A DFT Study of the Amadori rearrangement above a Phosphatidylethanolamine surface : Comparison to reactions in aqueous environment

Abstract

[eng] Mechanisms for Amadori rearrangements from Schiff bases from reactions between D-erythrose and ethylamine, glycine, and phosphatidylethanolamine (PE) based on Dmol3/DFT calculations were realized. For the case of PE, calculations were done under periodic boundary conditions (PBCs), in an amine-phospholipid monolayer model with two molecules of PE by cell. In the three cases, the reaction started with a neutral Schiff base, having in the case of PE surface model a positive charged amine group belonging to the adjacent PE molecule. The catalytic role of PE surface components such as amine and phosphate groups is highlighted. All models included water molecules forming hydrogen bond networks, these networks were involved in the reactions by stabilizing reaction intermediates and transition states and performing as proton-transfer carriers, important in all steps of reactions. In all the studied reactions, they take place in two steps, namely, (1) formation of a 1,2-enaminol intermediate and (2) ketonization to the Amadori rearrangement product, having the last step clear lower values for relative free energies in the case of stationary points of the reaction on PE surface. An alternative pathway in the first step of Amadori rearrangement above PE surface, starting since positive charged Schiff base, was also evaluated, obtaining values for the free energy barrier similar to the step, starting from neutral Schiff base form. On the basis of our results, it is possible then to hypothesize that the cell membrane phospholipid surface environment modifies the kinetic behavior of some biological reactions, enhancing some of them through a catalyst effect.