Reactivity of a phospholipid monolayer model under periodic boundary conditions: a density functional theory study of the Schiff base formation between phosphatidylethanolamine and acetaldehyde.

A mechanism for the formation of the Schiff base between an acetaldehyde and an amine-phospholipid monolayer model based on Dmol3/density functional theory calculations under periodic boundary conditions was constructed. This is the first time such a system has been modeled to examine its chemical reactivity at this computation level. Each unit cell contains two phospholipid molecules, one acetaldehyde molecule, and nine water molecules. One of the amine-phospholipid molecules in the cell possesses a neutral amino group that is used to model the nucleophilic attack on the carboxyl group of acetaldehyde, whereas the other has a charged amino group acting as a proton donor. The nine water molecules form a hydrogen bond network along the polar heads of the phospholipids that facilitates very fast proton conduction at the interface. Using periodic boundary conditions afforded proton transfer between different cells. The reaction takes place in two steps, namely, (1) formation of a carbinolamine and (2) its dehydration to the Schiff base. The carbinolamine is the primary reaction intermediate, and dehydration is the rate-determining step of the process, consistent with available experimental evidence for similar reactions. On the basis of the results, the cell membrane surface environment may boost phospholipid glycation via a neighboring catalyst effect.