Zinc and copper metallodrugs: a 20-year perspective on therapeutic strategies and future directions.

This review explores the use of metallodrugs, compounds formed by coordinating metals with organic molecules, as a promising strategy to enhance therapeutic efficacy and address the limitations of conventional drugs. Essential metals, such as copper and zinc, play critical biological roles and can impart unique pharmacological properties, including improved solubility, bioactivity, and selectivity, while potentially reducing toxicity. Despite these advantages, modeling and characterizing metallodrugs remains challenging due to their variable oxidation states and diverse coordination geometries. Advanced techniques, such as NMR spectroscopy, X-ray crystallography, and mass spectrometry, are crucial for elucidating their structure and function. The future development of these drugs relies on refining these methodologies and implementing innovative delivery strategies, like metal-organic frameworks (MOFs), to create safer and more effective therapies. By strategically designing metal-ligand interactions, metallodrugs can achieve targeted bioactivity and overcome resistance mechanisms, positioning them as next-generation therapeutics with the potential to transform treatments in oncology, infectious diseases, and beyond.