# Unconventional chalcogen-containing azolylidene metal complexes as potential anticancer therapeutics

## TL;DR

This paper explores new metal complexes with chalcogen-containing ligands that show potential as anticancer drugs by altering their electronic and biological properties.

## Contribution

The study introduces and evaluates unconventional chalcogen-containing azolylidene ligands in metal complexes for their anticancer potential.

## Key findings

- Chalcogen incorporation modulates ligand-metal interactions and cytotoxicity in ovarian cancer cells.
- Electronic and steric properties of (N,Y)HC ligands influence biological activity of metal complexes.
- New metallocarbene drug candidates emerge from substituting nitrogen with chalcogens in N-heterocyclic carbenes.

## Abstract

Organometallic compounds with N-heterocyclic carbene (NHC) ligands have been studied for their anticancer and antimicrobial properties, with imidazole and benzimidazole derivatives being the predominant scaffolds for potential NHC-containing drugs. In contrast, chalcogen-containing azolylidene ligands, (N,Y)HCs (Y = O, S, Se), remain largely unexplored in both medicinal inorganic chemistry and, more generally, in inorganic chemistry. Consequently, to study the effect of the incorporation of a chalcogen atom in the ligand, classical (N,N)HC complexes of platinum, gold and ruthenium were selected based on their previously reported biological activity and proposed mechanisms of action, and their (N,Y)HC (Y = O, S, Se) analogues were synthesised. The electronic and steric properties of the ligands and complexes were explored and their biological activity was evaluated. The introduction of a chalcogen atom within the heterocyclic scaffold of the ligands was found to modulate their interaction with biomolecules and regulate the cytotoxicity of the metal complexes towards ovarian cancer cells.

Substituting a nitrogen for a chalcogen in N-heterocyclic carbenes alters the electronic and steric features of the resulting metal complexes, influencing their biological activity and creating new opportunities for metallocarbene drug candidates.