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International audience; Molecular imaging is a biomedical research discipline that has quickly emerged to afford the observation, characterization, monitoring, and quantification of biomarkers and biological processes in living organism. It covers a large array of imaging techniques, each of which provides anatomical, functional, or metabolic information. Multimodality, as the combination of two or more of these techniques, has proven to be one of the best options to boost their individual properties, hence offering unprecedented tools for human health. In this review, we will focus on the combination of positron emission tomography and fluorescence imaging from the specific perspective of the chemical synthesis of dual imaging agents. Based on a detailed analysis of the literature, this review aims at giving a comprehensive overview of the chemical strategies implemented to build adequate imaging tools considering radiohalogens and radiometals as positron emitters, fluorescent dyes mostly emitting in the NIR window and all types of targeting vectors.

Publisher: American Chemical Society; International audience; Propargylated bambus[4,6]urils were prepared by an efficient one-step condensation of dipropargylglycoluril with formaldehyde under microwave irradiation. Their functionalization by click chemistry (CuAAC) afforded new multivalent architectures decorated with 8 or 12 ligands. Grafting of glycosides provided water-soluble glycobambus[4,6]uril platforms with glucosyl12BU[6] showing good affinity toward iodide anion in aqueous medium.

International audience; Characterizing how multidrug-resistant bacteria circumvent the action of clinically used or novel antibiotics requires a detailed understanding of how the antibiotics interact with and cross bacterial membranes to accumulate in the cells and exert their action. When monitoring the interactions of drugs with bacteria it remains challenging to differentiate functionally relevant internalized drug levels from non-specific binding. Fluorescence is a method of choice for observing dynamics of biomolecules. In order to facilitate studies involving aminoglycoside antibiotics, we have generated fluorescently labeled aminoglycoside derivatives with uptake and bactericidal activities similar, albeit with a moderate loss, to those of the parent drug. The method combines fluorescence microscopy with fluorescence-activated cell sorting (FACS) using neomycin coupled to non-permeable cyanine dyes. Fluorescence imaging allowed membrane-bound antibiotic to be distinguished from molecules in the cytoplasm. Patterns of uptake were assigned to different populations in the FACS analysis. Our study illustrates how fluorescent derivatives of an aminoglycoside enable a robust characterization of the three components of uptake: membrane binding, EDPI, and EDPII. Because EDPI levels are weak compared to the two other types of accumulation and critical for the action of these drugs, the three components of uptake must be taken into account separately when drawing conclusions about aminoglycoside function.

International audience; 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 O$_2$ and show that one of them, namely per-hydroxylated cucurbit[5]uril, (OH)$_{10}$CB[5], is able to significantly bind dioxygen gas at physiological temperature, even in the presence of sodium chloride at the concentration of injectable solution in blood. As cucurbit[n]urils studied up to now reveal low toxicity, per-hydroxylated cucurbit[5]uril appears as a promising precursor to design a host able to transport O$_2$ in a haemoglobin substitute solution.

Sulfide-functionalized bambus[4]urils ((RS)8 BU[4]) and bambus[6]urils ((RS)12 BU[6]) were synthesized through thiol-ene click coupling reactions (TEC) of allylbambus[n]urils. Thiosugars were grafted to BU[4] and BU[6]. Synthesis of BU[6] derivatives always requires the use of a template anion (iodide, chloride, or bromide), which is enclosed in the cavity of BU[6]. We show that this anion influences the reactivity of bambus[6]urils. An encapsulated iodide makes allyl functions of allyl12 BU[6] less reactive towards TEC and hydrogenation reactions in comparison to the corresponding chloride or bromide inclusion complexes. This is critical for the chemical reactivity of BU[6] and even more to determine their anion-binding properties. We report a new, facile and fast method using AgSbF6 to prepare anion-free BU[6]. NMR spectroscopic methods were used to estimate association constants of these new empty BU[6] with different anions. Quantum chemical calculations were employed to rationalize the observed results. These new functionalized bambusuril scaffolds in alternate conformations could find applications as multivalent binders.

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 is sufficient to enhance the solubility in water by a factor of 170 with respect to CB[6], and Cy6CB[6] is around 30 times more soluble than Cy1CB[6]. The cyclohexane moieties, by limiting or impeding the formation of intermolecular C–H···O hydrogen bonds, may explain this increase in solubility. The effect of modification of the molecular shape on the solubility was assessed by liquid-state NMR spectroscopy and DFT calculations.

Microwave irradiations allow the preparation of unsaturated bambusurils in 85% yield compared to 20% yield under classical reaction conditions. Five new bambusurils were synthesized including unsaturated derivatives Allyl(8)BU[4] and Allyl(12)BU[6] bearing diallylglycoluril units. The reactivity of Allyl(8)BU[4] was tested in a variety of organic reactions showing that this macrocycle acts as a classical double bond-bearing product. The first monofunctionalized bambusuril Allyl(7)HepBU[4] prepared by a cross metathesis reaction is also reported.

The increasing need for site-specific protein decorations that mimic natural posttranslational modifications requires access to a variety of noncanonical amino acids with moieties enabling bioorthogonal conjugation chemistry. Here we present the incorporation of long-chain olefinic amino acids into model proteins with rational variants of pyrrolysyl-tRNA synthetase (PylRS). Nε-heptenoyl lysine was incorporated for the first time using the known promiscuous variant PylRS(Y306A/Y384F), and Nε-pentenoyl lysine was incorporated in significant yields with the novel variant PylRS(C348A/Y384F). This is the only example of rational modification at position C348 to enlarge the enzyme's binding pocket. Furthermore, we demonstrate the feasibility of our chosen amino acids in the thiol-ene conjugation reaction with a thiolated polysaccharide. ispartof: Molecules vol:21 issue:3 pages:287-296 ispartof: location:Switzerland status: published

WOS:000274843100020; International audience; alpha-Mono- or alpha-dialkylated aldehydes undergo cyclotrimerization in the presence of dibromotriphenylphosphorane (PPh(3)Br(2)) to afford cyclopentenones or tetrasubstituted tetrahydrofurans in good yields. These transformations proceed by a tandem aldol dimerization/Nazarov reaction or a tandem aldol dimerization/Prins cyclization.

Enzyme inhibition through mimicry of the transition state is a major area for the design of new therapeutic agents. Emerging evidence suggests that many retaining glycosidases that are active on alpha- or beta-mannosides harness unusual B2,5 (boat) transition states. Here we present the analysis of 25 putative beta-mannosidase inhibitors, whose Ki values range from nanomolar to millimolar, on the Bacteroides thetaiotaomicron beta-mannosidase BtMan2A. B2,5 or closely related conformations were observed for all tightly binding compounds. Subsequent linear free energy relationships that correlate log Ki with log Km/kcat for a series of active center variants highlight aryl-substituted mannoimidazoles as powerful transition state mimics in which the binding energy of the aryl group enhances both binding and the degree of transition state mimicry. Support for a B2,5 transition state during enzymatic beta-mannosidase hydrolysis should also facilitate the design and exploitation of transition state mimics for the inhibition of retaining alpha-mannosidases--an area that is emerging for anticancer therapeutics.

[reaction: see text] 1,3-Dimesitylimidazol-2-ylidene ruthenium benzylidene catalyst (RuCl2(=C(H)Ph)(PCy3)(IMes)) has been successfully employed in ring-closing metathesis reactions of acyclic diene sulfides, disulfides, and dithianes and in self-cross metathesis reactions of ene-sulfides, thioethers, and thiols.

The ruthenium catalysts (PCy3)2Ru(C(H)Ph)Cl2 (1), (PCy3)Ru(IMes)(C(H)Ph)Cl2 (2), (PCy3)Ru(SIMes)(C(H)Ph)Cl2 (3), (PCyp3)Ru(IMes)(CHCHC(CH3)2)Cl2 (4), and (PCy3)Ru(IPr)(3-phenylindenylid-1-ene)Cl2 (5), where IMes = 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene, SIMes = 1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene, IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene, Cy = cyclohexyl, and Cpy = cyclopentyl, have been grafted to polymer supports and found to be effective heterogeneous catalysts for ring-closing metathesis. In some cases, they are recyclable, show comparable reactivity to their homogeneous counterparts, tolerate functional groups, and perform very well with unsubstituted dienes.

There is growing interest in the development of molecular containers dedicated to gas trapping in water. Cucurbit[5]uril (CB[5]), the smallest member of a glycoluril macrocycles family (Figure 1), is able to interact with a large array of guest molecules, among which noble gases. The interaction of cucurbit[6]uril (CB[6]) with xenon, a promising noble gas for molecular imaging applications, was investigated in aqueous solution containing acids or salts designed to increase the solubility of the host molecule. However, it was shown that cations interact with the partial charges on oxygen atoms, while apolar molecules are encapsulated in the hydrophobic cavity of cucurbiturils. We already evidenced that the presence of these acids or salts alters the xenon in/out exchange for CB[6] (Figure S1 of the Supporting Information), confirming results obtained with CB*[6] (Figure 1a). In the literature, observation of xenon binding by cucurbituril derivatives in pure water was previously rendered possible only by grafting substituents, giving MeCB[5] and CB*[6] (Figure 1a). In order to understand the thermodynamics and kinetics of xenon binding in CB[5] , it seemed thus useful to study samples in deionized water. Although xenon binding in a crystalline form of native CB[5] was observed, no quantitative kinetics and thermodynamics data were reported for CB[5] or a derivative in aqueous solution. Herein, taking advantage of a solubility not so low in pure water, we show that CB[5] spontaneously incorporates xenon at 316 K with a quite high binding constant and a low in/out exchange rate. This exchange rate is even measurable at 293 K. In the presence of xenon, the H NMR spectrum of a D2O solution of CB[5] exhibits two series of signals characteristic of a slow exchange between two environments, one with and the other without xenon (Figure 1c). The Xe spectrum shows two signals (Figure 1d) also denoting a slow exchange. The signal at 196 ppm is assigned to free xenon in water and the signal at 225 ppm to xenon encapsulated in CB[5] (Xe@CB[5]), at a chemical shift close to that already observed in a crystal form of the molecule. The second signal exhibits a linear dependence of chemical shift with temperature between 277 and 334 K, with a slope of 117 3 ppbK 1 (Figure S2, Supporting Information). This may easily be explained by a deeper exploration of the CB[5] cavity by xenon in areas affected by the magnetic anisotropy effect of the carbonyl groups at higher temperatures. The xenon in/out exchange is also slow on the xenon longitudinal relaxation (T1) timescale. The T1 value of trapped Xe increases from 15 3 s to 28 5 s when temperature varies from 277 K to 315 K. The rather long T1 confirms previous results on CB*[6] and reflects the weakness of the proton– xenon dipolar interaction in a system where protons point outwards. The observed T1 value cannot be entirely explained by this mechanism, and other relaxation mechanisms such as chemical shift modulation must also be efficient. To our knowledge, CB[5] is the first example of a host molecule with which the xenon in/out exchange is slow on the relaxation timescale. This kinetics was characterized in more detail through gas-release experiments. Proton NMR spectra were recorded at repeated time intervals, in a situation where dissolved xenon tends to equilibrate with gaseous xenon. Figure 1. a) General formula of the cucurbiturils cited in the text. CB[5]: n=5, R=R’=H; CB[6]: n=6, R=R’=H. MeCB[5]: n=5, R=R’=CH3; CB*[6]: n=6, RR’= (CH2)4. b) Space-fill representation of a crystal structure of CB[5] , with both facing glycoluril units and attached methylene groups removed for clarity. A xenon atom is superimposed in the center of the molecule showing the geometry of the complex. c) H NMR spectrum of a 5.4 mm solution in D2O of CB[5] under 2.5 atm of xenon at 316 K. Signals assigned to CB[5] entrapping a xenon atom are denoted by *, while those standing for xenon-free cages are denoted by *. d) Xe NMR spectrum of a 0.25 mm D2O solution of CB[5] under 6 atm of xenon at 316 K at thermodynamic equilibrium, 20500 scans with a repetition rate of 3.8 s, Fourier transformed with a 6 Hz line broadening.

A gradient method to determine directly and quantitatively ternary phase diagrams is reported. The gradients are created in standard X-ray capillaries. 14C labeling and X-ray transmission measurements are used together in situ to obtain the exact sample composition along the gradient. Structural phase identification is obtained from SAXS analysis. Using this method, two cationic surfactant/glycolipid/water ternary systems have been investigated at different temperatures.

This paper describes our recent study of glycosyl phosphites for glycosylation reactions, with particular emphasis on the investigation of protecting group and stereochemistry effects on the anomeric reactivity and stereoselectivity, and the application of this methodology to the synthesis of Lewis X (Lex), Lewis Y (Ley), glycopeptides, and sialyl Lewis X (SLex) mimetics. Both α-O-fucosyl-l-threonine and α-O-fucosyl-(1R,2R)-2-aminocyclohexanol were found to be effective templates for the chemical/enzymatic synthesis of SLex mimetics, and some fucopeptides prepared were 5−10 times more active than SLex as inhibitors of E-selectin.

The reaction of iodotrimethylsilane with sugar lactones protected by ester groups leads to primary iodides of the same configuration.

The reaction of iodotrimethylsilane with sugar lactones protected by ester groups leads to primary iodides of the same configuration.

Basees sur une reaction de participation intramoleculaire de groupements benzyloxy ou amide, deux series de conditions experimentales ont ete respectivement mises au point pour la preparation des tetrahydrofuranes polyoxygenes de type 6 ou de la lactone 8 a partir des polyols acycliques precurseurs derives de sucres de type 4. Ces procedes decrivent une sequence reactionnelle en deux etapes de mesylation-cyclisation induite par les systemes LiOH/THF-H 2 O ou NaI/CH 3 CN au reflux ou une cyclisation en une etape assistee par le diethylaminotrifluorosulfurane (DAST) a -78 °C dans le dichloromethane. Ces cyclisations sont rapportees en considerant plus particulierement la synthese stereoselective de tetrahydrofuranes chiraux polyoxygenes. Des etudes de modelisation moleculaire ont ete realisees pour essayer de rationaliser les resultats de cyclisation observes impliquant les participations des groupements benzyloxy ou amide pour differents precurseurs de cyclisation.

alpha-Mono- or alpha-dialkylated aldehydes undergo cyclotrimerization in the presence of dibromotriphenylphosphorane (PPh(3)Br(2)) to afford cyclopentenones or tetrasubstituted tetrahydrofurans in good yields. These transformations proceed by a tandem aldol dimerization/Nazarov reaction or a tandem aldol dimerization/Prins cyclization.

Total synthesis of (−)-muricatacin, a natural acetogenin, has been achieved using as a key step a regio- and stereospecific ring-opening of a substituted vinyl epoxide under Lewis acid catalysis.

A Lewis acid-catalyzed, regiospecific opening of vinyl epoxides to β-hydroxy allyl-ethers was performed using equimolar quantities of both alcohols and oxiranes. BF 3 ·Et 2 O proved to be the most efficient catalyst for various substituted alcohols.

Adjacent tris(cyclic ethers) and enol ethers have been synthesized in good yields for the first time via a triple olefin metathesis reaction using Grubbs' catalyst RuCl2(C(H)Ph)(PCy3)2 (Cy = cyclohexyl), and the 1,3-dimesitylimidazol-2-ylidene ruthenium benzylidene catalyst RuCl2(C(H)Ph)(PCy3)(IMes) ((IMes) = 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene). The latter proved to be the most efficient catalyst in these transformations.

The ruthenium catalysts (PCy3)2Ru(C(H)Ph)Cl2 (1), (PCy3)Ru(IMes)(C(H)Ph)Cl2 (2), (PCy3)Ru(SIMes)(C(H)Ph)Cl2 (3), (PCyp3)Ru(IMes)(CHCHC(CH3)2)Cl2 (4), and (PCy3)Ru(IPr)(3-phenylindenylid-1-ene)Cl2 (5), where IMes = 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene, SIMes = 1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene, IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene, Cy = cyclohexyl, and Cpy = cyclopentyl, have been grafted to polymer supports and found to be effective heterogeneous catalysts for ring-closing metathesis. In some cases, they are recyclable, show comparable reactivity to their homogeneous counterparts, tolerate functional groups, and perform very well with unsubstituted dienes.

1,3-Dimesitylimidazol-2-ylidene ruthenium benzylidene catalyst (RuCl2(C(H)Ph)(PCy3)(IMes)) has been successfully employed in ring-closing metathesis reactions of acyclic diene sulfides, disulfides, and dithianes and in self-cross metathesis reactions of ene-sulfides, thioethers, and thiols.

A Lewis acid-catalyzed, regiospecific opening of vinyl epoxides to β-hydroxy allyl-ethers was performed using equimolar quantities of both alcohols and oxiranes. BF 3 ·Et 2 O proved to be the most efficient catalyst for various substituted alcohols.

Total synthesis of (−)-muricatacin, a natural acetogenin, has been achieved using as a key step a regio- and stereospecific ring-opening of a substituted vinyl epoxide under Lewis acid catalysis.

The first example of a non-enzymatic C-2 epimerization of aldonolactones is reported. The reaction of 2,3,4,6-tetra-O-benzyl-d-gluconolactone or 2,3,4,6-tetra-O-benzyl-d-mannonolactone with MgI(2) in EtOH afforded their respective C-2 epimer. Studies conducted in EtOD showing the incorporation of a deuterium atom only at the C-2 position of the epimerized product reveal an epimerization rather than a racemization reaction. A mechanism involving a chelation with a magnesium species is proposed to explain this C-2 inversion reaction.

An original convergent total synthesis of Solamin (type A annonaceous acetogenin) was achieved. The central THF core was obtained by means of a ring-closing metathesis (RCM) reaction using a ruthenium imidazolylidene complex. The RCM substrate was prepared from a vinyl-substituted epoxide by reaction with an allyl alcohol, both synthesized from propargylic alcohol. The flexibility of the strategy should be useful in preparing various natural and unnatural annonaceous acetogenins.

A series of monocyclic glycoamidines bearing different exocyclic amine, alcohol, or alkyl functionalities and bicyclic amidines derived from D-glucose and D-mannose were synthesized and tested as inhibitors of various glycosidases. All the prepared compounds demonstrated good to excellent inhibition toward glycosidases. In particular, the biscationic D-mannoamidine 9b bearing an exocyclic ethylamine moiety proved to be a selective competitive inhibitor of alpha- and beta-mannosidases (K(i) = 6 nM) making it the most potent inhibitor of these glycosidases reported to date. A favorable B(2,5) boat conformation might explain the selectivity of mannosidase inhibition compared to other glycosidases.

[reaction: see text] Adjacent tris(cyclic ethers) and enol ethers have been synthesized in good yields for the first time via a triple olefin metathesis reaction using Grubbs' catalyst RuCl(2)(=C(H)Ph)(PCy(3))(2) (Cy = cyclohexyl), and the 1,3-dimesitylimidazol-2-ylidene ruthenium benzylidene catalyst RuCl(2)(=C(H)Ph)(PCy(3))(IMes) ((IMes) = 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene). The latter proved to be the most efficient catalyst in these transformations.

Synthesis of 4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-y1)-[1,3]dioxolan-2-yl]-benzoic acid or SR11237, a specific ligand of Retinoid X Receptors, is described in a 3H-labelled version. The labelled retinoid was prepared in 5 steps and tritium was introduced through a final reduction of an aromatic dihalide moiety with 3 H 2 .

Design and synthesis of new Bambusurils for biological applications and molecular imagingBambus[n]urils, R₈BU[4] and R₁₂BU[6], are synthetic cyclic macromolecules that belong to the cucurbit[n]urils families. They are composed of n-substituted glycoluril units connected via n-methylene bridges. The R₁₂BU[6], are able to bind anion inside their cavity with a good association constant through hydrogen bonds.In our laboratory, bambusurils bearing allyl functions, named Allyl₈BU[4] and Allyl₁₂BU[6], were efficiently prepared. These bambusurils were functionalized by ring-closing metathesis or thiol-ene click coupling to introduce 1 to 12 functions like ester, acids and glycosides.To develop the family of bambusurils, new bambusurils with propargyl functions were synthesized. The synthesis of the Propargyl₈BU[4] and Propargyl₁₂BU[6] were optimized. Theses BUs were functionalized by click chemistry with different azides like ester, benzyl and glycoside to dispose of new multivalent systems with a valency of 8 for the BU[4] and 12 for the BU[6]. For the first time, glycoBambusurils functionalized with D-mannose derivatives were prepared, and their antibacterial activities were assayed. Moreover, iminosugar from the family of the azido alkylated déoxynojirimycine, were grafted on the PropargylBUs to afford new inhibitors of glycosidases. These results show the importance of bambusuril scaffold and of the multivalence effect improve the affinity of the glycoBUs for the target.The association constants of R₁₂BU[6] functionalized, soluble in aqueous media for iodide were determined by isothermal titration calorimetry. The results show a good affinity of R12BU[6] for iodide (Ka ≃ 10⁵ M⁻¹).We studied as well an application of bambusuril for molecular imaging. A new bambusuril with biological ligands was designed and synthesized to introduce a bimodal probe PET/Optical in the last step. This probe will allow the combination of clinical diagnostic with PET and optical imaging. A proof of concept was realized with a function ¹⁸F labelled.; Conception et synthèse de nouveaux Bambusurils pour des applications en biologie et en imagerie moléculaire. Les bambusurils, R₈BU[4] et R₁₂BU[6], sont des molécules cages synthétiques, constituées respectivement de 4 et 6 unités glycolurils. Ils diffèrent des cucurbiturils par la présence de glycolurils difonctionnalisés qui leur confèrent une topologie de type alternée et des propriétés supramoléculaires intéressantes. Les R₁₂BU[6] ont la capacité d’encapsuler un anion à l'intérieur de leur cavité avec une très grande affinité grâce à 12 liaisons hydrogènes. Au laboratoire, des bambusurils disposant de groupements allyles nommés Allyl₈BU[4] et Allyl₁₂BU[6] ont été synthétisés. Ils ont ensuite été fonctionnalisés par réactions de métathèse croisée et de thiol-ène click pour introduire facilement 8 à 12 thiols d'intérêts possédant des groupements esters, acides ou glycosides. Pour élargir la famille des bambusurils, de nouveaux bambusurils possédant des fonctions propargyliques ont été préparés. Ainsi, les Propargyl₈BU[4] et Propargyl₁₂BU[6] ont été obtenus avec de bons rendements. Ces bambusurils ont ensuite été post-fonctionnalisés avec différents azotures (esters, benzyl, glycosides, peptides) par réaction de chimie click pour conduire à de nouvelles plateformes multivalentes de valence 8 pour le BU[4] et 12 pour le BU[6]. Des glycoBUs fonctionnalisés par des dérivés du D-mannose ont été synthétisés pour la première fois, et leur activité antibactérienne a été évaluée. De plus, des iminosucres de la famille de la déoxynojirimycine azidoalkylée, ont également été greffés sur les PropargylBUs, pour conduire à de nouveaux inhibiteurs de glycosidases. Le squelette des bambusurils et la multivalence conduisent à des gains d'affinité importants par rapport aux analogues glycosides monovalents.L'affinité des R₁₂BU[6], hydrosolubles, a été évaluée pour les ions iodures par titration calorimétrique isotherme. Les résultats obtenus confirment la grande affinité des BU[6] pour cet anion dans l'eau (Ka ≃ 10⁵ M⁻¹).Une dernière application des bambusurils comme sonde d'imagerie a également été étudiée. Un nouveau bambusuril différemment substitué a été conçu et synthétisé pour permettre l'introduction d'une sonde bimodale TEP/Optique en dernière étape de synthèse. Cette sonde permettra la combinaison d'un double diagnostic médical par imagerie TEP et optique. Une preuve de concept a été réalisée avec l'introduction d'un groupement radiomarqué au ¹⁸F.

The cucurbituril family (CBn) constitutes a group of recent synthetic host-molecules. These compounds are formed by n glycoluril units and, since the beginning of the 2000’s, they have found their interest in multiple domains such as biology, chemistry and physics. They have joined the large group of synthetic receptors comprising cyclodextrins, calixarens, cryptophanes, carcerands and hemicarcerands. Gaz encapsulation in this family of compounds is misunderstood. In these PhD works, our interest concerned gaz complexation, especially xenon, into cucurbiturils.First, the synthesis of new hydrosoluble cucurbiturils to study their ability to encapsulate noble gaz and small alcans such as methan and ethan is described. Our final goal will be to define new rules concerning gaz encapsulation by cucurbiturils. Noble gaz from helium to krypton have been studied. Among these noble gaz, xenon is particularly interesting in the domain of biosensing, for the design of new diagnostic methods by MRI.In this manuscript, the synthesis of a family of hydrosoluble cyclohexylcucurbiturils and their ability to encapsulate xenon is described. Another new cucurbituril constituted by five glycoluril units and one glycoluril unit forming a six-membered ring, has also been prepared. The first two parts of the manuscript present the gaz encapsulation and the cucurbituril family. The third part describes our results concerning the new synthetized cucurbiturils. In the fourth part, we have developped a method based on metathesis reactions (ROM-CM) for preparing some precursors of acyclic congeneers of cucurbiturils. Lastly, the fifth part concerns results about gaz encapsulation. All of this study has been driven in collaboration with Laboratoire de Structure et Dynamique par Résonance Magnétique (CEA Saclay).; Les cucurbiturils (CBn) sont des molécules-cages synthétiques constituées d’un nombre n d’unités glycoluril et dont les applications en chimie, en biologie et en physique ont commencé à être exploitées au début des années 2000. Ces composés trouvent leur importance dans un grand nombre de domaines incluant la chimie en phase solide, le piégeage des contaminants en solution, la catalyse ou encore l’encapsulation de principes actifs pour des applications pharmaceutiques futures. Ces récentes molécules-cages rejoignent le large groupe des récepteurs synthétiques comprenant les cyclodextrines, les calixarènes, les cryptophanes, les carcérands et hémicarcérands. L’encapsulation des gaz dans ce type de structures est encore mal connue à l’heure actuelle et, dans ces travaux de thèse, notre intérêt s’est porté sur la complexation de gaz, notamment de xénon, dans les cucurbiturils.Ces travaux ont débuté par la synthèse de nouveaux cucurbiturils hydrosolubles dans le but d’étudier leur capacité d’encapsulation des gaz rares et de petits alcanes comme le méthane et l’éthane, notre objectif final étant de définir de nouvelles règles régissant l’encapsulation des gaz par les cucurbiturils. Les gaz rares allant de l’hélium au krypton ont été étudiés. Parmi ces gaz, le xénon hyperpolarisé a particulièrement retenu notre attention du fait de son intérêt dans la conception de biosondes pour le développement de nouvelles méthodes de diagnostic en IRM. Dans ce mémoire, la synthèse de nouveaux cyclohexylcucurbiturils mixtes hydrosolubles et leurs études en présence de xénon sont rapportées. Un nouveau cucurbituril mixte constitué de cinq unités glycoluril et d’une unité glycoluril à six chaînons a également été synthétisé. Les deux premiers chapitres constituent une introduction au phénomène d’encapsulation des gaz ainsi que des généralités sur la famille des cucurbiturils. Le troisième chapitre est consacré aux résultats obtenus au laboratoire sur la synthèse de nouveaux composés. Dans un quatrième chapitre, nous avons développé une méthode permettant la préparation de précurseurs d’analogues acycliques de cucurbiturils. Pour cela, la réaction de métathèse par ouverture de cycle associée à la métathèse croisée (ROM-CM) a été utilisée pour mener à bien cette synthèse. Enfin, un cinquième chapitre est consacré aux résultats concernant l’étude de l’encapsulation de gaz dans les nouveaux cucurbiturils synthétisés, étude effectuée en collaboration avec le Laboratoire de Structure et Dynamique par Résonance Magnétique du CEA de Saclay.