Zin, Nor Farah Hani Md and Ooi, Shirley Yee Shyen and Khor, Boon-Keat and Chear, Nelson Jeng-Yeou and Tang, Wai Kit and Siu, Chi-Kit and Razali, Mohd. R. . and Haque, Rosenani A. and Yam, WanSinn (2022) Cytotoxicity of asymmetric mononuclear silver(I)-N-heterocyclic carbene complexes against human cervical cancer: Synthesis, crystal structure, DFT calculations and effect of substituents. Journal of Organometallic Chemistry, 976. ISSN 0022-328X, DOI https://doi.org/10.1016/j.jorganchem.2022.122439.
Full text not available from this repository.Abstract
A new series of asymmetrical N,N'-disubstituted benzimidazolium derived N-heterocyclic carbene (NHC) ligands and their mononuclear silver(I)-NHC complexes are reported. The ligands were prepared from N- alkylation of 1-methylbenzimidazole with alkyl bromides (n = 10-18 in even parity), non-fluorinated or fluorinated benzyl bromides. In situ deprotonation of the ligands with silver oxide, followed by metathesis reaction with potassium hexafluorophosphate facilitated the formation of the mononuclear silver(I)-NHC complexes. Chemical structures of all the compounds were elucidated using Fourier transform infrared, H-1 and C-13 nuclear magnetic resonance (NMR) spectroscopy, and CHN elemental microanalysis. The coordination mode of the Ag(I)-NHC complexes was confirmed by single crystal XRD analysis. Single crystal analysis of ortho-fluorinated benzyl-containing complex showed that each complex consisted of one Ag(I) ion coordinated with two NHC ligands in a linear geometry in the presence of one PF6- anion in the lattice. Cytotoxic effects of the NHC ligands and their silver(I) complexes against human cervical cancer cells (HeLa) and normal human skin fibroblasts (Hs27) were investigated using the MTT assay. Cytotoxicity of these compounds was dependent on the N-substituents in the benzimidazolium moiety and the presence of silver ions. Benzylated ligands were non-active whilst their dialkylated analogues showed weak to excellent cytotoxic effects on HeLa cells. The incorporation of silver ions and elongation of alkyl chains significantly enhanced cytotoxicity. Density functional theory revealed that Ag-C bond strength was in-sensitive to the NHC ligand design, and about one-third of the overall complex binding enthalpy was con-tributed by the non-covalent interaction between the long alkyl chains. Long-chain ligands ( n = 16-18) and all silver(I)-NHC complexes exhibited superior cytotoxicity against HeLa cells (IC50 ranged between 1.18 mu M-9.38 mu M) as compared to that of the anticancer drug, Etoposide (IC50 = 25.67 mu M). (C) 2022 Elsevier B.V. All rights reserved.
| Item Type: | Article |
|---|---|
| Funders: | Ministry of Higher Education (MOHE) Malaysia through the Fundamental Research Grant Scheme (FRGS) (Grant No: 203/PKIMIA/6711795), Hong Kong Research Grants Council (Grant No: CityU 11304519 & CityU 11305420) |
| Uncontrolled Keywords: | Benzimidazole; N-heterocyclic carbene; Silver(I)-NH Ccomplexes; Single crystal XRD; Cytotoxicity |
| Subjects: | Q Science > QD Chemistry R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) |
| Divisions: | Deputy Vice Chancellor (Research & Innovation) Office > Institute of Research Management and Services |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 27 Nov 2023 01:46 |
| Last Modified: | 27 Nov 2023 01:46 |
| URI: | http://eprints.um.edu.my/id/eprint/41642 |
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