Evaluation of DNA Binding, Protein Interaction, and Cytotoxic Activity of a Mononuclear Copper(II) Complex

The reactivities towards DNA and protein of a benzimidazole derived mononuclear copper(II) complex, [Cu(EDTB)](NO3)2·C2H5OH (1) [EDTB = N,N,N′,N′‐tetrakis(2′‐benzimidazolyl methyl)‐1,2‐ethanediamine], were investigated under physiological conditions using UV/Vis absorption, fluorescence, and circular dichroism (CD). The experimental results suggest complex 1 could strongly bind to calf thymus DNA (CT‐DNA) and induce a remarkable conformational variation of DNA. The intrinsic binding constant Kb of complex 1 to DNA is 1.08(± 0.02) × 105 M–1 and the apparent binding constant Kapp is 3.9 × 106 M–1. The strong affinity was chiefly arising from intercalation of the benzimidazole aromatic rings of ligand system of 1 with the DNA base stack. Additionally, complex 1 could also interact with bovine serum albumin (BSA) and quench the intrinsic fluorescence of BSA. At higher concentration range of complex 1 (0–210 μM), the fluorescence quenching of BSA by complex 1 is a combined quenching (both dynamic and static) process; at lower concentration range of complex 1 (0–15 μM), the binding process is a single static mechanism with the binding constant (KA) ca. 105 M–1. Further, cytotoxic activity of complex 1 in vitro was evaluated against the human cervical cancer (HeLa), human lung cancer (A‐549), and human mammary cancer (MCF‐7) cell lines. The results reveal complex 1 demonstrates a significant inhibition against the three cell lines with the IC50 values falling in the 36.12–55.13 μM range.