We have studied the mechanism of the reaction between aminoguanidine (AG) and methylglyoxal (MG) by carrying out Dmol3/DFT calculations, obtaining intermediates, transition-state structures, and free-energy profiles for all of the elementary steps of the reaction. Designed models included explicit water solvent, which forms hydrogen-bond networks around the reactants and intermediate molecules, facilitating intramolecular proton transfer in some steps of the reaction mechanism. The reaction take place in four steps, namely: (1) formation of a guanylhydrazone-acetylcarbinol adduct by condensation of AG and MG; (2) dehydration of the adduct; (3) formation of an 1,2,4-triazine derivative by ring closure; and (4) dehydration with the formation of 5-methyl 3-amino-1,2,4-triazine as the final product. From a microkinetic point of view, the first dehydration step was found to be the rate-determining step for the reaction, with the reaction having an apparent activation energy of 12.65 kcal mol-1. Additionally, some analogous structures of intermediates and transition states for the reaction between AG and 2,3-dicarbonyl- phosphatidylethanolamine, a possible intermediate in Amadoriglycated phosphatidylethanolamine (Amadori-PE) autooxidation, were obtained to evaluate the reaction above a phosphatidylethanolamine (PE) surface. Our results are in agreement with experimental results obtaining by other authors, showing that AG is efficient at trapping dicarbonyl compounds such as methylglyoxal, and by extension these compounds joined to biomolecules such as PE in environments such as surfaces and their aqueous surroundings.
- DFT calculations