COMPUTER MODELING OF PHENYL ACETATE HYDROLYSIS IN WATER AND IN REACTION WITH BETA-CYCLODEXTRIN - MOLECULAR-ORBITAL CALCULATIONS WITH THE SEMIEMPIRICAL AM1 METHOD AND THE LANGEVIN DIPOLE SOLVENT MODEL
Vb. Luzhkov et Ca. Venanzi, COMPUTER MODELING OF PHENYL ACETATE HYDROLYSIS IN WATER AND IN REACTION WITH BETA-CYCLODEXTRIN - MOLECULAR-ORBITAL CALCULATIONS WITH THE SEMIEMPIRICAL AM1 METHOD AND THE LANGEVIN DIPOLE SOLVENT MODEL, Journal of physical chemistry, 99(8), 1995, pp. 2312-2323
The Langevin dipole (LD) solvent model is used with the AM1 semiempiri
cal quantum mechanical method to compare reaction pathways in the gas
phase and in polar solution for phenyl acetate cleavage by hydroxide i
on and by beta-cyclodextrin. The gas-phase results show that nucleophi
lic substitution at the acyl carbon atom of phenyl acetate by the hydr
oxide ion exhibits a downhill potential profile. The introduction of s
olvent effects using the LD model results in correct reproduction of t
he experimental values for the activation barrier and the heat of hydr
olysis. The reaction of the alkoxide ion of cyclodextrin with bound ph
enyl acetate in the gas phase is found to have a positive energy of ac
tivation, which is further increased in the presence of polar solvent.
The results show that acylation at the S'-hydroxyl of cyclodextrin is
favored over the 2'-position by about 15 kcal/mol due to less structu
ral reorganization of the macrocycle during hydrolysis at the S'-site.
The results also show that attack at the 3'-hydroxyl lowers the activ
ation energy barrier by about 10 kcal/mol compared to attack by hydrox
ide ion in solution. The results are discussed in terms of the known p
hysicochemical properties of cyclodextrins and their inclusion complex
es.