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

Abstract

<p>Two nickel(II) complexes with substituted bipyridine ligand of the type [Ni(NN)₃](ClO₄)₂, where NN is 4,4′-dimethyl-2,2′-bipyridine (dimethylbpy) (<b>1</b>) and 4,4′-dimethoxy-2,2′-bipyridine (dimethoxybpy) (<b>2</b>), have been synthesized, characterized, and their interaction with DNA and bovine serum albumin (BSA) studied by different physical methods. X-ray crystal structure of <b>1</b> shows a six-coordinate complex in a distorted octahedral geometry. DNA-binding studies of <b>1</b> and <b>2</b> reveal that both complexes sit in DNA groove and then interact with neighboring nucleotides differently; <b>2</b> undergoes a partial intercalation. This is supported by molecular-docking studies, where hydrophobic interactions are apparent between <b>1</b> and DNA as compared to hydrogen bonding, hydrophobic, and <i>π–π</i> interactions between <b>2</b> 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 <b>1 </b>><b> 2</b>. In terms of interaction with BSA, the results of spectroscopic methods and molecular docking show that <b>1</b> binds with BSA only via hydrophobic contacts while <b>2</b> 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 <i>in vitro</i> 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, <b>1</b> and <b>2</b> display cytotoxicity activity against selected cell lines.</p> <p></p> <p>Communicated by Ramaswamy H. Sarma</p