Solvent‐assisted formation of ruthenium(II)/copper(I) complexes containing thiourea derivatives: Synthesis, crystal structure, density functional theory, enzyme mimetics and in vitro biological perspectives

Abstract

N,N‐[(diethylamino)(thiocarbonyl)]‐substituted benzamidine ligands have been synthesized from the reaction of N,N‐[(diethylamino)(thiocarbonyl)]benzimidoyl chloride with functionalized amines such as 2‐aminophenol and 2‐picolylamine. The reaction of N,N‐[(diethylamino)(thiocarbonyl)]‐2‐hydroxyphenylbenzamidine (H2L1) with ruthenium(II) precursor [RuHCl(CO)(PPh3)3] afforded complex 1 of the type [Ru(L1)(CO)(PPh3)2] in which the ligand coordinated in tridentate ONS mode. The reaction of H2L1 with copper precursor [Cu(CH3COO)(PPh3)2] induced C═N bond cleavage of the ligand and afforded complex 3 of the type [Cu(1,1‐DT)(Cl)(PPh3)2] (1,1‐DT = 1,1‐diethylthiourea) in which the ligand coordinated in a monodentate fashion. The ligand N,N‐[(diethylamino)(thiocarbonyl)]‐2‐picolylbenzamidine (HL2) reacted with ruthenium(II) and copper(I) precursors to form complex 2 of the type [Ru(1,1‐DT)(Cl2)(CO)(PPh3)2] and complex 3, respectively, in which the ligand underwent C═N cleavage and coordinated in a monodentate fashion via C═S group. In complexes 1 and 2, the two triphenylphosphine co‐ligands coordinated in trans position whereas, in complex 3, the two triphenylphosphine co‐ligands coordinated in cis position. All the compounds were characterized using infrared, UV–visible, (1H, 13C, 31P) NMR, ESI‐MS and elemental analyses. The molecular structures of ligand H2L1 and complexes 1–3 were determined using X‐ray crystallography, which confirmed the coordination mode of the ligands with metals. The crystal structure of complexes 1 and 2 revealed a distorted octahedral geometry around the ruthenium ion and the structure of complex 3 indicated a tetrahedral geometry around the copper ion. With the X‐ray structures, density functional theory computations were carried out to determine the electronic structure of the compounds. The interactions of complexes 1–3 with calf thymus DNA and bovine serum albumin protein were investigated using UV–visible and fluorescence spectroscopic and viscometric methods. Catecholase‐ and phosphatase‐like activities promoted by complexes 1–3 under physiological conditions have been studied. In vitro anticancer activities have been demonstrated by MTT assay, acridine orange/ethidium bromide and diamidino‐2‐phenylindole staining against various cancerous cell lines.