Copper(II) complexes with N′-methylsarcosinamide selective for human bladder cancer cells

Abstract

Two copper(II) complexes, [CuCl2(SarMeam)2]·H2O (1) and [Cu(NO3)2(SarMeam)2] (2) were obtained by reactions of N′-methylsarcosinamide (SarMeam) with copper(II) chloride and copper(II) nitrate in aqueous solutions. The complexes were characterized by X-ray crystallography, IR and UV-Vis spectroscopy, thermal analysis (TG-DTA) and DFT calculations. The octahedral coordination environments around the copper(II) ions in complexes 1 and 2 consisted of two N,O-bidentate N′-methylsarcosinamide ligands and two chloride or nitrate ions, respectively, forming trans isomers. The [CuCl(H2O)(SarMeam)2]+ and [Cu(H2O)2(SarMeam)2]2+ species formed upon dissolution of 1 by successive substitution of coordinated chloride ions with water molecules, while dissolution of 2 led exclusively to the formation of [Cu(H2O)2(SarMeam)2]2+. [Cu(OH)(H2O)(SarMeam)2]+ species formed in basic solutions by deprotonation of coordinated ligands and then transformed to a planar [Cu(SarMeam−H)2]. Complexes 1 and 2 decomposed in highly acidic or basic solutions, giving [Cu(H2O)6]2+ or Cu(OH)2, respectively. The water-soluble complexes 1 and 2 were biologically evaluated and tested on human bladder cancer T24 and UM-UC-3 cell lines and a panel of Gram-negative and Gram-positive bacteria. They showed excellent potency towards human bladder cancer T24 cell line and no activity against bacterial strains. At the same time no toxicity was noticed on normal human cells, as observed by the cell viability and comet assay on peripheral blood leukocytes.