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在还原环境中,反式-Cr(环脒)(ONO)(2)+ 光生成一氧化氮。可溶性鸟苷酸环化酶的激活和动脉血管舒张。

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

机构信息

Department of Chemistry and Biochemistry, University of California, Santa Barbara, Santa Barbara, California 93106-9510, USA.

出版信息

J Med Chem. 2010 Jan 28;53(2):715-22. doi: 10.1021/jm9013357.

DOI:10.1021/jm9013357
PMID:19950902
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.

摘要

三价铬亚硝酰基配合物反式-Cr(环戊二烯)(ONO)(2)(+)(1)是一种很有前途的光化学前体,可将一氧化氮递送到生理靶标。在这里,我们证明在含有巯基还原剂(如生物抗氧化剂谷胱甘肽(GSH))的溶液中,用可见光波长激发 1 会导致即使在厌氧条件下也会发生永久性反应,从而导致高量子产率的一氧化氮释放。在这种条件下形成的一氧化氮即使在 1 的微摩尔浓度下并且使用低强度光源也足以激活酶可溶性鸟苷酸环化酶(sGC)。我们还证明,使用便携式蓝色 LED 在 nM 浓度范围内对 1 进行光解会导致猪冠状动脉环的血管舒张,这一过程也归因于 sGC 的一氧化氮激活。

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