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

Nitrite (NO₂ ^- ) and nitric oxide (NO) interconversion is crucial for maintaining optimum NO flux in mammalian physiology. Herein we demonstrate that [L₂ Cu^II (nitrite)]⁺ moieties (in 2 a and 2 b; where, L = Me₂ PzPy and Me₂ PzQu) with distorted octahedral geometry undergo facile reduction to provide tetrahedral [L₂ Cu^I ]⁺ (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 [L₂ Cu^II (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 ¹⁴ N/¹⁵ N-FTIR analyses. A detailed study reveals that the bidirectional NO_x -reactivity, namely, nitrite reductase (NIR) and NO oxidase (NOO), at a common Cu^II site, is governed by the geometric-preference-driven facile Cu^II /Cu^I 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.