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UBC Theses and Dissertations

Exchange and oxidation reactions of 6,7,8-trimethyllumazine and its dihydroderivative McAndless, John M.


The potential use of 6,7,8-trimethyllumazine (6,7,8-trimethyl-2,4-dioxopteridine) and Its dihydro derivative as a redox couple for the pteridine and flavin systems is investigated. The syntheses of the above compounds and related lumazine derivatives are described and their spectroscopic and chromatographic properties are tabulated. While examining the p.m.r. spectra of 6,7,8-trimethyllumazine (TML) and 7,8-dihydro-6,7,8-trimethyl-lumazine (DHTML) in deuterium oxide media, the hydrogens of the C-7 methyl group and of the C-6 methyl group in the former and latter compounds respectively were observed to undergo exchange. In the pH range -0.4 to 8.0, the exchange of TML is subject to general acid-base catalysis. The pseudo first-order exchange rate constant (k₁) was found to be the sum of several catalytic terms. Prom measurements of the exchange rate-buffer dependency at various pH values, the following values of the specific catalytic constants (in l.mole⁻¹min⁻¹) have been calculated: K[subscript H]+= 1.2, k[subscript H3PO4] = 0.41, k[subscript H2PO4]- = 0.14, k[subscript HPO4]-2 = 52.9 The mechanism of the acid- and base-catalyzed exchange of TML is outlined. The relatively facile exchange is explained in terms of the formation of neutral and ionic intermediates which have long conjugated bonding arrangements. Pseudo first-order rate constants have been tabulated for the general acid-catalyzed exchange of DHTML in the pH range -0.4 to 8.2 leading to an unusual pH-rate profile. The marked decrease in exchange rates and anomalous rate plots in the more acidic pH regions is attributed to acid-catalyzed covalent hydration across the C(6)-N(5) double bond and equilibration of hydrated and unhydrated cations. Evidence for hydration is presented and the exchange mechanism is discussed. The ferricyanide oxidation of DHTML was investigated in the pH range 5 to 12.5 by spectrophotometry and potentiometric techniques. The second-order reaction proceeds in a complicated sequence of steps, some of which are dependent upon the ionization of the reaction intermediate, trimethyl-lumazine. Beyond pH 11, the oxidation rate is directly proportional to the hydroxide ion concentration. At pH 12, the absence of a primary isotope effect and the inhibitory effect of added ferrocyanide indicate that the oxidation proceeds via an initial rapid and reversible one-electron abstraction from the anionic form of DHTML. The resulting mesoroeric radical can undergo further reactions with ferricyanide ion or with hydroxide ion. A very negative ΔS‡ value was obtained for the reaction at pH 12, consistent with a reaction between ions of the same charge. A study of the effects of potassium ion on the oxidation rate indicates the partial participation of the associated species KFe(CN)₆⁻² in the reaction. A limited study of the reaction between trimethyl-lumazine and ferricyanide was undertaken. The hydroxylated anion of TML reacts via a highly coloured intermediate to produce 7-oxo-6,8-dimethyllumazine. Further investigation into the reaction is required.

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