Structural Aspects of Stereodifferentiation in the Solid State

Harata, Kazuaki

doi:10.1021/cr9700134

Cited by 384 publications

(314 citation statements)

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“…1 On the other hand, crystal polymorphism, the inverse of isostructurality, 2 was also demonstrated for cyclodextrins in our recent report on the structural characterization of two crystalline forms of the inclusion complex b-cyclodextrin-methyl paraben, isolated at different temperatures. 3 The present report relates to the polymorphism of permethylated b-cyclodextrin [heptakis(2,3,6-tri-O-methyl)-b-cyclodextrin, commonly known as TRIMEB], widely used as a solubilising agent and as host for the encapsulation of organic molecules, 4 including drugs. 5 In 1994, we isolated single crystals of this host as the monohydrate from an aqueous solution of TRIMEB maintained at 50 uC.…”

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New crystalline forms of permethylated β-cyclodextrin

et al. 2004

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Two new crystalline forms of permethylated b-cyclodextrin are reported that contain methylglucose residues exclusively in the 4 C 1 conformation, in contrast to the known monohydrate, in which a single methylglucose residue adopts the 1 C 4 conformation.In recent reports, we have focused on two intriguing aspects of the solid-state chemistry of cyclodextrins, namely isostructurality and polymorphism, both of which have practical implications for the continued use of these molecules as drug carriers. Systematic classification of the crystal structures of native and derivatised cyclodextrins, and their inclusion complexes, into isostructural series has proven useful in our laboratory for the definitive identification from X-ray powder diffraction of new inclusion complexes formed by these macrocyclic oligosaccharides. 1 On the other hand, crystal polymorphism, the inverse of isostructurality, 2 was also demonstrated for cyclodextrins in our recent report on the structural characterization of two crystalline forms of the inclusion complex b-cyclodextrin-methyl paraben, isolated at different temperatures. 3 The present report relates to the polymorphism of permethylated b-cyclodextrin [heptakis(2,3,6-tri-O-methyl)-b-cyclodextrin, commonly known as TRIMEB], widely used as a solubilising agent and as host for the encapsulation of organic molecules, 4 including drugs. 5 In 1994, we isolated single crystals of this host as the monohydrate from an aqueous solution of TRIMEB maintained at 50 uC. X-Ray structural analysis revealed that six of the seven methylglucose residues adopt the normal 4 C 1 conformation while the seventh is in the inverted 1 C 4 conformation. 6 A second structure determination of this phase was subsequently reported. 7 To our knowledge, this remains the only known case of ring-inversion in cyclodextrin solid-state chemistry. The resultant, highly distorted conformation of the TRIMEB molecule contrasted strongly with the more regular conformations it adopts in its inclusion complexes.We refer to the above crystal monohydrate as Form 1, in view of our recent isolation of two new crystalline modifications of TRIMEB, namely a trihydrate (Form 2) and an anhydrate (Form 3), which are the subject of this report. These new forms are isostructural with respect to the host molecule, the latter having all seven methylglucose residues in the normal 4 C 1 conformation. Both crystal forms were isolated from failed attempts to obtain inclusion complexes of TRIMEB with drug molecules.{ In all of the experiments performed, the starting host material corresponded to the known monohydrate, Form 1. The trihydrate (Form 2) crystallised from a solution containing TRIMEB and the antihypertensive drug atenolol (4-[2-hydroxy-3-[(1-methylethyl)-amino)propoxy]benzeneacetamide, either in the form of enantiopure (S)-atenolol or as the racemate), in 1 : 1 host-guest molar ratio, as well as from a solution containing TRIMEB and the analgesic drug bucetin (N-(4-ethoxyphenyl)-3-hydroxybutanamide) in 1 : 1 molar ratio. When the cry...

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New crystalline forms of permethylated β-cyclodextrin

et al. 2004

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“…3) (5). In the cage-type assemblies, CD molecules are arranged in a zig-zag fashion, and both ends of the cavity are blocked by adjacent CD molecules to form isolated 'cages'.…”

Section: B Formation Of Crystalline Cyclodextrin Structures Of Variomentioning

confidence: 99%

Formation and Function of Nano- and Microstructures by the Self-assembly of Cyclic Oligosaccharides ‘Cyclodextrins’

Kida

2011

TIGG

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Recently, much attention has been paid to studies on nano-and microstructures formed by the self-assembly of cyclodextrins (CDs) in the fields of supramolecular chemistry and material science. CDs can adopt various types of assembly modes in aqueous solution, as well as crystal structures. Channel-type assemblies of γ-CD (γ-CD channel ) formed unique micrometer-sized cubes and rods. By using γ-CD channel as a host, the inclusion of guest molecules dissolved in oils, which has been believed to be impossible, can be realized. Furthermore, γ-CD channel showed excellent oil dispersion, and formed organogels in a variety of oils and organic solvents at ambient temperature. This article reviews the formation behavior and function of nano-and microstructures formed by the self-assembly of CDs. A. IntroductionCyclodextrins (CDs), which are produced from starch by the action of cyclodextrin glucanotransferase, are a class of cyclic oligosaccharides consisting of several α-(1,4)-linked D-glucopyranose units (Fig. 1). CDs composed of 6, 7, and 8 glucosidic units are called α-, β-, and γ-CDs, respectively, and have been used extensively. They have a cavity of sub-

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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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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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Structural Aspects of Stereodifferentiation in the Solid State

Cited by 384 publications

References 120 publications

New crystalline forms of permethylated β-cyclodextrin

New crystalline forms of permethylated β-cyclodextrin

Formation and Function of Nano- and Microstructures by the Self-assembly of Cyclic Oligosaccharides ‘Cyclodextrins’

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

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