Kinetics and mechanism of interaction of Pt(II) complex with bio-active ligands and <i>in vitro</i> Pt(II)-sulfur adduct formation in aqueous medium: bio-activity and computational study

<p>Kinetics of interaction between [Pt(pic)(H<sub>2</sub>O)<sub>2</sub>](ClO<sub>4</sub>)<sub>2</sub>, <b>2</b> (where pic = 2-aminomethylpyridine) with the selected ligands DL-methionine (DL-meth) and DL-penicillamine (DL-pen) have been studied spectrophotometrically in aqueous medium separately as a function of [<b>2</b>] as well as [ligand], pH and temperature at constant ionic strength. The association equilibrium constants (<i>K</i><sub>E</sub>) for the outer sphere complex formation have been evaluated together with the rate constants for the two subsequent steps. Activation parameters (enthalpy of activation ΔH<sup>≠</sup> and entropy of activation ΔS<sup>≠</sup>) were calculated from the Eyring equation. An associative mechanism of substitution is proposed for both reactions on the basis of the kinetic observations, evaluated activation parameters, and spectroscopic data. Structural optimizations, HOMO-LUMO energy calculation, and Natural Bond Orbital (NBO) analysis of <b>2</b>–<b>4</b> were carried out with Density Functional Theory. Bonding mode of thiol and thio-ether is confirmed by spectroscopic analyses and NBO calculation. Cytotoxic properties of <b>2</b>–<b>4</b> were explored on A549 carcinoma cell lines; DNA-binding properties of the complexes were also investigated by gel electrophoresis.</p>