Electrochemical and Spectroscopic Investigations of Bismuth Pharmaceuticals
Authors: Pena Dominik , Cheek Graham 
Published: July 2021

Introduction
The use of bismuth compounds as pharmaceutical agents for gastric maladies has a long history.1 Many techniques have been used to characterize the mode of operation of these compounds; however, electrochemical methods have not been fully utilized in this regard. The sulfhydryl side chain of the amino acid L-cysteine and related compounds can form complexes with bismuth(III) ions,1 so that the effect of L-cysteine added to solutions of bismuth(III) compounds is expected to greatly affect the electrochemical behavior of this system. Previous work in this laboratory has involved electrochemical investigation of both L-cysteine in various media2, and the interaction of bismuth(III) compounds with L-cysteine.3 The present work involves the interaction of L-cysteine with bismuth-containing pharmaceuticals.
Results and Discussion
Bismuth(III) nitrate has been chosen for the initial studies, followed by work with bismuth(III) citrate and bismuth(III) salicylate, both of which are used in commonly available pharmaceuticals. Our studies have been carried out in 0.100 M HCl and 0.100 M HNO3 in order to simulate the pH level of gastric contents. The electrochemical techniques cyclic voltammetry and square wave voltammetry were used in this work, and some comparisons between the results are intended for presentation. Voltammetric scans have been carried out at both glassy carbon and boron-doped diamond electrodes in order to avoid the reduction of protons, which would occur at platinum and gold electrodes. Although the solubility of Bi(NO3)3 in 0.10 M HNO3 is rather low, initial studies revealed that the addition of L-cysteine to the solution greatly increased the solubility of bismuth(III) nitrate, as seen by an increase in the bismuth(III) reduction current as well as the subsequent stripping current of the bismuth deposit.
Bismuth(III) salicylate was found to be soluble at the 1 mM level in 0.100 HNO3, and L-cysteine additions produced potential shifts in the voltammetric processes for the bismuth(III) system. These results support the complexation of bismuth(III) salicylate by L-cysteine, even under these very acidic conditions. This work has now been extended to bismuth(III) citrate in 0.10 M HCl, with overall similar results. Studies in pH 7.4 MOPS buffer have also been carried out to simulate pH levels in other parts of the human body. The electrochemical behavior of bismuth(III) nitrate in pH 7.4 MOPS (3-(N-morpholino)propanesulfonic acid)4 buffer was investigated in this regard. Whereas bismuth(III) nitrate (nominal 1.0 mM) was essentially insoluble in this medium, additions of L-cysteine produced voltammetric currents typical of the 1 mM concentration level. As at pH 1.00, initial reduction of bismuth(III) was followed by bismuth stripping peaks at more positive potentials. This behavior supports the complexation of bismuth(III) ion by L-cysteine. Further evidence of this complexation was found by UV-VIS studies of bismuth(III) nitrate in pH 7.4 MOPS buffer with incremental additions of L-cysteine. An absorbance band at 325 nm appeared as L-cysteine was added, the absorbance of which remained constant after the 1:2 Bi3+: L-cysteine point. These results indicate formation of Bi(Cys)2 under these conditions. As a whole, the present studies indicate the ability of bismuth(III) compounds to interact with L-cysteine at pH 1.0 and pH 7.4.
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