Configuration-Controlled Crystal and/or Gel Formation of Protectedd-Glucosamines Supported by Promiscuous Interaction Surfaces and a Conformationally Heterogeneous Solution State

The configuration-dependent self-association mode of the two anomers ofO-Ac,N-Fmoc-d-glucosamine, a foldamer building block, leading to gel and/or single crystal formation is described. The beta-anomer of the sugar amino acid (2) forms a gel from various solvents (confirmed by SEM, rheology measurements, NMR, and ECD spectroscopy), whereas the alpha-anomer (1) does not form a gel with any solvent tested. Transition from the solution state to a gel is coupled to a concurrent shift of the Fmoc-groups: from a freely rotating (almost symmetrical) to a specific, asymmetric orientation. Whereas the crystal structure of the alpha-anomer is built as an evenly packed 3D system, the beta-anomer forms a looser superstructure of well-packed 2D layers. Modeling indicates that in the lowest energy, but scarcely sampled conformer of the beta-anomer, the Fmoc-group bends above the sugar moiety, stabilized by intramolecular CH <->pi interactions between the aromatic rings. It is concluded that possessing an extended and promiscuous interaction surface and a conformationally heterogeneous solution state are among the basic requirements of gel formation for a candidate molecule.