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

The configuration‐dependent self‐association mode of the two anomers of O‐Ac,N‐Fmoc‐d‐glucosamine, a foldamer building block, leading to gel and/or single crystal formation is described. The β‐anomer of the sugar amino acid (2) forms a gel from various solvents (confirmed by SEM, rheology measurements, NMR, and ECD spectroscopy), whereas the α‐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 α‐anomer is built as an evenly packed 3D system, the β‐anomer forms a looser superstructure of well‐packed 2D layers. Modeling indicates that in the lowest energy, but scarcely sampled conformer of the β‐anomer, the Fmoc‐group bends above the sugar moiety, stabilized by intramolecular CH↔π 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. When everything gels: The gel formation capacity of two anomers of a protected sugar amino acid is investigated. It is established—by using both experimental (SEM, rheology measurements, NMR, and ECD spectroscopy) and theoretical methods—that aggregation/gelation is promoted by a conformationally heterogeneous solution state and promiscuous interaction surfaces of the monomers.