Theoretical analysis of trans-[PtCl2(NH3)(thiazole)] and trans-[PtCl2(thiazole)2] binding to biological targets - Factors influence binding kinetics and adduct stability

Full reaction energy profiles for trans-[PtCl2(NH3)(thiazole)] and trans-[PtCl2(thiazole)(2)] binding to sulfur- and nitrogen-containing biorelevant ligands were constructed by the density functional theory (DFT) method. Calculated results demonstrate that trans-platinum complexes can interact with biological targets, affording cis and trans products via very similar transition states. For different substituents, sulfur-containing ligands constitute kinetically preferred targets for platination, whereas the platination of nitrogen-containing ligands is more favorable thermodynamically. This is consistent with previous experimental studies. Calculated results also suggest that the trans effect, the influence of the ligand, the size of the ligand, and hydrogen bonding play important roles in binding kinetics and stabilizing adducts.