Rational design of organometallic therapeutics: leveraging metal–metal bonds for biomedical innovation

Metal-metal interactions play a crucial role in determining the molecular geometry, stability, and biological activity of many compounds. In recent years, organometallic compounds have gained significant importance in medicinal chemistry due to their structural and functional properties in treating various ailments. A virtually limitless number of structures and conformations can result from the enormous range of oxidation states, coordination numbers, and geometries that metal ion coordination complexes and organometallic compounds can adopt, depending on their nature. Understanding the types of metal-metal bonds formed by various elements across the periodic table, their thermodynamic and electronic properties, and their influence on physicochemical properties such as lipophilicity, solubility, and bioavailability becomes essential. Various drug design strategies employ approaches that involve metal-metal bonding, supported by ligand engineering, bridging ligands, and supramolecular or bimetallic complexes. However, off-target effects, toxicity, complexity, stability issues and regulatory considerations pose as key challenges in this task. Future directions focus on emerging applications of metallopharmaceuticals in cancer, antibacterial therapies, as well as their integration with nanotechnology and advanced drug delivery. This review highlights the insights into the concepts of metal-metal interactions, which are crucial for expanding the scope and applications of medicinal chemistry.