TUD Organische ChemieImmelStructuresCHIME - Cycloaltrins (Informations)View or Print this frame onlyView or Print (this frame only)

Cycloaltrins (CAs)

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<->OS2<->1C4 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 4C1OS21C4 reaction coordinate indicates cooperative conformational transitions 1C4OS2<->3,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.

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  1. SYBYL-MOLCAD module: (a) J. Brickmann, MOLCAD - MOLecular Computer Aided Design, Technical University of Darmstadt, 1992. The major part of the MOLCAD program is included in the MOLCAD-module of the SYBIL package of TRIPOS Associates, St. Louis, USA. - (b) J. Brickmann and M. Waldherr-Teschner, Labo (Hoppenstedt Verlag, Darmstadt) 1989, 10, 7-14; Informationstechnik (Oldenburg Verlag, München) 1991, 33, 83-90. - (c) J. Brickmann, J. Chim. Phys. 1992, 89, 1709-1721. - (d) M. Waldherr-Teschner, T. Goetze, W. Heiden, M. Knoblauch, H. Vollhardt, and J. Brickmann, in: Advances in Scientific Visualization (Eds.: F. H. Post, A. J. S. Hin), Springer Verlag, Heidelberg, 1992, pp. 58-67. - (e) J. Brickmann, T. Goetze, W. Heiden, G. Moeckel, S. Reiling, H. Vollhardt, and C.-D. Zachmann, Interactive Visualization of Molecular Scenarios with MOLCAD/SYBIL, in: Data Visualization in Molecular Science - Tools for Insight and Innovation (Ed.: J. E. Bowie), Addison-Wesley Publishing Company Inc., Reading, Mass., 1995, pp. 83-97.

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