A theoretical study on reaction pathways to carbanions

Different substituents (NO2, C6H5, NH2, NH-CH=CH-CHO) to a methylene group were taken into account to investigate under which conditions the mechanism of formation of carbanions by proton transfer to abase (methylamine) can b e favorable, as a preliminary study of the reaction catalyzed by semicarbaz ide-sensitive amine oxidases. Three different approaching paths of methylam ine to C-alpha in NO2-CalphaH2-NO2, and the relevant potential energy surfa ces, were examined at the SCF/3-21G and 6-31G* levels. The proton transfer along the first two paths occurred with a similar barrier, which became fai rly consistent after including the MP2 correlation correction, with either basis set, while the last approaching path was abandoned. For the other mod el systems the minimum was searched only at the 3-21G level in the vicinity of the first reaction path. The substitution of a nitro group with a pheny l group sharply raised the barrier for the proton transfer to methylamine. Also by substituting the second nitro group with either -NH2 or -NH-CH-CH-C HO, a steep uphill pathway was found. A more realistic model of the substra te-cofactor complex, namely the Schiff base between benzylamine and pyridox al, again produced a barrier, almost matching that obtained for C6H5-Calpha H2-NO2. In both cases, the energy profiles for the rotation about the CC,NC dihedral and the proton shift tautomers were also considered at the 3-21G and 6-31G* levels. A preliminary scan of the effect of methyl (or methylpho sphate) substitutions to the pyridoxal ring was performed and the stability of the Schiff bases involving other cofactors was also considered. (C) 200 0 Elsevier Science Ltd. All rights reserved.