Activation of G proteins by neuropeptide Y and gamma-aminobutyric acid(B) receptor agonists in rat cerebral cortical membranes through distinct modes of action

We investigated the pharmacological profile of MEN 11270, or H-D-Arg-Arg-Pro-Hyp-Gly-Thi-c(Dab-DTic-Oic-Arg)c(7gamma-10 alpha), a conformationally constrained derivative of the B2 kinin receptor antagonist Icatibant. MEN 11270 bound with high-affinity to the B2 kinin receptor constitutively expressed by WI38 human fibroblasts, inhibiting 3H-bradykinin (BK) with a pKi value of 10.3 +/- 0.08 (n = 5). The rank order of affinity of several peptide and nonpeptide antagonists was also assessed: Icatibant (pKi = 10.6) approximately MEN 11270 (pKi = 10.3) approximately B9430 (pKi = 10.0) > B9858 (pKi = 8.0) > FR173657 (pKi = 7.6) > WIN64338 (pKi = 7.2) > Lys-[des-Arg9, Leu8]-BK (pKi < 6) > [des-Arg9,Leu8]-BK (pKi < 5). MEN 11270 showed a low affinity in inhibiting 3H-Lys-[des-Arg9]-BK binding at the human B1 kinin receptor constitutively expressed by the same cells (pKi 6.0 +/- 0.33; n = 3). MEN 11270 showed no binding affinity (pIC50 < 5.5) at 29 different receptors and ion channels. In the human umbilical vein contraction assay, MEN 11270, shifted the concentration-response curve to BK to the right in a concentration-dependent manner (pA2 8.14 +/- 0.22, n = 7). The Schild plot was linear (slope 0.95 +/- 0.11), consistent with a competitive antagonism. In the same bioassay, MEN 11270 (10 microM) did not affect the concentration-response curve to the B1 agonist Lys-[des-Arg9]-BK nor the contractile responses elicited by noradrenaline or serotonin. These findings indicate MEN 11270 as an antagonist at the human B2 kinin receptor, with potency and selectivity comparable to those of the linear peptide antagonist, supporting the hypothesis that a constrained C-terminal beta-turn conformation preserves a high affinity for the interaction of Icatibant with the B2 kinin receptor.     

New perspective of a nano-metal preparation pathway based on the hexahydro-closo-hexaborate anion

Today, metal-based nanomaterials play an increasingly important role in the energy, environment, medical and health fields. In order to meet the needs of various fields, it is necessary to continuously develop advanced technologies for preparing metal-based materials. Inspired by previous research, the results of a proof-of-concept experiment show that the hexahydro-closo-hexaborate anion (closo-[B₆H₇]⁻) in the borane cluster family has properties similar to NaBH₄. Closo-[B₆H₇]⁻ can not only convert common precious metal ions such as Au³⁺, Pd²⁺, Pt⁴⁺ and Ag⁺ to the corresponding zero-valence state, but also convert some non-precious metals such as Cu²⁺ and Ni²⁺ to the zero-valent or oxidation state. Closo-[B₆H₇]⁻ moderate reduction to cause rapid aggregation of metal-based materials is not easy compared with NaBH₄. Compared with closo-[B₁2H₁₂]²⁻, closo-[B₆H₇]⁻ achieves the conversion of Pt⁴⁺ to Pt⁰ under ambient conditions, and its reduction performance extends to non-precious metals. The excellent stability and easy modification characteristics determine the universality of the closo-[B₆H₇]⁻ reduction strategy for metal ions.

Today, metal-based nanomaterials play an increasingly important role in the energy, environment, medical and health fields.     

Synthesis and study of C-substituted methylthio derivatives of cobalt bis(dicarbollide)

The C-methylthio derivatives of cobalt bis(dicarbollide) were synthesized by reaction of anhydrous CoCl₂ with nido-carborane [7-MeS-7,8-C₂B₉H₁₁]⁻ and isolated as a mixture of rac-[1,1′-(MeS)₂-3,3′-Co(1,2-C₂B₉H₁₀)₂]⁻ and meso-[1,2′-(MeS)₂-3,3′-Co(1,2-C₂B₉H₁₀)₂]⁻ isomers. The structures of both isomers were studied using DFT quantum chemical calculations. The most preferable geometry of rotamers and the stabilization energy of C-methylthio derivatives of cobalt bis(dicarbolide) were calculated. The (BEDT-TTF)[1,1′-(MeS)₂-3,3′-Co(1,2-C₂B₉H₁₀)₂] salt was prepared and its structure was determined by single crystal X-ray diffraction. The cisoid conformation of the rac-[1,1′-(MeS)₂-3,3′-Co(1,2-C₂B₉H₁₀)₂]⁻ anion is stabilized by short intramolecular CH⋯S hydrogen and BH⋯S chalcogen bonds between the dicarbollide ligands, that is in good agreement with the data of quantum chemical calculations.

The C-methylthio derivatives of cobalt bis(dicarbollide) rac-[1,1′-(MeS)₂-3,3′-Co(1,2-C₂B₉H₁₀)₂]⁻ and meso-[1,2′-(MeS)₂-3,3′-Co(1,2-C₂B₉H₁₀)₂]⁻ were synthesized and studied by DFT calculations and X-ray diffraction.     

Solvent extraction of rare earths elements from nitrate media in DMDOHEMA/ionic liquid systems: performance and mechanism studies

Extraction of La(iii), Eu(iii) and Fe(iii) was compared in n-dodecane and two ionic liquids (ILs) (1-ethyl-1-butylpiperidinium bis (trifluoromethylsulfonyl)imide [EBPip⁺] [NTf₂⁻] and 1-ethyl-1-octylpiperidinium bis (trifluoromethylsulfonyl)imide [EOPip⁺] [NTf₂⁻]). Using the extractant N,N′-dimethyl-N,N′-dioctylhexylethoxymalonamide (DMDOHEMA), the effect of pH was investigated in detail to recover extraction mechanisms. The use of ILs as the organic solvent instead of n-dodecane, greatly enhances extraction efficiency, and an ionic liquid with a shorter alkyl chain [EBPip⁺] [NTf₂⁻] provides higher extraction than [EOPip⁺] [NTf₂⁻]. The mechanistic study points out that for low nitric acid concentrations ([HNO₃] ≤ 0.01 M), metal is extracted via a cation of the ionic liquids, while for higher nitric acid concentrations ([HNO₃] ≥ 1.0 M), extraction occurs through pure solvation mechanism of DMDOHEMA as in conventional diluents. This latter case is of high interest for applications, as higher extraction can be obtained without any loss of ILs by ion exchange mechanisms.

Extraction of La(iii), Eu(iii) and Fe(iii) was compared in n-dodecane and in two ionic liquids (ILs) [EBPip⁺] [NTf₂⁻] and [EOPip⁺] [NTf₂⁻]. Extraction mechanisms have been investigated as a function of pH.     

The unique sandwich K6Be2B6H6 cluster with a real borozene B6H6 core

Theoretical evidence is reported for a boron-based K₆Be₂B₆H₆ sandwich cluster, showing a perfectly D_6h B₆H₆ ring, being capped by two tetrahedral K₃Be ligands. Due to the comfortable charge transfer, the sandwich is viable in [K₃Be]³⁺[B₆H₆]⁶⁻[BeK₃]³⁺ ionic complex in nature. The [B₆H₆]⁶⁻ core with 6π aromaticity vividly imitates the benzene (C₆H₆), occurring as a real borozene. In contrast, the tetrahedral [K₃Be]³⁺ ligand is 2σ three-dimensional aromatic, acting as the simple superatom. Thus, this complex possesses a collectively three-fold 2σ/6π/2σ aromaticity. The interlaminar interaction is governed by the robust electrostatic attraction. The unique chemical bonding gives rise to interesting dynamic fluxionality.

The fascinating sandwich K₆Be₂B₆H₆ cluster with a real borozene ring, being stabilized collectively by three-fold 2σ/6π/2σ aromaticity.     

Synthesis of cyanooxovanadate and cyanosilylation of ketones

The cyanosilylation was performed by using metavanadate catalysts, and in situ measurements revealed the formation of [VO₂(CN)₃]²⁻ and [VO₄TMS₂]⁻ under reaction conditions. The reaction of [VO₂(CN)₃]²⁻, trimethylsilyl cyanide (TMSCN), and water afforded [VO₄TMS₂]⁻ and CN⁻, which reacted with ketones to yield the corresponding cyanohydrin trimethylsilyl ethers over [VO₂(CN)₃]²⁻. Compound [VO₂(CN)₃]²⁻ showed high catalytic performance for cyanosilylation of various carbonyl compounds. In the case of n-hexanal, turnover frequency reached up to 250 s⁻¹.

Two key catalytic vanadium species involved in cyanosilylation of ketones were observed by in situ measurement.     

Efficient access to amides of the carborane carboxylic acid [1-(COOH)–CB11H11]−

The preparation of the carborane acid chloride [1-(COCl)–CB₁₁H₁₁]⁻ from the carboxylic acid [1-(COOH)–CB₁₁H₁₁]⁻ is reported. This acid chloride exhibits remarkable inertness towards moisture and can be stored under ambient conditions for several months. Reaction with amines affords secondary and tertiary carborane amides [1-(CONR¹R²)–CB₁₁H₁₁]⁻ in moderate to high yields under mild conditions. Two of the amide products were characterized by X-ray crystallography in addition to spectroscopic analysis. Preliminary studies show that the amides can be reduced to the corresponding amines and that the acid chloride has the potential to serve as a starting material for carborane ester formation.

The preparation of the carborane acid chloride [1-(COCl)–CB₁₁H₁₁]⁻ from the carboxylic acid [1-(COOH)–CB₁₁H₁₁]⁻ and subsequent amide formation are reported.     

The synthesis of a 99mTc-labeled tetravalent targeting probe upon isonitrile coordination to 99mTcI for enhanced target uptake in saturable systems

The presence of excess unlabeled ligands in the injectate hinders the target uptake of ^99mTc-labeled targeting vectors. To address the issue, we previously developed a chemical design which provides a ^99mTc-labeled trivalent RGD probe upon CN-βAla-Gly-Gly-c(RGDfK) (L_β) coordination to [^99mTc][Tc(CO)₃]⁺ core at pH 6.0. In this study, we extended our coordination mediated synthesis of the trivalent RGD probe to that of a tetravalent one. Our initial attempts reacting L_β with [^99mTc][Tc(CO)₃]⁺ core at pH 8.0 failed to provide [^99mTc][Tc(CO)₂(L_β)₄]⁺ due to the formation of multiple side products. A γ-aminobutylic acid (GABA) based isonitrile ligand CN-GABA-Gly-Gly-c(RGDfK) (L_G), on the other hand, avoided the side reaction and selectively provided [^99mTc][Tc(CO)₂(L_G)₄]⁺ (^99mTc-[L_G]₄) at pH 8.0. ^99mTc-[L_G]₄ exhibited higher binding affinity to integrin α_vβ₃ than its unlabeled ligand, and visualized U87MG tumor without tedious post-labeling purification. These results indicate that the metal coordination-mediated syntheses of ^99mTc-labeled multivalent probes have been successfully applied to a tetravalent one, which would allow a wider range of choices for designing novel ^99mTc-labeled multivalent probes of high in vivo target uptake.

The difference in 2-proton''s acidity between L_β and L_G led to dramatically different results of their reactions with [^99mTc][Tc(CO)₃(OH₂)₃]⁺.     

Syntheses,spectroscopic, redox,and structural properties of homoleptic Iron(III/II) dithione complexes

Two sets of Fe^III/II dithione complexes [Fe^II(ⁱPr₂Dt⁰)₃][PF₆]₂ ([1][PF₆]₂), [Fe^II(Me₂Dt⁰)₃][PF₆]₂ ([2][PF₆]₂), and [Fe^III(ⁱPr₂Dt⁰)₃][PF₆]₃ ([3][PF₆]₃), [Fe^III(Me₂Dt⁰)₃][PF₆]₃ ([4][PF₆]₃), and compound [Fe^III(ⁱPr₂Dt⁰)₃][FeCl₄][PF]₂ ([3][FeCl₄][PF₆]₂) were synthesized from N,N′-diisopropyl piperazine-2,3-dithione (ⁱPr₂Dt⁰) and N,N′-dimethyl piperazine-2,3-dithione (Me₂Dt⁰) ligands. Complexes [1][PF₆]₂–[4][PF₆]₃ have been characterized by NMR, IR, and UV-visible spectroscopies, and by electrochemistry. The molecular structures of [2][PF₆]₂ and [3][FeCl₄][PF₆]₂ have been determined by X-ray crystallography. Complexes [2][PF₆]₂ and [3][FeCl₄][PF₆]₂ both crystallized in the monoclinic space group P2₁/n. Both complexes exhibit distorted octahedral geometry and the three coordinated ligands in each complex exhibit different dithione folding. Complexes [1][PF₆]₂–[4][PF₆]₃ exhibit a single Fe^III/II based couple and three quasi-reversible ligand-based redox couples. The electronic spectra of [1][PF₆]₂–[4][PF₆]₃ show intense MLCT bands that indicate strong mixing between metal and ligand orbitals. DFT calculations were used to provide a framework for understanding the electronic origin of their redox chemistry and spectroscopic features.

Two sets of Fe^III/II complexes, synthesized from N,N′-diisopropyl piperazine-2,3-dithione (ⁱPr₂Dt⁰) and N,N′-dimethyl piperazine-2,3-dithione (Me₂Dt⁰) ligands, exhibit electronically asymmetrical ligands with metal–ligand orbital mixing.     

Role of tribochemistry reactions of B4C on tribofilm growth at a PEEK–steel interface in simulated body fluids

Corrosion and wear products of metallic implants can lead to severe adverse tissue reactions. However, there is an absence of effective means to reduce the tribocorrosion of metal. The main purpose of this study is to reveal a mechanism of engineering a barrier layer on metal surfaces via adding functional particles into the polymer counterpart. B₄C and BN particles were compounded into a polyetheretherketone (PEEK) matrix and their tribological performance of PEEK-based composites sliding against stainless steel was compared in simulated body fluid. Results demonstrate that the addition of B₄C reduces significantly friction and wear. In particular, the addition of only 1 vol% B₄C reduces wear of PEEK by up to 94.8%, and tribocorrosion of steel is also obviously mitigated. It is discovered that hydrolysis of B₄C particles triggered by friction and deposition of Ca²⁺ and phosphate ions dominate formation of the barrier layer at the friction interface. The barrier layer endows the PEEK–metal sliding pair simultaneously enhanced anti-wear and anti-corrosion performance.

Hydrolysis of B₄C particles triggered by friction and deposition of Ca²⁺ and phosphate ions dominate formation of the barrier layer. The barrier layer endows the PEEK–metal sliding pair enhanced anti-wear and anti-corrosion performance.     

Triiodothyronine and amiodarone effects on β3-adrenoceptor density and lipolytic response to the β3-adrenergic agonist BRL 37344 in rat white adipocytes

Summary— The β-adrenergic effects of catecholamines are potentiated by thyroid hormones in adipose tissue. Amiodarone (AM) is structurally similar to thyroid hormones and was used to explore the mechanism of the triiodothyronine (T₃) effect on β-adrenergic receptors (β-ARs) in adipose tissue. AM decreases the expression of some T₃ sensitive genes in various tissues and antagonizes the effect of T₃ on its nuclear receptors. In this study, the T₃, AM and AM + T₃ effects on the β1- and β₃-AR density were assessed on rat white adipocytes by radioligand binding using [³H]CGP 12177 after characterization of these subtypes by displacement of [³H]CGP 12177 binding by isoproterenol, BRL 37344 and noradrenaline. BRL 37344 was used to study β₃-AR lipolysis. White adipocytes from hyperthyroid rats had increased responsiveness (E_max × 2) and sensitivity (+ 38%) to BRL 37344, while those given AM alone had decreased values. Moreover, AM antagonized the T₃ effect on lipolysis. The β₁-binding characteristics (receptor density [B_max]: 45 ± 4 fmol/mg of proteins; dissociation factor [K_d]: 0.96 ± 0.10 nM) were not modified by either compound. Finally, T₃ significantly increased β₃-AR density (587 ± 69 versus 363 ± 25 fmol/mg of proteins) and K_d (38 ± 2 versus 23 ± 3 nM), while AM alone had no effect and did not antagonize the T₃ effect on β₃-AR number. In conclusion, the hyperthyroid state in the rat potentiated the lipolytic response of white adipocytes to a specific β₃-agonist and increased the β₃-AR density without changing in β₁-AR number and affinity. Furthermore, the lack of antagonism between AM and T₃ on β₃-AR expression suggests that T₃ does not work directly on the β₃-AR gene. Moreover, AM induced a functional tissular hypothyroid-like effect and its antilipolytic effect probably occurred at a postreceptor level.     

Synthesis,structures, and catalytic efficiency in ring opening polymerization of rac-lactide with tridentate vs. bidentate cobalt(ii), zinc(ii), and cadmium(ii) complexes containing N-substituted N,N-bis((3,5-dimethyl-1H-pyrazol-1-yl)methyl)amine ligands

A series of Co(ii), Zn(ii), and Cd(ii) complexes supported by 1-(3,5-dimethyl-1H-pyrazol-1-yl)-N-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)-N-(furan-2-ylmethyl)methanamine (L_A) and N,N-bis((3,5-dimethyl-1H-pyrazol-1-yl)methyl)-4-isopropylaniline (L_B) were synthesized. The direct chelation of CoCl₂·6H₂O, ZnCl₂, and CdBr₂·4H₂O by the ligands produced [L_nMX₂] (L_n = L_A or L_B; M = Zn or Co, with X = Cl; M = Cd, with X = Br) complexes in high yields. Structural studies revealed that [L_BCoCl₂] and [L_BZnCl₂] adopted distorted tetrahedral geometries, as L_B coordinated the metal centers in a bidentate fashion, while L_A coordinated the metal centers in a tridentate fashion through the nitrogen atoms of the pyrazole and amine moieties, so that [L_ACoCl₂] and [L_AZnCl₂] exhibited trigonal bipyramidal geometries and [L_ACdBr₂] a square pyramidal geometry. [L_BCdBr₂] has two Cd-containing structures per unit cell, whereby one Cd center adopted a distorted tetrahedral geometry and the other exhibited square bipyramidal geometry. The in situ-generated alkyl derivatives of the synthesized complexes were assessed in the ring-opening polymerization of rac-lactide. Heterotactic polylactides (PLAs) were furnished with all complexes. The [L_BZnCl₂]/MeLi system produced PLA with a superior heterotactic bias (P_r up to 0.94) at −25 °C. PLAs with wide-ranging polydispersity indices (1.16–2.23) and low molecular weights were produced in all cases, irrespective of the specific M(II) center and ancillary ligand utilized.

Co(ii), Zn(ii), and Cd(ii) complexes supported by bis-pyrazolyl ligands were applied to the ring-opening polymerization of rac-lactide to produce heterotactic polylactides (PLAs) with superior heterotactic bias i.e. P_r up to 0.94 at −25 °C.     

Erratum: Calibration of diffuse correlation spectroscopy with a time-resolved near-infrared technique to yield absolute cerebral blood flow measurements: errata

Abstract: The authors provide corrections to tabular data and a figure, which do not alter the conclusions of the original paper [Biomed. Opt. Express 2, 2068 (2011)].OCIS codes: (170.1470) Blood or tissue constituent monitoring, (170.3660) Light propagation in tissues, (170.3890) Medical optics instrumentationDue to an error in the analysis of the diffuse correlation spectroscopy data, all the absolute αD_B values reported in the article [1] should be multiplied by a factor of two. Consequently, the αD_B values in Table 2 of Ref. [1] should be replaced by those in the following Table 1:

Table 1

(with corrected αD_B values): αD_B and CBF values obtained from the experimental data presented in Fig. 3 of Ref. [1]

Hierarchical self-assembly of discrete bis-[2]pseudorotaxane metallacycle with bis-pillar[5]arene via host–guest interactions and their redox-responsive behaviors

A discrete rhomboidal metallacycle R functionalized with bis-[2]pseudorotaxane of [Cu(phenanthroline)₂]⁺ derivatives was successfully synthesized via coordination-driven self-assembly. Furthermore, the host–guest complexation of such a bis-[2]pseudorotaxane metallacycle with a bis-pillar[5]arene (bisP5) allowed for the formation of a new family of cross-linked supramolecular polymers R⊃(bisP5)₂, which displayed interesting redox-responsive properties. By taking advantage of the substantial structural differences between the coordination geometries of [Cu(phenanthroline)₂]⁺ and [Cu(phenanthroline)₂]²⁺, the weight-average diffusion coefficients D of the supramolecular polymer were adjusted through changing the redox state of the Cu(i)/Cu(ii) complexes.

We presented a new family of supramolecular polymers cross-linked by bis-[2]pseudorotaxane metallacycles with interesting redox-responsive behavior.     

The nature of metal–metal bonding in Re-, Ru- and Os-corrole dimers

Studies of multiple bonding between transition metal complexes offer fundamental insight into the nature of bonding between metal ions and facilitate predictions of the physical properties and the reactivities of metal complexes containing metal–metal multiple bonds. Here we report a computational interrogation on the nature of the metal–metal bonding for neutral, oxidized, and reduced forms of dinuclear rhenium and osmium corrole complexes, [{Re[TpXPC]}₂]^0/1+/1− and [{Os[TpXPC]}₂]^0/1+/1−, using a complete active space self-consistent (CASSCF) methodology and density functional theory (DFT) calculations. For [{Re[TpXPC]}₂]⁰, [{Ru[TpXPC]}₂]⁰, and [{Os[TpXPC]}₂]⁰, CASSCF calculations shows that the effective bond order is 3.29, 2.63, and 2.73, respectively. On their oxidized forms, [{Re[TpXPC]}₂]¹⁺, [{Ru[TpXPC]}₂]¹⁺, and [{Os[TpXPC]}₂]¹⁺ molecules, the results indicate an electron removal from a ligand-based orbital, where [{Re[TpXPC]}₂]¹⁺ gives slightly different geometry from its neutral form due to populating the δ* orbital. In this regard, the CASSCF calculations give an effective bond order of 3.25 which is slightly lower than in the [{Re[TpXPC]}₂]⁰. On their reduced forms, the electron addition appears to be in the metal-based orbital for [{Re[TpXPC]}₂]¹⁻ and [{Ru[TpXPC]}₂]¹⁻ whereas in the ligand-based orbital for the Os-analogue which has no effect on the Os–Os bonding, an effective bond order of 3.18 and 2.17 is presented for the [{Re[TpXPC]}₂]¹⁻ and [{Ru[TpXPC]}₂]¹⁻, respectively, within the CASSCF simulations. These results will further encourage theoreticians and experimentalists to design metalloporphyrin dimers with distinct metal–metal bonding.

Our CASSCF calculations on the first oxidation and reduction processes of the synthesised [{Re[TpXPC]}₂]⁰, [{Ru[TpXPC]}₂]⁰, and [{Os[TpXPC]}₂]⁰ molecules revealed a pronounced effect on the nature of the metal–metal bonding.     

Perfect cubic La-doped boron clusters La6&[La@B24]+/0 as the embryos of low-dimensional lanthanide boride nanomaterials

La-doped boron nanoclusters have received considerable attention due to their unique structures and bonding. Inspired by recent experimental observations of the inverse sandwich D_8h La₂B₈ (1) and triple-decker C_2v La₃B₁₄⁻ (2) and based on extensive global searches and first-principles theory investigations, we present herein the possibility of the perfect cubic La-doped boron clusters O_h La₆&[La@B₂₄]⁺ (3, ¹A_1g) and O_h La₆&[La@B₂₄] (4, ²A_2g) which appear to be the embryos of the metallic one-dimensional La₁₀B₃₂ (5) nanowire, two-dimensional La₃B₁₀ (6) nanosheet, and three-dimensional LaB₆ (7) nanocrystal, facilitating a bottom-up approach to build cubic lanthanide boride nanostructures from gas-phase clusters. Detailed molecular orbital and bonding analyses indicate that effective (d–p)σ, (d–p)π and (d–p)δ covalent coordination interactions exist in La₆&[La@B₂₄]^+/0 (3/4) clusters, while the 1D La₁₀B₃₂ (5), 2D La₃B₁₀ (6), and 3D LaB₆ (7) crystals exhibit mainly electrostatic interactions between the trivalent La centers and cubic B₂₄ frameworks, with weak but discernible coordination contributions from La (5d) ← B (2p) back-donations. The IR and Raman spectra of La₆&[La@B₂₄]^+/0 (3/4) and band structures of La₁₀B₃₂ (5) and La₃B₁₀ (6) are computationally simulated to facilitate their future characterizations.

Perfect cubic clusters O_h La₆&[La@B₂₄]^+/0 are predicted at first-principles levels to be the embryos of 1D La₁₀B₃₂, 2D La₃B₁₀, and 3D LaB₆ lanthanide boride nanomaterials in a bottom-up approach.     

Synthesis and characterization of methylammonium phosphates as crystalline approximants for anhydrous,low melting phosphate glasses

Low-melting methylammonium phosphate glasses are synthesized from crystalline starting agents. To this end crystalline tris(methylammonium) cyclotriphosphate [CH₃NH₃]₃P₃O₉, was synthesized by a novel and simple synthesis route from P₄O₁₀ and N-methylformamide. It, undergoes an irreversible phase transition to methylammonium catena-polyphosphate [CH₃NH₃]PO₃. The crystal structure of the catena-polyphosphate was solved and refined from X-ray powder diffraction data by the Rietveld method using constraints obtained by solid-state ³¹P and ¹H NMR spectroscopy. This compound crystallizes in a triclinic space group with a = 13.2236(9), b = 7.8924(6), c = 4.6553(2) Å, α = 91.068(4), β = 87.840(5) and γ = 106.550(3)°. Quantum chemical calculations confirm that the obtained structure lies at an energetic minimum. Finally the reaction of tris(methylammonium) cyclotriphosphate and P₄O₁₀ into methylammonium phosphate glass is presented. The synthesized, water-free phosphate glass shows a very low glass transition temperature T_g of 33 °C, which was verified by dynamic scanning calorimetry and NMR. The chain-like crystal structure of the high-temperature methylammoniumphosphate [CH₃NH₃]PO₃ serves as an approximation for the short-range order of the glass.

The novel glass shows the lowest glass transition temperature known for binary phosphate glass systems without acidic protons.     

Characterisation and mechanisms of bradykinin-evoked pain in man using iontophoresis

Bradykinin (BK) is an inflammatory mediator that can evoke oedema and vasodilatation, and is a potent algogen signalling via the B1 and B2 G-protein coupled receptors. In naïve skin, BK is effective via constitutively expressed B2 receptors (B2R), while B1 receptors (B1R) are purported to be upregulated by inflammation. The aim of this investigation was to optimise BK delivery to investigate the algesic effects of BK and how these are modulated by inflammation. BK iontophoresis evoked dose- and temperature-dependent pain and neurogenic erythema, as well as thermal and mechanical hyperalgesia (P < 0.001 vs saline control). To differentiate the direct effects of BK from indirect effects mediated by histamine released from mast cells (MCs), skin was pretreated with compound 4880 to degranulate the MCs prior to BK challenge. The early phase of BK-evoked pain was reduced in degranulated skin (P < 0.001), while thermal and mechanical sensitisation, wheal, and flare were still evident. In contrast to BK, the B1R selective agonist des-Arg9-BK failed to induce pain or sensitise naïve skin. However, following skin inflammation induced by ultraviolet B irradiation, this compound produced a robust pain response. We have optimised a versatile experimental model by which BK and its analogues can be administered to human skin. We have found that there is an early phase of BK-induced pain which partly depends on the release of inflammatory mediators by MCs; however, subsequent hyperalgesia is not dependent on MC degranulation. In naïve skin, B2R signaling predominates, however, cutaneous inflammation results in enhanced B1R responses.