Allylic Nitro Compounds as Nitrite Donors

Abstract

Allylic nitro compounds were synthesized and evaluated as organic sources of nitrite and nitric oxide. Unactivated allylic nitro compounds do not spontaneously release nitrite and nucleophile promoted nitrite release is slow. However, 2-(nitromethyl)-cyclohex-1-ene-3-one spontaneously dissociates in buffer (pH = 7.4) to release nitrite with a k obs = 1.6 × 10 −5 s −1 . In the presence of Lcysteine, this compound rapidly yields nitrite and reacts with hemoglobin similarly to sodium nitrite. Structural modifications and the nature and amount of nucleophile modulate the rate of nitrite release. In the presence of L-cysteine and ascorbic acid, this compound forms nitric oxide. Together, these results reveal a new structural architecture for the tunable liberation of nitrite and nitric oxide from organic compounds.

Kinetics and mechanism of the Co(II)-assisted oxidation of l-ascorbic acid by dioxygen and nitrite in aqueous solution

“…Now nitrite has been proposed to play an important role in blood regulation 23 and hypoxic nitric oxide homeostasis. [28][29][30] Nitrite has also been proposed as a potential therapeutic in the treatment of various diseases, including cystic fibrosis. [31][32][33][34] Several years ago a previously unknown function for hemoglobin as an enzymatic nitrite reductase was identified.…”

Endogenous generation of nitro-fatty acid hybrids having dual nitrate ester (RONO2) and nitroalkene (RNO2) substituents

“…Nitrite generation may derive from decomposition mechanisms of NO 2 –ONO 2 -CLA derivatives via nucleophilic substitution of the –NO 2 group under neutral conditions [ 44 ] or alkaline deprotonation of the hydrogen α to the –ONO 2 group [ 45 ]. The detection of a nitro-keto-CLA-TAG product upon the base-catalyzed decay of NO 2 –ONO 2 -CLA-TAG in organic milieu supports this mechanism, that would yield a carbonyl product ( Suppl.…”

Recent advancement in drug development of nitro(NO2)‐heterocyclic compounds as lead scaffolds for the treatment of Mycobacterium tuberculosis

“…In recent years, various molecules with nitro(NO 2 ) moieties have been synthetized, characterized, and biologically evaluated (Chakrapani et al, 2006; Nishiwaki, 2020; Wyllie et al, 2013). However, few of these molecules were tested against infectious diseases (e.g.…”