title: Silver(I) complexes of mono- and bidentate N-heterocyclic carbene ligands: synthesis, crystal structures, and in vitro antibacterial and anticancer studies.
abstract: A series of benzimidazole-based N-heterocyclic carbene (NHC) proligands {1-benzyl-3-(2-methylbenzyl)-benzimidazolium bromide/hexafluorophosphate (1/4), 1,3-bis(2-methylbenzyl)-benzimidazolium bromide/hexafluorophosphate (2/5) and 1,3-bis(3-(2-methylbenzyl)-benzimidazolium-1-ylmethylbenzene dibromide/dihexafluorophosphate (3/6)} has been synthesized by the successive N-alkylation method. Ag complexes {1-benzyl-3-(2-methylbenzyl)-benzimidazol-2-ylidenesilver(I) hexafluorophosphate (7), 1,3-bis(2-methylbenzyl)-benzimidazol-2-ylidenesilver(I) hexafluorophosphate (8) and 1,3-bis(3-(2-methylbenzyl)-benzimidazol-2-ylidene)-1-ylmethylbenzene disilver(I) dihexafluorophosphate (9)} of NHC ligands have been synthesized by the treatment of benzimidazolium salts with Ag2O at mild reaction conditions. Both, NHC proligands and Ag-NHC complexes have been characterized by (1)H and (13)C{(1)H} NMR and FTIR spectroscopy and elemental analysis technique. Additionally, the structure of the NHC proligand 5 and the mononuclear Ag complexes 7 and 8 has been elucidated by the single crystal X-ray diffraction analysis. Both the complexes exhibit the same general structural motif with linear coordination geometry around the Ag centre having two NHC ligands. Preliminary in vitro antibacterial potentials of reported compounds against a Gram negative (Escherichia coli) and a Gram positive (Bacillus subtilis) bacteria evidenced the higher activity of mononuclear silver(I) complexes. The anticancer studies against the human derived colorectal cancer (HCT 116) and colorectal adenocarcinoma (HT29) cell lines using the MTT assay method, revealed the higher activity of Ag-NHC complexes. The benzimidazolium salts 4-6 and Ag-NHC complexes 7-9 displayed the following IC50 values against the HCT 116 and HT29 cell lines, respectively, 31.8 ± 1.9, 15.2 ± 1.5, 4.8 ± 0.6, 10.5 ± 1.0, 18.7 ± 1.6, 1.20 ± 0.3 and 245.0 ± 4.6, 8.7 ± 0.8, 146.1 ± 3.1, 7.6 ± 0.7, 5.5 ± 0.8, 103.0 ± 2.3 μM.
authors.affiliation: The School of Chemical Sciences, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia. Electronic address: rosenani@usm.my.
authors.forename: Rosenani A
authors.initials: RA
authors.lastname: Haque
authors.affiliation: The School of Chemical Sciences, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia.
authors.forename: Sze Yii
authors.initials: SY
authors.lastname: Choo
authors.affiliation: Centre for Nano and Material Sciences, Jain University, Jain Global Campus, Bangalore 562 112, Karnataka, India.
authors.forename: Srinivasa
authors.initials: S
authors.lastname: Budagumpi
authors.affiliation: The School of Chemical Sciences, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia.
authors.forename: Muhammad Adnan
authors.initials: MA
authors.lastname: Iqbal
authors.affiliation: The School of Biological Sciences, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia.
authors.forename: Amirul
authors.initials: A
authors.lastname: Al-Ashraf Abdullah
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects*; D002243:Carbolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004926:Escherichia coli / Q000187:drug effects*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012834:Silver / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D002243:Carbolines; D006571:Heterocyclic Compounds; D008024:Ligands; D009942:Organometallic Compounds; D012834:Silver; C100106:dicarbine
keywords: Ag–NHC complex; Antibacterial agent; Anticancer agent; Carbene complex; HCT 116; HT29