Nitrite and Nitric Oxide Interconversion at Mononuclear Copper(II): Insight into the Role of the Red Copper Site in Denitrification

Abstract

AbstractNitrite (NO2−) and nitric oxide (NO) interconversion is crucial for maintaining optimum NO flux in mammalian physiology. Herein we demonstrate that [L2CuII(nitrite)]+ moieties (in 2 a and 2 b; where, L = Me2PzPy and Me2PzQu) with distorted octahedral geometry undergo facile reduction to provide tetrahedral [L2CuI]+ (in 3 a and 3 b) and NO in the presence of biologically relevant reductants, such as 4‐methoxy‐2,6‐di‐tert‐butylphenol (4‐MeO‐2,6‐DTBP, a tyrosine model) and N‐benzyl‐1,4‐dihydronicotinamide (BNAH, a NAD(P)H model). Interestingly, the reaction of excess NO gas with [L2CuII(MeCN)2]2+ (in 1 a) provides a putative {CuNO}10 species, which is effective in mediating the nitrosation of various nucleophiles, such as thiol and amine. Generation of the transient {CuNO}10 species in wet acetonitrile leads to NO2− as assessed by Griess assay and 14N/15N‐FTIR analyses. A detailed study reveals that the bidirectional NOx‐reactivity, namely, nitrite reductase (NIR) and NO oxidase (NOO), at a common CuII site, is governed by the geometric‐preference‐driven facile CuII/CuI redox process. Of broader interest, this study not only highlights potential strategies for the design of copper‐based catalysts for nitrite reduction, but also strengthens the previous postulates regarding the involvement of red copper proteins in denitrification.