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

摘要

New [RuCl2(1,5cod)(L1)] (1), [RuCl2(1,5cod)(L2)] (2), [RuCl2(1,5cod)(L3)1 (3), [RuCl2(1,5cod)(L4)] (4), [RuCl2(1,5cod)(L5)] (5) (L = (p-R-N-(pyridin-2-ylmethylene)aniline), R = H (L1), Cl (12), OCH3 (L3), CH3 (L4), L5 = (9-ethyl-N-(pyridin-2-ylmethylene)9H-carbazole-3-amine and 1,5cod = eta(4)-cyclooctadiene) complexes were synthesized and characterized by H-1 and C-13 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 pi-bonds of the cydooctadiene 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 (K-b) 1.77 x 10(5) dm(3) mol(-1) (1), 1.07 x 10(5) dm(3) mol(-1) (3) and 1.07 x 10(5) dm(3) mol(-1) (5) respectively. Circular dichroism (CD) studies revealed decreased alpha-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. (C) 2016 Elsevier Ltd. All rights reserved.