Investigation on the Scavenging Mechanism of 1,4‐Dicarbonyls by Pyridoxamine: A Density Functional Theory Study

Abstract

AbstractThe dicarbonyl compound 4‐oxopentanal (OPA) is one of the reactive carbonyl species formed in a variety of metabolic reactions in vivo, which could react with lysyl residues to form pyrrolic compounds and exhibit severe toxicity. Pyridoxamine (PM) could effectively scavenge such reactive carbonyl compounds. The reaction mechanism of PM with OPA was investigated by density functional theory (DFT) B3LYP at 6‐31G∗︁ basis level together with MP2/6‐31+G∗︁∗︁ single point calculation on the stationary points. The results indicated that this reaction could be achieved through two continuous steps. Firstly, PM and OPA would generate a tetrahydropyrrole compound via two possible reaction pathways. Subsequently, two molecules of water would be removed to achieve the final pyrrole‐type compound through two parallel paths. In addition, it is possible to form an imine intermediate in this reaction, which seems more like a by‐product from our calculation. In the end, the steric hindrance of the acetyl group was discussed. All the results agreed with experiment very well.