alpha-CD Cavity Research Articles

Theoretical Studies on Inclusion Complexes of Cyclodextrins

Quantum chemical calculations and molecular dynamics simulations are carried out to study the host-guest inclusion complexes of cyclodextrins (alpha-, beta-, and gamma-CDs) with small guest molecules such as H(2)O, NH(3), NH(4)(+), C(6)H(6), and bisimidazolyl compounds. The uptake ability of the CDs to accommodate the small molecules inside the cavity is examined by the sequential addition of 10 molecules of water or ammonia using the semiempirical (PM3) method. In the case of benzene, this was done up to six molecules. PM3 calculations indicate that alpha-, beta-, and gamma-CD can accommodate three, seven, and nine water molecules, respectively. In the case of NH(3) as guest molecule, alpha-, beta-, and gamma-CDs can accommodate up to two, five, and six molecules, respectively. Semiempirical calculations indicate that two benzene molecules can be accommodated in the alpha-CD cavity, whereas beta- and gamma-CD cavities adopt three and four benzene molecules, respectively. Molecular dynamics simulations were carried out for 1.0 ns on benzene and bisimidazolyl complexes of CDs in explicit solvent (TIP3P water model). The interaction energies calculated by the MM/PBSA method reveal that ligand 1,6-bis(imidazol-l-lyl) hexane (B) and 1,4-bis(imidazol-l-lylmethyl) benzene (C) molecules prefer to form 1:1 complexes with alpha-, beta-, and gamma-CDs. However, C preferentially forms 1:2 complexes with alpha-CDs. Ligands 1,10-bis(imidazol-l-lyl) decane (A) and 4,4'-(bis(imidazol-l-ylmethylene))biphenyl (D) form 1:2 complexes with alpha-, beta-, and gamma-CDs in head-to-head (HH) orientation of CDs. The stability of inclusion compounds depends on the type of CD and the physicochemical properties of the involved guest. Both of these methods (semiempirical and MD simulations) reveal that beta-CDs form more stable complexes compared with alpha- and gamma-CDs with C, D, NH(4)(+), and C(6)H(6), whereas alpha-CD forms more stable complexes with A and B.

Switching of polymerization activity of cinnamoyl-α-cyclodextrin

Cinnamoyl alpha-cyclodextrin (alpha-CD) has been found to initiate polymerization of delta-valerolactone (delta-VL) to give a polymer in high yield. By the presence of the cinnamoyl group, hydrogen bond was formed between the carbonyl oxygen of delta-VL and the hydroxyl group of CD to activate the monomer, which was observed by FT-IR measurements. However, the cinnamoyl group at the C(3)- and C(6)-positions of alpha-CD did not affect the polymerization ability. Only that of the C(2)-position showed high polymerization activity. The polymerization activity could be switched by the photoisomerization of the cinnamoyl group attached to the rim of alpha-CD. Specific monomer recognition and polymerization in the active site of the alpha-CD cavity was changed by the photoisomerization.

Tuning dual emission behavior of p-dialkylaminobenzonitriles by supramolecular interactions with cyclodextrin hosts

Ground state absorption and steady-state and time-resolved fluorescence measurements have been carried out to understand the host-guest interactions of p-diethylaminobenzonitrile (DEABN) and p-dimethylaminobenzonitrile (DMABN) dyes with alpha-cyclodextrin (alpha-CD) and beta-cyclodextrin (beta-CD) hosts. DEABN and DMABN dyes show both locally excited (LE) state and intramolecular charge transfer (ICT) state emissions in solution. The LE and ICT emissions of the dyes are seen to get modulated in the presence of alpha-CD and beta-CD hosts. The results indicate that the dyes form 1 : 1 inclusion complexes with both the hosts. Comparing the binding constants and the fluorescence characteristics of different dye x CD systems it is inferred that DEABN adopts a completely different orientation on complexation with alpha-CD than in the other cases of dye.CD systems. It is indicated that while in all other cases of dye x CD systems the N,N-dialkyl group of the dyes enters the host cavity leaving the C[triple bond, length as m-dash]N group projected out into the water phase, the DEABN dye enters the alpha-CD cavity (smallest CD) with its C[triple bond, length as m-dash]N group entering the host cavity. The differences in the orientation of the dye in the host cavities is understood to be determined by the requirement of maximum van der Waals contact of the encapsulated dye with the host cavity for maximum stability of the complex and the relative sizes of the substituents of the dye compared to the host cavities. From the observation that the binding constants for the present dye x CD systems are not that significantly high, it is inferred that the hydrophobic interaction mainly govern the inclusion complex formation in the present systems.

Drug‐binding hydrogels of hyaluronic acid functionalized with β‐cyclodextrin

Hyaluronic acid (HA) hydrogels are attractive materials for biomedical applications because they are porous, water-swelling, biocompatible, biodegradable, and resistant to non-specific cell adhesion. A limitation of HA hydrogels is that incorporation of bioactive drugs can be restricted by low solubility of drug within the hydrogel environment. Our goal was to synthesize HA hydrogels that bind drug through hydrophobic interactions as a method for increasing drug loading. We functionalized photocrosslinked HA hydrogels with a methacryloyl derivative of beta-cyclodextrin (betaCD). betaCD is a molecular "basket" with a hydrophilic exterior and a hydrophobic cavity. Inclusion complexes are formed when betaCD hosts all or part of a hydrophobic drug within the cavity. HA hydrogels functionalized with methacryloyl-betaCD monomer gained the property of inclusion complexation which greatly enhanced the uptake of a model hydrophobic drug, hydrocortisone. Pre-incubation of the hydrogels with adamantane carboxylic acid (ACA) inhibited hydrocortisone uptake by competition for betaCD cavities. In addition, control hydrogels of HA functionalized with alphaCD monomer were not efficient at hydrocortisone uptake because the alphaCD cavity is too small for efficient complexation. These experiments confirmed that the betaCD monomer enhances drug loading by the mechanism of inclusion complexation. Drug-binding HA-betaCD hydrogels may be further engineered to create HA-based biomaterials with a built in drug delivery capability.

Molecular Motions of .ALPHA.-Cyclodextrin on a Dodecyl Chain Studied by Molecular Dynamics Simulations

Motions of an alpha-cyclodextrin (alpha-CD) molecule on a dodecyl chain adopting the all-trans conformation were investigated in the presence of water by molecular dynamics simulations with CVFF force fields, where the trimethylammonium group of dodecyltrimethylammonium bromide (DTAB) is protruded outside the secondary hydroxyl rim of alpha-CD (the secondary-in structure). The alpha-CD molecule shuttled rapidly on the chain without decomplexation. This rapid motion is consistent with the NMR data. The plane formed by 6 O4 atoms of alpha-CD is most populated between the C6 and C7 atoms of DTAB. This structure is very close to that estimated by NMR. The alpha-CD molecule underwent a restricted rotation in a range of 60 degrees with regard to the plane of the dodecyl chain: this plane at the most population is middle between the two diagonal lines of the normal hexagon formed by 6 O4 atoms of alpha-CD. The published NMR data were reanalyzed in terms of the rotation angle, and a slightly better structure was obtained. The distortion of the alpha-CD cavity from the normal hexagon was decreased upon complex formation with DTAB. The deviation of the center of alpha-CD from the center of the dodecyl chain predicted by molecular dynamics simulations is consistent with the NMR data. The secondary-in structure is energetically more stable than the primary-in structure, as calculated by molecular mechanics with CVFF and Amber force fields. This result is consistent with the NMR data. Molecular dynamics simulations were also carried out for the primary-in structure. Some of the results are close to those of the secondary-in structure.

Interaction of Cyclodextrins with Aliphatic Acetate Esters and Aroma Components of La France Pear

The interaction between aliphatic acetate esters, which are the major flavor components of La France pear (Pyrus communis L.), and cyclodextrins (CDs) was studied to obtain fundamental data for preparing powdered pear flavor materials. The complexing abilities of alpha-, beta-, or gamma-CD with six kinds of aliphatic acetate esters were compared. alpha-CD formed the highest numbers of complexes with all of the esters. All of the CDs produced complexes more readily with the more hydrophobic esters. Among our samples of freeze-dried pear juice containing dissolved alpha-, beta-, or gamma-CD, the juice with alpha-CD retained the greatest amount of esters. These data demonstrate that alpha-CD is an effective material with which to prepare powdered pear flavor materials. The nuclear Overhauser effect, measured by (1)H NMR spectra, of an alpha-CD-butyl acetate or alpha-CD-hexyl acetate complex showed that these esters were included in the alpha-CD cavity.

Orientational isomers of α-cyclodextrin [2]semi-rotaxanes with asymmetric dicationic threads

Two series of novel dicationic threading molecules [Quin(CH2)10R]2+ and [3,5-Lut(CH2)10R]2+, where Quin+ = quinuclidinium, 3,5-Lut+ = 3,5-lutidinium, and R+ = N(CH3)3+ and N(CH3)2CH2CH3+, form [2]semi-rotaxanes with [small alpha]-cyclodextrin (alpha-CD) in aqueous solution. The quinuclidinium and 3,5-lutidinium are sufficiently bulky to prevent threading while the R+ groups allow for slow threading by alpha-CD at 25 degrees C. The resulting [2]semi-rotaxanes exist in two orientational isomers owing to the asymmetry of both the alpha-CD cavity and the threading molecules. Two-dimensional 1H NMR spectroscopy and kinetics experiments reveal that the isomer in which the narrower rim (primary OHs) is positioned near the R+ group is the kinetically preferred isomer, while the other isomer is the thermodynamically preferred product. The kinetics and mechanism of the formation, dissociation, and interconversion of the two isomers have been determined at 25 degrees C.

Inclusion Complex Formation between α‐Cyclodextrin and Biodegradable Aliphatic Polyesters

Inclusion complexes (ICs) between alpha-cyclodextrin (alpha-CD) and three kinds of biodegradable aliphatic polyesters with different sequence lengths of the monomeric repeating units poly(3-hydroxypropionate) [P(3HP)], poly(4-hydroxybutyrate) [P(4HB)] and poly(epsilon-caprolactone)(PCL) were prepared by mixing a solution of alpha-CD with that of the polymer, followed by stirring. The ICs were obtained as insoluble precipitates and characterized by FT-IR, WAXD and DSC. All measurements showed that the polymer chains of all three kinds of polyester were included into the alpha-CD cavity and formed ICs with different stoichiometries. WAXD patterns and thermal analysis indicated that these ICs possessed a channel structure and the crystallization of the polyester chains was suppressed upon inclusion into the alpha-CD cavity.