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Molecular Modeling of Saccharides, Part XIX.
Cyclofructins with Six to Ten β(1→2)-linked Fructofuranose Units: Geometries, Electrostatic Profiles, Lipophilicity Patterns, and Potential for Inclusion Complex Formation.
S. Immel, G. E. Schmitt, and F. W. Lichtenthaler, Carbohydr. Res. 1998, 313, 91-105.
Abstract / Fulltext PDF
Cyclofructins composed of six (α-CF, 1) to ten (e-CF, 5) β(1→2)-linked fructofuranose units (i.e. cyclo[D-Fruf β(1→2)]n with n = 6 - 10) were subjected to conformational analysis using "Monte-Carlo" simulations based on the PIMM91 force-field[1]. Breaking the molecular symmetry partially by alternating inclination of the spiro-type anellated fructofuranoses relative to the crown ether-like macroring - i.e. the 3-OH groups pointing either towards or away from the molecular center - substantially lowers the strain energy of the cyclofructins. The global energy-minimum geometries of the even-membered macrorings exhibit Cn/2 rotational symmetry, whilst the odd-membered cyclofructins adopt C1 symmetry. Identical conformations of the solid-state geometry of -cyclofructin (1) and its computer-generated form manifest the reliability of the computational analysis. Calculation of the molecular surfaces for the energy-minimum structures establishes a disk-type shape of the cyclofructins with six to eight residues (1, 2, and 3). Ring enlargement to nine (δ-CF, 4) and ten residues (e-CF, 5) leads to torus-shaped molecules with central cavities capable of forming inclusion complexes. The color-coded projection of molecular lipophilicity patterns (MLPs) and electrostatic potential profiles (MEPs) onto these surfaces displays the crown ether-like properties of the disk-shaped cyclofructins, favoring the complexation of metal cations via strong electrostatic interactions through the 3-OH groups located on the hydrophilic molecular side. The central cavities of 4 and 5 are characterized not only by significantly enhanced hydrophobicity, but also by highly negative electrostatic potentials around the narrow aperture of the tori made up by the 3-OH / 4-OH groups, and positive potentials on the opposite rim. On the basis of the data presented, 4 and 5 are capable to form inclusion complexes, the cavity of 5 being approximately as large as the one of -cyclodextrin. The inclusion complex geometries of cyclofructononaoside (4) with β-amino propionic acid (β-alanin) and γ-amino butyric acid, as well as of the complex formed by cyclofructodecaoside (5) with p-amino benzoic acid were calculated. In all cases, the hydrophobic spacer between the hydrophilic head groups of the guest is masked by deep incorporation into the cyclofructin cavity. Analysis of the electrostatic interactions at the interface of the zwitterionic guest molecules with the oppositely polarized host molecule predicts a high degree of regiospecificity for complex formation.
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