Nitric Oxide Photogeneration from trans-Cr(cyclam)(ONO)(2)(+) in a Reducing Environment. Activation of Soluble Guanylyl Cyclase and Arterial Vasorelaxation

TitleNitric Oxide Photogeneration from trans-Cr(cyclam)(ONO)(2)(+) in a Reducing Environment. Activation of Soluble Guanylyl Cyclase and Arterial Vasorelaxation
Publication TypeJournal Article
Year of Publication2010
AuthorsOstrowski, AD, Deakin, SJ, Azhar, B, Miller, TW, Franco, N, Cherney, MM, Lee, AJ, Burstyn, JN, Fukuto, JM, Megson, IL, Ford, PC
JournalJournal of Medicinal Chemistry
Volume53
Pagination715-722
Date PublishedJan
Type of ArticleArticle
ISBN Number0022-2623
Accession NumberISI:000273672100018
Keywords2-photon excitation, apoptosis, coordinated nitrite, cr(iii) complexes, induced, isolated tail artery, nitrosyl complexes, pendant chromophores, photochemical release, roussins red salt, smooth-muscle photorelaxation
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 mu M 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.

Short TitleJ. Med. Chem.