Phenol Nitration Induced by an {Fe(NO)₂}¹⁰ Dinitrosyl Iron Complex

Abstract

Cellular dinitrosyl iron complexes (DNICs) have long been considered NO carriers. Although other physiological roles of DNICs have been postulated, their chemical functionality outside of NO transfer has not been demonstrated thus far. Here we report unprecedented dioxygen reactivity of an N-bound {Fe(NO)2}10 DNIC, [Fe(TMEDA)(NO)2] (1). In the presence of O2, 1 becomes a nitrating agent that converts 2,4,-di-tert-butylphenol to 2,4-di-tert-butyl-6-nitrophenol via formation of a putative iron-peroxynitrite [Fe(TMEDA)(NO)(ONOO)] (2) that is stable below −80 °C. Iron K-edge X-ray absorption spectroscopy on 2 supports a five-coordinated metal center with a bound peroxynitrite in a cyclic bidentate fashion. The peroxynitrite ligand of 2 readily decays at increased temperature or under illumination. These results suggest that DNICs could have multiple physiological or deleterious roles, including that of cellular nitrating agents.

Reactions of Co(III)–Nitrosyl Complexes with Superoxide and Their Mechanistic Insights

“…2 However, NO overproduction leads to toxicological behavior because of its radical character and ability to form reactive nitrogen species (RNS), such as nitrogen dioxide (NO 2 ) and peroxynitrite (PN, − OON=O). 3 These RNS may result from NO oxidation in the presence of O 2 , 4 H 2 O 2 , superoxide radical 3d,5 and/or transition metal ions. 6 In these contexts, important enzymes are available in-vivo to maintain proper levels of NO.…”

Synthetic Modeling Chemistry of Iron–Sulfur Clusters in Nitric Oxide Signaling

“…However, when O 2 is added to a mixture of 5 and DBP, nitration still occurs (NO 2 -DBP = 58%). 40 We have been unable to crystallize the final product generated from the reaction of 5 and O 2 at RT. However, with [Fe(dmp)(NO) 2 ], where dmp = 2,9-dimethyl-1,10-phenanthroline, which shows similar nitrating chemistry to 5 under aerobic conditions, 41 we obtained a final roomtemperature-stable product that could be characterized by spectroscopic methods and X-ray crystallography.…”

“…Comparison of the edge energies of 5 and 6 showed a shift of +1.8(4) eV, consistent with formal oxidation of the iron center in 5 by one electron. 40 The EXAFS region for 6 was best modeled as a five coordinate Fe species with a coordinated bidentate O 2 NO − moiety ( Figure 3B; best fit includes: shell #1:2 N scatterers; O 2 NO shell: 1 O 2 NO scatterer, r 1 = 1.91(1) Å, r 2 = 1.91 Å (restrained); NO shell: 1 NO scatterer, r = 1.67(1) Å). 40 Peroxynitrite can often be detected via its characteristic oxidation and/or nitration chemistry, especially that of phenolic substrates.…”

“…40 The EXAFS region for 6 was best modeled as a five coordinate Fe species with a coordinated bidentate O 2 NO − moiety ( Figure 3B; best fit includes: shell #1:2 N scatterers; O 2 NO shell: 1 O 2 NO scatterer, r 1 = 1.91(1) Å, r 2 = 1.91 Å (restrained); NO shell: 1 NO scatterer, r = 1.67(1) Å). 40 Peroxynitrite can often be detected via its characteristic oxidation and/or nitration chemistry, especially that of phenolic substrates. When 1 equiv of 2,4-di-tert-butylphenol (DBP) is added to 6, and the reaction mixture is warmed to room temperature, 2,4-di-tert-butyl-6-nitrophenol is observed along with the oxidative coupling product (Scheme 6).…”

“…When 1 equiv of 2,4-di-tert-butylphenol (DBP) is added to 6, and the reaction mixture is warmed to room temperature, 2,4-di-tert-butyl-6-nitrophenol is observed along with the oxidative coupling product (Scheme 6). 40 These reaction products do not form when DBP is added af ter warming the solution of 6 to RT, signifying that intermediate 6 is a crucial species in phenol nitration and oxidation. At room temperature, 6 is too unstable to be observed by UV−vis spectroscopy.…”