Novel Ruthenium(II) and Gold(I) NHC Complexes: Synthesis, Characterization, and Evaluation of Their Anticancer Properties

Abstract

The synthesis, characterization, and biological evaluation of novel Ru(II)- and Au(I)-N-heterocyclic carbenes is reported. The NHC-ruthenium(II) complexes (1–6) were synthesized by reacting the appropriately substituted imidazolium bromides with Ag2O, forming the NHC-silver bromide in situ followed by transmetalation with dimeric p-cymene ruthenium(II) dichloride. In an analogous manner the NHC-gold(I) chloride complexes (NHC-Au(I)Cl) 7–9 were synthesized, utilizing dimethylsulfido gold(I) chloride as the transmetalating agent. The ligand exchange on the NHC-gold(I) chlorides was achieved by either reacting the complexes with silver acetate to yield the NHC-gold(I) acetates (NHC-Au(I)OAc) 10–12 or reacting the NHC-gold(I) chlorides under basic conditions with 2′,3′,4′,6′-tetra-O-acetyl-1-thio-β-d-glucopyranose (SR) to give the NHC-gold(I)-(2′,3′,4′,6′-tetra-O-acetyl-β-d-glucopyranosyl-1-thiolate) complexes (NHC-Au(I)SR) 13–15. The Ru(II)-NHC complex 1 and the Au(I)-NHC complex 9 were characterized by single-crystal X-ray diffraction. Also the IC50 values of these 15 complexes were determined by an MTT-based assay against the human cancer cell lines Caki-1 (renal) and MCF-7 (breast). The Ru(II) complexes 1–6 revealed the following IC50 values against Caki-1 of >500, 94 (±5), 93 (±2), 170 (±20), 39 (±5), and 13 (±2) μM and against MCF-7 of >500, 80 (±15), 19 (±1), 7.1 (±1.2), 2.4 (±0.7), and 7.0 (±1.2) μM, respectively. IC50 values of 67 (±7), 16 (±2), 41 (±1), 31 (±2), 42 (±5), 18 (±1), 14 (±2), 17 (±2), and 58 (±2) μM against Caki-1 and 8.4 (±0.4), 30 (±3), 12 (±1), 23 (±3), 12 (±1), 25 (±3), 6.1 (±1.5), 9.3 (±1.6), and 14 (±2) μM against MCF-7 were found for the Au(I) complexes 7–15.