Ab initio and DFT calculations on the initial step in thiamin catalysis

The diphosphate ester (ThDP) of thiamin (vitamin B 1) is an important cofactor of enzymes within the carbohydrate metabolism. The initial reaction step shared by all ThDP-dependent enzymes is the deprotonation of the C2–H of the thiazolium ring. The replacement of the 4′-amino group by a hydroxyl on...

Full description

Saved in:
Bibliographic Details
Published in:Journal of molecular structure. Theochem 2003-07, Vol.630 (1), p.275-281
Main Authors: Friedemann, Rudolf, Naumann, Stefan
Format: Article
Language:English
Subjects:
Protonation and deprotonation energy
Reaction coordinate
Tautomers
Transition state
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The diphosphate ester (ThDP) of thiamin (vitamin B 1) is an important cofactor of enzymes within the carbohydrate metabolism. The initial reaction step shared by all ThDP-dependent enzymes is the deprotonation of the C2–H of the thiazolium ring. The replacement of the 4′-amino group by a hydroxyl one in the pyrimidine ring leads to the oxy-ThDP analogue which is known as an antagonist in thiamin catalysis. Ab initio and DFT calculations on the MP2/6-31G* and B3LYP/6-31G* level were performed to study the proton relay function in thiamin and oxythiamin systems. Both MP2 and B3LYP calculations show significant differences of the reaction coordinate of the ylide formation in the systems. Tautomers, protonated and deprotonated species of both systems show different trends regarding their stability. The influence of correlation effects on the results is discussed by comparison with the HF-SCF/6-31G* data. Frequency calculations on the B3LYP/6-31G* level were performed to characterize the minima and transition state structures, respectively.
ISSN:0166-1280
1872-7999
DOI:10.1016/S0166-1280(03)00174-X