Naphthalene Derived Terpyridine Attached Copper (II) Complexes: Effect of Planarity and Steric Hinderance on DNA Interaction

The heteroleptic copper(II) complexes with mixed ligand systems, [Cu(L)(Bpy)](ClO₄)₂; 1, [Cu(L)(dmBpy)](ClO₄)₂; 2, [Cu(L)(Phen)](ClO₄)₂; 3, and [Cu(L)(dmPhen)](ClO₄)₂; 4 (where L = 4^/-(naphthalen-1-yl)-2,2^/:6^/,2^//-terpyridine), Bpy = 2,2^/-bipyridine, dmBpy = 6,6^/-dimethyl-2,2^/-bipyridine, Phen = 1,10-phenanthroline and dmPhen = 2,9-dimethyl-1,10-phenanthroline) were synthesised and characterised methodically via different analytical and spectroscopic techniques. The interactions of all complexes with double-stranded salmon sperm DNA (ss-DNA) were monitored by UV-vis spectroscopy, fluorescence spectroscopy, circular dichroism (CD) and in silico molecular docking. The binding constant (K_b) as well as Stern-Volmer constant (K_SV) values of all complexes was in the order of 10⁴ M^-1. These studies suggested that 3 is showing the highest affinity towards DNA amongst the four complexes. The in vitro DNA cleavage activity was also performed using supercoiled circular (SC) plasmid DNA. Further, the cytotoxicity and evaluation of ROS generation of all complexes were analysed using MCF7 and MDA-MB-231 cancer cell lines. The IC₅₀ values for 3 against both cancer cell lines were lowest amongst the four complexes which is in accordance with the other experimental findings. The cytotoxicity experiment was also repeated with non-cancer human cell line HEK293. Our study lays the foundation for the design of bio-inspired mixed-metal complexes, which exhibit potential for further molecular and mechanistic investigations aimed at developing cost-effective, non-platinum-based metallodrugs.