Experimental and computational study of Ni(II) and Zn(II) complexes of isatin-3-thiosemicarbazone: Structure, biological activity and ct-DNA binding study

Reaction of ssatin-3-thiosemicarbazone (H2itsc) with nickel(II) and zinc(II) acetate in a 1:2 (M : L) molar ratio yielded the complexes of stoichiometry, [M(Hitsc)2] (M = Ni, 1 and Zn, 2). Complexes were characterized using FTIR, elemental analysis, NMR (1H and 13C) spectroscopy, mass spectrophotometry and X-ray crystallography. In complex 1, two isatin-3-thiosemicarbazone ligands are attached to Ni(II) through O, N, Sdonor atoms in trans position to form octahedral geometry, whereas in complex 2, two thio- ligands are attached to ZnII via N, Satoms to give distroted tetraderal geometry. Compounds were evaluated for various biological activities (anti- tubercular and anticancer activity). Molecular docking studies and DNA (PDB ID: 1BNA) have supported the experimental data with minimum binding energies of-6.6 kcal/mol (H2itsc),-11.0 kcal/mol (1) and-9.7 kcal/ mol (2). The bioavailability of most active compound (2) was confirmed by its strong binding affinities with HSA (binding constant = 2.01x105 M- 1). The binding interaction of 2 with ct-DNA was also checked using UV-visible and fluorescence spectroscopy. A high quenching of 91-94 % obtained in emission peak of ct-DNA on addition of 2 indicates its strong binding. A high binding constant of 6.5x105 M- 1 with 0.94 binding sites agrees with the experimental anticancer activity.