Organometallic compounds as antimicrobial agents: emerging chemical types, mechanistic insights and future directions

The relentless surge of antimicrobial resistance (AMR) across bacterial, fungal, viral, and parasitic pathogens constitutes a catastrophic threat to global healthcare, rapidly rendering conventional organic anti-infectives obsolete and demanding the urgent development of innovative chemical scaffolds.

This expert opinion examines recent breakthroughs in bioorganometallic drug design. It evaluates the structural classification, multi-targeted mechanisms of action, non-canonical pathways, and preclinical efficacy of emerging organometallic compounds-specifically metallocenes, N-heterocyclic carbenes, half-sandwich arenes, and tricarbonyl complexes-combating drug-resistant infections.

Organometallic platforms offer an unparalleled structural toolkit to overcome cross-resistance due to their modular geometries and ability to trigger simultaneous lethal mechanisms. To advance these candidates into human clinical trials and address lingering toxicity concerns, future research must prioritize optimizing the kinetic stability of metal-compounds networks to prevent premature in vivo speciation. Furthermore, integrating smart, pathogen-specific delivery vectors (such as peptide or antibody conjugates) will dramatically expand their therapeutic windows, facilitating the clinical translation of next-generation bioorganometallic anti-infectives.