Laser-polarized xenon for the study of biological cells

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NMR Using Solution Flow Circuit and Inductively-Coupled Microcoils

International audienceInvestigation of systems in evolution such as chemical reactions via NMR can be rendered com-fortable if the intrinsic lack of sensitivity of this technique is circumvented and provided that quantitative data are obtained. Here we present an integrated device based on a 3D-printed mini bubble-pump associated with fluidics and micro-detection that overcomes the sensitivity problems inherent to slow return of magnetization to equilibrium in liquid-state NMR. The use of a closed-loop circuit of the solution near the NMR magnetic center presents two main advantages: pre-polarization is achieved for the whole solution volume, this volume can be reduced to tens of microliters. This device is installable into every commercial liquid probehead without modification; it is easily inserted from the top of the NMR magnet. A gas flow driven by a programmable syringe pump actuates a mini bubble-pump which leads to circulation of the liquid sample. A part of the solution circuit crosses the NMR detection region consisting of a micro-solenoid inductively coupled to the coil of the commercial probehead. In order to optimize this coupling a rod fixed on the upper part of the insert and ended by a Vernier placed on top of the magnet enables angular positioning of the micro-coil. The two resonance frequencies created by the coupling allow one to observe nuclei inaccessible with the host probe alone, or to study two different nuclei with the optimized detection allowed by the micro coil. To further increase the signal-to-noise ratio, this system can also be used to effi-ciently dispense gaseous species such as hyperpolarized xenon and parahydrogen to the solution. The performances of this device, in particular with cryoprobes, will be presented

Industrial and academic approaches to the search for alternative melatonin receptor ligands: An historical survey.

The search for melatonin receptor agonists formed the main part of melatonin medicinal chemistry programs for the last three decades. In this short review, we summarize the two main aspects of these programs: the development of all the necessary tools to characterize the newly synthesized ligands at the two melatonin receptors MT1 and MT2 , and the medicinal chemist’s approaches to find chemically diverse ligands at these receptors. Both strategies are described. It turns out that the main source of tools were industrial laboratories, while the medicinal chemistry was mainly carried out in academia. Such complete accounts are interesting, as they delineate the spirits in which the teams were working demonstrating their strength and innovative character. Most of the programs were focused on non-selective agonists and few of them reached the marked. In contrast, discovery of MT1-selective agonists and melatonergic antagonists with proven in vivo activity and MT1 or MT2-selectivity is still in its infancy, despite the considerable interest that subtype selective compounds may bring in the domain, as the physiological respective roles of the two subtypes of melatonin receptors, is still poorly understood. Poly-pharmacology applications and multitarget ligands have also been considered

New developments related to fast and multiplexed detection of 129Xe NMR biosensor

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Dernières avancées sur l'utilisation du xénon polarisé comme biosonde

International audienc

Dernières avancées sur l'utilisation du xénon polarisé comme biosonde

International audienc

Understanding a host-guets model system through 129Xe NMR experiments and theoretical chemistry

International audienc

Understanding a Host-guest model system through 129Xe NMR experiments and theoretical chemistry

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

International audienceThe known xenon-binding (±)-cryptophane-111 (1) has been functionalized with six [(η5-C5Me5)RuII]+ ([Cp*Ru]+) moieties to give, in 89% yield, the first water-soluble cryptophane-111 derivative, namely [(Cp*Ru)61]Cl6 ([2]Cl6). [2]Cl6 exhibits a very high affinity for xenon in water, with a binding constant of 2.9(2) × 104 M−1 as measured by hyperpolarized 129Xe NMR spectroscopy. The 129Xe NMR chemical shift of the aqueous Xe@[2]6+ species (308 ppm) resonates over 275 ppm downfield of the parent Xe@1 species in (CDCl2)2 and greatly broadens the practical 129Xe NMR chemical shift range made available by xenon-binding molecular hosts. Single crystal structures of [2][CF3SO3]6·xsolvent and 0.75H2O@1·2CHCl3 reveal the ability of the cryptophane-111 core to adapt its conformation to guests

Synthesis of a Functionalizable Water-Soluble Cryptophane-111

The development of optimized xenon host systems is of crucial importance for the success of molecular imaging using hyperpolarized ¹²⁹Xe 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 expeditious synthesis of a water-soluble and functionalizable cryptophane-111 is described