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(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.