Heteroleptic tris-chelate ruthenium(II) complexes of N,N-disubstituted-N′-acylthioureas: Synthesis, structural studies, cytotoxic activity and confocal microscopy studies

Abstract

Ruthenium complexes have been assessed as anti-tumor agents against cancer cells. In this project, new heteroleptic ruthenium(II) complexes with general formulae [Ru(L)(bipy)(dppb)](PF 6) (where L = N,N-disubstituted-N 0-acylthiourea, bipy = 2,2 0-bipyridine and dppb = 1,4-bis(diphenylphosphino)butane) were synthesized and characterized by elemental analysis, IR and NMR (1 H and 31 P{ 1 H}) spectroscopies, molar conductivity measurements and single crystal X-ray diffractometry. The IR and NMR data suggest the coordination of the ligands to the Ru(II) metal center through the thiocarbonyl and carbonyl groups. The structures of the new complexes were further studied by X-ray crystallography, which confirmed the coordination of the ligands with the metal through the sulfur and oxygen atoms, leading to the formation of distorted octahedral complexes. The N,N-disubstituted-N 0-acylthioureas and their complexes were screened with respect to their in vitro cytotoxicity. All compounds exhibited considerable antiproliferative activity against MCF-7 (human breast tumor cells ATCC HTB-26), DU-145 (human prostate tumor cells ATCC HTB-26), and relatively low toxicity against fibroblast L929 cells (health cell line from mouse ATCC CCL-1). A preliminary study regarding the mechanism of action of these compounds by confocal microscopy shows alterations of the actin filaments leading to modifications in cytoskeletal supporting the cell death and that the cell nucleus is not main target of these complexes.

The trans -[Ru(PPh 3 ) 2 ( N , N -dimethyl- N ′-thiophenylthioureato-k 2 O,S)(bipy)]PF 6 complex has pro-apoptotic effects on triple negative breast cancer cells and presents low toxicity in vivo

“…For the complex (3) the distance of CeS, 1.723(7) Ǻ, is longer than the CeS bond distance of neutral species (1.661-1.676 Å), and the angles and distances found for the complex (3) are comparable to those found for other metalo-acylthiourea compounds [34,[40][41][42]. The distance of CeO, 1.270(8) Å is a little longer than those found for typical C]O bonds, indicating its double-bond character, which is an evidence of resonance character in the ring formed by SeRueO, in the complex [34,[40][41][42].…”

Mono(2,2′‐bipyridyl)RuII Complex with Four Dimethyl Sulfoxide Ligands as Precursor for cis‐Bis‐heteroleptic RuII Complex: Syntheses, Structures, and Substitution Reactions

“…The Bz ligand could be released from the latter by photo‐irradiation in MeCN to form [RuCl 2 (N‐N)(MeCN) 2 ], along with a small amount of [RuCl(N‐N)(MeCN) 3 ]Cl. In 2017, Barolli and co‐workers reported new heteroleptic tris‐chelate Ru II complexes, [Ru(L‐L)(bpy)(dppb)](PF 6 ) 2 [L‐L = N , N′ ‐disubstituted‐ N′ ‐acylthiourea; dppb = 1,4‐bis(diphenylphosphanyl)butane], starting from the reaction of of [RuCl 2 (dppb)(PPh 3 ) 2 ] with bpy in dichloromethane to generate the penultimate intermediate, cis ‐[RuCl 2 (dppb)(bpy)] . In this case, the synthesis of the heteroleptic bis‐chelate Ru II complexes could be achieved due to the special mono(dppb)Ru II complex and use of dichloromethane.…”

Crystal Structure and Cyclic Voltammetric Studies on the Metal Complexes of N-(Dimethylcarbamothioyl)-4-fluorobenzamide

“…The synthesis of new benzoylthiourea compounds also becomes widespread due to their potential application in biological [8][9][10][11][12] and analytical chemistry [13][14][15][16][17]. The ability of thiourea derivatives to complex with transition metal cations is well known [18,19].…”