X-ray crystallographic determination of the absolute configuration of (+)flurbiprofen utilizing .BETA.-cyclodextrin complexation.

Uekama, Kaneto; Imai, Teruko; Hirayama, Fumitoshi; Otagiri, Masaki; Harata, Kazuaki

doi:10.1248/cpb.32.1662

Cited by 22 publications

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“…The dimer cavity is more than twice as large as the cavity of a single molecule and can accommodate two or more guest molecules. β-CD forms 2:3 complexes with p -iodophenol 55 and 1-propanol 55 while flurbiprofen, , benzocaine, ethyl cinnamate, and 1-adamantanecarboxylic acid 60 form 2:2 complexes. In the 2:3 complexes, each β-CD molecule accommodates a guest molecule at its primary hydroxyl side, while the third guest molecule is sandwiched between the β-CD macrocycles.…”

Section: B β-Cyclodextrin1 Cage-type Packing Structurementioning

confidence: 99%

Structural Aspects of Stereodifferentiation in the Solid State

1998

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Section: B β-Cyclodextrin1 Cage-type Packing Structurementioning

confidence: 99%

Structural Aspects of Stereodifferentiation in the Solid State

1998

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“…In the solid phase, x-ray diffraction studies of inclusion complexes with chiral guest molecules can provide direct information regarding the mechanism of chiral recognition. In the relatively few studies with native cyclodextrins, mixed results have been reported (9)(10)(11)(12)(13)(14)(15). The most complete studies are those in which structures are determined for complexes formed with both enantiomers separately and for the racemate (9)(10)(11)(12)(13)(14).…”

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confidence: 99%

“…In the relatively few studies with native cyclodextrins, mixed results have been reported (9)(10)(11)(12)(13)(14)(15). The most complete studies are those in which structures are determined for complexes formed with both enantiomers separately and for the racemate (9)(10)(11)(12)(13)(14). For example, significant discrimination was observed for the ␤-CD inclusion complex with (R,S)-fenoprofen (11) in the solid state, whereas there was no apparent discrimination for (R,S)-flurbiprofen (9)(10)(11)(12)(13)(14).…”

mentioning

confidence: 99%

“…The most complete studies are those in which structures are determined for complexes formed with both enantiomers separately and for the racemate (9)(10)(11)(12)(13)(14). For example, significant discrimination was observed for the ␤-CD inclusion complex with (R,S)-fenoprofen (11) in the solid state, whereas there was no apparent discrimination for (R,S)-flurbiprofen (9)(10)(11)(12)(13)(14). These results and others suggest that features such as guest fit to the cavity, solvent interactions, hydrogen bonding potential of the guest molecules, and host crystal packing arrangement combine to play a significant role in chiral discrimination.…”

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Chiral discrimination in cyclodextrin complexes of amino acid derivatives: β-cyclodextrin/ N -acetyl- l -phenylalanine and N -acetyl- d -phenylalanine complexes

Alexander

Clark

Brett

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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In a systematic study of molecular recognition of amino acid derivatives in solid-state ␤-cyclodextrin (␤-CD) complexes, we have determined crystal structures for complexes of ␤-cyclodextrin͞N-acetyl-L-phenylalanine at 298 and 20 K and for N-acetyl-D-phenylalanine at 298 K. The crystal structures for the N-acetyl-L-phenylalanine complex present disordered inclusion complexes for which the distribution of guest molecules at room temperature is not resolvable; however, they can be located with considerable confidence at low temperature. In contrast, the complex with N-acetyl-D-phenylalanine is well ordered at room temperature. The latter complex presents an example of a complex in this series in which a water molecule is included deeply in the hydrophobic torus of the extended dimer host. In an effort to understand the mechanisms of molecular recognition giving rise to the dramatic differences in crystallographic order in these crystal structures, we have examined the intermolecular interactions in detail and have examined insertion of the enantiomer of the D-complex into the chiral ␤-CD complex crystal lattice.C hiral cyclodextrin (CD) hosts have been used extensively as models for investigating chiral and molecular recognition. Solution studies of CD inclusion complexes (1-3) and determination of binding constants (2), have provided thermodynamic data useful for chromatographic applications (4-8). In the solid phase, x-ray diffraction studies of inclusion complexes with chiral guest molecules can provide direct information regarding the mechanism of chiral recognition. In the relatively few studies with native cyclodextrins, mixed results have been reported (9-15). The most complete studies are those in which structures are determined for complexes formed with both enantiomers separately and for the racemate (9-14). For example, significant discrimination was observed for the ␤-CD inclusion complex with (R,S)-fenoprofen (11) in the solid state, whereas there was no apparent discrimination for (R,S)-flurbiprofen (9-14). These results and others suggest that features such as guest fit to the cavity, solvent interactions, hydrogen bonding potential of the guest molecules, and host crystal packing arrangement combine to play a significant role in chiral discrimination.We have initiated a study in which the crystal lattice of ␤-cyclodextrin complexes that crystallize in the intermediate (Im) packing motif (16-18) has been characterized as a binding pocket useful for the crystallographic study of structural aspects of molecular recognition at high resolution (19). Briefly, the crystal lattice consists of close packed hydrogen bonded dimers of the host ␤-cyclodextrin molecules stacked, with an intervening layer of water molecules, along the a-axis. Typically two amino acid derivative guest molecules are included in the extended torus of the host dimer. To differing extents, the more hydrophilic backbones of the guest molecules interact with water molecules between the sheets and, in most cases, via bridging water molec...

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“…209,210 Στη στερεά κατάσταση, κρυσταλλογραφικές µελέτες συµπλόκων εγκλεισµού κυκλοδεξτρίνης µε χειρόµορφα µόρια µπορούν να προσφέρουν σηµαντικές πληροφορίες ως προς το µηχανισµό της χειροµορφικής αναγνώρισης. Από τις ελάχιστες περιπτώσεις κρυστάλλων συµπλόκων φυσικών κυκλοδεξτρινών µε χειρόµορφα µόρια, [211][212][213][214][215] εξάγεται το συµπέρασµα ότι παράγοντες όπως η προσαρµογή του ξενιζοµένου µορίου στην υδροφοβική κοιλότητα, οι αλληλεπιδράσεις µεταξύ των µορίων διαλύτη, οι δεσµοί υδρογόνου µεταξύ των ξενιζοµένων µορίων και η διευθέτηση των µορίων της κυκλοδεξτρίνης στο κρυσταλλικό πλέγµα παίζουν σηµαντικό ρόλο στη µοριακή αναγνώριση.…”

Section: κρυσταλλική δοµή του συµπλόκου εγκλεισµού β-κυκλοδεξτρίνης -ν-ακέτυλO-l-θρυπτοφάνηςunclassified

Κρυσταλλογραφική Μελέτη Δομής Βιολογικών Μακρομορίων

Chatziefthimiou¹,

Χατζηευθυμίου²

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X-ray crystallographic determination of the absolute configuration of (+)flurbiprofen utilizing .BETA.-cyclodextrin complexation.

Cited by 22 publications

References 0 publications

Structural Aspects of Stereodifferentiation in the Solid State

Structural Aspects of Stereodifferentiation in the Solid State

Chiral discrimination in cyclodextrin complexes of amino acid derivatives: β-cyclodextrin/ N -acetyl- l -phenylalanine and N -acetyl- d -phenylalanine complexes

Κρυσταλλογραφική Μελέτη Δομής Βιολογικών Μακρομορίων

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