Cyclodextrin derivatives complexes

Isoxazolines 38 and 39 were obtained in different ratios by direct cycloaddition of 4-t-butylbenzonitrile oxide with acids 35 (R = H, path B) and by the intermediate formation of cyclodextrin derivatives 36 and 37 followed by basic hydrolysis and acidification (path A). The reversed regioselectivity as well as an increased rate of the cycloaddition step could be explained through the temporary association of the nitrile oxide with the cyclodextrin to give the inclusion complex 40 <06CEJ8571>. 

Addition of an aqueous solution of PEG to a saturated aqueous solution of a-CD at room temperature did not lead to complex formation unless the average molecular weight of PEG exceeded 200 [46]. Moreover, carbohydrate polymers such as dextran and pullulan failed to precipitate complexes with PEG, and the same was true for amylose, glucose, methyl glucose, maltose, maltotriose, cyclodextrin derivatives, such as glucosyl-a-CD and maltosyl-a-CD, and water-soluble polymers of a-CD crosslinked by epichlorohydrin. These facts suggested to Harada et al. the direction for further research. 

Polymerization in P-cyclodextrin (CD) complexes with monomer offers a route to polymerization, as well as other organic reactions, in water without the need for organic solvents [Ritter and Tabatabai, 2002]. P-Cyclodextrins are toms-shaped, cyclic oligosaccharides obtained by degradation of starch. The hydroxyl groups of the glucose repeat unit of CD are located on the outer surface. This makes the outer surface hydrophilic, whereas the inner surface and cavity are hydrophobic. Water-insoluble monomers become solubilized in water when mixed with CD or CD derivatives because the monomers are absorbed into the cavity. This allows polymerization in aqueous, not organic media, with water-soluble initiators. 

Even more generally applicable are GC columns with chiral metal chelates as stationary phases (complexation gas chromatography)26 (Table 6). Quite recently, chiral GC methods have been developed on the basis of cyclodextrin derived stationary phases27. 

In analogy to the carboxylate binding by zinc-containing cyclodextrin 10 (see Sect. 2), Lewis acidic centers such as a copper(II) histamine unit may also serve for the chelation of the (deprotonated) 2-aminoacetate substructure of a-amino acids [51], Rizzarelli, Marchelli et al. used a respective j8-cyclodextrin derivative for the formation of the ternary complexes 36 and 37 with racemic... 

Nakajima et al. (1) prepared liquid crystalline polyrotaxane derivatives containing the mesogenic group 4-cyano-4 -hydroxybiphenyl attached to the a-cyclodextrin component of linear polyethylene glycol containing an a-cyclodextrin inclusion complex with an adamantane termini. 

Muller, B.W. and Albers, E. (1991). Effect of hydrotropic substances on the complexation of sparingly soluble drugs with cyclodextrin derivatives and the in uence of cyclodextrin complexation on the pharmacokinetics. Pharm. Sci., 80, 599. 

Lanthanide complexes of mono- and tetra-amide /1-cyclodextrin derivatives of DOTA have been characterized [140]. The proton NMR spectra of the Eu3+ complexes in methanol-d, show that, while the tetra-amide complex occurs in solution exclusively as a C4-symmetry SAP structure, the mono-amide complex, with less than C4-symmetry, occurs predominantly as two SAP isomers (A/XXXX and Al8885), with the presence of a small amount of the twisted SAP isomer. Luminescence and relaxivity measurements confirm that the Eu3+, Tb3+ and Gd3+ complexes of the eight-coordinate mono-amide ligand possess one bound water molecule, while the tetra-amide complexes have q = 0. The relaxivity of the /LCD mono-amide Gd3+ complex is enhanced when non-covalently bound to a second Gd3+ complex bearing two phenyl moieties (MS-325, AngioMARK , EPIX/Mallinckrodt). 

Arima, H., et al. 1992. Enhanced rectal absorption and reduced local irritation of the antiinflammatory drug ethyl 4-biphenylylacetate in rats by complexation with water-soluble (3-cyclodextrin derivatives and formulation as oleaginous suppository. J Pharm Sci 81 1119. 

Zwitterionic cyclodextrins were designed and synthesized by Tabushi a long time ago as artificial receptors for amino acids in water [25]. Only a very low enantioselectivity was detected for Trp. Inoue also studied the complexation of two new P-cyclodextrin derivatives bearing m-toluidinyl and [(9-fluorenyl)-amino]alkylamino groups with various D/L-amino acids by fluorescence spectroscopy in buffered (pH=7.2) aqueous solution. An enantioselectivity as high as 33 was found for D/L-leucine and the former host [26]. 

Certain fundamental characteristics of MECC that influence retention have been investigated (5). The technique has been used in the analysis of a variety of samples including phenolic compounds (1), phenylthiohydantoin—amino acids (6), and metabolites of vitamin Bg (7). In related electrokinetic separation techniques, substituted benzene compounds have been separated based on the formation of inclusion complexes with an ionic cyclodextrin derivative in the mobile phase (8) and polyaromatic hydrocarbons have been separated based on solvophobic interactions with a tetraakyl— ammonium ion in the mobile phase (9). The effects of injection procedures on efficiency have also been studied (10). 

The utility of the highly soluble 6-cyclodextrin derivatives (soluble polymer and dimethyl-6-cyclodextrin) in RPTLC is illustrated in the separation of barbiturates. The lipophilicity of a barbiturate or any guest decreases when included in a cyclodextrin-cavity. Therefore its mobility is modified in reversed phase thin layer chromatography. With this simple and rapid method, the stability of a complex can be estimated empirically (Table II). The "b" value of the following equation is characteristic for the complex stability (in water ethanol =4 1 solution, R determined at 5 different cyclodextrin concentrations for 21 barbiturates) ... 

The first electrically driven enantioseparations involved the addition of a chiral selector to the mobile phase in CE. This selector is usually a complexing agent and acts as a pseudo-stationary phase. The separation is accomplished by the difference in the distibution equilibria between the pseudo-stationary phase and the enantiomers [134], The most common additives incorporated into these CE experiments were cyclodextrins and cyclodextrin derivatives [135-138], However, these experiments required the replacement of the chiral selector after each electrophoretic run. 

Even though cyclodextrins drug complexes seem to decrease ocular toxicity of irritant drugs, cyclodextrins themselves may exhibit ocular toxicity and should therefore be screened by performing corneal sensitivity studies. Among all cyclodextrin derivates investigated, hydroxy-propyl-P-cyclodextrin showed the most favorable properties in terms of toxicity [1],... 

Muller, B. W., and Brauns, U. (1986), Hydroxypropyl-P-cyclodextrin derivatives Influence of average degree of substitution on complexing ability and surface activity, J. Pharm. Set, 75, 571-572. 

Liu,FY.,Kildsig,D. O., and Mitra,A. K. (1992),Complexation of 6-acyl-O-P-cyclodextrin derivatives with steroids, effects of chain length and substitution degree, Drug Del. Ind. Pharm., 18,1599-1612. 

Badawy, S.I.F. Ghorab, M.M. Adeyeye, C. Study of the complexation between danazol and hydrophilic cyclodextrin derivatives. Pharm. Res. 1995,12 (9), S204. 

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