Computational Modeling of Inclusion Complexes of beta-Cyclodextrin With Enantiomers of Salsolinol, N-Methyl-salsolinol, and 1-Benzyl-tetrahydroisoquinoline

Capillary electrophoresis with beta-CD as a chiral selector has successfully separated the two enantiomers of salsolinol, N-methyl-salsolinol, and 1-benzyl-tetrahydroisoquinoline (BTIQ). The migration times of each enantiomer in capillary electrophoresis reflect the stability of their beta-CD inclusion complexes. This paper reports a computational modeling study of the inclusion Complexes of beta-cyclodextrin (beta-CD) with salsolinol, N-methyl-salsolinol, and BTIQ by using PM3 (Parametric Method 3) semiempirical molecular orbital calculations and the ONIOM hybrid method. Two types of the inclusion complexes, cis- and trans-orientations, are considered for each enantiomer of the guest molecules, salsolinol, N-methyl-salsolinol, and BTIQ. In the cis-orientation, the nitrogen in the salsolinol, N-methyl-salsolinol, and BTIQ points toward the secondary hydroxyls of the beta-CD, while in the trans-orientation, the nitrogen in salsolinol, N-methyl-salsolinol, and BTIQ points toward the primary hydroxyls of the beta-CD. We found that the stabilization energies of these inclusion complexes from these PM3 and ONIOM different methods correlate very well with the migration order deduced from the study of capillary electrophoretic separation. (C) 2008 Wiley Periodicals, Inc. Int J Quantum Chem 109: 81-90, 2009