Reaction mechanisms between methylamine and a few Schiff bases: Ab initio potential energy surfaces of a catalytic step in semicarbazide sensitive amino oxidases (SSAO)

Abstract

The potential energy surfaces for the transamination reaction catalyzed by SSAO were explored for some of the possible reactants considered in a preliminary investigation (Comput Chem 2000, 24, 311). The proton transfer to methylamine (as a model of the catalytic base belonging to the enzyme active site)—either from the keto or enol form of the reactant Schiff bases with one of the possible cofactors, pyridoxal phosphate, PLP (using as a model the pyridoxal ring protonated at N)—was investigated. The enol form seems to be preferred in the region of the neutral intermediate, because even the keto form undergoes a spontaneous rearrangement to the enol form once the Cα proton is delivered to methylamine, producing methylammonium. When the proton is returned back to the Schiff base (on C1), the adduct is about 1.4 kcal/mol more stable than the reactants, while a canonical electron distribution is obtainable only for the enol form. The proton transfer to methylamine was also studied in the presence of the other possible cofactor (para or ortho) topaquinone, TQ. A steep uphill pathway, similar to the keto-pyridoxal Schiff base one, is obtained using the Schiff base with pTQ, which requires a rearrangement to the final intermediate. On the contrary, using the oTQ structures with the quinonoid O on the same side of methylamine, the proton abstracted from the Schiff base goes spontaneously onto the other quinonoid oxygen. The effect on the barrier heights produced by the presence of a variety of functional groups in the vicinity of the pyridoxal ring nitrogen was also examined. © 2001 John Wiley & Sons, Inc. Int J Quant Chem, 2001