Experimental and Theoretical Studies on Piperidine Based Heteroleptic Schiff base Ni(II) and Cu(II) Complexes Investigating DNA/Protein Binding and Anticancer Activities

Abstract

Two versatile heteroleptic Ni(II) and Cu(II) complexes, namely [Ni(L)(µ1,1-N3)(DMF)]2 (1) and [Cu(L)(2,2′-bpy)] (ClO4) (2) [HL = (E)-4-bromo-2-(((piperidine-2-ylmethyl)imono)methyl)phenol), 2,2′-bpy = 2,2′-bipyridine], have been synthesized and characterized meticulously through different experimental analyses. Single-crystal X-ray diffraction analyses reveal that the varying nuclearity of two complexes can be attributed to the different binding modes (bridging and chelating) of the coligand residues. Following their successful synthesis, both complexes are exploited to check their DNA and protein binding efficacy as a primary task towards biomedical applications, particularly in anticancer activities. Different biophysical studies confirm their strong DNA and protein binding ability. The electronic absorption spectral studies indicate remarkably high binding constant values (order ~ 105) for both complexes in their interactions with DNA and HSA. Complexes 1 and 2 show different binding modes with DNA as revealed from various experimental observations, including fluorescence displacement assays and DNA melting studies. The determined thermodynamic parameter values for complex-DNA/HSA interaction support the spontaneous interaction of the complexes towards DNA and HSA. A theoretical approach using molecular docking studies successfully explained the fact that how structural diversity of the complexes influences the interaction ability of the complexes to biomacromolecules and validates the experimental findings. In continuation, the cytotoxic effect of both complexes is assessed on HeLa (cervical cancer cell) and WI32 fibroblast (normal cell) cell lines via a dose-dependent manner. The LD50 values display higher anticancer properties of Complex 2 compared to Complex 1. Additionally, Complex 2 shows effective DNA cleavage activity. Finally, the ROS generation ability and apoptotic cell death mechanism induced by complex 2 are also confirmed by staining studies.