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 a base (methylamine) can be favorable, as a preliminary study of the reaction catalyzed by semicarbazide-sensitive amine oxidases. Three different approaching paths of methylamine to C(alpha) in NO2-C(alpha)H2-NO2, and the relevant potential energy surfaces, 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 fairly consistent after including the MP2 correlation correction, with either basis set, while the last approaching path was abandoned. For the other model 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 phenyl 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-CHO, a steep uphill pathway was found. A more realistic model of the substrate-cofactor complex, namely the Schiff base between benzylamine and pyridoxal, again produced a barrier, almost matching that obtained for C6H5-C(alpha)H2-NO2. In both cases, the energy profiles for the rotation about the CC(alpha)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 methylphosphate) substitutions to the pyridoxal ring was performed and the stability of the Schiff bases involving other cofactors was also considered.