R.N. Goyal

Redox chemistry of guanine and 8-oxyguanine and a comparison of the peroxidase-catalyzed and electrochemical oxidation of 8-oxyguanine

Abstract The electrochemical oxidation of guanine and 8-oxyguanine has been studied over a wide pH range in aqueous solution. Guanine is initially oxidized in a

Futher insights into the electrochemical oxidation of uric acid

The electrochemical oxidation of uric acid has been studied between pH 1.5 and 9.5 in phosphate buffers using thin-layer spectroelectrochemistry to generate and study UV-absorbing intermediates. Some intermediates and all important products have been separated and analyzed by gas chromatography—mass spectrometry. It is concluded, on the basis of this and preceding studies, that uric acid is initially oxidized in a 2e-2H+ reaction to a very unstable quinonoid diimine (half-life \ 22 ms). At pH ⩾ 6 the anion of the latter species is attacked by water to give an anionic imine-alcohol that undergoes a ring contraction reaction to give 1-carbohydroxy-2,4,6, 8-tetraaza-3,7-dioxo-4-ene-bicyclo-(3,3,0)-octane (BCA). This then decomposes to allantoin. At pH 3–5.6 a neutral quinonoid diimine is generated upon 2e-2H+ oxidation of uric acid. In high-phosphate buffers H2PO4− attacks the diimine, whereas in low-phosphate buffers solvent (H2O) attacks the diimine. In high-phosphate buffers analysis of absorbance vs. time curves obtained following oxidation of uric acid in a thin-layer cell allows three intermediate species to be inferred. In low-phosphate buffers only two intermediates may be inferred. Mechanisms are advanced to rationalize these observations and to account for the end products formed, i.e. allantoin, 5-hydroxyhydantoin-5-carboxamide and, at pH 3, alloxan.

Electrochemical oxidation of hypoxanthine

Abstract The electrochemical oxidation of hypoxanthine (6-oxypurine) in aqueous solution has been studied. The evidence strongly supports the view that hypoxanthine is initially electrooxidized in a 2 e −2H + reaction to give 6,8-dioxypurine. The latter compound is more easily oxidized than hypoxanthine and is immediately further electrooxidized to 6,8-dioxypurine-diimine in a 2 e −2H + reaction. Thus, the primary electrooxidation of hypoxanthine is a 4 e −4H + process to 6,8-dioxypurine-diimine. This diimine is not very stable, although it can be reduced to 6,8-dioxypurine under cyclic voltammetric conditions. A UV-absorbing intermediate is formed upon electrochemical oxidation of hypoxanthine which may be easily observed using thin-layer spectroelectrochemical techniques. The same UV-absorbing intermediate is generated upon electrooxidation of 6,8-dioxypurine. Controlled potential electro-oxidation of hypoxanthine results in the transfer of between 4 e and 6 e per molecule depending upon the time of the electrolysis conditions involved. Under conventional controlled, potential electrolysis conditions close to 6 e are transferred and three major products are formed: 5-imino-2,4-imidazoledione, 5-hydroxyhydantoin-5-carboxamide and 4-amino-4-carboxyimidazole-5-one. Tentative reaction schemes are proposed to explain the formation of these products.

5,5′‐Dihydroxy‐4,4′‐Bitryptamine: A Potentially Aberrant, Neurotoxic Metabolite of Serotonin

Abstract: Previous investigators have detected unknown oxidized forms of 5‐hydroxytryptamine (5‐HT) in the CSF of Alzheimers disease (AD) patients. Furthermore, an unidentified autoxidation product of this neurotransmitter is an inhibitor of acetylcholinesterase (AChE), an enzyme compromised in the Alzheimer brain. In this study it is demonstrated that the major product of autoxidation of 5‐HT is 5,5′‐dihydroxy‐4,4′‐bitryptamine (DHBT). Central administration of DHBT to mice at a dose of 40 μg (free base) evokes profound behavioral responses, which persist until the animals die (∼24 h). One hour after central administration of DHBT, the levels of norepinephrine, dopamine, 5‐HT, and acetylcholine and their metabolites in whole brain are greatly elevated. Disturbances to the catecholaminergic and serotonergic systems were still evident shortly before the death of animals. DHBT is also shown to be a noncompetitive inhibitor of AChE in vitro. These observations suggest that if DHBT is formed as an aberrant metabolite of 5‐HT in the human brain, it could potentially be neurotoxic and contribute to the neuronal degeneration and other neurochemical and neurobiochemical changes associated with AD or perhaps other neurodegenerative diseases.

A comparison of the peroxidase-catalyzed and electrochemical oxidation of uric acid

Abstract The oxidation of uric acid by hydrogen peroxide in the presence of type VIII peroxidase has been studied between pH 5.2 and 8. Intermediates generated in the reaction have been characterized in terms of their U.V. spectra and kinetics of decay. In addition at least one U.V.-absorbing intermediate has been trapped, converted to its trimethylsilyl derivative and identified by gas chromatography-mass spectrometry. This intermediate is 1-carbohydroxy-2,4,6,8-tetraza-3,7-dioxo-4-ene-bicyclo-(3, 3, 0)-octane. At pH ⩾ 7 the product is allantoin while at lower pH 5-hydroxyhydantoin-5-carboxamide is also formed as a major product. The intermediates and products formed and spectral and kinetic measurements observed during and after peroxidase-catalyzed oxidation of uric acid are virtually identical to those noted upon electrochemical oxidation. It has thus been concluded that the mechanisms of electrochemical and enzymic oxidation of uric acid are, in a chemical sense, indentical.

Electrochemical and peroxidase-catalyzed redox chemistry of 9-Methyl uric acid

Abstract The electrochemical and peroxidase/H2O2 oxidation of 9-methyl uric acid has been studied over a wide pH range. Electrochemical, spectral, kinetic and analytical results support the view that the electrochemical and enzymic oxidations proceed by virtually identical mechanisms.

The electrochemical and peroxidase-catalyzed redox chemistry of 9-β-D-ribofuranosyluric acid

Abstract The electrochemical oxidation of 9-β-D-ribofuranosyluric acid ( I ) at a pyrolytic graphite electrode proceeds via an initial 2 e reaction to give an unstable quinonoid intermediate. Nucleophilic attack by water on this intermediate leads to isomeric tertiary alcohol intermediates. The latter have been characterized by electrochemical reduction to a dihydro product which readily dehydrates to regenerate I . The tertiary alcohol intermediates can undergo a ring-opening reaction at pH≥6 to give a spectrally distinct and reversibly reducible pyrimidine derivatives(s) which slowly decompose to give alloxan or alloxanic acid and urea riboside. Alternatively, the tertiary alcohol can further hydrate to yield, ultimately, 5-hydroxyhydantoin-5-carboxamide-3-riboside or undergo a ring contraction reaction and hydrolysis leading to allantoin riboside. The peroxidase-catalyzed oxidation appears to follow essentially the same chemical pathway.

485—Spectroelectrochemical evidence for imine-alcohol intermediate formed upon electrochemical oxidation of uric acid

Abstract Electrochemical oxidation of uric acid in phosphate-containing supporting electrolytes between pH 3–9 at a reticulated vitreous carbon electrode in a thin-layer spectroelectrochemical cell leads to formation of U.V.-absorbing intermediate species. Electrochemical reduction of the intermediate-containing solution leads to the partial regeneration of uric acid. This behavior provides compelling evidence that an imine-alcohol is one of the U.V.-absorbing intermediate species since only this compound may be expected to be reduced to a species which can regenerate uric acid.

Electrochemical and enzymic oxidation of biological purines

Summary The electrochemical and enzymic oxidations of uric acid, various N-methylated uric acids and of guanine, 8-oxyguanine and uric acid-9-riboside have been studied. The voltammetric, spectral and kinetic evidence supports the conclusion that the electrochemical and enzymic (peroxidase) reactions proceed by similar, if not identical, chemical mechanisms.

Electrochemical and enzymatic oxidation of 3,9-dimethyl uric acid

Summary The electrochemical oxidation of 3,9-dimethyl uric acid in aqueous solution has been studied between pH 3.3 and 8.8 at graphite electrodes. A single 2 e−1—i H+ oxidation voltammetric peak is observed corresponding to the formation of a very unstable cationic diimine intermediate. This reacts very rapidly with water to give an imino-alcohol intermediate. The latter intermediate may be observed as a U.V.-absorbing species (λmax=290 nm between pH 3.3–8.8) and by means of its voltammetric reduction peak noted on cyclic voltammetry of 3,9-dimethyl uric acid. The location of the absorption spectrum of this imino-alcohol has been used to deduce its probable structure and the structures of imino-alcohol intermediates formed on oxidation of other uric acid derivatives. Hydration of the imino-alcohol gives the 4,5-diol of 3,9-dimethyl uric acid which decomposes to the final reaction products. The observed first-order rate constant for the latter reaction between pH 3.3 and 8.8 is 0.20±0.05 s−1. Oxidation of 3,9-dimethyl uric acid in the presence of peroxidase and H2O2 gives rise to an intermediate which has identical spectral and electrochemical properties and very similar kinetic properties to the imino-alcohol intermediate generated electrochemically. Accordingly, it appears that the electrochemical and peroxidase-catalyzed oxidations of 3,9-dimethyl uric acid proceed via identical reaction mechanisms.