|TUD Organische Chemie||Immel||Structures||CHIME - Cycloaltrins (Informations)||View or Print (this frame only)|
Molecular Modeling of Saccharides, Part XXI.
Solution Geometries and Lipophilicity Patterns of α-Cycloaltrin.
S. Immel, K. Fujita, and F. W. Lichtenthaler, Chem. Eur. J. 1999, 5, 3185-3192.
Abstract / Fulltext PDF
The structural characteristics of α-cycloaltrin (α-CA), readily available from α-cyclodextrin by a straightforward four-step protocol with 2,3-anhydro-α-cyclomannin as the key intermediate, has been unraveled using X-ray techniques, 800 MHz spectra (D2O at 30 and 4°C) and molecular modeling (MD in water). In the solid-state, the altropyranoid rings adopt nearly perfect 4C1 and 1C4 chairs in an alternating sequence, entailing the macrocycle to be devoid of a through going cavity. Analysis of the conformational properties of α-cycloaltrin (α-CA) in aqueous solution by 800 MHz 1H, 200 MHz 13C NMR, and molecular dynamics (MD) simulations points towards a complex equilibrium of 4C1OS21C4 altropyranose units. Although the 3JH-H coupling constants do not reveal a preference for the alternating 4C1 / 1C4 or the all-OS2 conformation of α-CA, low-temperature 13C NMR line-broadening indicates at least two different conformations of the altrose residues.
From HTA calculations i.e. toward vacuum boundary conditions, the allskew (twistboat) 0S2 geometry emerges as the global energy minimum structure. In water, the altropyranoid rings in α-cycloaltrin adopt various conformations within the 1C4 3H2 0S2 range.
Both α-CA geometries are stable during 600 ps MD simulations without conformational transitions, but constrained MDs forcing one altropyranose unit to vary along the 4C1→OS2→1C4 reaction coordinate indicates cooperative conformational transitions 1C4→OS23,OB of neighboring units and statistical scrambling of the pyranose geometries in the macrocycle. In particular, the all-OS2 conformation of α-CA features a central cavity capable to form inclusion complexes, whereas alternate forms may have surface indentations only.
The MOLCAD program mediated computation of the molecular lipophilicity patterns (MLPs), projected in color-coded form onto the respective contact surfaces allow the detailed localization of hydrophobic and hydrophilic domains, which determine to a substantial degree the capabilities of this cyclooligosaccharide for inclusion complex formation.