On mechanism of reduction on DME of some compounds with local anesthetic activity N-oxides containing tertiary amine

Abstract

It has been shown for the first time the obtaining of N-oxides of dymedrol (DMD) and bupivacaine (BVK). Bupivacaine is a local anesthetic of amide group. Dymedrol (diphenhydramine hydrochloride) is an antihistamine that reduces the effects of natural chemical histamine in the body. The N-oxides of DMD and BVK are formed during chemical oxidation with potassium peroxymonosulfate (KPMS). The first step was investigation of the optimal conditions for oxidation reaction to reach the maximum yield of final products (N-oxides). The investigated conditions were pH, time of oxidation and ratio of reagents. The needed time for oxidation of DMD and BVK is 10 min. At least two-fold excess of KPMS must be in the solution in recount to analyte concentration, but not higher than 10 -4 M. The maximum concentration of BVK and DMD N-oxides was obtained in weakly basic medium (pH 8.5–9.3). The second step was optimization of conditions for polarographic reduction of BVK and DMD N-oxides on the dropping mercury electrode (DME). The best medium for electrochemical reduction was the medium of phosphate buffer solution with pH in the range 5–6. On polarogramms it was observed only one irreversible peak in full pH range studied. The rate of electrochemical reaction is diffusion-controlled with weak adsorption of BVK, other local anesthetics (LA) (lidocaine, mepivacaine and trimecaine) and DMD N-oxides on DME surface confirmed by studying of effect of scan rates on polarogramms characteristics. The reduction potentials of peak linearly depend on solution pH. Thus, the electrochemical reduction of LA and DMD N-oxides includes protonation reaction stage. Based on literature survey and our calculations it was suggested that reduction mechanism of BVK and DMD N-oxides consist in monoelectron transfer resulting in anion-radical formation proceeding one proton adjunction. Keywords : polarography, N-oxides, local anesthetics, dymedrol, bupivacaine.