Patrick Berthault

Patrick Berthault
Atomic Energy and Alternative Energies Commission | CEA · Institut rayonnement matière de Saclay (IRAMIS)

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161
Publications
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3,507
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Publications

Publications (161)
Article
Full-text available
Purpose: To detect carnosine, anserine and homocarnosine in vivo with chemical exchange saturation transfer (CEST) at 17.2 T. Methods: CEST MR acquisitions were performed using a CEST-linescan sequence developed in-house and optimized for carnosine detection. In vivo CEST data were collected from three different regions of interest (the lower le...
Article
Purpose The use of dielectric pads to redistribute the radiofrequency fields is currently a popular solution for 7 T MRI practical applications, especially in brain imaging. In this work, we tackle several downsides of the previous generation of dielectric pads. This new silicon carbide recipe makes them MR invisible and greatly extends the perform...
Article
Full-text available
A new water-soluble xenon host system with great promise for the 129Xe NMR-based biosensing approach is presented: the syn-cryptophane-222-hexacarboxylate. It compares favorably with its already known anti diastereomer, on the...
Article
Full-text available
The availability of a benchtop nuclear magnetic resonance (NMR) spectrometer, of low cost and easily transportable, can allow detection of low quantities of biosensors, provided that hyperpolarized species are used. Here we show that the micromolar threshold can easily be reached by employing laser-polarized xenon and cage molecules reversibly host...
Preprint
Full-text available
The availability of a benchtop NMR spectrometer, of low cost and easily transportable, can allow detection of low quantities of biosensors, provided that hyperpolarized species are used. Here we show that the micromolar threshold can easily be reached, by employing laser-polarized xenon and cage-molecules reversibly hosting it. Indirect detection o...
Article
Platinum nanoparticles were stabilized at the surface of carbon nanotubes and the nanohybrid was valorized as catalyst for the hydrosilylation of alkenes and alkynes. The heterogeneous catalyst operated under sustainable...
Article
We report in this article the synthesis of a asymmetrical cryptophane derivative (possessing only C3-symmetry) bearing three phenol groups and three other carboxylic acid functions, each of these groups on the aromatic rings. Thanks to isothermal titration calorimetry experiments, we show that this compound binds large monovalent cations, such as C...
Article
Hydrotropes are used to solubilise poorly soluble solutes. Here the general features of the solution behaviour of the very common anionic hydrotrope sodium salicylate is investigated. With the use of density and scattering measurements, it is demonstrated that around the critical point neither pre-Ouzo structuring nor an Ouzo effect are present. By...
Article
Hyperpolarization techniques that can transiently boost nuclear spin polarization are generally carried out at low temperature - as in the case of dynamic nuclear polarization - or at high temperature in the gaseous state - as in the case of optically pumped noble gases. This review aims at describing the various issues and challenges that have bee...
Article
Full-text available
The study of the metabolome within tissues, organisms, cells or biofluids can be carried out by several bioanalytical techniques. Among them, nuclear magnetic resonance (NMR) is one of the principal spectroscopic methods. This is due to a sample rotation technique, high-resolution magic angle spinning (HR-MAS), which targets the analysis of heterog...
Article
Full-text available
Cucurbit[n]urils are rigid cage-molecules of pumpkin-like shape, made of n-glycoluril units, able to bind mainly neutral molecules and cations. In this work, we investigate the binding of three cucurbit[5]uril derivatives with dioxygen O2 and show that one of them, namely per-hydroxylated cucurbit[5]uril, (OH)10CB[5], is able to significantly bind...
Article
In this article, we present the synthesis of new cryptophane-type hosts capable of binding xenon in aqueous media and which may be useful for the development of xenon-based MRI derivatives. The synthetic route proposed was chosen in order to facilitate both the introduction of water-solubilizing substituents as well as the functionalization of the...
Article
A bimodal probe for protein detection that combines hyperpolarized ¹²⁹Xe NMR and fluorescence spectroscopy has been optimized. Fluorescence detection is performed by a ligand, CrAsH, that recognizes a target peptide fused to the specific protein. Detection through ¹²⁹Xe NMR spectroscopy is based on a cryptophane cage hosting xenon. More information...
Article
Hierarchically nested hosts offer new opportunities to control the guest binding of the inner host, functionalize the cavity of the outer host, and investigate communication between different layers. Here we report a self-assembled triazatruxene-based FeII4L4 capsule, which was able to encapsulate a covalent cage, cryptophane-111 (CRY). The resulti...
Article
The full understanding of biological phenomena involves sensitive and non –invasive detection. Here we report the optimization of a probe for intracellular proteins that combines the advantages of fluorescence and hyperpolarized 129Xe NMR detection. The fluorescence detection part is composed of six residues containing a tetracysteine tag (‐CCXXCC‐...
Article
The analysis of complex mixtures of dissolved molecules is a major challenge, especially for systems that gradually evolve, e.g., in the course of a chemical reaction or in the case of chemical instability. 1D NMR is a fast and non‐invasive method suitable for detailed molecular analysis, though of low sensitivity. Moreover, the spectral resolution...
Article
Whereas the synthesis of the anti-cryptophane-A (1) derivative is known for nearly 40 years, the preparation of its diastereomer (cryptophane-B according to Collet’s nomenclature) has never been reported. Thus, the synthesis of the cryptophane-B derivative represents a real challenge for chemists interested in the preparation of these hollow molecu...
Article
A device is proposed to enhance the NMR sensitivity of slowly-relaxing nuclei, taking advantage of a controlled solu-tion flow within a microfluidic circuit and micro-sized NMR detection. At the difference of our previous work (Carret at al., Anal. Chem. 2017, 89 (5), 2995–3000), this set-up can be easily installed on any commercial NMR probehead a...
Article
In the search for powerful non-invasive methods for pH measurement, NMR usually suffers from biases, especially for heterogeneous samples or tissues. In this Communication, using the signals of hyperpolarized 129Xe encapsulated in a pair of water-soluble cryptophanes, we show that a differential pH measurement can be achieved, free from most of the...
Article
Cryptophanes, cage-molecules constituted of aromatic bowls, are now well recognized as powerful xenon hosts in 129Xe NMR-based biosensing. In the quest of a dual probe that can be addressed only by NMR we have studied three cryptophanes bearing a tether with an unsaturated bond. The idea behind this is to build probes that can be detected both via...
Article
Although Non-Small Cell Lung Cancer (NSCLC) is one of the main causes of cancer death, very little improvement has been made in the last decades regarding diagnosis and outcomes. In this study, a bimodal fluorescence/(129)Xe NMR probe containing a xenon host, a fluorescent moiety and a therapeutic antibody has been designed to target the Epidermal...
Article
A straightforward and practical access to various C1-symmetric cyclotriveratrylene derivatives from a monohalogenated cyclotriphenolene is described. This unique scaffold can also be used as a precursor for the rapid construction of monofunctionalizable cryptophane-based biosensors for hyperpolarized 129Xe MRI.
Article
Full-text available
Xenon is a first-rate sensor of biological events, due to its large polarizable electron cloud inducing significant modification of NMR parameters through slight changes in its local environment. The use of xenon as a sensor is of increasing interest for sensitive magnetic resonance imaging, since its signal can be enhanced by several orders of mag...
Article
Cs (cesium) and Tl (thallium) are known to be very toxic for the environment and human health. Thus, the synthesis of molecular receptors aimed at extracting these two elements from the environment is strongly desired. In this article, we report the synthesis of the two enantiomers of a water-soluble cryptophane-223 (1) and the study of their inter...
Article
We report the laser-polarized 129Xe and 1H NMR spectra of a series of cryptophane derivatives that differ only by the number of methoxy groups attached on their benzene rings and the arrangement syn or anti of the linkers (compounds 6a-s, 9a-s, 12a-s). All these compounds bind xenon even though the characteristic signal of the gas encapsulated in t...
Article
In this Article we show that circulation of the sample in a closed-loop circuit combined to micro sized detection can lead to a significant signal NMR enhancement. We present an optimized NMR device based on a mini bubble-pump associated to fluidics and microdetection that can be installed on a commercial NMR spectrometer. In addition to a signific...
Patent
The invention relates to a measuring cell for Nuclear Magnetic Resonance, or NMR, in solution allowing the introduction of a gas into said solution. The measuring cell comprises at least one detection volume intended to be placed in a static magnetic field of an NMR spectrometer, and comprises in said detection volume a gas introduction zone , a me...
Article
The advent of spin-hyperpolarization techniques designed to overcome the sensitivity issue of nuclear magnetic resonance owing to polarization transfer from more ordered systems has recently raised great enthusiasm. However, the out-of-equilibrium character of the polarization requires a close proximity between the area of production and the site o...
Article
Full-text available
Signal amplification by reversible exchange (SABRE) is a promising method to increase the sensitivity of nuclear magnetic resonance (NMR) experiments. However, SABRE-enhanced NMR 1H signals are short-lived and SABRE is often used to record 1D NMR spectra only. When the sample of interest is a complex mixture, this results in severe overlaps for 1H...
Article
Full-text available
Recombinant proteins bearing a tag are crucial tools for assessing protein location or function. Small tags such as Cys4 tag (tetracysteine; Cys-Cys-X-X-Cys-Cys) are less likely disrupt protein function in the living cell than green fluorescent protein. Herein we report the first example of the design and synthesis of a dual fluorescence and hyperp...
Article
We report the synthesis of new water-soluble cryptophane host molecules that can be used for the preparation of 129Xe NMR-based biosensors. We show that the cryptophane-223 skeleton can be modified in order to introduce a unique secondary alcohol to the propylenedioxy linker. This chemical functionality can then be exploited to introduce a function...
Article
Among the species in which nuclear spin can be transiently polarized, xenon has a special place for the study of biological processes due to its physical properties. It has no toxicity, it can be easily handled due to a freezing point at 162 K. Importantly, its large electron cloud gives this atom specific chemical affinities, and a large variabili...
Article
Full-text available
Dissolution of hyperpolarized species in liquids of interest for NMR is often hampered by the presence of bubbles that degrade the field homogeneity. Here a device constituted by a bubble pump and a miniaturized NMR cell fitting both inside the narrow bore of an NMR magnet is built by 3D printing. 129Xe NMR experiments performed with hyperpolarized...
Article
Full-text available
Capping of cyclotriphenolene (3a) by the more available cyclotriguaiacylene (3c) or trisbromocyclotriphenolene (3b) gives the first rim-functionalized cryptophane-111 derivatives. Groups amenable to modification suggest their candidacy for the development of 129Xe NMR based sensors. Crystal structures of the xenon complexes reveal high cavity packi...
Article
Gaining an understanding of the nature of host–guest interactions in supramolecular complexes involving heavy atoms is a difficult task. Described herein is a robust simulation method applied to complexes between xenon and members of a cryptophane family. The calculated chemical shift of xenon caged in a H2O2 probe, as modeled by quantum chemistry...
Article
Gaining an understanding of the nature of host–guest interactions in supramolecular complexes involving heavy atoms is a difficult task. Described herein is a robust simulation method applied to complexes between xenon and members of a cryptophane family. The calculated chemical shift of xenon caged in a H2O2 probe, as modeled by quantum chemistry...
Article
An approach for sensitive magnetic resonance detection of metal cations is proposed. Combining the use of hyperpolarized 129Xe NMR and of a cage-molecule functionalized by a ligand able to chelate different cations, we show that simultaneous detection of lead, zinc and cadmium ions at nanomolar concentration is possible in short time, thanks to fas...
Article
When working with hyperpolarized species, it is often difficult to maintain a stable level of magnetization over consecutive experiments, which renders their detection at the trace level cumbersome, even when combined with chemical exchange saturation transfer (CEST). We report herein the use of ultra-fast Z-spectroscopy as a powerful means to dete...
Article
The binding properties of water-soluble cryptophane 1 towards cesium and thallium cations, in basic solution, have recently been reported. In this article, we show that water-soluble cryptophane-222 (2), cryptophane-223 (3) and cryptophane-233 (4), bearing zero, one and two propylenedioxy linkers, respectively, also efficiently bind these two catio...
Article
Full-text available
Four new cucurbiturils CynCB[6] containing n (n = 1, 2, 4, 5) cyclohexyl equatorial units have been synthesized to complete the family of known Cy3CB[6] and Cy6CB[6] derivatives. A new CB[6] member bearing a propanediurea unit has also been prepared. The CB[6] derivatives show better solubility in pure water than native CB[6]. One cyclohexyl unit i...
Article
The development of optimized xenon host systems is of crucial importance for the success of molecular imaging using hyperpolarized (129)Xe MRI. Cryptophane-111 is a promising candidate because of its encapsulation properties. The synthesis of cryptophane-111-based biosensors requires both water-solubilizing and chemically activatable groups. An exp...
Article
We describe the synthesis of a highly water-soluble cryptophane 1 that can be seen as a universal platform for the construction of (129) Xe magnetic resonance imaging (MRI)-based biosensors. Compound 1 is easily functionalized by Huisgen cycloaddition and exhibits excellent xenon-encapsulation properties. In addition, 1 is nontoxic at the concentra...
Article
Binding properties of cesium and thallium cations by an enantiopure cryptophane derivative PP-1 have been investigated in water under basic conditions. The binding process has been evidenced using electronic circular dichroism (ECD), and binding constants of the Cs(+)@PP-1 and Tl(+)@PP-1 complexes have been determined from isothermal titration calo...
Article
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 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 o...
Article
Xenon‐Kapsel: Ein ,,intelligenter“ Zn2+‐Sensor für die Kernspintomographie (MRI) basiert auf 129Xe‐NMR‐Spektroskopie. Zn2+‐Ionen ändern die Resonanzfrequenz von Xenon, das in einem Cryptophan mit anhängendem Nitrilotriessigsäure‐Liganden eingeschlossen ist (siehe Bild). Mit hyperpolarisiertem Gas können mit diesem Konstrukt 100 nM Zink mit einer Xe...
Article
Full-text available
We report on multiple echo measurements in hyperpolarized liquids using optically pumped spin-1/2 noble gas atoms: either 129Xe dissolved in cyclohexane or 3He dissolved in superfluid 4He. An NMR pulse sequence 90◦ − τ − 90◦ (with slice-selective flipping pulses for 129Xe experiments) was used and long echo trains have been observed in the presence...
Article
The school covers several topics in the field of structural NMR. In the first part, following an introduction on general principles, the basic knowledge in isotropic and anisotropic media is given. The second part deals with the structural studies of biological systems and materials while the third gives an overview of a some advanced concepts incl...
Article
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 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 ga...
Article
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 unusual post-synthetic sulfonation procedure.
Article
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...
Article
Full-text available
Xenon–cucurbituril binding: The smallest member of the cucurbituril family is able to slowly trap xenon in water even at room temperature with quite a high binding constant. At higher temperatures, the binding is weaker and the exchange kinetics higher, inducing potential applications for the reversible trapping of gases.
Article
The 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 met...
Article
Methylated and partially methylated cyclodextrin homo- and heterodimers linked by diamidosuccinic bridges were synthesised and their inclusion properties were evaluated using NMR and isothermic microcalorimetric measurements ITC. The selective binding of ligands, such as bisadamantyl derivatives, to the cavities of unprotected cyclodextrin dimers s...
Article
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 host systems. However to avoid formation of self-organized systems, these hydrophobic cage molecules can be rendered water soluble by introduction of ionic grou...
Article
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)...
Article
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 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 s...
Article
Nanofabrication by molecular self-assembly involves the design of molecules and self-assembly strategies so that shape and chemical complementarities drive the units to organize spontaneously into the desired structures. The power of self-assembly makes it the ubiquitous strategy of living organized matter and provides a powerful tool to chemists....
Article
Full-text available
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 in discrete locations with tritium enables accurate measurement of long-range distances owing to the high gyromagnetic ratio of this nucleus, without structu...
Article
Spin-noise appeal: Detection of NMR spin-noise is very appealing when dilute hyperpolarized species are considered. Continuous monitoring of the noise absorption at the Larmor frequency enables determination of T(1) and T(2)*, independently of the static magnetic field. An inductively coupled microcoil located inside the NMR tube (see picture) allo...
Article
When a system composed of dissolved laser-polarized xenon with negative spin temperature is put inside a high field NMR magnet, a series of spontaneous maser emissions can be observed. We report here their spectral and temporal features using a processing model derived from the solution of the Bloch equations in the presence of radiation damping. W...
Article
We have studied the dialysis of surfactant mixtures of two oppositely charged surfactants (catanionic mixture) by combining HPLC, neutron activation, confocal microscopy, and NMR. In mixtures of n-alkyl trimethylammonium halides and n-fatty acids, we have demonstrated the existence of a specific ratio between both surfactant contents (anionic/catio...
Article
Full-text available
The synthesis and functionalisation of zeolite nanoparticles designed for laser-polarized Xe-129 NMR experiments in solution are described. These nanoparticles were functionalized by using original synthesis pathways through semicarbazide COCHO chemistry in order to ensure anchoring of a peptide for targeting biological receptors and attachment of...
Article
Xe-129 MRI is applied to cage molecules in which hyperpolarized xenon exhibits a specific spectral signature. In a few tens of seconds a net spatial discrimination is achieved between xenon in two different hosts dissolved in two immiscible media at submillimolar concentrations by using a gradient echo sequence with interleaved frequency selection....
Article
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 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...
Article
The cover picture illustrates the observation of multiple chaotic maser emissions in NMR. In their article on page 1395, Marion et al. show that dissolved 129Xe—in which the nuclear magnetization enhanced by optical pumping (apparatus shown in background, credit Stropa/CEA) is anti-aligned with the static magnetic field—is able to emit spontaneousl...
Article
Full-text available
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, 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 incr...