. The computed bond distances match the ones obtained by SCXRD, with the largest deviations from the SCXRD structure on the 103 Pd-P and the Pd-N bond lengths. A summary of the results obtained is reported in Table 3.3. For compound 3 calculations were performed in both dichloromethane and acetonitrile solutions. No significant differences in the results were observed between the two solvents. Table 3.3 Summary of the energy minima obtained by geometry optimization calculations. Functional, solvent Compound Energy (Hartree) ÎE (Ecis - Etrans) (Hartree) ÎE (Ecis - Etrans) (kcal/mol) wB97xd, CH3CN 3 (cis2) -1690.30107708 0.00442112 2.77 3 (cis) -1690.29957826 0.00591994 3.71 3 (trans) -1690.30549820 M06, CH3CN 3 (cis2) -1689.720432 0.00461655 2.90 3 (cis) -1689.718734 0.00631366 3.96 3 (trans) -1689.725048 wB97xd, DCM 3 (cis2) -1690.29745916 0.00436452 2.74 3 (cis) -1690.29565698 0.00616670 3.87 3 (trans) -1690.30182368 wB97xd, DCM 3-PPh3 -2593.66165985 0.00798870 5.01 3-PPh3 -2593.66191861 0.00772994 4.85 (4.51)a 3-PPh3 -2593.66964855 M06, DCM 3-PPh3 (cis2) -2592.78330227 0.00721856 4.53 3-PPh3 (cis) -2592.78351522 0.00700561 4.40 (4.72) a 3-PPh3 (trans) -2592.79052083 B2PLYPD3, DCM 3-PPh3 (cis) -2591.82093224 0.00753486 4.73 3-PPh3 (trans) -2591.82846710 a Harmonic zero-point energy corrections. 104 Chapter 4:! Pt complexes with crown ether functionality 4.1.! Introduction Supramolecular chemists have synthesized a wide variety of compounds able to reversibly encapsulate molecules in their cavities or pockets.176 These complexes are referred to as host-guest systems. Host-guest systems have two components: a host molecule that possesses a cavity and recognition sites toward specific guests, and a guest molecule that can recognize and bind to the host molecule. The encapsulation of the guest happens through reversible supramolecular interactions, such as hydrogen bonding, van der Waals forces, metal coordination, hydrophobic association, and Ï-Ï interactions.177,178 Due to the reversibility of the interactions, in most of the host-guest systems, the host is able to capture and release the guest in a controlled manner.179â181 Crown ethers are cyclic hosts composed of several ethyleneoxy groups that are widely used in supramolecular chemistry. Depending on the number of ethyleneoxy groups, they have cavities of different sizes. The crown ether cavity is hydrophilic, and the oxygen atoms can act as a Lewis bases, complexing and trapping cations, while the rest of the molecule is hydrophobic, making crown ethers soluble in nonpolar solvents. Consequently, crown ethers have been investigated for applications in cation extraction and membrane transport.182 They also play an important role in the synthesis of interlocked structures.183â186 The incorporation of a photoluminescent unit into a crown ether derivative is a way of generating species with tunable photophysical properties by coordination of guests inside the crown ether cavity. Transition metal complexes are known to have interesting photophysical properties, as they present metal-based (d-d), ligand-based (Ï-Ï*), metal-to-ligand (MLCT), and ligand-to-metal (LMCT) transitions in the UV-Vis spectrum.21,187â190 These spectral bands change 105 when a transition metal complex featuring a crown ether functionality is coordinating a guest.191â193 In this thesis we focus on square-planar Pt2+ cyclometalated phenylpyridine (ppy) complexes. These complexes are usually emissive due to triplet ligand-centered (3LC), metal-to-ligand charge transfer (3MLCT) and metalâligand-to-ligand charge transfer (3MLLâCT) excited states.194 They tend to form aggregates and excimers, particularly when a rigid ligand that generates Ï-Ï interactions is used, causing strong red shifts in the emission spectra.195 These complexes also stack in the axial direction, due to Pt-Pt interactions.196 The stacked compounds are usually phosphorescent in the solid state but show a weaker luminescence in dilute solutions as these interactions subside.23,197â202 Literature examples of cyclometalated platinum complexes featuring a crown ether functionality are limited.191â193,203â205 Figure 4.1 shows two examples reported in the literature of Pt2+ complexes in which a crown ether functionality is in communication with the Pt2+ center through a conjugated network.192,193 The complex reported in Figure 4.1a presents strong UV-Vis MLCT absorption bands and shows an electronic response upon addition of Na+ measured by cyclic voltammetry (CV). The complex shown in Figure 4.1b demonstrates significant shifts with well-defined isosbestic points in the UV-Vis spectrum upon coordination of Na+, K+ and Ba2+ into the crown ether cavity. 106 Figure 4.1 Examples reported in literature of platinum(II) complexes that contain crown ether functionality reported by (a) Ji et al.192 and (b) Yam et al.193 In this chapter I discuss Pt2+ coordination to two different types of phenylpyridine ligands featuring glycolic functionalities to generate two target complexes (Figure 4.2). One of the target complexes is the biscyclometalated Pt2+ cis isomer (cis-Pt(II)-9, Figure 4.2a). In this complex the platinum atom is part of a ring that includes a glycolic chain and closes the metallomacrocycle. Preparation of this complex is expected to be challenging due to the high flexibility of the ligand which can lead to the formation of dimers and oligomers, with both trans and cis stereochemistry. The second target complex, (Pt(II)-19, Figure 4.2b), is obtained by reaction with a preorganized ligand. We anticipated that ligand preorganization would facilitate the cyclometalation reaction with platinum, disfavouring the formation of oligomers. The properties of these two complexes upon coordination of cations into the crown ether cavity are expected to be different, since in cis-Pt(II)-9, the platinum would be in direct communication with the cation, while in Pt(II)-19, the communication would be interrupted by a bridging oxygen atom. Furthermore, using crown ethers of bigger size would allow for coordination of organic cations for the synthesis of interlocked structures, such as rotaxanes or pseudorotaxanes. 107 Figure 4.2 Two target complexes discussed in this chapter: (a) cis-Pt(II)-9 and (b) Pt(II)-19. 4.2.! Results and discussion 4.2.1! Initial strategy for the synthesis of cis-Pt(II)-9 The initial strategy for synthetizing the Pt2+ biscyclometalated cis complex (cis-Pt(II)-9) was to prepare ligand 7-Ac (Figure 4.3). Coordination to Pt2+ to give cis-Pt-(7-Ac)2, deprotection of the ligand, and subsequent crown ether functionalization would afford the target molecule, cis-Pt(II)-9. From the reaction plan, it is evident that obtaining the cis stereoisomer in the cyclometalation reaction is key to successfully making the target cis-Pt(II)-9 complex. Figure 4.3 Reaction plan for the synthesis of cis-Pt(II)-9. There are several reported literature procedures to synthetize cis biscyclometalated Pt2+ complexes with phenylpyridine ligands.198,206,207 One option involves the use of ortho-lithiated 2-phenylpyridines as ligands and trans-Pt(SEt2)Cl2 as the platinum source.198 Another procedure consists of forming the monocyclometalated complex first, using K2PtCl4 or Pt(dmso)2Cl2, and 108 then obtaining the cis product by reaction with Na2CO3 and a further equivalent of the phenylpyridine ligand.206 High boiling point solvents are frequently employed in platinum cyclometalation reactions, such as p-xylene, toluene,206 and acetic acid (AcOH).208â211 Scheme 4.1 shows the synthetic route for the preparation of compound 7-Ac and its reactions with Pt2+. Different reaction conditions were tried, inspired by literature reports. Reaction with K2PtCl4 in AcOH produced the monocyclometalated complex Pt(7-Ac)2Cl. This complex had trans stereochemistry, and subsequent attempts to complete the reaction by addition of AgPF6 to precipitate the chloride atom were unsuccessful. Different reaction conditions (Pt(dmso)2Cl2 and Na2CO3 in p-xylene) produced compound Pt(7-Ac)(dmso)Cl, and when higher temperature conditions were employed, deprotection of the ligand occurred, giving compound Pt(7)(dmso)Cl as product. 109 Scheme 4.1 Reaction scheme for the synthesis of 7-Ac and the three products obtained by cyclometalation reaction with Pt2+: Pt(7-Ac)2Cl, Pt(7-Ac)(dmso)Cl, and Pt(7)dmsoCl. The molecular structures of the complexes obtained were confirmed by SCXRD analysis (Figure 4.4). In Pt(7-Ac)2Cl, the square-planar platinum atom coordinates to two 7-Ac ligands. One of the ligands is bound to the metal through the pyridine nitrogen and the phenyl ortho-carbon atoms. The other 7-Ac ligand is coordinated trans to the pyridine nitrogen at an angle perpendicular to the platinum coordination plane. The phenyl ring α-proton in the cyclometalated ligand points directly toward the pyridine ring of the non-cyclometalated ligand. This generated a 1H NMR signal that is considerably upfield for an aromatic proton (Figure C-14, 5.86 ppm). The molecular structure of Pt(7-Ac)(dmso)Cl is consistent with literature reports for analogous complexes, where 110 the square-planar platinum center coordinates a DMSO molecule through its sulfur atom, trans to the pyridine nitrogen.208,212,213 Based on these results, we redesigned the synthetic strategy to obtain the target complex by preparing a tetradentate ligand. Figure 4.4 SCXRD structures for the compounds (a) Pt(7-Ac)2Cl and (b) Pt(7-Ac)(dmso)Cl. 4.2.2! Flexible ligand Since the initial strategy for the synthesis of cis-Pt(II)-9 was unsuccessful, a different approach was tried. The full ligand containing the ethylene glycol chain was synthesized first (compound 9, Scheme 4.2), and then reacted with a platinum(II) source. Compound 9 was prepared in 64% yield through a substitution reaction between 2 equiv of 4-(pyridin-2-yl)phenol (compound 7) and tetraethylene glycol bis(p-toluenesulfonate) (compound 8). In order to investigate whether the length of the ethylene glycol chain affects the reactivity of the ligand with platinum, a second ligand was prepared using pentaethylene glycol as precursor. Starting from pentaethylene glycol and by following the same reaction scheme, compound 10 and the compound 11 (92% yield) were prepared. 111 The reaction of compound 9 (or 11) with platinum can generate different types of structures. Figure 4.5 shows two possible products. The cis-Pt(II)-9 complex is the desired product, but a trans complex could form as well, likely as a dimer or an oligomer in which ligand 9 bridges two different platinum centers. Oligomer formation is expected to decrease in highly diluted conditions. Statistically, in a dilute solution, it is more likely that two reactive groups from the same molecule (in this case the phenylpyridine functionalities) will be closer to each other and coordinate to the same platinum atom forming a monomer, whereas in a concentrated solution it is more likely that there would be competing interactions from another independent molecule, or from two different platinum atoms. For this reason, the reaction was diluted from 16 mM to 4 mM, until no oligomers could be detected. Scheme 4.2 (a) Reaction scheme for the synthesis of compound 8 and 9. (b) Structures of compounds 10 and 11. 112 Figure 4.5 Two of the possible products with different stereochemistry that could be obtained from the reaction of 9 with Pt2+. The presence of oligomers in the crude reaction mixture is indicated by the appearance of broad signals in the 1H NMR spectrum (Figure 4.6a). Different dilution conditions (16 â 4 mM) and different solvents (benzonitrile and AcOH) were used. Almost no broad peaks were observed when AcOH was employed at 4 mM concentration (Figure 4.6b). Figure 4.6 Portions of the 1H NMR (400 MHz, CDCl3) spectra of the crude product from the reaction between compound 9 and K2PtCl4 in AcOH at different concentrations: (a) 16 mM and (b) 4 mM. The broad peaks 113 corresponding to the oligomers are indicated in red, and the sharp peaks corresponding to Pt(II)-9-Cl are indicated in blue. Full spectra shown in Figure C-15. The reaction scheme and the pure reaction productâs 1H NMR spectrum are reported in Figure 4.7. The presence of 15 non-equivalent aromatic hydrogen signals indicates that the product is not symmetric and only one cyclometalation occurred. The pyridine ring α-protons shifted from 8.65 ppm in the ligand to two non-equivalent signals at 9.68 and 9.32 ppm in the complex, as a consequence of the deshielding effect produced by metal coordination. In addition, one of the phenyl ring α-protons underwent a significant upfield shift, from 7.93 ppm to 5.70 ppm. A similar change in chemical shift was observed in Pt(7-Ac)2Cl. This suggested that the product obtained is Pt(II)-9-Cl and has ligand coordination analogous to Pt(7-Ac)2Cl. As expected, the same changes in chemical shift and splitting, for all the resonances, were observed when the reaction was performed with compound 11 as the ligand, giving Pt(II)-11-Cl with 11% yield. 114 Figure 4.7 Reaction scheme and 1H NMR spectrum (400 MHz, CDCl3) of compound Pt(II)-9-Cl. Residual solvent peak is indicated with *. The suggested molecular structures for Pt(II)-9-Cl and Pt(II)-11-Cl were confirmed by SCXRD analysis (Figure 4.8). The crystal structures of these two compounds are analogous to the one of Pt(7-Ac)2Cl, as in all the complexes one of the phenylpyridine groups is perpendicular to the platinum square-planar coordination plane and in the trans position with respect to the second pyridine ring. 115 Figure 4.8 SCXRD structures of compounds (a) Pt(II)-9-Cl and (b) Pt(II)-11-Cl. Since target complex cis-Pt(II)-9 was not formed under dilute conditions, cation-templation was tried. Cations are typically used as templates in the synthesis of crown ethers because the ethylene glycol chain can pre-arrange around them into a cyclic structure, favoring intramolecular reactions.214 Similarly, using a cation during the cyclometalation reaction could help preorganize the ligand and prevent the formation of the trans stereoisomer, as well as bringing the phenylpyridine units in close proximity with each other. Several cations compatible with the crown ether cavity sizes were tried. Addition of NaBF4 and KBF4 to the reaction mixture once again produced compound Pt(II)-9-Cl and Pt(II)-11-Cl, but when the cyclometalation reaction was performed with addition of Cs2CO3, a new set of peaks was observed by 1H NMR spectroscopy (along with the peaks corresponding to compound Pt(II)-9-Cl). The 1H NMR spectrum of the pure reaction product (Figure 4.9) showed 14 non-equivalent aromatic protons, one of them significantly downfield (red) and one significantly upfield (blue). The presence of 14 aromatic protons signals suggested that the product is a biscyclometalated complex (the 116 monocyclometalated Pt(II)-9-Cl compound showed 15 aromatic proton signals). However, the 14 aromatic protons are not equivalent, suggesting that the product is not symmetric, unlike the target molecule cis-Pt(II)-9. An octahedral cis Pt4+ complex (Pt(IV)-9-Cl2), would explain the 1H NMR result, where the chloride atoms are adjacent to each other and the phenylpyridines are sitting in different planes. The octahedral geometry would also justify the upfield shift of the protons that are pointing inside the phenyl rings of the second phenylpyridine unit, similar to what was observed for compounds Pt(II)-9-Cl and Pt(7Ac)2Cl. In compound Pt(II)-9-Cl, two downfield signals were observed for the pyridine α-protons (9.14 and 9.52 ppm). In compound Pt(IV)-9-Cl2, only one of the pyridine α-protons underwent a downfield shift at 9.80 ppm. This suggests that the second pyridine α-proton is shifted upfield by interaction with a phenyl ring, indicating a cis stereochemistry of the pyridine rings. 117 Figure 4.9 Reaction scheme and 1H NMR (400 MHz, CDCl3) of compound Pt(IV)-9-Cl2. Residual solvent peak is indicated with *. The same reaction was performed using ligand 11 and the 1H NMR spectrum of the complex obtained showed the same chemical shifts in the aromatic region as Pt(IV)-9-Cl2 (Figure C-18). A single crystal of compound Pt(IV)-11-Cl2 was grown by vapour diffusion of isopropyl ether into a solution of Pt(IV)-11-Cl2 in CH3CN (Figure 4.10). The crystal structure obtained for Pt(IV)-11-Cl2 confirms that it is an octahedral complex of Pt4+, with the two pyridine rings in a cis arrangement, different from what was observed in the square-planar compounds Pt(II)-9-Cl and Pt(II)-11-Cl, where they were in trans arrangement. Additionally, an Pt(IV)-11-Cl2, a CH3CN molecule crystallizes inside the pseudo-crown ether cavity, showing that the cavity is active for interaction with hydrogen-donor guests. 118 Figure 4.10 SCXRD structure of compound Pt(IV)-11-Cl2, with a CH3CN molecule coordinating inside the cavity. The new products were obtained in the presence of Cs+ ions, but they did not form in the presence of Na+ and K+. This is probably related to the larger ionic radius of Cs+ (1.70 Ã ) compared to Na+ and K+ (1.02 Ã and 1.38 Ã , respectively).215 Ligands 9 and 11 do not feature an entire crown ether functionality, and as a consequence, their interaction with small cations such as Na+ and K+ would produce what is represented in Figure 4.11a, which is not a suitable prearrangement toward biscyclometalation. In contrast, the larger ionic radius of Cs+ allows it to bind to two 18-crown-6 molecules by fitting in between them.216,217 Based on literature reports, we postulate that it would most likely bind as represented in Figure 4.11b, with a 2:1 stoichiometry between ligand and cation. This prearrangement of the ligands appears to be more suitable for cyclometalation reaction and for monomer formation. 119 Figure 4.11 Schematic representation of cation templation on ligands 9 and 11 with (a) Na+, K+, and (b) Cs+. 4.2.2.1!Host-guest properties of Pt(II)-9-Cl, Pt(II)-11-Cl, Pt(IV)-9-Cl2 and Pt(IV)-11-Cl2 Despite the synthesis of the target molecule cis-Pt(II)-9 being unsuccessful, four platinum complexes featuring a pseudo-crown ether cavity were prepared. The host-guest properties of these compounds were investigated and are reported herein. Pt(II)-9-Cl is a yellow complex that appears fluorescent under UV light (λ = 366 nm), both in solution and in the solid state. Upon addition of NaBF4, the fluorescence under UV light was attenuated. This qualitative observation suggested that the complex would undergo a change in the UV-Vis emission spectrum by coordination of alkali cations into the pseudo-crown ether functionality. For this reason, a preliminary 1H NMR study was performed (Figure 4.12). Changes in the 1H NMR spectrum were observed when 1 equiv of NaBF4 or KBF4 were added to Pt(II)-9-Cl. The peaks at 9.21 and 9.58 ppm (indicated in red in Figure 4.12) shifted to 9.14 ppm and 9.52 120 ppm, respectively, while the peak at 5.67 ppm (indicated in blue in Figure 4.12) shifted to 5.57 ppm, and the glycolic region changed shape and splitting. Figure 4.12 Stacked 1H NMR (400 MHz, CD2Cl2) spectra of Pt(II)-9-Cl, Pt(II)-9-Cl + 1eq KBF4 and Pt(II)-9-Cl + 1eq NaBF4. Residual solvent peak is indicated with *. The UV-Vis spectrum of complex Pt(II)-9-Cl in a 25 µM CH3CN solution is reported in Figure 4.13. A low energy transition, at 398 nm, is attributed to MLCT absorption. At high energy, (λ < 350 nm), the spectrum presented a very intense band corresponding to ligand-based Ï-Ï* transitions. Addition of NaBF4 and KBF4 (5 and 20 equiv) quenched the intensity of these absorptions. The spectra of compounds Pt(II)-9-Cl + Na+ or K+ (CH3CN, 250 µM) reported in Figure 4.13 presents less intense peaks than the spectrum of pure compound Pt(II)-9-Cl, showing 121 that the complex is suitable for cation sensing applications. The molar extinction coefficient for the MLCT transition is 2.7 Ã 103 M-1 cm-1 in Pt(II)-9-Cl and decreases to 0.1 Ã 103 M-1 cm-1 when 5 equiv of Na+ or K+ are added; the ligand-based transitions decreased by one order of magnitude as well (from 104 to 103 M-1 cm-1). These absorption properties are different from what was observed for simple crown ethers. Pederson reported that a new peak appears at λ > 275 nm with cation binding to crown ether and the UV-Vis spectrum does not present a significant change in intensity.64 In addition, it has been previously reported that when an alkali metal is bound inside a crown ether cavity that is part of a photoresponsive molecule, the absorption spectrum shows isosbestic points, indicating the formation of a new species, whereas the change in the absorbance intensity strongly depends on the nature of the cation and of the crown-ether-derivative used.193,203,218â220 Figure 4.13 UV-Vis spectra of compounds Pt(II)-9-Cl (CH3CN, 25 µM) and compound Pt(II)-9-Cl (CH3CN, 250 µM) after the addition of NaBF4 or KBF4 (5 and 20 equiv). 00.20.40.60.81200 250 300 350 400 450 500Absλ (nm)Pt(II)595ClPt(II)595Cl9+959eq Na+Pt(II)595Cl9+9209eq Na+Pt(II)595Cl9+959eq K+Pt(II)595Cl9+9209eq K+122 UV-Vis studies on Pt(IV)-9-Cl2 and Pt(IV)-11-Cl2 (CH3CN, 50 µM) only showed broad transitions at high energy corresponding to Ï-Ï* absorptions and no significant change in the spectra was observed by addition of 5 equiv of KBF4 (Figure C-38). On the macroscopic level they did not appear fluorescent under UV light (366 nm). Even though Pt(IV)-9-Cl2 and Pt(IV)-11-Cl2 are probably not suitable for cation sensing applications, the crystal structure of compound Pt(IV)-11-Cl2 showed that CH3CN can coordinate inside the crown ether, suggesting that the cavity could be active for host-guest chemistry applications with linear organic cations. For this reason, Pt(IV)-11-Cl2 was mixed with the organic salts shown in Figure 4.14 (dibenzylammonium hexafluorophosphate, N,Nâ-dimethyl-4,4â-bipyridinium hexafluorophosphate, and 1,2-bis(4,4â-bipyridinium)ethane hexafluorophosphate) with the purpose of forming the corresponding [2]pseudorotaxane complexes. These molecules and their derivatives have been widely used in host-guest chemistry as they have acidic protons as recognition sites for crown ethers and end-cap fragments (the phenyl and pyridine rings) that can subsequently be functionalized.221â226 Figure 4.14 Molecular structure of (a) dibenzylammonium hexafluorophosphate, (b) N,Nâ-dimethyl-4,4â-bipyridinium hexafluorophosphate, and (c) 1,2-bis(4,4â-bipyridinium)ethane hexafluorophosphate. Pt(IV)-11-Cl2 and dibenzylammonium hexafluorophosphate (1:1 ratio) were dissolved in an NMR tube at 25 °C in a 1:1 mixture of CDCl3 and CD3CN, solvents that usually promote a b c123 association processes in these types of systems.225,227 The reaction was monitored for 6 d and, after the second day, the 1H NMR spectrum of the reaction stopped changing. We concluded that the reaction reached equilibrium after two days and we calculated the association constant by integrating the 1H NMR signals corresponding to the association complex, the free dibenzylammonium salt and compound Pt(IV)-11-Cl2. The calculated association constant was 800 M-1 (25 °C, 1:1 CDCl3/ CD3CN). Formation of the pseudorotaxane was also confirmed by LRMS (ESI), with the detection of mass m/z 1006.5, corresponding to the association complex between Pt(IV)-11-Cl2 and dibenzylammonium. A section of the 1H NMR spectrum obtained is reported in Figure 4.15. All the chemical shifts were maintained and two new doublets with the same shape appeared at 6.50 and 6.61 ppm, indicating the formation of the new species. The aromatic protons generating the doublet signals shown in Figure 4.15 are in close proximity to the ethylene glyclol chain, and, as a consequence, more affected by the formation of the [2]pseudorotaxane, shifting one upfield and the other one downfield. The presence of two distinct sets of peaks, corresponding to the free compounds and to the association complex, indicates that the exchange between species at equilibrium is slower than the 1H NMR timescale. The integration ratio between the new peaks and the peaks corresponding to Pt(IV)-11-Cl2 is 1:1. The 1H NMR shifts observed remained when the solvent was evaporated and the compound was dissolved in pure CD3CN, whereas the integration ratio changed and the new binding constant at 25 °C was calculated to be 1500 M-1 (Figure C-21). The higher association constant can depend on higher the solubility of the benzylammonium salt in pure CH3CN. The complex is insoluble in THF whereas in DMSO dissociation of the dibenzylammonium occurs due to competition effects between DMSO and the crown ether binding sites, both of which act as very good hydrogen acceptors (Figure C-22). 124 Figure 4.15 Portion of 1H NMR (400 MHz, 1:1 CDCl3/CD3CN) spectra of (a) Pt(IV)-11-Cl2 and (b) Pt(IV)-11-Cl2 + dibenzylammonium hexafluorophosphate. Full spectra reported in Figure C-20. When the same experiment was performed with N,Nâ-dimethyl-4,4â-bipyridinium hexafluorophosphate (Figure 4.14) a macroscopic change in colour was observed, as the yellow solution became darker. The methyl groups positioned at the moleculeâs extremities in N,Nâ-dimethyl-4,4â-bipyridinium are the recognition sites for the crown ether functionality, and their corresponding chemical shift at 4.20 ppm remained unchanged after addition of the organic salt to Pt(IV)-11-Cl2. It is likely that N,Nâ-dimethyl-4,4â-bipyridinium forms an external association complex that cannot be detected by 1H NMR spectroscopy because it is in fast exchange. No change, either macroscopic or spectroscopic, was observed when 1,2-bis(4,4â-bipyridinium)ethane hexafluorophosphate (Figure 4.14c) was used, suggesting that this compound does not associate with Pt(IV)-11-Cl2. 125 1,2-Bis(4,4â-bipyridinium)ethane is a relatively rigid molecule, when compared to dibenzylammoniumm, as the four acidic hydrogen atoms in the ethane linker are in anti position with each other. In order to have association with the crown ether, four oxygen atoms would need to interact with the acidic methylene hydrogen atoms and keep the molecule in place inside the cavity by hydrogen bonding. As the guest is a rigid molecule, the crown ether would need to adopt a suitable geometry, disfavouring the formation of the association complex. In contrast, dibenzylammoniumm has only two hydrogen atoms that do not restrict the conformation of the host; two oxygen atoms of the crown ether may hydrogen bond to the NH2+ group and the other four oxygen atoms will interact with the acidic methylene hydrogen atoms, allowing the crown ether to freely arrange around the ion in the most suitable conformation. This result shows that Pt(IV)-11-Cl2 is suitable as a host compound for the formation of rotaxanes. The benzylammonium molecule can be functionalized and the extremities blocked with bulky groups. It would also be of interest to study the redox properties of Pt(IV)-11-Cl2 by cyclic voltammetry (CV) and investigate how the association with benzylammonium affects the reduction potential of the platinum complex. In summary, the four platinum complexes featuring a pseudo-crown ether cavity showed potential applications for host-guest chemistry. However, in all of these complexes the phenylpyridine units are arranged perpendicular to each other and not coplanar, as they would have been for the target cis biscyclometalated compounds. The perpendicular geometry of the phenylpyridine groups has several limitations. Namely, the geometry disfavours Ï-Ï stacking and the platinum is not accessible for Pt-Pt interactions, which are typically responsible for the formation of stacked structures and the interesting luminescence properties of platinum 126 phenylpyridine complexes.23,195â202 For this reason, we decided to redesign the ligand and we used a new strategy (ligand preorganization) to obtain cis biscyclometalated products. 4.2.3! Synthesis of a preorganized tetradentate ligand The synthesis of the target compound, cis-Pt(II)-9 was unsuccessful due to the high flexibility of ligand 9. For this reason a new, preorganized ligand was designed, compound 16 (Scheme 4.3). In compound 16, two 2-phenylpyridine units are bridged together so that the ligand is already arranged into a cis stereochemistry. This should facilitate coordination with Pt2+ as well as the formation of the biscyclometalated cis complex. Compound 16 does not contain any crown ether functionality, but it features two methoxy groups. It can be used as a model ligand to investigate the cyclometalation reaction with Pt2+, after which it can be functionalized to incorporate the full crown ether. In addition, literature reports of similar tetracoordinated biscyclometalated platinum complexes show that they are highly luminescent, as the rigid framework can add thermal stability and reduce non-radiative decay pathways.194,228â230 The synthesis of 16 is reported in Scheme 4.3. Compound 12 was first prepared by following a reported procedure231 and was then brominated with NBS to give 13. The hydroxyl groups were then protected with iodomethane to give compound 14, after which two cross-coupling reactions catalyzed by Pd(PPh3)4 afforded compound 16. 127 Scheme 4.3 Reaction scheme for the synthesis of compound 16. The cyclometalation reaction of compound 16 produced a mixture of Pt2+ and Pt4+ biscyclometalated complexes, Pt(II)-16 and Pt(IV)-16-Cl2 (Scheme 4.4). This showed that preorganization successfully directed the synthesis towards the formation of the cis isomer. The formation of the oxidized species Pt4+ is probably due to the presence of chlorides in solution and to some air that probably entered the reaction flask. In addition, the low solubility of K2PtCl4 in AcOH may promote the oxidation of Pt2+ when heated. Unsurprisingly, if the reaction is performed under air, compound Pt(IV)-16-Cl2 is the sole product. Purification of Pt(II)-16 was performed by exploiting the solubility difference of the two complexes, since the Pt4+ complex is less soluble in DCM than the Pt2+ complex. Therefore, the crude reaction mixture was dissolved in DCM and filtered to remove Pt(IV)-16-Cl2. In addition, the glacial AcOH used as reaction solvent was 128 degassed by three freeze-pump-thaw cycles to minimize the presence of oxygen and reduce the formation of Pt(IV)-16-Cl2. Scheme 4.4 Reaction scheme for the cyclometalation reaction of compound 16 with Pt2+. Figure 4.16 shows stacked 1H NMR spectra for compounds 16, Pt(II)-16 and Pt(IV)-16-Cl2. The 1H NMR spectra for each of the platinum complexes showed 6 different proton environments, proving that the obtained products are the biscyclometalated complexes. The peak corresponding to the pyridine α-proton for ligand 16 appeared at 8.53 ppm. Upon coordination to platinum the α-protons were deshielded and the corresponding peak was shifted downfield to 9.08 and 9.29 ppm in Pt(II)-16 and Pt(IV)-16-Cl2, respectively. This is in line with the expectation that coordination to platinum and oxidation of the metal center would both act to deshield ligand protons. The 1H NMR singlet corresponding to the methoxy protons was also shifted downfield, from 3.86 ppm in 16 to 3.94 and 4.01 ppm in Pt(II)-16 and Pt(IV)-16-Cl2, respectively. 129 Figure 4.16 Stacked 1H NMR (400 MHz, DMSO-d6) spectra of (a) compound 16, (b) Pt(II)-16 and (c) Pt(IV)-16-Cl2. A single crystal suitable for SCXRD analysis of compound Pt(II)-16 was grown by vapour diffusion of hexanes into a DCM solution of the complex. The solution is yellow but the complex crystalizes as orange blocks. The bright colour is probably due to the formation of dimers through Ï-Ï and Pt-Pt stacking that are evident in the crystal lattice (Figure 4.17a), with distance between two platinum atoms in the dimers being 3.1 Ã . From the side view of the molecule, Pt(II)-16 is almost planar, with the methoxy groups pointing in opposite directions. It is expected that a similar Pt2+ complex would be obtained by substitution of the methoxy groups with crown ether functionality. In an early attempt to grow a single crystal of Pt(II)-16 from the crude reaction mixture by vapour diffusion of hexanes into a DCM solution, two different types of crystals were observed: yellow needles and red plates. SCXRD analysis revealed that the yellow needles corresponded to Pt(IV)-16-Cl2 (Figure 4.17c), which had been identified by 1H NMR spectroscopy from the crude 130 reaction mixture. The less intense colour, compared to Pt(II)-16, is due to the absence of Pt-Pt stacking because the axial positions are occupied by two chlorides atoms. Surprisingly, the additional set of crystals isolated as red plates corresponded to a Pt3+ complex, Pt(III)-16-Cl (Figure 4.17b), where two Pt3+ atoms are bound to each other with a distance of 2.7 Ã , which is smaller than the one observed for Pt-Pt interactions. Literature reports of Pt3+ complexes are limited.194,232â235 These complexes are usually dimers in which a bridging ligand between two octahedral platinum centers promotes the formation of a Pt-Pt bond. However Pt(III)-16-Cl does not have any bridging ligand but is a dimer in which each octahedral platinum atom coordinates ligand 16 at the equatorial positions and a chloride atom at the axial positions. This geometry forces the phenylpyridine groups to stack perpendicularly to each other. For this reason the ligands do not have a flat geometry as in Pt(II)-16 but they repel each other, bending towards the chloride atoms. Figure 4.17 SCXRD structures for compounds (a) Pt(II)-16, (b) Pt(III)-16-Cl and (c) Pt(IV)-16-Cl2. 131 Preparing and isolating complex Pt(III)-16-Cl for full spectroscopic characterization was unsuccessful, probably due to the fact that that Pt3+ complexes disproportionate in solution into the more stable Pt2+ and Pt4+ complexes.233 Its formation in the solid state was likely due to the presence of both the Pt(II)-16 and Pt(IV)-16-Cl2 complexes. UV-Vis studies performed on Pt(II)-16 showed three main absorption bands (Figure 4.18a): the low energy small shoulder in the 420â470 nm region is attributed to MCLT transitions, whereas the higher energy peaks (388, 320 and 266 nm) are attributed to ligand-based Ï-Ï* transitions.229 The emission spectrum (4 µM in DCM, λexc: 370 nm) showed a structured peak in the 470â570 nm region (Figure 4.18b) that becomes weaker with increasing of the concentration, consistent with reports of similar complexes.230 No broad peaks due to excimer formation were observed when the concentration was increased to 10 µM. Less intense absorptions and no emission were observed in CH3CN, probably because a coordinating solvent can interact with the platinum atom. Figure 4.18 (a) UV-Vis spectrum in DCM 35 µM (b) Emission spectrum in DCM (4 µM, λexc: 370 nm). 00.20.40.60.81250 350 450 550Absλ (nm)a b01020304050450 500 550 600 650Intensity8(a.u.)λ8(nm)132 The formation of the biscyclometalated complex with the model ligand 16 was a promising result for the synthesis of a biscyclometalated complex containing crown ether functionality. Therefore, ligand 19 was prepared according to the route shown in Scheme 4.5. Compound 13 was first reacted with compound 8 to include the crown ether functionality. Subsequently two cross-coupling reactions with Pd(PPh3)4 produced ligand 19. Scheme 4.5 Reaction scheme for the synthesis of compound 19. Figure 4.19 shows a comparison between the crystal structures of ligands 9 and 19. In compound 9âs crystal structure the two phenylpyridine units are far from each other. For this reason, compound 9 is expected to be more flexible in solution than compound 19, and it tends to form oligomers when reacted with platinum. However, it is noticeable that in compound 19 there is rotation around the phenyl-pyridine bond and the two pyridine nitrogen atoms are pointing in opposite directions. Therefore, the possibility of forming oligomers when reacting with platinum cannot be excluded for compound 19. 133 Figure 4.19 SCXRD structures for compounds (a) 9, and (b) 19. Reaction of compound 19 with K2PtCl4 was performed in glacial AcOH with tetrabutylammonium bromide (n-Bu4NBr) (Scheme 4.6). The presence of n-Bu4NBr increased the solubility of the platinum salt helping the cyclometalation reaction and reducing platinum oxidation. Pt(II)-19 was obtained with 43% yield. Performing the reaction in air without n-Bu4NBr produced exclusively the oxidized compound Pt(IV)-19-Cl2. 134 Scheme 4.6 Reaction scheme for the synthesis of compounds Pt(II)-19, and Pt(IV)-19-Cl2. Figure 4.20 shows the stacked 1H NMR spectra for compounds 19, Pt(II)-19, and Pt(IV)-19-Cl2. The pyridine α-proton signal appeared at 8.61 ppm in compound 19. This 1H NMR peak was shifted downfield to 8.90 ppm in Pt(II)-19 as a consequence of the coordination to platinum. In Pt(IV)-19-Cl2 the proton was even more deshielded and the signal shifted to 9.03 ppm. The same pattern was observed in the 1H NMR spectra of compound 16, Pt(II)-16, and Pt(IV)-16-Cl2 (Figure 4.16). 135 Figure 4.20 Stacked 1H NMR (400 MHz, CD2Cl2) spectra of (a) compound 19, (b) Pt(II)-19, and (c) Pt(IV)-19-Cl2. Residual solvent peaks are indicated with *. A single crystal of Pt(IV)-19-Cl2 in the form of a yellow needle was grown by vapour diffusion of hexanes into a DCM solution. Figure 4.21 shows the crystal structure obtained. The crown ether functionality bends out of the ligand-platinum square-planar plane and the two chlorides occupy the axial positions, similar to what was observed for compound Pt(IV)-16-Cl2. The square-planar geometry around the platinum is slightly distorted by the oxygen bridge between the two phenyl rings, similar to what was observed with compound Pt(IV)-16-Cl2 (Figure 4.17). 136 Figure 4.21 SCXRD structures of compound Pt(IV)-19-Cl2 (a) top view, and (b) side view. Vapour diffusion of hexanes into a DCM solution of Pt(II)-19 produced orange-plate-crystals suitable for SCXRD analysis. Figure 4.22 shows the crystal structure obtained for Pt(II)-19. Similar to what was observed for Pt(II)-19-Cl2, the crown ether functionality bends out of the ligand-platinum plane and the square-planar geometry around the platinum is slightly distorted. Pt(II)-19 packs in the solid state forming dimers due to Ï-Ï stacking and Pt-Pt interactions, with the distance between the two platinum atoms being 3.4 Ã , comparable with that obtained for the model complex Pt(II)-16 (3.1 Ã ). This is an exciting finding as it suggests that the supramolecular chemistry of Pt(II)-19, even in a rotaxane, could be a very rich area to explore owing to the possibility of metal-metal bonding. 137 Figure 4.22 SCXRD structures of compound Pt(II)-19 (a) top view, and (b) side view. Ligand preorganization was a successful synthetic strategy to prepare the cis biscyclometalated complexes Pt(II)-16 and Pt(II)-19. It was also observed that addition of n-Bu4NBr helps prevent platinum oxidation and the formation of Pt4+ complexes. Future work will be investigating the absorption and emission properties of Pt(II)-19 in the presence of Na+, K+ and Cs+, to see if the complex has potential applications in cation sensing. In addition, the same complex featuring bigger ether cavities could be prepared for the purpose of forming supramolecular association complexes, such as rotaxanes and pseudorotaxanes. 4.3.! Conclusions In summary, several Pt2+ and Pt4+ complexes were synthesized and characterized, first using a bidentate functionalized phenylpyridine ligand, 7-Ac, then with two flexible tetradentate ligands featuring an ethylene glycol chain, compounds 9 and 11, and finally using two preorganized tetradentate ligands, compounds 16 and 19, the latter containing a full crown ether functionality. 138 The synthetic challenges related to the flexibility of ligands 9 and 11 were addressed through two strategies, high dilution and cation templation. By following these two approaches, four new complexes of Pt2+ and Pt4+ were prepared (Pt(II)-9-Cl, Pt(II)-11-Cl, Pt(IV)-9-Cl2, and Pt(IV)-11-Cl2). The complexes feature a pseudo-crown ether cavity that can host metal ions and linear organic cations, showing promising applications in cation sensing and rotaxane formation. A [2]pseudorotaxane between Pt(IV)-11-Cl2 and dibenzylammonium was formed. We plan to further investigate the host-guest properties of this association complex by performing CV experiments to calculate their redox potentials, since different oxidation states are accessible for the platinum atoms. In conclusion, ligand preorganization was a successful strategy to obtain the target cis biscyclometalated complexes. By using two rigid preorganized ligands, five new complexes of platinum, in three different oxidation states (Pt2+, Pt3+ and Pt4+) were prepared (Pt(II)-16, Pt(III)-16-Cl, Pt(IV)-19-Cl2, Pt(II)-19, and Pt(II)-19-Cl2). Particularly exciting was the formation of a Pt3+ species, as +3 is an uncommon oxidation state for platinum, especially if the ligand is not bridging the two platinum atoms.194,232â235. In addition, we observed that platinum oxidation can be prevented by the addition of n-Bu4NBr in the reaction mixture under N2. In this way, we were able to selectively obtain complex Pt(II)-19. We are currently studying potential application of compound Pt(II)-19 for cation recognition. 4.4.! Experimental section Materials and equipment. Solvents and starting materials were used as received from the supplier. CDCl3, THF-d8 and CD3CN were purchased from Cambridge Isotope Laboratories. CD2Cl2 and DMSO-d6 were purchased from Sigma Aldrich. The reactions were performed under air, unless differently specified in the synthesis. Dry solvents were obtained from INERT column 139 solvent purification system. Single crystal X-ray diffraction data (SCXRD) raw data were collected on a Bruker APEX DUO and on a Bruker APEX X8 diffractometers. Nuclear magnetic resonance (NMR) spectra were recorded Bruker AV-400 and AV-300 spectrometers. High resolution electrospray ionization mass spectra (HRMS) were obtained on a Micromass LCT time-of-flight (TOF) mass spectrometer equipped with an electrospray ion source. UVâVis data were collected with a Cary 5000 UVâVisâNIR Spectrometer using a 1 cm pathlength quartz cuvette. Fluorescence spectra were collected on a Agilent Cary Eclipse Fluorescence Spectrometer with a Xenon flash lamp. Compound 7 was prepared according to a literature procedure.236 NMR data were consistent with those previously reported. Compound 7-Ac. H2SO4 (conc., 3-4 drops) was added to a stirred suspension of 7 (0.50 g, 2.9 mmol) in acetic anhydride (2.7 mL, 29 mmol). The reaction is exothermic and develops heat. The resultant yellow suspension was allowed to cool to room temperature before H2O (0.25 mL) was added. The reaction was stirred for 30 min, and then K2CO3 (10% aq.) was added dropwise until the pH was neutral. The resulting white precipitate was isolated by filtration and washed with H2O. Yield: 0.499 g (2.35 mmol, 81%). Data for 7-Ac. 1H NMR (300 MHz, CDCl3): δ 8.69 (ddd, 1H, J = 4.8, 2.0, 1.0 Hz), 8.02 (d, 2H, J = 8.2 Hz), 7.80â7.68 (m, 3H), 7.22 (d, 2H, J = 7.2 Hz), 2.33 (s, 3H). 13C NMR (75 MHz, CDCl3): # 169.5, 156.7, 151.5, 149.8, 137.2, 137.0, 128.2, 122.3, 122.0, 120.6. LRMS (ESI): Calcd for C13H11NO2Na [7-Ac + Na]: m/z 236.2. Found m/z 236.3. Compound 8. Tetraethylene glycol (10 mL, 60 mmol) was dissolved in DCM (100 mL) and p-toluenesulfonyl chloride (23 g, 0.12 mol) was added to the solution cooled in an ice-bath. Freshly ground KOH (20 g, 0.36 mol) was added in small portions such that the temperature never 140 exceeded 5 °C. The reaction was stirred for 3 h at 0 °C under N2 atmosphere. The resulting suspension was poured into an ice-water bath (150 mL), DCM was added, and the organic layer separated. The aqueous layer was extracted with DCM (3 Ã 100 mL). Combined organic layers were mixed, dried with MgSO4, and evaporated under reduced pressure. The resulting oil was dissolved in hot ethanol (350 mL) and cooled in the freezer (at -20 °C) for 2 d, after which the solution was decanted, and the remaining colorless oil was dried by high vacuum. Yield: 19 g (38 mmol, 63%). Data for compound 8. 1H NMR (400 MHz, CDCl3): # 7.78 (d, 4H, J = 8.0 Hz), 7.33 (d, 4H, J = 8.0 Hz), 4.14 (t, 4H, J = 4.0 Hz), 3.67 (t, 4H, J = 4.0 Hz), 3.55 (s, 8H), 2.43 (s, 6H). 13C NMR (100 MHz, CDCl3): # 144.9, 133.0, 129.8, 128.0, 70.8, 70.6, 69.4, 68.7, 21.5. LRMS (ESI): Calcd for C30H33N2O5 [9 + Na+]: 524.2 m/z. Found 525.1 m/z. Compound 9. A solution of 7 (826 mg, 4.84 mmol) and 8 (1.1 g, 2.2 mmol) in dry THF (50 mL) was slowly added to a refluxing suspension of NaH (1.6 g, 60% mineral oil, 40 mmol) in dry THF (90 mL), the mixture was heated to reflux under N2 for 2 d after which the reaction was allowed to cool to room temperature. Excess NaH was quenched with MeOH and the solvents were evaporated under reduced pressure. The residue was portioned between CHCl3 (50 mL) and H2O (50 mL) and the aqueous layer was extracted with CHCl3 (3 Ã 50 mL). The combined organic phases were dried with MgSO4 and the solution was evaporated under reduced pressure. Compound 9 was purified by flash chromatography with a silica column [eluent, 20% hexane in ethyl acetate] to obtain a white powder, which was further purified by recrystallization in CH3CN. Yield: 700 mg (1.40 mmol, 64%). A single crystal suitable for SCXRD analysis was grown by vapour diffusion of pentane into a solution of 9 in acetone. 141 Data for compound 9. 1H NMR (400 MHz, CDCl3): # 8.65 (d, 2H, J = 8.0 Hz), 7.93 (d, 4H, J = 8.0 Hz), 7.71 (t, 2H, J = 8.0 Hz), 7.65 (d, 2H, J = 8.0 Hz), 7.17 (t, 2H, J = 8.0 Hz), 7.01 (d, 4H, J = 8.0 Hz), 4.19 (t, 4H, J = 4.0 Hz), 3.89 (t, 4H, J = 4.0 Hz), 3.74 (m, 8 H). 13C NMR (100 MHz, CDCl3): # 159.8, 157.2, 149.6, 136.8, 132.2, 128.2, 121.5, 119.9, 114.9, 71.0, 70.8, 69.8, 67.6. LRMS (ESI): Calcd for C30H33N2O5 [9 + H+]: 501.2 m/z. Found 502.1 m/z. UVâVis [CH3CN; λmax, nm (εmax (M-1 cm-1)]: 295 (2.8 Ã 104). Compound 10. Pentaethylene glycol (4.4 mL, 21 mmol) was dissolved in DCM (40 mL) and p-toluenesulfonyl chloride (8.3 g, 0.04 mol) was added to the solution cooled in an ice-bath. Freshly ground KOH (7.1 g, 0.13 mol) was added in small portions such that the temperature never exceeded 5 °C. The reaction was stirred for 3 h at 0 °C under N2 atmosphere. The suspension was poured into an ice-water bath (50 mL), DCM was added, and the organic layer separated. The aqueous layer was extracted with DCM (3 Ã 100 mL), the combined organic layers were mixed, dried with MgSO4 and evaporated under reduced pressure. The resulting oil was dissolved in hot ethanol (100 mL) and cooled in the freezer (at -20 °C) for 2 d. Finally, the solution was decanted, and the remaining colorless oil was dried by high vacuum. Yield: 7.1 g (13 mmol, 62%). Data for compound 10. 1H NMR (400 MHz, CDCl3): # 7.81 (d, 4H, J = 7.3 Hz), 7.36 (d, 4H, J = 8.8 Hz), 4.17 (t, 4H, J = 4.4 Hz), 3.70 (t, 4H, J = 4.4 Hz), 3.62 (s, 4 H), 3.60 (s, 8H), 2.45 (s, 6 H). 13C NMR (100 MHz, CDCl3): 144.7, 132.7, 129.7, 127.7, 70.4, 70.3, 70.2, 69.2, 68.4, 21.4. LRMS (ESI): Calcd for C24H35O10S2+[10 + H+]: 547.2 m/z. Found 547.2 m/z. Compound 11. A solution of 7 (1.3 g, 7.6 mmol) and 10 (1.9 g, 3.4 mmol) in dry THF (100 mL) was slowly added to a refluxing suspension of NaH (2.8 g, 60% mineral oil, 71 mol) in dry THF (100 mL). The mixture was heated to reflux under N2 for 2 d, after which the reaction was allowed to cool to room temperature. Excess of NaH was quenched with MeOH and the 142 solvents were evaporated under reduced pressure. The residue was portioned between CHCl3 (50 mL) and H2O (50 mL), the aqueous layer was extracted with CHCl3 (3 Ã 50 mL) and the combined organic phases were dried with MgSO4 and taken to dryness by rotatory evaporation. Compound 11 was purified by recrystallization from CH3CN. Yield: 1.7 g (0.003 mol, 92%). Data for compound 11. 1H NMR (400 MHz, CDCl3): δ 8.66 (d, 1H, J = 4.6 Hz), 7.95 (d, 2H, J = 8.8 Hz), 7.74 (t, 1H, J = 6.9 Hz), 7.68 (d, 1H, J = 8.0 Hz), 7.20 (t, 1H, J = 7.2 Hz), 7.01 (d, 2H, J = 8.8 Hz), 4.19 (t, 2H, J = 4.2 Hz), 3.88 (t, 2H, J = 3.9 Hz), 3.78 â 3.68 (m, 6H). 13C NMR (100 MHz, CDCl3): 159.7, 157.1, 136.7, 132.1, 128.2, 121.5, 119.8, 114.8, 70.9, 70.7, 69.7, 67.5. LRMS (ESI): Calcd for C32H35N2O6 [11 + H+]: 545.3 m/z. Found 545.3 m/z. UVâVis [CH3CN; λmax, nm (εmax (M-1 cm-1)]: 292 (2.3 Ã 104). Pt(dmso)2Cl2 was prepared according to a literature procedure.237 NMR data were consistent with those previously reported. Pt(7-Ac)(dmso)Cl was prepared similarly to a literature procedure.206 7-Ac (86 mg, 0.40 mmol), Pt(dmso)2Cl2 (100 mg, 0.24 mmol), and sodium carbonate, Na2CO3 (85 mg, 0.80 mmol) were suspended in p-xylene (15 mL) under N2 and heated to 105 °C for 4 d. The cooled reaction mixture was concentrated and purified by flash chromatography with a silica column [eluent, 20% hexane in ethyl acetate] to afford Pt(7-Ac)(dmso)Cl as a yellow solid. Yield: 74 mg (0.14 mmol, 60%). A single crystal suitable for SCXRD analysis was grown by slow evaporation of a solution of Pt(7-Ac)(dmso)Cl in DCM. Data for Pt(7-Ac)(dmso)Cl. 1H NMR (300 MHz, CDCl3): δ 9.61 (dd, 1H, J = 6 and 1.5 Hz, JHPt = 36 Hz), 8.13 (d, 1H, J = 2.4 Hz, JHPt = 51 Hz), 7.89 (ddd, 1H, J 7.5, Hz, 6.6 and 1.5 Hz), 7.71 (d, 1H, J = 7.8 Hz), 7.56 (d, 1H, J = 8.1 Hz), 6.98 (dd, 1H, J = 8.1 and 2.4 Hz), 3.65 (s, 6H, 143 JHPt = 24 Hz), 2.30 (s, 3H). LRMS (ESI): Calcd for C15H16ClNO3SPtNa [Pt(7-Ac)(dmso)Cl + Na+]: m/z 543.0. Found m/z 544.2. Pt(7)(dmso)Cl was prepared similarly to Pt(7-Ac)(dmso)Cl. 7-Ac (86 mg, 0.40 mmol), Pt(dmso)2Cl2 (0.100 g, 0.24 mmol), and sodium carbonate, Na2CO3 (85 mg, 0.80 mmol) were suspended in p-xylene (15 mL) under N2 and heated to reflux for 4 d. The cooled reaction mixture was concentrated and was purified by flash chromatography with a silica column [eluent, 20% hexane in ethyl acetate] to afford Pt(7)(dmso)Cl as a yellow solid. Yield: 61 mg (0.13 mmol, 53%). Data for Pt(7)(dmso)Cl. 1H NMR (300 MHz, DMSO-d6): δ 9.69 (s, 1H), 9.37 (dd, 1H, J = 6.0 and 1.2 Hz, JHPt = 33 Hz), 8.01 (m, 1H), 7.92 (m, 1H), 7.67 (d, 1H, J = 2.4 Hz, JHPt = 52 Hz), 7.60 (d, 1H, J = 8.5 Hz), 7.32 (m, 1H), 6.57 (dd, 1H, J = 8.5 and 2.5 Hz). 13C NMR (75 MHz, DMSO-d6): δ 165.4, 159.1, 148.7, 142.3, 141.1, 135.4, 126.0, 120.8, 120.7, 118.3, 111.8 ppm. LRMS (ESI): Calcd for C13H13ClNO2SPt [Pt(7)(dmso)Cl - H]: m/z 477.0. Found m/z 478.1. FT-IR (ATR, cm-1): 1020 (s), 1122 (s), 1223 (s), 1435 (s), 1552 (s), 1583 (s), 2123 (m), 2254 (m), 2920 (m), 3082 (m), 3000-3500 (b). Pt(7-Ac)2Cl was prepared similarly to a literature procedure.208 7-Ac (105 mg, 0.49 mmol) and K2PtCl4 (100 mg, 0.24 mmol) were suspended in glacial AcOH (50 mL) under N2 and heated to 75 °C for 15 h. The cooled reaction mixture was concentrated. The residue was dissolved in DCM and washed with HCl (2.5 M, 20 mL) and H2O (20 mL), dried over MgSO4, and concentrated. Yield: 566 mg (0.86 mmol, 36%). A single crystal suitable for SCXRD was grown by vapour diffusion of hexanes into a solution of Pt(7-Ac)2Cl in DCM. Data for Pt(7-Ac)2Cl. 1H NMR (300 MHz, CDCl3): δ 9.59 (dd, 1H, J = 5.7 and 0.9 Hz, JHPt = 38 Hz), 9.20 (dd, 1H, J = 5.7 and 1.8 Hz, JHPt = 44 Hz), 8.06 (m, 2H), 7.97 (m, 1H), 7.76 (m, 144 1H), 7.63 (m, 1H), 7.49 (d, 1H, J = 8.1 Hz), 7.41 (m, 1H), 7.36 (d, 1H, J = 8.4 Hz), 7.08 (m, 3H), 6.75 (dd, 1H, J = 8.4, 2.1 Hz), 5.85 (d, 1H, J = 2.3 Hz, JHPt = 54 Hz), 2.24 (s, 3H), 2.22 (s, 3H). LRMS (ESI): Calcd for C26H20ClN2O4Pt [Pt(7-Ac)2Cl - H]: m/z 654.1. Found m/z 655.4. Pt(II)-9-Cl. A mixture of 9 (200 mg, 0.40 mmol), K2PtCl4 (166 mg, 0.40 mmol) in 96 mL of AcOH was degassed and heated under reflux under N2 for 24 h. The solvent was removed under vacuum and the residue was purified by flash chromatography with a silica column [eluent, 4:3:3 hexane/DCM/acetone] as eluent to obtain the pendant compound as a yellowish powder. Yield: 120 mg (0.16 mmol, 41%). A single crystal suitable for SCXRD analysis was grown by vapour diffusion of diethyl ether into a solution of Pt(II)-9-Cl in CHCl3. Data for Pt(II)-9-Cl. 1H NMR (400 MHz, CD2Cl2): # 9.59 (d, 1H, J = 8.0 Hz) 9.21 (d, 1H, J = 8.0 Hz), 8.19 (d, 2H, J = 8.0 Hz), 7.95 (t, 1H, J = 8.0 Hz), 7.75 (t, 1H, J = 8.0 Hz), 7.70 (d, 1H, J = 8.0 Hz), 7.45 (d, 1H, J = 8.0 Hz), 7.33 (t, 1H, J = 4.0 Hz), 7.27 (d, 1H, J = 8.0 Hz), 7.07 (d, 2H, J = 8.0 Hz), 6.54 (dd, 1H, J = 8.0, 4.0 Hz), 5.67 (d, 1 H), 4.20 (m, 2H), 3.99 (m, 2 H), 3.51â3.75 (m, 12H). 13C NMR (100 MHz, CDCl3): # 167.1, 161.4, 160.4, 159.2, 154.8, 151.2, 141.9, 138.8, 137.7, 132.9, 131.2, 128.4, 127.2, 124.4, 123.0, 120.7, 118.1, 117.5, 115.9, 115.0, 109.5, 71.4, 71.0, 70.9, 70.6, 69.9, 69.3, 68.0, 67.7. LRMS (ESI): Calcd for C30H31N2O5Pt [Pt(II)-9-Cl - Cl]: m/z 694.2. Found m/z 694.7. UVâVis [CH3CN; λmax, nm (εmax (M-1 cm-1)]: 264 (4.0 Ã 104), 284 (3.3 Ã 104), 398 (2.7 Ã 103). Data for Pt(II)-9-Cl + 5 equiv NaBF4. UVâVis [CH3CN; λmax, nm (εmax (M-1 cm-1)]: 264 (2.5 Ã 103), 284 (2.2 Ã 103), 398 (1.0 Ã 102). Data for Pt(II)-9-Cl + 20 equiv NaBF4. UVâVis [CH3CN; λmax, nm (εmax (M-1 cm-1)]: 264 (1.5 Ã 103), 284 (1.3 Ã 102), 398 (4.4 Ã 10). 145 Data for Pt(II)-9-Cl + 5 equiv KBF4. UVâVis [CH3CN; λmax, nm (εmax (M-1 cm-1)]: 264 (1.3 Ã 103), 284 (1.1 Ã 103), 398 (8.9 Ã 10). Data for Pt(II)-9-Cl + 20 equiv KBF4. UVâVis [CH3CN; λmax, nm (εmax (M-1 cm-1)]: 264 (3.9 Ã 102), 284 (3.2 Ã 102). Pt(IV)-9-Cl2. A mixture of 8 (100.0 mg, 0.20 mmol), K2PtCl4 (83.0 mg, 0.20 mmol) and CsCO3 (651.6 mg, 2.0 mmol) in 11 mL of AcOH was degassed and heated at 110 °C under N2 for 24 h. The solvent was removed under vacuum. The residue was partitioned between CHCl3 and H2O. The organic layer was extracted and washed with H2O (3 Ã 15 mL). CHCl3 was evaporated and the crude product was washed 3 times with 10 mL of hexanes. CHCl3 was added and the suspension was filtered to give the product as a brown precipitate. Yield: 99.1 mg (0.130 mmol, 65%). Data for Pt(IV)-9-Cl2. 1H NMR (400 MHz, CDCl3): # 9.81 (d, 1H, J = 5.5 Hz), 8.03 (t, 1H, J = 7.3 Hz), 7.94 (m, 2H), 7.71 (d, 2H, J = 4.9 Hz), 7.59 (d, 2H, J = 8.8 Hz), 7.53 (t, 1H, J = 6.1 Hz), 7.37 (d, 1H, J = 6.1 Hz), 6.99 (d, 1H, J = 8.8, 2.7 Hz), 6.86 (m, 1H), 6.61 (dd, 1H, J = 8.5, 2.4 Hz), 6.02 (d, 1H, J = 2.4 Hz), 4.5â3.5 (m, 16H). Calcd for C30H30ClN2O5Pt [Pt(IV)-9-Cl2 â Cl-]: m/z 728.1. Found m/z 728.3. UVâVis [CH3CN; λmax, nm (εmax (M-1 cm-1)]: 295 (1.2 Ã 104), 327 (1.2 Ã 104). Pt(II)-11-Cl. A mixture of 11 (50.0 mg, 0.092 mmol) and K2PtCl4 (38.1 mg, 0.092 mmol) in 25 mL of AcOH was heated at 100 °C under N2 for 24 h. The solvent was removed under vacuum and the residue was purified by flash chromatography with a silica column [eluent, 3:3:4 hexane/DCM/acetone] to obtain the pendant compound as a yellowish powder. Yield: 7.6 mg (0.010 mmol, 11%). A single crystal suitable for SCXRD analysis was grown by vapour diffusion of diethyl ether into a solution of Pt(II)-11-Cl in DCM. 146 Data for Pt(II)-11-Cl. 1H NMR (400 MHz, CDCl3): # 9.63 (d, 1H, J = 5.7 Hz), 9.26 (d, 1H, J = 5.8 Hz), 8.19 (d, 2H, J = 8.6 Hz), 7.91 (t, 1H, J = 7.7 Hz), 7.71 (t, 1H, J = 7.7 Hz), 7.65 (d, 1H, J = 7.7 Hz), 7.40 (d, 1H, J = 8.0 Hz), 7.30 (t, 1H, J = 6.8 Hz), 7.23 (d, 1H, J = 8.5 Hz), 7.02 (t, 1H, J = 6.3 Hz), 6.95 (d, 2H, J = 8.7 Hz), 6.54 (dd, 1H, J = 8.5 and 2.3 Hz), 5.67 (d, 1H, J = 2.3 Hz), 4.21â3.94 (m, 4 H), 3.48â3.79 (m, 16 H). LRMS (ESI): Calcd for C32H35N2O6Pt [Pt(II)-11-Cl â Cl-]: 738.2 m/z. Found 738.4 m/z. Pt(IV)-11-Cl2. A mixture of 11 (100.0 mg, 0.184 mmol), K2PtCl4 (76.3 mg, 0.184 mmol) and CsCO3 (599.5 mg, 1.84 mmol) in 11 mL of AcOH was degassed and heated at 110 °C under N2 for 24 h. The solvent was removed under vacuum. The residue was partitioned between CHCl3 and H2O. The organic layer was extracted and washed with H2O (3 Ã 15 mL). The CHCl3 was evaporated, and the crude was dissolved in a 1:4 mixture of DCM and MeOH. Addition of diethyl ether produces a fine precipitate that was centrifuged and washed with hexanes to give a purple solid. Yield: 69.6 mg (0.0874 mmol, 46%). A single crystal suitable for SCXRD analysis was grown by vapour diffusion of isopropyl ether into a solution of Pt(II)-11-Cl in CH3CN. Data for Pt(IV)-11-Cl2. 1H NMR (400 MHz, CD2Cl2) δ 9.81 (d, 1H, J = 4.7 Hz), 8.02 (t, 1H, J = 7.0 Hz), 7.97 â 7.89 (m, 2H), 7.71 (d, 2H, J = 3.8 Hz), 7.59 (dd, 2H, J = 8.7 and 1.8 Hz), 7.51 (t, 1H, J = 6.4 Hz), 7.36 (d, 1H, J = 6.0 Hz), 6.99 (dd, 1H, J = 8.6 and 2.4 Hz), 6.85 (td, 1H, J = 5.7 and 3.6 Hz), 6.62 (dd, 1H, J = 8.6 and 2.4 Hz), 6.13â5.91 (m, 1H), 4.50â4.21 (m, 2H), 4.12â3.43 (m, 18H). 13C NMR (100 MHz, CD2Cl2): δ 165.0, 161.7, 160.8, 148.0, 146.3, 146.1, 140.4, 138.4, 134.0, 133.6, 126.80, 126.76, 123.8, 122.7, 120.5, 120.2, 118.4, 115.8, 114.3, 111.9, 71.21, 71.19, 70.97, 70.92, 70.87, 69.9, 69.7, 68.5, 67.9. LRMS (ESI): Calcd for [Pt(IV)-11-Cl2 + H+]: 808.1 m/z. Found 807.4 m/z. UVâVis [CH3CN; λmax, nm (εmax (M-1 cm-1)]: 330 (1.4 Ã 104, 1 shoulder). 147 Pt(IV)-11-Cl2 + dibenzylammonium hexafluorophosphate. A 2.5 mM solution of Pt(IV)-11-Cl2 (5 mg, 6.25 Ã 10-3 mmol) and dibenzylammonium hexafluorophosphate (2 mg, 6.25 Ã 10-3 mmol) in a 1:1 mixture of CD3CN/CDCl3 was prepared in an NMR tube that was kept at 25 °C. The reaction was monitored by 1H NMR spectroscopy and equilibrium was reached after 2 d. The association constant was calculated to be 800 M-1. The solvent was then evaporated and a 2.5 mM solution in CD3CN was prepared at 25 °C. The binding constant in CD3CN is 1500 M-1. The formation of the association complex was confirmed by mass-spectrometry. LRMS (ESI): Calcd for [Pt(IV)-11-Cl2 + dibenzylammonium+]: 1005.3 m/z. Found 1006.5 m/z. The same procedure was followed with N,Nâ-dimethyl-4,4â-bipyridinium hexafluorophosphate and with 1,2-bis(4,4â-bipyridinium)ethane hexafluorophosphate. Compound 12 was prepared according to a literature procedure.231 NMR data were consistent with those previously reported. Compound 13. A solution of N-bromosuccinimide (2.0 g, 4.5 mmol) in DMF (5 mL) was slowly added at 0 °C (over 20 min) to a solution containing 12 (1.0 g, 4.9 mmol) in 5 mL of DMF. After 1 h the reaction was quenched with H2O (15 mL) and stored overnight. The resulting brown solid was separated by filtration, washed with H2O and recrystallized with CHCl3 and hexanes to obtain a white crystalline powder. Yield: 900 mg (2.52 mmol, 51%). Data for compound 13. 1H NMR (400 MHz, CDCl3) # 7.20 (dd, 2H, J = 8.5, 1.8 Hz) 7.00 (d, 2H, J = 1.8 Hz), 6.94 (d, 2H, J = 8.6 Hz), 5.86 (s, 2H). 13C NMR (100 MHz, CDCl3) # 146.7, 144.1, 127.9, 121.32, 118.5, 111.5. LRMS (ESI): Calcd for C12H7Br2O3 [13 â H+]: 359.0 m/z. Found 359.0 m/z. Compound 14. To a solution of 13 (1.2 g, 3.4 mmol) in acetone (30 mL), K2CO3 (4.8 g, 34.4 mmol) and iodomethane (560 µL, 8.9 mmol) were added. The suspension was heated to reflux 148 for 18 h. After cooling to room temperature, the solid component was removed by filtration and the filtrate was concentrated by rotatory evaporation. The resulting residue was dissolved in CH2Cl2 and filtered once again to give, after evaporation, a white solid. Yield: 900 mg (1.47 mmol, 67%). Data for compound 14. 1H NMR (400 MHz, CDCl3) # 7.22 (dd, 2H, J = 8.0, 4.0 Hz), 6.95 (d, 2H, J = 4.0 Hz), 6.87 (d, 2 H, J = 12.0 Hz), 3.86 (s, 6H). 13C NMR (100 MHz, CDCl3) # 149.8, 146.1, 127.2, 121.9, 114.0, 112.5, 56.3. LRMS (ESI): Calcd for C14H12Br2O3Na [14 + Na+]: 410.9 m/z. Found 410.9 m/z. Compound 15. A mixture of 14 (1.3 g, 3.4 mmol), bis(pinacolato)diboron (1.9 g, 7.4 mmol), potassium acetate (1.9 g, 19.7 mmol), Pd(PPh3)4 (0.390 g, 0.338 mmol) and 1,4-dioxane (16 mL) was stirred at 80 °C for 24 h under N2 and then the 1,4-dioxane was removed by rotatory evaporation. H2O (75 mL) was added to the resulting black powder, and the mixture was extracted with benzene (3 Ã 75 mL). The combined organics were washed with brine and then dried over anhydrous MgSO4. The solvent was removed by rotary evaporation and the resulting brown oil was purified by flash chromatography with a silica column [eluent, 20% ethyl acetate in hexanes, Rf = 0.35] to give 15 as a white powder. Yield: 1.0 g (2.1 mmol, 62%). Data for compound 15. 1H NMR (400 MHz, CDCl3) δ 7.55 (dd, 2H, J = 8.3, 1.3 Hz), 7.26 (d, 2H, J = 1.3 Hz), 6.97 (d, 2H, J = 8.3 Hz), 3.88 (s, 6H), 1.30 (s, 24H). 13C NMR (100 MHz, CDCl3) δ 153.4, 145.5, 131.2, 124.7, 111.7, 83.6, 55.8, 24.8. LRMS (ESI): Calcd for C26H37B2O7 [15 + H+]: 483.3 m/z. Found 483.2 m/z. Compound 16. Compound 15 (0.705 g, 1.46 mmol), 2-bromopyridine (0.420 mL, 4.40 mmol), sodium carbonate (0.913 g, 8.65 mmol), and Pd(PPh3)4 (0.169 g, 0.146 mmol) were dissolved in a mixture of H2O (9 mL) and 1,4-dioxane (27 mL). The reaction mixture was stirred 149 at reflux under N2 for 24 h and was concentrated by rotary evaporation. H2O (150 mL) was added to the mixture and, after 15 min of sonication, the contents were extracted with DCM (4 Ã 60 mL) and dried over anhydrous MgSO4. Concentrating the reaction mixture under vacuum produced a brown powder, which was purified by flash chromatography with a silica column [eluent, 45% hexanes in ethyl acetate, Rf = 0.38] to afford 16 as a white powder. Yield: 0.312 g (0.812 mmol, 55%). Data for compound 16. 1H NMR (400 MHz, CDCl3) δ 8.60 (ddd, 2H, J = 4.8, 1.9, 0.9 Hz), 7.81 (dd, 2H, J = 8.6 Hz, 2.2 Hz), 7.66 (td, 2H, J = 7.9, 1.3 Hz), 7.56 (s, 2H), 7.54 (d, 2H, J = 1.9 Hz), 7.14 (ddd, 2H, J = 7.6, 4.8, 0.9 Hz), 7.10 (d, 2H, J = 8.6 Hz), 3.93 (s, 6H). 13C NMR (100 MHz, CDCl3) δ 156.4, 151.3, 149.6, 146.1, 136.8, 132.6, 122.8, 121.7, 120.1, 117.5, 112.7, 56.2. LRMS (ESI): Calcd for C24H21N2O3 [16 + H+]: 385.2 m/z. Found 385.2 m/z. UVâVis [DCM; λmax, nm (εmax (M-1 cm-1)]: 293 (2.4 Ã 104, 1 shoulder). Compound Pt(II)-16. A 250 mL two-neck flask was charged with 14 (0.100 g, 0.260 mmol) and K2PtCl4 (0.108 g, 0.260 mmol) and was degassed and backfilled with nitrogen gas three times. Glacial AcOH (62 mL) underwent 3 freeze-pump-thaw cycles with liquid nitrogen and was transferred to the reaction vessel via cannulation. The reaction mixture was heated to 100 °C for 24 h under N2, after which the mixture was filtered, and the solvent was removed under vacuum. The resulting black powder was washed with hexanes (3 Ã 30 mL) and dissolved in 50 mL of DCM, after which it was filtered to give a clear yellow solution. Upon removal of the solvent, Pt(II)-16 was afforded as a bright orange powder. Yield: 0.128 g (0.222 g, 85% yield). A single crystal suitable for SCXRD analysis was grown by vapour diffusion of hexanes into a solution of Pt(II)-16 in DCM. 150 Data for compound Pt(II)-16. 1H NMR (400 MHz, DMSO-d6) δ 9.08 (d, 2H, J = 8.0 Hz), 8.17 (d, 2H, J = 8.0 Hz), 8.07 (t, 2H, J = 8.0 Hz), 7.69 (d, 2H, J = 8.0 Hz), 7.50 (t, 2H, J = 8.0 Hz), 6.94 (d, 2H, J = 8.0 Hz), 3.94 (s, 6H). 1H NMR (100 MHz, CD2Cl2) δ 8.95 (dt, 2H, J = 5.6, 1.0 Hz), 7.96 (m, 4H), 7.40 (td, 2H, J = 5.6, 2.7 Hz), 6.95 (d, 2H, J = 8.3 Hz), 4.09 (s, 6H). 13C NMR (100 MHz, DMSO-d6) δ 164.3, 150.0, 148.6, 139.8, 139.0, 138.6, 126.7, 122.1, 119.7, 119.2, 107.6, 55.9. HRMS (ESI/TOF-Q). Calcd for C24H18N2O3Na194Pt [Pt(II)-16 + Na+]: m/z 599.0842. Found: m/z 599.0446. UVâVis [CH2Cl2; λmax, nm (εmax (M-1 cm-1)]: 263 (2.5 Ã 104), 316 (2.2 Ã 104), 383 (1.9 Ã 104). Fluorescence [CH2Cl2; λmax, nm]: 507, 540. Compound Pt(IV)-16-Cl2. A mixture of 16 (42 mg, 0.11 mmol) and K2PtCl4 (46 mg, 0.11 mmol) in 25 mL of glacial AcOH was refluxed under air for 2 d. The resulting green precipitate was filtered washed with AcOH and dried for 2 h. Yield: 30 mg (0.05 mmol, 43%). A single crystal suitable for SCXRD analysis was grown by vapour diffusion of hexanes into a solution of Pt(IV)-16-Cl2 in DCM. Data for compound Pt(IV)-16-Cl2. 1H NMR (400 MHz, DMSO-d6) δ 9.29 (d, 2H, J = 6.7 Hz), 8.47 (d, 2H, J = 8.2 Hz), 8.20 (t, 2H, J = 7.3 Hz), 7.92 (d, 2H, J = 8.5 Hz), 7.70 (t, 2H, J = 7.3 Hz), 7.11 (d, 2H, J = 8.5 Hz), 4.00 (s, 6H). LRMS (ESI): Calcd for C24H18Cl2N2O3PtNa [Pt(IV)-16-Cl2 + Na+]: 670.0 m/z. Found 671.1 m/z. UVâVis [DCM; λmax, nm (εmax (M-1 cm-1)]: 292 (8.4 Ã 103), 357 (5.5 Ã 103). Compound 17. Procedure adapted from modified literature procedures.238 NaH (60% dispersion in mineral oil, 5.4 g, 135 mmol) and was dissolved in dry THF (150 mL) and was stirred at 60 °C under N2. To the stirring solution, a mixture of 13 (2.5 g, 6.8 mmol) and 8 (4.1 g, 8.2 mmol) in dry THF was added over 24 h. The reaction was stirred at 60 °C for 24 h, quenched with MeOH and concentrated under vacuum. The resulting white powder was partitioned between H2O 151 (125 mL) and CHCl3 (100 mL) and extracted with CHCl3 (3 Ã 100 mL). The combined organics were washed with 1 M HCl (1 Ã 100 mL), with H2O (1 Ã 100 mL) and with brine (1 Ã 100 mL) and dried over anhydrous MgSO4. Removal of the solvent by rotary evaporation produced a white powder, which was washed with hexanes (5 Ã 30 mL), decanted and dried, producing 17 as a white powder. Yield: 1.8 g (3.5 mmol, 51%). Data for compound 17. 1H NMR (400 MHz, CDCl3) δ 7.18 (dd, 2H, J = 8.6, 2.5 Hz), 6.97 (d, 2H, J = 2.2 Hz), 6.88 (d, 2H, J = 8.8 Hz), 4.17 (t, 4H, J = 4.4 Hz), 3.80 (t, 4H, J = 4.4 Hz), 3.65 (m, 8H). 13C NMR (100 MHz, CDCl3) δ 148.9, 146.6, 126.9, 122.0, 116.0, 112.7, 71.3, 70.8, 69.5, 69.2. LRMS (ESI): Calcd for C20H21Br2O6 [17 + Na+]: 541.0 m/z. Found 541.0 m/z. Compound 18. Compound 17 (1.5 g, 2.9 mmol), bis(pinacolato)diboron (1.6 g, 6.4 mmol), potassium acetate (0.759 g, 7.73 mmol), Pd(PPh3)4 (0.334 g, 0.289 mmol) were dissolved in 1,4-dioxane (30 mL). The reaction mixture was stirred under N2 at 80 °C for 24 h after which it was concentrated under vacuum. H2O (150 mL) was added to the mixture, and the suspension was sonicated for 10 min. The contents were extracted with benzene (4 Ã 60 mL). The combined organics were washed with brine (60 mL), dried over anhydrous MgSO4 and concentrated by rotary evaporation. The resulting brown oil was purified by flash chromatography with a silica column [eluent, 5% MeOH in DCM, Rf = 0.35] to afford 18 as a brown oil. Yield: 1.5 g (2.4 mmol, 84%). Data for compound 18. 1H NMR (400 MHz, CDCl3) δ 7.52 (dd, 2H, J = 8.3, 1.6 Hz), 7.30 (d, 2H, J = 1.3 Hz), 6.97 (d, 2H, J = 8.0 Hz), 4.22 (t, 4H, J = 4.4 Hz), 3.80 (t, 4H, J = 4.4 Hz) 3.65 (m, 8H), 1.31 (s, 24H). 13C NMR (100 MHz, CDCl3) δ 152.5, 145.9, 130.9, 124.8, 113.4, 83.6, 71.3, 70.7, 69.6, 68.7, 25.0, 24.8. LRMS (ESI): Calcd for C32H47B2O10 [18 + H+]: 613.3 m/z. Found 613.4 m/z. 152 Compound 19. Compound 18 (0.100 g, 0.163 mmol), Na2CO3 (0.173 g, 1.63 mmol), Pd (PPh3)4 (0.020 g, 0.017 mmol), 2-bromopyridine (0.050 mL, 0.49 mmol) were dissolved in 1,4-dioxane (27 mL) and H2O (9 mL). The reaction mixture was stirred at reflux under N2 for 24 h. Upon cooling to room temperature, the solvent was removed under vacuum. H2O (40 mL) was added and the resulting brown solid, that was extracted with DCM (3 Ã 40 mL), washed with brine (1 Ã 60 mL), dried over anhydrous MgSO4, and concentrated under vacuum. The crude product was purified by flash chromatography with a silica column [eluent, 5% MeOH in DCM, Rf = 0.17] to afford 19 as a brown oil. Yield: 0.014 g (0.028mmol, 17%). A single crystal suitable for SCXRD analysis was grown by vapour diffusion of hexanes into a solution of 19 in DCM. Data for compound 19. 1H NMR (400 MHz, CDCl3) δ 8.60 (dd, 2H, J = 4.8, 0.6 Hz), 7.77 (dd, 2H, J = 8.6, 2.2 Hz), 7.68 (td, 2H, J = 7.9, 1.9 Hz), 7.57 (m, 4H) J = 2.2 Hz), 7.16 (ddd, 2H, J = 8.6, 4.8, 1.3 Hz), 7.11 (d, 2H, J = 8.6 Hz), 4.28 (t, 4H, J = 4.8 Hz), 3.85 (t, 4H, J = 4.8 Hz), 3.69 (m, 8H). 13C NMR (100 MHz, CDCl3,) δ 156.7, 150.7, 149.6, 146.6, 136.7, 132.9, 122.5, 121.7, 120.1, 117.6, 114.7, 71.5, 70.9, 69.8, 69.2. LRMS (ESI): Calcd for C30H30N2O6Na [19 + Na+]: 537.2 m/z. Found 537.3 m/z. Compound Pt(II)-19 was prepared according to a modified literature procedure.239 A 100 mL three-neck round-bottom flask was charged with compound 19 (40 mg, 0.08 mmol), K2PtCl4 (37 mg, 0.09 mmol), and n-Bu4NBr (3.2 mg, 0.01 mmol) and 30 mL of glacial AcOH was added. The mixture was bubbled with nitrogen for 30 min and then stirred at room temperature for 12 h. The reaction mixture was then heated to 110 °C for 72 h, after which 100 mL of H2O were added and the mixture was cooled to room temperature. The precipitate was collected through filtration, washed three times with H2O and dried under air. The collected solid was purified by flash chromatography with a silica column [eluent, 2.5â10% MeOH in DCM, Rf = 0.21] to afford Pt(II)-153 19 as an orange powder. Yield: 24 mg (0.03 mmol, 43%). A single crystal suitable for SCXRD analysis was grown by vapour diffusion of hexanes into a solution of Pt(II)-19 in DCM. Data for compound Pt(II)-19. 1H NMR (400 MHz, CD2Cl2) δ 9.00 (d, 2H, J = 4.9 Hz), 7.91 (m, 4H), 7.52 (d, 2H, J = 8.5 Hz), 7.33 (m, 2H), 6.89 (d, 2H, J = 8.2 Hz), 4.35 (t, 4H, J = 4.9 Hz), 4.06 (t, 4H, J = 4.9 Hz), 3.74â3.87 (m, 8H). LRMS (ESI): Calcd for C30H28N2O6Cl2PtNa [Pt(II)-19 + Na+]: 730.2 m/z. Found: 731.4 m/z. Compound Pt(IV)-19-Cl2. AcOH (23 mL) was added to a 100 mL round-bottom flask charged with 19 (50 mg, 0,10 mmol) and K2PtCl4 (44 mg, 0.11 mmol). The reaction mixture was stirred at 110 °C for 5 d. The resulting red solid was filtered under vacuum. Yield: 40 mg (0.05 mmol, 53%). A single crystal suitable for SCXRD analysis was grown by vapour diffusion of hexanes into a solution of Pt(IV)-19-Cl2 in DCM. Data for compound Pt(IV)-19-Cl2. 1H NMR (400 MHz, CD2Cl2) δ 9.01 (d, 2H, J = 5.5 Hz), 8.12 (d, 2H, J = 7.9 Hz), 8.02 (t, 2H, J = 9.6 Hz), 7.66 (d, 2H J = 5.8 Hz), 7.57 (t, 2H, J = 7.2 Hz), 7.00 (d, 2H, J = 8.5 Hz), 4.38 (t, 4H, J = 4.4 Hz), 4.06 (t, 4H, J = 4.8 Hz), 3.82â3.70 (m, 8H). LRMS (ESI): Calcd for C30H28N2O6Cl2PtNaCl2 [Pt(IV)-19-Cl2 + Na+]: 800.1 m/z. Found: 801.4 m/z. UVâVis characterization. UVâVis data were collected with a Cary 5000 UVâVisâNIR spectrometer. Compounds 9, 11, Pt(II)-9-Cl (both pure and with the addition of 5 and 20 equiv of NaBF4 and KBF4), Pt(IV)-9-Cl2, Pt(IV)-11-Cl2 (both pure and with the addition of 5 equiv of KBF4) were dissolved in CH3CN and the spectra were collected in a range of concentrations (from 25 µM to 250 µM). Compounds 16, Pt(II)-16 and Pt(IV)-16-Cl2 were dissolved in DCM and the spectra were collected at concentrations of 25 µM for 16 and Pt(IV)-16-Cl2, and 35 µM for Pt(II)-16. 154 Fluorescence characterization. Fluorescence emission data were collected with an Agilent Cary Eclipse Fluorescence Spectrophotometer. Compound Pt(II)-16 was dissolved in DCM and degassed with Ar. The spectra were collected over a range of concentrations (from 4 µM to 10 µM). Binding constant determination. The binding constant calculation for the association complex between Pt(IV)-11-Cl2 and dibenzylammonium hexafluorophosphate was calculated by integrating the 1H NMR signals corresponding to the association complex, compound Pt(IV)-11-Cl2 and dibenzylammonium hexafluorophosphate once the reaction reached equilibrium, at 25 °C in a 1:1 mixture of CD3CN/CHCl3 and in CD3CN. Single-crystal X-ray diffraction. SCXRD raw data were collected on a Bruker APEX DUO diffractometer using graphite-monochromated Mo Kα radiation (λ = 0.71073) at 90 K, and processed using APEX2143 or APEX3,167 with the exception of Pt(IV)-11-Cl2 and Pt(IV)-19-Cl2 data, which was collected on a Bruker X8 at 100 K. Data were collected to a resolution of 0.77 Ã , with the exception of Pt(II)-11-Cl (0.83 Ã ), Pt(IV)-11-Cl2 (0.84 Ã ) and 9 (0.84 Ã ). Pt(7-Ac)2Cl structure was solved using SHELXS 86,144 whereas Pt(IV)-16 and Pt(IV)-19-Cl2 structure were solved using SIR 92.145 All the other structures were solved using SUPERFLIP146 and refined using full-matrix least-squares on F2 within the CRYSTALS147 suite. Hydrogen atoms were initially refined with restraints on bond lengths and angles, after which the positions were used as the basis for a riding model.148 All non-hydrogen atoms were refined anisotropically. In case of highly disordered solvent molecules PLATON/SQUEEZE149 was used. A summary of the crystallographic data is reported in Table 4.1, Table 4.2, Table 4.3, Table 4.4, and Table 4.5. 155 Table 4.1 Summary of crystallographic data for compounds Pt(7-Ac)2Cl and Pt(7-Ac)(dmso)Cl. Compound Pt(7-Ac)2Cl Pt(7-Ac)(dmso)Cl Chemical formula C26H21ClN2O4Pt C15H16ClNO3PtS Formula weight 656.01 520.91 a (Ã ) 17.178(4) 5.9898(4) b (Ã ) 9.280(2) 9.2192(7) c (Ã ) 31.856(8) 28.918(2) ! (°) 90 90 β (°) 90 91.8815(13) γ (°) 90 90 Unit cell volume (Ã 3) 5078(2) 1596.0(2) Temperature (K) 90 90 Crystal system orthorhombic monoclinic Space group P c a 21 P 21/n Z 8 4 Absorption coefficient (µ/mm-1) 5.665 9.100 Total number of reflections 60697 27199 Unique reflections 11534 3656 Final R1 values (I > 2"(I)) 0.0829 0.0208 Final wR(F2) values (all data) 0.2189 0.0385 156 Table 4.2 Summary of crystallographic data for compounds Pt(II)-9-Cl, Pt(II)-11-Cl and Pt(IV)-11-Cl2. Compound Pt(II)-9-Cl Pt(II)-11-Cl Pt(IV)-11-Cl2 Chemical formula C30H31ClN2O5Pt, CHCl3 2(C32H35ClN2O6Pt) 2(C32H34Cl2N2O6Pt), 3(C2H3N) Formula weight 849.51 1504.25 1740.35 a (Ã ) 21.445(4) 26.2523(17) 10.7903(11) b (Ã ) 19.740(3) 9.5789(6) 18.531(3) c (Ã ) 19.603(3) 27.3495(17) 19.625(2) ! (°) 90 90 64.267(4) β (°) 113.282(3) 118.6363(14) 86.028(4) γ (°) 90 90 78.411(6) Unit cell volume (Ã 3) 7623(2) 6036.3(7) 3462.2(8) Temperature (K) 90 90 100 Crystal system monoclinic monoclinic triclinic Space group C 2/c P 21/n P -1 Z 8 4 2 Absorption coefficient (µ/mm-1) 3.997 4.781 4.257 Total number of reflections 47306 46774 22383 Unique reflections 8830 11079 11946 Final R1 values (I > 2"(I)) 0.0322 0.0489 0.0976 Final wR(F2) values (all data) 0.0856 0.1002 0.2415 157 Table 4.3 Summary of crystallographic data for compounds Pt(II)-16, Pt(III)-16 and Pt(IV)-16. Compound Pt(II)-16 Pt(III)-16-Cl2 Pt(IV)-16-Cl2 Chemical formula C24H18N2O3Pt, CH2Cl2 C48H36Cl2N4O6Pt2 C24H18Cl2N2O3Pt, CH2Cl2 Formula weight 662.44 1225.87 733.35 a (Ã ) 28.515(3) 10.1084(10) 14.6171(15) b (Ã ) 10.2393(12) 15.6988(17) 17.1109(17) c (Ã ) 16.1187(17) 12.3890(12) 19.911(2) ! (°) 90 90 90 β (°) 109.331(3) 93.321(2) 90 γ (°) 90 90 90 Unit cell volume (Ã 3) 4441.0(9) 1962.7(3) 4980.0(9) Temperature (K) 90 90 90 Crystal system monoclinic monoclinic orthorhombic Space group C 2/c P 21/n P b c a Z 8 2 8 Absorption coefficient (µ/mm-1) 6.592 7.317 6.096 Total number of reflections 33042 9315 51400 Unique reflections 6801 4482 5748 Final R1 values (I > 2"(I)) 0.0242 0.0369 0.0332 Final wR(F2) values (all data) 0.0516 0.0855 0.0836 158 Table 4.4 Summary of crystallographic data for compounds 9 and 19. Compound 9 19 Chemical formula C30H32N2O5 C30H30N2O6, H2O Formula weight 500.59 7.3610(3) a (Ã ) 8.048(2) 5.9898(4) b (Ã ) 8.740(3) 25.5081(9) c (Ã ) 35.834(10) 14.0025(5) ! (°) 90 90 β (°) 92.014(6) 91.535(2) γ (°) 90 90 Unit cell volume (Ã 3) 2518.9(13) 2628.24(17) Temperature (K) 90 90 Crystal system monoclinic monoclinic Space group P 21 P 21/n Z 4 4 Absorption coefficient (µ/mm-1) 0.090 0.096 Total number of reflections 25933 31662 Unique reflections 6223 6022 Final R1 values (I > 2"(I)) 0.1473 0.0384 Final wR(F2) values (all data) 0.3836 0.0941 159 Table 4.5 Summary of crystallographic data for compounds Pt(II)-19 and Pt(IV)-19-Cl2. Compound Pt(II)-19 Pt(IV)-19-Cl2 Chemical formula C30H28N2O6Pt, CH2Cl2 C30H28Cl2N2O6Pt, CH2Cl2 Formula weight 792.55 863.49 a (Ã ) 18.024(4) 26.395(5) b (Ã ) 9.985(2) 8.1629(12) c (Ã ) 16.308(3) 14.113(2) ! (°) 90 90 β (°) 104.715(6) 90 γ (°) 90 90 Unit cell volume (Ã 3) 2838.7(10) 3040.7(9) Temperature (K) 90 100 Crystal system monoclinic orthorhombic Space group P 21/c P n a 21 Z 4 4 Absorption coefficient (µ/mm-1) 5.181 5.015 Total number of reflections 20537 40505 Unique reflections 6514 6888 Final R1 values (I > 2"(I)) 0.0417 0.0337 Final wR(F2) values (all data) 0.1063 0.0815 160 Chapter 5:! Conclusion and future directions 5.1.! Conclusions The objectives of this thesis can be summarized by two main goals, both involving supramolecular chemistry. The first goal was to use a supramolecular transformation, such as ligand exchange, to change the reactivity of an unstrained platinum containing metallomacrocycle for use in ROMP reactions. To achieve this goal we used the coordination of a bulky ligand to a palladium center in an unstrained metallomacrocycle to provide steric hindrance, blocking ring-closing and favouring polymerization upon interaction with the second generation Grubbs catalyst. The second goal was to synthetize Pt2+ biscyclometalated phenyl pyridine complexes featuring a crown ether functionality for applications in cation recognition and for the formation of supramolecular assemblies such as rotaxanes and pseudorotaxanes. In Chapter 2 it is demonstrated that macrocyclization is a way to control the rate of ligand exchange at a palladium center. An NNN pincer macrocyclic palladium complex (3) and its corresponding open form (5) have been synthesized (Figure 5.1). Ligand exchange on the palladium atom between acetonitrile and six different ligands was investigated for both compounds 3 and 5. For ligands with little steric bulk, the exchange is rapid and there is no significant difference between the metallomacrocycle and the open complex. When the ligands have more steric bulk, the exchange is substantially slower, and the ligands exchange much faster on the open complex than on the metallomacrocycle. In addition, kinetic studies also revealed that the ligand exchange reaction on the palladium atom proceeds through an associative mechanism and, as a consequence, more steric crowding around a metal center inhibits the ligand exchange process. Finally, compound 3 was shown to be in equilibrium with a tetrameric macrocycle of metallomacrocycles, which was isolated and structurally characterized by SCXRD. To the best of 161 my knowledge, only two other similar palladium-containing aggregates have been reported in the literature so far.59,60 In Chapter 3 it is described how we exploited ligand exchange to further control the supramolecular chemistry of compound 3 (Figure 5.1a). The NNN pincer macrocyclic palladium complex presents a double bond functionality that can react with the second generation Grubbs catalyst to form a polymer via a ROMP reaction. However, compound 3 is unstrained, since the palladium atom coordinates a small acetonitrile molecule. For this reason, when compound 3 was reacted with the second generation Grubbs catalyst, a mixture of cis and trans isomers was obtained, showing that the metallomacrocycle ring-opened and ring-closed again. Ligand exchange on the palladium center between acetonitrile and a bulkier ligand, 2,6-lutidine, was used as driving force to stabilize the ring-opened form of the unstrained monomer, preventing ring-closure and making the ring-opening step irreversible. 2,6-Lutidineâs coordination to the palladium atom and subsequent reaction with the second generation Grubbs catalyst produced a ring-expanded metallomacrocycle with two palladium centers. However, the formation of oligomers is not excluded, but the poor solubility of the products made the full characterization challenging. These results demonstrated that a supramolecular modification such as ligand coordination can be used to modulate ring-expansion of an unstrained palladium-containing pincer macrocycle. In addition, coordination of PPh3 to palladium and reaction with the second generation Grubbs catalyst allowed complete conversion of the cis isomer into the trans isomer. These results show that ligand exchange can be used in RCM to control the stereochemistry of the products and to convert a cis macrocyclic alkene entirely into a trans macrocyclic alkene. 162 Figure 5.1 Structures of: (a) macrocycle 3; (b) model compound 5 and (c) ligands that were exchanged with acetonitrile. In Chapter 4, several Pt2+ and Pt4+ complexes were synthesized and characterized, first using a functionalized phenylpyridine as a bidentate ligand. We then progressed to using two flexible tetradentate ligands featuring a pseudocrown ether functionality, and finally two preorganized tetradentate ligands, one of which contained a full crown ether functionality. The synthetic challenges related to obtaining biscyclometalated platinum monomeric complexes with phenylpyridine-containing ligands were addressed by using different approaches: high dilution, cation coordination and ligand preorganization. Using these different approaches, we were able to obtain several interesting complexes. The monocyclometalated platinum complexes with the flexible ligand showed to be promising for cation recognition; the biscyclometalated complexes with the flexible ligand instead, appeared promising for making pseudorotaxanes and rotaxanes. NO ONNO OPdNNO ONN PdNNPN NNNN35a bc163 In addition, cyclometalation reaction with the preorganized ligand allowed to obtain a series of Pt2+, Pt3+ and Pt4+ complexes. 5.2.! Reflection I think the main goals of this thesis were achieved. The strategy of using a supramolecular modification to ring-expand or polymerize an unstrained metallomacrocycle was successful. We showed that using a supramolecular approach could be a strategy to expand the type and the number of substrates that can be used in ROMP reactions. However, GPC analysis in chloroform is needed to complete the characterization of the insoluble products obtained. This research has also expanded our knowledge on the effects of macrocyclization on the ligand exchange at a palladium center. The synthesis of Pt2+ biscyclometalated phenyl pyridine complexes featuring a crown ether functionality turned out to be challenging. The initial goal to obtain the target cis biscyclometalated complex with a pseudo-crown ether functionality was not achieved. However, despite the synthetic challenges, we were able to develop consistent procedures to obtain similar platinum complexes with different oxidation states (+2, +3 and +4). We were able to prepare a full set of complexes with promising applications in host-guest chemistry, either in cation recognition or rotaxane formation. In addition, particularly exciting was the formation of a Pt3+ species, as +3 is an uncommon oxidation state for platinum.194,232â235 In conclusion, this research did not proceed as we initially planned but despite that, we were able to expand our knowledge regarding the synthesis, properties and potential applications of biscyclometalated phenylpyridine platinum complexes. 164 5.3.! Future directions One of the next steps on the supramolecular polymerization project will be obtaining a GPC trace in chloroform, to characterize the poorly soluble precipitate obtained when the complex coordinating 2,6-lutidine was reacted with the second generation Grubbs catalyst. GPC would enable us to confirm whether the insoluble product is polymer or oligomer. The supramolecular polymerization reaction can also be performed with other ligands. Preliminary experiments have so far been performed with pyridine and acridine. However, the products obtained are highly insoluble in all common organic solvents, and therefore we could not complete their characterization. It would be interesting to repeat these experiments with a macrocycle that would generate more soluble and easier to characterize polymers, starting with 4-tert-butyl-2,6-dicarboxylic acid as a precursor, which can be prepared from reported procedures,240,241 and following Scheme 5.1. 165 Scheme 5.1 Proposed scheme to make a new macrocycle that would generate more soluble polymers. In addition, further computational calculations on the reaction intermediates and possible transition states are also necessary in order to fully explain the reasons behind the different stereospecificity of the ring-closing step, when the second generation Grubbs catalyst is reacted with the acetonitrile-coordinating complex versus the PPh3-coordinating one. The geometry optimization results performed suggest that the difference in stereospecificity is not only due to the relative thermodynamic stability of the cis versus trans isomers. It probably depends on how the four-atom cyclic intermediate formed by reaction with the Ru-catalyst rearranges in the transition state. During the ring-closing process, the PPh3 influences the orbitalsâ rotation toward one favoured conformation. More calculations on the intermediate and the possible transitions states will help elucidating the reaction path. N N OOHOOHN OClOClN OHNONHOH OHN OHNONHO ONH2OH+1)$KMnO4,$H2O$reflux,$18$h2)$HCl,$pH$=$5K2CO3,$2:butanonecis:1,4:dichloro:2:butene,reflux,$120$h1)$Et3N,$THF$:78$°C,$N22)$8$h,$RTSOCl2,$DMF$N2,$reflux, 8$h,$N2166 Regarding the platinum chemistry, after improving the synthetic procedure, a cis biscyclometalated Pt2+ complex with a full 18-crown-6 functionality was prepared in 43% yield. The next step would be to investigate its optical properties by UV-Vis and fluorescence spectroscopy, and monitor how they change upon addition of NaBF4 and KBF4. Of particular interest, would be the addition of Cs+ because it is known to coordinate between two different crown ether functionalities.216 The interaction of the crown ethers with Cs+ combined with these complexesâ Pt-Pt stacking properties could promote the formation of dimers or supramolecular polymers. In addition, more cis biscyclometalated Pt2+ complexes can be prepared featuring a bigger crown ether functionality (Figure 5.2). This would allow it to coordinate larger cations as well as organic salts such as dibenzylammonium hexafluorophosphate and result in the formation of rotaxanes and pseudorotaxanes. 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(c) The 1H NMR spectrum acquired after cooling the solution back to 25 °C shows that the process is not reversible. 187 Figure A-4 1H NMR spectrum of compound 3* (CD2Cl2, 400 MHz). Residual solvent peak is labeled as *. * 188 Figure A-5 1H NMR spectrum of compound 5 (CD2Cl2, 400 MHz). Residual solvent peak is labeled as *. Figure A-6 1H NMR spectrum of compound 5 ((CD3)2SO, 400 MHz). * H2O Free CH3CN 189 Figure A-7 1H-1H COSY NMR spectroscopy experiment of compound 3-pyr (C2D2Cl4, 400 MHz). 2D Spectrum collected at 113 ËC. 190 Figure A-8 1H-1H COSY NMR spectroscopy experiment of compound 3-DMAP (C2D2Cl4, 400 MHz). 2D Spectrum collected at 113 ËC. 191 Figure A-9 NOESY NMR spectroscopy experiment of compound 3-DMAP (C2D2Cl4, 400 MHz). 2D Spectrum collected at 113 ËC. 192 Figure A-10 1H-1H COSY NMR spectroscopy experiment of compound 3-pyr (CD2Cl2, 400 MHz). 2D spectrum collected at -56 ËC. 193 Figure A-11 1H-1H COSY NMR spectroscopy experiment of compound 3-DMAP (CD2Cl2, 400 MHz). 2D Spectrum collected at -81 ËC. 194 Figure A-12 HSQC NMR spectroscopy experiment of compound 3-DMAP (CD2Cl2, 400 MHz). 2D Spectrum collected at -81 ËC. 195 Appendix B: 1H NMR and 13C NMR spectroscopy data (1D and 2D) for Chapter 3. Figure B-1 Polymerization reaction on 3-lut monitored by 1H NMR (400 MHz, THF-d8, 50 °C) spectroscopy. 196 Figure B-2 13C NMR (100 MHz, CDCl3) spectrum of compound 3-lut-prec. Residual solvent peaks are indicated with *. 197 Figure B-3 1H DOSY NMR (400 MHz, CDCl3,) experiment on compound 3-lut-prec. 198 Figure B-4 13C NMR (100 MHz, CDCl3,) for compound 3-PPh3-trans. Residual solvent peaks are indicated with *. Figure B-5 13C NMR (100 MHz, CDCl3,) for compound 6. Residual solvent peaks are indicated with *. **199 Appendix C: Supplementary information for Chapter 4. Figure C-1 1H NMR (300 MHz, CDCl3) spectrum of compound 7-Ac. Residual solvent peaks are indicated with *. Figure C-2 13C NMR (75 MHz, CDCl3) spectrum of compound 7-Ac. Residual solvent peaks are indicated with *. 200 Figure C-3 1H NMR (400 MHz, CDCl3) spectrum of compound 8. Residual solvent peaks are indicated with *. Figure C-4 13C NMR (100 MHz, CDCl3) spectrum of compound 8. Residual solvent peaks are indicated with *. 201 Figure C-5 1H NMR (400 MHz, CDCl3) spectrum of compound 9. Residual solvent peaks are indicated with *. Figure C-6 13C NMR (100 MHz, CDCl3) spectrum of compound 9. Residual solvent peaks are indicated with *. 202 Figure C-7 1H NMR (400 MHz, CDCl3) spectrum of compound 10. Residual solvent peaks are indicated with *. Figure C-8 13C NMR (75 MHz, CDCl3) spectrum of compound 10. Residual solvent peaks are indicated with *. 203 Figure C-9 1H NMR (400 MHz, CDCl3) spectrum of compound 11. Residual solvent peaks are indicated with *. Figure C-10 1H NMR (100 MHz, CDCl3) spectrum of compound 11. Residual solvent peaks are indicated with *. 204 Figure C-11 1H NMR (300 MHz, CDCl3) spectrum of compound Pt(7-Ac)(dmso)Cl. Residual solvent peaks are indicated with *. Figure C-12 1H NMR (300 MHz, DMSO-d6) spectrum of compound Pt(7)(dmso)Cl. 205 Figure C-13 13C NMR (75 MHz, DMSO-d6) spectrum of compound Pt(7)(dmso)Cl. Figure C-14 1H NMR (300 MHz, CDCl3) spectrum of compound Pt(7-Ac)2Cl. Residual solvent peaks are indicated with *. 206 Figure C-15 1H NMR (400 MHz, CDCl3) spectra of the crude product of reaction between compound 9 and K2PtCl4 in AcOH at different concentrations: (a) 16 mM and (b) 4mM. Some of the broad peaks corresponding to the oligomers are indicated in red, and the some of the sharp peaks corresponding to Pt(II)-9-Cl are indicated in blue. Figure C-16 13C NMR (100 MHz, CDCl3) spectrum of compound Pt(II)-9-Cl. Residual solvent peaks are indicated with *. 207 Figure C-17 1H NMR (400 MHz, CDCl3) spectrum of compound Pt(II)-11-Cl. Residual solvent peaks are indicated with *. Figure C-18 1H NMR (400 MHz, CD2Cl2) spectrum of compound Pt(IV)-11-Cl2. Residual solvent peaks are indicated with *. 208 Figure C-19 13C NMR (100 MHz, CD2Cl2) spectrum of compound Pt(IV)-11- Cl2. Figure C-20 1H NMR (400 MHz, 1:1 CDCl3/CD3CN) spectrum of compounds (a) Pt(IV)-11-Cl2, (b) Pt(IV)-11-Cl2 + 1 equiv of dibenzylammonium hexafluorophosphate and (c) dibenzylammonium hexafluorophosphate. *abc209 Figure C-21 1H NMR (400 MHz, CD3CN) spectrum of compounds (a) Pt(IV)-11-Cl2 and (b) Pt(IV)-11-Cl2 + 1 equiv of dibenzylammonium hexafluorophosphate. Figure C-22 1H NMR (400 MHz, DMSO-d6) spectrum of compound Pt(IV)-11-Cl2 + 1 equiv of dibenzylammonium hexafluorophosphate. *ab210 Figure C-23 1H NMR (400 MHz, 1:1 CDCl3/CD3CN) spectrum of compound Pt(IV)-11-Cl2 + 1 equiv of N,Nâ-dimethyl-4,4â-bipyridinium hexafluorophosphate. Residual solvent peaks are indicated with *. Figure C-24 1H NMR (400 MHz, 1:1 CDCl3/CD3CN) spectrum of compound Pt(IV)-11-Cl2 + 1 equiv of 1,2-bis(4,4â-bipyridinium)ethane hexafluorophosphate. Residual solvent peaks are indicated with *. 211 Figure C-25 1H NMR (400 MHz, CDCl3) spectrum of compound 13. Residual solvent peaks are indicated with *. Figure C-26 13C NMR (100 MHz, CDCl3) spectrum of compound 13. Residual solvent peaks are indicated with *. 212 Figure C-27 1H NMR (400 MHz, CDCl3) spectrum of compound 14. Residual solvent peaks are indicated with *. Figure C-28 13C NMR (100 MHz, CDCl3) spectrum of compound 14. Residual solvent peaks are indicated with *. 213 Figure C-29 1H NMR (400 MHz, CDCl3) spectrum of compound 15. Residual solvent peaks are indicated with *. Figure C-30 13C NMR (100 MHz, CDCl3) spectrum of compound 15. Residual solvent peaks are indicated with *. 214 Figure C-31 13C NMR (100 MHz, CDCl3) spectrum of compound 16. Residual solvent peaks are indicated with *. Figure C-32 13C NMR (100 MHz, DMSO-d6) spectrum of compound Pt(II)-16. Figure C-33 1H NMR (400 MHz, CDCl3) spectrum of compound 17. Residual solvent peaks are indicated with *. 215 Figure C-34 13C NMR (100 MHz, CDCl3) spectrum of compound 17. Residual solvent peaks are indicated with *. Figure C-35 1H NMR (400 MHz, CDCl3) spectrum of compound 18. Residual solvent peaks are indicated with *. 216 Figure C-36 13C NMR (100 MHz, CDCl3) spectrum of compound 18. Residual solvent peaks are indicated with *. Figure C-37 13C NMR (100 MHz, CDCl3) spectrum of compound 19. Residual solvent peaks are indicated with *. 217 Figure C-38 UV-Vis spectra (CH3CN, 50 µM) of compounds (a) Pt(IV)-9-Cl2, Pt(IV)-9-Cl2 + 5 equiv KBF4, (b) Pt(IV)-11-Cl2, and Pt(IV)-11-Cl2 + 5 equiv KBF4.
Thesis/Dissertation
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Chemistry
Vancouver : University of British Columbia Library
Attribution-NonCommercial-NoDerivatives 4.0 International
Graduate
Supramolecular chemistry of palladium and platinum-containing macrocycles : from ring-expansion to host-guest complexes
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