Dataset Information

Molecular recognition of N-acetyltryptophan enantiomers by ?-cyclodextrin.

ABSTRACT: The enantioselectivity of ?-cyclodextrin (?-CD) towards L- and D-N-acetyltryptophan (NAcTrp) has been studied in aqueous solution and the crystalline state. NMR studies in solution show that ?-CD forms complexes of very similar but not identical geometry with both L- and D-NAcTrp and exhibits stronger binding with L-NAcTrp. In the crystalline state, only ?-CD-L-NAcTrp crystallizes readily from aqueous solutions as a dimeric complex (two hosts enclosing two guest molecules). In contrast, crystals of the complex ?-CD-D-NAcTrp were never obtained, although numerous conditions were tried. In aqueous solution, the orientation of the guest in both complexes is different than in the ?-CD-L-NAcTrp complex in the crystal. Overall, the study shows that subtle differences observed between the ?-CD-L,D-NAcTrp complexes in aqueous solution are magnified at the onset of crystallization, as a consequence of accumulation of many soft host-guest interactions and of the imposed crystallographic order, thus resulting in very dissimilar propensity of each enantiomer to produce crystals with ?-CD.

SUBMITTER: Chatziefthimiou SD

PROVIDER: S-EPMC5564276 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Molecular recognition of <i>N</i>-acetyltryptophan enantiomers by β-cyclodextrin.

Chatziefthimiou Spyros D SD Inclán Mario M Giastas Petros P Papakyriakou Athanasios A Yannakopoulou Konstantina K Mavridis Irene M IM

Beilstein journal of organic chemistry 20170809

The enantioselectivity of β-cyclodextrin (β-CD) towards L- and D-<i>N</i>-acetyltryptophan (NAcTrp) has been studied in aqueous solution and the crystalline state. NMR studies in solution show that β-CD forms complexes of very similar but not identical geometry with both L- and D-NAcTrp and exhibits stronger binding with L-NAcTrp. In the crystalline state, only β-CD-L-NAcTrp crystallizes readily from aqueous solutions as a dimeric complex (two hosts enclosing two guest molecules). In contrast, c ...[more]

PMID: 28904606

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Project description:BackgroundFlunarizine dihydrochloride (FLN) is used in the prophylactic treatment of migraine, vertigo, occlusive peripheral vascular disease and epilepsy. Cyclodextrins (CDs) are chiral, truncated cone shaped macrocycles known for their inner hydrophobic and outer hydrophilic site. They form complexes with hydrophobic drug molecules and enhance the solubility and bioavailability of such compounds by enhancing drug permeability through mucosal tissues. NMR spectroscopy and computational docking have been recognized as an important tool for the interaction study of CDs-drug inclusion complexes in solution state.ResultsThe structural assignments of FLN and β-CD protons were determined by 1H NMR and 2D 1H-1H COSY NMR spectroscopy. 1H NMR spectroscopic studies of FLN, β-CD and their mixtures confirmed the formation of β-CD-FLN inclusion complex in solution. 1H NMR titration data for β-CD-FLN inclusion complex showed 1:1 stoichiometry, an association constant of K a = 157 M-1 and change in Gibbs free energy of ∆G = - 12.65 kJ mol-1. The binding constant of the β-CD inclusion complex with two nearly similar structures, FLN and cetirizine dihydrochloride, were compared. Two-dimensional 1H-1H ROESY spectral data and molecular docking studies showed the modes of penetration of the aromatic rings from the wider rim side into the β-CD cavity. The possible geometrical structures of the β-CD-FLN inclusion complex have been proposed in which aromatic rings protrude close to the narrower rim of the β-CD truncated cone.ConclusionNMR spectroscopic studies of FLN, β-CD and FLN:β-CD mixtures confirmed the formation of 1:1 inclusion complex in solution at room temperature. Two-dimensional 1H-1H ROESY together with molecular docking study confirmed that the F-substituted aromatic ring of FLN penetrates into β-CD truncated cone and the tail of aromatic rings were proximal to narrower rim of β-CD. The splitting of aromatic signals of FLN in the presence of β-CD suggests chiral differentiation of the guest FLN by β-CD.

Dataset Information

Molecular recognition of N-acetyltryptophan enantiomers by ?-cyclodextrin.

Publications

Molecular recognition of <i>N</i>-acetyltryptophan enantiomers by β-cyclodextrin.

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