Phenylalanine Residues Are Very Rapidly Damaged by Nitrate Radicals (NO₃ ⋅) in an Aqueous Environment

Kinetic studies revealed that nitrate radicals (NO₃ ⋅), which are formed through reaction of the noxious air pollutants nitrogen dioxide (NO₂ ⋅) and ozone (O₃ ), very rapidly oxidize phenylalanine residues in an aqueous environment, with overall rate coefficients in the 10⁸ -10⁹  M^-1  s^-1 range. With amino acids and dipeptides as model systems, the data suggest that the reaction proceeds via a π-complex between NO₃ ⋅ and the aromatic ring in Phe, which subsequently decays into a charge transfer (CT) complex. The stability of the π-complex is sequence-dependent and is increased when Phe is at the N terminus of the dipeptide. Computations revealed that the considerably more rapid radical-induced oxidation of Phe residues in both neutral and acidic aqueous environments, compared to acetonitrile, can be attributed to stabilization of the CT complex by the protic solvent; this clearly highlights the health-damaging potential of exposure to combined NO₂ ⋅ and O₃ .