Homo- and Heteroleptic trimethoxy terpyridine-Cu(II) complexes: Synthesis, Characterization, DNA/BSA Binding, DNA Cleavage and Cytotoxicity Studies

In the current study, four novel mononuclear Cu(II) complexes with terpyridine (L) and different co-ligands (phen, bipy, 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 the complexes was determined by elemental analysis and other spectroscopic techniques (UV-vis spectroscopy, FTIR, ESI-MS, EPR, 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). The DNA binding studies were performed using fluorescence assay and the binding constants were calculated using Stern-Volmer equation as well as modified Stern-Volmer equation. The magnitude of Kapp of all the complexes was 105 M-1, indicating moderate intercalative binding between CT-DNA and complexes. The agarose gel electrophoresis clearly reflected upon the ability to cleave double stranded pET-28b plasmid in presence of external reducing agent (3-mercapto propionic acid). Steady-state fluorescence quenching was performed to understand the interactions with BSA. The studies suggested a mixed quenching mechanism with an initial static process. Further, antiproliferative activity of the complexes was evaluated against lung cancer A549 cells as well as primary mice splenocytes. Interestingly, the complexes show 25-200 folds greater toxicity towards A549 cells than primary splenocytes indicating selectivity towards the former. The good binding behavior of all the four complexes with DNA and BSA, and the cytotoxicity data renders these compounds as promising potent anticancer drugs.