Nitric oxide photogeneration from trans-Cr(cyclam)(ONO)(2)(+) in a reducing environment. activation of soluble guanylyl cyclase and arterial vasorelaxation

Alexis D Ostrowski, Sherine J Deakin, Bilal Azhar, Thomas W Miller, Nestor Franco, Melisa M Cherney, Andrea J Lee, Judith N Burstyn, Jon M Fukuto, Ian L Megson, Peter C Ford

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35 Citations (Scopus)

Abstract

The chromium(III) nitrito complex trans-Cr(cyclam)(ONO)(2)(+) (1) is a very promising photochemical precursor for nitric oxide delivery to physiological targets. Here, we demonstrate that visible wavelength excitation of 1 in solutions containing thiol reductants such as the biological antioxidant glutathione (GSH) leads to permanent reaction even under anaerobic conditions, resulting in high quantum yield NO release. The nitric oxide formed under such conditions is sufficient, even at muM concentrations of 1 and using a low-intensity light source, to activate the enzyme soluble guanylyl cyclase (sGC). We also demonstrate that photolysis of 1 in the nM concentration range with a portable blue LED leads to vasorelaxation of porcine coronary arterial rings, a process also attributed to the NO activation of sGC.
Original languageEnglish
Pages (from-to)715-22
Number of pages8
JournalJournal of Medicinal Chemistry
Volume53
Issue number2
DOIs
Publication statusPublished - 2010

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    Ostrowski, A. D., Deakin, S. J., Azhar, B., Miller, T. W., Franco, N., Cherney, M. M., Lee, A. J., Burstyn, J. N., Fukuto, J. M., Megson, I. L., & Ford, P. C. (2010). Nitric oxide photogeneration from trans-Cr(cyclam)(ONO)(2)(+) in a reducing environment. activation of soluble guanylyl cyclase and arterial vasorelaxation. Journal of Medicinal Chemistry, 53(2), 715-22. https://doi.org/10.1021/jm9013357