NO-releasing Mechanisms

Two general mechanisms exist for NO release from oximes 1. hydrolysis to hydrox-ylamine followed by hydroxylamine oxidation and 2. direct oxidation and decomposition of the oxime. 

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Metal-NO complexes Structures, Syntheses, Properties and NO-releasing Mechanisms... 

C-Nitroso compounds, oximes, N-hydroxyguanidines and N-hydroxyureas each contain an N-O bond and release nitric oxide (NO) or one of its redox forms under some conditions. The nitrogen atom of a C-nitroso compound formally exists in the +1 oxidation state, the same oxidation state as nitroxyl (HNO), the one-electron reduced form of N O. The nitrogen atoms of oximes, N-hydroxyguanidines, and N-hydroxyureas each formally exist in the -1 oxidation state, the same oxidation state as hydroxylamine. Consequently, the direct formation of NO (formal oxidation state = +2) from any of these species requires oxidation, one electron for a C-nitroso compound and three electrons for an oxime, N-hydroxyguanidine or N-hydroxyurea. This chapter summarizes the syntheses and properties, NO-releasing mechanisms and the known structure-activity relationships of these compounds. 

The results presented also give valuable insights into the substrate flux within multimodular PKSs. If a multitude of reversible reactions do indeed exist during biosynthesis, as proposed in Scheme 6.2, then the driving force effectively pushing intermediates through the biosynthetic assembly line is the concentration of extender unit (typically malonyl-CoA) within the cell. Modular type I PKSs which have had their TE domain rendered inactive, have been shown to harbour ACPs saturated with intermediates, forming a molecular traffic-jam [21]. The data presented here support these observations, as with no release mechanism available, acyl intermediates will be in equilibrium between the upstream ACP and the KS, a proportion of which wiU be located on the PPant arm of the ACP. 

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