Medicinal Organometallics of Iron: From Ferrocene Derivatives to Redox-Active Drug Candidates

Iron-based organometallics represents a rapidly advancing frontier in medicinal chemistry. They are distinguished by their ability to integrate redox activity, structural adaptability, and biological targeting into the therapeutic design. The journey from the discovery of ferrocene to the development of ferrocenyl hybrids, heme mimetics, and catalytic Fe complexes reflects the evolution of this field from structural curiosity to clinically relevant innovation. Unlike conventional small molecules, iron organometallics can cycle between multiple oxidation states (Fe²+/Fe³+), catalyze ROS/RNS generation, and mimic natural metalloenzymes. This versatility offers unique opportunities in precision therapy. Recent advances have highlighted their applicability to multiple therapeutic domains. In oncology, ferroptosis and chemodynamic therapy (CDT) leverage the catalytic chemistry of iron to induce lipid peroxidation and oxidative collapse in resistant tumors. In infectious diseases, ferrocenyl antimalarials and antibacterial hybrids exhibit pathogen-specific iron uptake and redox vulnerability. In inflammatory and neurodegenerative disorders, catalase- and peroxidase-mimicking complexes remodel redox homeostasis to protect the tissues from oxidative injury. Emerging applications include the use of CO-releasing iron carbonyls (CORM-Fe) and stimuli-responsive nanocarriers. These tools enable controlled gasotransmitter release and site-specific activation, thereby further expanding the therapeutic toolbox. Despite these advances, translation faces challenges such as systemic toxicity, protein corona formation, unpredictable pharmacokinetics, and regulatory gaps that remain barriers to clinical progression. Future research directions include precision nanomedicine, biomarker-guided patient selection, and AI-assisted molecular design. These approaches enable the fine-tuning of redox properties and targeted delivery. Synergistic strategies combining iron organometallics with chemotherapy, radiotherapy, and immunotherapy promise to overcome resistance, while amplifying therapeutic efficacy.

کلیدواژه ها:

Organometallic iron ، Ferrocene ، ROS ، Drug Candidates ، ferroptosis ، chemodynamic therapy ، Nanocarriers