Cyclodextrins interactions

Until 1984, all of the stopped-flow and temperature-jump kinetic studies of alpha cyclodextrin inclusion-complex formation were explainable in terms of a single-step, binding mechanism. According to this mechanism, the observed rate constant, kobs, (for stopped-flow) and the reciprocal relaxation time, 1/t, (for temperature-jump) should show a linear dependence on the edpha cyclodextrin concentration. Sano and coworkers, however, in the case of the iodide-alpha cyclodextrin interaction, and Hersey and Robinson,in the case of various azo dye-alpha cyclodextrin interactions (see Fig. 7), found that certain guest species exhibit a limiting value of kobs and 1/t at high concentrations of alpha cyclodextrin. This behavior can most simply be explained in terms of a mechanism of the type,... 

Cyclodextrins are commonly available in three different sizes (i.e., a, /3, -y), and further CD derivatives are now commercially obtainable. Native CDs are often used in CE, since they are not very expensive and numerous compounds are baseline-resolved in chiral separation using CD as buffer additives. /3 -Cyclodextrin interacts with a wide variety of compounds, but... 

One additional advantage of chiral CE over chromatographic techniques is that both the chiral selector and the analyte reside in a free solution in this technique. This makes the investigation of chiral drug-cyclodextrin interactions technically much easier, cheaper, and faster, because unlike chromatographic techniques there is no need to immobilize the receptor (selectors). However, an even more important advantage is that there is no effect of immobilization on the degree of freedom of the selector and the effects of a solid matrix are absent. 

The main disadvantage of CE for the investigation of interactions between chiral drugs and cyclodextrins is that CE does not provide any direct information on the structure of selector-selectand complexes. In the next section, some complementary techniques for the investigation of chiral drug-cyclodextrin interactions are discussed and parallels are drawn between these techniques and CE. 

IV. COMPLEMENTARY TECHNIQUES FOR INVESTIGATION OF CHIRAL DRUG/CYCLODEXTRIN INTERACTIONS... 

In summary, molecular modeling when used in combination with instrumental techniques, especially 1D-ROESY and X-ray crystallography, may significantly contribute to understanding the nature of the intermolecular forces responsible for chiral drug-cyclodextrin interactions and chiral recognition. 

Cooper, A. Lovatt, M. Nutley, M.A. Energetics of protein-cyclodextrin interactions. J. Inclusion Phenom. Mol. Recognit. Chem. 1996, 25 (1-3), 85-88. 

Sharma, A. Janis, L.S. Lipoprotein-cyclodextrins interaction. Clin. Chim. Acta 1991, 199 (2), 129-137. 

Roessler BJ, Bielinska AU, Janczak K, Lee I, Baker JR (2001) Substituted P-cyclodextrins interact with PAMAM dendrimer-DNA complexes and modify transfection efficiency. Biochem Biophys Res Commun 283 12-129... 

Mathivet, T. Meliet. C. Castanet. Y. Mortreux. A. Caron, L. Tilloy. S. Monflier, E. Rhodium catalyzed hydroformylation of water insoluble olefins in the presence of chemically modified P-cyclodextrins Evidence for ligand-cyclodextrin interactions and effect of various parameters on the activity and the aldehydes selectivity. J. Mol. Catal., A Chem. 2001, 176. 105-116. 

Harada and coworkers reported forming a photoresponsive hydrogel system by combination of a-cyclodextrin, dodecyl-modified poly(acrylic acid), and a photoresponsive competitive guest, 4,4 -azodibenzoic acid. An aqueous solution of dodecyl-modified poly(acrylic acid) exhibits a gel-like behavior, because polymer chains form a network structure via hydrophobic associations of Ci2 side chains. When a-cyclodextrin is added to the gel-like aqueous solution, the gel is converted to a sol mixture because hydrophobic interactions of Ci2 side chains are dissociated by the formation of inclusion complexes of a-cyclodextrin with the C12 side chains. Upon addition of 4,4 -azodibenzoic acid to the binary sol mixture of the modified poly(acrylic acid) and a-cyclodextrin, the cyclodextrin interacts predominantly with 4,4 -azodibenzoic acid ... 

Key Words. Sorbate-cyclodextrin interaction. Effect of water vapour. Gas-solid chromatography. Analytical applications. 

Mura, P. Maestrelli, F. Cirri, M. Furlanetto, S. Pinzauti, S. (2003). Differential Scanning Calorimetry as An Analytical Tool in the Study of Drug-Cyclodextrin Interactions. Journal of Thermal Analysis and Calorimetry, Vol. 73, No. 2, (August 2003), pp. 635-645, ISSN 1388-6150... 

The discovery and chemistry of the non-reducing, chemically stable 2-0-a-D-glucopyranosyl-L-ascorbic acid has been reviewed, and a new synthesis of it has been described in which L-ascorbate and a-cyclodextrin interact in the presence of a cyclomaltodextrin glucanotransferase from Bacillus stearothermophilus. Other products with higher maltooligosaccharides linked to 0-2 of the ascorbate were also formed, but glucoamylase could be used to convert these to more 2-0-a-glucopyranosyl-L-ascorbic acid.7 ... 

Although the chiral recognition mechanism of these cyclodexttin-based phases is not entirely understood, thermodynamic and column capacity studies indicate that the analytes may interact with the functionalized cyclodextrins by either associating with the outside or mouth of the cyclodextrin, or by forming a more traditional inclusion complex with the cyclodextrin (122). As in the case of the metal-complex chiral stationary phase, configuration assignment is generally not possible in the absence of pure chiral standards. 

R SiH and CH2= CHR interact with both PtL and PtL 1. Complexing or chelating ligands such as phosphines and sulfur complexes are exceUent inhibitors, but often form such stable complexes that they act as poisons and prevent cute even at elevated temperatures. Unsaturated organic compounds are preferred, such as acetylenic alcohols, acetylene dicarboxylates, maleates, fumarates, eneynes, and azo compounds (178—189). An alternative concept has been the encapsulation of the platinum catalysts with either cyclodextrin or in thermoplastics or siUcones (190—192). 

Cyclodextrin stationary phases utilize cyclodextrins bound to a soHd support in such a way that the cyclodextrin is free to interact with solutes in solution. These bonded phases consist of cyclodextrin molecules linked to siUca gel by specific nonhydrolytic silane linkages (5,6). This stable cyclodextrin bonded phase is sold commercially under the trade name Cyclobond (Advanced Separation Technologies, Whippany, New Jersey). The vast majority of all reported hplc separations on CD-bonded phases utilize this media which was also the first chiral stationary phase (csp) developed for use in the reversed-phase mode. 

The applications of quantitative structure-reactivity analysis to cyclodextrin com-plexation and cyclodextrin catalysis, mostly from our laboratories, as well as the experimental and theoretical backgrounds of these approaches, are reviewed. These approaches enable us to separate several intermolecular interactions, acting simultaneously, from one another in terms of physicochemical parameters, to evaluate the extent to which each interaction contributes, and to predict thermodynamic stabilities and/or kinetic rate constants experimentally undetermined. Conclusions obtained are mostly consistent with those deduced from experimental measurements. 

It is known that several intermolecular interactions are responsible for cyclodextrin complexation, acting simultaneously. These interactions are separable from one another by quantitative structure-reactivity analysis. Furthermore, correlations obtained by the analysis can be discussed in direct connection with actual interactions already elucidated experimentally for the action site of cyclodextrin. Thus, the results must serve to make the background of the correlation analysis more concrete. 

Several intermolecular interactions have been proposed and discussed as being responsible for the formation of cyclodextrin inclusion complexes in an aqueous solution 6-10). They are... 

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. 

Matsui441 has computed energies (Evdw) due to the van der Waals interaction between a-cyclodextrin and some guest molecules by the use of Hill s potential equation 451 ... 

In this equation, AG°CS is taken to be negligible for p- and y-cyclodextrin systems and to be constant, if there is any, for the a-cyclodextrin system. The AG W term is virtually independent of the kind of guest molecules, though it is dependent on the size of the cyclodextrin cavity. The AG dw term is divided into two terms, AG°,ec and AGs°ter, which correspond to polar (dipole-dipole or dipole-induced dipole) interactions and London dispersion forces, respectively. The former is mainly governed by the electronic factor, the latter by the steric factor, of a guest molecule. Thus, Eq. 2 is converted to Eq. 3 for the complexation of a particular cyclodextrin with a homogeneous series of guest molecules ... 

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