Synthesis, crystal structures, characterization and biological studies of nitrile-functionalized silver(I) N-heterocyclic carbene complexes

Abstract

The synthesis of a series of silver(I) complexes (3a–d), [1-(2′/3′-methylbenzyl)-3-(2″/3″-benzonitrile)benzimidazol-2-ylidenesilver(I)]PF6, of nitrile-functionalized N-heterocyclic carbenes (NHCs) based on benzimidazole core and their characterization and biological evaluations have been reported. The NHC precursors (1a–d and 2a–d) have been synthesized from successive N-alkylation of benzimidazole with appropriate substituted benzyl halides. Their corresponding bis-NHC silver(I) complexes, 3a–d, have been prepared from the reaction of the nitrile-functionalized benzimidazolium salts with silver(I) oxide in methanol/acetonitrile at mild reaction conditions in good yield (65–73%). Both, salts and complexes, were characterized by 1H and 13C NMR, FT-IR spectroscopic and elemental analysis techniques. The molecular structures of the silver(I)–NHC complexes, 3a and 3c, were elucidated by X-ray diffraction technique. Both the complexes displayed weak π–π stacking interactions between benzimidazole and benzyl benzene rings. All four silver(I) complexes exhibited potent antimicrobial activity against a Gram negative (Escherichia coli) and Gram positive (Staphylococcus aureus and Bacillus subtilis) bacteria. Also the IC50 values of both, salts (2a–d) and complexes (3a–d) have been determined by an MTT-based assay method against the human colon cancer cell line, HCT 116. Complexes 3a–d displayed three- to fivefold increase in the anticancer activity with the IC50 values 18.8±1.3, 20.6±1.5, 19.2±1.0, 14.9±0.8μM compared to the anticancer potential of salts 2a–d (64.3±2.5, 58.3±4.5, 83.9±1.5, 72.4±1.0μM), respectively.