Theoretical studies on the electronic and energetic properties of the aminopyrimidine part of thiamin diphosphate.

Ab initio calculations on the HF-SCF 6-31g* level were performed on tautomers as well as protonated and deprotonated species of thiamin. Aspects of the proton relay function of the 4'-aminopyrimidine ring in the thiamin catalysis were studied on model systems. The acidity of the 4'-amino group increases in the N1' and N3' protonated thiamin systems. Starting from the 4'N deprotonated thiamin, the calculated reaction coordinate of the ylide formation suggests the cocatalytic function of the 4'-amino/imino group. Some structural, energetic, and electronic properties of the model systems are discussed with respect to key steps in the catalytic mechanism.