Ab initio molecular orbital calculations have been used to study the oxidation of ammonia by a series of substituted methyl hydroperoxides XCH(2)OOH (X = H, NH2, OH, F, HC=NH, HCO). Geometries of reactants and transition states were fully optimized at the MP2/6-31G* level, and relative energies were computed at the MP4/6-31G*//MP2/6-31G* level. The barrier height for the oxidation of ammonia with CH3OOH is predicted to be 46.6 kcal/mol. Activation energies for oxygen atom transfer from substituted CH3OOH (XCH(2)OOH) to ammonia range 44.4 to 35.0 kcal/mol, suggesting that electronegative substituents exert a relatively small influence on the reactivity of alkyl hydroperoxides. Substituted methyl hydroperoxides X-CH2OOH (X=-CH=NH2+,H3N+) bearing a positive charge are highly efficient oxygen donors. The barrier height for the oxidation of ammonia by H3N+-CH2OOH is reduced to 10.3 kcal/mol, and when a disubstituted protonated methyl hyperoxide (H3N+, CHO) is used as the oxygen donor, the predicted barrier is 2.9 kcal/mol. These data suggest that through-space coulombic effects are much more effective than through-bond inductive effects in activating an alkyl hydroperoxide toward oxygen donation. Extension of these arguments to the origin of the atypical reactivity of flavin hydroperoxides suggests that protonation of 4 alpha-flavin hydroperoxide at N-1 or N-5 would stabilize the transition state for oxygen atom transfer.