Silver(I) N‑Heterocyclic Carbene Complexes Derived from Clotrimazole: Antiproliferative Activity and Interaction with an Artificial Membrane-Based Biosensor

Heba A. Mohamed, Samantha Shepherd, Nicola William, Helen A. Blundell, Madhurima Das, Christopher M. Pask, Benjamin R. M. Lake, Roger Phillips, Andrew Nelson, Charlotte E. Willans

Research output: Contribution to journalArticle

Abstract

With the aim of combining the potential anticancer properties of both clotrimazole, an imidazole based antifungal agent, and silver(I) N-heterocyclic carbenes, 13 novel silver(I) N-heterocyclic carbene complexes derived from clotrimazole were synthesized. The complexes were fully characterized, and the partition coefficient of each was determined to provide a measure of hydrophobicity. The antiproliferative properties of the complexes against cancerous and noncancerous cell lines found optimum cytotoxicity when the complex displays an "intermediate lipophilicity", which describes a complex that possesses both water-soluble groups and lipophilic aromatic groups. The silver complexes were screened on a synthetic biomembrane-like device using a chip-based phospholipid-coated Pt/Hg electrode embedded in a flow cell system. The results are recorded as rapid cyclic voltammograms (RCVs), which give insight into the interactions of the complexes with a cell membrane. Interestingly the principle of "intermediate lipophilicity" also applies to the monolayer interaction to which the silver atom significantly implements an irreversibility.

Original languageEnglish
Pages (from-to)1318-1331
Number of pages14
JournalOrganometallics
Volume39
Issue number8
Early online date20 Mar 2020
DOIs
Publication statusPublished - 27 Apr 2020

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