Combined computational and experimental studies on cysteine-sulfadiazine adduct formation

The electrochemical characterization of sulfadiazine-cysteine (SD-CYS) adduct formation was performed in phosphate buffer (pH 7) on the basis of voltammetric current and peak potential measurements. Due to the association of cysteine with sulfadiazine, the reduction peak currents of mercuric and mercurous cysteine thiolates decreased and their peak potentials simultaneously shifted to less negative potentials. By using the current changes of mercurous cysteine thiolate, it was determined that cysteine and sulfadiazine are associated with a 1:1 stoichiometry with a conditional association constant of 1.99 ×104 M−1 . In addition to experimental studies, a computational approach was carried out to study the geometrical parameters, electron densities, and UV-Vis absorption spectra of sulfadiazine and SDCYS adduct in water. Calculated (B3LYP/6-311++G(d,p) level) and experimental UV-Vis absorption spectra of the compounds were found to be in good agreement in water. The computational study suggests that cysteine bound to the C(5) on the pyrimidine ring via SH-group nucleophilic attack. Computational results reveal that sulfadiazine and its derivatives effectively bind cysteine and may lead to new molecules/drugs to target cysteine.