Please use this identifier to cite or link to this item: http://localhost:8081/xmlui/handle/123456789/1246
Authors: Bhargava, Sandhya
Issue Date: 1990
Abstract: The electrochemical behaviour of biologically important organic compounds can provide a useful and often uniquely valuable insight into the generally complex mechanisms of enzymic and perhaps, in vivo redox reactions. As most of these molecules possess an extensive delocalized iT-electron system, they are generally good electron donors and/or acceptors and readily take part in biologically electron transfer reactions. Nevertheless, compounds in biological systems are usually complex and the 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 phenomenon on a certain reaction, would be to start by examining the electrochemical behaviour of a simple compound containing the required group. Therefore, a research programme was initiated to study synthesis as well as electrochemical behaviour of some biologically important antibacterial compounds and the results of these investigations are presented in this thesis. The first chapter comprises general introduction in which a brief report on the electrochemistry of various class of compounds, selected for the present investigation, has been presented. The second chapter of the thesis describes the synthesis of some 4-substituted 1,2,6-thiadiazine-l, 1-dioxides, as possible hypoglycaernic agents by incorporating a sulfonamide moiety. As incorporation of an aryazo moiety results in the enhancement of ii potency of drugs, the sulfonamide moiety has been introduced through an azo linkage in thiadiazines. The synthesis has been achieved in two steps. In the first step diazotisation of appropriate sulfonamide followed by its coupling with reactive methylene compounds like acetylacetone, benzoylacetone and dibenzoyl methane gave different hydrazones. The sulfonamide used were sulfanilamide, sulfamerazine, sulfadiazine, sulfacetamide, sulfapyridine, sulfaguanidine, sulfaproxyline and sulfamethazole. In the second step, these hydrazones were treated with sulfamide and subsequently cyclized to furnish the corresponding 4-(p-sulfamoylphenylazo)-3,5- disubstituted (2H)-1,2,6-thiadiazine-l, 1-dioxides. The synthesised compounds were characterized on the basis of elemental analysis, m.p., IR, mass and NMR spectra. Sulfadrugs undergo oxidation in the human metabolism and these oxidation products are claimed to be responsible for the bacteriostatic action of this class of compound. The third chapter elucidates the electrochemical oxidation mechanism of two important sulfonamides, viz., sulfanilamide and sulfamerazine. Sulfanilamide undergo oxidation at PGE in a well defined 2e, 2H+ voltammetric peak in the pH range 2.0-10.3. The peak current of oxidation peak la increases with increasing concentration in the concentration range 0.2-3.0 mM and ip versus concentration plot is a straight line. The peak current function (ip/Ac\fh) has been found to be constant with scan rate indicating that the electrode reaction is diffusion controlled in this concentration range. The pKa value of sulfanilamide has beer, determined by plotting absorbance at X.nax iii against pH and the resulting curve gave inflection point at 2.4 and 5.2 which are in good agreement with the breaks observed in the Ep versus pH relation. The products of electrooxidation have been found to be pH dependent. In H2SO. media and in phosphate buffers of pH 4.4 four products have been obtained whereas at pH 4.4 only two products have been isolated and characterized by TLC, m.p., IR, UV and NMR spectra. The other drug, sulfamerazine, also undergo oxidation at PGE in 2e, 2H+ process in the pH range 3.0- 10.8. The Ep versus pH plot for the oxidation peak exhibited a break at around pH 6.8 which corresponded to the pKa of sulfamerazine. As a result of electrooxidation, sulfamerazine gave azo product in the entire pH range studied. On the basis of experimental results, tentative mechanisms have been proposed. The studies on the electrochemical behaviour of azo compounds has been the subject of investigation for a long time due to their application in dyes and pharmacy. Azoxy compounds, on the other hand, have not attracted considerable attention inspite of the importance of azoxy group in enhancing the antibiotic as well as antifungal nature of an organic compound. Keeping in view the importance of azoxy compounds, the redox behaviour of azoxybenzene-4,4'-disulfonamide was studied and is described in the fourth chapter of the thesis. The electrochemical reduction of azoxyberizene-4,4,-disulfonamide occurred in B.R. buffers of pH range 3.0-10.6 in a single well defined, pH dependent peak. Voltammetric studies has shown that reduction peak Ic is diffusion controlled upto a concentration of about 0.8 mM whereas at higher iv concentration there is an indication of weak adsorption of the reactant. Peak I'c has been found to be due to strong adsorption of product. The coulometric studies indicated the involvement of four electrons in reduction. The product of electroreduction has been found as hydrazo derivative which is characterized by TLC, m.p., IR and mass spectra. A tentative mechanism has been suggested to account for the formation of hydrazo product. The fifth chapter of the thesis describes electrochemical behaviour of 3-(p-sulfamoylphenylhydrazono)-2,4-pentanedione in the phosphate buffers of pH range 3.0-10.4. Experimental evidences show that this hydrazone undergoes electrooxidation as well as reduction at pyrolytic graphite electrode. The electrooxidation of 3-(p-sulfamoylphenylhydrazono)- 2,4-pentanedione at its oxidation peak la is a pH-dependent irreversible process. The Ep versus pH plot exhibited break at around pH 3.9 and 9.5. The sweep rate studies have indicated the involvement of adsorption complications in the process and limited solubility of hydrazone permitted its estimation only in the concentration range 0.1-0.5 mM. The electrooxidation occurs in a 2e, 2H+ single step to give benzenesulfonamide and 2,3,4- pentanetrione which have been identified by UV, IR, mass, NMR and melting point determination. The electroreduction of 3-(p-sulfamoylphenylhydrazono)- 2,4-pentanedione, on the other hand, has been found to occur in a 4e, 4H+ process to give sulfanilamide and 3- amino-2,3,-pentanetrione as the final products. The electrochemical oxidation of benzeneoid amino compounds has been the subject of investigation for a long time, whereas, very little attention has been paid to heterocyclic amines probably due to their resemblance with benzenoid amines. Literature survey revealed that a systematic study on electrochemical oxidation of 3-amino-5- methylisoxazole has not been carried out inspite of its importance as a basic unit of antibacterial, anti-inflammatory, analgesic and antipyretic compounds. The last chapter of the thesis deals with the electrooxidation of 3-amino-5-methylisoxazcle at pyrolytic graphite electrode using voltammetry, coulometry and spectral techniques. This study was undertaken to establish whether the isoxazole under investigation behaves like benzenoid amino compound or follow a different course of electrooxidation. The peak current versus concentration plot is a straight line in the concentration range 0.5-5.0 mM. The peak current function (ip/AcV ) value was found to be constant with sweep rate indicating the electrode reaction to be diffusion controlled in this range. Coulometric studies has shown the involvement of two electrons in oxidation. The azo compound has been found as the main oxidation product and a tentative scheme has been proposed to explain its redox behaviour.
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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