ß-Cyclodextrin dimers linked through their secondary faces with rigid spacer arms as hosts for bile salts.

A convenient synthesis of ß-cyclodextrin dimers in which the two cyclodextrin units are linked by rigid tethers of relatively short length through their secondary sides is reported. Compounds hexa-2,4-diynediyl- and 1,4-phenylenediethyne-briged ß-cyclodextrin dimers are obtained in good yields from mono-2-O-propargyl-ß-cyclodextrin through Pd-mediated oxidative homo- and heterocoupling reactions. Isothermal titration calorimetry and NMR spectroscopy (PGSE and 2D-ROESY) are used to determine the thermodynamic parameters (K, ΔH, and TΔS°) for the complexation of such ß-cyclodextrin dimers with sodium cholate, deoxycholate, and chenodeoxycholate as well as to estimate the size of the supramolecular structures. The binding of bile salts is enhanced relative to that of native ß-cyclodextrin. Although chenodeoxycholate salt binds in a 1:1 fashion, cholate and deoxycholate salts bind in a 1:2 sequential mode.

Ferrocene-carbohydrate conjugates as electrochemical probes for molecular recognition studies.

We report two methods that have allowed the attachment of glucose, mannose and lactose to one or both of the cyclopentadienyl rings of ferrocene. The resulting ferrocene-carbohydrate conjugates were synthesised by the reaction of thioglycosides with ferrocenemethanol and 1,1'-ferrocenedimethanol in acidic media. A second method based on the regiospecific copper(I)-catalysed cycloaddition of propargyl glycoside, azidomethyl and bis(azidomethyl)ferrocene as well as azidoethyl glycoside and ethynylferrocene was also used and led to the synthesis of 1,2,3-triazole-containing glycoconjugates. The electrochemical behaviour of the synthesised glycoconjugates was investigated. In addition, their binding interactions with beta-cyclodextrin were studied by means of NMR spectroscopy, isothermal titration calorimetry, and cyclic and differential pulse voltammetric experiments. These techniques allowed the determination of the thermodynamic parameters of the complexes, the stability constants for the complexes formed with both the neutral and the oxidised states of the ferrocenyl glycoconjugates, the mode of inclusion and the diffusion coefficients for both the glycoconjugates and the complexes.

Synthesis of nitrogen-functionalized beta-cycloaltrins.

We report the synthesis of functionalized beta-cycloaltrins having azido groups at C-3, C-6, and both C-3 and C-6 by nucleophilic epoxy ring-opening of per-2,3-anhidro-beta-cyclomannin derivatives. The value of these compounds as templates for further functionalization is exemplified by the conversion of heptakis(3,6-diazido-3,6-dideoxy)-beta-cycloaltrin into the per-3,6-diamino, per-3,6-diacetamido, per-3,6-dichloroacetamido, and per[3,6-bis(N'-ethylureido)] derivatives in good yields.

Diverse motifs of mannoside clustering on a beta-cyclodextrin core.

[reaction: see text] A new method for the synthesis of beta-cyclodextrin-based cluster mannosides by application of the Sonogashira cross-coupling reaction is described. The method allows for the persubstitution of the beta-cyclodextrin at either 2- and 3-positions to give two types of heptavalent clusters, at both 2- and 6-positions to give clusters with 14 mannopyranoside units and at 2-, 3-, and 6-positions to obtain clusters with 21 mannopyranoside ligands.

Dendritic galactosides based on a beta-cyclodextrin core for the construction of site-specific molecular delivery systems: synthesis and molecular recognition studies.

In order to evaluate the ability of multivalent glycosides based on a beta-cyclodextrin core as site-specific molecular carriers, a study on both the inclusion complexation behaviour and lectin binding affinity of branched and hyperbranched beta-cyclodextrins is presented. A series of cluster galactosides constructed on beta-cyclodextrin scaffolds containing seven 1-thio-beta-lactose or beta-lactosylamine bound to the macrocyclic core through different spacer arms were synthesised. In addition, the first synthesis of three first-order dendrimers based on a beta-cyclodextrin core containing fourteen 1-thio-beta-D-galactose, 1-thio-beta-lactose and 1-thio-beta-melibiose residues was performed. Calorimetric titrations performed at 25 degrees C in buffered aqueous solution (pH 7.4) gave the affinity constants and the thermodynamic parameters for the complex formation of these beta-cyclodextrin derivatives with guests sodium 8-anilino-1-naphthalenesulfonate (ANS) and 2-naphthalenesulfonate, and lectin from peanut (Arachis hypogaea) (PNA). The persubstitution of the primary face of the beta-cyclodextrin with saccharides led to a slight increase of the binding constant values for the inclusion complexation with ANS relative to the native beta-cyclodextrin. However, the increase of the steric congestion due to the presence of the saccharide residues on the narrow rim of the beta-cyclodextrin may cause a decrease of the binding ability as shown for sodium 2-naphthalenesulfonate. The spacer arms are not passive elements and influence the host binding ability according to their chemical nature. PNA forms soluble cross-linked complexes with cluster galactosides and lactosides scaffolded on beta-cyclodextrin but not with cluster galactopyranosylamines or melibiose. Both, perbranched and hyperbranched beta-cyclodextrins, form stronger complexes with PNA than the monomeric analogues. However, the use of hyperbranched CDs does not contribute to the improvement of the complex stability relative to heptakis-glycocyclodextrin derivatives. Finally, a titration experiment with PNA and a complex formed by a heptakis lactose beta-cyclodextrin derivative with sodium 2-naphthalenesulfonate showed the formation of a soluble cross-linked complex with stronger affinity constant and higher stoichiometry than those observed for the complex formation of PNA with the same heptakis-lactose beta-cyclodextrin derivative, suggesting the formation of a three component complex.