A DFT Study of the Nitric Oxide and Tyrosyl Radical Interaction: A Proposed Radical Mechanism

Abstract

The present study employs a complete theoretical investigation, at the B3LYP/cc-pVTZ level of theory, of the interactions between the tyrosyl radical and nitric oxide, exploring in detail the nitrotyrosine formation radical mechanism. Tyrosyl radicals play an essential role in catalytic reactions of numerous enzymes and biological systems have regulated appropriate mechanisms for their formation. Nitric oxide reacts with the tyrosyl radical and affords a weak intermediate complex which, through a sequence of non-ionic water catalyzed and biologically feasible intermediate reactions, yields the iminoxyl radical. The iminoxyl radical further combines with hydroxyl radical, a species present in pathophysiological conditions, to yield nitrotyrosine.

Underappreciated and Complex Role of Nitrous Acid in Aromatic Nitration under Mild Environmental Conditions: The Case of Activated Methoxyphenols

“…The formation of a phenoxy radical by the first NO 2 • molecule and a subsequent recombination with the second NO 2 • molecule seemed most likely. Several other scientists have also proposed an aromatic nitration through the formation of a phenoxy radical in the atmosphere and biological systems rather than the OH • -Ar adduct formation in the first reaction step of aromatic nitration (note: daytime OH • or nighttime NO 3 • was always required in the first step of the phenoxy radical formation). − In contrast, Zhang et al suggest a water-assisted addition of NO 2 • to the OH • -Ar or NO 3 • -Ar adducts in the gas-phase formation of nitrated polycyclic aromatic hydrocarbons. The reaction between the light-excited nitrophenols and NO 2 • in the presence of oxygen has further been proposed for the formation of dinitrophenol in atmospheric waters …”

Toward an Understanding of the Ambiguous Electron Paramagnetic Resonance Spectra of the Iminoxy Radical from o-Fluorobenzaldehyde Oxime: Density Functional Theory and ab Initio Studies

“…Iminoxy radicals are relatively stable and were detected by means of electron paramagnetic resonance (EPR) spectroscopy in different biological systems inter alia in photosystem II and prostaglandin H synthase-2 systems . These radicals were demonstrated to originate from tyrosine as iminoxyls were derived from the peroxidase oxidation of 3-nitroso- N -acetyl- l -tyrosine and peroxidase oxidation of free l -tyrosine in the presence of nitric oxide; the mechanism of the reaction was later proposed on the basis of density functional theory (DFT) . Iminoxyls were found to be the intermediate product of the reaction between nitrogen oxide and the anticancer drug etoposide (VP-16) diminishing its cytotoxic activity toward cancer cells .…”

“…3 These radicals were demonstrated to originate from tyrosine as iminoxyls were derived from the peroxidase oxidation of 3-nitroso-N-acetyl-Ltyrosine and peroxidase oxidation of free L-tyrosine in the presence of nitric oxide; 4 the mechanism of the reaction was later proposed on the basis of density functional theory (DFT). 5 Iminoxyls were found to be the intermediate product of the reaction between nitrogen oxide and the anticancer drug etoposide (VP-16) diminishing its cytotoxic activity toward cancer cells. 6 These radicals were also identified in lichens thalli collected from atmospherically polluted environments and also generated in laboratory conditions as a result of the nitrogen dioxide action on these composite organisms.…”

The diacetyliminoxyl radical in oxidative functionalization of alkenes

“…24,25,38,42 From the vast majority of N-oxyl radicals, imine-N-oxyl radicals (oxime radicals) stand apart being a rare example of persistent σ-type radicals. 43 They were observed during the microsomal cytochrome dependent oxidation of N-hydroxyguanidines and amidoximes, 44 tyrosine oxidation in the presence of nitric oxide, [45][46][47][48][49] and in coating compositions containing oximes as anti-skinning agents. 50 Despite the fact that these radicals have been known since 1964, 51 they have found wide application in organic synthesis only recently, mainly in intramolecular cyclizations of oximes with the functionalization of C-H and CvC bonds (Scheme 1a).…”