BIOSYNTHESIS OF NITRIC-OXIDE - QUANTUM-CHEMICAL MODELING OF N-OMEGA-HYDROXY-L-ARGININE FORMATION

The electronic structure (charge distribution, bond indices, character of the frontier orbitals) and geometry (bond distances and angles) of L-arginine and N-methyl-L-arginine were determined by means of the IN DO procedure. The method was also adopted to model the conversion of L -arginine into N-hydroxy-L-arginine in biological systems. This reveal ed that the approach of diatomic O species does not result in reaction , whereas the approach of either an O atom or an O2- ion leads to inse rtion of oxygen and formation of hydroxy-L-arginine. The insertion of oxygen between the nitrogen and hydrogen atoms leads to more stable pr oducts than insertion into the C-H bond. The same results were obtaine d for N-methyl-L-arginine, and are consistent with the hypothesis that the inhibitive effect of N-substitution in L-arginine is of no import ance for the first step in the biosynthesis of NO (hydroxylation proce ss). The mechanistic considerations based on the charge distribution a nd frontier orbital characteristics led to the conclusion that the mos t probable mechanism of L-arginine hydroxylation consists in electroph ilic attack of [FeO](3+) at the N-omega-H bond, initiated by the reduc tion of L-arginine(+), followed by insertion of oxygen and product oxi dation.