Cyclodextrins functional structure

Figure 1. Functional structural scheme of cyclodextrins. (Reprinted with permission from Ref. 1. Copyright 1982 Akademlal Klado.)...

The property of cyclodextrins of primary interest in this text is the formation of hydrogen-bonding networks in the crystalline state. These networks are extensive because the cyclodextrin crystal structures contain not only the three donor hydroxyl groups and five potential acceptor oxygen atoms characteristic of the glucose unit, but also many waters of crystallization. The total number of donors and acceptors respectively is 18 and 30 for a-cyclodextrin, 21 and 35 for /7-cyclodextrin, and 24 and 40 for y-cyclodextrin, to which is added the double donor and double acceptor function of each of the water molecules.3... 

The condensation reactions described above are unique in yet another sense. The conversion of an amine, a basic residue, to a neutral imide occurs with the simultaneous creation of a carboxylic acid nearby. In one synthetic event, an amine acts as the template and is converted into a structure that is the complement of an amine in size, shape and functionality. In this manner the triacid 15 shows high selectivity toward the parent triamine in binding experiments. Complementarity in binding is self-evident. Cyclodextrins for example, provide a hydrophobic inner surface complementary to structures such as benzenes, adamantanes and ferrocenes having appropriate shapes and sizes 12) (cf. 1). Complementary functionality has been harder to arrange in macrocycles the lone pairs of the oxygens of crown ethers and the 7t-surfaces of the cyclo-phanes are relatively inert13). Catalytically useful functionality such as carboxylic acids and their derivatives are available for the first time within these new molecular clefts. 

Recently, we have also prepared nanosized polymersomes through self-assembly of star-shaped PEG-b-PLLA block copolymers (eight-arm PEG-b-PLLA) using a film hydration technique [233]. The polymersomes can encapsulate FITC-labeled Dex, as model of a water-soluble macromolecular (bug, into the hydrophilic interior space. The eight-arm PEG-b-PLLA polymersomes showed relatively high stability compared to that of polymersomes of linear PEG-b-PLLA copolymers with the equal volume fraction. Furthermore, we have developed a novel type of polymersome of amphiphilic polyrotaxane (PRX) composed of PLLA-b-PEG-b-PLLA triblock copolymer and a-cyclodextrin (a-CD) [234]. These polymersomes possess unique structures the surface is covered by PRX structures with multiple a-CDs threaded onto the PEG chain. Since the a-CDs are not covalently bound to the PEG chain, they can slide and rotate along the PEG chain, which forms the outer shell of the polymersomes [235,236]. Thus, the polymersomes could be a novel functional biomedical nanomaterial having a dynamic surface. 

Structurally developed cyclodextrins. Effective procedures for the selective functionalization of peripheral hydroxyl groups on the cyclodextrins have been developed. A motivation for these studies has been to produce suitably functionalized hosts which will induce enhanced reaction rates... 

Numerous examples of modiflcations to the fundamental cyclodextrin structure have appeared in the literature.The aim of much of this work has been to improve the catalytic properties of the cyclodextrins, and thus to develop so-called artificial enzymes. Cyclodextrins themselves have long been known to be capable of catalyzing such reactions as ester hydrolysis by interaction of the guest with the secondary hydroxyl groups around the rim of the cyclodextrin cavity. The replacement, by synthetic methods, of the hydroxyl groups with other functional groups has been shown, however, to improve remarkably the number of reactions capable of catalysis by the cyclodextrins. For example, Breslow and CO workersreported the attachment of the pyridoxamine-pyridoxal coenzyme group to beta cyclodextrin, and thus found a two hundred-fold acceleration of the conversion of indolepyruvic acid into tryptophan. 

Potentiometric sensing based on type 3 derivatives of a-, P-, and y-cyclodextrins has been reported.We have been interested in the type 1 cyclodextrin derivatives developed by Tagaki, e.g., host 41. This type of cyclodextrin derivative is characteristic in that the primary hydroxyl groups at the C-6 positions are exhaustively substituted with long alkyl chains. At the surface of an oiganic membrane, this structural feature allows the secondary hydroxyl side (wider open end of the cavity) to face the aqueous solution to accommodate a guest molecule. The interfacial receptor functions of these cyclodextrin hosts have been confirmed mainly by rt-A isotherm studies. 

In order to prepare certain excellent and sophisticated enzyme models, preparation of cyclodextrins having one or more functional groups is essential. At the same time, firm experimental evidence for their structures should be provided. 

Figure 1.1 Molecular structure of functionalized -cyclodextrin and the corresponding binary complex with p-nitrophenyl acetate.

Bouquet -shaped molecules based on either a polyether macrocycle [8.205] or a /3-cyclodextrin (/3-CD) [8.206] core, such as 114 and 115 respectively, have been synthesized and their polycarboxylate forms have been incorporated into vesicle bilayer membranes [8.207]. They present structural features suitable for studies of chundle-type molecular channels (1) the functionalized cyclic annulus possesses substrate selection properties (2) it bears axially oriented bundles of oxygen-containing chains, which provide binding sites for metal cations and are long enough for the molecule to span a typical lipid membrane (the overall length with the chains... 

Tong, W.Q., Lach, J. L., Chin, T. F., and Guillory, J. K. 1991b. Structural effects on the binding of amine drugs with the diphenylmethyl functionality to cyclodextrin I a microcalorimetric stffflfyarm. Res. 

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