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 Ag 2 O, forming the NHC-silver bromide in situ followed by transmetalation with dimeric p-cymene ruthenium(II) dichloride. In an analogous manner the NHCgold(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 NHCgold(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 IC 50 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 IC 50 values against Caki-1 of >500, 94 (±5), 93 (±2), 170 (±20), 39 (±5), and 13 (±2) μM and against

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The antimicrobial drug candidate 1,3-dibenzyl-4,5-diphenyl-imidazol-2-ylidene silver(I) acetate (SBC3) was evaluated for its ability to function in vivo using larvae of Galleria mellonella. A SBC3 concentration of 25 lg/ml inhibited the growth of Staphylococcus aureus by 71.2 % and Candida albicans by 86.2 % in vitro. Larvae inoculated with 20 ll of SBC3 solution showed no ill effects up to a concentration of 250 lg/ml but administration of 500 lg/ml resulted in a 40 % reduction in larval survival and administration of a dose of 1,000 lg/ml resulted in total larval death at 24 h. Larvae inoculated with S. aureus or C. albicans and subsequently administered SBC3 showed increased survival. Administration of SBC3 to larvae did not boost the insect immune response as indicated by lack of an increase in the density of circulating haemocytes (immune cells). The abundance of a number of proteins involved in the insect immune response was reduced in larvae that received 20 ll SBC3 solution of 100 lg/ml. This is the first demonstration of the in vivo activity of SBC3 against S. aureus and C. albicans and demonstrates that SBC3 does not stimulate a non-specific immune response in larvae.

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