Synthesis, characterisation and biological evaluation of novel bisimidazolium mononuclear and dinuclear silver(I)-N-heterocyclic carbene complexes with long N-alkyl chains

• Main Authors: Khe, Jia Ming, Fong, Zhijack, Lee, Wai Leng, Tan, Kong Wai, Ting, Adeline Su Yien, Cheow, Yuen Lin
• Format: Article
• Published: Elsevier 2024
• Subjects: QD Chemistry
• Online Access: http://eprints.um.edu.my/45365/; https://doi.org/10.1016/j.jorganchem.2024.123076
• Institution: Universiti Malaya

Current drug research has been focusing on silver N -heterocyclic carbene (NHC) complex. Its metal-ligand bonds are stabilised by the strong -electron donor nature of NHC, ultimately increasing its antimicrobial properties. A series of imidazolium salts and their corresponding Ag(I)-NHC complexes with different NHC side chains in terms of alkyl chain length and mono/biscarbene functionalities have been successfully synthesised, characterised, and evaluated for their potential antimicrobial activities. It was shown that the imidazolium salts and Ag(I)-NHC complexes with long aliphatic alkyl N -1/ N -3 side chains and bisimidazolium ligands possess promising bioactivities in general, with minimum inhibitory concentration (MIC) against microbes ranging from 0.12 to 7.81 mu g/mL against selected six Gram-positive bacterial strains ( Staphylococcus aureus and Enterococcus faecalis ), two Gram-negative bacteria ( Escherichia coli and Shigella flexneri ) and two fungal strains ( Candida albicans ) for 2 -7d & Ag-2 -7d . It was found that the compounds with biscarbene structures ( 6d & Ag-6d ) possess less toxic effects against immortalised human keratinocyte (HaCaT) cells. However, it must be noted that the toxic effect against HaCaT is higher among Ag(I)-NHC complexes ( Ag-4d & Ag-6d ) than their corresponding imidazolium salts ( 4d & 6d ) in general. Hence, the variation of side chains, number of imidazolium centres and their respective cytotoxic effect provide insights into the future drug modification towards enhanced antimicrobial activities with minimal side effects.