MOLECULAR-DYNAMICS STUDY OF THE TAUTOMERIC EQUILIBRIUM IN THE MANNICHBASE

The density functional theory ab initio quantum mechanical and molecul ar dynamics thermodynamic integration methods have been used to study the intramolecular proton transfer equilibrium in 2-[N,N-dimethylamino methyl]-3,4,6-trichlorophenol. The model of slow proton transfer react ion was applied, where the geometry and charge data were linearly inte rpolated between two states calculated at the Becke3LYP 6-31G(d,p) lev el. This avoids the difficulties connected with the different time sca les of proton transfer reaction and solvent relaxation processes. The calculated free energy differences obtained from ab initio calculation s including the Tomasi model of the solvent reaction field (1.16 kcal mol(-1)) and from ab initio plus molecular dynamic thermodynamic integ ration calculations (1.7 +/- 1.8 kcal mol(-1))are in agreement with th e experimental value 0.12 +/- 0.02 kcal mol(-1). (C) 1998 Elsevier Sci ence B.V.