STUDIES ON REDOX REACTIONS OF SOME ORGANIC COMPOUNDS OF BIOLOGICAL IMPORTANCE

Abstract

The problem of elucidation of the redox mechanism of biological processes, being fascinating in itself, has been a challenging field because of great complexity of the mechanistic steps and products formed. In spite of recent work in this field, the mechanistic aspects of many of these reactions are still obscure. Electrochemical techniques such as cyclic voltammetry, controlled potential electrolysis, etc., together with other instrumental methods such as molecular spectroscopy and mass spectrometry, have the potential to provide useful insights into the possible enzyme-catalyzed redox reactions. There is a significant body of evidence that suggests that electrochemical reactions occurring in vitro at electrode-solution interface are superficially similar with that of enzymatic reactions at enzyme-solution interface in vital life processes. Compounds in biological systems, however, are usually complex and biologically active site is probably deep within the molecular frame work. Hence, the best way to obtain an interpretation, closer to actual situation of the biological phenomena on a certain reaction, would be to start by examining the electrochemical behaviour of a simple compound. In view of such an importance of electrochemical investigations, the redox behaviour of different types of biologically important organic compounds, such as, heterocyclic amino compounds, azodyes, methylated xanthines (derivatives of purine) and sulfa drug is elucidated using various electrochemical techniques in combination with other sophisticated spectroscopic and analytical techniques. In (i) spite of the importance of this class of organic compounds in medicine and biology, the studies on their reaction mechanism are still obscure and therefore have been investigated in detail. The interesting results of electrochemical studies of some biologically significant organic compounds are presented in following chapters of the thesis. The first chapter of the thesis is 'General Introduction* and presents a brief review and significant results relevant to the present study on the electrochemical investigations of the various compounds selected. 2-Aminobenzimidazole (2-ABI) and its derivatives are of considerable medicinal and agricultural importance since a long time as they are good inhibitors of growth of certain yeast and bacteria and also show a significant fungicidal activity in soil. The second chapter of the thesis describes the electrochemical oxidation of 2-aminobenzimidazole at pyrolytic graphite electrode. Linear sweep voltammetry of 2-ABI exhibited a well defined anodic peak (I ) in the entire pH range 2.0 - 10.8. The peak potential a was linearly dependent on pH and shifted towards less positive potential with the increase in pH. In cyclic sweep voltammetry at a sweep rate of 100 mVs , two anodic peaks (I and II ) were observed. In the reverse sweep two cathodic peaks (I and III ) were noticed. The initial step in the oxidation at physiological pH was found to involve a le, IH reaction leading to the formation of a free radical species, which rapidly dimerizes to give hydrazo intermediate. Further oxidation of hydrazo species in a 2e, 2H reaction leads to the formation of azobenzimidazole. Alternatively, the le, IH oxidation of protonated 2-ABI gives a cationic free radial, which on loss of proton followed by disproportionation gives S-tetrazine derivative of (ii) 2-aminobenzimidazole. The mechanisms corresponding to both the peaks have been suggested. The redox chemistry of azo compounds has attracted considerable attention due to the bacterial reduction of a number of azo compounds by various microorganisms. In view of the importance of azo molecules in biological systems it was found interesting to elucidate the redox behaviour of azobenzene-4,4'-disulfonamide, an oxidation product of a well known antibacterial drug, sulfanilamide and forms the third chapter of the thesis. Linear sweep voltammetry of the azo compound exhibited one sharp pH dependent reduction peak (I ) in the entire pH range studied. In cyclic sweep voltammetry in addition to peak I a pH dependent anodic peak I was also observed in the reverse c a sweep. The 2e, 2H reduction of this compound was found to give hydrazobenzene disulfonamide which has been characterised by using FTIR, m.p., mass and NMR spectra. Under controlled potential electrolysis, a 4e, 4H mechanism was observed. The presence of two electron withdrawing -SO NH groups was found to cause the slow disproportionation (K'/H+ = 3.0x10 lmol sec ) of the hydrazo compound and sulfanilamide has been found as the major product of reduction. A plausible mechanism for the ECE reduction of azobenzene-4,4'-disulfonamide is suggested in this chapter. The fourth chapter of the thesis deals with the electrochemical behaviour of a biologically important purine; 3-methylxanthine. Such compounds have attracted considerable attention in the last decade because of their wide applications as diuretics. In view of the importance of methylated xanthine compounds it was considered interesting to elucidate the electrochemical behaviour of 3-methylxanthine at pyrolytic graphite electrode. (ill) Linear sweep voltammetry of 3-methylxanthine exhibited one well defined oxidation peak (I ). The peak potential of this peak was SI linearly dependent on pH. The cyclic voltammetric studies in the large concentration range, sweep rate and pH range were carried out. The ip vs. concentration behaviour indicated adsorption at the surface of electrode. Adsorption complication was further confirmed by the increase in peak current function with increase in sweep rate. The coulometric studies suggested that the oxidation of 3-methylxanthine involves overall 4e, 4H+ in the electrochemical process. The products of oxidation were determined at pH 3.0 and 7.0. An EC mechanism for the electrooxidation of 3-methylxanthine is suggested. The fifth chapter of the thesis deals with the electrochemical oxidation of the well known antibacterial drug, sulfamethoxazole, at pyrolytic graphite electrode. Linear sweep voltammetry of sulfamethoxazole at a sweep rate 10 ms_1 exhibited a single well defined, pH dependent oxidation peak. The E vs pH plot exhibited two breaks at about pH 3.2 and 6.8 and P corresponded to the pK values of the species. Effect of pH, concentration and sweep rate were studied using cyclic voltammetric technique and results are discussed in detail in this chapter. On the basis of linear and cyclic sweep voltammetry, coulometry, spectral studied during electrooxidation and product identification, a mechanism for the oxidation of sulfamethoxazole has been suggested to account for the formation of azobenzene-4,4*-(methoxyzolyl) disulfonamide as the major product. Most of the compounds selected in the present studies are characterised as being quite good electron donors and/or acceptors. It is therefore believed that the electron transfer reactions of these (iv) compounds and the consequences of such electron transfer will provide significant information to the understanding of their biological electron transfer reactions.