The role of N,N-chelate ligand on the reactivity of (η⁶-p-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.

Keywords:

• Ruthenium
• kinetics
• substitution
• thiourea
• nucleophile
• binding
• CT-DNA
• bovine serum albumin

Acknowledgements

We thank Craig Grimmer and Caryl Janse van Rensburg for characterization of the complexes.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

We gratefully acknowledge the financial support accorded to Gershom Mutua by Masinde Muliro University of Science and Technology (Kenya) and University of KwaZulu-Natal (South Africa).