Exploring ruthenium(II)-arene-nitrite complexes for NO release and vasodilatory applications

Malekshah, R. E.; Huang, S.-E.; Sun, Y.-H.; Hung, X.-F.; Kao, C.-L.; Chu, Y.-T.; Yeh, J.-L.*; Hsu, S. C. N.*

Inorg. Chem. Commun. 2026, 183, 115848. (IF-5.9)

https://doi.org/10.1016/j.inoche.2025.115848

KMU Researchers Develop Ruthenium-Based Nitric Oxide Donors for Potential Cerebrovascular Therapy

A research team led by Professor Sodio C. N. Hsu at Kaohsiung Medical University has developed a series of novel ruthenium(II)-arene nitrite complexes capable of efficiently releasing nitric oxide (NO), a critical signaling molecule involved in vascular relaxation, blood flow regulation, and neurological function. Deficiency of NO is associated with cardiovascular disorders, stroke, and neuroinflammatory diseases, making controlled NO delivery an important therapeutic goal.

The team synthesized and characterized four ruthenium-nitrite complexes and evaluated their biological performance. Cellular studies using BV2 microglial cells demonstrated minimal toxicity at therapeutically relevant concentrations, while NO-release assays showed that complexes 1 and 4 generated substantially higher levels of nitric oxide than commonly used NO donors, including DETA-NONOate and Spermine-NONOate. Complex 1 exhibited the strongest NO-releasing capability, achieving nearly double the release level observed with standard donor compounds.

To assess their therapeutic potential, the researchers examined vascular relaxation in rat thoracic aorta tissues. Remarkably, complexes 1 and 4 induced 97.5% and 92.1% vasorelaxation, respectively, approaching the performance of sodium nitroprusside, a clinically used vasodilator. Computational studies further revealed that complex 1 possesses the lowest energy barrier for NO release, explaining its superior biological activity.

These findings establish ruthenium-arene nitrite complexes as promising next-generation NO-donor platforms. The work provides a foundation for developing safer and more effective therapies for cerebrovascular diseases, neuroinflammation, ischemic stroke, and other conditions associated with impaired nitric oxide signaling.