Computational insights into Ru(ii)–coumarin complexes as potential anticancer agents: a DFT, QTAIM, NCI-RDG, molecular docking and molecular dynamics approach

Abstract

Ru(II) complexes have been explored as promising candidates for novel anticancer agents, due to their significant bioactivity, selective cytotoxicity, and ability to induce apoptosis via multiple signalling pathways, with coumarin derivatives serving as effective ligands to enhance their therapeutic efficacy. DFT calculations are highly useful in comprehensively analyzing the electronic structures, and physicochemical and thermodynamic properties of these metal complexes. For example, MEP maps are used to visualize the molecular charge distribution, while NBO analysis is employed to investigate the charge transfer interactions. The donor–acceptor behaviour of the metal–ligand complexes is also examined to gain deeper insights into their electronic properties and potential reactivity. QTAIM analysis confirms that weak H-bonding and vdW interactions significantly stabilize the studied adducts, particularly [RuCl₂(yc4)₂(DMSO)₂]·2H₂O and AT/GC base pair complexes. Molecular docking is further employed to investigate the DNA-binding affinity and interaction mechanisms of these complexes, with a specific focus on AT/GC nucleobases. The molecular docking results provide insights into the stability of the adducts and reveal their preferred binding sites within DNA nucleobases. Finally, molecular dynamics simulation calculations were employed to complement DFT and docking analyses. Again, MM/PBSA free energy and H-bond analyses indicate stronger thermodynamic interactions of the [RuCl₂(yc4)₂(DMSO)₂]·2H₂O complex with AT-rich regions. Hence, this in silico study on Ru(II)–coumarin complexes offers valuable insights for the rational design of metal-based anticancer therapeutics.