Homo- and heteroleptic trimethoxy terpyridine–Cu(ii) complexes: synthesis, characterization, DNA/BSA binding, DNA cleavage and cytotoxicity studies

Abstract

In the current study, four novel mononuclear Cu(II) complexes with terpyridine (L) and different co-ligands (phen, bipy, and imd) were synthesized and characterized in detail, where L is 4′-(3,4,5-trimethoxyphenyl)-2,2′:6′,2′′-terpyridine. The identity and purity of all complexes were determined by elemental analysis, spectroscopic techniques (UV-vis, FTIR, ESI-MS, and EPR) and CV, including single crystal X-ray determination of three complexes ([Cu(L)(phen)](ClO₄)₂ (C-I), [Cu(L)₂](ClO₄)₂ (C-II) and [Cu(L)(imd)(ClO₄)](ClO₄) (C-IV). DNA binding studies were performed using fluorescence assay and the binding constants were calculated using the Stern–Volmer equation and the modified Stern–Volmer equation. The magnitude of K_app of all complexes was 10⁵ M⁻¹, indicating moderate intercalative binding between CT-DNA and the complexes. Agarose gel electrophoresis clearly reflected their ability to cleave a double stranded pET-28b plasmid in the presence of an external reducing agent (3-mercapto propionic acid). Steady-state fluorescence quenching was performed to understand their interactions with BSA. The studies suggested a mixed quenching mechanism with an initial static process. Furthermore, the antiproliferative activity of the complexes was evaluated against lung cancer A549 cells and primary mice splenocytes. Interestingly, the complexes show 25–200 fold greater toxicity towards the A549 cells than primary splenocytes, indicating their selectivity towards the former. The good binding behavior of all four complexes towards DNA and BSA and their cytotoxicity render these compounds promising potent anticancer drugs.