CONFORMATIONAL POTENTIAL ENERGY SURFACES OF TRANSITION-STATE ANALOGUES OF THIAMIN: COMPARISON OF AM1, MNDO AND MOLECULAR MECHANICS STUDIES

Abstract Thiamin thiazolone (TT) and thiamin thiothiazolone (TTT) were originally thought to be the transition-state analogues of thiamin, although later evidence indicates that they are the intermediate analogues. Relaxed 2-D conformational potential energy maps of both compounds were obtained using the semiempirical AM1 and MNDO and the molecular mechanics (MM) methods. The AM1 method failed to reproduce the crystal S form of TTT by overestimating the contribution of the intramolecular NH …S hydrogen-bonding interaction energy. The MNDO method failed to reproduce the crystal V form of TT with an intramolecular NH…O hydrogen bond. The MM method gave reasonable results for both compounds, indicating that conformation differences do exist between congeneric TT and TTT.