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The coordination chemistry of rhenium, group 13 and lanthanide metal complexes : towards new radiotherapeutic… Kovacs, Michael S. 2001

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T H E COORDINATION C H E M I S T R Y OF R H E N I U M , GROUP 13 A N D LANTHANIDE METAL COMPLEXES: T O W A R D S N E W RADIOTHERAPEUTIC A G E N T S by Michael S. Kovacs  B.Sc. (Hons.), McMaster University, 1996  A THESIS SUBMITTED IN P A R T I A L F U L F I L L M E N T OF THE REQUIREMENTS FOR THE D E G R E E OF DOCTOR OF PHILOSOPHY in THE F A C U L T Y OF G R A D U A T E STUDIES (Department of Chemistry)  We accept this thesis as conforming to the required standard  THE UNIVERSITY OF BRITISH C O L U M B I A May 2001 © Michael S. Kovacs, 2001  In presenting this thesis in partial fulfillment of the requirements for an advanced degree at the University of British Columbia, I agree that the Library shall make it freely available for reference and study. I further agree that permission for extensive copying of this thesis for scholarly purposes may be granted by the head of my department or by his or her representatives. It is understood that copying or publication of this thesis for financial gain shall not be allowed without my written permission.  Michael S. Kovacs  Department of Chemistry The University of British Columbia Vancouver, Canada  Date: May 16, 2001.  Abstract  Complexes incorporating the  [Re=0]  3+  core have been synthesized with ligands  containing the new methyl substituted phosphine/phenolate PO and PO2 donor sets, (2hydroxy-5-methylphenyl)diphenylphosphine methylphenyl)phenylphosphine  [NH ][Re0 ] in C H 4  4  yield.  3  Reaction  (H(MePO))  (H2(Me2P02)).  and  bis(2-hydroxy-5-  Reaction of either wer-[ReOCl3(PPh3) ] or 2  O H with H(MePO) led to formation of [ReOCl(MePO) ] (2.1) in good 2  of  [NH ][Re0 ] 4  [ReO(Me2P02)(H(Me2P02))] (2.2),  4  with  H (Me P0 ) 2  2  2  in  CH OH 3  afforded  also in good yield. X-ray crystallographic analyses of  2.1 and 2.2 demonstrated that both complexes are neutral and octahedral, and contain the oxo moiety. The two phosphorus donors are cis to one another in 2.1 and 2.2 with a phenol donor trans to the oxo moiety. 2.2 has a tridentate  H(Me2PC>2)  Me2P02 ligand as  well as a bidentate  ligand wherein one of the phenol donors is protonated and not bound to the  metal centre. Two complexes have been structurally characterized from the reaction of (0hydroxyphenyl)diphenylphosphine [Re(Hhypy)(hypy)(PO)(HPO)]Cl  (HPO) (3.1)  and  with  [ReCl(Hypy)(hypy)(PO)] (3.2)  N N C H N , Hhypy = H N N C 5 H 4 N , hypyH = N N C H N H ) . 5  4  demonstrated  [Re(Hhypy)(hypyH)Cl3]:  5  4  (hypy =  X-ray crystallography  that both are Re(III) complexes; 3.1 is monocationic with a N3OP2  coordination sphere while 3.2 is neutral with a CIN3OP coordination sphere.  Two  phosphorus atoms are bound to 3.1 and are orientated trans to one another. One PO ligand is bidentate while the second is monodentate with an unbound, protonated phenol. One hypy is bidentate with the a-nitrogen protonated to give a coordinated diazene (Hhypy), the  second hypy is bound as a bent diazenido group. The structure of 3.2 is nearly identical to that of 3.1 except that the monodentate HPO is replaced by a chloride. The tripodal amine-phosphinate ligands, tris(4-(phenylphosphinato)-3-benzyl-3azabutyl)amine  (H3ppba-2HC1H20) and tris(4-(phenylphosphinato)-3-azabutyl)amine  (H3ppaHClH20) were synthesized and reacted with A l , G a , I n 3 +  (Ln ). 3+  3+  3+  and the lanthanides  At 2:1 H ppba to metal ratios, complexes of the type [M(H ppba)2] 3  3  3+  (M=A1 , 3+  G a , In , H o - L u ) were isolated. The bicapped [GafH ppba)2](N03)2Cl-3CH OH was 3+  3+  3+  3+  3  3  structurally characterized and was shown indirectly by various techniques  to be  isostructural with the other [M(H3ppba)2] complexes. Also, at 2:1 H ppba to metal ratios, 3+  3  complexes of the type [M(H ppba) ] (M=La -Tb ) were characterized, and the X-ray 5+  4  3+  3+  2  structure of [Gd(H ppba) ](N0 )4Cl-3CH30H was determined.  At 1:1 H ppba to metal  ratios,  3+  4  complexes  2  of the  3  type  [M(H4ppba)]  4+  3  (M=La -Er ) 3+  were  isolated and  characterized. Elemental analysis and spectroscopic evidence supported the formation of a 1:1 monocapped complex. Reaction of 1:1 ratios of Hbppa with Ga of [Ga(ppa)]-3H20.  results in formation  The formation of an encapsulated 1:1 complex is supported by  elemental analysis and spectroscopic evidence.  - iii -  Table of Contents  Abstract  ii  Table of Contents  iv  Lists of Figures  vii  Lists of Tables  ix  Lists of Abbreviations  xi  Acknowledgments  xv  Dedication  xvi  Chapter One  Chapter Two  Introduction 1.1.  General Introduction  1  1.2.  References  15  Phosphine-Phenolate Complexes Containing the [Re=0]  3+  Core  2.1.  Introduction  17  2.2.  Experimental  20  2.3.  Results and Discussion  23  2.3.1. [Re=0] Complex of H(MePO)  23  3+  2.3.2. [Re=0] Complex of H ( M e P 0 )  26  2.3.3. Reaction of 2.1 and 2.2 with Hydrazines  29  2.4.  Conclusions  31  2.5.  References  32  3+  2  - iv -  2  2  Chapter Three  Phosphine-Phenolate Complexes Containing Rhenium-Hydrazine Cores 3.1.  Introduction  35  3.2.  Experimental  40  3.3.  Results and Discussion  44  3.3.1. [Re(Hhypy)(hypyH)Cl ] + HPO  44  3  3.3.2. [Re(Hhypy)(hypyH)Cl ] + H P 0 3  2  51  2  & H (Me P0 ) 2  2  3.3.3. [Re(N PhMe) (MePO) ][BPh4]  53  3.4.  Conclusions  57  3.5.  References  58  2  Chapter Four  2  2  2  Lanthanide(III) and Group 13 Metal Complexes Containing Tripodal Amine Phosphinate Ligands 4.1.  Introduction  61  4.2.  Experimental  66  4.3.  Results and Discussion  72  4.3.1. Synthesis of the Tripodal Amine-  72  Phosphinate Ligands H ppba & H ppa 3  3  4.3.2. 2:1 Complexes of H ppba with the 3  75  Group 13 Metals and the Lanthanides 4.3.3. 1:1 Complexes of H ppba with the 3  85  Lanthanides 4.3.4.  1:1 Complex of G a -v-  3+  and H ppa 3  90  Chapter Four (cont.) 4.4. 4.5.  Chapter Five  Conclusions  93  References  95  Conclusions and Further Thoughts 5.1.  General Conclusions  97  5.2.  Suggestions for Future Work  100  5.3.  References  102  Appendix  103  - vi -  Lists of Figures  Figure  Description  Page  1.1.  Two currently approved radiopharmaceuticals:  3  (left)  99m  (right) 1.2.  Tc-sestamibi (Cardiolite®);  99m  T c - D , L - H M - P A O (Ceretec®).  Two examples of the bifunctional chelate approach:  6  (left) DMP444; (right) RP419. 1.3.  (left) Ethylenediaminetetramethylenephosphonate, E D T M P ;  10  (right) Ethylenediaminetetraacetate, E D T A . 1.4.  1,4,7,10-cyclododecyltetraamine-  11  tetramethylenephosphonate, DOTMP. 2.1.  ORTEP diagram of [ReOCl(MePO) ], 2.1 (with the solvent  24  2  molecules and H-atoms omitted); 50% thermal probability ellipsoids are shown. 2.2.  ORTEP diagram of [ReO(Me P02)(H(Me P02))], 2.2 (with 2  27  2  the solvent molecules and H-atoms omitted); 50% thermal probability ellipsoids are shown. 3.1.  Selected Rhenium Hydrazine Complexes Containing  37  Halide and Phosphine Ligands. 3.2.  ORTEP diagram of the cation [Re(Hhypy)(hypy)(PO)(HPO)] , +  3.1 (with the solvent molecules, H-atoms and the counteranions omitted); 50% thermal probability ellipsoids are shown.  vn -  46  Figure  Description  Page  3.3.  ORTEP diagram of [ReCl(Hhypy)(hypy)(PO)], 3.2;  49  50% thermal probability ellipsoids are shown. 3.4.  Four Possible Diastereomers of 3.5.  55  4.1.  Examples of amine-phosphinate ligands:  64  (left) DOTA-type ligands; (right) tris(4-(phenylphosphinato)3-methyl-3-azabutyl)amine, (H3ppma). 4.2.  ORTEP diagram of the [Ga(H ppba) ] cation with the 3+  3  2  76  solvent molecules and the aromatic rings removed for clarity; 50% thermal probability ellipsoids are shown. 4.3.  IR spectra of [M(H ppba) ](N0 ) Cl, M as indicated.  80  4.4.  Selected IR spectra of [M(H ppba) ](N0 ) Cl,  82  3  2  3  2  4  2  3  4  M as indicated. The IR spectrum of 4.1 (M=Ga) is included for comparison. 4.5.  ORTEP diagram of the [Gd(H ppba) ] cation with the 5+  4  2  83  solvent molecules and the aromatic rings removed for clarity; 50% thermal probability ellipsoids are shown. 4.6.  IR spectra of [Ln(H ppba)](N03) Cl, Ln as indicated. 4  3  88  The IR spectrum of 4.1 (M=Ga) is included for comparison. 4.7.  IR spectra of [Ga(ppa)] -3H 0 (4.4) (top) and  91  2  H ppa-HC1H 0 (bottom). 3  4.8.  2  ' H N M R spectra (300 MHz) of [Ga(ppa)]-3H 0 (4.4) 2  (top) and H p p a H C l H 0 (bottom) in d -methanol; 3  2  4  (* = H 0 and C H O H impurities). 2  3  - viii -  92  Lists of Tables  Table  Description  Page  1.1.  Selected P-Emitting Radionuclides  7  Proposed for Therapeutic Use. 2.1.  Selected Bond Lengths (A) and Angles (deg)  25  in [ReOCl(MePO) ] (2.1). 2  2.2.  Selected Bond Lengths (A) and Angles (deg)  28  in [ReO(Me P02)(H(Me P02))] (2.2). 2  3.1.  2  Selected Bond Lengths (A) and Angles (deg)  47  in [Re(Hhypy)(hypy)(PO)(HPO)]Cl (3.1). 3.2.  Selected Bond Lengths (A) and Angles (deg)  50  in [ReCl(Hhypy)(hypy)(PO)] (3.2). 3.3.  Selected ' H & P N M R spectral data for 3 I  52  [Re(Hhypy)(hypy)(PO)(HPO)]Cl (3.1), [ReCl(Hhypy)(hypy)(PO)] (3.2), [Re(Hhypy)(hypy)(HP0 )(H P0 )]Cl (3.3), and 2  2  2  [Re(Hhypy)(hypy)(H(Me P02))(H (Me2P02))]Cl(3.4). 2  4.1.  2  Preparative details for the synthesis of  69  [M(H ppba) ](N0 ) Cl-xCH OH. 3  4.2.  2  3  2  3  Preparative details for the synthesis of  69  [M(H ppba) ](N0 ) Cl-xCH OH. 4  4.3.  2  3  4  3  Preparative details for the synthesis of [M(H ppba)](N0 ) Cl-xH 0. - ix 4  3  3  2  70  Table  Description  Page  4.4.  Selected bond lengths (A) and bond angles (deg)  77  in [Ga(H ppba) ](N0 ) Cl-3CH OH (4.1). 3  2  3  2  3  4.5.  +LSIMS data for all 2:1 H ppba complexes.  79  4.6.  Elemental analyses for selected 2:1 H ppba complexes.  81  4.7.  Selected bond lengths (A) and bond angles (deg)  84  3  3  in [Gd(H ppba) ](N0 ) Cl-3CH OH (4.2). 4  2  3  4  3  4.8.  +LSIMS data for all 1:1 H ppba complexes.  86  4.9.  Elemental analyses for all 1:1 H ppba complexes.  89  Al.  Selected Crystallographic Data for All Metal Complexes.  108  A2.  Bond Lengths (A) for [ReOCl(MePO) ] (2.1).  109  A3.  Bond Angles (deg) for [ReOCl(MePO) ] (2.1).  110  A4.  Bond Lengths (A) for [ReO(Me P0 )(H(Me P0 ))] (2.2).  112  A5.  Bond Angles (deg) for [ReO(Me P02)(H(Me P0 ))] (2.2).  113  A6.  Bond Lengths (A) for [Re(Hhypy)(hypy)(PO)(HPO)]Cl (3.1).  115  A7.  Bond Angles (deg) for [Re(Hhypy)(hypy)(PO)(HPO)]Cl (3.1).  117  A8.  Bond Lengths (A) for [ReCl(Hhypy)(hypy)(PO)] (3.2).  121  A9.  Bond Angles (deg) for [ReCl(Hhypy)(hypy)(PO)] (3.2).  122  A10.  Bond Lengths (A) for [Ga(H ppba) ](N0 ) Cl-3CH OH (4.1).  124  All.  Bond Angles (deg) for [Ga(H ppba) ](N0 ) Cl-3CH OH (4.1).  126  A12.  Bond Lengths (A) for [Gd(H ppba) ](N0 ) Cl-3CH OH (4.2).  129  A13.  Bond Angles (deg) for [Gd(H ppba) ](N0 ) Cl-3CH OH (4.2).  130  3  3  2  2  2  2  2  2  3  2  2  3  4  3  2  2  4  -x-  2  3  3  2  2  2  3  2  4  3  3  3  4  3  List of Abbreviations  Abbreviation  Meaning  A  angstrom, 1 x 10" metre  Anal  analytical  ATPase  adenosine triphosphatase  p  beta particles  BAM  biologically active molecule  °C  degrees Celsius  Calcd  calculated  Ci  Curie (3.7 x 10 disintegrations per second)  cm"  10  10  1  wavenumber(s) (reciprical centimetre)  8  chemical shift in parts per million (ppm) from a standard (NMR)  d  doublet (NMR)  dd  doublet of doublets (NMR)  deg  degree(s)  diphos  1,2-bis-(diphenylphosphino)ethane  DMF  dimethylformamide  DMSO DOTA  dimethylsulfoxide 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate  DOTMP  1,4,7,10-cyclododecyltetraaminetetramethylenephosphonate  DTPA  diethylenetriaminepentaacetate  EDTA  ethylenediaminetetraacetate  EDTMP  ethylenediaminetetramethylenephosphonate - xi -  eV  electron volt(s)  FDA  food and drug administration  FT  fourier transform  y  gamma rays  g  gram(s); gas  h  hour(s)  HEDP  hydroxyethylene diphosphonate  H(MePO)  (2-hydroxy-5 -methylphenyl)diphenylphosphine  H2(Me2PO)  bis(2-hydroxy-5-methylphenyl)phenylphosphine  HM-PAO  3,6,6,9-tetramethyl-4,8-diazaundecane-2,10-dione dioxime  HPO  (o-Hydroxyphenyl)diphenylphosphine  H2PO2  bis(o-hydroxyphenyl)phenylphosphine  H3ppa  tris(4-(phenylphosphinato)-3 -azabutyl)amine  Happba  tris(4-(phenylphosphinato)-3 -benzyl-3 -azabutyl)amine  Hbppma  tris(4-(phenylphosphinato)-3-methyl-3-azabutyl)amine  HPLC  high performance liquid chromatography  HPS  (o-thiophenyl)diphenylphosphine  HYNIC hypy H PO x  N-oxysuccinimidylhydrazinonicotinamide 2-hydrazinopyridine  x  general term for a phenylphosphine-phenol ligand  Hz  hertz (s" )  IR  infrared  J  coupling constant (NMR)  K  Kelvin(s)  1  - xii -  L  litre  Ln  lanthanides  LSIMS  liquid secondary ion mass spectrometry  \i  micro (10~ )  m  milli (IO" )  M  molar (moles/litre for concentration); metal; mega (10 )  MAb  monoclonal antibody  min  minute(s)  mom  methoxymethyl  MRI  magnetic resonance imaging  m/z  mass to charge ratio (in mass spectrometry)  v  stretching frequency  NCA  no carrier added  NMR  nuclear magnetic resonance  ORTEP  Oak Ridge Thermal Ellipsoid Program  pH  negative logarithm of the proton concentration or activity  pK  6  3  6  a  negative logarithm of the acid dissociation constant (K ) a  ppm  parts per million  s  second(s); singlet (NMR)  S  goodness of fit (X-ray crystallography)  T  temperature  ti/2  half-life  TMEDA  tetramethylethylenediamine  TMS  tetramethylsilane (NMR) - xiii -  V  volume  y  year(s)  Z  number of molecules per unit cell (X-ray crystallography)  - xiv -  Acknowledgments  First and foremost, I must acknowledge Professor Chris Orvig for his careful guidance, continuous support and boundless enthusiasm. He allowed me the freedom to explore my scientific interests, and taught me by example how optimism, careful observation and a lot of hard work can turn a perceived failure into an unmitigated success. I would like to thank Dr. Kathie Thompson, my eternal coffee companion and expert parenting consultant, for sharing in many interesting conversations, both scientific and personal.  I would also like to thank Professor Harvey "Uncle" Schugar for his  guidance and personal insight while working in our group on sabbatical. Acknowledgment is made to Dr. Brian Patrick and the late Dr. Steve Rettig of U B C , and Dr. Tom Emge at Rutgers, for their help in determining the X-ray crystal structures. I gratefully acknowledge the assistance of the support staff in the department, particularly Ms. Liane Darge and Ms. Marietta Austria (NMR), Mr. Peter Borda (elemental analysis) and the entire mass, spectrometry staff.  I am indebted to N S E R C , DuPont  Pharmaceuticals and the U B C Chemistry Department for financial support. I acknowledge my Equipe Orvig Team collaborators Mark Lowe, Peter Hein, and Sherwin Sattarzadeh, as well as my colleagues Leon, Marco, Pete, Ashley, "Grandpa" Buglyo, Paul, Ika, Lenny, Jason, Barry, Dave, Alex and other past and present members of the Orvig Group for the good times and happy memories. Finally, I must acknowledge my wife Ann Marie for providing her never ending caring and support throughout the long course of my academic studies. I would also like to thank my parents, my sister, as well as Ann's parents and sisters for their patience, support and understanding. - xv -  / dedicate this thesis to my wife Jinn Marie, and my 6eautifuC 6a6y girC<EmiCy CaroCine, with att my Cove.  - xvi -  Chapter One Introduction  1.1. General Introduction  Nuclear medicine is a branch of medicine dealing with the use of radioactive isotopes in the diagnosis and treatment of disease. Celebrating its centennial at the time of this writing, nuclear medicine began in 1901 with the use of naturally occurring radium to treat skin lesions by Henri Danlos, a French physician. However, the concept ]  was largely limited until the 1930's and 1940's because very few radioactive sources of sufficient intensity and variety existed before that time. The problem was solved when Enrico Fermi successfully built the world's first nuclear reactor in 1935 and discovered that radioisotopes could be artificially synthesized by neutron bombardment.  The  invention of the cyclotron by E.O. Lawrence in 1930 also circumvented this problem; Fermi and Lawrence were awarded Nobel prizes back-to-back in 1938/39 for their efforts. The infrastructure of nuclear reactors and cyclotrons that now exists supplies the world demand for the approximately 35 radioactive isotopes approved for use in the preparation of radiopharmaceuticals. The vast majority of radiopharmaceuticals approved for clinical use are diagnostic drugs: compounds that are used to measure biological function and diagnose disease. More than 85% of these diagnostic drugs incorporate the workhorse of nuclear medicine, technetium-99m (  99m  T c ) . - The nuclear properties of 2  5  use in diagnostic radiopharmaceuticals.  9 9 m  9 9 m  T c are ideal for its widespread  T c emits a y-ray of 140 keV (89%), which is  -1 -  perfectly suited for detection by the types of gamma cameras used in most hospitals. Its 6 h half-life is short enough to minimize the radiation dose to the patient, but it also allows sufficient time to synthesize the radiopharmaceutical, assess its purity, administer it to the patient, allow for biodistribution, and perform the actual imaging. The isotope requires no significant infrastructure to be present at the site of administration. Unlike isotopes that must be prepared in a reactor or cyclotron,  9 9 m  T c can be  obtained from the convenient M o / " T c generator system that was developed in 1961 at 9 9  m  the Brookhaven National Laboratory. "Mo  - ^  L  -  9 9 m  Tc  —  ^  "Tc  "Ru  The parent nuclide M o is synthesized by neutron bombardment and is incorporated in 9 9  an alumina column as ["M0O4] ". The long half-life of M o allows it to be synthesized 9 9  2  off site with minimal loss of activity. A transient equilibrium exists between M o and its 9 9  short-lived daughter; this equilibrium allows the isolation of no-carrier-added  9 9 m  T c every  23-24 h. Elution of the column with sterile saline solution obtains [ Tc04]" exclusively, 99m  through an ion exchange effect; ["M0O4] " is 100% retained under these conditions. It is 2  important to remember that [TCO4]" must be the starting material for any proposed Tcbased radiopharmaceutical. Beginning with the use of [ Tc04]" as a thyroid-imaging agent, technetium99m  based diagnostic agents have gone through several design cycles in becoming a mature discipline. Initially, [  99m  T c 0 ] " was used either directly (e.g. as an I" mimic for thyroid 4  imaging), or was used in simple labeling experiments. Examples of the latter include Tcsulphur colloid and Tc-labeled erythrocytes (red blood cells) for the imaging and measurement of blood flow and associated abnormalities. These, and many such similar -2-  diagnostic agents, are still in use, but in general they are poorly characterized and very little is known of their chemical structure. The so-called "technetium essential" complexes comprise most of the first generation of technetium-based diagnostic agents.  The Tc in these complexes is an  integral part of the function and structure; hence the radiopharmaceutical would not remain intact and would not be delivered to the target i f the Tc therein were absent. The design of this generation of diagnostic agents was much more methodical and deliberate. This was fueled largely by the pioneers who had a great role in the elucidation of the basic coordination chemistry of Tc. Two highly successful diagnostic agents that were the result of these efforts are shown in Figure 1.1.  +  R  R R = CH C(CH )20CH3 2  Figure 1.1.  3  Two currently approved radiopharmaceuticals:  (Cardiolite®); (right)  99m  T c - D , L - H M - P A O (Ceretec®).  5  (left)  99m  Tc-sestamibi  99m  2,4,6,7* T  Tc-sestamibi (Cardiolite®) is approved for myocardial perfusion imaging. n e  radiopharmaceutical is an octahedral, monocationic Tc(I) complex containing  six neutral isonitrile ligands. The complex was originally believed to be a K mimic that +  is taken up into actively contracting heart muscle by N a / K +  membrane protein involved in the energetics of all cell types.  +  ATPase, an integral However, competition  2  experiments later demonstrated this to be false, although it is still believed that the mechanism of uptake is related to its mimicry of K . > +  8  Under mildly stressful  9  conditions, sufficient uptake of the complex into the heart provides a suitable target to background ratio for imaging (1.5% of the injected dose). In areas of the heart that are not receiving adequate blood flow, uptake of the complex is restricted and "cold" spots in the diagnostic image are observed. 99m  T c - D , L - H M - P A O (Ceretec®) elaborated the use of coordination chemistry in  the design of radiopharmaceuticals even further and was the first Tc-based diagnostic agent to be fully characterized prior to FDA approval. 2  10  This neutral [Tc=0] complex 3+  is approved for cerebral blood flow imaging to evaluate stroke and other cerebral diseases,  and  is  designed  to  penetrate  the  blood-brain-barrier  by  Stereochemistry plays a vital role in the pharmacokinetics of this complex.  diffusion. The D,L  diastereomer is retained in the brain sufficiently long to obtain a diagnostic image, but the meso diastereomer diffuses back out of the brain too quickly.  11  Efforts to advance diagnostic agents to the next generation have been focused on the development of "technetium tagged" radiopharmaceuticals.  5  Techniques related to  the synthesis of complex biomolecules, as well as knowledge of their biochemical targets, have benefited immensely from advances in molecular biology and genetic engineering. * Tc-sestamibi is also marketed under the trade name Miraluma® for early stage breast cancer imaging. 99m  -4-  Therefore, the ability to label a wide variety of these biomolecules with Tc for diagnostic purposes is highly desirable.  Metal-labeled BAM  S c h e m e 1.1  For the general purpose of polypeptide labeling, the bifunctional chelate approach has received extensive attention (NB:  The linker does not necessarily need to be a  chelate by definition, but rather any ligating group). The functional groups on the chelate are designed to form a bridging spacer between the polypeptide and the metal. The most successful  bifunctional  ligating  oxysuccinimidylhydrazinonicotinamide  group  (FfYNIC).  12  to  date  is  N-  The activated ester is first reacted  with the amine side chain of the biologically active molecule (BAM) to make a hydrazine-conjugate (Scheme 1 . 1 ) . The hydrazine functional group is then reacted with -5-  Tc to form a stable metal-labeled B A M .  Since H Y N I C only forms a monodentate  complex with Tc, careful consideration must be given to introduce the coligands L in order to stabilize the resulting conjugate.  Figure 1.2. Two examples of the bifunctional chelate approach: (left) DMP444; (right) RP419.  12  R represents the GPIIb/IIIa platelet receptor antagonist.  There are several applications of the bifunctional chelate approach, two of which (Figure 1.2) involve the Tc labeling of the GPIIb/IIIa cyclic platelet receptor antagonist. " 12  17  The GPIIb/IIIa receptor is involved in blood clotting and recognizes the  Arg-Gly-Asp tripeptide sequence.  A H Y N I C bioconjugate of the antagonist has been  used to image thrombi in canine models.  16  DMP444 uses a system of two different  coligands to stabilize the complex, namely triglycine and triphenylphosphinetrisulfonate (TPPTS). A n example of a non-HYNIC bioconjugate, RP419 uses a N S bifunctional 2  chelate to bridge the [Tc=0] core to the same GPIIb/IIIa antagonist. 3+  17  2  Therapeutic radiopharmaceuticals are molecules labeled with isotopes for the express purpose of killing diseased tissue (notably cancerous tumors) with ionizing radiation.  18  The idea was first put to clinical use in 1941 when  treat thyroid cancer, a practice still in use today.  19  l 3 1  F was administered to  Early treatment of bone cancers used  simple inorganic ions such as chromic P-phosphate colloid and S r 32  analogue).  18  89  2+  chloride (a C a  2+  Both minerals are taken up by the main mineral component of bone,  hydroxyapatite, particularly in areas of rapid bone growth such as a tumour.  Sr  chloride was used for over 50 years and was finally approved by the U.S. Food and Drug Administration (FDA) in 1995 for this application.  18  Table 1.1. Selected p-Emitting Radionuclides Proposed for Therapeutic Use. Radionuclide  89  Sr  90y  y energy, M e V  ti/2, days  Ep max, MeV  14.3  1.71  50.5  1.46  2.7  2.27  8.0  0.81  0.364 (81%)  149  Pm  2.2  1.07  0.286 (3%)  ,53  Sm  1.9  0.8  0.103 (29%)  166  Ho  1.1  1.6  0.81 (6.3%)  l 7 7  Lu  6.7  0.50  186  Re  3.8  1.07  0.113 (6.4%) 0.208 (11%) 0.137(9%)  ,88  Re  0.7  2.11  0.155 (15%)  These three relatively primitive treatments share several features in common with any therapeutic radiopharmaceutical.  A l l three isotopes are P-emitters (Table 1.1).  High-energy electrons emitted from the nuclei of these radionuclides provide a homogeneous radiation dose with the power to kill the targeted tissue. The p energy determines the distance over which the radiation dose can be delivered (anywhere from 2 mm for the weakest to 12 mm for the strongest).  Other radionuclides that decay by  emission of a particles or Auger electrons have also been proposed, but have not received as much attention. In order for the dose to reach the target, therapeutic radiopharmaceuticals must also have a suitable half-life. There is no "best" half-life; rather, the optimum half-life depends on the in vivo localization and clearance times. The goal is to optimize uptake in order to deliver the maximum radiation dose to the target tissue. If the half-life is too short, decay will occur before the radionuclide reaches its intended target, a problem common with monoclonal antibodies (MAbs), which have long residence times. Too long a half-life is also not desirable; most of the radiation dose will be excreted long after the radionuclide has cleared the intended target. A long half-life also requires that a higher dose of radionuclide be given, a practice that inevitably increases the radiation dose to non-target tissues and causes unwanted side effects. Radionuclides must also be available with high specific activity, i.e. at the nocarrier-added (NCA) level (> 2-5 Ci/ug). Because of the constraints of decay properties, half-life, specific activity, availability, and cost, the number of radionuclides suitable for use in therapy is relatively limited. Since the elements most commonly used in organic  chemistry do not meet these requirements, the role of inorganic chemistry becomes all the more important in the design of therapeutic radiopharmaceuticals (Table 1.1). A l l the requirements stated above relate to the actual radionuclides themselves. The key to a successful radiotherapeutic agent is to design a molecule that has significant uptake in the target vs. the background (> 10%). With I", S r l31  89  2+  or P , the delivery of 3 2  the radiation dose to the target is accomplished by using small inorganic ions that are natural substrates for the target (or nearly so in the case of S r ) . 89  2+  For various reasons,  the utility of these three isotopes is largely limited to their current applications. Radioiodine labeling of organic molecules is commonplace, but the physical properties of 131  I limit its utility. A l l of the proposed isotopes in Table 1.1, with the exception of those  mentioned above, are not natural substrates and have no known biological roles. Much as Tc-based  diagnostics  have  benefited  from  sophisticated  approaches  based  on  coordination chemistry, it is hoped that the design of radiotherapeutic agents can also be accomplished with the study of relevant metal ions and appropriate ligands. The final consideration for a radiotherapeutic agent based on a metal complex is stability. There is little point to design and introduce a complex, i f it is subsequently demetallated, particularly i f the intact complex is required for the therapeutic agent to work. Ligand design becomes crucial in this regard; the resulting complexes must be kinetically inert and thermodynamically stable in vivo, yet they must still allow for a mechanism of clearance after the radiation dose is delivered. In 1997,  153  S m - E D T M P (Quadramet®) was the first coordination complex  designed for radiotherapeutic use to be approved by the U.S. FDA. The complex is used for the palliation of skeletal metastases associated with cancer. The E D T M P ligand is the  tetra-substituted methylenephosphonate analogue of E D T A (Figure 1.3). The complex is prepared in a 250-300:1 ligand-to-metal ratio and is administered intravenously. The phosphonate group is believed to act as a phosphate analogue; the complex is taken up into hydroxyapatite wherein the  1 5 3  Sm  3 +  becomes incorporated into the bone matrix. At  an administered dose of 1 mCi/kg body weight, significant pain relief was demonstrated in 70-80% of the patients studied during clinical trials. that required using S r 89  18  This dose is approximately % of  chloride; side effects related to bone marrow suppression are  2+  seen in both treatments, but the patients recovered twice as fast.  18  In a recent study, bone  uptake of S m - E D T M P was shown to be 29.2% of the total injected dose after 3 hours, l53  and 47.7% after 24 hours. 0 2  O Figure  1.3.  O (left)  O  Ethylenediaminetetramethylenephosphonate,  O EDTMP;  (right)  Ethylenediaminetetraacetate, E D T A .  Referring to Table 1.1, there are two clear groups of isotopes that are most relevant to the field of radiotherapeutic agents, i.e. rhenium and the lanthanides. The latter are already implemented in the form of  153  S m - E D T M P , but the potentially useful  lanthanides are by no means restricted to Sm. published on  166  Preliminary work has already been  H o - D O T M P , a tetra methylene-substituted cyclen complex (Figure  - 10-  1.4).  18  The ability to adapt proven ligand systems to the lanthanides, all of which exhibit  similar chemical properties across the series, is highly desirable. In theory, the nuclear properties of the various lanthanides could be incorporated into similar ligand systems in order to fine-tune the therapeutic properties of the resulting radiopharmaceutical by adjusting both the ligand and the metal ion.  Figure 1.4. 1,4,7,10-cyclododecyltetraaminetetramethylenephosphonate,  DOTMP.  The chemistry of the lanthanides has been under extensive recent investigation, particularly because of applications as fluorescent probes and as contrast agents in magnetic resonance imaging ( M R I ) . ' 21  22  With few exceptions, the entire lanthanide  series is trivalent under ambient conditions (Ln ). 3+  The screening of nuclear charge by  the f electrons is inefficient, which results in the lanthanide contraction; the ionic radii decrease by 10-15% across the series. The electron density of the f electrons is arranged such that little interaction occurs with coordinated ligands. This results in many of the observed properties, e.g. the complete lack of ligand field effects and long fluorescence lifetimes.  Ln  3 +  are hard oxophilic metals; ligand donor atom design has been almost  exclusively limited to hard nitrogen and oxygen atoms in amines, carboxylates and phosphonates. Uncomplexed L n  3 +  ions are extensively hydrolyzed at physiological pH;  multidentate chelating ligands are necessary to provide thermodynamic stability, prevent -11 -  hydrolysis and protect the metal against complexation/reaction with endogenous ligands in vivo. Rhenium, the 3  rd  row congener of technetium, is an even more attractive  proposition to include in a radiotherapeutic agent. The ionic radii of Tc and Re are very similar due to the aforementioned lanthanide contraction and the range of accessible oxidation states is comparable. In principle, one should be able to redesign established Tc-containing diagnostics and subsequently use them as Re-based therapeutics. ' '  4 18 23  *  186  There are two proposed isotopes of rhenium, namely  188  Re and  Rhenium-186 is capable of delivering a sizeable dose of radiation ( p  max  Re (Table 1.1). = 1.07 MeV) over  an extended period of time due to its relatively long (3.8 day) half-life. disadvantage of  186  R e lies in its preparation by neutron bombardment; it is nearly  impossible to produce the isotope at the N C A level. I86  Clinical trials have shown that the  18  R e complex of hydroxyethylene diphosphonate (HEDP) is an effective agent for the  palliation of bone cancer metastases, analogous to the the same metastases. '  24 25  In a recent study,  ,86  Sm-EDTMP,  20  99m  T c - H E D P complex that images  R e - H E D P was shown to have 13.7% bone  uptake after 3 hours, and 21.8% after 24 hours. l53  The primary  20  Although uptake is not as high as  the uptake is still adequate for therapy. Rhenium-188 delivers a dose  with higher tissue-penetrating power ( p 1RR  1RR  Re can be obtained from a  max  = 2.12 MeV) to a distance of 11 mm. Since  1 RR  W/  Re generator, it offers a distinct advantage over  isotopes such as rhenium-186 that must be synthesized off-site by neutron activation, or many other isotopes requiring sizable infrastructure for their preparation. disadvantage of  l88  18  The primary  R e is its short half-life of 17 h, a problem largely circumvented by the  availability of the generator system. - 12-  The challenges that must be overcome to extend this chemistry to rhenium are significant, however. Foremost from the clinical standpoint is the much stricter target to background ratios that must be achieved for therapeutic vs. diagnostic use. Rhenium is more kinetically inert than technetium and it is also much more difficult to reduce from [MO4]" ( M = Tc, Re), the preferred starting material in nuclear medicine. The differences in oxidative strength may also be problematic because oxidation to [Re04]~ in vivo provides an efficient mechanism of elimination. For these reasons, it may require considerable research to extend working diagnostic technetium systems to potentially therapeutic rhenium systems. The main purpose of this project was to investigate the fundamental coordination chemistry of Re and the lanthanides. The ligands were chosen with careful consideration given to the intended application of the resulting complexes as radiotherapeutic agents. Chapter 2 describes the preparation of Re complexes with phosphine-phenolate ligands, a proven system that is known to form stable complexes of Re and T c .  R  R  26  R  H P 0 (R=H) H (Me P0 ) (R=Me) H (f-Bu P0 ) (R=f-Bu)  HPO (R=H) H(MePO) (R=Me) H(f-BuPO) (R=f-Bu)  2  2  2  - 13 -  2  2  2  2  2  It was hoped that these complexes would provide a simple route to form "rhenium tagged" therapeutics via the H Y N I C bifunctional chelate approach. Chapter 3 describes the preparation of ternary complexes of rhenium containing phosphine-phenolate ligands and organohydrazines. These complexes are models that prove the possible utility of phosphine-phenolate ligands in the H Y N I C system. Chapter 4 describes the preparation of lanthanide complexes containing tripodal amine phosphinate ligands, and their group 13 ( A l , G a 3+  3+  and In ) analogues. 3+  ppba (R=Bz) ppa(R=H)  The purpose is to design new ligand systems for metal essential radiotherapeutic agents, analogous to  153  Sm-EDTMP.  As mentioned above, multidentate ligands containing  oxygen and nitrogen are ideal for the chelation of lanthanides.  The introduction of  phosphinate groups as oxygen donors into a tren-based tripod was investigated, and the resulting lanthanide and group 13 complexes are reported.  - 14-  1.2. References  1) Grigg, E. R. N . Diagnostic Nuclear Medicine; Gottschalk, A . and Potchen, E. J., Ed.; Williams & Wilkins: Baltimore, 1976, pp 1. 2) Jurisson, S.; Desilets, C. P.; Jia, W.; Ma, D. Chem. Rev. 1993, 93, 1137. 3) McCarthy, T. J.; Schwarz, S. W.; Welch, M . J. J. Chem. Ed. 1994, 71, 830. 4) Dil worth, J. R.; Parrott, S. J. Chem. Soc. Rev. 1998, 27, 43. 5) Jurisson, S. S.; Lydon, J. D. Chem. Rev. 1999, 99, 2205. 6) Schwochau, K. Angew. Chem., Int. Ed. Engl. 1994, 33, 2258. 7) Horn, R. K.; Katzenellenbogen, J. A. Nucl. Med. Biol. 1997, 24, 485. 8) Deutsch, E.; Bushong, W.; Glavan, K . A . ; Elder, R. C ; Sodd, V . J.; Scholz, K . L . ; Fortman, D. L.; Lukes, S. J. Science 1981, 214, 85. 9) Piwnica-Worms, D.; Kronauge, J. F.; Holman, B. L.; al, e. J. Nucl. Med. 1988, 29, 55. 10) Jurisson, S.; Schlemper, E. 0.; Troutner, D. E.; Canning, L . R.; Nowotnik, D. P.; Neirinckx, R. D. Inorg. Chem. 1986, 25, 543. 11) Sharp, P. F.; Smith, F. W.; Gemmell, H . G.; Lyall, D.; Evans, N . T. S.; Gvozdanovic, D.; Davidson, J.; Tyrrell, D. A.; Pickett, R. D.; Neirinckx, R. D. J. Nucl. Med. 1986, 27, 171. 12) Liu, S.; Edwards, D. S. Chem. Rev. 1999, 99, 2235. 13) Liu, S.; Edwards, D . S.; Looby, R. J.; Harris, A . R.; Poirier, M . J.; Barrett, J. A . ; Heminway, S. J.; Carroll, T. R. Bioconjugate Chem. 1996, 7, 63. 14) Edwards, D. S.; Liu, S. Transition Met. Chem. 1997, 22, 425.  - 15 -  15) Edwards, D. S.; Liu, S.; Barrett, J. A . ; Harris, A . R.; Looby, R. J.; Ziegler, M . C ; Heminway, S. J.; Carroll, T. R. Bioconjugate Chem. 1997, 8, 146. 16) Barrett, J. A . ; Crocker, A . C ; Damphousse, D. J.; Heminway, S. J.; Liu, S.; Edwards, D. S.; Lazewatsky, J. L.; Kagan, M . ; Mazaika, T. J.; Carroll, T. R. Bioconjugate Chem. 1997, 8, 155. 17) Liu, S.; Edwards, D. S.; Barrett, J. A. Bioconjugate Chem. 1997, 8, 621. 18) Volkert, W. A . ; Hoffman, T. J. Chem. Rev. 1999, 99, 2269. 19) Becker, D. V . ; Swain, C. T. Semin. Nucl. Med. 1996, 26, 155. 20) Brenner, W.; Kampen, W. U.; Kampen, A . M . ; Henze, E. J. Nucl. Med. 2001, 42, 230. 21) Lauffer, R. B . Chem. Rev. 1987, 87, 901. 22) Caravan, P.; Ellison, J. J.; McMurry, T. J.; Lauffer, R. B. Chem. Rev. 1999, 99, 2293. 23) Heeg, M . J.; Jurisson, S. S. Acc. Chem. Res. 1999, 32, 1053. 24) Deklerk, J. M . H.; Vanhetschip, A . D.; Zonnenberg, B. A.; Vandijk, A . ; Quirijnen, J. M . S. P.; Blijham, G. H.; Vanrijk, P. P. J. Nucl. Med. 1996, 37, 244. 25) Elder, R. C ; Yuan, J.; Helmer, B.; Pipes, D.; Deutsch, K.; Deutsch, E. Inorg. Chem. 1997, 36, 3055. 26) Luo, H.; Setyawati, I.; Rettig, S. J.; Orvig, C. Inorg. Chem. 1995, 34, 2287.  -16-  Chapter T w o  Phosphine-Phenolate Complexes Containing the [Re=0]  Core  2.1. Introduction The [ M = 0 ]  3+  core (M=Tc, Re) is ubiquitous, particularly in the Tc complexes  used in diagnostic nuclear medicine (e.g. Ceretec®, Figure 1.1).'~ The M(V) oxidation 3  state is easily accessible from [MO4]" (M(VII)) starting materials by reduction, and most M(V) complexes are stable under ambient conditions. [M=0] temperature-independent  species exhibit weak,  paramagnetism and are diamagnetic.  complexes containing the [ M = 0 ]  3+  The majority of  4  core have either 5 coordinate square pyramidal  geometry or 6 coordinate octahedral geometry. A large series of 6 coordinate [Re=0]  3+  complexes containing phosphines and  halides has been known for many years, e.g. /ner-ReOCl3(PPh3) . ' These complexes are 4 5  2  most commonly made by reacting a strong hydrohalic acid solution containing [ReC»4]~ ("hydroperrhenic acid") with the appropriate phosphine. reduction/complexation occurs and the [Re=0]  3+  Under these conditions,  complexes are isolated in near  quantitative yield. The complexes exhibit excellent hydrolytic stability and are air stable. This class of complexes, although highly useful as starting materials, is not directly suitable for application in nuclear medicine because of the presence of the labile halide groups. Phosphine-phenolate ligands of the type HPO and H P 0 (H PO ) (Scheme 2.1) 2  2  x  x  and related systems have been reported to form oxo, nitrido and imido M(V) complexes - 17-  with rhenium and technetium. "' 6  3  Similar to the highly successful N S3. and N S4_ X  X  X  donor sets which favour the formation of square pyramidal [Re=Oj complexes, 3+  14-17  X  the  H P O ligands were originally designed to incorporate a mixed soft/hard donor set in x  x  order to stabilize intermediate oxidation states of Tc and Re. In this regard they have been highly successful; all of the complexes reported before this study contain Re(V), and most contain the [Re=0]  3+  core. The complexes retain many of the properties of  compounds such as mer-ReOCl3(PPh ) , including octahedral geometry, but reduce the 3  2  number of, or eliminate completely, the labile halide ligands.  pet ether, 273K ^ n-BuLi, T M E D A *  0 . ^O.  R=H: (oHydroxyphenyl)diphenylphosphine, HPO R=Me: (2-Hydroxy-5-methylphenyl)diphenylphosphine), H(MePO) R=f-Bu: (5-tert-Butyl-2-hydroxyphenyl)diphenylphosphine, H(f-BuPO)  pet ether, 273K _ n-BuLi, T M E D A '  R  R=H: Bis(o-hydroxyphenyl)phenylphosphine, H P0 R=Me: Bis(2-hydroxy-5-methylphenyl)phenylphosphine, H (Me P0 R=f-Bu: Bis(5-fert-butyl-2-hydroxyphenyl)phenylphosphine, H (f-Bu P0 ) 2  2  2  2  2  Scheme 2.1  - 18-  2  2  2  HCI(g) /  anhydrous MeOH  A series of jrara-substituted alkyl HPO and H2PO2 derivatives have been synthesized in our group by modifying the published preparations for H P O (Scheme 2.1).  19  1 8  and H2PO2  6  The synthetic methodology is relatively unchanged except for the use of  j^ara-substituted phenols in the first step. After mom (methoxymethyl) protection, the />ara-substituted phenols are ortho lithiated and then reacted with the appropriate chlorophenylphosphines, which are subsequently deprotected. The difficulty of isolating pure product increases dramatically both with the size and number of alkyl substituents. Compared to the unsubstituted compounds, the methyl and f-butyl derivatives have enhanced solubility in organic solvents. In particular, the H2PO2 system shows remarkably higher solubility on going from the unsubstituted to the /-butyl-substituted compound.  In addition to enhancing solubility, the alkyl substituents also provide  convenient ' H and  1 3  C N M R handles in the metal complexes. The resulting changes in  lipophilicity were undertaken to allow isolation of crystals for X-ray structural analysis, which have been difficult to obtain, particularly in the case of H PC»2 complexes. 2  In this chapter, the synthesis and subsequent characterization of new complexes based on the [Re=0] reported. starting  3+  core with the alkyl derivatives H(MePO) and H2(Me2PC»2) is  Preparation of these complexes was achieved from a variety of rhenium materials,  including  [ReC^]",  a  necessary  radiopharmaceutical agent. The ability of these new [Re=0]  requirement  for  any  complexes to react with  various organohydrazines was also investigated. The resulting H Y N I C model could be used to evaluate the feasibility of using P O ligands in the H Y N I C system. x  - 19-  2.2. Experimental  Materials. (2-Hydroxy-5-methylphenyl)diphenylphosphine (H(MePO)) , bis(219  hydroxy-5-methylphenyl)phenylphosphine (H (Me2P02)) 2  19  and mer-[ReOCl (PPh ) ] 3  3  20  2  were synthesized by published methods. A l l solvents were of H P L C grade and were obtained from Fisher. When anhydrous solvents were required, they were dried using conventional procedures.  Reactions were carried out under Ar, although all of the  21  product metal complexes were found to be air and moisture stable. Concentrated HC1 and NEt were obtained from commercial sources (Fisher) and were used without further 3  purification.  2-Hydrazinopyridine, 2-hydrazino-2-imidazoline, phenylhydrazine, N , N -  phenylmethylhydrazine and N,N-dimethylhydrazine were used as obtained from Aldrich. [NH ][Re04] was a gift from Johnson-Matthey and was also used without purification. 4  Instrumentation.  Mass spectra were obtained with either a Kratos M S 50  (electron impact ionization, EIMS) or a Kratos Concept II H32Q instrument (Cs -LSIMS +  with positive ion detection).  Infrared (IR) spectra in the range 4000-500 cm" were 1  recorded as K B r disks with a Mattson Galaxy Series 5000 FTIR spectrophotometer. Microanalyses for C, H , N , and C l were performed by Mr. P. Borda in this department. "H N M R spectra were recorded on a Bruker AC-200E (200 MHz) N M R spectrometer with 8 referenced downfield from external TMS.  31  P{'H} N M R spectra were recorded  on Bruker AC-200E (81 MHz) or Bruker AMX-500 (202.5 MHz) spectrometers with 8 referenced to external 85% aqueous phosphoric acid.  -20-  Preparation of Compounds. [ReOCl (PPh ) ] (84 mg, 0.10 mmol) 3  3  [ReOCl(MePO) ], (2.1). 2  Method A :  mer-  and H ( M e P O ) C H O H (74 mg, 0.23 mmol) were  20  2  3  dissolved in ethanol (10 mL), and refluxed under A r for 30 minutes. Three drops of triethylamine were added and the subsequent mixture was refluxed for a further 60 minutes. The solvent was removed; the green solid was redissolved into a minimum amount of CH C1 . Diethyl ether (20 mL) was added and the solution was cooled; the 2  2  resulting white precipitate of [NHEt ]Cl was removed by filtration and w-pentane (200 3  mL) was added to the green solution to produce a green precipitate, after partial removal of solvent. The green precipitate was filtered, washed liberally with «-pentane and dried in vacuo to yield 48 mg (59 %). The product was soluble in acetone, acetonitrile, CHC1 and  CH C1 , 2  2  but  insoluble in E t 0 2  and H-pentane Anal.  Calcd  (found)  3  for  C H C 1 0 P R e : C, 55.64 (55.72); H , 3.93 (3.97); C l 4.32 (4.22). (+)LSIMS: m/z = 38  32  3  2  785 ([M-C1] ). IR (cm" ): 957 (Re=0). ' H N M R (CD C1 ) 5: 7.8-6.0 (overlapping, 26 +  1  2  2  H , aromatic H), 2.26 (s, 3H, CH ), 2.20 (s, 3H, CH ). 3  31  3  P{'H} N M R (CD C1 , 202.5 2  2  MHz) 8: 15.25 (d, J ' = 10 Hz), 2.05 (d, J > = 10 Hz). Crystals suitable for X-ray 2  2  P P  PP  structure analysis were grown by slow diffusion of pentane into a C H C 1 solution of the 2  2  complex. Method B: To a 25 mL ethanol solution of [NH ][Re0 ] (78.8 mg, 0.294 mmol) 4  4  and H ( M e P O > C H O H (248 mg, 0.765 mmol) was added one drop of concentrated HC1. 3  This solution was refluxed for two hours under Ar; triethylamine (150 mg, 0.15 mmol) was then added, and the solution was further refluxed overnight. The resulting green solution was filtered, and then purified on a silica gel column using 20:1 C H C 1 / C H 0 H 3  3  eluent (TLC Rf 0.69, green). After removal of the solvent, the solid was recrystallized  -21 -  from a saturated solution of CHCI3 and n-pentane, and was dried in vacuo overnight. The resulting olive green solid was found to be identical to 2.1 synthesized by method A , yield 118 mg (49%). [ReO(Me2P02)(H(Me P02))], (2.2).  To a 20 m L ethanol  2  solution of  [NH ][Re0 ] (30 mg, 0.11 mmol) and H2(Me P02)»CH OH»HCl (100 mg, 0.25 mmol) 4  4  2  was added one drop of concentrated HC1.  3  This solution was refluxed for several hours  under Ar, triefhylamine (100 mg, 0.1 mmol) was then added, and the solution was further refluxed overnight. The resulting green solution was filtered and then purified on a silica gel column using 20:1 CHCI3/CH3OH eluent (TLC R 0.75, green). After removal of the f  solvent, a green solid was isolated and dried in vacuo, yield 40 mg (43%). Anal. Calcd (found) for G ^ C ^ R e ^ O :  C, 55.74 (55.62); H , 4.33 (4.33). (+)LSIMS: m/z = 845  ([M+H] ). IR (cm" ): 965 (Re=0). ' H N M R (CD OD) 5: 7.9-5.7 (overlapping, 22H +  1  3  aromatic H), 2.27 (s, 3H, CH ), 2.21 (s, 3H, CH ), 2.12 (s, 3H, CH ), 2.09 (s, 3H, CH ). 3  31  3  3  3  P { ' H } N M R (CD3OD, 202.5 MHz) 5: 21.14 (d, J ' = 4 Hz), 12.69 (d, J . = 4 Hz). 2  2  P P  P P  Crystals suitable for X-ray structure analysis were grown by slow evaporation of an acetonitrile/methanol/acetone solution of the complex.  X-ray crystallographic analyses of 2.1 and 2.2. Please refer to the appendix for experimental details, and for complete tables of bond lengths and bond angles.  -22-  2.3. Results and Discussion  2.3.1. [Re=Or Complex of H(MePO) [ReOCl(MePO) ] (2.1) was prepared in good yield by reaction of H(MePO) with 2  /wer-[ReOCl3(PPh3)2] under basic conditions.  The complex was also made from  [NH ][Re04] by reduction of the metal in the presence of H(MePO) and HC1, an 4  important result because of the preference for [  186/188  ReC>4]" as a starting material in  nuclear medicine. After sufficient time for the reduction, the reaction mixture was made basic; the complex was formed and isolated in good yield.  The mechanism of the  reduction was not investigated in detail, but the reaction does not produce the oxide of H(MePO) as an oxidation product. 2.1 is soluble in organic solvents such as methanol and dichloromethane, but is insoluble in diethyl ether or less polar solvents. The diagnostic Re=0 stretch in the IR spectrum of 2.1 at 957 cm" is consistent 1  with values for related rhenium oxo complexes. ' The +LSIMS spectrum shows only a 6 7  small trace of the parent peak at m/z 820 and is dominated by the parent minus chloride cation peak at m/z 785. The presence of one chloride was verified by elemental analysis. The complex does not precipitate upon addition of sodium tetraphenylborate, indicating that it is neutral and not cationic in solution. The ' r l N M R spectrum of 2.1 shows two methyl resonances, as expected for a bis complex of low symmetry. The 26:6 integration between the aromatic and the methyl 31  groups is consistent with the proposed formulation. The two doublets in the  P NMR  spectrum possess a J(p,p) coupling constant of 10 Hz, consistent with two mutually cis 2  phosphorus nuclei in dichloromethane solution. The related complex [ReOCl(PO)2] is also cis-(F,F) when synthesized in alcohol solution. The addition of the methyl group -236  does not create enough steric hindrance for the complex to convert to the trans-(P,P) stereoisomer. Only the one stereoisomer reported appears to form in this reaction. Single crystals for an X-ray structural analysis of 2.1 were obtained by slow diffusion of pentane into a dichloromethane solution of the purified complex (Table 2.1, Figure 2.1). The complex is a neutral, distorted octahedral [Re=0 ] complex with a 3+  P2O3CI coordination sphere.  Two pentane molecules are incorporated in the crystal  lattice per complex, for a total of 16 in the unit cell. As expected, the MePO ligands act as uninegative, bidentate chelates with the oxo group and the chloride filling the remaining octahedral coordination sites. One Me-PO ligand occupies two equatorial sites and the other occupies both an equatorial site and the axial site trans to the oxo group.  Figure 2.1: ORTEP diagram of [ReOCl(MePO)2], 2.1 (with the solvent molecules and H-atoms omitted); 50% thermal probability ellipsoids are shown. -24-  The Re=0 bond length of 1.680 A is identical to that in the reported structure of [ReOCl(PO)2].  7  The Re-P bond lengths are comparable, with Re-P trans to the chloride  slightly elongated compared to Re-P trans to the phenolic O donor. This is contrary to the reported [ReOCl(PO)2] structure wherein both bond lengths are circa 0.04 A longer and the opposite effect was observed. It is possible that the methyl groups on the phenol ring are causing electronic effects. If this is the case, the effects are not centered at the phenolic oxygen because the Re-0 bond lengths remain essentially unchanged. The cis Re-Cl bond length is 0.14 A shorter than that reported previously, but the isotropic refinement of the structure revealed that there may be some disorder in the chloro position affecting the reported bond length.  Table 2.1: Selected Bond Lengths (A) and Angles (deg) in [ReOCl(MePO) ] (2.1). 2  Re=0(3)  1.680(4)  Cl(l)-Re-0(3)  98.23(16)  Re-Cl(l)  2.264(4)  PO)-Re-O(l)  100.69(5)  Re-P(l)  2.4457(15)  P(l)-Re-0(2)  83.41(12)  Re-P(2)  2.4206(17)  P(l)-Re-0(3)  91.00(14)  Re-O(l)  2.013(4)  P(2)-Re-0(1)  160.08(10)  Re-0(2)  2.044(3)  P(2)-Re-0(2)  77.96(12)  Cl(l)-Re-P(l)  162.66(10)  P(2)-Re-0(3)  87.18(14)  Cl(l)-Re-P(2)  94.44(12)  0(l)-Re-0(2)  82.57(15)  Cl(l)-Re-0(1)  81.89(15)  0(l)-Re-0(3)  112.70(16)  Cl(l)-Re-0(2)  91.57(14)  0(2)-Re-0(3)  162.80(15)  -25-  The bond angles indicate that the coordination in 2.1 is best described as distorted octahedral.  Most of the bond angles are similar to those in [ReOCl(PO)2] with one  notable exception: the bidentate phenol ring that is coordinated both through an axial and equatorial position is twisted away from the chloride.  The Cl(l)-Re-0(2) angle is  compressed 7° as the phenol is brought closer to the chloride and the Cl(l)-Re-0(2) angle is opened by 5°. This, in effect, moves the ring and its methyl group away from the proximity of the chloride. This effect is likely a combination of the increased steric bulk of the methyl group and the shortened Re-Cl bond length.  2.3.2. [Re=OJ Complex of H (Me P0 ) 3+  2  2  [ReO(Me P0 )(H(Me P0 ))] 2  2  2  2  (2.2) was synthesized from [NH ][Re0 ] by  2  4  4  reducing perrhenate in the presence of the ligand and HC1. As with 2.1, no phosphine oxide products were detected in the reaction mixture. After reduction, addition of excess base formed a green complex that was soluble in ethanol. This enhanced solubility is presumably due to the methyl groups since the analogue [ReO(P0 )(HP0 )] is insoluble 2  in ethanol.  6  2  Pure 2.2 was isolated in reasonable yield after purification using silica gel  chromatography. The formation of a rhenium oxo complex is evident from the 965 cm"  1  band in the infrared spectrum, and its formulation is supported by the +LSIMS spectrum. As expected for a bis complex, the H N M R spectrum shows four methyl resonances !  31  which integrate to give the theoretical 22:12 aromatic:mefhyl ratio.  The  P NMR  spectrum shows two doublets with a J(P,P) coupling constant of 4 Hz, consistent with two 2  mutually cis phosphorus nuclei in solution. At 25°C, there is no indication of any exchange between the free arm of the bidentate ligand with the tridentate M e P 0 ligand. 2  -26-  2  Figure 2.2: ORTEP diagram of [ReO(Me P02)(H(Me P02))], 2.2 (with the 2  2  solvent molecules and H-atoms omitted); 50% thermal probability ellipsoids are shown.  Single  crystals  acetonitrile/methanol/acetone  were  isolated  solution of the  from  a  purified  slowly  complex.  monometallic compound has a distorted octahedral geometry with a  evaporated The  P2O4  discrete, donor set  (Table 2.2, Figure 2.2). One M e 2 P 0 ligand is bound in a facial, tridentate fashion with P 2  and O atoms occupying equatorial positions, and the remaining oxygen occupying the axial position trans to the oxo linkage.  The second M e P 0 2  2  ligand is bound in an  equatorial bidentate fashion with the remaining O protonated and uncoordinated to Re. The addition of acetonitrile to the crystal growing solution was necessary and suitable crystals could not be obtained without it. -27-  Indeed, the crystal structure shows two  acetonitrile molecules per complex, one of which is hydrogen bound to the free phenolic O H with a N - 0 contact of 2.82(1) A.  Table  2.2:  Selected  Bond  Lengths  (A)  and  Angles  (deg)  in  [ReO(Me P02)(H(Me P02))] (2.2). 2  2  Re=0(5)  1.666(4)  P(2)-Re-0(1)  79.7(1)  Re-P(l)  2.410(2)  P(2)-Re-0(2)  160.9(1)  Re-P(2)  2.458(2)  P(2)-Re-0(3)  82.3(1)  Re-O(l)  2.035(4)  P(2)-Re-0(5)  93.9(2)  Re-0(2)  2.018(4)  0(l)-Re-0(2)  88.1(2)  Re-0(3)  2.003(4)  0(l)-Re-0(3)  85.1(2)  P(l)-Re-P(2)  108.24(5)  0(l)-Re-0(5)  163.6(2)  P(l)-Re-0(1)  75.0(1)  0(2)-Re-0(3)  82.0(2)  P(l)-Re-0(2)  82.4(1)  0(2)-Re-0(5)  101.5(2)  P(l)-Re-0(3)  155.0(1)  0(3)-Re-0(5)  109.2(2)  P(l)-Re-0(5)  93.0(1)  A search of the Cambridge Crystallographic Database  22  reveals that 2.2 is the  second rhenium PO2 complex structure to be reported, after [ReO(PO)(P02)].  6  The  Re=0 bond length in 2.2 (1.666(4) A) is consistent; Re-P bond lengths are typical, but the bidentate Re-P bond is significantly longer than in its tridentate analogue. This may be caused by the additional steric hindrance of the free, phenolic O H and its concomitant hydrogen-bonded acetonitrile. The phenol O H on the bidentate ligand is distorted away -28-  from the oxo group by over 10° from the 90° octahedral ideal. This distortion towards the axially coordinated phenol ring may add further steric stress to the bidentate ligand. Similarly, the tridentate ligand is distorted away from the oxo group. This is necessary for the axial phenol group to coordinate trans to the oxo group. The resulting 163.6(2)° 0(l)-Re-0(5) angle is far from linear and suggests that the tridentate ligand is under strain.  In both cases, the phosphine atoms lie within a few degrees of the ideal 90°,  relative to the oxo.  2.3.3. Reaction of 2.1 and 2.2 with Hydrazines There are examples in the literature of the successful bioconjugation of [Tc=0] complexes with the bifunctional chelate H Y N I C .  2 3 - 2 8  3+  Typically, a HYNIC-labeled  biomolecule is reacted with pertechnetate in the presence of the ligand and a reducing agent. In some cases, the reducing agent is not necessary due to the reductive capacity of the hydrazine.  29  Reactions of various hydrazines with 2.1 and 2.2 were attempted in  order to extend this type of chemistry to rhenium, and to test the feasibility of this approach. Under no conditions would a hydrazine complex form with 2.1 or 2.2, even at a 20:1 hydrazine:Re ratio.  None of 2-hydrazinopyridine, 2-hydrazino-2-imidazoline,  phenylhydrazine, N,N-phenylmethylhydrazine or N,N-dimethylhydrazine produced any product.  In each case, 2.1 or 2.2 were recovered from the reaction mixture in near  quantitative yield. In order to drive the elimination of the Re=0 oxygen atom as water (Scheme 1.1) to form a hydrazine complex, temperatures as high as 180°C were used, with and without molecular sieves, but all attempts were unsuccessful. NaBH  4  as  a  reducing  agent  did  not  promote  formation  of  Addition of complex  by  reduction/complexation. Since hydrazine-containing complexes of Re are known to be -29-  accessible from halogen/phosphine complexes containing the [Re=0]  core (Chapter 3),  it is surprising that the reaction with 2.1 and 2.2 was unsuccessful. A n alternative route to H Y N I C bioconjugates of P O and hydrazines is possible: x  preformation of PO /hydrazine-containing metal complexes, followed by subsequent x  conjugation to the biomolecule. This idea will be explored further in Chapter 3. Perhaps the ligands are far too kinetically inert and thermodynamically stable to allow coordination of hydrazine and reduction of the metal with the concomitant elimination of the oxo group as water.  -30-  2.4. Conclusions  New alkylated derivatives of the H P O system have been synthesized and isolated in x  x  pure form. The presence of the methyl groups increased the solubility of the ligands, and of the final complexes, in organic solvents.  The methyl groups also provided a  convenient ' H N M R probe as the number of peaks provided an estimate of the purity and identity of the resulting complexes. 2.1 was obtained by reaction of H(MePO) with mer-[ReOCl3(PPli3)2] and in a reduction/complexation reaction from [NH4][ReC>4]. 2.2 was obtained by direct reaction of H2(Me2PC>2) with [NFL^fReCu]. The easy synthesis of each complex from [Re0 ]~ is 4  significant, since this is a strict requirement for any radiopharmaceutical that must incorporate rhenium.  The increased solubility was exploited to grow X-ray quality  crystals of 2.1 and 2.2; in the latter case, the second structurally characterized complex of its type. 2.1 and 2.2 have a cis-(P,P) arrangement of the ligands, both in solution and the solid state. The complexes appear to be inert and show no evidence of exchange between the ligands at the N M R timescale. In an attempt to form mixed P O / hydrazine complexes, 2.1 and 2.2 were reacted x  with a variety of hydrazines under a wide range of conditions. The P O ligands are x  clearly not suitable for this type of reaction since no products were isolated from these reactions.  -31 -  2.5. References  1) Jurisson, S.; Desilets, C. P.; Jia, W.; Ma, D. Chem. Rev. 1993, 93, 1137. 2) Dilworth, J. R.; Parrott, S. J. Chem. Soc. Rev. 1998, 27, 43. 3) Jurisson, S. S.; Lydon, J. D. Chem. Rev. 1999, 99, 2205. 4) Rouschias, G. Chem. Rev. 1974, 74, 531. 5) Fergusson, J. E. Coord. Chem. Rev. 1966, 459. 6) Luo, H.; Setyawati, I.; Rettig, S. J.; Orvig, C. Inorg. Chem. 1995, 34, 2287. 7) Bolzati, C.; Tisato, F.; Refosco, F.; Bandoli, G ; Dolmella, A . Inorg. Chem. 1996, 35, 6221. 8) Loiseau, F.; Connac, F.; Lucchese, Y . ; Dartiguenave, M . ; Fortin, S.; Beauchamp, A . L.; Coulais, Y . Inorg. Chim. Acta 2000, 306, 94. 9) Loiseau, F.; Lucchese, Y . ; Dartiguenave, M . ; Coulais, Y . Polyhedron 2000,19, 1111. 10) Connac, F.; Lucchese, Y . ; Gressier, M . ; Dartiguenave, M . ; Beauchamp, A . L . Inorg. Chim. Acta 2000, 304, 52. 11) Nock, B . ; Maina, T.; Tisato, F.; Papadopoulos, M . ; Raptopoulou, C. P.; Terzis, A . ; Chiotellis, E. Inorg. Chem. 1999, 38, 4197. 12) Nock, B.; Maina, T.; Tisato, F.; Papadopoulos, M . ; Raptopoulou, C. P.; Terzis, A . ; Chiotellis, E. Inorg. Chem. 2000, 39, 2178. 13) Nock, B.; Maina, T.; Tisato, F.; Raptopoulou, C. P.; Terzis, A . ; Chiotellis, E. Inorg. Chem. 2000, 39, 5197. 14) Chi, D. Y . ; O'Neil, J. P.; Anderson, C. J.; Welch, M . J.; Katzenellenbogen, J. A . J. Med. Chem. 1994, 37, 928.  -32-  15) Meegalla, S.; Plossl, K . ; Kung, M.-P.; Stevenson, D. A . ; Liable-Sands, L . M . ; Rheingold, A . I.; Kung, H . F.  Am. Chem. Soc. 1995,117, 1137.  16) Papadopoulos, M . S.; Pirmettis, I. C ; Pelecanou, M . ; Raptopoulou, C. P.; Terzis, A . ; Stassinopoulou, C. I.; Chiotellis, E. Inorg. Chem. 1996, 35, 7377, and references therein. 17) Hansen, L.; Lipowska, M . ; Melendez, E.; Xu, X . ; Hirota, S.; Taylor, A . T.; Marzilli, L. G. Inorg. Chem. 1999, 38, 5351 and references therein. 18) Rauchfuss, T. B. Inorg. Chem. 1977,16, 2966. 19) Kovacs, M . S.; Hein, P.; Sattarzadeh, S.; Patrick, B. O.; Emge, T. J.; Orvig, C. , Submitted for publication. 20) Chatt, J.; Rowe, G. A . J. Chem. Soc. 1962, 4019. 21) Perrin, D. D.; Armarego, W. L . F.; Perrin, D. R. Purification of Laboratory Chemicals; 2nd ed.; Pergamon Press: Toronto, 1980. 22) Allen, F. H . ; Kennard, O. Chemical Design Automation News 1993, 5, 31. 23) Liu, S.; Edwards, D. S.; Looby, R. J.; Harris, A . R.; Poirier, M . J.; Barrett, J. A . ; Heminway, S. J.; Carroll, T. R. Bioconjugate Chem. 1996, 7, 63. 24) Liu, S.; Edwards, D. S.; Harris, A . R.; Singh, P. R. Appl. Radiat. Isot. 1997, 48, 11031111. 25) Edwards, D. S.; Liu, S.; Barrett, J. A . ; Harris, A . R.; Looby, R. J.; Ziegler, M . C ; Heminway, S. J.; Carroll, T. R. Bioconjugate Chem. 1997, 8, 146. 26) Barrett, J. A . ; Crocker, A . C ; Damphousse, D. J.; Heminway, S. J.; Liu, S.; Edwards, D. S.; Lazewatsky, J. L.; Kagan, M . ; Mazaika, T. J.; Carroll, T. R. Bioconjugate Chem. 1997, 8, 155. 27) Larsen, S. K . ; Solomon, H . F.; Caldwell, G.; Abrams, M . J. Bioconjugate Chem. 1995, 6, 635. -33-  28) Rajopadhye, M . ; Harris, T. D.; Yu, K.; Glowacka, D.; Damphousse, P. R.; Barret, J. A.; Heminway, S. J.; Edwards, D. S.; Carroll, T. R. Bioorg. Med. Chem. Lett. 1997, 7, 955. 29) Abrams, M . J.; Juweid, M . ; tenKate, C. I.; Schwartz, D. A.; Hauser, M . M . ; Gaul, F. E.; Fuccello, A . J.; Rubin, R. H.; Strauss, H. W.; Fischman, A. J. 2022.  -34-  Nucl. Med. 1990, 31,  Chapter Three Phosphine-Phenolate Complexes Containing Rhenium-Hydrazine Cores  3.1. Introduction  As previously noted in Chapter 2, the synthesis of hydrazine-containing ternary complexes failed when [ReOCl(MePO) ] (2.1) and [ReO(Me P02)(H(Me P02))] (2.2) 2  2  2  were reacted directly with various organohydrazines. Therefore, it is not possible to use the synthetic route shown pictorially in Scheme 1.1. A possible alternative route to H Y N I C complexes is through the preformed chelate approach (Scheme 3.1).  [M0 ]" 4  +  L  +  -N  N  % N. L %,/ L L  Metal-labeled BAM  Scheme 3.1 -35-  BAM  1  The preformation of hydrazine-containing metal complexes, followed by reaction with H P O and subsequent conjugation to the biomolecules offers many advantages over x  x  indirect labeling approach (Scheme 1.1), wherein the hydrazine and biomolecules are incorporated into the complex last. To compensate for the increased kinetic inertness of rhenium relative to technetium, conditions may be required that are too harsh for the biomolecule to tolerate. This synthetic route is advantageous because the complex can be formed under relatively harsh conditions before the biomolecule is introduced.  R I N-H I  R  N II N I M  N—R  R I N  H I M  Diazene  N II N I M  H  N'  Linear diazenido  Bent Isodiazene  Linear isodiazene  H—N I M  H—N I M Hydrazido (1-)  M Neutral hydrazino  2  * N I M  R I N  Bent diazenido  Scheme 3.2  The coordination chemistry of rhenium with hydrazines is rich and varied. " 3  22  There are at least 7 known coordination modes known with various oxidation states of metal and hydrazine (Scheme 3.2).  17  Most of these compounds are mixed complexes of  a hydrazine with phosphines and halogens, and most have been made by convenient reduction of mer-[ReOCl (P) ] (P = PPh or PMe Ph) to form five or six coordinate 3  2  3  2  ^hydrazine complexes, with the hydrazine ligands cis to each other (Figure 3.1). 9,11,12,16  6-  it is curious that many hydrazines are reactive with mer-[ReOCl (P) ] (P = PPh 3  -36-  2  3  or PMe2Ph), but not with the PO -containing complexes 2.1 and 2.2, since both contain x  the [Re=0] core with mixed phosphines and halogens. 3+  Cl  I  Ph3P  n  Br Br  Re^PPh3  \/  Ph3P  PhN/ \l Ph  +  ?'  Re^PPhg  I  Cl  P h N / N Ph  +  Re—PPh  3  PhMeN/ Yl MePh  X  2  H  2  2  Figure 3.1: Selected Rhenium Hydrazine Complexes Containing Halide and Phosphine Ligands.  As alluded to above, [ReCl(N Ph)2(PPh )2] (Figure 3.1, left) is formed by direct 2  3  reaction of [ R e O C ^ P P h ^ ] with phenylhydrazine.  18  The para-bromophenylhydrazine  analogue has been structurally characterized as a five coordinate complex with the two diazenido  ligands  cis  to  each  other.  There  11  is  extensive  evidence  that  [ReCl(N2Ph) (PPh3)2] reacts in halogenated solvents to form a six coordinate p-chloro 2  bridged dimer.  If HC1 is added to a solution of the complex, the protonated six  9  coordinate complex [ReCl2(N Ph)(HN2Ph)(PPh3)2] is isolated; the analogous bromo 2  complex can be isolated by substituting HBr. [ReCl(N Ph) (PPh3)2] 2  with  2  Br2  affords  [ReBr2(N2Ph) (PPri3)2][Br] (Figure 3.1, centre). 2  the 18  9  Interestingly, the oxidation of six  coordinate  Re  complex,  Linear isodiazene complexes containg  rhenium, phosphines and halides are also known. The reaction of [ R e O C ^ P P h ^ ] with N,N-phenylmethylhydrazine  in  methanol  yields  five  coordinate  [ReCl2(N PhMe) (PPh )][BPh4] (Figure 3.1, right) after the addition of N a B P l u . 2  2  12  3  There has been a burgeoning interest in synthesizing complexes with the [Re(Hhypy)(hypy)] core (hypy = N C H N ) as models for the H Y N I C bioconjugation 2+  2  of metal complexes (Scheme 3.3). ' 23  24  5  4  The [Re(Hhypy)(hypyH)Cl ] parent complex can -373  be synthesized by reaction of [Re0 ]" with 2-hydrazinopyridine hydrochloride in 4  methanol. '  The ligand reduced Re(VII) to Re(III) after which the oxidized  23 25  organodiazenes (hypy) coordinated to the metal in a unique bidentate bent diazene (Hhypy) and in a monodentate linear diazenido fashion with the pyridine nitrogen protonated in the latter case (hypyH). The chloro complex is not expected to be stable in vivo. Since the initiation of our studies, others have tried to stabilize the core through the formation of ternary complexes, demonstrating that thiols, including HPS (the thiol equivalent of HPO), could be used to form complexes with the [Re(Hhypy)(hypy)] core.  24  O 2-hydrazinopyridine (hbhypy)  HYNIC  [Re0]" + 4  [Re(Hhypy)(hypyH)CI ] 3  Scheme 3.3  In order to stabilize this core towards hydrolysis in vivo, we thought that the H P O ligands could be bound to the metal as ancillary ligands. Recently, a variety of x  x  tethered "3+2" rhenium oxo complexes with mixed N S . X  -38-  3  X  and PO have been  elaborated. " 26  28  These compounds appear to be very stable - some were able to withstand  a glutathione challenge experiment for 24 h .  No known ternary complexes of  26  hydrazine/diazo ligands and H P O have been included in the literature prior to this x  report.  x  The ability of H P O to stabilize intermediate oxidation states and to form x  x  hydrolytically stable complexes indicates that the ligand may well be an excellent choice for use in the H Y N I C system. To this end, we decided to investigate the reactivity of these ligands with the [Re(Hhypy)(hypy)] core. 2+  To further explore the reactivity of H P O , attempts were made to synthesize x  x  mixed hydrazine-PO complexes starting from the known complexes in Figure 3.1. It x  was hoped that the P O ligands would displace PPI13 and halide ligands to form more x  hydrolytically stable complexes.  The discovery of new hydrazine-based cores is  attractive for a number of reasons.  Besides the obvious patent implications, the  elimination of the potentially interfering pyridyl donor in H Y N I C may result in a more simplified scheme to functionalize biomolecules.  The N,N-phenylmefhylhydrazine  complexes are particularly attractive; only four of the possible seven hydrazine coordination modes (Scheme 3.2) are possible due to the methyl group (two are possible if only the N=N modes are considered).  -39-  3.2. Experimental  Materials. (o-Hydroxyphenyl)diphenylphosphine  (HPO) , 29  bis(o-hydroxyphenyl)phenylphosphine  (H PO )30,  (2-hydroxy-5-methylphenyl)diphenylphosphine  (H(MePO)) ,  bis(2-hydroxy-5-methylphenyl)phenylphosphine  (H (Me P0 ))3i,  2  2  31  2  2  2  [ReCl(N Ph) (PPh ) ] , [ReBr (N Ph) (PPh ) ] [Br] , [ReCl (N PhMe) (PPh )] [BPI14] 18  2  2  3  18  2  2  2  2  3  2  2  2  2  and [Re(hypy)(hypyH)Cl ] ' were synthesized by published methods. 23 25  3  12  3  A l l solvents  were of H P L C grade and were obtained from Fisher. When anhydrous solvents were required, they were dried using conventional procedures.  32  Reactions were carried out  under Ar, although all of the product metal complexes were found to be air and moisture stable.  NEt  3  (Fisher),  Br , 2  2-hydrazinopyridine,  phenylhydrazine  and N , N -  phenylmethylhydrazine were obtained from commercial sources (Aldrich) and were used without further purification. [NH ][Re04] was a gift from Johnson-Matthey and was also 4  used without purification. Instrumentation. Experimental details are identical to those outlined in Section 2.2 with the following exceptions: *H N M R spectra were recorded on Bruker AC-200E (200 M H z ) or Bruker AV-300 (300 MHz) N M R spectrometers with 5 referenced downfield from external TMS.  31  P { ' H } were recorded on Bruker AC-200E (81 MHz) or  Bruker AV-300 (121.5 MHz) N M R spectrometers with 5 referenced to external 85% aqueous phosphoric acid. Preparation of Compounds. [Re(Hhypy)(hypy)(PO)(HPO)]Cl, (3.1). Method A : [Re(Hhypy)(hypyH)Cl ] (62 mg, 0.118 mmol) and HPO (93 mg, 0.294 mmol) were 3  dissolved in 15 mL methanol. The reaction flask was flushed with A r for 20 minutes, -40-  after which time triethylamine (32 mg, 0.317 mmol) was added. The solution began to turn red immediately and was refluxed overnight. The resulting red solution was purified on a silica gel column using 10:1 C H C l / M e O H eluent (TLC R =0.12, red). 3  f  After  removal of the solvent, the red product was recrystallized from CH2CI2/CH3OH, and dried  in  vacuo,  yield  80  mg  (64  %).  Anal.  Calcd.  (found)  for  C 6H36ClN 02P2Re-CH Cl2: C, 52.64 (53.11); H , 3.57 (4.03); N , 7.84 (8.13). (+)LSIMS: 4  6  2  m/z = 955 ([M] ). *H N M R (CD C1 ) 8: 8.66 (dd, I H , a-nitrogen H, J -p) = 5.1 Hz, +  3  2  3  2  (H  J -p') = 1.2 Hz), 7.9-6.4 (overlapping multiplets, 36H). (H  32.9 (d, J(P, ) = 202 Hz), 14.1 (d, J , 2  2  P  ( P  P )  3 1  P N M R (CD C1 , 81 MHz) 5: 2  2  = 202 Hz). Crystals suitable for X-ray structure  analysis were grown by slow diffusion of cyclohexane into a chlorobenzene/toluene solution of the isolated complex. Method B : [NH ][Re0 ] (100 mg, 0.373 mmol) and 2-hydrazinopyridine-2HCl 4  4  (270 mg, 1.492 mmol) were combined and stirred into 40 mL methanol. The solution color quickly changed to purple; the reaction solution was refluxed for 30 minutes. After allowing the solution to cool, HPOHC1 (500 mg 1.59 mmol) in 10 mL methanol was added, followed by N E t (300 mg, 2.97 mmol). The mixture was refluxed overnight, and 3  afforded a red mixture of products.  The products were separated on silica gel and  isolated: 3.1 (190 mg, 48%), 3.2 (26 mg, 10%). [ReCl(Hhypy)(hypy)(PO)], (3.2). [ReCl(Hhypy)(hypy)(PO)] (20 mg, 24 %) was isolated, on a silica gel column using 10:1 C H C 1 / C H 0 H eluent, as a byproduct of the 3  reaction of 3.1 (TLC R = 0.54). IR(cm"'): 1579 ( v f  3  N=N  ) , 1551 ( v  N=N  ) . (+)LSIMS: m/z =  677 ([M-C1] ). ' H N M R (CD C1 ) 8: 8.02 (d, I H , a-nitrogen H, J ,p) = 6.1 Hz), 7,7+  3  2  2  6.5 (overlapped multiplets, 22H).  (H  3 1  P N M R (CD C1 , 81 MHz) 8: 25.5 (s). Crystals 2  -41 -  2  suitable for X-ray structure analysis were obtained by slowly evaporating a solution of the complex in C H C l / M e O H . 2  2  [Re(Hhypy)(hypy)(HP0 )(H P0 )]Gl (3.3). 2  2  This complex was synthesized  2  using method A for 3.1 with the substitution of H P 0 for HPO. 2  ([M] ). ' H N M R +  8: 8.50 (dd, I H , cc-nitrogen H, J -p) = 1.0 Hz, J .p') = 4.9  (CD3OD)  3  J , P ) = 207 Hz), ( P  13.5 (d, J 2  ( P  3  (H  Hz), 7.9-6.0 (overlapping multiplets, 34H). 2  (+)LSIMS: m/z = 987  2  ,  P )  = 202  3 1  P N M R (CD OD, 81 M H z ) 8: 31.8 (d, 3  Hz).  [Re(Hhypy)(hypy)(H(Me P0 ))(H (Me P0 )]Cl 2  (H  2  2  2  (3.4).  2  This complex was  synthesized using method A of the synthesis for 3.1 with the substitution of H ( M e P 0 ) 2  for HPO.  2  Only the major product was isolated and characterized. Recrystallization from  C H C 1 / C H 0 H afforded pure product, yield 60 mg (45%). 2  2  2  3  Anal. Calcd (found) for  C o H N 0 P R e C H C l : C, 54.30 (54.70); H , 4.29 (4.51); N , 7.45 (7.51). (+)LSIMS: 5  4 6  6  4  2  2  2  m/z = 1043 ([M] ). *H N M R (CD C1 ) 8: 8.45 (dd, I H , cc-nitrogen H, +  2  3  J H-P<) (  2  3  P )  ( H  - ) = P  1.1 Hz,  3  3  J(P,  J  = 5.0 Hz), 7.9-6.4 (overlapping multiplets, 30H), 2.17 (s, 3H, CH ), 2.07 (s, 3H,  C / / ) , 1.99 (s, 3H, CH ), 1.80 (s, 3H, CH ). 2  3  = 205 Hz), 12.8  2  (d, J P , ) = 202 2  (  P  3 1  P N M R (CD C1 , 81 MHz) 8: 32.8 (d, 2  2  Hz).  [Re(N PhMe) (MePO) ][BPh ] (3.5). [ReCl (N PhMe) (PPh )][BPh ] (300 mg, 2  2  2  4  2  2  2  3  4  0.278 mmol) was dissolved in 50 mL methanol. H(MePO) (204 mg, 0.707 mmol) was added as a 10 mL methanol solution, followed by the dropwise addition of N E t (120 mg, 3  1.18 mmol).  The mixture was stirred overnight at 25°C.  After the removal of  approximately half of the solvent, a brown precipitate formed, which was isolated by filtration, and purified on a silica gel column (TLC Rf= 0.68) using 9:1 C H C 1 : C H 0 H as 3  the eluent (110 mg, 30%).  3  Anal. Calcd (found) for C76H BN O P Re-0.5CHCl :  C, 66.20 (66.80); H , 4.97 (5.04); N , 4.04 (3.95). -42-  68  (+)LSIMS:  4  2  2  3  m/z = 1009 ([M] ), +  889 ([M-N PhMe] ). IR (cm" ): 1593 (N=N). ' H N M R (CD C1 , 300 MHz) 8: 7.8-6.5 +  1  2  2  2  (overlapping, 56 H , aromatic H), 3.46 (s, 6H, CH ), 2.31 (s, 6H, CH ). 3  3  3 1  P NMR  (CD C1 , 121.5 MHz) 8: 29.4 (s). 2  2  X-Ray Crystallographic Analyses of 3.1 and 3.2. Please refer to the appendix experimental details, and complete tables of bond lengths and bond angles.  -43 -  3.3. Results and Discussion  3.3.1. [Re(Hhypy)(hypyH)Cl ] + HPO 3  [Re(Hhypy)(hypyH)Cl3] reacts with HPO directly in methanolic solution in the presence of base to form a mixture of products.  Two products in the mixture were  isolated and characterized after purification on a silica gel column.  The salt  [Re(Hhypy)(hypy)(PO)(HPO)]Cl (3.1) was the major component (64%); all three chlorine atoms were replaced to give a N3OP2 coordination sphere.  Neutral  [ReCl(Hhypy)(hypy)(PO)] (3.2) was isolated as a minor component (24%). A 20:1 molar ratio of HPO:Re improved the yield of 3.1 only slightly and impurities, notably 3.2, were still present. There is evidence for the presence of other species in the mixture, but they were present in amounts too small to purify and characterize properly. Complexes 3.1 and 3.2 can also be formed directly from [NH4][Re04] in a "one pot" reaction; reduction/complexation of the perrhenate with 2-hydrazinopyridine in HC1 proceeds rapidly in methanol. Addition of excess HPO and sufficient base to neutralize the acid rapidly causes the solution to change color from purple to red. Purification on silica gel affords the same two complexes isolated by the direct route in only slightly diminished yields. The ability to synthesize complexes in a "one pot" reaction is highly desirable for preparative nuclear medicine, because the required starting material therein is perrhenate. Strong IR absorptions at 1580 cm" and 1550 cm' are indicative of doubly bonded 1  1  N=N organodiazo coordination in both complexes. The presence of these two identical bands in 3.1 and 3.2 suggests that both hydrazine ligands remain coordinated and retain -44-  significant double bond character in both cases. Clearly the complexes do not contain the Re(V) oxo core; there are no bands in the range 850 - 1050 cm" . The majority of the 1  spectral features in the infrared spectra are due to the bands arising from the supporting framework of the organic ligands. The ' H N M R spectrum of 3.1 consists of a very complex aromatic region (not assigned), the a-nitrogen proton, and the phenolic proton.  In CH2CI2 one of the  hydrazines retains the doubly bent, a-protonated, diazo mode of the starting material [Re(Hhypy)(hypyH)Cl3].  The a-nitrogen proton appears as an exchangeable, sharp  doublet of doublets at 8.79 ppm. This peak is shifted considerably downfield from that in the starting material, where the protonated pyridyl and a-nitrogen proton appear to be under exchange as a broad peak at 4.22 ppm.  23  There is possibly a weak hydrogen  bonding interaction with the free pyridine of the monodentate hypy. This interaction is seen in the crystal structure of the complex (vide infra) and is apparently retained in 31  solution. The coupling pattern is consistent with two chemically inequivalent P nuclei. The exchangeable phenolic proton appears as a broad resonance centered at 2.25 ppm in CH C1 solution. The ' H N M R spectrum strongly supports a diamagnetic, monocationic 2  2  Re(III) metal center. The  3 1  P N M R spectrum of 3.1 is consistent with the presence of two chemically  inequivalent, coordinated phosphines. In sharp contrast to the oxo complexes 2.1 and 2.2, the 202 Hz coupling constant of the two A B doublets is a strong indication that the phosphorus nuclei are coordinated trans to each other in 3.1 in CH2CI2. At 25°C, there is no indication of any fluxional process that exchanges the bidentate and monodentate PO ligands. -45 -  Single crystals of 3.1 for an X-ray structural analysis were obtained by the slow diffusion of cyclohexane into a chlorobenzene/toluene solution of the purified complex (Table 3.1, Figure 3.2). The coordination is best described as distorted octahedral with a N3OP2 coordination sphere about Re. Using the formalism of the Re(III) starting material [Re(Hhypy)(hypyH)Cl3], the complex is a Re(III) cation with a chloride counteranion.  Figure 3.2: ORTEP diagram of the cation [Re(Hhypy)(hypy)(PO)(HPO)] , 3.1 (with the +  solvent molecules, H-atoms and the counteranions omitted); 50% thermal probability ellipsoids are shown.  -46-  Table 3.1: Selected Bond Lengths (A) and Angles (deg) in [Re(Hhypy)(hypy)(PO)(HPO)]Cl (3.1).  Re-N(l)  1.980(4)  P(l)-Re-N(l)  94.91(14)  Re-N(3)  2.158(5)  P(l)-Re-N(3)  86.03(13)  Re-N(4)  1.780(5)  P(l)-Re-N(4)  94.83(15)  Re-O(l)  2.032(3)  P(2)-Re-0(1)  86.18(9)  Re-P(l)  2.4137(14)  P(2)-Re-N(l)  98.19(14)  Re-P(2)  2.4666(14)  P(2)-Re-N(3)  96.52(13)  N(l)-N(2)  1.299(7)  P(2)-Re-N(4)  86.66(15)  N(4)-N(5)  1.240(7)  0(1)-Re-N(l)  160.03(16)  0(1)-Re-N(4)  109.65(15)  0(1)-Re-N(3)  87.92(13)  N(l)-Re-N(3)  72.26(17)  Re-N(l)-N(2)  126.3(4)  N(l)-Re-N(4)  90.11(18)  N(l)-N(2)-C(19)  110.7(5)  N(3)-Re-N(4)  162.35(16)  Re-N(4)-N(5)  177.0(4)  P(l)-Re-P(2)  166.82(4)  N(4)-N(5)-C(24)  118.5(5)  P(l)-Re-0(1)  80.98(9)  The two diazo groups are cis to one another and both bond lengths therein are well within the range for N=N double bonds. One hypy is bidentate; the protonated diazo and pyridyl nitrogens form a 5-membered ring with a bite angle of 72.26(17)°. The other hypy is monodentate and is bound through the diazo group only. The diazo group on the bidentate hypy is best described as a "doubly bent" diazene ligand since the Re-N(l)N(2) and the N(l)-N(2)-C(19) bond angles are both within 10° of 120°. The monodentate -47-  diazo group has a nearly linear Re-N(4)-N(5) bond angle, a bent N(4)-N(5)-C(24) bond angle 120°, and should be regarded as a "singly bent" diazenido ligand. The Re-N(l) bond length of 1.980(4) A is significantly longer than the Re-N(4) bond length of 1.780(5) because of the a-nitrogen proton on N(l). There is a weak 2.870(8) A hydrogen bond contact between N ( l ) and the monodentate pyridyl nitrogen N(6), which is deprotonated. structure.  The a-nitrogen proton H(95) was included in the refinement of the  The N(2)-N(l)-N(6) angle of 134.8(3)° and the N(l)-H(95)-N(6) angle of  149(5)° indicate some strain associated with this interaction. The interaction of N ( l ) and N(6) through H(95) may contribute to the large ' H N M R chemical shift of the a-nitrogen proton that is retained in solution. As indicated in the P N M R spectrum, the two phosphorus nuclei are trans, with 3 1  a P(l)-Re-P(2) bond angle of 166.82(4) A. One of the PO ligands is bidentate, forming a 5-membered ring with a bite angle of 80.98(9)°. The second PO ligand is bound only through the phosphorus, with the protonated phenolic oxygen pointing away from the metal center.  The bidentate Re-P(l) bond is approximately 0.05 A shorter than the  monodentate Re-P(2) bond. The two hypy groups are slightly distorted away from P(l) and cause some steric crowding, hence the longer bond to P(2), and the displacement of P(2) towards 0(1). The H N M R spectrum of the minor product [ReCl(Hhypy)(hypy)(PO)] (3.2) !  shows roughly the same spectral features, with the omission of the free phenolic proton. The a-nitrogen proton appears as a doublet at 8.02 ppm, indicating coupling to only one 3 I  P nucleus in solution. If insufficient base is added to completely deprotonate the  pyridine in the starting material, the ' H N M R resonance of the doublet appears at 3.96 ppm. As in the starting material, the protonated pyridyl proton is under exchange with -48-  the a-nitrogen proton; however, the peak remains a distinct doublet and does not broaden to a singlet. The P N M R spectrum of 3.2 has the expected singlet at 25.5 ppm. Again, 3 1  the N M R evidence supports the presence of a diamagnetic Re(III) metal center.  F i g u r e 3.3: ORTEP diagram of [ReCl(Hhypy)(hypy)(PO)], 3.2; 50% thermal probability ellipsoids are shown.  In most regards, the structure of 3.2 is very similar to that of 3.1 (Table 3.2, Figure 3.3). Crystals were obtained by slow evaporation of a CH2CI2 / CH3OH solution of the complex. A distorted octahedral N3POCI donor set surrounds the formally Re(III) metal center, resulting in a neutral complex. The arrangement of the two hypy ligands is identical to that in 3.1, including the weak pyridine - a-nitrogen contact. The chloride is trans to the phosphorus donor of the bidentate PO ligand. -49-  The Re-Cl bond is  approximately 0.15 A longer than the cis Re-Cl bond measured in the structure of [ReOCl(MePO)2]. The two hypy ligands are pushed away from the bidentate phosphorus donor and distort the C l sharply towards the oxygen donor resulting in a P(l)-Re-Cl bond angle of 161.77(5)°.  Table 3.2: Selected Bond Lengths (A) and Angles (deg) in [ReCl(Hhypy)(hypy)(PO)] (3.2).  Re-Cl(l)  2.414(2)  N(4)-Re-0(1)  160.1(2)  Re-N(l)  1.779(5)  N(4)-Re-P(l)  96.14(14)  Re-N(4)  1.942(5)  N(4)-Re-Cl(l)  99.13(14)  Re-N(6)  2.137(5)  N(6)-Re-0(1)  88.3(2)  Re-O(l)  2.035(4)  N(6)-Re-P(l)  88.12(13)  Re-P(l)  2.400(2)  N(6)-Re-Cl(l)  87.20(13)  N(l)-N(2)  1.237(7)  0(1)-Re-P(l)  80.74(11)  N(4)-N(5)  1.312(7)  0(1)-Re-Cl(l)  81.51(11)  N(l)-Re-N(4)  90.7(2)  P(l)-Re-Cl(l)  161.77(5)  N(l)-Re-N(6)  162.4(2)  Re-N(l)-N(2)  174.7(4)  N(l)-Re-0(1)  109.15(18)  N(l)-N(2)-C(l)  118.9(5)  N(l)-Re-P(l)  96.30(15)  Re-N(4)-N(5)  128.7(4)  N(l)-Re-Cl(l)  93.44(15)  N(4)-N(5)-C(6)  108.4(5)  N(4)-Re-N(6)  71.9(2)  -50-  3.3.2. [Re(Hhypy)(hypyH)Cl ] + H P 0 & H ( M e P 0 ) 3  2  2  2  2  2  Originally it was hoped that a six coordinate Re(III) complex resembling [Re(hypy)(PO) ] could be synthesized and isolated from the reaction. Since the initiation 2  of our work, a complex of this type has been isolated and characterized from the analogous PS system, [Re(hypy)(PS) ]. 2  24  There appears to be no evidence for the  formation of its PO analog, although in the mixture there are small amounts of other species that cannot be fully characterized. The presence of the H-bonded meridional "belt" of hypy ligands appears to be a stable structural motif in this system. Attempts to displace the second hypy ligand by using a 20:1 HPO:Re ratio were unsuccessful. If base is omitted from the synthesis, the starting material remains largely unreacted and is recovered in near quantitative yield. The phenolic oxygen donor also appears to play a key role in the behavior of the complexes; the relatively soft Re(III) center may be unable to accommodate two such hard phenolic donors.  In addition to the "belt" effect, the second hypy may also be  regarded as a softer donor that is able to stabilize the Re(III) centre better than the hard phenolate oxygen donors.  The remaining coordination site trans to the bidentate  phosphine displays a distinct preference for soft donors such as Cl", the phosphine of PO, or in the case of the analogous PS complex, the thiophenolate donor.  24  This preference of the metal center for a relatively soft donor set may explain the inability of 2.1 and 2.2 to accept a hydrazine donor and/or reduce the metal center. Coordination to the sterically-crowded octahedral Re center would likely have to occur through a dissociative mechanism. The kinetic inertness and thermodynamic stability of the bidentate and tridentate donors in 2.1 and 2.2 may be too great for the incoming hydrazine to overcome.  Remembering that many diazenido complexes have been -51 -  synthesized from [ReOCl3(PPh )], the chelate effect of the P O ligands in 2.1 and 2.2 is 3  x  likely responsible for raising the energy barrier too high for diazenido complex formation to occur. Table 3.3: Selected ' H & P N M R spectral data for [Re(Hhypy)(hypy)(PO)(HPO)]Cl 3 1  (3.1), [ReCl(Hhypy)(hypy)(PO)] (3.2), [Re(Hhypy)(hypy)(HP0 )(H P0 )]Cl (3.3), and 2  2  2  [Re(Hhypy)(hypy)(H(Me P0 ))(H (Me P0 ))]Cl(3.4). 2  Complex  2  2  2  2  Alkyl ' H N M R Signals  a-nitrogen ' H N M R  (ppm)  Signals (ppm) and  3.1  3.2  3 1  P N M R Signals (ppm)  3 3 J(H-P)/ J(H-P')  and J( p) P;  8.66 (dd)  14.1 (d), 32.0(d)  1.2/5.1 Hz  202 Hz  8.02 (d)  25.5 (s)  6.1 Hz 3.3  3.4  1.80 (s)  8.50 (dd)  13.5 (d), 31.8(d)  1.0/4.9 Hz  207 Hz  8.45 (dd)  12.8 (d), 32.8 (d)  1.1/5.0 Hz  205 Hz  Complexes of this system have also been made with P 0 and M e P 0 ; in both 2  2  2  cases, octahedral Re(III) complexes with the donor set N30P were isolated as the major 2  products. It was hoped that the chelate effect of three free phenolic donors would drive the formation of a N 0 P coordination sphere, but this was clearly not the case. Crystal 2  2  2  -52-  structures were not obtained but the N M R data (Table 3.3) are consistent with the structures presented above. The methyl groups para to the phenol provide a convenient !  H N M R "handle". [Re(Hhypy)(hypy)(HP0 )(H P0 )]Cl (3.3) showed a clear trans-(V,V) coupling 2  2  2  present in the P N M R spectrum. This complex was extremely difficult to separate from 3 1  the mixture so only the H and P N M R spectral data are reported. On the basis of these l  3 1  data, the complex is completely analogous to the structurally characterized PO complex, with  three  protonated  phenols  not  coordinated  to  the  metal  centre.  [Re(Hhypy)(hypy)(H(Me P0 ))(H (Me P0 ))]Cl (3.4) also appears to have the same 2  2  2  2  2  structure as the PO complex. There are four methyl resonances in the ' H N M R spectrum with a 1:1:1:1 integration. This information, combined with a trans-(?,V) coupling in the 3 1  P N M R spectrum, strongly suggests that the structural motif remains unchanged. The  bidentate H ( M e P 0 ) ligand has one free phenol, and the monodentate P-bound 2  2  H ( M e P 0 ) ligand must have two. Hindered rotation about the Re-P bond results in the 2  2  2  two singlets of equal integration for the magnetically equivalent methyl groups of the monodentate H ( M e P 0 ) ligand. The retention of both hypy ligands is still clearly 2  2  2  favored over the three phenolic O donors. Clearly, P 0  2  ligands are not very suitable to  act as ancillary ligands in this system.  3.3.3. [ R e ( N P h M e ) ( M e P O ) ] [ B P h ] 2  2  2  4  To explore the possibility of discovering new potentially useful rhenium hydrazine cores, the preparation of new ternary complexes containing P O ligands was x  attempted.  [ReCl(N Ph) (PPh ) ], 2  2  3  2  [ReBr (N Ph) (PPh ) ][Br] 2  2  2  3  2  and  [ReCl (N PhMe) (PPh )][BPh4] were each reacted with 3 equivalents of H(MePO) in 2  2  2  3  -53 -  methanol. It was hoped that the PPI13 and halide ligands would be displaced by two MePO ligands to form hydrolytically stable ternary complexes containing MePO and hydrazines.  In the case of the five coordinate complexes, it was expected that the  corresponding six coordinate MePO complex would be isolated. Under similar reaction conditions, it was found that all three reactions had one distinct disadvantage; the formation of mixtures often precluded the isolation of pure complex. In the case of [ReCl(N Ph)2(PPh )2] and [ReBr2(N Ph)2(PPh )2][Br], numerous 2  3  2  3  spots were visible on the T L C plate. Attempts to isolate the major products of these reactions by silica gel chromatography were unsuccessful because multiple products were identified by ' H and  3 1  P N M R spectroscopy in the major bands that were isolated.  Attempts to crystallize pure products were equally unsuccessful. Reaction of H(MePO) with [ReCl (N PhMe) (PPh )][BPli4] was more of a 2  success.  2  2  3  Although it also formed a mixture, a product with the composition  [Re(N PhMe) (MePO) ][BPli4] (3.5) was isolated from the mixture by crystallization. 2  2  2  The +LSIMS mass spectrum clearly shows a large cationic peak at m/z 1009 that corresponds to the [Re(N PhMe) (MePO) ] parent. There is no indication of the peak +  2  2  2  corresponding to the starting material at m/z 759.  12  The IR spectrum of the complex has  one v(N=N) absorption at 1593 cm" , compared to the two v(N=N) absorptions seen in the 1  starting material at 1560 and 1580 cm" . 1  12  This observation supports the formation of a  six coordinate complex with higher symmetry than the five coordinate starting material. Elemental analyses were somewhat poor on complex 3.5 and are not reported. It is clear that the isolated complex is contaminated with some unreacted H(MePO) and efforts to remove this impurity were unsuccessful. Attempts to isolate crystals suitable for a X-ray structural characterization were also unsuccessful. -54-  ' H and P N M R spectroscopies also support the formation of a six coordinate 3 1  complex. Two singlets that integrate as 6 H each are seen at 3.46 and 2.31 ppm in the *H N M R spectrum. These signals correspond to the methyl groups on the hydrazines, and the methyl groups on the MePO ligands. The P N M R spectrum has one singlet at 29.4 3 1  ppm, shifted upfield 7 ppm from the starting material which was reported at 36 ppm.  12  Given the composition of 3.5, there are 4 possible diastereomers that could be formed (Figure 3.4).  ^  ^—O  ^=<  N PhMe  +  MePhN  2  \ /  .CeH.  H C6  Rg_.piL.CgHj. j  H5C6---P HsC6  MePhN  /\  Qy-f'  / 2  5  X  ^  N PhMe  R  H5C6  —  5  C  e  p  2  N PhMe 2  \ / Re—  |+  o  0  / \  MePhN2'  B  \ H5C6— H  e  2  MePhN  +  V  H5C6---P  o-  C  2  HCT<  5  cis hydrazine  2  ^-0  v  /\  trans phosphorus  C h  ^  ^CeHs  Re—P —CsH  -o  trans hydrazine trans phosphorus  2  \ /  HsCe—?  y~\  N PhMe  2  p^y?  C*"  5  CeHs  trans hydrazine  cis hydrazine cis phosphorus  cis phosphorus C  C1  2 v  Figure 3.4. Four Possible Diastereomers of 3.5.  Of the 4 possible diastereomers, only D can be discounted on the basis of N M R evidence. A, B and C are all predicted to have 2 magnetically equivalent pairs of methyl groups in the H N M R spectrum, and one P N M R resonance. However, the formation !  3 1  -55-  of the C2 symmetric diastereomer C is most probable because the cw-configuration of the N2PhMe groups minimizes 7t-bonding competition for the rhenium d-orbitals.  12  This  simple explanation may hold some merit; there appears to be no literature precedent for a complex containing two hydrazine ligands coordinated trans to each other. The only possible exception may be complexes of the type /ra^-[W(N )2(diphos)2], where the 2  terminal dinitrogen ligands are coordinated trans to each other.  33  There is a possible  explanation to this exception; 7i-bonding in these complexes is known to be practically non-existent since there is little elongation of the N=N bond.  -56-  3.4. Conclusions  The reaction of [Re(Hhypy)(hypyH)Cl3] with the PO ligand in the presence of base afforded 3.1 and 3.2 as a mixture. The major product of the reaction was the cationic 3.1. The neutral minor product 3.2 was easily separated from the cationic 3.1 on silica gel. Crystal structures were obtained for both complexes. 3.1, a cationic Re(III) complex,  was found to have a N3OP2 coordination sphere.  3.2, a neutral Re(III)  complex, had a N3OPCI donor set. Both exhibited the same [Re(Hhypy)(hypy)]  core  with the two P atoms (or P and C l atoms in the case of 3.2) trans to each other. The +LSIMS, IR and N M R data are consistent with the crystal structures of each. The same reaction was extended to the H2PO2 and H2(Me2P02) ligands to obtain 3.3 and 3.4 respectively as the major products.  ' H and  3 1  P N M R spectral evidence shows these  products to have the same structure in solution as the structurally characterized 3.1. The methyl groups were a useful  N M R probe for 3.4, where the  1:1:1:1  pattern indicated  one bidentate and one tridentate Me2P02 ligand on Re(III). Three of the four phenolic arms remain protonated and uncoordinated in 3.4. Clearly, the mismatched donor sets of PO2 and Me2P02 would be unfavorable from a clinical standpoint. 3.5 was synthesized by reaction of [ReCl (N PhMe)2(PPh )][BPh4] with H(MePO) in methanol. 2  2  3  The  +LSIMS, IR and N M R data are consistent with the formation of a six coordinate cation, wherein the two hydrazine ligands are cis to each other, and the two phosphorus nuclei are trans to each other. No X-ray structural data was obtained for 3.5.  -57-  3.5. References  1) Liu, S.; Edwards, D. S.; Barrett, J. A . Bioconjugate Chem. 1997, 8, 621. 2) Dilworth, J. R.; Parrott, S. J. Chem. Soc. Rev. 1998, 27, 43. 3) Nicholson, T.; Mahmood, A . ; Morgan, G.; Jones, A . G.; Davison, A . Inorg. Chim. Acta 1991,179, 53. 4) Nicholson, T.; Zubieta, J. Polyhedron 1988, 7, 171. 5) Chatt, J.; Dilworth, J. R.; Leigh, G. L.; Gupta, V . D. J. Chem. Soc (A) 1971, 2631. 6) Duckworth, V . F.; Douglas, P. G.; Mason, R.; Shaw, B . L . J. Chem. Soc, Chem. Comm. 1970, 1083. 7) Mason, R.; Thomas, K . M . ; Zubieta, J. A . ; Douglas, P. G.; Galbraith, A . R.; Shaw, B . L. J. Am. Chem. Soc. 1974, 96, 260. 8) Douglas, P. G.; Galbraith, A . R.; Shaw, B. L . Transition Met. Chem. 1975/76,1, 17. 9) Dilworth, J. R.; Harrison, S. A . ; Walton, D. R. M . ; Schweda, E. Inorg. Chem 1985, 24, 2594. 10) Mohd, H . ; Leigh, G. J. J. Chem. Soc, Dalton Trans. 1986, 213. 11) Nicholson, T.; Lombardi, P.; Zubieta, J. Polyhedron 1987, 6, 1577. 12) Dilworth, J. R.; Jobanputra, P.; Parrott, S. J.; Thompson, R. M . ; Povey, D. C.; Zubieta, J. A . Polyhedron 1992,11, 147. 13) Dilworth, J. R.; Jobanputra, P.; Miller, J. R.; Parrott, S. J.; Chen, Q.; Zubieta, J. Polyhedron 1993, 72,513. 14) Ribeiro, M . T. A . ; Pombeiro, A . J. L.; Dilworth, J. R.; Zheng, Y . ; Miller, J. R. Inorg. Chim. Acta 1993, 277, 131.  -58-  15) Coutinho, B.; Dilworth, J . R.; Jobanputra, P.; Thompson, R. M . ; Schmid, S.; Strahle, J.; Archer, C. M . J. Chem. Soc, Dalton Trans. 1995, 1663. 16) Hirsch-Kuchma, M . ; Nicholson, T.; Davison, A . ; Davis, W. M . ; Jones, A . G . J. Chem. Soc., Dalton Trans. 1997, 3185. 17) Hirsch-Kuchma, M . ; Nicholson, T.; Davison, A . ; Jones, A . G. J. Chem. Soc, Dalton Trans. 1997,3189. 18) da Costa, M . T. A . R. S., Dilworth, J.R., Duarte, M.T., Fraiisto da Silva, J.J.R., Galvao, A . M . , Pombeiro, A.J.L. J. Chem. Soc. Dalton Trans. 1998, 2405. 19) Chakraborty, I.; Bhattacharyya, S.; Banerjee, S.; B.K., D.; Chakravorty, A . J. Chem. Soc, Dalton Trans. 1999, 3747. 20) Albertin, G.; Aritoniutti, S.; Bacchi, A . ; Ballico, G. B.; Bordignon, E.; Pelizzi, G ; Ranieri, M . ; Ugo, P. Inorg. Chem. 2000, 39, 3265. 21) Albertin, G.; Antoniutti, S.; Bacchi, A.; Bordignon, E.; Miani, F.; Pelizzi, G . Inorg. Chem. 2000, 39, 3283. 22) Banerjee, S.; Bhattacharyya, S.; B.K., D.; Menon, M . ; Chakravorty, A . Inorg. Chem. 2000, 39, 6. 23) Rose, D. J.; Maresca, K . P.; Nicholson, T.; Davison, A . ; Jones, A . G.; Babich, J.; Fischman, A . ; Graham, W.; DeBord, J. R. D.; Zubieta, J. Inorg. Chem. 1998, 37, 2701. 24) Perez-Lourido, P.; Romero, J.; Garcia-Vazquez, J. A . ; Sousa, A . ; Maresca, K . P.; Zubieta, J. Inorg. Chem. 1999, 38, 1511. 25) Nicholson, T.; Cook, J.; Davison, A . ; Rose, D. J.; Maresca, K . P.; Zubieta, J. A . ; Jones, A . G. Inorg. Chim. Acta 1996, 252, 421. 26) Nock, B.; Maina, T.; Tisato, F.; Papadopoulos, M . ; Raptopoulou, C. P.; Terzis, A . ; Chiotellis, E. Inorg. Chem. 1999, 38, 4197. -59-  27) Nock, B.; Maina, T.; Tisato, F.; Papadopoulos, M . ; Raptopoulou, C. P.; Terzis, A . ; Chiotellis, E. Inorg. Chem. 2000, 39, 2178. 28) Nock, B.; Maina, T.; Tisato, F.; Raptopoulou, C. P.; Terzis, A.; Chiotellis, E. Inorg. Chem. 2000, 39,5197. 29) Rauchfuss, T. B. Inorg. Chem. 1977,16, 2966. 30) Luo, H.; Setyawati, I.; Rettig, S. J.; Orvig, C. Inorg. Chem. 1995, 34, 2287. 31) Kovacs, M . S.; Hein, P.; Sattarzadeh, S.; Patrick, B . O.; Emge, T. J.; Orvig, C. , Submitted for publication. 32) Perrin, D. D.; Armarego, W. L . F.; Perrin, D. R.  Purification of Laboratory  Chemicals; 2nd ed.; Pergamon Press: Toronto, 1980. 33) Dori, Z. Comprehensive Coordination Chemistry; Wilkinson, G., Gillard, R. D. and McCleverty, J. A., Ed.; Pergamon Press: New York, 1987; Vol. 3, pp 1011.  \  -60-  Chapter Four Lanthanide(III) and Group 13 Metal Complexes Containing Tripodal Amine Phosphinate Ligands  4.1. Introduction  For many years, the group 13 metals ( A l , G a , In , Tl ) and the lanthanides 3+  3+  3+  +  (Ln ) have either been employed, or have been investigated for potential use in nuclear 3+  medicine.  67  Ga(III) and In(III) have been used in diagnostic agents, the former for m  imaging certain types of cancer, and the latter as pretargeting agents for cancer imaging and therapy.  1  The use of T 1 as a myocardial imaging agent predates the use of 201  +  for this application, although  201  9 9 m  Tc  T 1 imaging has been largely supplanted by Tc-based +  diagnostic agents such as Cardiolite® (Figure 1.1).  The use of the lanthanides as  therapeutic agents has received extensive attention since the US Food and Drug Administration approval of  153  Sm(EDTMP) (Figure 1.3) for bone pain palliation in  terminal cancer patients. Gd(III) has received extensive attention due to its use in M R I contrast agents.  2  The lanthanides have the ability to form complexes with a variety of coordination numbers and geometries. Work has been published by our group on the coordination chemistry of the group 13 metals and lanthanides with a variety of amine phenolates, Schiff bases, amine phosphinates and amine pyridyl carboxylates.  3-10  This work has  yielded a number of interesting mononuclear, dinuclear and trinuclear complexes with coordination numbers from six to nine (Scheme 4.1). Given that most of the lanthanides -61 -  are paramagnetic (which negates the use of N M R spectroscopy in most cases), and that the coordination chemistry of the lanthanides is quite complex, great care must be exercised to characterize structurally the resulting complexes. X-ray crystallography is an indispensable tool, provided that proper precautions are taken to ensure that the crystal is representative of the bulk sample, either in solution or in the solid state.  +  Sandwich dimer  Scheme 4.1  Encapsulated trinuclear complex  10  The lanthanide coordination chemistry of a huge variety of chelating ligands containing N and O donor atoms has been investigated.  2  The large majority of these  ligands contain between 2-10 amine and carboxylate donors, typically with 2-3 carbon spacers between the amines. Examples using linear and cyclic amines exist, D T P A and D O T A being two of the most successful.  2  The poor hydrolytic stability of amine-  carboxylate complexes at low pH is one problem that has been difficult to solve with these systems.  The problem arises due to the relatively high p K values of the a  carboxylate groups. Phosphinate donors offer a potential solution to this problem with -62-  their much lower p K values. Unlike the dianionic phosphonate group (RPO3 ") they 2  a  carry the same charge as a carboxylate group. HOOC HOOC  /  \  COOH  s  N1  N1  N  K  HOOC^  r  hi  o ^ o u COOH  >  COOH H  D T P A  O  O  C  /  W  <  COOH  D O T A  Efforts to explore amine-phosphinate ligands with the group 13 metals and the lanthanides have focused on DOTA-type ligands and tren-based tripodal ligands (Figure 4.1). The former have been more thoroughly investigated, and a variety of work has been published on their synthesis, structures of their lanthanide complexes, solution behavior and luminescence properties.  11-16  1:1 complexes with the lanthanides have been obtained  with this type of ligand system and the resulting stereochemistry has been extensively investigated. '  15 17-20  In addition to the clockwise and counterclockwise wrapping isomers,  six diastereomers have been characterized using a variety of N M R techniques. '  15 17-20  The D O T A phosphinate ligands have also been modified to act as bifunctional chelates  2 1  The tripodal ligand H3ppma was found to form 2:1 bicapped complexes with group 13 metals and the lanthanides. ' '  8 9 22  unique  2 7  Al,  71  G a , and  ll5  The S 6 symmetry of these bicapped complexes made  I n N M R spectroscopic studies amenable that allowed the  determination of stability constants below the pH limit of traditional potentiometric techniques.  8  -63 -  R  R  \  0=P / HO R  \  P=0 N N  N.  OH R  N;  0=:P  P =O  R R R R R  = PhCH = Me = 2-MeOC H CH = 3-MeOC H CH = 4-MeOC H CH 2  6  4  6  4  2 2  6  4  2  O'  X  / HO  OH  Figure 4.1. Examples of amine-phosphinate ligands: (left) DOTA-type ligands; (right) tris(4-(phenylphosphinato)-3-methyl-3-azabutyl)amine, (Fbppma).  Encapsulated 1:1 complexes were not obtained in the tripodal amine-phosphinate system. For application in nuclear medicine, this result is a significant setback because 1:1  encapsulated  complexes are ideal.  Such a complex should have higher  thermodynamic stability than a 2:1 bicapped complex; the coordination sphere would contain only donors from the ligand, unlike in the monocapped case, where kinetically labile water molecules or counterions are coordinated. Encapsulated 1:1 complexes are also much less sensitive to entropic effects that occur at extreme dilution. Kinetically inert complexes with high thermodynamic stability are required to prevent demetallation of the complex in vivo.  H ppa  H ppba  3  3  -64-  To investigate the possibility of isolating 1:1 encapsulated complexes containing group 13 metals or the lanthanides, modifications were made to the tripodal amine phosphinate ligands. Attempts were made to prepare new ligands with modifications occurring at the phosphinate R group and/or the amine R group. Although modification at the phosphinate R group was unsuccessful, synthesis of the benzylated aminephosphinate ligand tris(4-(phenylphosphinato)-3-benzyl-3-azabutyl)amine (H ppba) was 3  successful. Two distinct classes of 2:1 complexes, and one class of 1:1 complex were prepared and characterized with the group 13 metals ( A l , G a , In ) and the 3+  lanthanides. phosphinate  H.3ppba was  ligand  3+  3+  also used as a synthetic precursor to obtain the unique amine-  tris(4-(phenylphosphinato)-3-azabutyl)amine  (H3ppa)  by N -  debenzylation. Fbppa contains the ammonium salt of a secondary amine. The secondary amine functionality has been elusive in amine phosphinate systems until this report.  -65-  4.2. Experimental  When  Materials.  A l l solvents were of HPLC grade and were obtained from Fisher.  anhydrous  solvents were required they  procedures.  23  were  dried using conventional  Ligand synthesis was carried out under Ar; metal complexes were  prepared in air and were found to be completely air and moisture stable. H P L C grade methanol (Fisher), tris(2-aminoethyl)amine (W.R. Grace & Co.), benzaldehyde (Aldrich), NaBH  4  (Fisher), 37% aqueous formaldehyde (Fisher), concentrated HC1 (Fisher),  phenylphosphinic acid (Aldrich), 10% Pd on C (Aldrich), and prepurified H2() (Praxair) g  were all obtained from commercial sources and were used without further purification. A l l hydrated metal salts were used as received and were obtained from Johnson Matthey. Instrumentation. Experimental details are identical to those outlined in Section 2.2 with the following exceptions: *H N M R spectra were recorded on Bruker AC-200E (200 M H z ) or Bruker AV-300 (300 MHz) N M R spectrometers with 8 referenced 1 ^  downfield from external TMS.  1J  1  C('H} N M R spectra were recorded on a Bruker A C -  200E (50 MHz) spectrometer with 8 referenced downfield from external T M S .  31  P{'H}  N M R spectra were recorded on a Bruker AV-300 (121.5 MHz) N M R spectrometer with 8 referenced to external 85% aqueous phosphoric acid. A Parr model 4753 pressure vessel and a model 4316 gauge block assembly equipped with a 140 bar burst plate were used for the hydrogenation reaction. Preparation  of  Compounds.  Tris(2-benzylaminoethyl)amine.  24  Benzaldehylde (17.5 g, 165 mmol) was added dropwise to a solution of tris(2aminoethyl)amine (7.3 g, 50 mmol) in ethanol (150 mL). The mixture was stirred for 3 -66-  hours, during which it changed to a dark yellow colour. The mixture was cooled in an ice bath, NaBFL; (7.2 g, 190 mmol) was added, and the reaction was allowed to warm to room temperature over 3 hours. The reaction mixture was extracted with 3 x 50 mL portions of diethyl ether and the combined organic layers were subsequently extracted with 200 mL 1M HC1. The HC1 layer was then made basic (pH 11) by addition of K C 0 2  3  and subsequently extracted with another 3 x 50 mL portions of diethyl ether. The final organic layers were combined, dried over anhydrous MgSC^ and then filtered; the solvent was removed and the pale yellow oil was dried in vacuo for 20 hours (yield 9.4 g, 79%). *H N M R (CDCI3, 200 MHz) 5: 7.38-7.12 (overlapped multiplets, 15H), 3.71 (s, 6H, benzyl H), 2.65 (s, 3H), 2.62 (s, 3H), 2.58 (s, 3H), 2.56 (s, 3H).  , 3  C {'H} N M R (CDCI3,  50 MHz) 5: 134.2 (s, 3C), 123.2 (s, 6C), 123.1 (s, 6C), 121.9 (s, 3C), 48.7 (s, 3C), 48.3 (s, 3C),41.6 (s, 3C). Tris(4-(phenylphosphinato)-3-benzyl-3-azabutyI)amine,  H3ppba-2HCI-H20.  Tris(2-benzylaminoethyl)amine (2.0 g, 4.8 mmol) was dissolved in 10 mL methanol. Concentrated HC1 (20 mL) was added dropwise, followed by phenylphosphinic acid (2.1 g, 15 mmol). The temperature was raised to reflux; 37% aqueous formaldehyde was added dropwise over a 30 min period, and the reaction was refluxed for a further 5 h. After cooling, acetone was added to the creamy yellow-coloured suspension to precipitate the product completely. The product was recovered by filtration and was recrystallized from boiling ethanol to afford the pure white product (yield = 3.8 g, 81%). Anal. Calcd. (found) for C 8H57N 06P3-2HC1-H20: C, 59.44 (59.44); H , 6.34 (6.18); N , 5.78 (5.95). 4  (+)LSIMS:  4  m/z = 879 ([M+H] ). +  ' H N M R (CD OD, 300 MHz) 5: 3  -67-  7.75-7.15  (overlapped multiplets, 30H), 4.45 (s, 6H), 3.63 (s, 6H), 3.39 (s, 12H).  3 1  P NMR  ( C D O D ) 5 : 23.2 (s). 3  Tris(4-(phenylphosphinato)-3-azabutyl)amine,  H3ppa-HCFH 0. 2  H3ppba-2HC1H 0 (500 mg, 0.510 mmol) was dissolved in 50 mL methanol, to which 2  10% Pd on C (300 mg, 0.282 mmol) was added as an ethanol suspension (NB: dry 10% Pd on C will burn if added directly to methanol). The mixture was stirred at room temperature and reacted with H ( ) (70 bars, 48 hours). 2  g  The catalyst was removed by  filtration on a fine frit, the solvent was removed, and the hygroscopic white product was recrystallized from a hot ethanol/acetone mixture (yield 150 mg, 44%). Anal.  Calcd.  (found) for C H39N 0 P3HC1-H 0: C, 48.91 (49.18); H , 6.38 (6.38); N , 8.45 (7.95). 27  4  6  2  (+)LSIMS: m/z = 609 ([M+H] ). H N M R (CD OD, 300 MHz) 5: 7.87 (s, 6H), 7.50 (s, +  ]  3  9H), 3.16 (s, 12H), 2.95 (s, 6H). P N M R (CD OD, 121.5 MHz) 5: 21.1 (s). 3 1  3  Synthesis of metal complexes. Detailed procedures are given for representative examples of [M(H ppba) ] (M=A1 , G a , In , H o - L u ) , [M(H ppba) ] (M=Ln 3+  3  Tb ) and [M(H ppba)] 3+  4  3+  3+  3+  3+  3+  5+  2  4+  4  (M=La -Tm ) complexes. 3+  3+  3+  2  Characterization data for all  compounds prepared are listed in Tables 4.1, 4.2, 4.3, 4.5, 4.6, 4.8, 4.9 and Figures 4.3, 4.4, 4.6. General  preparative  method  for  the  synthesis  of  [M(H3ppba) ](N03)2Cl-3CH OH (M=Ga ), (4.1). To a solution of H ppba-2HC1H 0 3+  2  3  3  2  (100 mg, 0.103 mmol) in 5 mL C H O H was added a solution of G a ( N 0 ) - 6 H 0 (18.7 3  3  3  2  mg, 0.052 mmol) in 0.5 mL C H O H . Upon standing for 48 hours at room temperature, 3  colourless prismatic crystals formed, of which one was extracted for X-ray structural analysis. The remaining crystals were recovered by filtration (yield 90 mg, 84%).  -68-  Table 4.1. Preparative details for the synthesis of [M(H ppba) ](N0 ) Cl-xCH OH. 3  2  3  2  3  Yield  Product  M -salt starting material 3+  A1(N0 ) -9H 0  [Al(H ppba) ](N0 ) Cl-3CH OH  84%  Ga(N0 ) -6H 0  [Ga(H ppba)2](N0 )2Cl-3CH OH (4.1)  84%  In(N0 ) H 0  [In(H ppba) ](N0 ) Cl-3CH OH  73%  Ho(N0 ) -5H 0  [Ho(H ppba) ](N0 ) Cl-3CH OH  45%  Er(N0 ) -5H 0  [Er(H ppba) ](N0 ) Cl-3CH OH  28%  Tm(N0 ) -5H 0  [Tm(H ppba) ](N0 ) Cl-3CH OH  52%  Yb(N0 ) -5H 0  [Yb(H ppba) ](N0 ) Cl-3CH OH  46%  Lu(N0 ) -5H 0  [Lu(H ppba) ](N0 ) Cl-2CH OH  31%  3  3  3  2  3  3  2  3  3  2  3  2  3  3  3  2  3  3  2  3  2  2  3  3  2  3  3  3  2  3  3  3  2  3  3  3  2  2  3  3  2  3  3  2  2  3  2  3  2  2  3  3  3  2  3  3  3  2  3  3  2  3  Table 4.2. Preparative details for the synthesis of [M(H ppba) ](N0 ) Cl-xCH OH. 4  2  3  4  Yield  Product  M -salt starting material J+  3  La(N0 ) -6H 0  [La(H ppba) ](N0 ) Cl-xCH OH  Ce(N0 ) -6H 0  [Ce(H ppba) ](N0 ) Cl-xCH OH  Pr(N0 ) -6H 0  [Pr(H ppba) ](N0 ) Cl-xCH OH  Nd(N0 ) -5H 0  [Nd(H ppba) ](N0 ) Cl-xCH OH  Sm(N0 ) -6H 0  [Sm(H ppba) ](N0 ) Cl-xCH OH  Eu(N0 ) -6H 0  [Eu(H ppba) ](N0 ) Cl-5CH OH  8%  Gd(N0 ) -6H 0  [Gd(H ppba) ](N0 ) Cl-3CH OH (4.2)  13%  Tb(N0 ) -5H 0  [Tb(H ppba) ](N0 ) Cl-10CH OH  11%  Dy(N0 ) -5H 0  [Dy(H ppba) ](N0 ) ClxCH OH  3  3  3  2  3  3  2  3  3  2  3  3  3  3  3  3  2  3  3  3  3  3  2  2  2  2  2  4  2  4  3  2  4  3  2  4  4  4  2  4  3  2  3  4  3  3  3  4  3  2  4  3  3  2  3  4  2  2  3  4  3  4  4  4  3  4  3  4  3  3  4  3  *Yields are not reported for complexes that were not isolated in pure form (vide infra).  -69-  Table 4.3. Preparative details for the synthesis of [M(H ppba)](N0 ) Cl-xI-[ 0. 4  3  3  2  Yield  Product  M -salt starting material J+  La(N0 ) -6H 0  [La(ppba)](N0 ) Cl-3H 0  15%  Ce(N0 ) -6H 0  [Ce(ppba)](N0 ) Cl-5H 0  16%  Pr(N0 ) -6H 0  [Pr(ppba)](N0 ) Cl-4H 0  18%  Nd(N0 ) -5H 0  [Nd(ppba)](N0 ) Cl-4H 0  16%  Sm(N0 ) -6H 0  [Sm(ppba)](N0 ) Cl-3H 0  24%  Eu(N0 ) -6H 0  [Eu(ppba)](N0 ) Cl-3H 0  34%  Gd(N0 ) -6H 0  [Gd(ppba)](N0 ) Cl-3H 0 (4.3)  33%  Tb(N0 ) -5H 0  [Tb(ppba)](N0 ) Cl-3H 0  30%  Dy(N0 ) 5H 0  [Dy(ppba)](N0 ) Cl-3H 0  30%  Ho(N0 ) -5H 0  [Ho(ppba)](N0 ) Cl-3H 0  22%  Er(N0 ) -5H 0  [Er(ppba)](N0 ) Cl-3H 0  14%  3  3  3  3  3  3  3  3  3  3  3  3  3  3  General  preparative  [M(H ppba) ](N03)4Cl-3CH OH. 4  2  3  2  2  3  3  2  2  3  2  3  3  2  3  3  3  2  2  3  3  2  3  3  3  2  3  3  3  2  3  2  3  2  2  3  3  2  2  3  3  2  3  3  3  2  3  3  3  2  2  3  2  3  2  method  for  (M=Gd ), 3+  the  (4.2).  To  synthesis  of  a  of  solution  H ppba-2HC1-H 0 (100 mg, 0.103 mmol) in 5 mL C H O H was added a solution of 3  2  3  G d ( N 0 ) - 6 H 0 (23.2 mg, 0.0515 mmol) in 0.5 mL C H O H . 3  3  2  3  During one week of  standing at room temperature, colourless hexagonal plates formed, one of which was extracted for X-ray structural analysis.  The remaining crystals were recovered by  filtration (yield 15 mg, 13%.).  -70-  General preparative method for the synthesis of [M(H ppba)](N03)3Cl'3H 0. 4  2  (M=Gd ), (4.3). To a solution of H ppba-2HC1-H 0 (100 mg, 0.103 mmol) in 5 mL 3+  3  2  C H O H was added a solution of Gd(N0 ) -6H 0 (46.4 mg, 0.103 mmol) in 0.5 mL 3  3  3  2  C H O H . A precipitate immediately formed out of the mixture and a finely-divided white 3  powder was isolated by filtration (yield 45 mg, 33%). The insolubility of the white powder made it impossible to obtain crystals for X-ray structural analysis. [Ga(ppa)]-3H 0, (4.4). To a solution of H ppa-HCl-H 0 (50 mg, 0.071 mmol) in 2  3  2  5 mL C H O H was added a solution of Ga(N0 ) -6H 0 (25.8 mg, 0.071 mmol) in 0.5 mL 3  3  3  2  C H O H . A fine white powder formed over 48 h at room temperature and was isolated by 3  filtration (yield 29 mg, 56%). Anal.  Calcd. (found) for C 7H36N 06P3Ga-3H 0: C, 2  44.47 (44.89); H , 5.80 (5.83); N , 7.68 (7.81).  4  2  (+)LSIMS: m/z = 675 ([M+H] ). IR +  spectrum: refer to Figure 4.7. ' H and P N M R spectra: refer to Figure 4.8. 3 I  X-Ray Crystallographic Analyses of 4.1 and 4.2. Please refer to the appendix for experimental details, and for complete tables of bond lengths and bond angles.  -71 -  4.3. Results and Discussion  4.3.1. Synthesis of the Tripodal Amine-Phosphinate Ligands H ppba & H ppa 3  3  H ppba 3  Scheme 4.2  The synthesis of new amine-phosphinate ligands was accomplished by adapting the Moedritzer-Irani reaction  25  to react phenylphosphinic acid with a benzylated  derivative of tren in the presence of formaldehyde (Scheme 4.2). The synthesis of tris(2benzylaminoethyl)amine (the benzylated derivative of tren) was accomplished by standard methods. The Moedritzer-Irani reaction requires that secondary amines be used to prevent the addition of two methylene-phosphinic acid groups to each amine. The product of the reaction is a tertiary amine; the mechanism proceeds similarly to the wellknown Mannich reaction.  26  The formaldehyde condenses with the hydrogen on the  secondary amine and the hydrogen on the phosphinic acid; the two are joined together via a methylene bridge.  The reaction proceeds cleanly under these conditions, but the -72-  presence of HC1 and a zwitterionic product severely limits its utility to compounds that can be isolated from the reaction mixture. Recrystallization of the product from the reaction  of  benzylated  tren  and  phenylphosphinic  (phenylphosphinato)-3-benzyl-3-azabutyl)amine  acid  affords  pure  tris(4-  (H3ppba-2HC1H20) in good yield.  Unfortunately, this ligand is only soluble in methanol, hot ethanol, hot isopropanol, D M S O and D M F . Therefore, the coordination chemistry of this ligand is limited to these solvents only.  f~  \ NH  \  1/  /  HN  \  /  O  R  .  OH  / H  /  2  %/  >•  P  H  NH  CH 0  \  H  \\  R E F L U X  /  R  -0'\  R  0  R=Me or Bz  Phosphinic acid excess  \  \ / , % V R  o  6MHCI  H  >  H  J  N  N  0  °*>P\  "°  ^  \ ) 1  Not possible to purify H  °"  CH2Q/  -N  ,\  o  N  X P  HO  ^  X N  - R / 1  .OH  Not possible to purify  "O ^ — O H  Scheme 4.3  Reaction of methylated or benzylated tren with phosphinic acids other than phenylphosphinic acid did not afford pure product (Scheme 4.3). The original goal was to synthesize tripodal amine-phosphinate ligands with R groups other than phenyl at the phosphinic acid to encourage formation of 1:1 encapsulated complexes with group 13 metals and the lanthanides. The addition of formaldehyde in the first step (Scheme 4.3) -73 -  must  be  made  slowly  (CH20H)2P(0)OH. •  27  1  monitored by  H and  zwitterionic product.  to  prevent  formation  of the  unwanted  side  product  The Moedritzer-Irani reaction appeared to proceed and was 31  P N M R spectroscopy, but we were unable to isolate the Reaction of the amine-phosphinic acid tripod with excess  formaldehyde appeared to form the amine-hydroxymethylenephosphinic acid tripod, but the product was also not possible to isolate (Scheme 4.3).  The possibility of modification at the amine was also investigated. As mentioned above, the benzyl-substituted amine-phosphinate synthesized.  tripod H3ppba was successfully  It was not expected that the presence of the three bulky benzyl groups  would encourage 1:1 encapsulated complex formation.  Removal of these groups by  catalytic hydrogenation, however, afforded the novel secondary amine tripod tris(4(phenylphosphinato)-3-azabutyl)amine (Hsppa-HCl-FkO) (Scheme 4.4).  The reaction is  easily monitored by the loss of the methylene resonance of the benzyl group in the ' H N M R spectrum at 4.45 ppm. Catalytic hydrogenation of N-benzyl groups is known to be difficult because of the propensity of free amines to poison the Pd catalyst. -74-  28  High  pressure and a large excess of Pd catalyst were required for this reaction to proceed. Hydrogenation reactions are known to produce pure products in high yield; the products of the reaction are H ppa and toluene, and the problem of purifying the zwitterionic 3  product from the Moedritzer-Irani reaction is avoided. H ppa is highly water-soluble; the 3  ligand is also soluble in alcohols such as methanol and ethanol.  4.3.2. 2:1 Complexes of H ppba with the Group 13 Metals and the Lanthanides 3  Complexes of the ligand H ppma (Figure 4.1) were clearly shown to be 2:1 3  bicapped complexes of the type [M(H ppma)2](N0 ) , where M=A1 , G a , I n and 3+  3  Ln . > > 3+  8  9  22  3  3+  3+  3  Therefore, the first step of this study was to prepare 2:1 ligand:metal  complexes for comparison. A l l complexes were prepared under similar conditions, and two distinct classes of 2:1 bicapped complexes were identified. Reaction of one equivalent of G a ( N 0 ) y 6 H 0 with two equivalents of 3  2  H ppba-2HC1H 0 in methanol results in the formation of the 2:1 bicapped complex 3  2  [Ga(H ppba) ](N0 )2Cl-3CH OH (4.1). 3  2  3  3  Indicating that complex formation occurs in  methanol solution, the P N M R singlet of H ppba shifted upfield from 23.2 ppm to 14.4 3  ppm for the complex, but little other information is obtained from N M R spectroscopy. A number of metal salts were tried, including chloride, triflate and perchlorate, but only the mixed nitrate/chloride product formed crystals that were amenable to X-ray structural analysis and had consistent composition. Reactions with A l , In , and the lanthanides 3 +  Ho  3+  through L u  3 +  3+  formed the same type of tricationic complex. Isolated yields ranged  from 31-84%. In the case of the lanthanides, the complexes appeared to have somewhat higher solubility, and yields were difficult to improve. Any attempt to improve the yields  -75-  by removing the solvent resulted in the formation of glassy solids with inconsistent compositions according to their elemental analyses.  Figure 4.2.  ORTEP diagram of the [Ga(H3ppba)2] cation with the solvent molecules J+  and the aromatic rings removed for clarity; 50% thermal probability ellipsoids are shown.  A n X-ray structural analysis was performed on a crystal of 4.1 isolated from the reaction of ffjppba with G a  3+  (Figure 4.2, Table 4.4). The G a  3+  ion is clearly bicapped by  two H3ppba ligands; examination of the bond lengths and a difference map indicate that all three of the pendant N atoms are protonated on each H ppba ligand. The ligands are 3  best regarded as neutral zwitterions, thus, the complex has an overall +3 charge. The -76-  Ga  ion is coordinated only by the phosphinato O atom donors with an average Ga-0  bond length of 1.95 A.  The two I-^ppba ligands are related to each other through a  crystallographic inversion center at the G a  3+  ion. Although the portion of the unit cell  containing [Ga(H3ppba)2] is well established, large void spaces exist where satisfactory 3+  modeling of mixed NO3", Cl" and CH3OH was not possible. Correction of the disordered 3+  data in the void spaces resulted in R l = 0.048. The elemental analyses for the Ga  and  other H3ppba complexes strongly support the proposed composition. Table  4.4.  Selected  bond  lengths  (A)  and  bond  angles  (deg)  in  [Ga(H ppba)2](N03)2Cl-3CH OH (4.1). 3  3  Ga-O(l)  1.9498(14)  0(l)-Ga-0(3')  88.88(6)  Ga-0(3)  1.9512(15)  0(l)-Ga-0(5')  88.93(6)  Ga-0(5)  1.9515(15)  0(3)-Ga-0(5)  91.10(6)  PO)-O(l)  1.5052(15)  0(3)-Ga-0(5')  88.90(6)  P(l)-0(2)  1.4927(18)  0(l)-P(l)-0(2)  120.10(9)  P(l)-C(3)  1.833(2)  0(1)-P(1)-C(3)  104.05(9)  P(l)-C(4)  1.796(2)  0(1)-P(1)-C(4)  110.50(10)  Ga-0(1)-P(l)  143.84(9)  0(2)-P(l)-C(3)  110.76(10)  0(l)-Ga-0(3)  91.12(6)  0(2)-P(l)-C(4)  109.84(10)  0(l)-Ga-0(5)  91.07(6)  C(3)-P(l)-C(4)  99.50(10)  0(1)-Ga-0(1')  180.00  Analogous to the structurally characterized [In(H ppma)2] 3  complexes, ' there is nearly S6 symmetry around the G a -778 9  3+  or [Lu(H3ppma)2J  ion.  In the case of  [In(H3ppma)2] , the crystallographic symmetry imposed perfect 90° and 180° angles 3+  between the O atoms of the phosphinato ligands. The 180° angles in [Lu(H3ppma)2] 8  3+  are crystallographically imposed, and the 88.72(6)° and 91.28(6)° angles are close to 90°.  9  The unique bond angles in 4.1 are 180.00°, 91.12(6)° and 88.88(6)°, therefore, the structure is also an octahedral complex with nearly perfect Se symmetry.  The bond  lengths in each of the three complexes are comparable when the ionic radii are corrected for the three different metals. Also analogous to the two known H ppma complexes, the coordination of each 3  phosphinato O atom introduces a chiral center at each P atom. '  8 9  In the 4.1 crystal  structure, only the RRRSSS diastereomer is observed. In order to accommodate the bulk of the phenyl rings on the phosphinate group, the only other diastereomer that is chemically possible is the RRSSSR.  8  There is no evidence for the presence of this  diastereomer in the solid state in any of the studies to date. +LSIMS data for the entire series of complexes demonstrate clearly that 2:1 complexes are formed (Table 4.5). Peaks are seen in each case corresponding to the monocationic 2:1 and 1:1 complexes. Since the ligand peak at 879 is also observed in every case, it is reasonable to conclude that the 1:1 complex is formed by fragmentation in the mass spectrometer and may be regarded as an experimental artifact. IR spectroscopy shows that A l  , Ga , In  and the lanthanides Ho  through L u  are completely isostructural (Figure 4.3). The IR spectra have several notable features in the region shown. The peak around 1450 cm" is attributed to v(P-Ph); the sharp peak at 1  1383 cm" arises from 1  v(NC>3);  the three large peaks at ca. 1190, 1130, 1070 cm" are 1  attributed to v(P-O); and the peaks around 700 cm" are due to v(P-C) and v(P-Ph). The 1  intensity and position of all of these peaks remains relatively unchanged in all of the -78-  spectra, except in that of Dy  and Ho , which appear to show some additional spectral  features (vide infra).  Table 4.5. +LSIMS data for all 2:1 H ppba complexes. 3  [Al(H ppba) ](N0 ) Cl-3CH OH  [M(Hppba)] m/z 903  [Ga(H ppba) ](N0 ) Cl-3CH OH  945  1825  [In(H ppba) ](N0 ) Cl-3CH OH  991  1869  [La(H ppba)2](N0 ) Cl-xCH OH  1015  1895  [Ce(H ppba) ](N0 ) Cl-xCH OH  1016  1896  [Pr(H ppba) ](N0 ) ClxCH OH  1017  1897  [Nd(H ppba) ](N0 ) Cl-xCH OH  1020  1899  [Sm(H ppba) ](N0 ) Cl-xCH OH  1028  1906  [Eu(H ppba) ](N0 ) Cl-5CH OH  1029  1908  [Gd(H ppba) ](N0 ) Cl-3CH OH  1034  1912  [Tb(H ppba) ](NO ) CM0CH OH  1035  1913  [Dy(H ppba) ](N0 ) Cl-xCH OH  1040  1918  [Ho(H ppba) ](N0 ) Cl-3CH OH  1041  1919  [Er(H ppba) ](N0 ) Cl-3CH OH  1044  1922  [Tm(H ppba) ](N0 ) Cl-3CH OH  1045  1924  [Yb(H ppba) ](N0 ) Cl-3CH OH  1050  1928  [Lu(H ppba) ](N0 ) Cl-2CH OH  1051  1930  Complex 3  2  3  3  2  3  2  3  2  3  2  3  2  4  3  3  4  2  4  4  4  2  4  3  3  3  2  3  2  3  3  3  3  3  3  4  2  2  2  3  4  3  3  3  4  3  2  3  4  3  2  3  3  4  3  2  3  3  4  2  4  3  3  2  4  3  4  3  2  3  4  3  2  4  4  3  2  3  2  2  2  3  3  3  -79-  +  [MH (ppba) ] m/z 1782 4  2  +  1500  1000  500  Wawrwmbeis  1500  1000  500  Wavsnttmbers  Figure 4.3. IR spectra of [M(H ppba)2](N0 )2Cl, M as indicated. 3  3  For the series of lanthanides La  through Dy , however, the IR spectra were  found to differ greatly from the " G a  3+  4.6) of the E u , G d  complexes indicate that complexes of the type  3+  3 +  and T b  3+  type" structures. The elemental analyses (Table  [Ln(H4ppba)2] are formed wherein the apical nitrogen of each ligand is protonated to 5+  afford a +5 complex. Obtaining good elemental data for this class of complex was difficult.  Isolated yields were quite low (10-15%), and only E u , G d  and T b  3+  complexes were isolated in pure form. Satisfactory elemental analyses for the L a - S m  3+  3+  -80-  3 +  and Dy  complexes were never obtained. Lying on the border between the +5 and +3  complexes, it is possible that D y  3+  formed a mixture of both complex types.  appearance of new features in the IR spectrum of the D y  3+  The  complex supports this  hypothesis.  Table 4.6. Elemental analyses for selected 2:1 H ppba complexes. 3  C  H  N  Calcd. (found)  Calcd. (found)  Calcd. (found)  [Al(H ppba)2](N03)2Cl-3CH OH  58.28 (58.59)  6.22 (6.35)  6.86 (6.69)  [Ga(H ppba)2](N0 ) Cl-3CH OH  57.08 (57.39)  6.10(6.13)  6.72 (6.37)  [In(H ppba) ](N0 ) Cl-3CH OH  55.87 (56.21)  5.97 (5.83)  6.58 (6.50)  [Eu(H ppba) ](N0 ) Cl-5CH OH  51.46 (51.45)  5.90 (5.66)  7.13 (7.34)  [Gd(H ppba) ](N0 ) Cl-3CH OH  51.77 (52.81)  5.62 (5.68)  7.32 (6.79)  [Tb(H ppba) ](NO ) C110CH OH  50.47 (50.00)  6.23 (5.84)  6.66 (6.61)  [Ho(H ppba) ](N0 ) Cl-3CH OH  54.59 (54.75)  5.83 (5.59)  6.43 (6.81)  [Er(H ppba) ](N0 ) Cl-3CH OH  54.53 (54.83)  5.82 (5.57)  6.42 (6.71)  [Tm(H ppba) ](N0 ) Cl-3CH OH  54.49 (54.91)  5.82 (5.61)  6.42 (6.65)  [Yb(H ppba) ](N0 ) Cl-3CH OH  54.33 (54.75)  5.89 (5.59)  6.40 (6.67)  [Lu(H ppba) ](N0 ) Cl-2CH OH  54.59 (54.88)  5.70 (5.68)  6.50 (6.37)  Complex  3  3  3  3  3  2  4  3  2  4  3  3  3  3  2  3  4  3  3  3  3  3  3  2  2  2  2  3  4  3  2  3  4  3  2  3  3  3  2  3  3  2  2  4  2  2  2  2  3  3  3  -81 -  1500  1000  500  1500  1000  Wwenumbers  Figure 4.4.  500  Wavsnumbsrs  Selected IR spectra of [M(H4ppba)2](N0 ) Cl, M as indicated. The IR 3  4  spectrum of 4.1 (M=Ga) is included for comparison.  Despite the fact that pure complexes could not be obtained for all of the early Ln  3 +  series, the +LSIMS data and IR spectroscopy (Figure 4.4) indicates that these  complexes have similarities to the E u , G d 3+  3 +  and T b  3+  complexes. The large shift in  frequency of the IR bands associated with P and O bonding may be attributed to a change in the intramolecular H-bonding involving the protonated N atoms. If this is the case, the positions of the transitions in the IR spectra are a remarkably sensitive probe of the intramolecular H-bonding. Although the S m those of the G d  3 +  and T b  3+  3+  complex has an identical IR spectrum to  complexes, strangely the E u -82-  3+  complex does not, even though  its elemental analysis supports its formulation as [Eu(H4ppba)2] . The N d 5+  identical to the E u  3+  spectrum. The early L n  of 2:1 and 1:1 complexes (vide infra).  3 +  j +  spectrum is  may have a propensity to form a mixture  This may explain why satisfactory elemental  analyses could not be obtained for L a - S m , and may also explain the presence of the 3+  3+  2:1 peaks in the +LSIMS spectra.  Figure 4.5.  ORTEP diagram of the [Gd(H ppba)2] cation with the solvent molecules 5+  4  and the aromatic rings removed for clarity; 50% thermal probability ellipsoids are shown.  From the reaction mixture of G d  3 +  and F^ppba, a single crystal was obtained and  was used in an X-ray structural analysis (Figure 4.5, Table 4.7). The complex has a -83 -  bicapped structure similar to that found in 4.1. Each arm of the tripod is related to the other arms by six-fold crystallographic symmetry. Both the pendant amines and the apical  amines  are  protonated  to  afford  the  product  [Gd(H ppba) ](N0 )4Cl-3H 0 (4.2). The geometry around G d 4  2  3  3 +  2  complex  as  is nearly octahedral,  with unique bond angles of 180.00°, 87.52(6)° and 92.48(6)° between the O phosphinato donor atoms. As in 4.1, the P atoms in 4.2 have a RRRSSS configuration and this is the only diastereomer seen in the solid state. The presence of the [M(H ppba) ] complex in 5+  4  2  the unit cell is very clear, but the six-fold symmetry of the R 3 unit cell complicated the identification of the five counterions and the C H 3 O H in the large void spaces of the unit cell. This disorder was modeled with help from the analytical data and was refined to R l = 0.034.  Table  4.7.  Selected  bond  lengths  (A)  and  bond  angles  (deg) in  [Gd(H ppba)2](N03)4Cl-3CH OH (4.2). 4  3  180.00  Gd-0(2)  2.2841(17)  0(2)-Ga-0(2*)  P(l)-0(1)  1.500(2)  0(l)-P(l)-0(2)  117.45(11)  P(l)-0(2)  1.5104(16)  0(1)-P(1)-C(1)  112.67(11)  P(l)-C(l)  1.797(3)  0(1)-P(1)-C(7)  108.17(10)  P(l)-C(7)  1.845(3)  0(2)-P(l)-C(l)  107.45(11)  Gd-0(2)-P(l)  143.85(10)  0(2)-P(l)-C(7)  107.94(10)  87.52(6)  C(l)-P(l)-C(7)  101.97(12)  0(2)-Ga-0(2*)  f  0(2)-Ga-0(2*)  t  92.48(6)  The O atoms are related to each other by symmetry.  -84-  T  The switch from [M(H ppba) ] (M=La -Tb ) to [M'(H ppba) ]' (M'=A1 , 5+  4  j+  3+  +  2  3  J+  2  G a , In , H o - L u ) is an interesting phenomenon that we did not witness in the 3+  3+  3+  3+  H3ppma system. It is possible that the size of the metal ion and the nature of the H bonding network in the uncoordinated upper part of the tripodal ligand have some role in this behavior. It is a well-known fact that early lanthanide trivalent metal ions are larger than late lanthanide trivalent metal ions. The 90° angles between the phosphinate O donors in 4.1 have two unique angles of 88.88(6)° and 91.12(6)°, whereas the unique angles in the 4.2 are 87.52(6)° and 92.48(6)°. It is possible that the larger L n tolerate this compression of the bond angles better than the smaller L n  3 +  3 +  ions can  and group 13  metal ions. As a result of the compression at the bottom of the tripod, the upper tripod can open up and a rearrangement of the H-bonding network can occur (including the apical N proton) to produce the observed +5 complex. This explanation is also supported by the dramatic change in the P=0 and P-0 stretching frequencies in the IR spectra of the complexes.  4.3.3. 1:1 Complexes of Ffjppba with the Lanthanides In order to investigate further the strange behavior of the 2:1 L a - S m 3+  3+  complexes, including the possibility of 1:1 complex formation, a study of the system in 1:1 ratios was initiated.  Under similar conditions to those which produced the 2:1  complexes, 1:1 ratios of M(NO)3 (M=La -Lu ) and H3ppba were reacted in methanol. 3+  3+  These reactions afforded complexes of the type [M(H4ppba)] in 14-34% yield. Upon 4+  mixing of the starting materials, a finely-divided precipitate immediately formed for most of the lanthanides. Towards the end of the series (Tm -Lu ), no precipitate formed and 3+  prismatic crystals  3+  appeared corresponding to the [M(H.3ppba) ] complexes over a 3+  2  -85-  period of 48 hours. This was verified crystallographically for the Yb  complex (the full  solution of the structure was not completed once this was discovered). Unlike those of the 2:1 complexes, the +LSIMS mass spectra of the complexes show no substantial evidence of 2:1 peaks (Table 4.8).  1:1  In some of the  complexes, 2:1 peaks were observed at trace levels (20x gain). The possibility exists that a small excess of ligand may have been present in these cases. Lanthanide nitrate salts are very hygroscopic and the excess water would not have been accounted for i f it were present.  Table 4.8 +LSIMS data for all 1:1 H ppba complexes. 3  [La(ppba)](N0 ) Cl-3H 0  [M(Hppba)] m/z 1015  [Ce(ppba)](N0 ) Cl-5H 0  1016  [Pr(ppba)](N0 ) Cl-4H 0  1017  [Nd(ppba)](N0 ) Cl-4H 0  1020  [Sm(ppba)](N0 ) Cl-3H 0  1028  [Eu(ppba)](N0 ) Cl-3H 0  1029  [Gd(ppba)](N0 ) Cl-3H 0  1034  [Tb(ppba)](N0 ) Cl-3H 0  1035  [Dy(ppba)](N0 ) Cl-3H 0  1040  [Ho(ppba)](N0 ) Cl-3H 0  1041  [Er(ppba)](N0 ) Cl-3H 0  1044  Complex 3  3  3  2  3  3  2  3  2  3  3  3  3  3  3  3  3  2  2  3  3  3  2  2  3  3  3  2  2  3  3  2  2  -86-  +  The IR spectra of the 1:1 complexes L a - E r 3+  are remarkably similar (Figure  3+  4.6). The v(N03) peak is at 1384 cm" , which is the same frequency as that seen in the 1  2:1 complexes. With the exception of complexes of L a  3 +  Sm , and E r 3+  3+  which have an  additional peak at 1238 cm" , all the other complexes share similar features in the v(PO) 1  region of the spectrum (1303, 1181, 1134, 1054 cm" ). The IR spectrum of the H o 1  3+  complex has a peak at 1238 cm" which is seen as a small shoulder on the broad peak at 1  1181 cm" . The fact that this same peak is seen the 2:1 N d 1  3 +  and E u  3 +  IR spectra (Figure  4.4) supports the possibility that a 1:1 complex may be present depending on the exact conditions of preparation of the early lanthanide 2:1 complexes. The IR spectra of the late lanthanide 2:1 complexes (Figure 4.3) demonstrate that these metals have no propensity to form 1:1 complexes under these conditions.  -87-  1500  1000  500  1500  Wave numbers  1000  500  Wave numbers  Figure 4.6. IR spectra of [Ln(H ppba)](N03) Cl, Ln as indicated. The IR spectrum of 4  3  4.1 (M=Ga) is included for comparison.  With a small variation in hydration, the elemental analyses for the 1:1 complexes are very consistent (Table 4.9).  A l l the complexes appear to have the formulation  [M(H ppba)](N03)3Cl-xH 0. As expected, the carbon content is much lower than in any 4  2  of the 2:1 complexes (Table 4.7), and the nitrogen content is much higher, owing to the -88-  lack of a second carbon-rich ligand. The analyses of the H o  3+  and E r  3+  complexes appear  to have slightly higher levels of carbon, perhaps because of the preference of the late L n to form 2:1 complexes in this system.  Table 4.9. Elemental analyses for all 1:1 H3ppba complexes. C  H  N  Calcd. (found)  Calcd. (found)  Calcd. (found)  [La(ppba)](N03)3Cl-3H 0  44.54 (44.83)  4.98 (4.89)  7.57 (7.20)  [Ce(ppba)](N0 ) Cl-5H 0  43.30 (43.20)  5.15 (4.90)  7.36(7.15)  [Pr(ppba)](N0 ) Cl-4H 0  43.86 (44.12)  5.06 (4.94)  7.46 (7.04)  [Nd(ppba)](N0 ) Cl-4H 0  43.75 (44.04)  5.05 (4.89)  7.44 (7.02)  [Sm(ppba)](N0 ) Cl-3H 0  44.15 (43.94)  4.94 (4.68)  7.51 (7.25)  [Eu(ppba)](N0 ) Cl-3H 0  44.10(44.58)  4.93 (4.76)  7.50 (7.21)  [Gd(ppba)](N0 ) Cl-3H 0  43.92 (43.92)  4.91 (4.76)  7.47 (7.31)  [Tb(ppba)](N0 ) Cl-3H 0  43.86 (44.19)  4.91 (4.75)  7.46 (7.13)  [Dy(ppba)](N0 )3Cl-3H 0  43.74 (43.98)  4.89 (4.72)  7.44 (7.05)  [Ho(ppba)](N0 ) Cl-3H 0  43.66 (44.98)*  4.89 (4.69)  7.43 (6.98)  [Er(ppba)](N0 ) Cl-3H 0  43.59 (44.90)*  4.88 (4.82)  7.41 (6.91)  Complex  2  3  3  3  3  2  3  3  3  3  2  3  3  3  3  2  2  2  3  3  2  2  3  2  3  3  3  3  2  2  The high carbon content of these complexes is explained in the text.  Because all the 1:1 complexes precipitate as highly insoluble powders, no crystals suitable for an X-ray structural analysis could be obtained. The complexes only have limited solubility, even in solvents such as DMSO; after dissolution they are -89-  unrecoverable. The question remains as to what type of 1:1 complex they form (Scheme 4.1). Given that the elemental analysis supports the formulation [M(H ppba)] , wherein 4+  4  all four N atoms are protonated, it seems highly unlikely that an encapsulated complex is The v ( N 0 ) in the IR spectra is identical to that of the two structurally  formed.  3  characterized 2:1 complexes, therefore, coordinated to L n  it is unlikely that the N 0 " ligands are 3  in the 1:1 complexes.  Given this combined evidence, the most  reasonable assumption is that the complexes are monocapped, with 3-5 H2O molecules completing the coordination sphere.  4.3.4. 1:1 Complex of G a  3+  and H ppa 3  Reaction of tris(4-(phenylphosphinato)-3-azabutyl)amine (H ppa-HC1H20) with 3  G a ( N 0 ) - 6 H 2 0 in methanol at a 1:1 molar ratio results in the formation of a finely3  3  divided white precipitate after standing for 48 h. Elemental analysis of this precipitate gives the composition [Ga(ppa)]-3H20 (4.4).  Clearly, this is a very interesting result  because it is possible that an encapsulated 1:1 complex has formed.  The lack of  counterions strongly suggests that the pendant N donors are not protonated NH.2 , but +  rather the neutral N H .  Unlike the [M(H.4ppba)] complexes described previously, the 4+  formation of an encapsulated 1:1 complex is a distinct possibility. The +LSIMS data support the formulation as 1:1; a large peak at m/z 675 corresponding to [Ga(Hppa)] is +  seen.  Only a trace peak is seen at m/z 1285 corresponding to the 2:1 complex  [GaH (ppa) ] . +  4  2  The IR spectra of the H ppa ligand and 4.4 have several notable features (Figure 3  4.7). One of the v(PO) bands shifts from 1188 to 1181 cm" upon complex formation. 1  The band at 954 cm" in the free ligand disappears completely. There is no indication of a 1  -90-  free nitrate at ca. 1385 cm" . The broad v(NH) peak shifts from 3414 cm" in the free 1  1  uncomplexed ligand to 3421 cm" in the complex, which may indicate that the N donors 1  are involved in complex formation. The seemingly unusual strengthening of the N - H bond upon coordination may occur because the N atom is first deprotonated from NH2 to +  N H , then is subsequently coordinated to G a . 3+  Since this is a two step process, it is  difficult to state with absolute certainty that the N donors are coordinated to G a  3+  on the  basis of IR spectroscopy alone.  Figure 4.7. IR spectra of [Ga(ppa)]-3H 0 (4.4) (top) and H p p a H C l H 0 (bottom). 2  3  2  The P N M R spectrum of the complex in methanol is complicated and contains 3 1  at least seven resonances between 23.7-24.9 ppm, shifted downfield from the ligand in which it is seen as a singlet at 21.1 ppm. The ' H N M R spectra of the complex and the free ligand demonstrate significant shifts of the C H groups compared to the free ligand -91 2  (Figure 4.8). Although the speciation in solution is complicated, the shifts of the pendant CH2 arms are strongly indicative of pendant N atom coordination to the metal.  It is  plausible to regard the complex as encapsulated, but in the absence of X-ray structural data, it cannot be stated for certain.  1 1 1 1 1 1 1 1  9.0  1 1 1 1 1 1 1  8.0  Figure 4.8.  1 1 1 1 1 1 1 1 1  7.0  6.0  1 1 1 1 1 1 1  5.0  4.0  (ppm)  1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1  3.0  2.0  ' H N M R spectra (300 MHz) of [Ga(ppa)]-3H 0 (4.4) 2  H ppa-HC1H 0 (bottom) in d -methanol; (* = H 0 and C H O H impurities). 3  2  4  2  -92-  3  1.0  0.0  (top) and  4.4. Conclusions  In order to obtain 1:1 complexes of the group 13 metals A l , G a , I n 3 +  J+  and the  j+  lanthanides, two new amine-phosphinate tripod ligands were synthesized. H ppba was 3  synthesized by the Moedritzer-Irani reaction of tris(2-benzylaminoethyl)amine and phenylphosphinic acid to afford tris(4-(phenylphosphinato)-3-benzyl-3-azabutyl)amine (H ppba-2HC1H 0) in good yield. The reaction of H ppba-2HC1H 0 with H at 70 bar 3  2  3  2  2  with a 10% Pd on C catalyst yielded tris(4-(phenylphosphinato)-3-azabutyl)amine (H ppa), a water soluble tripodal amine phosphinate ligand containing three secondary 3  amine functional groups. H ppba-2HC1H 0 was reacted with A l , G a , I n 3 +  3  3+  3+  2  and L n  in 2:1 ratios and was found to form bicapped complexes of the type [M(H ppma) ] 3  3 +  3+  2  (M=A1 , G a , In , H o - L u ) or [M(H ppma) ] (M=La -Tb ). Crystal structures 3+  3+  3+  3+  3+  5+  4  were obtained for [Ga(H ppba) ] 3  2  3+  3+  3+  2  and [Gd(H.4ppba) ] , and a combination of IR 5+  2  spectroscopic, mass spectrometric and elemental analytical data were used to infer the structures of the remaining metal complexes. The bicapped geometry is formed by a pair of ligands coordinating to the metal centre through its phosphinate O atoms only. Either 3 or 4 of the nitrogen atoms on each ppba unit are protonated, and an H-bonded network is formed in the empty space of the tripod. 1:1 complexes of the type [M(H4ppba) ]  4+  2  (M=La -Er ) were obtained by the reaction of H ppba-2HC1-H 0 and the appropriate 3+  3+  3  metal salts at 1:1 molar ratios.  2  Although an X-ray structure was not obtained, the  combination of IR spectroscopic, mass spectrometric and elemental analysis data strongly support the formation of a monocapped complex wherein the nitrate counterions are not coordinated to the metal centre. 1:1 molar ratios of H p p a H C l H 0 and G a ( N 0 ) 6 H 0 3  in methanol afford the 1:1 complex [Ga(ppa)]-3H 0. 2  -93 -  2  Although ' H and  3  3 I  3  2  P NMR  spectroscopies, IR spectroscopy, +LSIMS and elemental analysis support the formation of a 1:1 encapsulated complex, the exact nature of the complex cannot be ascertained without an X-ray structural analysis.  -94-  4.5. References  1) Anderson, C. J.; Welch, M . J. Chem. Rev. 1999, 99, 2219. 2) Caravan, P.; Ellison, J. J.; McMurry, T. J.; Lauffer, R. B . Chem. Rev. 1999, 99, 2293. 3) Liu, S.; Rettig, S. J.; Orvig, C. Inorg. Chem. 1992, 31, 5400. 4) Liu, S.; Wong, E.; Karunaratne, V . ; Rettig, S. J.; Orvig, C. Inorg. Chem. 1993, 32, 1756. 5) Liu, S.; Wong, E.; Rettig, S. J.; Orvig, C. Inorg. Chem. 1993, 32, 4268. 6) Wong, E.; Liu, S.; Lugger, T.; Hahn, F. E.; Orvig, C. Inorg. Chem. 1995, 34, 93. 7) Wong, E.; Caravan, P.; Liu, S.; Rettig, S.; Orvig, C. Inorg. Chem. 1996, 35, 715. 8) Lowe, M . P.; Rettig, S. J.; Orvig, C. J. Am. Chem. Soc. 1996,118, 10446. 9) Lowe, M . P.; Caravan, P.; Rettig, S. J.; Orvig, C. Inorg. Chem. 1998, 37, 1637. 10) Setyawati, I. A . ; Liu, S.; Rettig, S. J.; Orvig, C. Inorg. Chem. 2000, 39, 496. 11) Broan, C. J.; Cole, E.; Jankowski, K . J.; Parker, D.; Pulukkody, K . ; Boyce, B . A . ; Nigel, R. A . B . ; Millar, K.; Millican, A . T. Synthesis 1992, 63. 12) Cole, E.; Copley, R. C. B.; Howard, J. A . K . ; Parker, D.; Ferguson, G.; Gallagher, J. F.; Kaitner, B . ; Harrison, A . ; Royle, L. J. Chem. Soc, Dalton Trans. 1994, 1619. 13) Aime, S.; Botta, M . ; Parker, D.; Williams, J. A . G. J. Chem. Soc, Dalton Trans. 1996, 17. 14) Huskowska, E.; Maupin, C. L . ; Parker, D.; Williams, J. A . G ; Riehl, J. P. Enantiomer 1997, 2, 381. 15) Aime, S.; Batsanov, A . S.; Botta, M . ; Dickins, R. S.; Faulkner, S.; Foster, C. E.; Harrison, A . ; Howard, J. A . K . ; Moloney, J. M . ; Norman, T. J.; Parker, D.; Royle, L . ; Williams, J. A . G. J. Chem. Soc, Dalton Trans. 1997, 3623. -95-  16) Aime, S.; Botta, M . ; Dickins, R. S.; Maupin, C. L.; Parker, D.; Riehl, J. P.; Williams, J. A . G. J. Chem. Soc., Dalton Trans. 1998, 881. 17) Pulukkody, J. P.; Norman, T. J.; Parker, D.; Royle, L.; Broan, C. J. J. Chem. Soc, Perkin Trans. 2 1993, 605. 18) Aime, S.; Batsanov, A . S.; Botta, M . ; Howard, J. A . K.; Parker, D.; Senanayake, K . ; Williams, J. A . G. Inorg. Chem. 1994, 33, 4696. 19) Sherry, A . D. J. Alloys Compd. 1997, 249, 153. 20) Kim, W. D.; Kiefer, G. E.; Huskens, J.; Sherry, A. D. Inorg. Chem. 1997, 36, 4128. 21) Liu, S.; Edwards, D. S. Bioconjugate Chem. 2001,12, 7. 22) Caravan, P.; Lowe, M . P.; Read, P. W.; Rettig, S. J.; Yang, L. W.; Orvig, C. J. Alloys Compd. 1997, 249, 49. 23) Perrin, D. D.; Armarego, W. L . F.; Perrin, D. R.  Purification of Laboratory  Chemicals; 2nd ed.; Pergamon Press: Toronto, 1980. 24) Naiini, A . ; Menge, W. M . P. B.; Verkade, J. G. Inorg. Chem. 1991, 30, 5009. 25) Moedritzer, K.; Irani, R. R. J. Org. Chem. 1966, 31, 1603. 26) March, J.  Advanced Organic Chemistry; 3rd ed.; John Wiley & Sons, Inc.: New  York, 1985. 27) Mollier, H . ; Vincens, M . ; Vidal, M . ; Pasqualini, R.; Duet, M . Bull. Soc. Chim. Fr. 1991,128, 787. 28) Greene, T. W.; Wuts, P. G. M . Protective Groups in Organic Synthesis; 3rd ed.; John Wiley & Sons, Inc.: New York, 1999.  -96-  Chapter Five Conclusions and Further Thoughts  5.1. General Conclusions  The metal complexes discussed in this thesis have the potential to be used as diagnostic or therapeutic agents in nuclear medicine, or to act as models for new potential agents.  Complexes containing the [Re=0]  core and phosphine-phenolate ligands  (H PO ) were prepared and structurally characterized. The possibility of forming ternary x  x  complexes with various hydrazines was explored to evaluate the potential of H P O to act x  x  as coligands in the H Y N I C bifunctional chelate system. A series of complexes were prepared by reaction of H P O x  x  with preformed rhenium-hydrazine cores, such as  [Re(Hhypy)(hypy)] and [Re(N PhMe) ] . The new tripodal amine-phosphinate ligands 3+  3+  2  2  H ppba and H ppa were synthesized and metal complexes containing A l , G a , I n and 3 +  3  Ln  3+  3+  3  3 +  ion were prepared. The complexes were prepared to investigate their possible use in  nuclear medicine, and to explore their fundamental coordination chemistry. In Chapter 2, [Re=0] H ( M e P 0 ) were prepared. 2  2  3+  complexes containing the ligands H(MePO) and  [ReOCl(MePO) ] (2.1) was prepared by reaction of  2  2  H(MePO) with wer-[ReOCl (PPh ) ] in ethanol and was structurally characterized. 3  3  2  During the course of these studies, an interesting reduction route was discovered and was used to prepare 2.1 from [ N H ^ R e O J .  Reduction was found to occur only in acidic  solution. Therefore, a two step approach was devised whereby the reduction occurred at low pH in ethanol, and subsequent metal complex formation proceeded upon raising the pH.  The  same  acid/base  reduction  approach  -97-  was  extended  to  synthesize  [ReO(Me P02)(H(Me P02)] (2.2) from [NH ][Re0 ] and the complex was structurally 2  2  4  4  characterized. 2.1 and 2.2 had m-(P,P) geometries in the solid state and in solution. Attempts to form ternary complexes containing various hydrazines with 2.1 and 2.2 were unsuccessful. The successful synthesis of rhenium-hydrazine-PO ternary complexes was x  accomplished in Chapter 3. Employing the reverse of the synthetic strategy attempted in Chapter 2, [ReCl3(Hhypy)(hypyH)J was reacted with excess HPO to afford a mixture of [Re(Hhypy)(hypy)(PO)(HPO)]Cl (3.1) and  [ReCl(Hhypy)(hypy)(PO)] (3.2).  The  mixture was subsequently separated by silica gel chromatography. A n X-ray structure of 3.1 was obtained; the cationic complex was shown to have octahedral geometry and an N3OP2 coordination sphere. One PO ligand was bidentate, the second was monodentate and protonated; they were coordinated trans to one other. The two hypy ligands were coordinated cis to each other in a monodentate diazenido / bidentate diazene fashion. The neutral complex 3.2 was also structurally characterized; the complex had octahedral geometry and an N3OP2CI coordination sphere, wherein the Cl" ligand replaced the monodentate HPO ligand seen in 3.1. Reaction of [ReCl (Hhypy)(hypyH)] with H2PO2 3  and  H (Me P02) 2  2  [Re(Hhypy)(hypy)(HP0 )(H P0 )]Cl  afforded  2  [Re(Hhypy)(hypy)(H(Me P02))(H (Me2P02))]Cl 2  2  2  2  (3.4), respectively.  (3.3)  and  Spectroscopic  evidence strongly indicated that 3.3 and 3.4 were isostructural with the structurallycharacterized cation 3.1. The reaction of H(MePO) with [ReCl2(N PhMe)2(PPh )][BPh ] 2  3  4  in methanol afforded [Re(N2PhMe)2(MeP0)2] [BPhu] (3.5). Elemental analysis data and spectroscopic evidence demonstrated that 3.5 is most likely an octahedral cation, with two N2PhMe ligands coordinated cis to one other, and the P atoms of the two MePO ligands coordinated trans to one other. The H P O ligands were shown to be capable of x  -98-  x  forming ternary complexes of rhenium containing hydrazines, provided that the hydrazine ligands were coordinated to the Re first. In Chapter 4, the tripodal amine-phosphinate ligands H3ppba and fbppa were synthesized.  The N-debenzylation of Fbppba by hydrogenation afforded the novel 3~i~  secondary amine tripod fbppa.  3~i~  3-1-  I-^ppba was reacted with A l , Ga , In  3~i*  and L n  nitrates in ligand : metal ratios of 2:1. Two distinct types of complex were isolated. The group 13 metals and H o - L u 3+  [M(H.4ppba)2] . 5+  3+  afforded [M(H ppba) ] , and L a - T b 3+  3  3+  afforded  3+  2  Examples of both types of complex were structurally characterized;  [Ga(H ppba)2](N0 ) Cl-3CH OH (4.1) and [Gd(H ppba)2](N0 ) Cl-3CH OH (4.2) are 3  3  2  3  4  3  4  3  both bicapped complexes wherein only the phosphinate groups coordinated to the metal ion. The complexes differ in the level of protonation in the unoccupied upper portions of the tripods. The structures of the remaining complexes were shown to be identical to 4.1 or 4.2 by a combination of IR spectroscopy, mass spectrometry and elemental analysis data.  At 1:1 ligand : metal ratios, H ppba reacted with nitrates of L a - E r 3+  3  [M(H.4ppba)] . 4+  3+  to form  Although a structural analysis could not be performed on any of the  complexes, experimental evidence supported the formation of a 1:1 monocapped complex, wherein the nitrate counterions were not coordinated to the metal center. The empty coordination sites were likely occupied by water. amine-phosphinate ligand H ppa with G a ( N 0 ) 3  3  3  Reaction of the secondary  at 1:1 ratios forms [Ga(ppa)]-3H.20.  Experimental evidence supported the formation of an encapsulated  1:1 complex;  however, the lack of a structural analysis prevented verification of encapsulated complex formation.  -99-  5.2. Suggestions for Future Work  The HPO, H2PO2, H(MePO) and H ( M e P 0 ) ligands have been shown to form 1  1  2  [Re=0]  2  2  complexes and complexes with two different rhenium-hydrazine cores. The  3+  analogous tert-butyl ligands, (5-ter/-butyl-2-hydroxyphenyl)diphenylphosphine (H(7BuPO)) and bis(5-fert-butyl-2-hydroxyphenyl)phenylphosphine (H2(/-Bu2P02)) have also been prepared. The tert-butyl ligands could introduce a significant amount of steric bulk 2  into the [Re=0]  3+  complexes, all of which had m-(P,P) stereochemistry in solution and  the solid state. A slight excess of H(r-BuPO) was reacted with [ReOCl3(PPh3) ] in ethanol, in a 2  manner identical to the preparation of 2.1. The +LSIMS data for the resulting complex shows peaks corresponding to [ReO(r-BuPO) (J-BuP0 )] (5.2) + H at m/z = 1217 and +  2  2  [ReO(^-BuPO) ] at m/z = 869. The latter type of peak was observed in 2.1 but the 2  former peak has not been seen before in complexes of this type. Elemental analyses of C and H support the formation of the neutral [ReOCl(/-BuPO) ] (5.1). The v(Re=0) at 960 2  cm" in the IR spectrum supports the formation of a [Re=0] 1  3+  complex. Preliminary P  N M R studies show a total of five resonances; two are coupled to each other with  3 I  Jp ) = (  ;P  6 Hz, the remaining three are singlets that are shifted significantly downfield from the doublets.  Two of the three singlets are large and it is possible that one is due to  contamination of the complex with oxidized H(/-BuPO). It is also possible that one of the large P N M R signals is due to a trans complex with identical composition to the cis 3 I  complexes. If a trans-(P,P) complex were to form, and both r-BuPO ligands were bound  - 100-  in the equatorial plane, no trans-(?,V) coupling would be observed since the P nuclei would be equivalent. Further investigation is warranted. The  large number of Happba complexes prepared in Chapter 4 were of  fundamental interest, but the lack of water solubility precluded the use of any of these complexes as diagnostic therapeutic agents. The formation of bicapped and monocapped complexes was also not favourable for this application.  P N M R studies could be used  to determine the stability constant of the complexes, but the study would have to be done in methanol solution. The results of such a study would not be comparable to studies done in aqueous solution and would be of limited utility. Hsppa was shown by various techniques to form a 1:1 encapsulated complex with Ga  3+  in methanol, and was highly water soluble. This is a significant result that merits  further investigation.  Complexes of A l , In  and Ln  should be synthesized and  characterized in solution, and i f possible, in the solid state. The water solubility of these complexes will likely make them amenable to study by a number of techniques that are not useful in methanol. Potentiometric studies have been of great value in characterizing the behavior of L n  3 +  and group 13 complexes in aqueous solution, and such studies  should be undertaken in this system. Unlike the H3ppma system, in which the complexes were all bicapped, " potentiometric titrations should be able to monitor the loss of the 3  5  amine protons, and allow the formation of 1:1 encapsulated complexes to be verified. It is also of interest to know whether any water molecules are bound to the metal ion. The l 7  0 N M R spectral shifts of natural abundance H2O in D y  3+  complexes have been used as  a method to determine the number of bound water molecules.  - 101 -  5  5.3. References  1) Luo, H.; Setyawati, I.; Rettig, S. J.; Orvig, C. Inorg. Chem. 1995, 34, 2287. 2) Kovacs, M . S.; Hein, P.; Sattarzadeh, S.; Patrick, B . O.; Emge, T. J.; Orvig, C. Submitted for publication. 3) Lowe, M . P.; Rettig, S. J.; Orvig, C. J. Am. Chem. Soc. 1996,118, 10446. 4) Caravan, P.; Lowe, M . P.; Read, P. W.; Rettig, S. J.; Yang, L . W.; Orvig,. C. J. Alloys Compd. 1997, 249, 49. 5) Lowe, M . P.; Caravan, P.; Rettig, S. J.; Orvig, C. Inorg. Chem. 1998, 37, 1637.  - 102-  Appendix  X-ray  crystallographic  analyses  [ReO(Me P02)(H(Me P02))] (2.2). 2  of  [ReOCl(MePO)2]  (2.1)  and  Data for 2.1 and 2.2 were collected on a  2  Rigaku/ADSC C C D diffractometer at U B C at -100(1)°C. A l l data were processed and corrected for Lorentz and polarization effects, and absorption (semi-empirical, based on symmetry analysis of redundant data).  Structure 2.1 was solved using heavy-atom  Patterson methods, while the structure of 2.2 was solved by direct methods. 1  structures were expanded using Fourier techniques. were carried out using S H E L X L - 9 7 .  4  3  2  Both  Final refinements for 2.1 and 2.2  Selected crystallographic data for the complexes  appears in Table A l . Complete lists of bond lengths and bond angles appear in Tables A2, A3, A4 and A5. Final unit cell parameters for 2.1 (2.2) were obtained by least-squares on the setting angles for 18480 (20525) reflections with 26 = 5.8 - 55.8° (6.0 - 55.9°). 2.1 was found to crystallize in space group C2/c with two molecules of «-pentane in the asymmetric unit. A l l non-hydrogen atoms other than therc-pentanecarbons were refined anisotropically. A l l hydrogens were included in fixed positions. Additionally, one phenyl ring [C(27) - C(32)] was disordered and modeled as a rigid group in two separate orientations, with relative populations of 0.72 and 0.28 for the major and minor orientations, respectively. 2.2 crystallizes in space group P2]2]2\ with two molecules of acetonitrile in the asymmetric unit. A l l non-hydrogen atoms were refined anisotropically. The lone hydroxyl hydrogen was refined isotropically, while all others were included in  - 103 -  fixed positions. The enantiomer reported here was chosen based on a refinement of the Flack parameter and by the results of a parallel refinement of both enantiomers. X-ray crystallographic analyses of [Re(Hhypy)(hypy)(PO)(HPO)] [Cl] (3.1). Data for 3.1 were collected on a Rigaku/ADSC C C D diffractometer at U B C at -100(1)°C. A l l data were processed and corrected for Lorentz and polarization effects, and absorption (semi-empirical, based on symmetry analysis of redundant data). structure of 3.1 was solved using heavy-atom Patterson methods'  The  and was expanded  using Fourier techniques. Final refinements for 3.1 were carried out using S H E L X L - 9 7 3  and selected crystallographic data for the complex appears in Table A l .  4  Complete lists  of bond lengths and bond angles appear in Tables A6 and A7. Final unit cell parameters for 3.1 were obtained by least-squares on the setting angles for 18480 reflections with 20 = 6.2 - 55.8°. 3.1 crystallizes in space group PI, with two chloride counterions in the asymmetric unit. A l l non-hydrogen atoms were refined anisotropically, while all hydrogens were included in fixed positions with the exception of H95, which was included in the refinement.. While it was evident that the large void spaces in the lattice allowed for the inclusion of disordered C H 3 O H solvent, the solvent molecules were indeed extremely disordered and impossible to model properly. As a consequence, P L A T O N was used to correct the data. The corrected data 5  set improved the R l value from 0.052 to 0.042. X-ray crystallographic analysis of [ReCl(Hhypy)(hypy)(PO)] (3.2). Data for 3.2 were collected on a Nonius CAD4 diffractometer at Rutgers with graphite monochromatized Cu Kct radiation (X = 1.5418 A ) at -120°C.  The three check  reflections measured every hour showed less than 1 % intensity variation. The data were  -104-  corrected for Lorentz effects and polarization, and absorption, the latter by a numerical S H E L X - 7 6 method. The structures were solved by direct methods using SHELXS-86. 6  7  A l l atoms were refined using S H E L X L - 9 7 based upon F bs^- The Uiso parameters of 4  0  H4, H8, H16 and HI 8 were fixed to 1.2 times the equivalent isotropic U of N4, C8, C16 and C18, respectively. Scattering factors (f , f, f ) are as described in S H E L X L - 9 7 .  4  0  Complete lists of bond lengths and bond angles appear in Tables A8 and A9. X-ray crystallographic analysis of [Ga(H ppba) ][(N03)2Cl]-3CH OH (4.1). 3  2  3  Data were collected on a Rigaku/ADSC C C D diffractometer at U B C at -100(1)°C. The structure was solved by direct methods and was expanded using Fourier techniques. 8  3  A l l hydrogen atoms other than those involved in hydrogen-bonding were included in calculated positions but were not refined.  The unit cell contains several void spaces  where solvents and counterions reside. While there are areas with significant electron density, no satisfactory models for Cl", NO3" or C H O H were possible. As a result, the 3  data were corrected for the electron density in these void spaces using P L A T O N .  5  The  corrected data greatly improved the residuals ( R l = 0.12 to 0.048). No inferences should be made as to the nature of the counterions or the amount of solvent molecules in the asymmetric unit. Readers should refer to elemental analysis results for the elucidation of the exact chemical composition of this material. Complete lists of bond lengths and bond angles appear in Tables A10 and A l 1. X-ray crystallographic analysis of [Gd(H ppba) ][(N03)4Cl]-3CH OH (4.2). 4  2  3  Data were collected on a Rigaku/ADSC C C D diffractometer at U B C at -100(1)°C. The structure was solved by direct methods and was expanded using Fourier techniques. 8  3  The material resides on a 3-fold inversion axis, with the Gd atom having a population of -105-  1/6. Both N ( l ) and N(2) appear to be protonated, with the protons found and refined from a difference map. The anions appear to be a disordered mixture of Cl" and N 0 " . 3  Restraints were used to fix the geometries of the two disordered NO3" fragments, and relative populations of 0.5 and 0.166667 were given to the major and minor fragments, respectively. A population of 0.166667 was also given to Cl(l). Unresolvable disordered solvent molecules reside in the large voids between the cationic Gd-complexes in the unit cell. The data were therefore corrected using P L A T O N / S Q U E E Z E .  5  R l was found to  drop from 0.079 to 0.034. Complete lists of bond lengths and bond angles appear in Tables A12 and A13.  References  1) Beurskens, P. T.; Admiraal, G.; Beurskens, W. P.; Garcia-Granda, S.; Gould, R. O.; Smits, J. M . M . ; Smykalla, C. The DIRDIF program system; Technical Report of the Crystallography Laboratory: University of Nijmegen, The Netherlands, 1992. 2) Altomare, A . ; Burla, M . C ; Cammalli, G.; Cascarano, M . ; Giacovazzo, C ; Guagliardi, A.; Moliterni, A . G. G.; Polidori, G.; Spagna, A . J. Appl. Cryst. 1999, 32, 115. 3) Beurskens, P. T.; Admiraal, G.; Beurskens, G ; Bosman, W. P.; de Gelder, R.; Israel, R.; Smits, J. M . M . The DIRDIF-94 program system; Technical Report of the Crystallography Laboratory: University of Nijmegen, The Netherlands, 1994. 4) Sheldrick, G. M . SHELXL-97, Program for Crystal Structure Refinement; University of Gottingen: Germany, 1997. 5) Spek, A . L . Acta Crystallogr. 1990, A46, 34.  - 106-  6) Sheldrik, G. M . SHELX76, Program for Crystal Structure Determination; University of Cambridge: England, 1976. 7) Sheldrik, G. M . SHELXS86, Program for the Solution of Crystal Structures; University of Gottingen: Germany, 1986. 8) Altomare, A.; Cascarano, M . ; Giacovazzo, C ; Guagliardi, A. J. Appl. Cryst. 1994, 26, 343.  - 107-  PL,  fN  © © ©  o ON  © NO ON  u  00  O CN  CN O CN  ON 00  <n oo  B c< ~  CN m  •  ON  ©  r--  ©  ©  00  >— ^ ^ ro  ro  1  00 ©  ON  P © © © ©  ©  ©  ^  NO  PL,  5  ^——  N  'S CN  o  oo  0*  O  O  CN  o ©  ON  rin in  ON  P ©  ss ©  ON  tn  CN  ©  ON ON ro ©  ©  <— oo i n i t CN 1  r--  ©  P P ~ H  s o  CN r l -  O  ©  ©  °. ^  <N CN  r--  00  w. © JT ON i ^ . CN m  o © o tn © © © ON ON ON CN  o  •c  <N  o  PL,  cd  ©  CN  m  © ON ON ON  CN -sf  •s  (N  <u  I ON  <—i  00 1—<  m  in  ©  T—4  I—1  in in © ©  m  ©  NO r-~ ON  X CN © ^ P P P ©  ©  I—J  W © © © ©  rj  o  NO  y  CN CN CN v©' in ON © i n ON oo ON  ©  ro © ON — i< © ^6 ON  00  ro ON  fN CN  I  oo ^—  tn  q  ©  o  o CN  ON)  in of ro  CN  ON  Pu  00  in  o o oo O N ON in ro  in  a  <u  tn  tn  o o c o  in  *s  OO •N—^  © © © ©  00  r-  00  1—H  00  ON  »—,  ©  CN ON CN ©  in ©  CN  |  ro rCN  o T-C  (N  ? p 2 2 O  ©  ©  u © © © ©  cu  fN  s  PH  O  o  ON  •s  in  o  CN ON  o  CN"  CN  oo © ^ oo ©  ON  ©  o ©  i—iCNONONONrO'sf^  ON  ro in in  ON MS O  oo ON  ©  ro ©  <  OH  o  m  *o o c o  00  in  g as cs S PI P  u C C - C O O  in" ON"  CN"  1  CN  s  ON  ro  ON CN  CN CN ON  in ©  © ©  ON  tn in •«t in © © ©  ON  in ro in ro oo  ON m  ON ©  'OO  CN  ro  r-  ©  b  ro  00  OO  ©  r~- T — i © >o  o  ©  ©  r-©  s ° ^  Al  (JL,  ©  in ©  00  ro —H  n  H  ©  CL I  ©  ©  h  ON ©  PH I  I o PL,  o  "  CN  I  >^ o t/3  i I—,  © © © ©  o  CN  NO  CN CN 0^  ON ON i n ON  •e  a! o u  CN  rs r  o  o. o C  c3  2 £  ^lo  Pi  00  Table A 2 . Bond Lengths (A) for [ReOCl(MePO) ] (2.1). 2  Rel Rel Rel Rel Rel Rel PI PI PI P2 P2 P2 P2 Ol 02 Cl Cl C2 C3 C4 C5 C5 C8 C8 C9 CIO Cll C12  -Cll -PI -P2 -01 -02 -03 -Cl -C8 -C14 -C20 -C27A -C33 -C27B -C2 -C21 -C2 -C6 -C3 -C4 -C5 -C6 -C7 -C9 -C13 -CIO -Cll -C12 -C13  2.264(4) 2.4457(15) 2.4206(17) 2.013(4) 2.044(3) 1.680(4) 1.797(6) 1.816(5) 1.821(7) 1.781(6) 1.842(7) 1.817(6) 1.783(19) 1.364(8) 1.334(7) 1.394(7) 1.389(9) 1.392(10) 1.376(13) 1.397(10) 1.404(10) 1.502(13) 1.390(9) 1.404(8) 1.393(10) 1.370(11) 1.404(10) 1.379(8)  C14 C14 C15 C16 C17 C18 C20 C20 C21 C22 C23 C24 C24 C27A C27A C27B C27B C28A C28B C29A C29B C30A C30B C31A C31B C33 C33 C34  - 109-  -C15 -C19 -C16 -C17 -C18 -C19 -C21 -C25 -C22 -C23 -C24 -C25 -C26 -C28A -C32A -C28B -C32B -C29A -C29B -C30A -C30B -C31A -C31B -C32A -C32B -C38 -C34 -C35  1.380(9) 1.384(8) 1.391(10) 1.377(10) 1.385(10) 1.380(9) 1.401(8) 1.408(9) 1.406(9) 1.367(9) 1.394(10) 1.376(10) 1.520(11) 1.389(11) 1.390(12) 1.39(3) 1.39(3) 1.390(11) 1.39(3) 1.392(13) 1.39(3) 1.389(14) 1.39(4) 1.390(11) 1.39(3) 1.414(8) 1.373(9) 1.388(9)  Table A3. Bond Angles (deg) for [ReOCl(MePO) ] (2.1). 2  C l l -Rel -PI C l l -Rel -P2 C l l -Rel - O l C l l -Rel -02 C l l -Rel -03 PI -Rel -P2 PI -Rel -01 PI -Rel -02 PI -Rel -03 P2 -Rel -01 P2 -Rel -02 P2 -Rel -03 -Rel -02 01 -Rel -03 Ol 02 -Rel -03 Rel -PI -Cl Rel -PI -C8 -C14 Rel -PI -PI -C8 Cl -PI -C14 Cl -C14 -PI C8 -C20 Rel -P2 -C27A Rel -P2 -C33 Rel -P2 -C27B Rel -P2 -C27A C20 -P2 -C33 C20 -P2 -C27B C20 -P2 C15 -C16 -C17 C16 -C17 -C18 C17 -C18 -C19 C14 -C19 -C18 P2 -C20 -C21 P2 -C20 -C25 C21 -C20 -C25 02 -C21 -C20 02 -C21 -C22 C20 -C21 -C22 C21 -C22 -C23 C22 -C23 -C24 C23 -C24 -C25 C23 -C24 -C26 C25 -C24 -C26 C20 -C25 -C24 -C27A -C28A P2 -C27A -C32A P2 C28A -C27A -C32A C28B -C27B -C32B P2 -C27B -C32B P2 -C27B -C28B C27A -C28A -C29A C27B -C28B -C29B C28A -C29A -C30A C28B. -C29B -C30B C29A -C30A -C31A C29B -C30B -C31B  162.66(10) 94.44(12) 81.89(15) 91.57(14) 98.23(16) 100.69(5) 81.00(12) 83.41(12) 91.00(14) 160.08(10) 77.96(12) 87.18(14) 82.57(15) 112.70(16) 162.80(15) 97.33(19) 111.92(19) 126.4(2) 107.5(3) 106.1(3) 105.8(2) 101.9(2) 114.6(3) 115.6(2) 122.8(8) 110.6(3) 108.2(3) 107.8(8) 120.1(6) 119.3(6) 120.8(6) 119.8(5) 113.1(5) 127.4(5) 119.5(5) 120.6(5) 120.7(5) 118.7(6) 120.1(6) 122.3(6) 117.9(6) 120.7(6) 121.4(7) 121.5(6) 118.6(5) 121.1(6) 120.1(7) 120.1(19) 124.5(18) 115.4(17) 120.0(7) 120(2) 120.0(8) 120(2) 119.9(7) 120(2)  C27A -P2 -C33 C27B -P2 -C33 -C2 Rel - O l Rel -02 -C2.1 -C2 PI •Cl -C6 PI -Cl -C6 C2 -Cl -C2 -Cl 01 -C2 -C3 Ol -C2 -C3 Cl -C4 C2 -C3 -C4 -C5 C3 C4 -C5 -C6 C4 -C5 -C7 -C5 -C7 C6 -C5 Cl -C6 -C9 PI -C8 PI -C8 -C13 -C8 -C13 C9 -C9 -CIO C8 C9 -CIO - C l l -C12 C10 - C l l -C12 -C13 Cll -C13 -C12 C8 -C14 -C15 PI -C14 -C19 PI C15 -C14 -C19 C14 -C15 -C16 C30A -C31 A -C32A C30B -C31B -C32B C27A -C32A -C31A C27B -C32B -C31B P2 -C33 -C38 C34 -C33 -C38 P2 -C33 -C34 C33 -C34 -C35 C34 -C35 -C36 C35 -C36 -C37 C36 -C37 -C38 C33 -C38 -C37 -H3 C2 -C3 C4 -C3 -H3 -C4 -H4 C3 -H4 -C4 C5 -C6 -H6 Cl -H6 C5 -C6 -H7A C5 -C7 -H7B C5 -C7 -C7 -H7C C5 -H7B H7A -C7 -H7C H7A -C7 -H7C H7B -C7 -H9 -C9 C8 -H9 CIO -C9 -C10 -H10 C9 -CIO -H10 Cll  - 110-  105.7(3) 99.8(8) 121.7(3) 126.3(4) 115.3(4) 124.6(4) 120.1(5) 121.6(5) 119.2(5) 119.2(6) 119.9(6) 122.7(7) 116.6(8) 121.6(8) 121.8(7) 121.6(6) 121.8(4) 118.9(4) 119.2(5) 119.8(6) 120.9(7) 119.9(6) 119.6(6) 120.6(5) 122.4(5) 117.9(4) 119.6(6) 120.3(6) 120.1(8) 120(2) 119.9(8) 120(2) 117.7(5) 119.4(5) 122.8(4) 120.2(6) 120.3(7) 119.6(7) 120.9(7) 119.5(6) 120.14 119.96 118.69 118.65 119.03 119.37 109.45 109.46 109.46 109.39 109.55 109.51 120.19 119.99 119.68 119.47  Table A 3 , (cont.) -Hll CIO - C l l -Hll C12 - C l l -C12 -H12 Cll C13 -C12 -H12 C8 - C13 -H13 C12 -C13 -H13 C14 -C15 -H15 C16 -C15 -H15 C15 -C16 -H16 C17 -C16 -H16 C16 -C17 -H17 C18 -C17 -H17 C17 -C18 -H18 C19 -C18 -H18 C14 -C19 -H19 C18 -C19 -H19 C21 -C22 -H22 C23 -C22 -H22 C22 -C23 -H23 C24 -C23 -H23 C20 -C25 -H25 C24 -C25 -H25 C24 -C26 -H26A C24 -C26 -H26B C24 -C26 -H26C H26A -C26 -H26B H26A -C26 -H26C H26B -C26 -H26C C33 -C38 -H38 C37 -C38 -H38 C39 -C40 -C41 C40 -C41 -C42 C41 -C42 -C43 C40 -C39 -H39A C40 -C39 -H39B C40 -C39 -H39C H39A -C39 -H39B H39A -C39 -H39C H39B -C39 -H39C C39 -C40 -H40A C39 -C40 -H40B C41 -C40 -H40A C41 -C40 -H40B H40A -C40 -H40B C40 -C41 -H41A C40 -C41 -H41B C42 -C41 -H41A C42 -C41 -H41B H41A -C41 -H41B C41 -C42 -H42A C41 -C42 -H42B C43 -C42 -H42A C43 -C42 -H42B H42A -C42 -H42B C42 -C43 -H43A C42 -C43 -H43B  119.97 120.10 120.27 120.18 119.68 119.76 119.91 119.76 120.03 119.90 120.33 120.36 119.65 119.54 120.07 120.08 119.91 119.98 118.99 118.71 119.21 119.29 109.43 109.41 109.38 109.54 109.51 109.55 120.18 120.35 126(4) 100(4) 91(4) 109.48 109.34 109.71 109.33 109.49 109.47 106.35 105.85 106.12 105.26 106.08 111.14 111.51 112.21 112.55 109.38 113.15 113.40 113.58 113.57 111.03 109.48 109.88  C27A -C28A -H28A C29A -C28A -H28A C27B -C28B -H28B C29B -C28B -H28B C28A -C29A -H29A C30A -C29A -H29A C28B -C29B -H29B C30B -C29B -H29B C29A -C30A -H30A C31A -C30A -H30A C29B -C30B -H30B C31B -C30B -H30B C30A -C31A -H31A C32A -C31A -H31A C30B -C31B -H31B C32B -C31B -H31B C27A -C32A -H32A C31A -C32A -H32A C31B -C32B -H32B C27B -C32B -H32B C35 -C34 - H34 C33 -C34 - H34 C36 -C35 - H35 C34 -C35 - H35 C35 -C36 -H36 C37 -C36 - H36 C36 -C37 - H37 C38 -C37 - H37 C42 -C43 - H43C H43A -C43 -H43B H43A -C43 -H43C H43B -C43 -H43C C45 -C46 • C47 C46 -C47 • C48 C46 -C45 - H45A C46 -C45 - H45B H45A -C45 -H45B C45 -C46 • H46A C45 -C46 • H46B C47 -C46 • H46A C47 -C46 • H46B H46A -C46 -H46B C46 -C47 • H47A C46 -C47 • H47B H47A C48 -C47 C48 -C47 -H47B H47A -C47 -H47B C47 -C48 •H48A C47 -C48 •H48B C47 -C48 •H48C H48A -C48 -H48B H48A -C48 -H48C H48B -C48 -H48C H44A -C44 -H44B H44A -C44 -H44C H44B -C44 -H44C  - Ill -  120.01 120.00 120.08 120.02 120.07 119.96 119.89 120.10 119.94 120.13 120.01 120.00 119.89 120.00 119.98 119.99 120.05 120.07 120.10 119.97 119.94 119.85 119.93 119.75 120.18 120.19 119.48 119.58 109.78 109.21 109.02 109.46 134(3) 156(3) 105.54 105.42 106.03 103.75 103.70 103.42 103.62 105.22 97.68 97.95 96.61 96.86 103.29 109.38 108.92 109.30 109.49 109.85 109.88 109.26 109.81 109.54  Table A4. Bond Lengths (A) for [ReO(Me P02)(H(Me P0 ))] (2.2). 2  Rel Rel Rel Rel Rel Rel PI PI PI P2 P2 P2 Ol 02 03 04 04 NI N2 Cl Cl C2 C3 C4 C4 C5 C8 C8 C37 C38 C39 C3 C5 C6 C7 C7 C7 CIO C12 C13 C14 C14 C14 C16 C17 C18 C19 C20 C23 C25 C26  -PI -P2 -01 -02 -03 -05 -C2 -C9 -C15 -C22 -C29 -C35 -Cl -C8 -C21 -C28 -H35 -C41 -C43 -C6 -C2 -C3 -C4 -C5 -C7 -C6 -C13 -C9 -C38 -C39 -C40 -H3 -H5 -H6 -H7B -H7A -H7C -H10 -H12 -H13 -H14B -H14C -H14A -H16 -H17 -H18 -H19 -H20 -H23 -H25 -H26  2.4103(15) 2.4576(15) 2.036(4) 2.019(4) 2.003(4) 1.665(4) 1.787(6) 1.803(7) 1.805(6) 1.795(6) 1.823(7) 1.821(7) 1.347(6) 1.354(7) 1.351(7) 1.377(7) 1.17(13) 1.139(13) 1.135(13) 1.407(8) 1.392(8) 1.392(8) 1.403(8) 1.413(9) 1.497(9) 1.373(9) 1.399(9) 1.388(8) 1.399(9) 1.382(9) 1.383(9) 0.9286 0.9297 0.9305 0.9609 0.9600 0.9604 0.9298 0.9294 0.9308 0.9610 0.9603 0.9603 0.9304 0.9317 0.9300 0.9300 0.9294 0.9315 0.9287 0.9299  2  C9 -C10 C10 - C l l -C14 Cll -C12 Cll C12 -C13 C15 -C16 C15 -C20 C16 -C17 C17 -C18 C18 -C19 C19 -C20 C21 -C26 C21 -C22 C22 -C23 C23 -C24 C24 -C25 C24 -C27 C25 -C26 C28 -C33 C28 -C29 C29 -C30 C30 -C31 C31 -C34 C31 -C32 C32 -C33 C35 -C40 C35 -C36 C36 -C37 C27 -H27C C27 -H27B C27 -H27A C30 -H30 C32 -H32 C33 -H33 C34 -H34C C34 -H34A C34 -H34B C36 -H36 C37 -H37 C38 -H38 C39 -H39 C40 -H40 C41 -C42 C42 -H42B C42 -H42C C42 -H42A C43 -C44 C44 -H44A C44 -H44B C44 -H44C  - 112-  2  1.403(9) 1.390(9) 1.509(10) 1.393(9) 1.378(9) 1.393(9) 1.398(8) 1.395(10) 1.371(11) 1.402(10) 1.382(8) 1.409(8) 1.403(9) 1.396(9) 1.397(8) 1.396(9) 1.501(10) 1.380(9) 1.394(8) 1.384(8) 1.403(8) 1.408(9) 1.509(12) 1.390(10) 1.367(10) 1.403(9) 1.378(9) 1.385(9) 0.9591 0.9601 0.9602 0.9297 0.9305 0.9309 0.9600 0.9597 0.9598 0.9303 0.9301 0.9293 0.9296 0.9306 1.449(14) 0.9597 0.9591 0.9594 1.416(13) 0.9607 0.9603 0.9611  T a b l e A 5 . Bond Angles (deg) for [ReO(Me P02)(H(Me P02))] (2.2). 2  PI PI PI PI PI P2 P2 P2 P2 01 OI 01 02 02 03 Rel Rel Rel C2 C2 C9 Rel Rel Rel C22 C22 C29 Rel PI C16 C15 C16 C17 C18 C15 03 C22 03 P2 C21 P2 C22 C23 C25 C23 C24 C21 04 04 C29 P2 P2 C28 C29 C30  -Rel -Rel -Rel -Rel -Rel -Rel -Rel -Rel -Rel -Rel -Rel -Rel -Rel -Rel -Rel -PI -PI -PI -PI -PI -PI -P2 -P2 -P2 -P2 -P2 -P2 -OI -C15 -C15 -C16 -C17 -C18 -C19 -C20 -C21 -C21 -C21 -C22 -C22 -C22 -C23 -C24 -C24 -C24 -C25 -C26 -C28 -C28 -C28 -C29 -C29 -C29 -C30 -C31  -P2 -01 -02 -03 -05 -01 -02 -03 -05 -02 -03 -05 -03 -05 -05 -C2 -C9 -C15 -C9 -C15 -C15 -C22 -C29 -C35 -C29 -C35 -C35 -Cl -C20 -C20 -C17 -C18 -C19 -C20 -C19 -C22 -C26 -C26 -C23 -C23 -C21 -C24 -C27 -C27 -C25 -C26 -C25 -C29 -C33 -C33 -C28 -C30 -C30 -C31 -C34  108.22(5) 75.00(11) 82.41(11) 154.95(12) 92.99(14) 79.70(12) 160.89(11) 82.29(12) 93.96(15) 88.17(15) 85.01(15) 163.63(17) 82.00(16) 101.44(18) 109.25(17) 102.9(2) 97.93(19) 128.3(2) 107.2(3) 110.7(3) 107.8(3) 96.9(2) 119.4(2) 122.7(2) 105.2(3) 104.3(3) 105.3(3) 126.8(3) 121.3(5) 119.4(6) 119.8(6) 120.6(6) 120.0(7) 119.8(6) 120.3(6) 122.6(5) 119.3(6) 118.1(6) 124.5(5) 119.6(5) 115.9(4) 121.8(6) 121.0(6) 121.7(6) 117.3(6) 122.5(5) 119.5(6) 117.8(5) 121.9(6) 120.3(6) 120.0(5) 120.5(5) 119.5(6) 120.7(6) 120.1(6)  Rel Rel C28 01 C2 OI PI Cl PI C2 C3 C5 C3 C4 Cl 02 C9 02 PI C8 PI C9 CIO C12 CIO Cll C8 PI C30 C31 C28 P2 C36 P2 C35 C36 C37 C38 C35 C2 C4 C4 C6 Cl C5 C4 C4 C4 H7A H7A H7B C9 Cll Cll C13  -113 -  2  -02 -03 -04 -Cl -Cl -Cl -C2 -C2 -C2 -C3 -C4 -C4 -C4 -C5 -C6 -C8 -C8 -C8 -C9 -C9 -C9 -CIO -Cll -Cll -Cll -C12 -C13 -C15 -C31 -C32 -C33 -C35 -C35 -C35 -C36 -C37 -C38 -C39 -C40 -C3 -C3 -C5 -C5 -C6 -C6 -C7 -C7 -C7 -C7 -C7 -C7 -CIO -CIO -C12 -C12  -C8 -C21 -H35 -C2 -C6 -C6 -C3 -C3 -Cl -C4 -C5 -C7 -Cl  -C6 -C5 -C13 -C13 -C9 -CIO -CIO -C8 -Cll -C14 -C14 -C12 -C13 -C12 -C16 -C32 -C33 -C32 -C36 -C40 -C40 -C37 -C38 -C39 -C40 -C39 -H3 -H3 -H5 -H5 -H6 -H6 -H7A -H7B -H7C -H7B -H7C -H7C -H10 -H10 -H12 -H12  121.6(4; 122.1(4; 113(5) 119.2(5; 119.3(5; 121.5(5; 128.2(4; 121.1(5; 110.6(4; 120.4(5; 117.4(5; 120.9(5; 121.8(5; 122.6(6; 119.2(5^ 119.1(5^ 118.5(6 122.5(6 124.5(4 119.9(6 115.6(5 121.6(5 121.3(6 121.2(6 117.5(6 121.5(6 120.9(6 119.2(5 117.3(6 122.7(6 119.4(6 120.2(5 118.6(6 121.1(5 121.5(6 119.5(6 119.5(6 120.5(6 120.4(6 119.80 119.82 118.67 118.68 120.40 120.42 109.50 109.41 109.48 109.42 109.56 109.46 119.29 119.06 119.24 119.26  Table A5. (cont.) C32 -C31 C12 -C13 -C14 Cll -C14 Cll -C14 Cll H14A -C14 H14A -C14 H14B -C14 C15 -C16 C17 -C16 C16 -C17 C18 -C17 C17 -C18 C19 -C18 C18 -C19 C20 -C19 C15 -C20 C19 -C20 C22 -C23 C24 -C23 C24 -C25 C26 -C25 C21 -C26 C25 -C26 C24 -C27 C24 -C27 C24 -C27 H27A -C27 H27A -C27 H42A -C42 H42B -C42 N2 -C43 C43 -C44 C43 -C44  -C34 -H13 -H14A -H14B -H14C -H14B -H14C -H14C -H16 -H16 -H17 -H17 -H18 -H18 -H19 -H19 -H20 -H20 -H23 -H23 -H25 -H25 -H26 -H26 -H27A -H27B -H27C -H27B -H27C -H42C -H42C -C44 -H44A -H44B  122.5(6) 119.54 109.53 109.46 109.51 109.48 109.49 109.36 120.13 120.04 119.78 119.64 120.05 119.99 120.13 120.07 119.88 119.78 119.09 119.09 118.76 118.70 120.30 120.25 109.49 109.49 109.40 109.48 109.44 109.56 109.46 179.7(10) 109.52 109.57  C8 • C13 H27B -C27 C29 -C30 C31 -C30 C31 -C32 C33 -C32 C28 -C33 C32 -C33 C31 -C34 C31 -C34 C31 -C34 H34A -C34 H34A -C34 H34B -C34 C35 -C36 C37 -C36 C36 -C37 C38 -C37 C37 -C38 C39 -C38 C38 -C39 C40 -C39 C35 -C40 C39 -C40 NI -C41 C41 -C42 C41 -C42 C41 -C42 H42A -C42 C43 -C44 H44A -C44 H44A -C44 H44B -C44  - 114-  -H13 -H27C -H30 -H30 -H32 -H32 -H33 -H33 -H34A -H34B -H34C -H34B -H34C -H34C -H36 -H36 -H37 -H37 -H38 -H38 -H39 -H39 -H40 -H40 -C42 -H42A -H42B -H42C -H42B -H44C -H44B -H44C -H44C  119.55 109.53 119.66 119.61 118.74 118.52 120.28 120.32 109.42 109.4 109.43 109.55 109.46 109.50 119.30 119.22 120.32 120.13 120.21 120.32 119.72 119.74 119.77 119.84 177.2(10) 109.46 109.40 109.48 109.47 109.53 109.45 109.37 109.38  Table A 6 . Bond Lengths (A) for [Re(Hhypy)(hypy)(PO)(HPO)]Cl (3.1). Rel Rel Rel Rel Rel Rel Rel Re2 Re2 Re2 Re2 Re2 Re2 PI PI PI P2 P2 P2 P3 P3 P3 P4 P4 P4 01 02 02 C7 C8 C9 CIO Cll C13 C13 C14 C15 C16 C17 C19 C20 C21 C22 C24 C25 C26 C27 C29 C29 C30 C31 C32 C33 C35 C35  -PI -P2 -01 -NI -N3 -N4 -H95 -N7 -N9 -N10 -03 -P3 -P4 -C7 -C13 -C6 -C35 -C29 -C41 -C59 -C52 -C53 -C87 -C81 -C75 -Cl -C30 -H93 -C8 -C9 -CIO -Cll -C12 -C14 -C18 -C15 -C16 -C17 -C18 -C20 -C21 -C22 -C23 -C25 -C26 -C27 -C28 -C30 -C34 -C31 -C32 -C33 -C34 -C36 -C40  2.4137(14) 2.4666(14) 2.032(3) 1.980(4) 2.158(5) 1.780(5) 2.28(7) 1.982(4) 2.149(5) 1.793(5) 2.027(3) 2.4101(14) 2.4544(14) 1.826(6) 1.813(5) 1.792(6) 1.822(5) 1.824(6) 1.832(6) 1.817(5) 1.792(6) 1.813(6) 1.830(5) 1.817(6) 1.819(6) 1.362(7) 1.347(8) 0.8392 1.385(8) 1.405(9) 1.376(10) 1.370(10) 1.391(9) 1.399(8) 1.391(8) 1.387(9) 1.382(9) 1.359(10) 1.381(9) 1.400(9) 1.368(10) 1.394(10) 1.377(9) 1.371(10) 1.386(11) 1.386(12) 1.377(14) 1.431(8) 1.383(9) 1.378(8) 1.387(10) 1.384(9) 1.376(8) 1.390(8) 1.398(8)  03 04 04 NI N2 N3 N3 N4 N5 N6 N6 NI N7 N8 N9 N9 N10 Nil N12 N12 N7 Cl Cl C2 C3 C4 C5 C7 C37 C38 C39 C41 C41 C42 C43 C44 C45 C2 C3 C4 C5 C8 C9 CIO Cll C12 C14 C15 C16 C17 C18 C20 C21 C22 C23  - 115 -  -C47 -C76 -H94 -N2 -C19 -C23 -C19 -N5 -C24 -C24 -C28 -H95 -N8 -C65 -C65 -C69 -Nil -C70 -C74 -C70 -H96 -C6 -C2 -C3 -C4 -C5 -C6 -C12 -C38 -C39 -C40 -C42 -C46 -C43 -C44 -C45 -C46 -H2 -H3 -H4 -H5 -H8 -H9 -H10 -Hll -H12 -H14 -H15 -H16 -H17 -H18 -H20 -H21 -H22 -H23  1.349(7) 1.326(8) 0.8401 1.299(7) 1.357(8) 1.357(7) 1.368(7) 1.240(7) 1.407(7) 1.347(9) 1.343(9) 1.32(8) 1.302(7) 1.375(7) 1.381(7) 1.346(7) 1.228(7) 1.406(7) 1.335(7) 1.350(7) 0.8789 1.396(9) 1.409(8) 1.372(10) 1.383(11) 1.375(8 1.412(9) 1.386(8) 1.366(10) 1.379(9) 1.383(9) 1.393(10) 1.398(9) 1.376(9) 1.358(10) 1.404(10) 1.384(9) 0.9506 0.9485 0.9506 0.9499 0.9487 0.9502 0.9489 0.9503 0.9497 0.9500 0.9505 0.9487 0.9503 0.9507 0.9501 0.9511 0.9492 0.9491  Table A6. (cont.) C36 C26 C27 C28 C31 C32 C33 C34 C36 C37 C38 C39 C40 C42 C43 C44 C45 C46 C47 C47 C48 C49 C50 C51 C53 C53 C54 C55 C56 C87 C88 C89 C90 C91 C48 C49 C50 C51 C54 C55 C56 C57 C58 C60 C61 C62 C63 C64 C66 C67  -C37 -H26 -H27 -H28 -H31 -H32 -H33 -H34 -H36 -H37 -H38 -H39 -H40 -H42 -H43 -H44 -H45 -H46 -C52 -C48 -C49 -C50 -C51 -C52 -C58 -C54 -C55 -C56 -C57 -C88 -C89 -C90 -C91 -C92 -H48 -H49 -H50 -H51 -H54 -H55 -H56 -H57 -H58 -H60 -H61 -H62 -H63 -H64 -H66 -H67  1.395(9) 0.9496 0.9487 0.9500 0.9506 0.9483 0.9493 0.9485 0.9503 0.9502 0.9497 0.9500 0.9488 0.9496 0.9487 0.9510 0.9497 0.9501 1.413(9) 1.378(8) 1.375(1 1) 1.393(13) 1.361(10) 1.403(9) 1.390(8) 1.387(8) 1.385(9) 1.369(10) 1.394(9) 1.391(8) 1.387(9) 1.366(10) 1.376(10) 1.398(9) 0.9506 0.9501 0.9498 0.9494 0.9492 0.9494 0.9494 0.9505 0.9508 0.9513 0.9506 0.9511 0.9502 0.9510 0.9498 0.9499  C25 C57 C59 C59 C60 C61 C62 C63 C65 C66 C67 C68 C70 C71 C72 C73 C75 C75 C76 C77 C78 C79 C81 C81 C82 C83 C84 C85 C87 C68 C69 C71 C72 C73 C74 C77 C78 C79 C80 C82 C83 C84 C85 C86 C88 C89 C90 C91 C92  - 116-  -H25 -C58 -C60 -C64 -C61 -C62 -C63 -C64 -C66 -C67 -C68 -C69 -C71 -C72 -C73 -C74 -C76 -C80 -Cll -CIS  -C79 -C80 -C86 -C82 -C83 -C84 -C85 -C86 -C92 -H68 -H69 -H71 -H72 -H73 -H74 . -H77 -H78 -H79 -H80 -H82 -H83 -H84 -H85 -H86 -H88 -H89 -H90 -H91 -H92  0.9500 1.386(9) 1.380(8) 1.389(8) 1.403(9) 1.382(9) 1.385(11) 1.385(9) 1.385(9) 1.372(10) 1.411(10) 1.384(9) 1.388(8) 1.377(9) 1.368(10) 1.405(10) 1.443(8) 1.391(9) 1.380(8) 1.377(11) 1.372(10) 1.384(8) 1.387(8) 1.399(9) 1.398(11) 1.362(12) 1.374(10) 1.383(9) 1.380(8) 0.9493 0.9507 0.9494 0.9496 0.9500 0.9494 0.9515 0.9487 0.9504 0.9512 0.9495 0.9514 0.9507 0.9510 0.9510 0.9496 0.9501 0.9510 0.9509 0.9491  Table A7. Bond Angles (deg) for [Re(Hhypy)(hypy)(PO)(HPO)]Cl (3.1). PI PI P1 PI PI P2 P2 P2 P2 Ol Ol 01 NI NI N3 N4 01 PI P2 NI N3 P4 P4 N7 P4 P4 03 03 C75 Re2 C81 C75 Rel C30 Re2 C76 Rel NI C19 Rel Rel Rel N4 C24 Rel N2 Re2 N7 C65 Re2 Re2 Re2 N10 C70 Re2  -Rel -Rel -Rel -Rel -Rel -Rel -Rel -Rel -Rel -Rel -Rel -Rel -Rel -Rel -Rel -Rel -Rel -Rel -Rel -Rel -Rel -Re2 -Re2 -Re2 -Re2 -Re2 -Re2 -Re2 -P4 -P4 -P4 -P4 -Ol -02 -03 -04 -NI -N2 -N3 -N3 -N3 -N4 -N5 -N6 -NI -NI -N7 -N8 -N9 -N9 -N9 -N10 -Nil -N12 -N7  -P2 -01 -NI -N3 -N4 -Ol -NI -N3 -N4 -NI -N3 -N4 -N3 -N4 -N4 -H95 -H95 -H95 -H95 -H95 -H95 -N7 -03 -N10 -N9 -N10 -N7 -N9 -C81 -C87 -C87 -C87 -Cl -H93 -C47 -H94 -N2 -C19 -C23 -C19 -C23 -N5 -C24 -C28 -H95 -H95 -N8 -C65 -C69 -C69 -C65 -Nil -C70 -C74 -H96  166.82(4) 80.98(9) 94.91(14) 86.03(13) 94.83(15) 86.18(9) 98.19(14) 96.52(13) 86.66(15) 160.03(16) 87.92(13) 109.65(15) 72.26(17) 90.11(18) 162.35(16) 55(2) 163(2) 92(2) 99(2) 35(2) 107(2) 97.54(14) 86.87(9) 91.34(18) 97.10(13) 85.52(15) 159.61(16) 87.42(13) 108.9(3) 111.8(2) 102.2(3) 105.2(3) 122.1(3) 109.54 123.3(3) 109.44 126.3(4) 110.7(5) 118.5(5) 113.0(4) 128.2(4) 177.0(3) 118.5(5) 116.5(7) 85(3) 146(3) 127.1(3) 110.1(4) 118.1(5) 127.8(4) 113.7(4) 176.2(4) 117.6(4) 116.1(5) 116.40  03 N7 P3 P3 P3 P3 N9 P3 Rel Rel Rel C7 C6 C6 Rel Rel Rel C29 C29 C35 C53 C52 Re2 C52 Re2 Re2 Re2 Re2 01 C2 01 Cl C2 C3 C4 Cl PI PI PI C8 PI C7 C8 C9 CIO C7 PI PI C14 C13 C14 C15 C16 C13 N3  117-  -Re2 -Re2 -Re2 -Re2 -Re2 -Re2 -Re2 -Re2 -PI -PI -PI -PI -PI -PI -P2 -P2 -P2 -P2 -P2 -P2 -P3 -P3 -P3 -P3 -P3 -P3 -P4 -P4 -Cl -Cl -Cl -C2 -C3 -C4 -C5 -C6 -C6 -C6 -C7 -C7 -C7 -C8 -C9 -CIO -Cll -C12 -C13 -C13 -C13 -C14 -C15 -C16 -C17 -C18 -C19  -N10 -N9 -N10 -03 -N7 -P4 -N10 -N9 -C7 -C6 ,-013 -C13 -C7 -C13 -C41 -C29 -C35 -C35 -C41 -C41 -C59 -C59 -C59 -C53 -C52 -C53 -C81 -C75 -C6 -C6 -C2 -C3 -C4 -C5 -C6 -C5 -C5 -Cl -C8 -C12 -C12 -C9 -CIO -Cll -C12 -Cll -C18 -C14 -C18 -C15 -C16 -C17 -C18 -C17 -C20  108.88(15) 72.31(17) 93.90(15) 80.89(9) 95.61(14) 166.85(4) 163.64(16) 87.16(13) 115.73(18) 99.9(2) 115.5(2) 106.9(3) 109.9(3) 108.5(3) 114.0(2) 110.2(2) 19.69(16) 08.6(3) 01.8(3) 00.8(3) 06.4(2) 09.7(3) 14.40(17) 10.8(3) 9.9(2) 15.58(18) 20.7(2) 107.1(2) 122.5(5) 118.6(6) 118.8(5) 119.8(6) 121.5(5) 120.2(6) 119.3(7) 120.6(5) 125.1(5) 114.1(4) 122.3(4) 119.7(5) 118.0(4) 119.2(5) 120.6(6) 119.9(6) 120.3(6) 120.3(6) 121.0(5) 119.2(4) 119.5(5) 120.3(5) 119.3(6) 120.3(6) 121.7(6) 118.9(6) 121.3(6)  Table A7. (cont.)  N8 N2 C19 C20 C21 N3 N5 N5 N6 C24 C25 C26 N6 P2 P2 C30 C29 02 02 C30 C31 C32 C29 C36 P2 P2 C35 C36 C37 C15 C13 C16 C14 C15 C17 C16 C18 C17 C13 C19 C21 C20 C22 C23 C21 C22 N3 C26 C24 C25 C27 C28 C26 N6 C27  -N7 -C19 -C20 -C21 -C22 -C23 -C24 -C24 -C24 -C25 -C26 -C27 -C28 -C29 -C29 -C29 -C30 -C30 -C30 -C31 -C32 -C33 -C34 -C35 -C35 -C35 -C36 -C37 -C38 -C14 -C14 -C15 -C15 -C16 -C16 -C17 -C17 -C18 -C18 -C20 -C20 -C21 -C21 -C22 -C22 -C23 -C23 -C25 -C25 -C26 -C26 -C27 -C27 -C28 -C28  -H96 -C20 -C21 -C22 -C23 -C22 -C25 -N6 -C25 -C26 -C27 -C28 -C27 -C34 -C30 -C34 -C31 -C31 -C29 -C32 -C33 -C34 -C33 -C40 -C36 -C40 -C37 -C38 -C39 -H14 -H14 -H15 -H15 -H16 -H16 -H17 -H17 -H18 -H18 -H20 -H20 -H21 -H21 -H22 -H22 -H23 -H23 -H25 -H25 -H26 -H26 -H27 -H27 -H28 -H28  116.47 121.4(6) 119.1(6) 119.9(6) 119.0(6) 122.2(6) 117.5(6) 118.4(5) 124.0(6) 118.7(7) 118.3(8) 119.2(7) 123.3(8) 121.0(4) 118.8(5) 119.8(5) 118.8(6) 124.0(5) 117.2(5) 120.2(5) 120.8(5) 120.0(6) 120.3(5) 119.8(5) 123.3(4) 116.7(4) 118.8(5) 121.1(6) 120.4(6) 119.82 119.90 120.40 120.30 119.89 119.83 119.12 119.14 120.58 120.53 120.35 120.56 120.07 120.01 120.48 120.54 118.86 118.96 120.70 120.65 120.90 120.81 120.44 120.36 118.35 118.38  N2 C38 C35 C42 P2 P2 C41 C42 C43 C44 C41 Cl C3 C4 C2 C5 C3 C6 C4 C7 C9 CIO C8 C9 Cll CIO C12 Cll C7 C31 C33 C32 C34 C29 C33 C35 C37 C38 C36 C37 C39 C40 C38 C39 C35 C43 C41 C42 C44 C45 C43 C46 C44 C45 C41  - 118-  -C19 -C39 -C40 -C41 -C41 -C41 -C42 -C43 -C44 -C45 -C46 -C2 -C2 -C3 -C3 -C4 -C4 -C5 -C5 -C8 -C8 -C9 -C9 -CIO -CIO -Cll -Cll -C12 -C12 -C32 -C32 -C33 -C33 -C34 -C34 -C36 -C36 -C37 -C37 -C38 -C38 -C39 -C39 -C40 -C40 -C42 -C42 -C43 -C43 -C44 -C44 -C45 -C45 -C46 -C46  -N3 -C40 -C39 -C46 -C42 -C46 -C43 -C44 -C45 -C46 -C45 -H2 -H2 -H3 -H3 -H4 -H4 -H5 -H5 -H8 -H8 -H9 -H9 -H10 -H10 -Hll -Hll -H12 -H12 -H32 -H32 -H33 -H33 -H34 -H34 -H36 -H36 -H37 -H37 -H38 -H38 -H39 -H39 -H40 -H40 -H42 -H42 -H43 -H43 -H44 -H44 -H45 -H45 -H46 -H46  117.3(5) 119.7(6) 120.2(6) 118.7(6) 120.3(5) 121.0(5) 121.0(7) 120.3(7) 120.3(6) 119.7(6) 120.0(6) 120.13 120.03 119.33 119.20 119.97 119.88 120.42 120.32 120.35 120.40 119.74 119.69 120.06 120.02 119.88 119.85 119.87 119.82 1119.5 119.63 119.93 120.10 119.82 119.84 120.58 120.62 119.46 119.48 119.87 119.70 120.14 120.16 119.93 119.85 119.50 119.51 119.88 119.83 119.82 119.88 120.17 120.17 120.02 119.97  Table A 7 . (cont.) C30 C32 C48 C47 C48 C49 C50 C47 P3 P3 P3 P3 C54 C53 C54 C55 C56 C53 P3 P3 C60 C59 C60 C61 C62 C59 N8 N8 N9 C65 P4 P4 C88 C87 C88 C89 C90 C87 C47 C49 C48 C50 C49 C51 C50 C52 C53 C55 C54 C56 C55 C57 C56 C58 C53  -C31 -C31 -C47 -C48 -C49 -C50 -C51 -C52 -C52 -C52 -C53 -C53 -C53 -C54 -C55 -C56 -C57 -C58 -C59 -C59 -C59 -C60 -C61 -C62 -C63 -C64 -C65 -C65 -C65 -C66 -C87 -C87 -C87 -C88 -C89 -C90 -C91 -C92 -C48 -C48 -C49 -C49 -C50 -C50 -C51 -C51 -C54 -C54 -C55 -C55 -C56 -C56 -C57 -C57 -C58  -H31 -H31 -C52 -C49 -C50 -C51 -C52 -C51 -C51 -C47 -C54 -C58 -C58 -C55 -C56 -C57 -C58 -C57 -C60 -C64 -C64 -C61 -C62 -C63 -C64 -C63 -N9 -C66 -C66 -C67 -C88 -C92 -C92 -C89 -C90 -C91 -C92 -C91 -H48 -H48 -H49 -H49 -H50 -H50 -H51 -H51 -H54 -H54 -H55 -H55 -H56 -H56 -H57 -H57 -H58  119.95 119.84 119.3(6) 120.5(7) 120.3(7) 120.4(8) 120.0(7) 119.3(5) 126.5(5) 114.1(4) 123.0(4) 118.2(4) 118.8(5) 120.2(6) 120.3(6) 120.8(6) 118.4(5) 121.4(5) 118.1(4) 121.6(4) 119.8(5) 120.6(6) 119.1(6) 120.2(6) 120.6(6) 119.7(5) 116.6(5) 121.1(5) 122.3(6) 118.7(6) 119.1(4) 122.2(4) 118.7(5) 119.9(6) 121.1(6) 119.6(6) 119.8(6) 120.7(6) 119.72 119.80 119.94 119.79 119.88 119.68 119.95 120.01 119.92 119.83 119.85 119.87 119.66 119.54 120.75 120.81 119.22  03 03 C66 C67 N9 Nil Nil N12 C70 C71 C72 N12 P4 P4 C76 04 04 C75 C76 C77 C78 C75 P4 C82 P4 C81 C82 C83 C84 C81 C60 C62 C61 C63 C62 C64 C59 C63 C65 C67 C66 C68 C67 C69 N9 C68 C70 C72 C71 C73 C72 C74 N12 C73 C76  - 119-  -C47 -C47 -C67 -C68 -C69 -C70 -C70 -C70 -C71 -C72 -C73 -C74 -C75 -C75 -C75 -C76 -C76 -C76 -C77 -C78 -C79 -C80 -C81 -C81 -C81 -C82 -C83 -C84 -C85 -C86 -C61 -C61 -C62 -C62 -C63 -C63 -C64 -C64 -C66 -C66 -C67 -C67 -C68 -C68 -C69 -C69 -C71 -C71 -C72 -C72 -C73 -C73 -C74 -C74 -C77  -C48 -C52 -C68 -C69 -C68 -N12 -C71 -C71 -C72 -C73 -C74 -C73 -C76 -C80 -C80 -C75 -Cll -Cll -CIS  -C79 -C80 -C79 -C82 -C86 -C86 -C83 -C84 -C85 -C86 -C85 -H61 -H61 -H62 -H62 -H63 -H63 -H64 -H64 -H66 -H66 -H67 -H67 -H68 -H68 -H69 -H69 -H71 -H71 -H72 -H72 -H73 -H73 -H74 -H74 -H77  118.9(6 121.6(5 119.7(6 118.7(6 122.3(5 118.5(5 117.3(5 124.2(5 117.9(6 119.8(6 118.3(6 123.7(5 118.5(5 121.0(4 119.3(5 117.3(5 125.2(6 117.4(6 122.3(6 120.2(6 120.1(7 120.7(6 122.0(5 120.2(6 117.7(5 117.9(7 121.9(8 119.4(7 120.9(7 119.6(6 120.35 120.52 119.94 119.90 119.60 119.79 120.07 120.22 120.66 120.63 120.18 120.07 120.68 120.58 118.93 118.76 120.95 121.11 120.14 120.06 120.81 120.90 118.22 118.13 118.90  Table  A  7  .  C57 C59 C61 C78 C80 C75 C79 C81 C83 C82 C84 C83 C85 C84 C86  (cont.) -C58 -C60 -C60 -C79 -C79 -C80 -C80 -C82 -C82 -C83 -C83 -C84 -C84 -C85 -C85  -H58 -H60 -H60 -H79 -H79 -H80 -H80 -H82 -H82 -H83 -H83 -H84 -H84 -H85 -H85  119.41 119.66 119.75 119.84 120.01 119.65 119.68 120.97 121.13 119.00 119.08 120.25 120.36 119.58 119.51  C78 C77 C79 C81 C85 C87 C89 C88 C90 C89 C91 C90 C92 C87 C91  -  120-  -C77 -C78 -C78 -C86 -C86 -C88 -C88 -C89 -C89 -C90 -C90 -C91 -C91 -C92 -C92  -H77 -H78 -H78 -H86 -H86 -H88 -H88 -H89 -H89 -H90 -H90 -H91 -H91 -H92 -H92  118.83 119.92 119.92 120.19 120.18 120.06 119.99 119.36 119.52 120.18 120.20 120.11 120.04 119.68 119.61  Table A8. Bond Lengths (A) for [ReCl(Hhypy)(hypy)(PO)] (3.2).  Rel Rel Rel Rel Rel Rel PI PI PI OI Nl N2 N3 N3 N4 N5 N6 N6 N4 Cl C2 C3 C4 C6 C7 C8 C9 Cll C15 C16 C18 C19 C20 C21  -Cll -PI -OI -Nl -N4 -N6 -Cll -C17 -C23 -C28 -N2 -Cl -Cl -C5 -N5 -C6 -C6 -CIO -H4N -C2 -C3 -C4 -C5 -C7 -C8 -C9 -CIO -C16 -H15 -H16 -H18 -H19 -H20 -H21  2.4136(16) 2.4000(16) 2.035(4) 1.779(5) 1.942(4) 2.136(5) 1.811(5) 1.798(5) 1.802(6) 1.337(7) 1.237(7) 1.431(8) 1.339(8) 1.340(8) 1.312(7) 1.381(7) 1.358(7) 1.363(8) 0.80(7) 1.386(9) 1.371(10) 1.377(11) 1.378(9) 1.389(8) 1.376(9) 1.379(8) 1.361(8) 1.400(8) 0.83(7) 0.98(7) 1.06(6) 0.85(8) 0.78(8) 0.80(7)  Cll C12 C13 C14 C15 C17 C17 C18 C19 C20 C21 C23 C23 C24 C25 C26 C27 C2 C3 C4 C5 C7 C8 C9 C10 C12 C13 C14 C22 C24 C25 C26 C27  - 121 -  -C12 -C13 -C14 -C15 -C16 -C18 -C22 -C19 -C20 -C21 -C22 -C28 -C24 -C25 -C26 -C27 -C28 -H2 -H3 -H4 -H5 -H7 -H8 -H9 -H10 -H12 -H13 -H14 -H22 -H24 -H25 -H26 -H27  1.394(8) 1.399(8) 1.380(9) 1.378(9) 1.377(8) 1.408(8) 1.395(8) 1.374(8) 1.383(9) 1.388(9) 1.373(9) 1.399(8) 1.393(8) 1.393(8) 1.393(9) 1.380(8) 1.399(8) 0.72(7) 0.98(7) 0.95(7) 0.84(7) 0.87(7) 0.85(8) 0.90(6) 0.86(8) 1.02(7) 0.90(7) 1.03(7) 1.09(9) 0.84(7) 0.98(6) 0.91(9) 0.86(8)  Table A9. Bond Angles (deg) for [ReCl(Hhypy)(hypy)(PO)] (3.2).  Cll Cll Cll Cll Cll PI PI PI PI OI OI 01 Nl Nl N4 Rel Rel Rel Cll Cll C17 Rel Rel Nl Cl Rel N4 Rel PI C17 C18 C19 C20 C17 C24 PI PI C23 C24 C25 C26 C23 OI OI Cl C3 C2 C4 C3 C5 N3 C4 C6 C8 C7  -Rel -Rel -Rel -Rel -Rel -Rel -Rel -Rel -Rel -Rel -Rel -Rel -Rel -Rel -Rel -PI -PI -PI -PI -PI -PI -OI -Nl -N2 -N3 -N4 -N5 -N6 -C17 -C18 -C19 -C20 -C21 -C22 -C23 -C23 -C23 -C24 -C25 -C26 -C27 -C28 -C28 -C28 -C2 -C2 -C3 -C3 -C4 -C4 -C5 -C5 -C7 -C7 -C8  -PI -OI -Nl -N4 -N6 -01 -Nl -N4 -N6 -Nl -N4 -N6 -N4 -N6 -N6 -Cll -C17 -C23 -C17 -C23 -C23 -C28 -N2 -Cl -C5 -N5 -C6 -C6 -C22 -C19 -C20 -C21 -C22 -C21 -C28 -C24 -C28 -C25 -C26 -C27 -C28 -C27 -C23 -C27 -H2 -H2 -H3 -H3 -H4 -H4 -H5 -H5 -H7 -H7 -H8  161.77(5) 81.54(12) 93.43(15) 99.14(14) 87.23(13) 80.72(12) 96.31(15) 96.13(14) 88.09(13) 109.16(18) 160.14(18) 88.31(17) 90.7(2) 162.44(19) 71.94(18) 121.00(17) 112.96(19) 99.8(2) 107.3(3) 105.4(3) 109.4(3) 123.4(4) 174.7(4) 118.9(5) 115.6(5) 128.7(4) 108.4(4) 114.5(4) 122.2(5) 120.7(5) 120.1(5) 119.5(6) 121.1(6) 119.9(5) 120.7(5) 125.2(5) 114.1(4) 120.3(6) 118.8(5) 121.2(6) 120.5(5) 118.6(5) 121.8(5) 119.6(5) 116(6) 125(5) 122(5) 118(5) 118(4) 123(5) 117(4) 118(4) 125(5) 116(5) 117(5)  Rel C6 N5 Rel N2 N2 N3 Cl C2 C3 N3 N5 N5 N6 C6 C7 C8 N6 PI PI C12 Cll C12 C13 C14 Cll C18 PI C8 CIO N6 C9 Cll C13 C12 C14 C13 C15 C14 C16 Cll C15 C17 C19 C18 C20 C19 C21 C20 C22 C17 C21 C23 C25 C24  - 122-  -N6 -N6 -N4 -N4 -Cl -Cl -Cl -C2 -C3 -C4 -C5 -C6 -C6 -C6 -C7 -C8 -C9 -C10 -Cll -Cll -Cll -C12 -C13 -C14 -C15 -C16 -C17 -C17 -C9 -C9 -C10 -C10 -C12 -C12 -C13 -C13 -C14 -C14 -C15 -C15 -C16 -C16 -C18 -C18 -C19 -C19 -C20 -C20 -C21 -C21 -C22 -C22 -C24 -C24 -C25  -C10 -C10 -H4N -H4N -C2 -N3 -C2 -C3 -C4 -C5 -C4 -C7 -N6 -C7 -C8 -C9 -C10 -C9 -C12 -C16 -C16 -C13 -C14 -C15 -C16 -C15 -C22 -C18 -H9 -H9 -H10 -H10 -H12 -H12 -HI 3 -H13 -H14 -H14 -H15 -H15 -H16 -H16 -H18 -H18 -H19 -H19 -H20 -H20 -H21 -H21 -H22 -H22 -H24 -H24 -H25  127.5(4) 118.0(5) 112(5) 120(4) 117.1(6) 118.9(5) 124.0(6) 118.6(7) 118.9(6) 118.4(6) 124.5(6) 121.2(5) 116.5(5) 122.4(5) 118.3(5) 119.6(6) 120.1(6) 121.7(5) 117.5(4) 123.0(4) 119.4(5) 120.5(5) 119.1(6) 120.5(6) 121.2(6) 119.4(5) 118.7(5) 119.0(4) 124(4) 116(4) 114(5) 124(5) 123(4) 117(4) 122(4) 119(4) 116(4) 123(4) 121(5) 118(5) 122(4) 119(4) 116(4) 123(4) 112(4) 127(4) 115(5) 125(6) 113(5) 125(5) 117(5) 123(5) 126(5) 114(5) 122(4)  Table A9. (cont.) C9 -C8 -H8 C25 -C26 -H26 C27 -C26 -H26  122(5) 117(5) 121(5)  C26 C26 C28  - 123 -  -C25 -C27 -C27  -H25 -H27 -H27  119(4) 124(5) 115(5)  Table A10. Bond Lengths (A) for [Ga(H ppba) ](N0 ) Cl-3CH OH (4.1). 3  Gal Gal Gal PI PI PI PI P2 P2 P2 P2 P3 P3 P3 P3 NI NI NI N2 N2 N2 N3 N3 N3 N4 N4 N4 N2 C30 C31 C33 C36 C36 C37 C38 C39 C40 C42 C43 C43 C44 C45 C46 C47 Cl Cl C2 C2 C3 C3 C5 C6 C7 C8 C9  -Ol -03 -05 -Ol -02 -C3 -C4 -03 -04 -C19 -C20 -05 -06 -C35 -C36 -Cl -C17 -C33 -C2 -C3 -CIO -C18 -C19 -C26 -C34 -C35 -C42 -H49 -C31 -C32 -C34 -C37 -C41 -C38 -C39 -C40 -C41 -C43 -C48 -C44 -C45 -C46 -C47 -C48 -HI A -H1B -H2A -H2B -H3A -H3B -H5 -H6 -H7 -H8 -H9  1.9498(14) 1.9512(15) 1.9515(15) 1.5052(15) 1.4927(18) 1.833(2) 1.796(2) 1.5047(15) 1.4925(17) 1.834(2) 1.791(2) 1.5048(16) 1.4919(17) 1.834(2) 1.795(2) 1.479(3) 1.482(3) 1.481(3) 1.514(3) 1.496(3) 1.523(3) 1.515(3) 1.496(3) 1.525(3) 1.512(3) 1.498(3) 1.524(3) 0.97(4) 1.368(5) 1.383(4) 1.521(4) 1.391(4) 1.388(4) 1.386(4) 1.386(5) 1.366(5) 1.385(4) 1.507(4) 1.392(4) 1.393(4) 1.385(4) 1.366(5) 1.376(5) 1.404(5) 0.9897 0.9900 0.9914 0.9894 0.9906 0.9900 0.9499 0.9501 0.9502 0.9503 0.9492  2  N3 N4 Cl C4 C4 C5 C6 C7 C8 C10 Cll Cll C12 C13 C14 C15 C17 C20 C20 C21 C22 C23 C24 C26 C27 C27 C28 C29 C10 C12 C13 C14 C15 C16 C17 C17 C18 C18 C19 C19 C21 C22 C23 C24 C25 C26 C26 C28 C29 C30 C31 C32 C33 C33 C34 - 124-  3  2  -H50 -H51 -C2 -C5 -C9 -C6 -C7 -C8 -C9 -Cll -C12 -C16 -C13 -C14 -C15 -C16 -C18 -C25 -C21 -C22 -C23 -C24 -C25 -C27 -C32 -C28 -C29 -C30 -H10B -H12 -H13 -H14 -H15 -H16 -H17A -H17B -H18A -H18B -H19A -H19B -H21 -H22 -H23 -H24 -H25 -H26A -H26B -H28 -H29 -H30 -H31 -H32 -H33A -H33B -H34A  3  0.90(3) 0.95(4) 1.520(4) 1.380(4) 1.389(4) 1.392(5) 1.366(5) 1.381(5) 1.391(4) 1.512(3) 1.394(4) 1.391(4) 1.402(4) 1.378(6) 1.372(5) 1.390(4) 1.521(4) 1.386(4) 1.397(4) 1.383(4) 1.377(5) 1.367(5) 1.389(4) 1.506(4) 1.388(4) 1.398(4) 1.405(5) 1.377(5) 0.9913 0.9491 0.9493 0.9501 0.9511 0.9490 0.9895 0.9913 0.9899 0.9901 0.9892 0.9910 0.9490 0.9500 0.9504 0.9498 0.9500 0.9896 0.9899 0.9512 0.9515 0.9485 0.9500 0.9506 0.9904 0.9906 0.9905  Table A10. (cont.) CIO C35 C35 C37 C38 C39 C40 C41  -HI OA -H35A -H35B -H37 -H38 -H39 -H40 -H41  0.9899 0.9899 0.9893 0.9493 0.9511 0.9502 0.9508 0.9500  C34 C42 C42 C44 C45 C46 C47 C48  - 125 -  -H34B -H42A -H42B -H44 -H45 -H46 -H47 -H48  0.9891 0.9901 0.9912 0.9490 0.9500 0.9492 0.9494 0.9496  Table A l l . Bond Angles (deg) for [Ga(H ppba) ](N0 )2Cl-3CH OH (4.1). 2  3  Ol -Gal -Gal 01 -Gal 01 Ol -Gal -Gal 01 -Gal 03 01 a -Gal 03 -Gal -Gal 03 O l a -Gal 0 3 a -Gal 05 -Gal O l a -Gal O l a -Gal 03 a -Gal -PI Ol Ol -PI -PI Ol 02 -PI 02 -PI -PI C3 -P2 03 03 -P2 03 -P2 -P2 04 04 -P2 C19 -P2 05 -P3 C42 -N4 Nl -Cl N2 -C2 PI -C3 -C4 C5 PI -CA PI -CA C4 -C5 C5 -C6 C6 -Cl -C8 Cl C4 -C9 N2 -CIO CIO - C l l CIO - C l l C12 - C l l -C12 Cll C12 -C13 C13 -C14 C14 -C15 -C16 Cll Nl -C17 N3 -C18 P2 -C19 P2 -C20 C21 -C20 P2 -C20  -03 -05 -Ol a -03 a -05 a -05 -03 -03 a -05 a -05 -05 -05 a -03 a -05 a -05 a -02 -C3 -C4 -C3 -C4 -C4 -04 -C19 -C20 -C19 -C20 -C20 -06 -H51 -C2 -Cl -N2 -C9 -C5 -C9 -C6 -C7 . -C8 -C9 -C8 -Cll -C16 -C12 -C16 -C13 -C14 -C15 -C16 -C15 -C18 -C17 -N3 -C25 -C25 -C21  91.12(6) 91.07(6) 180.00 88.88(6) 88.93(6) 91.10(6) 88.89(6) 180.00 88.90(6) 88.93(6) 88.90(6) 180.00 91.11(6) 91.07(6) 91.10(6) 120.10(9) 104.05(9) 110.50(10) 110.76(10) 109.84(10) 99.50(10) 120.25(9) 104.07(9) 110.40(10) 110.75(10) 109.74(10) 99.52(10) 120.27(9) 103(2) 112.3(2) 112.0(2) 114.25(15) 119.2(2) 119.9(2) 120.73(19) 120.6(3) 119.7(3) 120.8(3) 119.4(3) 120.3(3) 114.45(19) 121.6(2) 119.6(3) 118.7(2) 120.2(3) 119.7(3) 120.7(3) 119.8(3) 120.9(3) 112.2(2) 112.0(2) 114.17(15) 120.08(19) 118.8(2) 120.90(18)  05 05 06 06 C35 Gal Gal Gal Cl Cl C17 C2 C2 C3 C18 C18 C19 C34 C34 C35 CIO C3 C2 C26 C18 C19 C34 C35 C21 C22 C23 C20 N3 C26 C26 C28 C27 C28 C29 C30 C27 Nl N4 P3 P3 P3 C37 C36 C37 C38 C39 C36 N4 C44 C42  - 126-  3  -P3 -P3 -P3 -P3 -P3 -Ol -03 -05 -Nl -Nl -Nl -N2 -N2 -N2 -N3 -N3 -N3 -N4 -N4 -N4 -N2 -N2 -N2 -N3 -N3 -N3 -N4 -N4 -C22 -C23 -C24 -C25 -C26 -C27 -C27 -C27 -C28 -C29 -C30 -C31 -C32 -C33 -C34 -C35 -C36 -C36 -C36 -C37 -C38 -C39 -C40 -C41 -C42 -C43 -C43  3  -C35 -C36 -C35 -C36 -C36 -PI -P2 -P3 -C17 -C33 -C33 -C3 -CIO -CIO -C19 -C26 -C26 -C35 -C42 -C42 -H49 -H49 -H49 -H50 -H50 -H50 -H51 -H51 -C23 -C24 -C25 -C24 -C27 -C28 -C32 -C32 -C29 -C30 -C31 -C32 -C31 -C34 -C33 -N4 -C41 -C37 -C41 -C38 -C39 -C40 -C41 -C40 -C43 -C48 -C48  103.95(10) 110.33(10) 110.87(10) 109.82(10) 99.47(10) 143.84(9) 143.77(9) 143.82(9) 108.9(2) 108.73(19) 108.7(2) 111.06(18) 112.11(19) 111.54(19) 111.13(18) 111.97(19) 111.53(18) 111.31(18) 112.35(19) 111.35(18) 102(2) 106(2) 114(2) 103.9(19) 114.5(19) 103(2) 114(2) 104(2) 120.2(3) 120.3(3) 120.1(3) 120.5(3) 114.8(2) 119.3(2) 121.9(2) 118.7(3) 119.8(3) 119.9(3) 120.4(3) 120.2(3) 121.0(3) 112.1(2) 112.1(2) 114.07(16) 119.90(19) 120.88(18) 119.0(2) 120.3(3) 119.9(3) 120.0(3) 120.5(3 120.2(3) 114.6(2) 118.4(3) 119.8(2)  Table A l l . (cont.) C20 -C21 -C22 C43 -C44 -C45 C44 -C45 -C46 C45 -C46 -C47 C46 -C47 -C48 C43 -C48 -C47 -HI A NI -Cl NI -H1B -Cl C2 -HI A -Cl -H1B C2 -Cl -H1B HI A - C l -H2A N2 -C2 N2 -C2 -H2B -H2A -C2 Cl -C2 -H2B Cl -H2B H2A -C2 PI -C3 -H3A -H3B PI -C3 -H3A N2 -C3 -H3B N2 -C3 -H3B H3A -C3 -H5 C4 -C5 -C5 -H5 C6 -H6 C5 -C6 -C6 -H6 C7 C6 -C7 -H7 -C7 -H7 C8 C7 -C8 -H8 C9 -C8 -H8 P2 -C19 -H19B N3 -C19 -H19A N3 -C19 -H19B H19A -C19 -H19B C20 -C21 -H21 C22 -C21 -H21 C21 -C22 -H22 C23 -C22 -H22 C22 -C23 -H23 C24 -C23 -H23 C23 -C24 -H24 C25 -C24 -H24 C20 -C25 -H25 C24 -C25 -H25 -C26 -H26A N3 N3 -C26 -H26B C27 -C26 -H26A C27 -C26 -H26B H26A -C26 -H26B C27 -C28 -H28 C29 -C28 -H28 C28 -C29 -H29 C30 -C29 -H29 C29 -C30 -H30 C31 -C30 -H30 C30 -C31 -H31  120.1(3) 120.9(3) 120.2(3) 120.5(3) 119.8(3) 120.2(3) 109.11 109.08 109.12 109.17 107.97 109.22 109.14 109.18 109.25 107.95 108.72 108.71 108.65 108.64 107.68 119.69 119.73 120.07 120.24 119.55 119.63 120.22 120.35 108.76 108.72 108.67 107.55 119.96 119.98 119.86 119.91 119.89 119.77 119.96 119.96 119.80 119.75 108.59 108.63 108.61 108.54 107.47 120.13 120.06 119.98 120.13 119.81 119.76 119.98  C42 -C43 -C44 C4 -C9 • H9 C8 •C9 • H9 N2 -CIO -HI OA N2 -CIO -HI OB Cll -CIO -HI OA Cll -CIO -HI OB HI OA -CIO -HI OB -C12 -H12 Cll C13 -C12 -H12 C12 -C13 -H13 C14 -C13 -H13 C13 -C14 -H14 C15 -C14 -H14 C14 -C15 -H15 C16 -C15 -H15 Cll -C16 -H16 C15 -C16 -H16 NI -C17 -H17A NI -C17 -H17B C18 -C17 -H17A C18 -C17 -H17B H17A -C17 -H17B N3 -C18 -H18A N3 -C18 -H18B C17 -C18 -H18A C17 -C18 -H18B H18A -C18 -H18B P2 - C19 -H19A C31 -C32 -H32 NI -C33 -H33A NI -C33 -H33B C34 -C33 -H33A C34 -C33 -H33B H33A -C33 -H33B N4 -C34 -H34A -C34 -H34B N4 C33 -C34 -H34A C33 -C34 -H34B H34A -C34 -H34B P3 • C35 -H35A P3 C35 -H35B N4 -C35 -H35A N4 -C35 -H35B H35A -C35 -H35B C36 -C37 -H37 C38 -C37 -H37 C37 -C38 -H38 C39 -C38 -H38 C38 -C39 -H39 C40 -C39 -H39 C39 -C40 -H40 C41 -C40 -H40 C36 -C41 -H41 C40 -C41 -H41 - 127-  121.8(3) 119.81 119.90 108.71 108.67 108.63 108.61 107.57 119.90 119.86 120.17 120.14 119.67 119.63 120.09 120.10 119.52 119.58 109.20 109.22 109.17 109.11 107.83 109.16 109.25 109.21 109.14 107.96 108.77 119.57 109.16 109.21 109.11 109.19 107.93 109.26 109.23 109.14 109.13 107.88 108.79 108.81 108.73 108.74 107.50 119.84 119.87 120.02 120.08 119.98 120.00 119.79 119.66 119.85 119.92  Table A l l . (cont.) C32 C27 C43 C43 H42A C43 C45 C44 C46  -C31 -C32 -C42 -C42 -C42 -C44 -C44 -C45 -C45  -H31 -H32 -H42A -H42B -H42B -H44 -H44 -H45 -H45  119.78 119.46 108.63 108.64 107.52 119.51 119.56 119.88 119.92  N4 N4 C45 C47 C46 C48 C43 C47  - 128-  -C42 -C42 -C46 -C46 -C47 -C47 -C48 -C48  -H42A -H42B -H46 -H46 -H47 -H47 -H48 -H48  108.64 108.5 119.79 119.72 120.12 120.10 119.87 119.92  Table A12. Bond Lengths (A) for [Gd(H ppba)2](N03)4Cl-3CH OH (4.2). 4  Gdl PI PI PI PI 03A 03 B 05A 05B Nl Nl Nl N2 Nl N2 Cl Cl C2 C3 C4 C5 C8 C9 C9  -02 -Ol -02 -Cl -Cl  -N3A -N3B -N3A -N3B -Cl  -C8 -C15 -C16 -HI A -H2A -C2 -C6 -C3 -C4 -C5 -C6 -C9 -CIO -C14  2.2841(17) 1.500(2) 1.5104(16) 1.797(3) 1.845(3) 1.214(17) 1.07(3) 1.113(14) 1.22(3) 1.498(3) 1.524(3) 1.522(3) 1.514(3) 0.98(5) 0.89(7) 1.388(4) 1.393(4) 1.387(4) 1.378(5) 1.377(6) 1.396(5) 1.502(4) 1.384(4) 1.393(5)  3  CIO Cll C12 C13 C15 C2 C3 C4 C5 C6 C7 C7 C8 C8 CIO Cll C12 C13 C14 C15 C15 C16 C16  - 129-  -Cll -C12 -C13 -C14 -C16 -H2 -H3 -H4 -H5 -H6 -H7B -H7A -H8B -H8A -H10 -Hll -H12 -H13 -H14 -H15B -H15A -H16A -H16B  1.379(5) 1.392(7) 1.365(6) 1.397(5) 1.517(4) 0.9514 0.9511 0.9502 0.9497 0.9512 0.9889 0.9893 0.9906 0.9889 0.9496 0.9497 0.9500 0.9502 0.9508 0.9907 0.9902 0.9891 0.9907  Table A 1 3 . Bond Angles (deg) for [Gd(H ppba)2](N03)4Cl-3CH OH (4.2). 4  -Gdl 02 -Gdl 02 -Gdl 02 -Gdl 02 -Gdl 0 2 a -Gdl 0 2 a -Gdl 02 a -Gdl 0 2 a -Gdl 02 b -Gdl 0 2 b -Gdl 0 2 b -Gdl 0 2 c -Gdl 0 2 c -Gdl 0 2 d -Gdl -PI Ol -PI Ol -PI Ol 02 -PI 02 -PI -PI Cl G d l -02 C7 -NI C7 -NI C8 -NI C16 -N2 C16 -N2 C16_a -N2 C3 -C2 -C2 Cl C4 -C3 C2 -C3 -C4 C5 -C4 C3 C4 -C5 C6 -C5 -C6 Cl C5 -C6 NI -C7 NI -C7 H7A -C7 PI -C7 PI -C7 -C8 C9 NI -C8 NI -C8 H8A -C8 -C8 C9 02  -02 a -02 b -02 c -02 d -02 e -02 b -02 c -02 d -02 e -02 c -02 d -02 e -02 d -02 e -02 e -02 -Cl -C7 -Cl -C7 -C7 -PI -C8 -C15 -C15 -C16 a -C16 b -C16 b -H2 -H2 -H3 -H3 -H4 -H4 -H5 -H5 -H6 -H6 -H7A -H7B -H7B -H7B -H7A -H8A -H8A -H8B -H8B -H8B  87.52(6) 87.52(7) 180.00 92.48(6) 92.48(7) 87.52(6) 92.48(6) 180.00 92.48(6) 92.48(7) 92.48(6) 180.00 87.52(6) 87.52(7) 87.52(6) 117.45(11) 112.67(11) 108.17(10) 107.45(11) 107.94(10) 101.97(12) 143.85(10) 112.1(2) 111.03(19) 107.59(18) 109.0(2) 109.0(2) 109.0(2) 119.61 119.64 120.30 120.19 119.71 119.53 120.05 120.08 120.13 120.04 108.84 108.77 107.55 108.79 108.77 108.43 108.32 108.34 107.47 108.32  3  -HI A C15 -NI -HI A C7 -NI -HI A C8 -NI C16 -N2 -H2A C16 a -N2 -H2A C16 b -N2 -H2A 0 3 A -N3A - 0 5 A 0 3 B -N3B -05B PI -Cl - C6 C2 -Cl -C6 PI -Cl • C2 -C2 -C3 Cl -C4 C2 -C3 -C5 C3 -C4 C4 -C5 -C6 Cl -C6 -C5 PI -C7 - NI NI -C8 -C9 -C14 C8 -C9 CIO -C9 -C14 -CIO C8 -C9 C9 -CIO - C l l -C12 CIO - C l l -C12 -C13 Cll C12 -C13 -C14 C9 -C14 -C13 NI -C15 -C16 N2 -C16 -C15 Cll -CIO -H10 C9 -CIO -H10 -Hll CIO - C l l -Hll C12 - C l l -C12 -H12 Cll C13 -C12 -H12 C12 -C13 -H13 C14 -C13 -H13 C13 -C14 -H14 C9 -C14 -H14 C16 -C15 -H15A NI -C15 -H15A NI -C15 -H15B H15A -C15 -H15B C16 -C15 -H15B N2 -C16 -H16B N2 -C16 -H16A H16A -C16 -H16B C15 -C16 -H16A C15 -C16 -H16B  - 130-  104.1(19) 112.4(18) 109.2(16) 109.92(15) 109.92(16) 109.92(15) 122.2(14) 118(3) 121.1(2) 119.3(3) 119.7(2) 120.7(3) 119.5(3) 120.8(3) 119.9(3) 119.8(3) 113.9(2) 115.7(2) 119.1(3) 118.7(3) 121.9(3) 121.0(3) 119.9(4) 119.8(3) 120.4(3) 120.1(3) 113.4(2) 114.7(2) 119.54 119.46 120.05 120.03 120.07 120.10 119.81 119.79 120.02 119.87 108.81 108.97 108.94 107.61 108.92 108.56 108.64 107.47 108.61 108.66  

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