Biophysical characterization of centrosymmetric doubly bridged Cu(ii) complexes: comparative DNA/BSA binding and potential applications

Abstract

Triple-negative breast cancer (TNBC) lacks receptors and represents the most aggressive variant of the disease, rendering treatments exceedingly challenging and limiting the availability of targeted therapeutics. In line with more effective targeted therapies, in the present study, two copper complexes, [Cu₂(L1)₂Cl₂] (complex 1) and [Cu₂(L2)₂Cl₂] (complex 2), with N, N, O donor Schiff base ligands, where L1 = 4-bromo-2-((2-(pyridine-2-yl)ethylimino)methyl)phenol and L2 = 4-chloro-2-((2-(pyridine-2-yl)ethylimino)methyl)phenol, were synthesized and subjected to various studies to explore the structural insights, DNA/BSA binding interactions, and anti-breast cancer activity in the MDA-MB-231 cell line. The crystal structures of the complexes were determined using single-crystal X-ray diffraction, revealing that both complexes are centrosymmetric, with their inversion centers located between the two copper atoms at the center of mass of the complexes. DNA binding studies showed that complex 1 likely interacted with DNA through a partial intercalation-binding mode, while complex 2 bound via a partial groove-binding mode. Additionally, both complexes exhibited a single, static quenching mechanism in their binding interactions with BSA. Complex-2 exhibited greater cytotoxicity with an IC₅₀ of 34.66 μg mL⁻¹ compared with complex-1 (81.667 μg mL⁻¹). However, complex-1 induced a stronger apoptotic response, with 25.7% early and 58.9% late apoptotic cells, whereas complex-2 resulted in 30.9% early and only 17.8% late apoptotic cells. Both complexes showed anti-proliferative and anti-migratory effects in colony formation and wound healing assays, with complex-1 more effectively suppressing cell motility and wound closure. Complex-1 demonstrated excellent biocompatibility with no red blood cell damage compared with complex-2, which showed mild hemolytic activity, indicating the potential of complex-1 for safe intraperitoneal and oral delivery.