Computational modeling of inclusion complexes of β‐cyclodextrin with enantiomers of salsolinol, N‐methyl‐salsolinol, and 1‐benzyl‐tetrahydroisoquinoline

Abstract

Capillary electrophoresis with β-CD as a chiral selector has successfully separated the two enantiomers of salsolinol, N-methyl-salsolinol, and 1-benzyl-tetrahydroisoquinoline. The migration times of each enantiomer in capillary electrophoresis reflect the stability of their β-CD inclusion complexes. This paper reports a computational modeling study of the inclusion complexes of β-cyclodextrin (β-CD) with salsolinol, N-methyl-salsolinol, and 1-benzyltetrahydroisoquinoline by using PM3 (Parametric Method 3) semi-empirical molecular orbital calculations and the ONIOM hybrid method. Two types of the inclusion complexes, cis-and transorientations, are considered for each enantiomer of the guest molecules, salsolinol, N-methylsalsolinol, and 1-benzyl-tetrahydroisoquinoline. In the cis-orientation, the nitrogen in the salsolinol, N-methyl-salsolinol, and 1-benzyl-tetrahydroisoquinoline points toward the secondary hydroxyls of the β-CD, while in the trans-orientation, the nitrogen in salsolinol, N-methylsalsolinol, and 1-benzyl-tetrahydroisoquinoline points toward the primary hydroxyls of the β-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.

(R)-Salsolinol, a product of ethanol metabolism, stereospecifically induces behavioral sensitization and leads to excessive alcohol intake

“…This elution pattern is also supported by compu- tational modeling, evaluating the total energy for stabilization, demonstrating that the complex formed by (R)-SAL and β-cyclodextrin is stronger than the complex of (S)-SAL and β-cyclodextrin. Therefore, (S)-SAL elutes before (R)-SAL (Huang et al 2009). Figure 1b and c depicts the chromatograms obtained by injecting 50 μl of purified (R)-SAL and (S)-SAL, respectively, dissolved in aCSF, as used for their intracerebral administration.…”

“…packed with silica gel modified with β-cyclodextrin (MachereyNagel, Düren, Germany) kept at 30°C; (2) an isocratic pump adjusted to 0.80 ml/minute (Shimadzu LC-10AD, Kyoto, Japan); and (3) an LC-4C BAS amperometric detector (ED) set at a potential of 0.7 V. The mobile phase was 100 mM ammonium acetate containing 10 mM triethylamine (pH 4.0). Under these conditions and using a similar chiral HPLC system, it was reported that (S)-SAL was the first to elute (Baum & Rommelspacher 1994;Deng et al 1995;Naoi et al 1996;Liu et al 2000;Tóth et al 2001;Quan et al 2005;Cai & Liu 2008;Rojkovicova et al 2008;Huang et al 2009;Lee et al 2010).…”

“…Complete separation of (R)-SAL and (S)-SAL was achieved by high-performance liquid chromatography (HPLC) on a β-cyclodextrin-modified column, which has the ability to separate these enantiomers (Baum & Rommelspacher 1994;Quan et al 2005;Huang, Quan & Liu 2009). Studies were conducted to determine the differential effects of intra-VTA administration of (R)-or (S)-SAL on the generation of (1) conditioned place preference (CPP); (2) locomotor sensitization; and (3) voluntary ethanol consumption.…”

Chiral recognition of Propranolol enantiomers by β-Cyclodextrin: Quantum chemical calculation and molecular dynamics simulation studies

“…Li et al [17], have performed AM1 and PM3 calculations on a and b-CD and concluded that PM3 is a better quantum mechanical method than AM1 with respect to b-CD. Huang et al [19], have used capillary electrophoresis and PM3 method to study the inclusion complexes of b-CD with salsolinol, N-methyl-salsolinol, and 1-benzyl-tetrahydroisoquinoline enantiomers. They found that the stabilization energies of these inclusion complexes from PM3 method correlate very well with the migration order deduced from the study of capillary electrophoretic separation.…”

Computational studies of 1:2 complex between retinol propionate and β cyclodextrin

“…Theoretical computer modelling can also be used to assess steric interaction of complexation and have been used to predict the nature of drug-cyclodextrin interaction in either vacuum or ideal solutions [7].…”