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Ever since its discovery, hydrogen has been a source of fascination for the scientific community. As early as the sixteenth century, scholars reported a gas evolution reaction resulting from adding metal to acidic solutions. In 1766, Henry Cavendish recognized that the evolved gas was in fact hydrogen (Cavendish 1766; Al-Khalili 2010). Hydrogen is, after all, the most common element in the universe (Palmer 1997) and is responsible for the majority of the mass-to-energy conversion happening in the stars. It also forms the simplest atomic entity H, a combination of a single proton and a single electron, the simplest example of multi-atomic molecule H2, the simplest of all ionic species H+, and, of interest to electrochemists worldwide, presents the simplest electrochemical reaction2 2 2H e H + + « (5.1)On a (much) smaller scale, our planetary scale, it can also be a foundation of the carbon-free energy conversion scheme, the so-called “hydrogen economy,” a term coined and a concept formed in the early seventies by one of electrochemistry’s greatest minds, Dr. Bernhardt Patrick John O’Mara Bockris (Bockris and Appleby 1972), a big proponent of a global conversion from carbon-based energy carriers to the hydrogen-based ones.* Bockris’ dreams of hydrogen economy were perhaps well ahead of their time in the seventies and were not getting much of the traction back then. Today, however, the situation seems to be changing dramatically, and the vision of hydrogen economy may not be such a pipe dream anymore.

A rapid and stereodivergent access to polyhydroxylated 10-azabicyclo[4.3.1]decanes as new calystegine analogues by way of a double benzotriazolyl/carbon nucleophile exchange followed by a ring-closing metathesis was achieved. Preliminary evaluation of the new compounds as glucocerebrosidase inhibitors was also performed.

The electrochemical oxidation of full-size heparin (13–15 kDa) is demonstrated in 1 M H3PO4 at a glassy carbon electrode coated with a ruthenium oxide film. The pathway apparently is analogous to chemical oxidation by periodate. By comparison to currents from inorganic species, it is apparent that only about 2 electrons per mole are involved. Flow injection analysis (FIA) allowed determinations down to 2 μM heparin, but the calibration plot was nonlinear. Low molecular weight heparin (5–6 kDa) was not electroactive with this system. In basic solution at a glassy carbon electrode that is modified with a film of Cu2O, both full-size and low molecular weight heparin are oxidized. The pathways involved oxidative desulfation and attack on saccharide units with evolution of CO2. Linear calibration plots which extended into the sub-μM level were obtained by FIA. The detection limits, which were based on a value of 3 for the ratio of the signal to the standard deviation of replicates, were 9 nM for full-size and 20–30 nM for various low molecular weight heparin samples.

A polishable bulk-modified electrode is described that contains polymeric-mixed valent ruthenium oxide with cyano cross-links (mvRuCN) as a catalyst. Because mvRuCN is not available as an isolated compound, it was electropolymerized on graphite powder that was subsequently formed into a conducting composite with epoxy. Except for promoting oxidations at a more positive potential, this composite behaved the same as mvRuCN films on glassy carbon. Electrocatalytic oxidation of various N-nitrosamines, As(III), glutathione, isotocin, and myoglobin was observed. Flow-injection analysis of 50 μM N-nitrosodi-n-propylamine with amperometric detection at the bulk-modified composite electrode yielded currents of 2.5 ± 0.1 μA (5 trials) when the carrier solution is pH 1.5 phosphate buffer. The use of a micellar carrier,pH 1.5 phosphate buffer in 0.01 M hexadecyltrimethylammonium chloride, decreased the sensitivity of the flow-injection amperometric determination of N-nitrosodi-n-phenylamine by 50%, but otherwise, the behavior of the electrode was unchanged. The major advantages of the bulk-modified electrode over the surface-modified electrode jras the long-term stability (at least several months with dry storage) and polishability. Regarding trie latter, 19 replicates of the oxidation of As(III) yielded a relative standard deviation (RSD) of the current response of 3% when the surface was polished between each trial.

Either an iridium electrode that was anodically pretreated or a glassy carbon electrode that was coated with a film that contained iridium oxide promoted the oxidation of hydrogen peroxide. With flow injection methodology, linear calibration curves were obtained over the 2 × 10−5 −3.6 × 10−8M range with 0.1M KOH as the carrier. With solutions of pH ⩾ 11, oxidation occurred at applied potentials of near 0.0 V vs. SCE, which is much lower than potentials needed at bare Pt or glassy carbon. The low overpotential suggests applications to systems where oxidation of other species limits the use of bare electrodes. Cyclic voltammetric studies show that HO2− is the electroactive species and that catalysis rather than mediation promotes the charge transfer. Dissolved oxygen does not interfere with the measurement.

Pseudomonas 7A glutaminase-asparaginase (PGA) catalyzes the hydrolysis of D and L isomers of glutamine and asparagine. Crystals of PGA were reacted with diazo analogues of glutamine (6-diazo-5-oxo-L-norleucine, DON) and asparagine (5-diazo-4-oxo-L-norvaline, DONV), which are known inhibitors of the enzyme. The derivatized crystals remained isomorphous to native PGA crystals. Their structures were refined to crystallographic R = 0.20 and R(free) = 0.24 for PGA-DON and R = 0.19 and R = 0.23 for PGA-DONV. Difference Fourier electron density maps clearly showed that both DON and DONV inactivate PGA through covalent inhibition. Continuous electron density connecting the inhibitor to both Thr20 and Tyr34 of the flexible loop was observed providing strong evidence that Thr20 is the primary catalytic nucleophile and that Tyr34 plays an important role in catalysis as well. The unexpected covalent binding observed in the PGA-DON and PGA-DONV complexes shows that a secondary reaction involving the formation of a Tyr34-inhibitor bond takes place with concomitant inactivation of PGA. The predicted covalent linkage is not seen, however, suggesting an alternative method of inhibition not yet seen for these diazo analogues. These surprising results give insight as to the role of the flexible loop Thr and Tyr in the catalytic mechanism.

Pseudomonas 7A glutaminase-asparaginase (PGA) catalyzes the hydrolysis of D- and L-isomers of glutamine and asparagine. X-ray quality type-1 crystals of PGA have been obtained from 2.0 M ammonium sulfate. The space group is C222(1) with unit-cell dimensions a = 78.62, b = 135.80, and c = 137.88 A. The tetrameric molecule is located on a crystallographic 2-fold axis, and two subunits form the asymmetric portion of the unit cell. The structure was solved by the molecular replacement method and refined at 1.7 A resolution to an R = 19.9% with a good geometry of the model, G = 0.05. The resultant electron density maps enabled us to resolve individual constituent atoms of most residues and introduce minor revisions to the amino acid sequence. The catalytic loop, Thr20-Gly40, is in the closed conformation with excellent electron density in both subunits. A sulfate ion and an ammonium ion are bound in the substrate binding site and interect with the loop. This interaction appears to be responsible for the observed closed conformation. New arguments supporting Thr20 as the catalytic nucleophile in the asparaginase activity are proposed.

Enolase in the presence of its physiological cofactor Mg2+ is inhibited by fluoride and phosphate ions in a strongly cooperative manner (Nowak, T, Maurer, P. Biochemistry 20:6901, 1981). The structure of the quaternary complex yeast enolase-Mg(2+)-F(-)-Pi has been determined by X-ray diffraction and refined to an R = 16.9% for those data with F/sigma (F) > or = 3 to 2.6 A resolution with a good geometry of the model. The movable loops of Pro-35-Ala-45, Val-153-Phe-169, and Asp-255-Asn-266 are in the closed conformation found previously in the precatalytic substrate-enzyme complex. Calculations of molecular electrostatic potential show that this conformation stabilizes binding of negatively charged ligands at the Mg2+ ion more strongly than the open conformation observed in the native enolase. This closed conformation is complementary to the transition state, which also has a negatively charged ion, hydroxide, at Mg2+. The synergism of inhibition by F- and Pi most probably is due to the requirement of Pi for the closed conformation. It is possible that other Mg(2+)-dependent enzymes that have OH- ions bound to the metal ion in the transition state also will be inhibited by fluoride ions.

Formyltetrahydrofolate synthetase from Clostridium thermoaceticum has been crystallized using the hanging-drop method from ammonium sulphate and PEG solutions. Crystals are trigonal, the space group is R 32, a = 163 A, c = 259 A. A 4·2 A resolution data set has been collected. Analysis of the data using the self-rotation function shows that tetramers have approximate 222 symmetry and are positioned on a crystallographic 2-fold axis.

The nonracemic γ-silyloxy allylic stannanes (S)-8 and (R)-8 add to the (R,R)-tartrate derived enals 7 and 24 to afford the adducts alkadienol 9, 14, and alkatetraenediol 25. The bis-TBS derivatives 10, 15 and 22, upon hydroxylation with catalytic OsO 4 -NMO, yield the differentially protected polyols 11, 16, and 24

Comparaison entre les structures du chlorure de (uree) mercure et du chlorure de bis(ethyluree) mercure, donnant un exemple de l'effet de deformation, introduite dans la molecule uree par le pont ethylene, sur les proprietes de coordination de l'uree

Comparaison entre les structures du chlorure de (uree) mercure et du chlorure de bis(ethyluree) mercure, donnant un exemple de l'effet de deformation, introduite dans la molecule uree par le pont ethylene, sur les proprietes de coordination de l'uree

On account of the ubiquity of nitrogen heterocycles and their biological properties, the great attention is paid to developing methodologies of their synthesis and functionalization. For this purpose, the study of functionalization of enamides constitutes an important topic due to the utility of these motifs in the construction of complex heterocyclic derivatives. Palladium-catalyzed reactions of cross-coupling are rapid and efficient methods of choice for synthesis of enamides particularly starting from enol phosphates derived from lactams, imides or amides.The first chapter of the thesis evokes the original C-P coupling reaction of chiral and achiral secondary phosphine boranes with different enol phosphates in mild reaction conditions, leading to corresponding enamido-phosphine boranes. This methodology permits the construction of libraries of novels phosphines. Also, the reaction of nucleophilic addition of phosphide anions onto various enecarbamates acyclic was elaborated, giving an access to original beta-phosphino alpha-amino acids, bearing the quaternary carbon on alpha position to nitrogen.The second chapter is devoted to the preparation and characterization of organic chromophores based on the pyrazinic core, which are likely to exhibit the fluorescence properties. These compounds were designed to form new sensitizing systems for lanthanide cations and could be used as organic sensitizers for molecular imaging in near infrared.; En raison de l’omniprésence des hétérocycles azotés et de leurs propriétés biologiques, une attention particulière est accordée au développement de méthodologie pour leur synthèse et leur fonctionnalisation. L’étude de la fonctionnalisation d’énamides constitue une thématique importante car ces motifs s’avèrent être des outils synthétiques polyvalents permettant d’accéder à des dérivés hétérocycliques complexes. Les réactions de couplage Pd-catalysées constituent une méthode de choix rapide et efficace pour la synthèse d'énamides, notamment à partir de phosphates d'énols issus de lactames, d’imides ou d’amides. Le premier chapitre de ce travail porte sur le couplage organopalladié C-P de phosphines boranes secondaires chirales ou achirales avec des phosphates d’énols. Ce couplage C-P original, réalisé dans des conditions douces, conduit aux énamido-phosphines boranes correspondantes et offre de nombreuses possibilités pour la constitution d’une librairie de phosphines originales. Parallèlement à ce travail, l’addition nucléophile d’anions phosphures sur divers ène-carbamates acycliques conduit à des acides alpha-aminés béta-phosphorés originaux, porteurs d’un carbone quaternaire en alpha de l’azote. Le deuxième chapitre de la thèse porte sur la préparation et la caractérisation de chromophores organiques originaux basés sur un noyau pyrazinique et qui sont susceptibles de présenter des propriétés de fluorescence. Ces composés sont conçus pour former des nouveaux systèmes sensibilisateurs de cations de lanthanides, et être utilisés comme sensibilisateurs organiques pour l'imagerie moléculaire dans le proche infrarouge.

On account of the ubiquity of nitrogen heterocycles and their biological properties, the great attention is paid to developing methodologies of their synthesis and functionalization. For this purpose, the study of functionalization of enamides constitutes an important topic due to the utility of these motifs in the construction of complex heterocyclic derivatives. Palladium-catalyzed reactions of cross-coupling are rapid and efficient methods of choice for synthesis of enamides particularly starting from enol phosphates derived from lactams, imides or amides.The first chapter of the thesis evokes the original C-P coupling reaction of chiral and achiral secondary phosphine boranes with different enol phosphates in mild reaction conditions, leading to corresponding enamido-phosphine boranes. This methodology permits the construction of libraries of novels phosphines. Also, the reaction of nucleophilic addition of phosphide anions onto various enecarbamates acyclic was elaborated, giving an access to original beta-phosphino alpha-amino acids, bearing the quaternary carbon on alpha position to nitrogen.The second chapter is devoted to the preparation and characterization of organic chromophores based on the pyrazinic core, which are likely to exhibit the fluorescence properties. These compounds were designed to form new sensitizing systems for lanthanide cations and could be used as organic sensitizers for molecular imaging in near infrared.; En raison de l’omniprésence des hétérocycles azotés et de leurs propriétés biologiques, une attention particulière est accordée au développement de méthodologie pour leur synthèse et leur fonctionnalisation. L’étude de la fonctionnalisation d’énamides constitue une thématique importante car ces motifs s’avèrent être des outils synthétiques polyvalents permettant d’accéder à des dérivés hétérocycliques complexes. Les réactions de couplage Pd-catalysées constituent une méthode de choix rapide et efficace pour la synthèse d'énamides, notamment à partir de phosphates d'énols issus de lactames, d’imides ou d’amides. Le premier chapitre de ce travail porte sur le couplage organopalladié C-P de phosphines boranes secondaires chirales ou achirales avec des phosphates d’énols. Ce couplage C-P original, réalisé dans des conditions douces, conduit aux énamido-phosphines boranes correspondantes et offre de nombreuses possibilités pour la constitution d’une librairie de phosphines originales. Parallèlement à ce travail, l’addition nucléophile d’anions phosphures sur divers ène-carbamates acycliques conduit à des acides alpha-aminés béta-phosphorés originaux, porteurs d’un carbone quaternaire en alpha de l’azote. Le deuxième chapitre de la thèse porte sur la préparation et la caractérisation de chromophores organiques originaux basés sur un noyau pyrazinique et qui sont susceptibles de présenter des propriétés de fluorescence. Ces composés sont conçus pour former des nouveaux systèmes sensibilisateurs de cations de lanthanides, et être utilisés comme sensibilisateurs organiques pour l'imagerie moléculaire dans le proche infrarouge.