Cyclodextrin-based Systems

Since a very large number of rotaxanes and poly rotaxanes that contain cyclodextrins and cyclodextrin derivatives are known, discussion of only a representative selection of such compounds is presented in this section. 

In a related study, a- or P-cyclodextrin rotaxanes based on [(en)2CoNH2(CH2)2 S(CH2) jS(CH2)2NH2Co(en)2]Cl (where en = ethane-1,2-diamine) were synthe- 

Since these studies, many other rotaxanes incorporating cyclodextrins or their substituted derivatives have been reported, including other metal-containing systems. The latter include a series of a-cyclodextrin rotaxanes formed by the reaction of labile [Fe(CN)50H2J ions with pre-threaded l,l -(a,(o-alkanediyl)-bis(4,4 -bipyridinium) dicationic moieties (incorporating methylene chains between 8- and 12-members long).  

Related symmetrical systems, involving a-cyclodextrin threaded onto alkyl chains that are terminated by cationic aromatic (heterocyclic) end groups, are also known. Formation of the above species involves threading of the 4,4 -bipyri-dinium groups through the a-cyclodextrin such that the alkyl chain lies in the cavity, with the cationic bipyridinium end groups extending on either side. 

Yonemura, H. Saito, S. Matsushima, H. Nakamura and T. Matsuo, Tetrahedron Lett., 1989, 30, 3143 H. Saito, H. Yonemura, H. Nakamura and T. Matsuo, Chem. Lett., 1990, 535. 

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In addition, cyclodextrins incorporating a 2,6-bis(imino)pyridine unit have been used to support active iron polymerisation catalysts. Using the (i-cyclodextrin-based system 52, in the presence of a large excess of MAO, ethylene can be converted into HDPE (Fig. 16). Only low activities are, however, observed, which... 

In particular, a molecularly imprint-based CEC system was compared with an immobilised protein-based system and a cyclodextrin-based system for the enantiomer separation of )8-adrenergic antagonists. It was shown that the MIP-based system could separate all the analytes tested without any change in the experimental conditions (i.e electrolyte composition). This was not possible using the other systems. The chromatographic efficiency, however, was superior for the cyclodextrin-based system. The poor efficiency is a rather discouraging, yet common, feature of molecular imprint-based separation systems. Also, the protein-based systems showed poor efficiency in this study, but optimised conditions can improve this [72,73]. Nevertheless, the MIP-based and protein-based systems showed good selectivity. 

Matthijs, N., Perrin, C., Maftouh, M., Massart, D.L., Vander Heyden, Y. Knowledge-based system for method development of chiral separations with capillary electrophoresis using highly sulphated cyclodextrins. J. Pharm. Biomed. An. 2002, 27, 515-529. 

Hirayama, F., and Uekama, K. Cyclodextrin-based controlled drug release system. Adv. Drug Deliv. Rev. 36(1) 125-141, 1999. 

While lying outside the scope of the present discussion, it is noted that a range of polymeric systems incorporating cyclodextrin-based rotaxanes, often with unusual architectures, have been synthesised. 

Finally, as mentioned earlier, a considerable number of other cyclodextrin-based rotaxane and pseudorotaxane systems have been reported but, by and large, they represent variations on a theme with respect to the individual systems discussed in this section. 

Karakhanov, E. A., Zhuchkova, A. Y., Filippova, T. Y., Maksimov, A. L. Supramolecular cyclodextrin-based catalyst systems in Wacker oxidation. Neftekhimiya 2003,43, 302-307. 

Yui s group has investigated biodegradable polymers based on the cyclodextrin-based polyrotaxanes over the course of the last decade [128-139]. First, they prepared polyrotaxanes from a-cyclodextrin and PEG bisamine (Scheme 23) [128]. For example, l-phenylalanine was employed as an enzymatically hydrolyzable endcap. The in vitro degradation experiments using papain showed that a-cyclo dextrin was indeed released only when the terminal peptide linkages were hydrolyzed. They have prepared various kinds of polyrotaxanes based on cyclodextrin and have demonstrated that these polyrotaxanes are effective as drug delivery systems. 

Cyclodextrins have proven to be the most popular enzyme mimics, catalyzing various reactions. Cyclodextrin-based neoglycoenzymes with improved efficiency have also been designed and synthesized. Cyclodextrin-modified enzymes have potential application as biosensors as well as in the formulation of effective and biodegradable drug delivery systems for enzyme replacement therapy [84]. 

Cyclodextrin-based drug delivery systems The hydrophilic cyclodextrins have been extensively )plied to enhance the oral bioavailabilily of steroids, cardiac glycosides, nonsteroidal anti-inflammatory drugs, barbiturates, antiepileptics, benzodiazepines, antidiabetics, vasodilators, etc. Delayed and prolonged release of diltiazem and molsidormine was achieved by their complexation with CD derivatives, modified release of nifedipine can be achieved by its complexation with 2-HP-P-CD fiirosemide and piretanide (loop diuretics) release can be modified after complexation with DM-P-CD. Prednisolone dosage forms can be optimized also by complex-formation with 2-HP-P-CD. 

A more sophisticated (3-cyclodextrin-based catalytic system combining different functions in the same molecule was also conceived. Rhodium complexes of multi-component ligands featuring a chelating diphosphine covalently linked to the upper riin of P-cyclodextrin (Fig. 6) were used as catalysts for the hydrogenation and the hydroformylation of alkenes in water-organic two-phase systems. 

For a historically comprehensive review of the literature on the structure and properties of CDs and their inclusion complexes (both basics and applications) we refer to the special issue Cyclodextrins of Chem. Soc. Rev CD-based systems proved to be excellent tools for applications in chemical synthesis, analysis and separation science, biomimetic... 

Yui s group found the thermal stability of their biodegradable polyrotaxane was better than that of the separate components, poly( -lysine) and a-cyclodextrin [12,13]. In some crown ether based systems, as shown below, thermal stabihty decreases because of the lability of the cyclic components. 

Vyas, A., Saraf, S., Saraf, S. Cyclodextrin based novel drug dehvery systems. J. Inch Phenom. Macrocycl. Chem. 62(1-2), 23 2 (2008)... 

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