Interaction of bio-relevant thio-ether and thiols with dinuclear Pd(II) complex: Their kinetics, mechanism, bioactivity in aqueous medium and molecular docking

Abstract

The kinetics of interaction between [Pd(pic)(OH)]2(ClO4)2, 2 (pic= 2-aminomethylpyridine) with the selected ligands (L): DL-methionine (DL-meth), L-cysteine (L-cys) and N-acetyl-L-cysteine (N-ac-Lcys) have been studied under pseudo-first order condition using stopped-flow spectrophotometer in aqueous medium as a function of [complex 2] as well as [ligand], pH, and temperature at constant ionic strength. The ligand dependent second order reaction is found to take place in two consecutive steps in accordance with the rate law, k(obs) = k1[L]2 in which all these three reactions follow the third order kinetics. The first step of the reaction is dependent, while the second step is independent of [ligand] in all the cases. The activation parameters, :H# and :S# for the two-step reactions are evaluated from Eyring equation. An associative mode of activation (an associative mechanism) in the transition state along is proposed for all these substitution processes. Complex 2 and its substituted products [Pd(pic)DL-meth]+ 3; [Pd(pic)L-cys] 4; and [Pd(pic)N-acL-cys] 5 are characterized by UV-Vis, FT-IR, 1H-NMR and ESIMass spectroscopic method. Complex 2 - 5 show remarkable anticancer property on HeLa cell of about 70% at high concentration when compared to cis-platin and observed antibacterial property on both the gram positive (Bacillus subtilis) and gram negative (E.coli Dh5α) bacteria. In addition, DNA interaction with plasmid DNA is observed and computational molecular docking studies were carried out with an aim to establish the binding mode of complex 2 with B-DNA.