Metastable crystals of β-cyclodextrin complexes and the membrane diffusion model

Jogun, Kurt H.; Stezowski, John J.

doi:10.1038/278667a0

Cited by 29 publications

(11 citation statements)

References 4 publications

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“…For example, hydrate bCD·8H 2 O is formed by equilibration of bCD·11.2H 2 O with vapors of n -propanol liquid taken in excess (SI). These facts contradict to earlier observed crystallization of 3:2 and 2:1 guest–bCD clathrates from solution in n -propanol (60%)–water mixture. The same technique gave 1:2 clathrate with i -propanol .…”

Section: Results and Discussioncontrasting

confidence: 99%

Unusually High Efficiency of β-Cyclodextrin Clathrate Preparation by Water-Free Solid-Phase Guest Exchange

et al. 2013

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An effective preparation procedure is offered for β-cyclodextrin (bCD) clathrates with volatile guests of moderate hydrophilicity, which otherwise require a finely tuned optimization of the bCD/water/guest ratio. The proposed procedure includes guest exchange in a water-free bCD matrix. As a result, more stable clathrates with a higher inclusion capacity can be prepared than by direct saturation of dried or hydrated bCD. To find an optimal preparation method, the structure-property relationships were studied for four different ways of bCD clathrate formation with guests of varying molecular structure. The study was much simplified by used procedures excluding direct contact of guest and water liquids with bCD. Besides, in clathrate preparation experiments, the thermodynamic activities of water and guest were varied independently, which makes explicit the role of water in this process. Hydration of bCD reduces its inclusion threshold for hydrophobic guests by their activity (relative vapor pressure), giving favorable hydration effect for their inclusion. Besides, water competes with hydrophilic guests for binding sites in bCD at high water activities. Together with bCD dehydration by excess of hydrophilic guests, these observations give a complete thermodynamic picture, which may be fruitful for elaboration of guest encapsulation techniques by cyclodextrins.

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Section: Results and Discussioncontrasting

confidence: 99%

Unusually High Efficiency of β-Cyclodextrin Clathrate Preparation by Water-Free Solid-Phase Guest Exchange

et al. 2013

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“…The inclusion complexes of cyclodextrins (CDs) with drugs, hormones, pigments and flavors have become very attractive for pharmaceutical, cosmetic and food industrial applications1–3 since the solubility, stability and bioavailability of an included guest molecule in the host–guest complexes can be improved 2, 3. Although the existence of such inclusion complexes of CDs with compatible guest molecules has been demonstrated in both solid4–6 and liquid7–9 states, only recently has mass spectrometry (MS) been tested for their direct detection in the gas phase 10–12. The formation of specific non‐covalent complexes by association of guest compounds within the cavity of host molecules is currently an area of great interest in MS 13–15…”

Section: Introductionmentioning

confidence: 99%

Characterization of non‐covalent complexes of rutin with cyclodextrins by electrospray ionization tandem mass spectrometry

et al. 2004

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Electrospray ionization tandem mass spectrometry (ESI-MS(n)) and the phase solubility method were used to characterize the gas-phase and solution-phase non-covalent complexes between rutin (R) and alpha-, beta- and gamma-cyclodextrins (CDs). The direct correlation between mass spectrometric results and solution-phase behavior is thus revealed. The order of the 1 : 1 association constants (K(c)) of the complexes between R and the three CDs in solution calculated from solubility diagrams is in good agreement with the order of their relative peak intensities and relative collision-induced dissociation (CID) energies of the complexes under the same ESI-MS(n) condition in both the positive and negative ion modes. Not only the binding stoichiometry but also the relative stabilities and even binding sites of the CD-R complexes can be elucidated by ESI-MS(n). The diagnostic fragmentation of CD-R complexes, with a significant contribution of covalent fragmentation of rutin leaving the quercetin (Q) moiety attached to the CDs, provides convincing evidence for the formation of inclusion complexes between R and CDs. The diagnostic fragment ions can be partly confirmed by the complexes between Q and CDs. The gas-phase stability order of the deprotonated CD-R complexes is beta-CD-R > alpha-CD-R > gamma-CD/R; beta-CD seems to bind R more strongly than the other CDs.

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“…Initial phases were derived from isomorphous replacement of the ␤-CD coordinates from the thermodynamically stable npropanol complex (22,23). Waters of hydration and guest sites were located in difference electron density.…”

Section: Methodsmentioning

confidence: 99%

“…All diffraction measurements were conducted with graphite monochromated Ag K ␣ X-radiation ( ϭ 0.5608 Å) by using a Bruker AXS (Madison, WI) rotating anode x-ray source; data were measured in oscillation scan mode with a MARResearch (Hamburg, Germany) (18 cm) imaging plate area detector and processed by using the MARXDS program (21). Data collection and structure refinement are characterized in Table 1.Initial phases were derived from isomorphous replacement of the ␤-CD coordinates from the thermodynamically stable npropanol complex (22,23). Waters of hydration and guest sites were located in difference electron density.…”

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confidence: 99%

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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Metastable crystals of β-cyclodextrin complexes and the membrane diffusion model

Cited by 29 publications

References 4 publications

Unusually High Efficiency of β-Cyclodextrin Clathrate Preparation by Water-Free Solid-Phase Guest Exchange

Unusually High Efficiency of β-Cyclodextrin Clathrate Preparation by Water-Free Solid-Phase Guest Exchange

Characterization of non‐covalent complexes of rutin with cyclodextrins by electrospray ionization tandem mass spectrometry

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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