Fluorescent Copper(II) Complexes of Asymmetric Bis(Thiosemicarbazone)s: Electrochemistry, Cellular Uptake and Antiproliferative Activity

Two new Cu(II) complexes, of the type CuL1 and CuL2, of asymmetric bis(thiosemicarbazone) ligands were synthesized where L1=(E)‐2‐((E)‐3‐(2‐((E)‐2‐(naphthalen‐1‐yl methylene) hydrazine carbonothioyl) hydrazono) butan‐2‐ylidene) hydrazine carbothioamide and L2=(E)‐N‐methyl‐2‐(3‐oxobutan‐2‐ylidene) hydrazine carbothioamide and characterized by elemental analysis, HRMS, IR, EPR and cyclic voltammetry. The complexes undergo reversible one‐electron reduction at E1/2=∼−0.52 V vs Ag/AgCl. Interaction of CuL1 and CuL2 with human serum albumin monitored by fluorescence spectroscopy revealed static quenching with binding constants of the order of 105 M−1. Their cellular uptake and cytotoxicity were studied on MCF‐7 and NIH‐3T3 cells. The results indicate that CuL1 is more cytotoxic owing to its cellular permeability. Two new fluorescent bis(TSC) Cu(II) complexes, CuL1 and CuL2, have been demonstrated as effective antiproliferative agents for MCF‐7 breast cancer cell line. Both the complexes show negative redox potential of ∼−0.52 V vs Ag/AgCl electrode suggesting their possible accumulation in hypoxic tumor cells. Both the complexes exhibited higher cytotoxicity than cisplatin. Cellular uptake and cytotoxicity studies on MCF‐7 and NIH‐3T3 cells lines revealed that CuL1 is more selective towards the cancer cells.