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International audience; Aromatic oligoamide sequences able to fold into single helical capsules were functionalized with two types of side chains to make them be soluble in various solvents such as chloroform, methanol or water and their propensity to recognize tartaric acid was evaluated. Binding affinities to tartaric acid and binding thermodynamics in the different media were investigated by variable temperature 1 H NMR and ITC experiments, the two methods giving consistent results. We show that tartaric acid binding mainly rests on enthalpically favourable polar interactions that were found to be sufficiently strong to be effective in presence of a polar aprotic solvent (DMSO) and even in pure methanol. Binding in water was very low. The stronger binding interactions were found to be more susceptible to the effect of competitive solvents and to be compensated by unfavourable entropic effects. Thus, the best host in less polar medium eventually was found to be the worst host in protic solvents. An interesting case of entropically driven binding was evidenced in methanol.

The ab initio design of synthetic molecular receptors for a specific biomolecular guest remains an elusive objective, particularly for targets such as monosaccharides, which have very close structural analogues. Here we report a powerful approach to produce receptors with very high selectivity for specific monosaccharides and, as a demonstration, we develop a foldamer that selectively encapsulates fructose. The approach uses an iterative design process that exploits the modular structure of folded synthetic oligomer sequences in conjunction with molecular modelling and structural characterization to inform subsequent refinements. Starting from a first-principles design taking size, shape and hydrogen-bonding ability into account and using the high predictability of aromatic oligoamide foldamer conformations and their propensity to crystallize, a sequence that binds to β-D-fructopyranose in organic solvents with atomic-scale complementarity was obtained in just a few iterative modifications. This scheme, which mimics the adaptable construction of biopolymers from a limited number of monomer units, provides a general protocol for the development of selective receptors.