Please use this identifier to cite or link to this item: http://localhost:8081/xmlui/handle/123456789/1268
Authors: Verma, Madhu Shri
Issue Date: 1995
Abstract: Electrochemical investigations of biologically important compounds provide major challenges both from theoretical and mechanistic view point. The turn of the last two decades has seen a further combination of electrochemical techniques with spectroscopic or mass techniques to probe the deep insights into the redox mechanisms of such molecules. The superficial similarities between enzyme catalysed reactions and electrochemical reactions, particularly the requirement of specific orientation of the molecule at the electrode-solution or enzyme-solution interface further created interest in such studies. It is now generally accepted that electrochemical studies provide a unique and invaluable insight about the in-vivo redox chemistry of biomolecules. Purines are the building blocks of the two well known nucleic acids, viz., RNA and DNA, and hence are intimately involved in protein synthesis and in the transfer of genetic information. Simple purines like Xanthine, Hypoxanthine and Uric acid have been discovered as a constituent of human urine and other biological sources. In the present thesis an attempt has been made to study the electrochemical behaviour of some simple purines at solid electrodes. The present thesis is a small part of the big proposal submitted by Dr. R.N. Goyal in connection with redox chemistry of such type of biomolecules. The thesis has been divided into four chapters. 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. The second chapter of the thesis describes the electrochemical and enzymic oxidation of two N-methyluric acids, viz., 3-methyluric acid (I) and 7-methyluric acid (II) at pyrolytic graphite electrode. (i) CI] CH3 i N HN iT\ H H cm Linear sweep voltammetry of both N-methyluric acids exhibited a well defined anodic peak (Ia) in the pH range 3.2 - 11.3. The peak potential was dependent on pH and shifted to less positive potential with increase in pH. The Ep versus pH plots exhibited two breaks at around 5.6 and 8.6, in 3-methyluric acid and at around pH 5.4 in 7-methyluric acid which correspond to the pKa value of these molecules. In cyclic sweep voltammetry at a sweep rate of 100 mV s"1, one anodic peak (Ia) was observed. In the reverse sweep two cathodic peaks (Ic and IIC) were noticed in both the compounds. Controlled Potential Electrolysis indicated a 2e, 2H+ oxidation in both the cases in theentire pH range studied. The EC nature of the reaction was established using conventional tests in cyclic voltammetry. Using spectral studies, the UV-absorbing intermediate was detected, which decayed in pseudo first order reaction to give the final products ofthereaction. On the basis of products separation using gel-permeation chromatography and characterization using *HNMR, mass, m.p., etc., tentative mechanisms for the EC reaction have also been suggested. The enzymic oxidation ofthesecompounds were also studied by using horseradish peroxidase type VIII and catalysed by hydrogen peroxide. The formation of identical UV-absorbing intermediate, rate of its decay and appearance of peak IIC in the first cycle during enzymic oxidation clearly indicated that electrochemical and enzymic oxidation proceed by identical pathways. Thiopurines are most effective drugs available for the treatment of a number (ii) of types of leukemic and related neoplastic conditions. 6-Mercaptopurine (III) is one of the most effective drug used in cancer therapy. The third chapter of the thesis deals with the kinetics of decomposition of UV-absorbing intermediate generated during electrochemical oxidation of 6-mercaptopurine (6-MP). Spectroscopic techniques coupled with electrochemical oxidation have been used to study the redox-mechanism of 6-MP Linear sweep voltammetry of 6-mercaptopurine at a sweep rate of 10 mV s"1 exhibited one well defined oxidation peak (Ia) in the pH range 2.0 -10.0. If sweep was initiated in the reverse direction, a reduction peak (1IIC) was also noticed. This behaviour suggested that 6-MP can undergo oxidation as well as reduction at PGE. Spectroscopic tehcnique has been used to monitor the cleavage of the S-S bond in the UV-absorbing intermediate generated during electrooxidation. IR spectra during electrooxidation of 6-mercaptopurine provided information about the formation of several unstable intermediates. A tentative mechanism for the electrooxidation has also been suggested. The last chapter of the thesis is devoted to the electrochemical oxidation of 2-mercaptobenzoxazole (IV), which is used as antibacterial, antifungal and antiviral agent for the treatment of various diseases. a—N Ash civa (iii). 2-Mercaptobenzoxazole exhibited a single well-defined oxidation peak (I ) in the cyclic voltammetry at the PGE in the phosphate buffers (pH 2.5 - 10.3) of ionic strength 0.1 M. The peak potential of this peak is linearly dependent on pH and the E - pH plot showed a break at around pH 7.8, indicating the pKa value of the compound. Having scanned peak (Ia), two reduction peaks (Ic, llc) appear on reverse sweep at pH 2.5. Peak IIC disappears at pH > 6.8, and peak Ia was found to form a quasi-reversible couple with peak Ic It was also observed that peak Ic did not appear in cyclic voltammetry if the initial sweep direction was negative. Involvement of adsorption at the electrode surface was confirmed by the increase in peak current function (i /ACv1/2) with sweep rate. Cyclic voltammograms and UV spectra were recorded during thecourse of controlled potential electrolysis to obtain the information about UV-absorbing intermediates gener ated during the course ofelectrode reaction. The .products of the electrode reaction have been characterized. It is concluded on the basis of these studies that electrochemical studies provide a wealth of information about the chemical aspects of the enzyme catalyzed oxidation of biomolecules.
Other Identifiers: Ph.D
Research Supervisor/ Guide: Goyal, R. N.
metadata.dc.type: Doctoral Thesis
Appears in Collections:DOCTORAL THESES (chemistry)

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