Metal based N-heterocyclic carbene (NHC) complexes for biological applications

Abstract

Organometallic complexes exhibit diverse biological and catalytic properties due to variety of functional groups to their diverse chemical properties, coordination modes and reactivity. Among the other metal complexes, NHC-silver and selenium complexes have become attractive tool in medicinal chemistry due to high efficacy of silver metal and biocompatibility of selenium. The present work plan was also designed in this contribution to explore medicinal attributes of silver and selenium based N-heterocyclic carbene (NHC) complexes especially antimicrobial and anticancer traits. In this context, a series of silver and selenium complexes of azolium derivatives were synthesized and categorized in three sequences, mononuclear-NHC ligands (1a-4a), binuclear-NHC ligands (5a-7a) and tetranuclear-NHC ligands (8a-16a). These ligands were metalized with silver metal (5c-15c) as well as selenium adducts (1s-16s). The studied Ag (I) adducts were synthesized by in situ deprotonation of azolium moieties to generate multinuclear NHC ligands. Among these NHC salts some of ligands were nononuclear (1a-4a), binuclear ligands (5a-8a) and others wereof tetra nuclear (9a-16a) which showed different reactivity to afford silver complexes. In these ligands tetra-nuclear series showed lesser reactivity with silver metal as compared to mononuclear ligands that could be due to steric effect (bulky alkyl substituents), therefore, their silver complexes could not be synthesized. However their ligands were well characterized and evaluated for their applications as well. All the precursors and metal complexes were characterized by FTIR, UV-Vis spectroscopy, NMR, LC-MS as well as preliminary assessment like melting points. After successful synthesis, these metal complexes were tested for their antimicrobial potential against Staphylococcus aureus and Escherichia coli. All the synthesized ligands and their respective metal analogues have showed promising potentially active against bacterial cultures and interestingly silver complexes were found more active compared to their selenium complexes. But both types (silver and selenium) of complexes showed relatively better potentially comparing to corresponding NHC precursors. These complexes and some ligands were also investigated for their cytotoxic potential against MCF-7 cancer cell lines. Interestingly these metal analogues were found very active with concentration dependent growth inhibition profile in similar behavior as reported in literature for this class of compounds.