Olivier Perraud

Combined Cation–π and Anion–π Interactions for Zwitterion Recognition

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.

Oxidation of cycloalkanes by H2O2 using a copper–hemicryptophane complex as a catalyst

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.

The cooperative effect in ion-pair recognition by a ditopic hemicryptophane host.

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.

A New Class of C3-Symmetrical Hemicryptophane Hosts: Triamide- and Tren-hemicryptophanes

The first hemicryptophanes derived from tris(N-alkyl-carbamoylmethyl)amine and tris(2-aminoethyl)amine (tren) have been synthesized following a single synthetic pathway that allows the subsequent formation of the two heteroditopic hosts 3 and 4. X-ray crystal structures show a well-defined cavity encapsulating a solvent guest for both compounds emphasizing their complexation properties.

A Designed Cavity for Zwitterionic Species: Selective Recognition of Taurine in Aqueous Media

Taurine has been shown to play numerous important physiological roles in the human organism. As neurotransmitter, taurine is an activator and inhibitor of many receptors. It has been shown to be able to competitively bind at the GABAA receptor [6,7] and to help the prevention of epilepsy as an inhibitory neurotransmitter. Moreover, it has been found to be a neuroprotective agent through its ability to reduce intracellular free calcium concentrations and its anti-oxidative stress capacity. Most of these biological processes involve intermolecular interactions between host and guest partners. Thus, selective encapsulation of taurine in the cavity of an artificial host should lead to a better understanding of its recognition by biological receptors, and to practical applications, such as substrate-selective sensors, membrane transport and extraction of complex mixtures. Although several studies have been reported on the selective complexation of ammonium neurotransmitters, recognitions of zwitterionic ones by host molecules have been less studied, and are mostly based on crown ether and metal complexes. Indeed, taurine and related zwitterionic guests are strongly solvated species, which often makes their complexation energetically unfavorable because they must be removed from the water solution to a medium of much lower dielectric constant, and this acts often as a formidable and unsurpassable barrier to cross. Therefore, strong coordination bonds and/or ionic interactions are mainly involved to complex zwitterionic guests. As a consequence, most of these host–guest complexes are charged and the substrate is not completely desolvated, that is, encapsulated in the confined space of a closed molecular cage. Thus, biomimetic encapsulation of such compounds in a hydrophobic neutral pocket through endohedral weak interactions is still a challenge. Herein, we report the efficient and selective encapsulation of taurine by the specifically designed hemicryptophane host 1 in a competitive acetonitrile/water medium. In order to determine the main factors that intervene in the recognition of taurine (2), guests 3–12 were screened with 1 (Scheme 1). Hemicryptophanes are chiral host molecules that present heteroditopic cavities with all the requirements for catalytic and recognition properties. Recently, we showed that the recognition of ion pairs by the triamide hemicrypto-

Resolution and absolute configuration assignment of a chiral hemicryptophane molecular cage.

The racemic hemicryptophane molecular cage 2 was resolved by semipreparative HPLC on Whelk-O1 column. The absolute configuration of each isolated enantiomer was established from the analysis of their circular dichroism spectra and assigned as P-(+)-2 and M-(-)-2.

Improved hemicryptophane hosts for the stereoselective recognition of glucopyranosides

Four new enantiomerically and diastereomerically pure hemicryptophane hosts (M-SSS-2/P-SSS-2 and M-RRR-2/P-RRR-2 pairs) were designed for the recognition of sugar derivatives. Their absolute configuration was determined from the circular dichroism spectra and DFT calculations. The host molecules were then used for the stereoselective recognition of glucopyranosides. Binding constants were obtained from (1)H NMR titration experiments showing an increase of affinity for this class of receptors, associated with an improved diastereo- and enantio-differentiation.

Insights into the Complexity of Weak Intermolecular Interactions Interfering in Host-Guest Systems.

The recognition properties of heteroditopic hemicryptophane hosts towards anions, cations, and neutral pairs, combining both cation-π and anion-π interaction sites, were investigated to probe the complexity of interfering weak intermolecular interactions. It is suggested from NMR experiments, and supported by CASSCF/CASPT2 calculations, that the binding constants of anions can be modulated by a factor of up to 100 by varying the fluorination sites on the electron-poor aromatic rings. Interestingly, this subtle chemical modification can also reverse the sign of cooperativity in ion-pair recognition. Wavefunction calculations highlight how short- and long-range interactions interfere in this recognition process, suggesting that a disruption of anion-π interactions can occur in the presence of a co-bound cation. Such molecules can be viewed as prototypes for examining complex processes controlled by the competition of weak interactions.

Helical Chirality Induces a Substrate-Selectivity Switch in Carbohydrates Recognitions

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.