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A new method implemented into a computer program (ConArch+ ) has been developed and applied to demonstrate the successful implementation of residual dipolar couplings (RDCs) in distance geometry (DG) calculations for the configurational assignment of chiral compounds. Unlike established protocols, the new approach combines floating chirality (fc) in 4D- and 3D-distance bounds driven dynamics (DDD) calculations with structural information from RDCs. Thus, relative configurations of chiral compounds were generated only by observables (e.g., NOEs, RDCs) rendering tedious evaluations of calculated structures against RDCs obsolete. We demonstrate the potential of this novel procedure by the simultaneous determination of the configuration and the conformation of three natural products, (-)-isopinocampheol (1), tubocurarine (2), and vincristine (3), as well as for diisopropylidene-β-d-fructopyranose (4).

The synthesis, biochemical evaluation, and hydrolysis studies of a wide selection of alkyl- and halogen-substituted titanium salan alkoxides are presented herein. A systematic change in the employed alkoxides revealed that both the bulk of the salan ligands and the steric demand of the labile ligands are of great importance for the obtained biological activity. Surprisingly, these two factors are not independent from each other; lowering the steric demand of the alkoxide of a hitherto nontoxic complex renders it cytotoxic. Therefore, our data suggest that the overall size of the complex exerts a strong influence on its biological activity. To decide whether the correlation between the cytotoxicity and the steric demand of the whole complex is merely based on an altered hydrolysis or on the interaction with biomolecules, the behavior of selected complexes under hydrolytic conditions and the influence of transferrin were investigated. Complexes differing only in their labile alkoxy ligands gave the same hydrolysis products with similar hydrolysis rates but displayed cytotoxicities that differed in the range of one order of magnitude. Thus, it seems that the hydrolysis product is not the active species but rather that the unhydrolysed complex is important for the first interaction with a biomolecule. This promoted the idea of hydrolysis being a detoxification pathway. In accordance with the above conclusion, chloro-substituted complex [Ti(Ph(Cl)N(Me))(2)(O(iPr))(2)] displayed a high cytotoxicity (IC(50) approximately 5 microM) and surprisingly high hydrolytic stability (t(1/2)=108 h). These findings, together with the observed cytotoxicity in a cisplatin-resistant cell line, make halo-substituted salan complexes an interesting target for further studies.

Periodate oxidation of alpha-cyclodextrin followed by borohydride reduction readily provided an octadeca-hydroxymethyl-substituted 30-crown-12 polyacetal 1, its 30-membered macrocycle being composed of six meso-butanetetrol/glycolaldehyde acetal units, which is, consequently, optically inactive. Its solid-state molecular geometry emerged from the X-ray structural analysis of the well-crystallizing octadeca-acetate 2, which revealed the undulated macrocycle to be molded into three loops with a unique order of succession of the -CHR-CHR-O-CHR-O- units: alternating gauche- and anti-conformations of the meso-butanetetrol portions and consecutive disposition of the glycolaldehyde-acetoxymethyl groups above and below the mean-plane of the macrocycle. In solution, however, as evidenced by 1H- and 13C-NMR spectra, the macrocycle is highly flexible at ambient and higher temperatures, its mobility becoming distinctly restricted only below -20 degrees C.

Readily available from alpha-cyclodextrin in three steps, 2,3-anhydro-alpha-cyclomannin composed of six alpha-(1-->4)-linked 2,3-anhydro-D-mannopyranose residues, crystallizes well when precipitated from aqueous ethanol. An X-ray structure reveals the macrocycle to contain ethanol in its cavity, thus representing the first inclusion complex of a non-glucose cyclooligosaccharide. The wider rim of the torus-shaped macrocycle holds the six epoxide rings whose oxygens point away from the cavity, thereby sculpturing the unique over-all shape of a six-pointed star.

The first thoroughly flexible cyclooligosaccharide, α-cycloaltrin, adopts various geometries between disk-shaped (1 a) and torus-type (1 b) conformations in water. This altrose analogue of α-cyclodextrin constitutes an ideal model with which to probe the induced-fit mode of guest–host interactions.