Acyloxy nitroso compounds as nitroxyl (HNO) donors: kinetics, reactions with thiols, and vasodilation properties.
作者： Angela Brandon , Jaideep Honovar , Dario A. Vitturi , C. R. White , R. P. Patel
DOI: 10.1021/JM101432Z
关键词: Hydrolysis 、 Decomposition 、 Nitroso 、 Salt (chemistry) 、 Nitroso Compounds 、 Medicinal chemistry 、 Nuclear magnetic resonance spectroscopy 、 Organic chemistry 、 Kinetics 、 Chemistry 、 Nitroxyl
摘要: Acyloxy nitroso compounds hydrolyze to nitroxyl (HNO), a nitrogen monoxide with distinct chemistry and biology. Ultraviolet-visible spectroscopy mass spectrometry show hydrolysis rate depends on pH ester group structure the observed being trifluoroacetate (3) > acetate (1) pivalate (2). Under all conditions, 3 rapidly hydrolyzes HNO. A combination of spectroscopic, kinetic, product studies that addition thiols increases decomposition 1 2, leading conditions favor thiolates, thiolate directly reacts group, yielding oximes without HNO formation. Biologically, behaves like Angeli's salt, demonstrating thiol-sensitive nitric oxide-mediated soluble guanylate cyclase-dependent vasorelaxation, suggesting HNO-mediated vasorelaxation. The slow HNO-donor demonstrates weak thiol-insensitive indicating release kinetics determine bioavailability activity. These results acyloxy represent new donors capable vasorelaxation depending kinetics.
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