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

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(1) 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-beta-D-glucopyranose (SR) to give the NHC-gold(I)-(2',3',4',6'-tetra-O-acetyl-beta-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) mu M and against MCF-7 of >500, 80 (+/- 15), 19 (+/- 1), 7.1 (+/- 1.2), 2.4 (+/- 0.7), and 7.0 (+/- 1.2) mu M, respectively. IC50 values of 67 (+/- 7), 16 (+/- 2), 41 (+/- 1), 31 (+/- 2), 42 (+/- 5), 18 (+/- 1), 14 (+/- 2), 17 (+/- 2), and 58 (+/- 2) mu M 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) mu M against MCF-7 were found for the Au(I) complexes 7-15.