Binding interaction, conformational change, and molecular docking study of N-(pyridin-2-ylmethylene)aniline derivatives and carbazole Ru(II) complexes with human serum albumins

Abstract

New [RuCl2(1,5cod)(L1)] (1), [RuCl2(1,5cod)(L2)] (2), [RuCl2(1,5cod)(L3)] (3), [RuCl2(1,5cod)(L4)] (4), [RuCl2(1,5cod)(L5)] (5) (L=(p-R-N-(pyridin-2-ylmethylene)aniline), R=H (L1), Cl (L2), OCH3 (L3), CH3 (L4), L5=(9-ethyl-N-(pyridin-2-ylmethylene)9H-carbazole-3-amine and 1,5cod=η4-cyclooctadiene) complexes were synthesized and characterized by 1H and 13C NMR, melting point analysis, elemental analysis, HR-Mass spectrometry, FT-IR and UV–Vis spectroscopy. The single crystal X-ray structures of complexes 1, 2 and 3 revealed coordination of the ligands to the Ru(II) center in a bidentate manner via the N atoms. The geometry around the Ru(II) center is pseudooctahedral with the two Cl atoms and the π-bonds of the cyclooctadiene occupying the coordination sites. Interactions of Ru(II) complexes 1–5 with human serum albumins (HSA) were investigated using UV–Vis, synchronous emission and circular dichroism spectroscopy. The results demonstrated that the Ru(II) complexes 1–5 have significantly strong interaction with HSA proteins. Complexes 1, 3 and 5 showed moderate-to-high binding constants (Kb) 1.77×105dm3mol−1 (1), 1.07×105dm3 mol−1 (3) and 1.07×105dm3mol−1 (5) respectively. Circular dichroism (CD) studies revealed decreased α-helix content within HSA upon interaction with complexes 1–5, suggesting a conformational change of the HSA secondary structure. Also, molecular docking studies were carried out to identify the binding models of the HSA–Ru complexes and binding energy of complexes 1–5 in HSA, which further revealed the contribution of amino acid residues of HSA in Ru(II) complex binding.