Diphosphate Groups Research Articles

Biosynthesis of the Sesquiterpene Botrydial in Botrytis cinerea. Mechanism and Stereochemistry of the Enzymatic Formation of Presilphiperfolan-8β-ol

Presilphiperfolan-8beta-ol synthase, encoded by the BcBOT2 gene from the necrotrophic plant pathogen Botrytis cinerea, catalyzes the multistep cyclization of farnesyl diphosphate (2) to the tricyclic sesquiterpene alcohol presilphiperfolan-8beta-ol (3), the preursor of the phytotoxin botrydial, a strain-dependent fungal virulence factor. Incubation of (1R)-[1-(2)H]farnesyl diphosphate (2b) with recombinant presilphiperfolan-8beta-ol synthase gave exclusively (5R)-[5alpha-(2)H]-3b, while complementary incubation of (1S)-[1-(2)H]FPP (2c) gave (5S)-[5beta-(2)H]-3c. These results established that cyclization of farnesyl diphosphate involves displacement of the diphosphate group from C-1 with net inversion of configuration and ruled out the proposed intermediacy of the cisoid conformer of nerolidyl diphosphate (9) in the cyclization. While not a mandatory intermediate, (3R)-nerolidyl diphosphate was shown to act as a substrate surrogate. Cyclization of [13,13,13-(2)H(3)] farnesyl diphosphate (2d) gave [14,14,14-(2)H(3)]-3d, thereby establishing that electrophilic attack takes place exclusively on the si face of the 12,13-double bond of 2. The combined results provide a detailed picture of the conformation of enzyme-bound farnesyl diphosphate at the active site of presilphiperfolan-8beta-ol synthase.

Unraveling the Catalytic Pathway of Metalloenzyme Farnesyltransferase through QM/MM Computation.

The protein farnesyltransferase (FTase) is a Zn(2+)-metalloenzyme that catalyzes the farnesylation reaction, i.e., the transfer of the 15-carbon atom farnesyl group from farnesyl diphosphate (FPP) to a specific cysteine of protein substrates. Oncogenic Ras proteins, which are among the FTase substrates, are observed in about 20-30% of human cancer cells. Thus, FTase represents a target for anticancer drug design. Herein, we present a classical force-field-based and quantum mechanics/molecular mechanics (QM/MM) computational study of the FTase reaction mechanism. Our findings offer a detailed picture of the FTase catalytic pathway, describing structural features and the energetics of its saddle points. A moderate dissociation of the diphosphate group from the FPP is observed during the nucleophilic attack of the zinc-bound thiolate. At the transition state, a resonance structure is observed, which indicates the formation of a metastable carbocation. However, no stable intermediate is found along the reaction pathway. Thus, the reaction occurs via an associative mechanism with dissociative character, in agreement with the mechanism proposed by Fierke et al. ( Biochemistry 2000, 39, 2593-2602 and Biochemistry 2003, 42, 9741-9748 ). Moreover, a fluorine-substituted FPP analogue (CF3-FPP) is used to investigate the inhibitory effect of fluorine, which in turn provides additional agreement with experimental data.

A new lithium manganese phosphate with an original tunnel structure in the A2MP 2O 7 family

A new member of the A 2MP 2O 7 diphosphate family, Li 2MnP 2O 7, has been synthesized by solid-state reaction and characterized using single-crystal X-ray diffraction. Li 2MnP 2O 7 crystallizes in the monoclinic space group P2 1/ a (#14) with the cell parameters a=9.9158(6) Å, b=9.8289(6) Å, c=11.1800(7) Å, β=102.466(5)°, Z=8 and V=1063.9(1) Å 3. Its mixed framework exhibits an original Mn 2O 9 unit, built up of one MnO 5 trigonal bipyramid sharing one edge with one MnO 6 octahedron. These Mn 2O 9 units are sharing corners with P 2O 7 diphosphate groups, forming the undulating [Mn 4P 8O 32] ∞ layers. The [MnP 2O 7] ∞ 3D framework, resulting from the interconnection of the undulating [Mn 4P 8O 32] ∞ layers, exhibits different kinds of intersecting tunnels containing the Li cations.

New thallium diphosphates Tl2 Me(H2P2O7)2 · 2 H2O, Me = Mg, Mn, Co, Ni and Zn. Synthesis, single crystal X-ray structures and powder X-ray structure of the Mg phase

Abstract Crystals of thallium dihydrogendiphosphate Tl2 Me(H2P2O7)2 · 2 H2O (Me = Mg (1), Mn (2), Co (3), Ni (4) and Zn (5)), have been synthesized and analyzed by powder X-ray diffractometry (Mg phase) and single crystal X-ray diffractometry (other phases). They resulted to be isostructural within triclinic group P-1, with the following unit-cell parameters: a = 6.9620(1), b = 7.3635(1), c = 7.7713(1) Å, α = 81.8014(5), β = 70.8597(6), γ = 86.1373(7)°, V = 372.44(8) Å3 (1); a = 6.9577(6), b = 7.4745(6), c = 7.8248(7) Å, α = 80.723(2), β = 71.912(1), γ = 85.661(1)°, V = 381.62(6) Å3 (2); a = 6.9767(7), b = 7.3634(7), c = 7.7690(7) Å, α = 81.421(2), β = 71.114(2), γ = 86.424(2)°, V = 373.36(6) Å3 (3); a = 6.9658(7), b = 7.3079(7), c = 7.7016(7) Å, α = 81.801(2), β = 71.185(2), γ = 86.528(2)°, V = 367.27(6) Å3 (4) and a = 6.9628(7), b = 7.3625(7), c = 7.7401(8) Å, α = 81.590(2), β = 71.441(2), γ = 86.323(2)°, V = 372.04(6) Å3 (5). Me is octahedrally coordinated by two water molecules and four oxygen atoms belonging to two different diphos phate groups. Thallium cations make up interactions with oxygen atoms within Van der Waals coordination sphere, making up irregular coordination polyhedra. The framework of the present compounds can be described as a three-dimensional framework made from vertex-sharing polyhedra. The basic unit is the [Me(H2P2O7)2 · 2 H2O] moiety, which displays a crystallographic Ci symmetry, with the Me cation on the inversion centre. Such units are held together by an intricate scheme of Tl…O interactions; hydrogen bonds complete the network.

Molecular basis for the lack of enantioselectivity of human 3-phosphoglycerate kinase

Non-natural l-nucleoside analogues are increasingly used as therapeutic agents to treat cancer and viral infections. To be active, l-nucleosides need to be phosphorylated to their respective triphosphate metabolites. This stepwise phosphorylation relies on human enzymes capable of processing l-nucleoside enantiomers. We used crystallographic analysis to reveal the molecular basis for the low enantioselectivity and the broad specificity of human 3-phosphoglycerate kinase (hPGK), an enzyme responsible for the last step of phosphorylation of many nucleotide derivatives. Based on structures of hPGK in the absence of nucleotides, and bound to l and d forms of MgADP and MgCDP, we show that a non-specific hydrophobic clamp to the nucleotide base, as well as a water-filled cavity behind it, allows high flexibility in the interaction between PGK and the bases. This, combined with the dispensability of hydrogen bonds to the sugar moiety, and ionic interactions with the phosphate groups, results in the positioning of different nucleotides so to expose their diphosphate group in a position competent for catalysis. Since the third phosphorylation step is often rate limiting, our results are expected to alleviate in silico tailoring of l-type prodrugs to assure their efficient metabolic processing.

Synthesis and characterization of phosphates in the pseudo‐ternary melted systems Cs2O‐P2O5‐MIIO (MII – alkaline earth)

AbstractThe crystallization of alkali‐earth phosphates in the melts of Cs2O‐P2O5‐MIIO (MII – Ca, Sr, Ba) pseudo‐ternary systems have been investigated at various Cs/P molar ratios and at fixed value of MII/P equal to 0.15. Type of the phosphate which crystallizes in melts depends on the Cs/P initial ratio. Crystallization fields of CsMIIP3O9, MII2P2O7 and Cs2MIIP2O7 were briefly investigated and characterized. The new diphosphate Cs2CaP2O7 has been obtained and investigated by the single crystal and powder X‐ray diffraction and FTIR‐ spectroscopy. It crystallizes in C 2/m space group, with the following parameters of the monoclinic cell: a = 10.261(2), b = 5.9316(12), c = 7.2404(14) Å, β = 118.54(3)°. The architecture of [CaP2O7]2‐ anionic sublattice, which is built up from [CaO6] octahedra and [P2O7] bitetrahedra, interlinked via the common oxygen vertices, gives rise to formation of hexagonal tunnels along crystallographic direction b, where caesium atoms are located. One of the most remarkable features of the structure is specific positional disorder of the diphosphate group, which is connected with the existence of two equiprobable half‐occupied sites of the bridging oxygen. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)

Inositol Hexakisphosphate Kinase Products Contain Diphosphate and Triphosphate Groups

Eukaryotic cells produce a family of diverse inositol polyphosphates (IPs) containing pyrophosphate bonds. Inositol pyrophosphates have been linked to a wide range of cellular functions, and there is growing evidence that they act as second messengers. Inositol hexakisphosphate kinase (IP6K) is able to convert the natural substrates inositol pentakisphosphate (IP 5) and inositol hexakisphosphate (IP 6) to several products with an increasing number of phospho-anhydride bonds. In this study, we structurally analyzed IPs synthesized by three mammalian isoforms of IP6K from IP 5 and IP 6. The NMR and mass analyses showed a number of products with diverse, yet specific, stereochemistry, defined by the architecture of IP6K's active site. We now report that IP6K synthesizes both pyrophosphate (diphospho) as well as triphospho groups on the inositol ring. All three IP6K isoforms share the same activities both in vitro and in vivo.

Identification of amino acids and domains required for catalytic activity of DPPR synthase, a cell wall biosynthetic enzyme of Mycobacterium tuberculosis

Decaprenylphosphoryl-d-arabinose (DPA) has been shown to be the donor of the essential d-arabinofuranosyl residues found in the cell wall of Mycobacterium tuberculosis. DPA is formed from phosphoribose diphosphate in a four-step process. The first step is the nucleophilic replacement of the diphosphate group with decaprenyl phosphate. This reaction is catalysed by the integral membrane protein 5-phospho-alpha-D-ribose-1-diphosphate : decaprenyl-phosphate 5-phosphoribosyltransferase (DPPR synthase). The enzyme is essential for growth and thereby an important target candidate for the development of new tuberculosis drugs. Although membrane proteins are an important subset of targets for current antibacterial agents, details about the structures and the active sites of such proteins are often not readily available by X-ray crystallography. To begin a different approach to the issue, homologues from Mycobacterium smegmatis and Corynebacterium glutamicum were expressed in Escherichia coli and shown to be active DPPR synthases. This was followed by bioinformatic analyses of the aligned sequences and then by site-directed mutagenesis of amino acids identified as likely to be important for activity. The results suggested that the enzymic synthesis of decaprenyl-phosphate 5-phosphoribose (DPPR) occurs on the cytoplasmic side of the plasma membrane. Amino acid substitutions showed that the predicted cytoplasmic N-terminal region and two cytoplasmic loops are involved in substrate binding and/or catalysis along with parts of some adjoining inner membrane regions. The enzyme lacks the classical phosphoribose diphosphate (pRpp) binding site found in nucleic acid precursor enzymes of both prokaryotes and eukaryotes but instead contains a conserved NDxxD motif required for enzymic activity. Thus, it is plausible that this DPPR synthase has a pRpp binding site that is different from that of the classical eukaryotic enzymes, and further work to develop inhibitors against this enzyme is thereby encouraged.

Synthesis and characterization of alkali-metal tin(II) phosphates: Na 10Sn 31(HPO 4) 6(P 2O 7) 6(PO 4) 12 and K 2SnP 2O 7

Two new alkali-metal tin(II) phosphates – Na 10Sn 31(HPO 4) 6(P 2O 7) 6(PO 4) 12 ( 1) and K 2SnP 2O 7 ( 2) – were synthesized by high-temperature reactions and structurally characterized by single-crystal X-ray diffraction. Na 10Sn 31(HPO 4) 6(P 2O 7) 6(PO 4) 12 crystallized in the noncentrosymmetric space group P-62 c (No. 190) with a = 9.6445(1) Å, b = 9.6445(1) Å, c = 34.059(6) Å, V = 2743.6(7) Å 3 and Z = 1. K 2SnP 2O 7 crystallized in the monoclinic space group P2 1/ n with a = 9.856(3) Å, b = 6.7244(1) Å, c = 12.225(3) Å, β = 108.240(5)°, V = 769. 5(3) Å 3 and Z = 4. Both structures exhibit a novel open-framework structure. The crystal structure of 1 contains SnO 3 and SnO 4 polyhedra sharing corners with [HPO 4] 2−, [PO 4] 3− and [P 2O 7] 4− groups, which form tunnels of six rings filled with Na + cations and parallel to the c-axis, which are connected via O–Sn–O bridges to form a three-dimensional open framework. The crystal structure of 2 contains SnO 4 seesaw polyhedra sharing corners with diphosphate groups to form a three-dimensional [SnP 2O 7] 2− framework that exhibits a tunnel structure of 10- and 12-membered rings expanding along [011] and [100] with four arrays of K + cations located in channels of the framework.

Synthesis of Analogues of (E)-1-Hydroxy-2-methylbut-2-enyl 4-Diphosphate, an Isoprenoid Precursor and Human γδ T Cell Activator

(E)-1-Hydroxy-2-methyl-but-2-enyl 4-diphosphate (HMBPP) is an intermediate in the non-mevalonate pathway for the biosynthesis of isoprenoids and also serves as a very strong activator of human gamma delta T cells expressing Vgamma9Vdelta2 receptors. This paper describes the synthesis of analogues of HMBPP, in which the diphosphate group is replaced by potential isosteric moieties, i.e., carbamate, N-acyl-N'-oxy sulfamate, or aminosulfonyl carbamate functionalities. The potential of the synthesized analogues to stimulate Vgamma9/Vdelta2 T cell response or to inhibit GcpE and LytB, the last enzymes in the non-mevalonate pathway, was assessed.

New monodiphosphate Li9Cr3(P2O7)3(PO4)2: X-ray crystal structure and vibrational spectroscopy

The new monodiphosphate Li9Cr3(P2O7)3(PO4)2 was synthesized and analyzed by single-crystal X-ray diffraction, infrared and Raman spectroscopy. It crystallizes in the trigonal space group P-3c1 with the following unit cell constants: a = b = 9.684(1) Å, c = 13.605(1) Å, V = 1104.9(2) Å3. The three-dimensional framework is made up of [(CrP2O7)3(PO4)2]9– layers, with CrO6 octahedra sharing vertices and edges with mono- and diphosphate groups. Li cations, spread over three different sites, fill up the remaining cavities, stabilizing the framework via Li—O bonds, making up tetrahedral arrangements at Li(2) and Li(3), and a complex hexacoordination at Li(1). IR and Raman spectra of Li9Cr3(P2O7)3(PO4)3 confirm the centrosymmetric structure and the bent configuration of the POP bridge of the diphosphate group.

Purification, Sequencing, and Molecular Identification of a Mammalian PP-InsP5 Kinase That Is Activated When Cells Are Exposed to Hyperosmotic Stress

Mammalian cells utilize multiple signaling mechanisms to protect against the osmotic stress that accompanies plasma membrane ion transport, solute uptake, and turnover of protein and carbohydrates (Schliess, F., and Haussinger, D. (2002) Biol. Chem. 383, 577-583). Recently, osmotic stress was found to increase synthesis of bisdiphosphoinositol tetrakisphosphate ((PP)2-InsP4), a high energy inositol pyrophosphate (Pesesse, X., Choi, K., Zhang, T., and Shears, S. B. (2004) J. Biol. Chem. 279, 43378-43381). Here, we describe the purification from rat brain of a diphosphoinositol pentakisphosphate kinase (PPIP5K) that synthesizes (PP)2-InsP4. Partial amino acid sequence, obtained by mass spectrometry, matched the sequence of a 160-kDa rat protein containing a putative ATP-grasp kinase domain. BLAST searches uncovered two human isoforms (PPIP5K1 (160 kDa) and PPIP5K2 (138 kDa)). Recombinant human PPIP5K1, expressed in Escherichia coli, was found to phosphorylate diphosphoinositol pentakisphosphate (PP-InsP5) to (PP)2-InsP4 (Vmax = 8.3 nmol/mg of protein/min; Km = 0.34 microM). Overexpression in human embryonic kidney cells of either PPIP5K1 or PPIP5K2 substantially increased levels of (PP)2-InsP4, whereas overexpression of a catalytically dead PPIP5K1(D332A) mutant had no effect. PPIP5K1 and PPIP5K2 were more active against PP-InsP5 than InsP6, both in vitro and in vivo. Analysis by confocal immunofluorescence showed PPIP5K1 to be distributed throughout the cytoplasm but excluded from the nucleus. Immunopurification of overexpressed PPIP5K1 from osmotically stressed HEK cells (0.2 M sorbitol; 30 min) revealed a persistent, 3.9 +/- 0.4-fold activation when compared with control cells. PPIP5Ks are likely to be important signaling enzymes.

Energetics of copper diphosphates – Cu 2P 2O 7 and Cu 3(P 2O 6OH) 2

Differential scanning calorimetry and high temperature oxide melt solution calorimetry are used to study enthalpy of phase transition and enthalpies of formation of Cu 2P 2O 7 and Cu 3(P 2O 6OH) 2. α-Cu 2P 2O 7 is reversibly transformed to β-Cu 2P 2O 7 at 338–363 K with an enthalpy of phase transition of 0.15 ± 0.03 kJ mol −1. Enthalpies of formation from oxides of α-Cu 2P 2O 7 and Cu 3(P 2O 6OH) 2 are −279.0 ± 1.4 kJ mol −1 and −538.8 ± 2.7 kJ mol −1, and their standard enthalpies of formation (enthalpy of formation from elements) are −2096.1 ± 4.3 kJ mol −1 and −4302.7 ± 6.7 kJ mol −1, respectively. The presence of hydrogen in diphosphate groups changes the geometry of Cu(II) and decreases acid–base interaction between oxide components in Cu 3(P 2O 6OH) 2, thus decreasing its thermodynamic stability.

Structural characterization of natural rubber based on recent evidence from selective enzymatic treatments

A structural characterization of natural rubber (NR) was carried out by a combination of selective enzymatic treatment and high-resolution characterization techniques. The nitrogenous groups in NR from Hevea brasiliensis have been regarded as an important factor governing cured rubber properties, although there is no structural evidence to prove that relationship. The nitrogenous compounds in highly purified NR were characterized to determine the origin of the nitrogenous groups in NR. The rubber particles of fresh latex were purified by washing, i.e., a successive dilution of the cream fraction and concentration by centrifugation in the presence of a surfactant. The nitrogen content of the NR formed from the washed rubber particles decreased from 0.281% to 0.015% after washing 3-5 times; this content was similar to that of NR deproteinized by a proteolytic enzyme. The presence of 1-2 nitrogen atoms per rubber chain was estimated on the basis of nitrogen content and number-average molecular weight (Mn). The nitrogen content of fractionated rubber fractions from rubber particles washed for five times increased with increasing Mn. The nitrogenous groups in rubber chains are postulated to mostly originate from phospholipids associating with branch points and functional groups formed by oxidation and successive reactions in NR latex. An analysis of the structure of the chain end group (alpha-terminal) was carried out by treating the deproteinized NR (DPNR) latex with lipase, phosphatase, and phospholipases A(2), B, C and D. The enzymatic treatment of DPNR latex significantly decreased the long-chain fatty acid ester content in DPNR, and also the Mn and Higgins'k' constant, except for phospholipase D treatment. This indicates the presence of phospholipid molecules in NR, which connect rubber molecules together. (1)H-NMR results of rubber obtained from DPNR latex showed weak signals due to monophosphate, diphosphate and phospholipids at the alpha-terminal. Treating DPNR latex with lipase and phosphatase decreased the relative intensity of the (1)H-NMR signals corresponding to phospholipids; however, with the same treatment, no change in the signals due to mono- and diphosphates was observed. The presence of mono- and diphosphates as well as some phospholipid signals after lipase and phosphatase treatment indicates that mono- and diphosphate groups are directly linked to the modified structure at their alpha-terminals; such connections are considered to be due to the association or linkage of such groups with phospholipid.

TlHP2O7: structure determination from X-ray powder diffraction data

The crystal structure of monoclinic thallium(III) hydrogendiphosphate, TlHP2O7, has been solved from laboratory X-ray powder diffraction data and refined by the Rietveld method. All atoms occupy general positions. The TlIII ions have a distorted octa­hedral coordination environment of O atoms from four diphosphate groups. Adjacent TlO6 octa­hedra form edge-shared Tl2O10 dimers which share corners with PO4 tetra­hedra to build a three-dimensional polymeric structure.

Competitive inhibition of aristolochene synthase by phenyl-substituted farnesyl diphosphates: evidence of active site plasticity

Analogues of farnesyl diphosphate (FPP, ) containing phenyl substituents in place of methyl groups have been prepared in syntheses that feature use of a Suzuki-Miyaura reaction as a key step. These analogues were found not to act as substrates of the sesquiterpene cyclase aristolochene synthase from Penicillium roqueforti (AS). However, they were potent competitive inhibitors of AS with K(I)-values ranging from 0.8 to 1.2 microM. These results indicate that the diphosphate group contributes the largest part to the binding of the substrate to AS and that the active sites of terpene synthases are sufficiently flexible to accommodate even substrate analogues with large substituents suggesting a potential way for the generation of non-natural terpenoids. Molecular mechanics simulations of the enzyme bound inhibitors suggested that small changes in orientations of active site residues and subtle alterations of the conformation of the backbones of the inhibitors are sufficient to accommodate the phenyl-farnesyl-diphosphates.

Binding of Uridine 5‘-Diphosphate in the “Basic Patch” of the Zinc Deacetylase LpxC and Implications for Substrate Binding,

LpxC is a zinc metalloenzyme that catalyzes the first committed step in the biosynthesis of lipid A, a vital component of the outer membrane of Gram-negative bacteria. Accordingly, the inhibition of LpxC is an attractive strategy for the treatment of Gram-negative bacterial infections. Here, we report the 2.7 A resolution X-ray crystal structure of LpxC from Aquifex aeolicus complexed with uridine 5'-diphosphate (UDP), and the 3.1 A resolution structure of LpxC complexed with pyrophosphate. The X-ray crystal structure of the LpxC-UDP complex provides the first view of interactions likely to be exploited by the substrate UDP group in the "basic patch" of the active site. The diphosphate group of UDP makes hydrogen bond interactions with strictly conserved residue K239 as well as solvent molecules. The ribose moiety of UDP interacts with partially conserved residue E197. The UDP uracil group hydrogen bonds with both the backbone NH group and the backbone carbonyl group of E160, and with the backbone NH group of K162 through an intervening water molecule. Finally, the alpha-phosphate and uracil groups of UDP interact with R143 and R262 through intervening water molecules. The structure of LpxC complexed with pyrophosphate reveals generally similar intermolecular interactions in the basic patch. Unexpectedly, diphosphate binding in both complexes is accompanied by coordination to an additional zinc ion, resulting in the identification of a new metal-binding site termed the E-site. The structures of the LpxC-UDP and LpxC-pyrophosphate complexes provide new insights with regard to substrate recognition in the basic patch and metal ion coordination in the active site of LpxC.

Structure-activity relationships of uridine 5'-diphosphate analogues at the human P2Y6 receptor.

The structure-activity relationships and molecular modeling of the uracil nucleotide activated P2Y6 receptor have been studied. Uridine 5'-diphosphate (UDP) analogues bearing substitutions of the ribose moiety, the uracil ring, and the diphosphate group were synthesized and assayed for activity at the human P2Y6 receptor. The uracil ring was modified at the 4 position, with the synthesis of 4-substituted-thiouridine 5'-diphosphate analogues, as well as at positions 2, 3, and 5. The effect of modifications at the level of the phosphate chain was studied by preparing a cyclic 3',5'-diphosphate analogue, a 3'-diphosphate analogue, and several dinucleotide diphosphates. 5-Iodo-UDP 32 (EC50 = 0.15 microM) was equipotent to UDP, while substitutions of the 2'-hydroxyl (amino, azido) greatly reduce potency. The 2- and 4-thio analogues, 20 and 21, respectively, were also relatively potent in comparison to UDP. However, most other modifications greatly reduced potency. Molecular modeling indicates that the beta-phosphate of 5'-UDP and analogues is essential for the establishment of electrostatic interactions with two of the three conserved cationic residues of the receptor. Among 4-thioether derivatives, a 4-ethylthio analogue 23 displayed an EC50 of 0.28 microM, indicative of favorable interactions predicted for a small 4-alkylthio moiety with the aromatic ring of Y33 in TM1. The activity of analogue 19 in which the ribose was substituted with a 2-oxabicyclohexane ring in a rigid (S)-conformation (P = 126 degrees , 1'-exo) was consistent with molecular modeling. These results provide a better understanding of molecular recognition at the P2Y6 receptor and will be helpful in designing selective and potent P2Y6 receptor ligands.

Phosphate speciation in sodium borosilicate glasses studied by nuclear magnetic resonance

The structure of RNa2O·B2O3·KSiO2·xP2O5 (0.5<R<2; 0.86<K<3) borosilicate glasses has been studied by nuclear magnetic resonance (NMR). 31P magic angle spinning (MAS), double quantum-magic angle spinning (DQ-MAS) and 31P–11B transfer of populations under double resonance magic angle spinning (TRAPDOR MAS) NMR were used to determine the phosphate speciation in the glasses and their connectivity with the borosilicate network. The structure of the glass network was characterized with 11B, 29Si and 23Na MAS NMR. Ab initio calculations of the 31P chemical shielding were carried out in order to confirm the connectivity between phosphorus and the structural units of the borosilicate glass network. Na3PO4 (monophosphate), Na4P2O7 (diphosphate) and P–O–B species (mono- and diphosphate groups with borate units as the next nearest neighbors) are found all along the compositional range studied. The proportion of the P–O–B groups increases as the glass optical basicity decreases, while the proportions of mono- and diphosphate species decrease. The change in the glass transition temperature of the phospho-borosilicate glasses with respect to that of the borosilicate ones is discussed in terms of the structural characterization. The formation of phosphate species gives rise to the increase in Tg, which is attributed to the re-polymerization of the silicate network, while the formation of P–O–B bonds weakens the glass network and produces a decrease in the glass transition temperature.

From thorium phosphate hydrogenphosphate hydrate to β-thorium phosphate diphosphate: Structural evolution to a radwaste storage ceramic

β-Thorium phosphate diphosphate ( β-TPD), considered as a very promising radwaste storage material, was obtained from thorium phosphate hydrogenphosphate hydrate (TPHPH) precursor through dehydration and hydrogen phosphate condensation. The structures of TPHPH, intermediate α-thorium phosphate diphosphate ( α-TPD) and its hydrate ( α-TPDH) have been resolved ab initio by Rietveld analysis of their synchrotron diffraction patterns. All were found orthorhombic (space group Cmcm) and similarly composed of [ThPO 4] 4 4+ slabs alternating with disordered layers hosting either [HPO 4·H 2O] 2 4− (TPHPH), [P 2O 7·2H 2O] 4− ( α-TPDH), or [P 2O 7] 4− ( α-TPD), unlike the 3D structure of β-TPD. The diphosphate groups of α-TPD and α-TPDH are strongly bent. The irreversible transition to the final β-TPD consists in a shearing of the slabs and a reduction of the interslabs cavities that explains the stability of this high-temperature form.