Hemicryptophanes are host molecules with many applications as supramolecular catalysts or in ion selective recognition. A very convenient and efficient modular approach for the synthesis of hemicryptophane-tren (tren, tris(2-aminoethyl)-amine) derivatives has been developed. For instance, hemicryptophane 1 was synthesized at the gram scale in four steps from vanillyl alcohol compared to the previous seven-step procedure. The size, shape, and functionalities of the molecular cavity were also easily modified.

The heteroditopic hemicryptophane 1, which bears a tripodal anion binding site and a cation recognition site in the molecular cavity, proved to be an efficient ion-pair receptor. The hemicryptophane host binds anions selectively depending on shape and hydrogen-bond-accepting ability. It forms an inclusion complex with the Me(4)N(+) ion, which can simultaneously bind anionic species to provide anion@[1⋅Me(4)N(+)] complexes. The increased affinity of [1⋅Me(4)N(+)] for anionic species is attributed to a strong cooperative effect that arises from the properly positioned binding sites in the hemicryptophane cavity, thus allowing the formation of the contact ion pair. Density functional theory calculations were performed to analyze the Coulomb interactions of the ion pairs, which compete with the ion-dipole ones, that originate in the ion-hemicryptophane contacts.

Efficient alkane C-H bond oxidation was achieved using a newly designed Cu(II)-hemicryptophane complex. Protection of the copper site in the inner cavity of the host leads to enhanced yields and allows discriminating cyclohexane from cyclooctane or adamantane in competitive experiments.

Brothers and enemies: Anion-π and cation-π interactions act in a synergistic way when gathered in the molecular cavity of a hemicryptophane host, affording an efficient contribution (-170 kJ mol(-1)) in zwitterion recognition. NMR titration experiments and calculations reveal the positioning of the guest in the cavity of the heteroditopic receptor. This study emphasizes the importance of anion-π bonds in host-guest chemistry.

Inherently chiral hemicryptophanes were used to complex β- and α-glucoside derivatives with high diastereo- and enantio-selectivity. In most cases, the exclusive recognition by the M-hemicryptophane enantiomers was observed.

International audienceThe perfect host: Hemicryptophane 1 selectively binds taurine neurotransmitters in CD3CN/D2O. Association constants determined by DOSY NMR spectroscopy demonstrate that this recognition is highly selective over other related substrates. DFT calculations emphasize that only weak intermolecular interactions stabilize the host–guest association (see figure)

Hemicryptophane 3 was found to be an efficient and selective primary alkylammonium receptor. Binding constants are 1000-fold higher than those previously reported for hemicryptophane hosts. Efficient complexation of dopamine emphasizes the use of this host for neurotransmitter complexation. Density functional theory calculations were performed and highlight host-guest complementarities.

A new chiral hemicryptophane cage combining an electron-rich cyclotriveratrylene (CTV) unit and polar amine functions has been synthesized. The resolution of the racemic mixture has been performed by chiral HPLC, and the assignment of the absolute configuration of the two enantiomers has been achieved using ECD spectroscopy. In contrast with other hemicryptophane receptors, the two enantiomeric hosts display both remarkable enantioselectivities in the recognition of carbohydrates and good binding constants. Moreover, by switching the chirality of the CTV unit from M to P, a strong preference shift from glucose to mannose derivatives is observed.