| 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[1] 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
4C1
OS21C4
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[1] 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.
References