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 (Phe) residues in an aqueous environment, with overall rate coefficients in the 108-109 M-1 s-1 range. Using 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 the stabilization of the CT complex by the protic solvent, clearly highlighting the health-damaging potential of exposure to combined NO2● and O3.