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

N-Heterocyclic carbene (NHC) complexes bromo(1,3-dibenzyl-1,3-dihydro-2H-imidazol-2-ylidene)silver(I) (2a), bromo[1-(4-cyanobenzyl)-3-methyl-1,3-dihydro-2H-imidazol-2-ylidene]silver(I) (2b), and bromo[1-(4-cyanobenzyl)-3-methyl-1,3-dihydro-2H-benzimidazol-2-ylidene]silver(I) (2c) were prepared by the reaction of 1,3-dibenzyl-1H-imidazol-3-ium bromide (1a), 3-(4-cyanobenzyl)-1-methyl-1H-imidazol-3-ium bromide (1b), and 3-(4-cyanobenzyl)-1-methyl-1H-benzimidazol-3-ium bromide (1c), respectively, with silver(I) oxide. NHC Complexes chloro(1,3-dibenzyl-1,3-dihydro-2H-imidazol-2-ylidene)gold(I) (3a), chloro[1-(4-cyanobenzyl)-3-methyl-1,3-dihydro-2H-imidazol-2-ylidene]gold(I) (3b), and chloro[1-(4-cyanobenzyl)-3-methyl-1,3-dihydro-2H-benzimidazol-2-ylidene]gold(I) (3c) were prepared via transmetallation of corresponding (bromo)(NHC)silver(I) complexes with chloro(dimethylsulfido)gold(I). The complex 3a was characterized in two polymorphic forms by single-crystal X-ray diffraction showing two rotamers in the solid state. The cytotoxicities of all three bromo(NHC)silver(I) complexes and three (chloro)(NHC)gold(I) complexes were investigated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bormide (MTT)-based preliminary in vitro testing on the Caki-1 cell line in order to determine their IC 50 values. (Bromo)(NHC)silver(I) complexes 2a -2c and (chloro)(NHC)gold(I) complexes 3a -3c were found to have IC 50 values of 27 AE 2, 28 AE 2, 34 AE 6, 10 AE 1, 12 AE 5, and 12 AE 3 mm, respectively, on the Caki-1 cell line.

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From the reaction of 1H‐imidazole (1a), 4,5‐dichloro‐1H‐imidazole (1b), 1H‐benzimidazole (1c), 1‐methylimidazole (1d), 4,5‐dichloro‐1‐methylimidazole (1e) and 1‐methylbenzimidazole (1f) with p‐nitrobenzyl bromide (2), symmetrically and non‐symmetrically p‐nitrobenzyl‐substituted N‐heterocyclic carbene (NHC) [(3a–f)] precursors were synthesised. These NHC‐precursors were then reacted with silver(I) acetate to yield the NHC‐silver acetate complexes [1,3‐bis(4‐nitrobenzyl)imidazol‐2‐ylidene]silver(I) acetate (4a), [4,5‐dichloro‐1,3‐bis(4‐nitrobenzyl)imidazol‐2‐ylidene]silver(I) acetate (4b), [1,3‐bis(4‐nitrobenzyl)benzimidazol‐2‐ylidene]silver(I) acetate (4c), [1‐methyl‐3‐(4‐nitrobenzyl)imidazole‐2‐ylidene] silver(I) acetate (4d), [4,5‐dichloro‐1‐methyl‐3‐(4‐nitrobenzyl)imidazole‐2‐ylidene] silver(I) acetate (4e) and [1‐methyl‐3‐(4‐nitrobenzyl)benzimidazole‐2‐ylidene] silver(I) acetate (4f), respectively. The two NHC–silver(I) acetate complexes 4a and 4e were characterised by single‐crystal X‐ray diffraction. All compounds studied in this work were preliminary screened for their antimicrobial activities in vitro against Gram‐positive bacteria Staphylococcus aureus, and Gram‐negative bacteria Escherichia coli using the qualitative Kirby–Bauer disk‐diffusion method. All NHC–silver(I) acetate complexes exhibited medium to high antibacterial activity with areas of clearance ranging from 3 to 7 mm at the highest amount used, whereas the NHC‐precursors showed significantly lower activity. In addition, NHC–silver(I) acetate complexes 4a–f had their preliminary cytotoxicity tests on the human renal‐cancer cell line Caki‐1 and showed medium to high cytotoxicity with IC50 values ranging from 15 (+/–1) to 27 (+/–2) μM.

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