Cyclofructins with six to ten beta-(1-->2)-linked fructofuranose units: geometries, electrostatic profiles, lipophilicity patterns, and potential for inclusion complexation.
Cyclofructins composed of six (1, "CF6") to ten (5, "CF10") beta-(1-->2)-linked fructofuranose units were subjected to conformational analysis using Monte Carlo simulations based on the PIMM91 force-field. Breaking the molecular symmetry partially by alternating inclination of the spiro-type anellated fructofuranoses relative to the crown ether ring core, 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 CF6, CF8, and CF10 exhibit Cn/2 rotational symmetry, whilst the odd-membered macrocycles in CF7 and CF9 adopt C1 symmetry. Identical conformations of the solid-state geometry of CF6 (1) and its computer-generated form manifest the reliability of the computational analysis. The molecular surfaces calculated for the energy-minimum structures establish a disk-type shape for CF6 (1), CF7 (2), and CF8 (3), whereas further ring enlargement to CF9 (4) and CF10 (5) leads to torus-shaped molecules with through-going cavities. Color-coded projection of the molecular lipophilicity patterns (MLPs) and the electrostatic potential profiles (MEPs) onto these surfaces cogently displays the crown ether-like properties, 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 CF9 and CF10 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. Accordingly, CF9 and CF10 are capable to form inclusion complexes, the cavity of the latter being approximately as large as the one of alpha-cyclodextrin. Calculation of the inclusion complex geometries of CF9 with beta-alanine and of CF10 with p-aminobenzoic acid revealed the guest to be deeply incorporated into the respective cavities, masking the guest's hydrophobic parts. Analysis of the electrostatic interactions at the interface of the zwitter-ionic guests with the oppositely polarized hosts predicts a high degree of regiospecificity for complex formation.
Immel
S
S
Institut für Organische Chemie, Technische Universität Darmstadt, Germany.
Schmitt
G E
GE
Lichtenthaler
F W
FW
D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D005632:Fructose / Q000031:analogs & derivatives / Q000737:chemistry*; D005636:Fructosephosphates / Q000737:chemistry*; D006027:Glycosides / Q000737:chemistry*; D007091:Image Processing, Computer-Assisted; D007444:Inulin / Q000737:chemistry; D008055:Lipids; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D055672:Static Electricity
D005636:Fructosephosphates; D006027:Glycosides; D008055:Lipids; D005632:Fructose; D007444:Inulin