The Stability of Cyclodextrin Complexes in Solution.

Review: a history of cyclodextrins.

Methods for Selective Modifications of Cyclodextrins.

If the amylose fraction of starch is degraded by
glucosyltransferases, one or several turns of the
amylose helix are hydrolyzed off and their ends are
joined together, thereby producing cyclic oligosaccharides
called cyclodextrins (CDs) or cycloamyloses
(CAs).

Structures of the Common Cyclodextrins and Their Larger Analogues-Beyond the Doughnut.

The driving forces leading to the inclusion complexation of cyclodextrins were reviewed, which included the electrostatic interaction, van der Waalsinteraction, hydrophobic interaction, hydrogen bonding, release of conformational strain,exclusion of cavity-bound high-energy water, and charge–transferinteraction. It was shown that except for the release of conformation strain and exclusion of cavity-bound water, the otherinteractions were indeed contributive to the complex formation. However, it was concludedthat the enthalpy and entropy changes of the complexation were not good criteria to be used injudging whether a particular driving force was present or important, mainly because of theoccurrence of enthalpy-entropy compensation. On the other hand, the multivariate quantitativestructure-activity relationship analyses usually could illustrate which driving forces wereimportant in certain inclusion complexation systems.

The Driving Forces in the Inclusion Complexation of Cyclodextrins

“Induced-fit”-type complex formation of the model enzyme α-cyclodextrin

α-Cyclodextrin, a torus shaped molecule with a 5 A wide central cavity, forms a number of deep green, blue and black crystals when complexed with iodine/metal iodide. In contrast, β-cyclodextrin, having a 6 A cavity produces only one type of reddish-brown crystal, no matter what metal iodide is used. The complex (β-cyclodextrin)2 ·KI7·9H2O displays space groupP21 (pseudo-C2) with cell constantsa=19.609(5),b=24.513(7),c=15.795(6)A, β=109.50(2)°,Z=4. The crystal structure was solved inC2 on the basis of 3022 absorption corrected CuKα (Ni-filter) X-ray intensities and refined by full matrix least squares toR=17%. This relatively highR-factor is due to many weak reflections (pseudo-C2) and considerable disorder exhibited by water and iodine. In the complex, β-cyclodextrin adopts a ‘round’ shape with O(2)...O(3) interglucose hydrogen bonds formed and all O(6) hydroxyls pointing away from the cavity. Two molecules are arranged head-to-head to produce a dimer, and dimers are stacked such that a slightly zigzagged cylinder with a 6 A-wide cavity is formed. In the cavity described by each dimer, an I
 7
 −
 ion composed of I2·I
 3
 −
 ·I2 units is located, with I2 and I
 3
 −
 perpendicular to each other. K+ ions and 9 H2O molecules are found in interstices between the β-cyclodextrin cylinders. This zigzag polyiodide contrasts with the linear form observed in the 5 A wide α-cyclodextrin channels. It explains differences in color of the crystals and suggests that β-cyclodextrin polyiodide is not a good model for blue starch-iodine.

(β-Cyclodextrin)2·KI7·9 H2O. Spatial fitting of a polyiodide chain to a given matrix

α-Cyclodextrin (α-CD) liefert aus Wasser in Gegenwart von Krypton bei 3 und 14 atu kristalline Einschlusverbindungen der Zusammensetzung α-CD·(0.78H2O, 0.48 Kr)·5 H2O (A) und α CD·(0.28 H2O, 0.74 Kr)·5H2O (B). Beide sind isomorph, Raumgruppe P212121. Die Strukturen wurden aus etwa 3900 Rontgenreflexen gelost und bis zu einem R-Faktor von 8.8% verfeinert. Obwohl Kr mit 4 A van der Waals- Durchmesser etwa ebenso gros ist wie H2O3, sind die Strukturen der Kr-Addukte von der des reinen αCD·2H2O-Adduktes verschieden. Der 5.0 A grose Hohlraum im α-CD wird im H2O-Addukt durch Rotation zweier gegenuberliegender Glucosen zusammengezogen und dadurch gespannt. Im beinahe hexagonalen Kr-Addukt sind alle sechs Glucosen annahernd gleichwertig und das Kr besetzt statistisch funf verschiedene Lagen, um den 5.0 A weiten Innenraum auszufullen. Es wird gefolgert, das beim Austausch des Wassers gegen Gastmolekule frei werdende Konformations- und Wasserstoffbruckenenergie die Addukte stabilisiert. Dieser Mechanismus erklart, weshalb viele Gastmolekule mit so unterschiedlichen Eigenschaften eingeschlossen werden und wird im Zusammenhang mit der Enzym-Substrat-Wechselwirkung diskutiert.



Topography of Cyclodextrin Inclusion Complexes, VII* X-Ray Analysis of α-Cyclodextrin. Krypton Pentahydrate. On the Inclusion Mechanism of the Model Enzyme



When crystallized from water under krypton pressures of 43 PSI (A) and 200 PSI(B), α-cyclodextrin (α-CD) yields inclusion compounds of composition α-CD·(0.78 H2O, 0.48 Kr)·5H2O (A) and α-CD·(0.28 H2O, 0.74 Kr)·5H2O (B). Both the adducts are isomorphous, space group P212121. The structures were determined from about 3900 X-ray data and refined to an R-factor of 8.8%. Although Kr has nearly the same van der Waals diameter as H2O (4A), the structures of the Kr and of the recently determined α-CD·2H2O adduct are different. In the latter, the 5.0 A wide cavity of α-CD is diminished by rotation of two glucoses, rendering the α-CD conformation strained. in the almost hexagonal Kr-adduct, all six glucoses are approximately equivalent, the cavity is 5 A in diameter and the Kr is statistically disordered over five positions. It is concluded that α-CD adducts are stabilized through release of conformation- and hydrogen bonding energy when the “empty” α-CD·2H2O adduct transforms into any other adduct. This mechanism explains why so many different guest molecules are enclosed and bears some relation to enzyme-substrate interactions.

Topographie der Cyclodextrin‐Einschlußverbindungen, VII. Röntgenstrukturanalyse des α‐Cyclodextrin. Krypton‐Pentahydrats. Zum Einschlußmechanismus des Modell‐Enzyms

Mathias Noltemeyer

Papers

“Induced-fit”-type complex formation of the model enzyme α-cyclodextrin

(β-Cyclodextrin)2·KI7·9 H2O. Spatial fitting of a polyiodide chain to a given matrix

Topographie der Cyclodextrin‐Einschlußverbindungen, VII. Röntgenstrukturanalyse des α‐Cyclodextrin. Krypton‐Pentahydrats. Zum Einschlußmechanismus des Modell‐Enzyms

X‐Ray Structure Analysis of the α‐Cyclodextrin‐Krypton Inclusion Complex: A Noble Gas in an Organic Matrix

Röntgen‐Strukturanalyse des α‐Cyclodextrin‐Krypton‐Einschlußkomplexes: Ein Edelgas in organischer Matrix