Hydrophobic cyclodextrins

Scheme 1 Reaction pathway for the preparation of hydrophobic cyclodextrin derivatives with "inverse" substituion pattern. (TBDMS-Cl = tert-butyldimethyl-siiyl chloride, NBu F = tetra- -butylammonium fluoride.) [From Konig et al. (33).J...

With the advent of hydrophobic cyclodextrin derivatives, many chiral constituents of essential oils became the subject of a detailed investigation of their enantiomeric composition. Several essential oils are used as additives in pharmaceutical formulations, for example, pine needle oil or peppermint oil. They are not only used for their pleasant flavor or fragrance, monoterpene hydrocarbons like a-pinene 18], p-pinene [9], and... 

The effect of the hydrophobic cyclodextrin cavity of 7 was enhanced and the lifetime of the 7-oxygen adduct was prolonged to about 1 hr in the aqueous medium at —10 °C when a drop of benzene was dispersed in the aqueous medium of the deoxy-7 imidazole complex. The benzene was probably occluded in the cavity of the capping cyclodextrin However, the life-time decreased with temperature of the aqueous medium and the oxygen adduct was scarcely observed above 0 C. The steric and... 

A single PANl nanowire of 100 nm diameter was produced by electrochemical growth on gold electrodes modified with SAMs of thiolated cyclodextrins or 4-aminothiophenol (molecular templates) in alkanethiol [73,74]. Monomers were seeded to the surface within the isolated hydrophobic cyclodextrin cavities and initiated polymerization. While in these studies, the shape and directionality of the nanowires were not well controlled, they have demonstrated the possibility of growing individual CPNWs in selected locations using molecular templates. 

Y. Ikeda, K. Kimura, F. Hirayama, H. Arima, and K. Uekama, Controlled release of a water-soluble drug, captopril, by a combination of hydrophilic and hydrophobic cyclodextrin derivatives,/. Control Release, 66 (2-3), 271-280,2000. 

Cyclodextrins are macrocyclic compounds comprised of D-glucose bonded through 1,4-a-linkages and produced enzymatically from starch. The greek letter which proceeds the name indicates the number of glucose units incorporated in the CD (eg, a = 6, /5 = 7, 7 = 8, etc). Cyclodextrins are toroidal shaped molecules with a relatively hydrophobic internal cavity (Fig. 6). The exterior is relatively hydrophilic because of the presence of the primary and secondary hydroxyls. The primary C-6 hydroxyls are free to rotate and can partially block the CD cavity from one end. The mouth of the opposite end of the CD cavity is encircled by the C-2 and C-3 secondary hydroxyls. The restricted conformational freedom and orientation of these secondary hydroxyls is thought to be responsible for the chiral recognition inherent in these molecules (77). 

Fig. 8. A hydrophobic inclusion complex between a chiral analyte and a cyclodextrin.

Armstrong and Jin [15] reported the separation of several hydrophobic isomers (including (l-ferrocenylethyl)thiophenol, 1 -benzylnornicotine, mephenytoin and disopyramide) by cyclodextrins as chiral selectors. A wide variety of crown ethers have been synthesized for application in enantioselective liquid membrane separation, such as binaphthyl-, biphenanthryl-, helicene-, tetrahydrofuran and cyclohex-anediol-based crown ethers [16-20]. Brice and Pirkle [7] give a comprehensive overview of the characteristics and performance of the various crown ethers used as chiral selectors in liquid membrane separation. 

On the other hand, the values of AH° and AS° for a-cyclodextrin-l-alkanol systems are significantly more negative than those for the corresponding P-cyclOdextrin systems. 1-Alkanols must fit closely into the cavity of a-cyclodextrin, so that the com-plexation is governed by van der Waals interaction rather than by hydrophobic interaction. 

These equations show that hydrophobic and steric (van der Waals) interactions are of prime importance in the inclusion processes of cyclodextrin-alcohol systems. The coefficient of Es was positive in sign for an a-cyclodextrin system and negative for a P-cyclodextrin system. These clear-cut differences in sign reflect the fact that a bulky alcohol is subject to van der Waals repulsion by the a-cyclodextrin cavity and to van der Waals attraction by the p-cyclodextrin cavity. 

Upon formulating these relationships, phenols with branched alkyl substituents were not included in the data of a-cyclodextrin systems, though they were included in (3-cyclodextrin systems. In all the above equations, the n term was statistically significant at the 99.5 % level of confidence, indicating that the hydrophobic interaction plays a decisive role in the complexation of cyclodextrin with phenols. The Ibrnch term was statistically significant at the 99.5% level of confidence for (3-cyclo-dextrin complexes with m- and p-substituted phenols. The stability of the complexes increases with an increasing number of branches in substituents. This was ascribed to the attractive van der Waals interaction due to the close fitness of the branched substituents to the (3-cyclodextrin cavity. The steric effect of substituents was also observed for a-cyclodextrin complexes with p-substituted phenols (Eq. 22). In this case, the B parameter was used in place of Ibmch, since no phenol with a branched... 

Only the hydrophobic and steric terms were involved in these equations. There are a few differences between these equations and the corresponding equations for cyclo-dextrin-substituted phenol systems. However, it is not necessarily required that the mechanism for complexation between cyclodextrin and phenyl acetates be the same as that for cyclodextrin-phenol systems. The kinetically determined Kj values are concerned only with productive forms of inclusion complexes. The productive forms may be similar in structure to the tetrahedral intermediates of the reactions. To attain such geometry, the penetration of substituents of phenyl acetates into the cyclodextrin cavity must be shallow, compared with the cases of the corresponding phenol systems, so that the hydrogen bonding between the substituents of phenyl acetates and the C-6 hydroxyl groups of cyclodextrin may be impossible. 

The rate acceleration imposed by 0-cyclodextrin was explained in terms of a microsolvent effect 6> The inclusion of the substrate within the hydrophobic cavity of cyclodextrin simulates the changes in solvation which accompany the transfer of the substrate from water to an organic solvent. Uekama et al.109) have analyzed the substituent effect on the alkaline hydrolysis of 7-substituted coumarins (4) in the... 

Cyclodextrins (CDs) are cyclic a-l,4-linked D-(- -)-glucopyranose units (a-CD = six units jS-CD = seven units) that form inclusion complexes with a variety of hydrophobic molecules in aqueous medium [64]. 

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