Non–symmetrically p–nitrobenzyl–substituted N–heterocyclic carbene–silver(I) complexes as metallopharmaceutical agents

Abstract

In the present work, a series of eight new imidazole, 4,5–dichloroimidazole, 4,5–diphenylimidazole and benzimidazole based nitro–functionalized mono–N–heterocyclic carbene (NHC)–silver(I) acetate (7a–d) and bis–NHC–silver(I) hexafluorophosphate complexes (8a–d) were synthesised by the reaction of the corresponding azolium hexafluorophosphate salts (6a–d) with silver(I) acetate and silver(I) oxide in methanol and acetonitrile, respectively. All the synthesised compounds were fully characterized by various spectroscopic techniques and elemental analyses. Additionally, the structure of bis–(1–benzyl–3–(p–nitrobenzyl)–4,5–dichloroimidazole–2–ylidene)silver(I) hexafluorophosphate complex (8b) was confirmed by single crystal X–ray diffraction analysis. Preliminary in vitro antibacterial evaluation was conducted for all the compounds (6a–d), (7a–d), and (8a–d) by Kirby–Bauer's disc diffusion method followed by the determination of Minimum Inhibitory Concentration (MIC) from broth macrodilution method against five standard bacteria; two Gram–positive bacterial strains (Staphylococcus aureus and Bacillus subtilis) and three Gram–negative bacterial strains (Escherichia coli, Shigella sonnei, and Salmonella typhi). All the hexafluorophosphate salts (6a–d) were found inactive against the tested bacterial strains and their corresponding mono– and bis–NHC–silver(I) complexes (7a–d and 8a–d) exhibited moderate to high antibacterial activity with MIC value in the range 8–128 μg/mL. In addition, preliminary in vitro anticancer potential of all the silver(I) complexes (7a–d and 8a–d) was determined against the human derived breast adenocarcinoma cells (MCF 7) by MTT assay. All the mono– and bis–NHC–silver(I) complexes (7a–d and 8a–d) orchestrated high anticancer potential with IC50 values ranging from 10.39 to 59.56 nM. In comparison, mono– NHC–silver(I) complexes performed better than the bis–NHC–silver(I) complexes.