Jean-Pierre Dutasta

Azaphosphatranes as Structurally Tunable Organocatalysts for Carbonate Synthesis from CO2 and Epoxides

Three azaphosphatranes were used as organocatalysts for the synthesis of cyclic carbonates from CO2 and epoxides. They proved to be efficient single-component, metal-free catalysts for the reaction of simple or activated epoxides (styrene oxide, epichlorohydrin, glycidyl methyl ether) with CO2 under mild reaction conditions, displaying high stability and productivity over several days of reaction. Substitution patterns on the catalyst were shown to affect activity and stability. Kinetic analysis allowed investigation of the reaction mechanism.

Supramolecular Sensing with Phosphonate Cavitands

Phosphonate cavitands are an emerging class of synthetic receptors for supramolecular sensing. The molecular recognition properties of the third-generation tetraphosphonate cavitands toward alcohols and water at the gas-solid interface have been evaluated by means of three complementary techniques and compared to those of the parent mono- and diphosphonate cavitands. The combined use of ESI-MS and X-ray crystallography defined precisely the host-guest association at the interface in terms of type, number, strength, and geometry of interactions. Quartz crystal microbalance (QCM) measurements then validated the predictive value of such information for sensing applications. The importance of energetically equivalent multiple interactions on sensor selectivity and sensitivity has been demonstrated by comparing the molecular recognition properties of tetraphosphonate cavitands with those of their mono- and diphosphonate counterparts.

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.

Reversible, solvent-induced chirality switch in atrane structure: control of the unidirectional motion of the molecular propeller.

Here we demonstrate that atrane-hemicryptophane molecular cages exhibit a reversible change in chirality uniquely controlled by the solvent, thus establishing the feasibility of a new mode of stimulation for atrane-based molecular switches. The oxidovanadium(V) complexes of hemicryptophane molecules exist as diastereomeric mixtures because of the P or M handedness of the cyclotriveratrylene unit and the chiral ether groups with the S configuration. The Δ/Λ propeller-like arrangement of the atrane moiety introduces a new local dissymmetry because of the conformationally restricted helical structure. (1)H NMR experiments provided significant data for the Δ ⇆ Λ interconversion process, where the solvent profoundly influences the chirality sense of the propeller motion, making control of the chirality by the choice of solvent possible. The reversible chirality inversion process is induced by alternating changes of solvent from CDCl(3) to C(6)D(6). The ratio of the rates of the clockwise and anticlockwise tilting motions of the atrane structure shows that the solvent directs the rotational motion of the vanatrane moiety, so the propeller sense of the motion can be considered as unidirectional.

Optimization of Xenon Biosensors for Detection of Protein Interactions

Hyperpolarized 129Xe NMR spectroscopy can detect the presence of specific low‐concentration biomolecular analytes by means of a xenon biosensor that consists of a water‐soluble, targeted cryptophane‐A cage that encapsulates the xenon. In this work, we use the prototypical biotinylated xenon biosensor to determine the relationship between the molecular composition of the xenon biosensor and the characteristics of protein‐bound resonances. The effects of diastereomer overlap, dipole–dipole coupling, chemical‐shift anisotropy, xenon exchange, and biosensor conformational exchange on the protein‐bound biosensor signal were assessed. It was found that an optimal protein‐bound biosensor signal can be obtained by minimizing the number of biosensor diastereomers and using a flexible linker of appropriate length. Both the line width and sensitivity of chemical shift to protein binding of the xenon biosensor were found to be inversely proportional to linker length.

Cell uptake of a biosensor detected by hyperpolarized 129Xe NMR: The transferrin case

For detection of biological events in vitro, sensors using hyperpolarized (129)Xe NMR can become a powerful tool, provided the approach can bridge the gap in sensitivity. Here we propose constructs based on the non-selective grafting of cryptophane precursors on holo-transferrin. This biological system was chosen because there are many receptors on the cell surface, and endocytosis further increases this density. The study of these biosensors with K562 cell suspensions via fluorescence microscopy and (129)Xe NMR indicates a strong interaction, as well as interesting features such as the capacity of xenon to enter the cryptophane even when the biosensor is endocytosed, while keeping a high level of polarization. Despite a lack of specificity for transferrin receptors, undoubtedly due to the hydrophobic character of the cryptophane moiety that attracts the biosensor into the cell membrane, these biosensors allow the first in-cell probing of biological events using hyperpolarized xenon.

A Water-Soluble Xe@cryptophane-111 Complex Exhibits Very High Thermodynamic Stability and a Peculiar 129Xe NMR Chemical Shift

The known xenon-binding (±)-cryptophane-111 (1) has been functionalized with six [(η(5)-C(5)Me(5))Ru(II)](+) ([Cp*Ru](+)) moieties to give, in 89% yield, the first water-soluble cryptophane-111 derivative, namely [(Cp*Ru)(6)1]Cl(6) ([2]Cl(6)). [2]Cl(6) exhibits a very high affinity for xenon in water, with a binding constant of 2.9(2) × 10(4) M(-1) as measured by hyperpolarized (129)Xe NMR spectroscopy. The (129)Xe NMR chemical shift of the aqueous Xe@[2](6+) species (308 ppm) resonates over 275 ppm downfield of the parent Xe@1 species in (CDCl(2))(2) and greatly broadens the practical (129)Xe NMR chemical shift range made available by xenon-binding molecular hosts. Single crystal structures of [2][CF(3)SO(3)](6)·xsolvent and 0.75H(2)O@1·2CHCl(3) reveal the ability of the cryptophane-111 core to adapt its conformation to guests.

A Sensitive Zinc-Activated 129Xe MRI Probe†

The divalent zinc cation, Zn, is an indispensable and ubiquitous element of the body. As the second most abundant transition-metal ion in mammalian tissues, it is involved in many physiological and pathological processes. Zinc plays a vital role not only when bound to metalloproteins, but also in the form of mobile pools. A slight excess or lack of zinc ions can be connected to serious human afflictions, including heart disease, diabetes, cancer, and neurodegeneration such as Alzheimer s disease. Today, only two noninvasive techniques, optical imaging and magnetic resonance imaging (MRI), have the potential to offer real-time monitoring of the Zn distribution in different tissues of the body. However, optical methods suffer from limited penetration depth, which makes them unsuitable for global analysis of relatively large and opaque specimens, such as live animals. On the other hand, MRI is a particularly powerful modality used clinically for anatomic imaging and provides three-dimensional images with excellent resolution. However, conventional molecular MRI techniques that rely on the observation of water protons and require the introduction of contrast agents still suffer from reduced sensitivity and often lack selectivity. A few studies based on gadolinium complexes have been reported for Zn imaging. Nevertheless, to our knowledge, the detection threshold of free Zn ions is 30 mm, a value slightly above the total Zn concentration of 20 mm in blood. Therefore, the development of more sensitive methods is of crucial importance. Herein we propose the use of hyperpolarized Xe nuclear magnetic resonance (NMR) spectroscopy for the sensitive detection of Zn ions. To achieve this goal, the noble gas is encapsulated in dedicated host systems bearing a ligand that chelates the Zn ions. Cryptophanes, aromatic cage molecules made of cyclotriveratrylene groups, are perfectly suited to this purpose as 1) they can easily be rendered water-soluble, 2) the noble gas has a high affinity for their cavity, 3) when xenon is encapsulated, it takes a specific NMR frequency, and 4) xenon exchange in and out of the cavity insures a continuous refreshment of the Xe@cryptophane environment in hyperpolarization. Such a Xe biosensing approach has already been employed for detection of various biological systems, including enzymes and nucleic acids. Also, the first in-cell probing of biological events has been achieved: the endocytosis of transferrin could be detected by using Xe NMR spectroscopy. All these NMR spectroscopy studies based on the use of hyperpolarized xenon and molecular hosts are characterized by a high sensitivity. However, metal detection is a difficult challenge, which has never been achieved using such an approach. We aimed to design a responsive agent in which the chemical shift of encapsulated xenon would significantly vary when Zn ions are chelated to it. In this manner, a sensitive spectroscopic imaging based on this resonance-frequency variation can be envisioned. For this purpose, we designed sensor 1, which is made of three parts (Scheme 1): the cryptophane core hosting xenon, the spacer, and the chelating moiety. A short spacer was chosen to place the chelating moiety near the cryptophane cavity. As a zinc-chelating group we chose nitrilotriacetic acid (NTA), which is easily prepared from l-lysine. Sensor 1 was synthesized from cryptophane 2, which possesses six carboxylate groups ensuring solubility in water at physiological pH value. We were able to activate only one carboxylate group by esterification with N-hydroxysuccinimide. Then, the primary amino group of the enantiopure unit bearing the NTA moiety (l)-3 was directly coupled to this activated ester to form a chemically stable amide linkage. Thus, the use of host 2 in its racemic form (chirality is due to the helicity of the cryptophane) led to two diastereomers, which will be noted 1P and 1M (see the Supporting Information for the nomenclature). Compound 1 was obtained as a 50:50 diastereomeric mixture (1P + 1M), with a chemical purity higher than 95% after HPLC. For this sensor, the xenon binding constant is assumed to be in the same range as that of compound 2, that is, 6000m . As cryptophane 2 has already been shown to behave as a pH sensor, the present Xe NMR spectroscopy study was conducted in a phosphate buffer exempt of other ions, at pH 7.4. At this pH value, the affinity of the NTA group for Zn ions is well-documented (logK1> 10). [16] In the absence [*] N. Kotera, Dr. L. Delacour, Dr. T. Traor , D. A. Buisson, Dr. F. Taran, S. Coudert, Dr. B. Rousseau CEA Saclay, SCBM, iBiTec-S, Building 547, PC # 108 91191 Gif sur Yvette (France) E-mail: bernard.rousseau@cea.fr N. Tassali, E. L once, Dr. C. Boutin, Dr. P. Berthault CEA Saclay, IRAMIS, SIS2M, UMR CEA/CNRS 3299 Laboratoire Structure et Dynamique par R sonance Magn tique 91191 Gif sur Yvette (France) E-mail: patrick.berthault@cea.fr

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.