Synthesis, crystal structure and Hirshfeld surface analysis of copper(II) complexes: DNA- and BSA- binding, molecular modeling, cell imaging and cytotoxicity

In order to explore the structure–activity relationship of complexes, two copper(II) complexes, [Cu(dimethoxybpy)2](PF6)2 (1) and [Cu(dimethylbpy)2Cl]PF6 (2) (dimethoxybpy is 4,4′-dimethoxy-2,2′-bipyridine and dimethylbpy is 4,4′-dimethyl-2,2′-bipyridine), have been synthesized and characterized by several physicochemical techniques. The single-crystal X-ray structures of 1 and 2 exhibit distorted square-planar and distorted square-pyramidal structure, respectively. The Hirshfeld surface analysis and the associated 2D fingerprint plots of 1 and 2 have been also studied to evaluate intermolecular interactions. The DNA binding properties of 1 and 2 have been investigated by absorption and emission spectra, viscosity, cyclic voltammetry, circular dichroism and competitive DNA–binding studies, which indicate that the complexes interact with DNA through partial intercalation. The results of absorption and emission spectra, synchronous fluorescence and circular dichroism show that the complexes bind with BSA. The results exhibit that the complex 1 has stronger binding ability to DNA and BSA than the complex 2. Molecular docking technique has been used to evaluate and understand the interaction mode of 1 and 2 with DNA and BSA. The in vitro cytotoxicity of the complexes against MCF-7, A-549 and HT-29 cell lines has been assayed by MTT method. The complexes exhibit significant cytotoxicity in cell lines with IC50 values ranging from 1.5 to 53 μM. Based on the results of cytotoxicity, it would appear that the complex 2 has better cytotoxicity than the complex 1 under the same experimental conditions, suggesting that the hydrophobicity of methyl groups on the complex enhances the anticancer activity. The results of the microscopic analyses of cancer cells confirm the results of cytotoxicity.