Solís-Calero Christian, Ortega-Castro Joaquín, Hernández-Laguna Alfonso, Muñoz Francisco
Departament de Química, Institut d'Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, E-07122, Palma de Mallorca, Spain.
J Mol Model. 2014 Apr;20(4):2202. doi: 10.1007/s00894-014-2202-z. Epub 2014 Apr 5.
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 Amadori-glycated 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.
我们通过进行Dmol3/DFT计算研究了氨基胍（AG）与甲基乙二醛（MG）之间的反应机制，获得了反应所有基本步骤的中间体、过渡态结构和自由能剖面图。设计的模型包括明确的水溶剂，其在反应物和中间分子周围形成氢键网络，在反应机制的某些步骤中促进分子内质子转移。该反应分四个步骤进行，即：（1）AG与MG缩合形成胍腙 - 乙酰甲醇加合物；（2）加合物脱水；（3）通过闭环形成1,2,4 - 三嗪衍生物；（4）脱水形成5 - 甲基 - 3 - 氨基 - 1,2,4 - 三嗪作为最终产物。从微观动力学角度来看，发现第一步脱水是该反应的速率决定步骤，该反应的表观活化能为12.65 kcal mol⁻¹。此外，还获得了AG与2,3 - 二羰基 - 磷脂酰乙醇胺（一种可能参与Amadori糖化磷脂酰乙醇胺（Amadori - PE）自氧化的中间体）反应的一些中间体和过渡态的类似结构，以评估在磷脂酰乙醇胺（PE）表面上的上述反应。我们的结果与其他作者获得的实验结果一致，表明AG能有效捕获二羰基化合物如甲基乙二醛，进而在诸如表面及其水相环境等环境中，这些化合物能与生物分子如PE结合。
