Tris-chelated complexes of nickel(II) with bipyridine derivatives: DNA binding and cleavage, BSA binding, molecular docking, and cytotoxicity.

Two nickel(II) complexes with substituted bipyridine ligand of the type [Ni(NN)](ClO), where NN is 4,4'-dimethyl-2,2'-bipyridine (dimethylbpy) () and 4,4'-dimethoxy-2,2'-bipyridine (dimethoxybpy) (), have been synthesized, characterized, and their interaction with DNA and bovine serum albumin (BSA) studied by different physical methods. X-ray crystal structure of shows a six-coordinate complex in a distorted octahedral geometry. DNA-binding studies of and reveal that both complexes sit in DNA groove and then interact with neighboring nucleotides differently; undergoes a partial intercalation. This is supported by molecular-docking studies, where hydrophobic interactions are apparent between and DNA as compared to hydrogen bonding, hydrophobic, and interactions between and DNA minor groove. Moreover, the two complexes exhibit oxidative cleavage of supercoiled plasmid DNA in the presence of hydrogen peroxide as an activator in the order of >. In terms of interaction with BSA, the results of spectroscopic methods and molecular docking show that binds with BSA only via hydrophobic contacts while interacts through hydrophobic and hydrogen bonding. It has been extensively demonstrated that the nature of the methyl- and methoxy-groups in ligands is a strong determinant of the bioactivity of nickel(II) complexes. This may justify the above differences in biomolecular interactions. In addition, the cytotoxicity of the complexes on human carcinoma cells lines (MCF-7, HT-29, and U-87) has been examined by MTT assay. According to our observations, and display cytotoxicity activity against selected cell lines. Communicated by Ramaswamy H. Sarma.