A Cyclodextrin-Encapsulated Ruthenium-based NO/HNO Donor: Enhancing Aqueous Solubility and Modulating Reactivity for Biological Applications

This study presents a cyclodextrin-encapsulated ruthenium-based nitrosyl complex, cis-[Ru(pby)₂(2-MIM)(NO)₃](PF₆)₃ (FOR0811A), designed to enhance the aqueous solubility and modulate the reactivity of NO/HNO donors for biological applications. The inclusion complex with hydroxypropyl-β-cyclodextrin (HP-β-CD) was characterized by FTIR and Job's plot analysis, confirming a 1:1 stoichiometry. Notably, the encapsulation increased the complex's water solubility by 2.5-fold (3.66 mg/mL) while maintaining the characteristic νNO band. Ongoing studies employ spectrophotometric and amperometric techniques to evaluate NO/HNO release triggered by biological reductants and light. This approach addresses key limitations of metallodrugs, such as low solubility and rapid thiol reactivity, potentially improving their pharmacokinetic and therapeutic profiles for cardiovascular and other diseases.