Mechanistic insight into the tautomerization of histidine initiated by water-catalyzed N-H and C-H cleavages.

The N-H and C-H activation is of great significance in organic chemistry and chemical industry fields, especially, in the utilization of petroleum raw materials. High NδH (tautomer of natural histidine) content would increase Alzheimer's disease risk. To inhibit this and improve the activation of N-H and C-H bonds, the isomerization mechanism from NδH to NεH of histidine-containing dipeptide catalyzed by water cluster was explored. The results discovered that water cluster assists this reaction by reducing the activation energies from 68.20 to 9.60 kcal mol, and its size not only affects the reaction rate but also determines the reaction pathway in a degree. Moreover, water cluster, taken as a potential green catalyst, is more effective on the reactions involving N-H and C-H bond cleavages than reported common toxic organometallic compounds and has different catalytic mechanisms. This work also provides some theoretical guidance for the modulation of Alzheimer's disease induced by histidine isomerization.