Inclusion compounds of cationic, anionic, and neutral p-substituted derivatives of tert-butylbenzene complexed in beta-cyclodextrin and its ionic 6-mono and 6-hepta derivatives were systematically investigated by isothermal titration calorimetry (ITC). All inclusion compounds showed 1:1 stoichiometry with binding constants ranging from 10 to 3 x 10(6) M(-1). The binding free energies could be subdivided into apolar and electrostatic contributions. The electrostatic interactions could be quantitatively described by Coulomb's law by taking into account the degree of protonation of hosts and guests, the orientations of the guests within the hosts, and ion shielding as described by the Debye-Hückel-Onsager theory. The orientations of the guests within the cyclodextrin cavities were determined by ROESY NMR spectroscopy.

We report the computer-aided optimization of a synthetic receptor for a given guest molecule, based on inverse virtual screening of receptor libraries. As an example, a virtual set of beta-cyclodextrin (beta-CD) derivatives was generated as receptor candidates for the anticancer drug camptothecin. We applied the two docking tools AutoDock and GlamDock to generate camptothecin complexes of every candidate receptor. Scoring functions were used to rank all generated complexes. From the 10 % top-ranking candidates nine were selected for experimental validation. They were synthesized by reaction of heptakis-[6-deoxy-6-iodo]-beta-CD with a thiol compound to form the hepta-substituted beta-CDs. The stabilities of the camptothecin complexes obtained from solubility measurements of five of the nine CD derivatives were significantly higher than for any other CD derivative known from literature. The remaining four CD derivatives were insoluble in water. In addition, corresponding mono-substituted CD derivatives were synthesized that also showed improved binding constants. Among them the 9-H-purine derivative was the best, being comparable to the investigated hepta-substituted beta-CDs. Since the measured binding free energies correlated satisfactorily with the calculated scores, the applied scoring functions appeared to be appropriate for the selection of promising candidates for receptor synthesis.

Starch was oxidized with TEMPO for the synthesis of water-soluble copolymers of glucuronic acid and glucose. The carboxylate groups of these copolymers were conjugated with pteroic acid as cell-specific ligand for targeting to cancer cells. Stable spherical nanoparticles (NPs) were formulated mixing aqueous solutions of the anionic copolymers and of a cationic thioether of b-cyclodextrin (b-CD). Particle size distributions of NPs were investigated with DLS as the function of the charge ratio of the constituents. The smallest and most uniform particles with a diameter of about 130 nm were generated at a charge ratio of anion/cation close to 1, preferably 1.2. Stabilities and particle size distributions of these starch NPs were very satisfactory. The starch/b-CD NPs could be loaded with hydrophobic guest molecules like 1,4-dihydroxyanthraquinone (DHA), which served as a model for the important class of anthracycline antibiotics used in cancer therapy.

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