The role of<i>N,N</i>-chelate ligand on the reactivity of (η⁶-<i>p</i>-cymene)Ru(II) complexes: kinetics, DNA and protein interaction studies

Abstract

This study reports the kinetic studies of aqua complexes (Ru1–Ru6) as well as the calf-thymus DNA (CT-DNA) and bovine serum albumin binding studies of their chloro derivatives (Ru7–Ru11). The rate of substitution of the aqua ligand(s) in Ru1–Ru6 by thiourea nucleophiles (thiourea, N,N-dimethylthiourea and N,N,N′,N′-tetramethylthiourea) in 0.1 M HClO4/NaClO4 aqueous medium was investigated as a function of nucleophile concentration and temperature under pseudo-first order conditions. The reactivity of the binuclear and mononuclear complexes decreased in the order Ru3 > Ru4 > Ru5 > Ru6 and Ru1 > Ru2, respectively. The trend in reactivity of the binuclear complexes showed a dependence on the electronic and static factors of the rigid N,N-chelate bridging ligand in the complexes. The reactivity trends are well supported by the DFT-calculated data. The activation parameters (ΔH≠ > 0, ΔS≠ < 0) for the substitution process in all complexes support an associative mechanism of activation. The complexes effectively bind to CT-DNA via intercalation and this was corroborated by the molecular docking results. Likewise, the complexes bind favorably with bovine serum albumin. The order of CT-DNA and bovine serum albumin interactions with these complexes are in line with the trends in aqua ligand substitution.