Patrick Berthault

Publications of Patrick Berthault

• A Sensitive Zinc-Activated (129) Xe MRI Probe.

  Authors: Naoko Kotera, Nawal Tassali, Estelle Léonce, Céline Boutin, Patrick Berthault, Thierry Brotin, Jean-Pierre Dutasta, Léa Delacour, Ténin Traoré, David-Alexandre Buisson, Frédéric Taran, Sylvie Coudert, Bernard Rousseau

  Angewandte Chemie (International ed. in English). 03/2012;

  Xenon capsule: A smart (129) Xe NMR-based sensor of Zn(2+) ions for magnetic resonance imaging (MRI) is proposed. The resonance frequency of xenon encapsulated in a cryptophane that bears aXenon capsule: A smart (129) Xe NMR-based sensor of Zn(2+) ions for magnetic resonance imaging (MRI) is proposed. The resonance frequency of xenon encapsulated in a cryptophane that bears a nitrilotriacetic ligand moiety varies when Zn(2+) ions are present in solution. With hyper-polarized gas, such a construct enables detection of 100 nM zinc in one xenon batch, a threshold 300 times lower than achieved with gadolinium chelates.

• Hyperpolarized 129Xe NMR signature of living biological cells.

  Authors: Céline Boutin, Hervé Desvaux, Marie Carrière, François Leteurtre, Nadège Jamin, Yves Boulard, Patrick Berthault

  NMR in biomedicine. 12/2011; 24(10):1264-9.

  We show that the differentiation between internal and external compartments of various biological cells in suspension can be made via simple NMR spectra of hyperpolarized (129) Xe. The spectralWe show that the differentiation between internal and external compartments of various biological cells in suspension can be made via simple NMR spectra of hyperpolarized (129) Xe. The spectral separation between the signals of (129) Xe in these two compartments is already known for red blood cells, because of the strong interaction of the noble gas with hemoglobin. The observation of two separate peaks in the 200-ppm region can be seen with both eukaryotic and prokaryotic cells, some of which are not known to contain paramagnetic proteins in large quantities. Using different experiments in which the cells are lysed, swell or are blocked in G2 phase, we demonstrate that the low-field-shifted peak observed corresponds to xenon in the aqueous pool inside the cells and not in the membranes. The presence of this additional peak is a clear indication of cell integrity, and its integration allows the quantification of the total cell volume. The relaxation time of intracellular xenon is sufficiently long to open up promising perspectives for cell characterization. The exchange time between the inner and outer cell compartments (on the order of 30 ms) renders possible the targeting of intracellular receptors, whereas the observation of chemical shift variations represents a method of revealing the presence of toxic species in the cells.

• The first metal-free water-soluble cryptophane-111.

  Authors: Ténin Traoré, Guillaume Clavé, Léa Delacour, Naoko Kotera, Pierre-Yves Renard, Anthony Romieu, Patrick Berthault, Céline Boutin, Nawal Tassali, Bernard Rousseau

  Chemical communications (Cambridge, England). 09/2011; 47(34):9702-4.

  Cryptophane-111 is one of the best candidates for (129)Xe MRI-based applications. Herein, we report the first metal-free and water-soluble cryptophane-111 core which involves an efficient and unusualCryptophane-111 is one of the best candidates for (129)Xe MRI-based applications. Herein, we report the first metal-free and water-soluble cryptophane-111 core which involves an efficient and unusual post-synthetic sulfonation procedure.

• Cell uptake of a biosensor detected by hyperpolarized 129Xe NMR: the transferrin case.

  Authors: Céline Boutin, Antoine Stopin, Fatimazohra Lenda, Thierry Brotin, Jean-Pierre Dutasta, Nadège Jamin, Alain Sanson, Yves Boulard, François Leteurtre, Gaspard Huber, Aurore Bogaert-Buchmann, Nawal Tassali, Hervé Desvaux, Marie Carrière, Patrick Berthault

  Bioorganic & medicinal chemistry. 07/2011; 19(13):4135-43.

  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 constructsFor 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.

• Design and synthesis of new cryptophanes with intermediate cavity sizes.

  Authors: Naoko Kotera, Léa Delacour, Ténin Traoré, Nawal Tassali, Patrick Berthault, David-Alexandre Buisson, Jean-Pierre Dognon, Bernard Rousseau

  Organic letters. 04/2011; 13(9):2153-5.

  The development of molecular imaging using hyperpolarized xenon MRI needs highly optimized biosensors. Cryptophane-111 and cryptophane-222 are promising candidates that show complementaryThe development of molecular imaging using hyperpolarized xenon MRI needs highly optimized biosensors. Cryptophane-111 and cryptophane-222 are promising candidates that show complementary encapsulation properties although they only differ by the length of the three alkane linkers joining two cyclotriphenolene units. Cryptophanes containing both methoxy and ethoxy linkers have never been synthesized. Here we synthesize two new cages with intermediate internal volumes, in two steps from cyclotriphenolene.

• Interaction of xenon with cucurbit[5]uril in water.

  Authors: Gaspard Huber, François-Xavier Legrand, Véronique Lewin, Delphine Baumann, Marie-Pierre Heck, Patrick Berthault

  Chemphyschem : a European journal of chemical physics and physical chemistry. 03/2011; 12(6):1053-5.

• A water-soluble Xe@cryptophane-111 complex exhibits very high thermodynamic stability and a peculiar (129)Xe NMR chemical shift.

  Authors: Robert M Fairchild, Akil I Joseph, K Travis Holman, Heather A Fogarty, Thierry Brotin, Jean-Pierre Dutasta, Céline Boutin, Gaspard Huber, Patrick Berthault

  Journal of the American Chemical Society. 10/2010; 132(44):15505-7.

  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-111The 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.

• Effect of pH and counterions on the encapsulation properties of xenon in water-soluble cryptophanes.

  Authors: Patrick Berthault, Hervé Desvaux, Thierry Wendlinger, Marina Gyejacquot, Antoine Stopin, Thierry Brotin, Jean-Pierre Dutasta, Yves Boulard

  Chemistry (Weinheim an der Bergstrasse, Germany). 09/2010; 16(43):12941-6.

  In the (129)Xe NMR-based biosensing approach in which the hyperpolarized noble gas is transported to biological receptors for a sensitive molecular imaging, cryptophanes are excellent xenon hostIn the (129)Xe NMR-based biosensing approach in which the hyperpolarized noble gas is transported to biological receptors for a sensitive molecular imaging, cryptophanes are excellent xenon host systems. However to avoid formation of self-organized systems, these hydrophobic cage molecules can be rendered water soluble by introduction of ionic groups. We show that the sensitivity of xenon to its local environment and the presence of these ionic functions can lead to interesting properties. For a first water-soluble cryptophane derivative, we show that a precise monitoring of the local pH can be performed. For a second cryptophane, the presence of ionic groups close to the cryptophane cavity modifies the xenon binding constant and in-out exchange rate. The latter allows the tuning of physical properties of xenon-cryptophane interactions without resorting to a change of the cavity size. These results open new perspectives on the influence of chemical modifications of cryptophanes for optimizing the biosensor properties.

• Scalable synthesis of cryptophane-1.1.1 and its functionalization.

  Authors: Ténin Traoré, Léa Delacour, Sébastien Garcia-Argote, Patrick Berthault, Jean-Christophe Cintrat, Bernard Rousseau

  Organic letters. 03/2010; 12(5):960-2.

  Cryptophanes, cage molecules for which xenon exhibits a high affinity, are good candidates for xenon biosensing. Cryptophane-1.1.1 (1) exhibits the highest binding constant for xenon encapsulation inCryptophanes, cage molecules for which xenon exhibits a high affinity, are good candidates for xenon biosensing. Cryptophane-1.1.1 (1) exhibits the highest binding constant for xenon encapsulation in organic solution determined to date. This property suggests that the cryptophane-1.1.1 core (1) is optimal for sensing applications. A high-yielding scalable synthesis of compound 1 is reported as well as an easy way to functionalize it.

• Measurement of long-range interatomic distances by solid-state tritium-NMR spectroscopy.

  Authors: Alexander K L Yuen, Olivier Lafon, Thibault Charpentier, Myriam Roy, Francine Brunet, Patrick Berthault, Dimitrios Sakellariou, Bruno Robert, Sylvie Rimsky, Florence Pillon, Jean-Christophe Cintrat, Bernard Rousseau

  Journal of the American Chemical Society. 02/2010; 132(6):1734-5.

  For the structural determination of a ligand bound to an amorphous macromolecular system, solid-state NMR can be used to provide interatomic distances. It is shown here that selective labeling inFor the structural determination of a ligand bound to an amorphous macromolecular system, solid-state NMR can be used to provide interatomic distances. It is shown here that selective labeling in discrete locations with tritium enables accurate measurement of long-range distances owing to the high gyromagnetic ratio of this nucleus, without structural modification of the molecule. This approach gives access to the largest NMR distance ever measured between two nuclei (14.4 A). (3)H MAS NMR appears to be a promising tool for structural applications in the biological and material sciences.

• Nuclear Spin-Noise Spectra of Hyperpolarized Systems.

  Authors: Hervé Desvaux, Denis J-Y Marion, Gaspard Huber, Patrick Berthault

  Angewandte Chemie (International ed. in English). 06/2009;

• Sensitivity and multiplexing capabilities of MRI based on polarized 129Xe biosensors.

  Authors: Patrick Berthault, Aurore Bogaert-Buchmann, Hervé Desvaux, Gaspard Huber, Yves Boulard

  Journal of the American Chemical Society. 01/2009; 130(49):16456-7.

• Cryptophane-Xenon Complexes in Organic Solvents Observed through NMR Spectroscopy.

  Authors: Gaspard Huber, Lætitia Beguin, Hervé Desvaux, Thierry Brotin, Heather Fogarty, Jean-Pierre Dutasta, Patrick Berthault

  The journal of physical chemistry. A. 11/2008;

  The interaction of xenon with cryptophane derivatives is analyzed by NMR by using either thermal or hyperpolarized noble gas. Twelve hosts differing by their stereochemistry, cavity size, and theThe interaction of xenon with cryptophane derivatives is analyzed by NMR by using either thermal or hyperpolarized noble gas. Twelve hosts differing by their stereochemistry, cavity size, and the nature and the number of the substituents on the aromatic rings have been included in the study, in the aim of extracting some clues for the optimization of (129)Xe-NMR based biosensors derived from these cage molecules. Four important properties have been examined: xenon-host binding constant, in-out exchange rate of the noble gas, chemical shift, and relaxation of caged xenon. This work aims at understanding the main characteristics of the host-guest interaction in order to choose the best candidate for the biosensing approach. Moreover, rationalizing xenon chemical shift as a function of structural parameters would also help for setting up multiplexing applications. Xenon exhibits the highest affinity for the smallest cryptophane, namely cryptophane-111, and a long relaxation time inside it, convenient for conservation of its hyperpolarization. However, very slow in-out xenon exchange could represent a limitation for its future applicability for the biosensing approach, because the replenishment of the cage in laser-polarized xenon, enabling a further gain in sensitivity, cannot be fully exploited.

• Observation of noise-triggered chaotic emissions in an NMR-maser.

  Authors: Denis J-Y Marion, Gaspard Huber, Patrick Berthault, Hervé Desvaux

  Chemphyschem : a European journal of chemical physics and physical chemistry. 07/2008; 9(10):1395-401.

  We report a new phenomenon observed when the magnetization of dissolved hyperpolarized (129)Xe is intense and opposite to the Boltzmann magnetization. Without radio-frequency (rf) excitation, theWe report a new phenomenon observed when the magnetization of dissolved hyperpolarized (129)Xe is intense and opposite to the Boltzmann magnetization. Without radio-frequency (rf) excitation, the system spontaneously emits a series of rf bursts characterized by very narrow bandwidths (0.03 Hz at 138 MHz). This chaotic NMR-maser illustrates the increase in the complexity of spin dynamics at high magnetization levels by unveiling an inhomogeneous spatial organization of the xenon magnetization and an apparent dependence of the xenon transverse relaxation time on its polarization and/or on time.

• A cryptophane biosensor for the detection of specific nucleotide targets through xenon NMR spectroscopy.

  Authors: Vincent Roy, Thierry Brotin, Jean-Pierre Dutasta, Marie-Hélène Charles, Thierry Delair, François Mallet, Gaspard Huber, Hervé Desvaux, Yves Boulard, Patrick Berthault

  Chemphyschem : a European journal of chemical physics and physical chemistry. 11/2007; 8(14):2082-5.

• A cryptophane core optimized for xenon encapsulation.

  Authors: Heather A Fogarty, Patrick Berthault, Thierry Brotin, Gaspard Huber, Hervé Desvaux, Jean-Pierre Dutasta

  Journal of the American Chemical Society. 09/2007; 129(34):10332-3.

• 1H and 129Xe NMR absorption line shapes in the presence of highly polarized and concentrated xenon solutions in high magnetic field.

  Authors: Denis J-Y Marion, Gaspard Huber, Lionel Dubois, Patrick Berthault, Hervé Desvaux

  Journal of magnetic resonance (San Diego, Calif. : 1997). 08/2007; 187(1):78-87.

  The presence of highly concentrated dissolved laser-polarized xenon (approximately 1mol/L, polarization up to 0.2) induces numerous effects on proton and xenon NMR spectra. We show that the protonThe presence of highly concentrated dissolved laser-polarized xenon (approximately 1mol/L, polarization up to 0.2) induces numerous effects on proton and xenon NMR spectra. We show that the proton signal enhancements due to (129)Xe-(1)H cross-relaxation (SPINOE) and overall shifts of the proton resonances due to the average dipolar shift created by the intense xenon magnetization are correlated. Protons behave as very useful sensors of the xenon magnetization. Indeed the xenon resonances exhibit many features such as superimposition of narrow lines on the main resonance due to clustering effects, or such as a polarization-dependent line broadening that is tentatively assigned to the effects of temperature fluctuations that decorrelate some distant dipolar field effects from local interactions, transforming xenon spins from "like" to "unlike" spins. These spectral features make difficult the determination of the average dipolar field by means of the xenon resonance but have interesting consequences on the heteronuclear polarization transfer experiment in Hartmann-Hahn conditions (SPIDER).

• Water soluble cryptophanes showing unprecedented affinity for xenon: candidates as NMR-based biosensors.

  Authors: Gaspard Huber, Thierry Brotin, Lionel Dubois, Hervé Desvaux, Jean-Pierre Dutasta, Patrick Berthault

  Journal of the American Chemical Society. 06/2006; 128(18):6239-46.

  Cryptophanes bearing OCH(2)COOH groups in place of the methoxy groups represent a new class of xenon-carrier molecules soluble in water at biological pH. By using (1)H and (129)Xe NMR (thermally- andCryptophanes bearing OCH(2)COOH groups in place of the methoxy groups represent a new class of xenon-carrier molecules soluble in water at biological pH. By using (1)H and (129)Xe NMR (thermally- and laser-polarized dissolved gas), the structural and dynamical behaviors of these host molecules as well as their interaction with xenon are studied. They are shown to exist in aqueous solution under different conformations in very slow exchange. A saddle form present for one of these conformations could explain the (1)H NMR spectra. Whereas the cryptophanes in such a conformation are unable to complex xenon, unprecedented high binding constants are found for cryptophanes in the other canonical crown-crown conformation. These host molecules could therefore be valuable candidates for biosensing using (129)Xe MRI.

• Study of the hydrophobic cavity of beta-cryptogein through laser-polarized xenon NMR spectroscopy.

  Authors: Patrick Berthault, Gaspard Huber, Phuong Thu Ha, Lionel Dubois, Hervé Desvaux, Eric Guittet

  Chembiochem : a European journal of chemical biology. 02/2006; 7(1):59-64.

  The interaction of xenon with beta-cryptogein, a basic 10 kDa protein belonging to the elicitin family, has been studied by using dissolved thermal and laser-polarized gas in liquid-state NMR. 13CThe interaction of xenon with beta-cryptogein, a basic 10 kDa protein belonging to the elicitin family, has been studied by using dissolved thermal and laser-polarized gas in liquid-state NMR. 13C and 1H chemical-shift-mapping experiments were unfruitful, the proton lines only experienced a slight narrowing but no significant frequency variation when the xenon concentration was increased. Nevertheless magnetization transfer from hyperpolarized xenon to protons of the protein demonstrates an undoubted interaction and enables localization of the noble-gas-binding site. Due to the proton-proton cross-relaxation efficiency, however, this experiment is subjected to important spin-diffusion. An automatic procedure that takes spin-diffusion into account when assigning the protons that interact with xenon is then used. The binding site, as defined by 30 Xe--H interactions, is situated in the inner core of the protein. The protons that interact with xenon border the channel by which sterols are known to enter into the cavity. These results support the idea that xenon is a good probe for hydrophobic protein regions.

• Dynamics of xenon binding inside the hydrophobic cavity of pseudo-wild-type bacteriophage T4 lysozyme explored through xenon-based NMR spectroscopy.

  Authors: Hervé Desvaux, Lionel Dubois, Gaspard Huber, Michael L Quillin, Patrick Berthault, Brian W Matthews

  Journal of the American Chemical Society. 09/2005; 127(33):11676-83.

  Wild-type bacteriophage T4 lysozyme contains a hydrophobic cavity with binding properties that have been extensively studied by X-ray crystallography and NMR. In the present study, the monitoring ofWild-type bacteriophage T4 lysozyme contains a hydrophobic cavity with binding properties that have been extensively studied by X-ray crystallography and NMR. In the present study, the monitoring of 1H chemical shift variations under xenon pressure enables the determination of the noble gas binding constant (K = 60.2 M(-1)). Although the interaction site is highly localized, dipolar cross-relaxation effects between laser-polarized xenon and nearby protons (SPINOE) are rather poor. This is explained by the high value of the xenon-proton dipolar correlation time (0.8 ns), much longer than the previously reported values for xenon in medium-size proteins. This indicates that xenon is highly localized within the protein cavity, as confirmed by the large chemical shift difference between free and bound xenon. The exploitation of the xenon line width variation vs xenon pressure and protein concentration allows the extraction of the exchange correlation time between free and bound xenon. Comparison to the exchange experienced by protein protons indicates that the exchange between the open and closed conformations of T4 lysozyme is not required for xenon binding.