Enhanced stability and local structure in biologically relevant amorphous materials containing pyrophosphate

There is increasing evidence that amorphous inorganic materials play a key role in biomineralisation in many organisms, however the inherent instability of synthetic analogues in the absence of the complex in vivo matrix limits their study and clinical exploitation. To address this, we report here an approach that enhances long-term stability to >1 year of biologically relevant amorphous metal phosphates, in the absence of any complex stabilisers, by utilising pyrophosphates (P2O7 4-); species themselves ubiquitous in vivo. Ambient temperature precipitation reactions were employed to synthesise amorphous Ca2P2O7.nH2O and Sr2P2O7.nH2O (3.8 < n < 4.2) and their stability and structure were investigated. Pair distribution functions (PDF) derived from synchrotron X-ray data indicated a lack of structural order beyond ~8 A° in both phases, with this local order found to resemble crystalline analogues. Further studies, including 1H and 31P solid state NMR, suggest the unusually high stability of these purely inorganic amorphous phases is partly due to disorder in the P–O–P bond angles within the P2O7 units, which impede crystallization, and to water molecules, which are involved in H-bonds of various strengths within the structures and hamper the formation of an ordered network. In situ high temperature powder X-ray diffraction data indicated that the amorphous nature of both phases surprisingly persisted to ~450° C. Further NMR and TGA studies found that above ambient temperature some water molecules reacted with P2O7 anions, leading to the hydrolysis of some P–O–P linkages and the formation of HPO4 2- anions within the amorphous matrix. The latter anions then recombined into P2O7 ions at higher temperatures prior to crystallization. Together, these findings provide important new materials with unexplored potential for enzyme-assisted resorption and establish factors crucial to isolate further stable amorphous inorganic materials

Novel bicyclic hexanuclear copper(I) aggregate: Structure and solid state 31P CPMAS NMR spectra of [(Cu3L3)2] and [Cu(PPh3)2L] complexes of N-(diisopropoxythiophosphinyl)-N′-phenylthiourea (HL)

A new complex of N-thiophosphorylthiourea PhNHC(S)NHP(S)(OiPr)2 (HL) of formula [(Cu3L3)2] has been synthesized and characterized by single crystal X-ray diffraction, FT-IR, 1H, 31P NMR in solution and by 31P CPMAS NMR spectroscopy in the solid state. A comparison of the structure and the spectral parameters of [(Cu3L3)2] with those of the mononuclear analogue [Cu(PPh3)2L] was performed. In the solid state the aggregate [(Cu3L3)2] represents the first example of a spontaneous "side-by-side" association of two neutral cyclic [Cu3L3] moieties using two Cu-S-Cu bridges formed by the sulfur atoms of the PS-groups. The values of the 1J(31P-63,65Cu) and 2J(31P-31P) coupling constants of the [Cu(PPh3)2]+ moiety in the solid state spectra are reported. © 2008 Elsevier B.V. All rights reserved

A computationally-guided non-equilibrium synthesis approach to materials discovery in the SrO-Al₂O₃-SiO₂ phase field

Glass-crystallisation synthesis is coupled to probe structure prediction for the guided discovery of new metastable oxides in the SrO-Al2O3-SiO2 phase field, yielding a new ternary ribbon-silicate, Sr2Si3O8. In principle, this methodology can be applied to a wide range of oxide chemistries by selecting an appropriate non-equilibrium synthesis route

Complexes of N-thiophosphorylthioureas (HL) with copper(I). Crystal structures of [Cu3L3] and [Cu(PPh3) 2L] chelates

Reaction of the potassium salts of N-thiophosphorylated thioureas of common formula RC(S)NHP(S)(OiPr)2 [R = morpholin-N-yl (HLa), piperidin-N-yl (HLb), NH2 (HLc), PhCH 2NH (HLd)] with Cu(PPh3)3I in aqueous EtOH/CH2Cl2 leads to mononuclear [Cu(PPh 3)2L-S,S′] complexes. Using copper(i) iodide instead of Cu(PPh3)3I, polynuclear complexes [Cu n(L-S,S′)n] were obtained. The structures of these compounds were investigated by ES-MS, elemental analyses, 1H and 31P NMR in solution, IR and 31P solid-state MAS NMR spectroscopy. The crystal structures of [Cu3L3 a] and [Cu(PPh3)2Lb] were determined by single-crystal X-ray diffraction. © The Royal Society of Chemistry 2007

Copper(i) complexes with N-(diisopropoxythiophosphoryl)thiobenzamide PhC(S)NHP(S)(OiPr)2

Reaction of the potassium salt of N-thiophosphorylthiobenzamide PhC(S)NHP(S)(OiPr)2 (HL) with CuI in aqueous EtOH leads to the tetranuclear [Cu4L4] and the polynuclear [KCuL 2]n complexes, while the same reactions using the lithium or sodium salts of HL exclusively lead to the tetramer [Cu4L 4]. Reaction of KL with the mixture of CuI and 2,2′-bipyridine (bpy) or 1,10-phenanthroline (phen) leads to the mononuclear complexes [Cu(bpy)L] and [Cu(phen)L]. The same complexes were obtained by the reaction of [Cu4L4] with bpy or phen. © 2010 The Royal Society of Chemistry

J Clin Med

In cystic fibrosis (CF), cystic fibrosis transmembrane regulator (CFTR) dysfunction leads to digestive disorders that promote intestinal inflammation and dysbiosis enhancing gastrointestinal symptoms. In pancreatic insufficiency CF patients, both intestinal inflammation and dysbiosis, are associated with an increase in the fecal calprotectin (FC) level. However, associations between the FC level, gastrointestinal symptoms, and quality of life (QoL) remain poorly studied. We aimed to assess such associations in pancreatic insufficiency CF children. The FC level was measured in pancreatic insufficiency CF children's stool samples. Children and their parents completed two questionnaires: The Gastrointestinal Symptoms Scales 3.0-PedsQL(TM) and the Quality of Life Pediatric Inventory 4.0-PedsQL(TM). Lower scores indicated worse symptomatology or QoL. Thirty-seven CF children were included. A FC level above 250 µg/g was associated with worse gastrointestinal symptoms and QoL scores. The FC level was inversely correlated with several gastrointestinal scores assessed by children (i.e., Total, "Heart Burn Reflux", "Nausea and Vomiting", and "Gas and Bloating"). Several QoL scores were correlated with gastrointestinal scores. The FC level was weakly associated with clinical parameters. Some gastrointestinal and QoL scores were related to disease severity associated parameters. In CF, the FC level, biomarker previously related to intestinal inflammation and dysbiosis, was associated with worse digestive symptoms and QoL scores

The Polarization of Ambient Noise on Mars

Seismic noise recorded at the surface of Mars has been monitored since February 2019, using the InSight seismometers. This noise can reach −200 dB. It is 500 times lower than on Earth at night and it increases of 30 dB during the day. We analyze its polarization as a function of time and frequency in the band 0.03–1 Hz. We use the degree of polarization to extract signals with stable polarization independent of their amplitude and type of polarization. We detect polarized signals at all frequencies and all times. Glitches correspond to linear polarized signals which are more abundant during the night. For signals with elliptical polarization, the ellipse is in the horizontal plane below 0.3 Hz. In the 0.3-1Hz high frequency band (HF) and except in the evening, the ellipse is in the vertical plane and the major axis is tilted. While polarization azimuths are different in the two frequency bands, they both vary as a function of local hour and season. They are also correlated with wind direction, particularly during the daytime. We investigate possible aseismic and seismic origins of the polarized signals. Lander or tether noise can be discarded. Pressure fluctuations transported by wind may explain part of the HF polarization but not the tilt of the ellipse. This tilt can be obtained if the source is an acoustic emission coming from high altitude at critical angle. Finally, in the evening when the wind is low, the measured polarized signals may correspond to the seismic wavefield of the Mars background noise

Critical Role of Macrophages and Their Activation via MyD88-NFκB Signaling in Lung Innate Immunity to Mycoplasma pneumoniae

Mycoplasma pneumoniae (Mp), a common cause of pneumonia, is associated with asthma; however, the mechanisms underlying this association remain unclear. We investigated the cellular immune response to Mp in mice. Intranasal inoculation with Mp elicited infiltration of the lungs with neutrophils, monocytes and macrophages. Systemic depletion of macrophages, but not neutrophils, resulted in impaired clearance of Mp from the lungs. Accumulation and activation of macrophages were decreased in the lungs of MyD88−/− mice and clearance of Mp was impaired, indicating that MyD88 is a key signaling protein in the anti-Mp response. MyD88-dependent signaling was also required for the Mp-induced activation of NFκB, which was essential for macrophages to eliminate the microbe in vitro. Thus, MyD88-NFκB signaling in macrophages is essential for clearance of Mp from the lungs

Novel phosphate–phosphonate hybrid nanomaterials applied to biology

International audienceA new process for preparing oligonucleotide arrays is described that uses surface grafting chemistry which is fundamentally different from the electrostatic adsorption and organic covalent binding methods normally employed. Solid supports are modified with a mixed organic/inorganic zirconium phosphonate monolayer film providing a stable, well-defined interface. Oligonucleotide probes terminated with phosphate are spotted directly to the zirconated surface forming a covalent linkage. Specific binding of terminal phosphate groups with minimal binding of the internal phosphate diesters has been demonstrated. On the other hand, the reaction of a bisphosphonate bone resorption inhibitor (Zoledronate) with calcium deficient apatites (CDAs) was studied as a potential route to local drug delivery systems active against bone resorption disorders. A simple mathematical model of the Zoledronate/CDA interaction was designed that correctly described the adsorption of Zoledronate onto CDAs. The resulting Zoledronate-loaded materials were found to release the drug in different phosphate-containing media, with a satisfactory agreement between experimental data and the values predicted from the model

NMR-Based Structural Modeling of Graphite Oxide Using Multidimensional 13C Solid-State NMR and ab Initio Chemical Shift Calculations

Chemically modified graphenes and other graphite-based materials have attracted growing interest for their unique potential as lightweight electronic and structural nanomaterials. It is an important challenge to construct structural models of noncrystalline graphite-based materials on the basis of NMR or other spectroscopic data. To address this challenge, a solid-state NMR (SSNMR)-based structural modeling approach is presented on graphite oxide (GO), which is a prominent precursor and interesting benchmark system of modified graphene. An experimental 2D C-13 double-quantum/single-quantum correlation SSNMR spectrum of C-13-labeled GO was compared with spectra simulated for different structural models using ab initio geometry optimization and chemical shift calculations. The results show that the spectral features of the GO sample are best reproduced by a geometry-optimized structural model that is based on the Lerf-Klinowski model (Lerf, A. et al. Phys. Chem. B 1998, 102, 4477); this model is composed of interconnected sp(2), 1,2-epoxide, and COH carbons. This study also convincingly excludes the possibility of other previously proposed models, including the highly oxidized structures involving 1,3-epoxide carbons (Szabo, I. et al. Chem. Mater. 2006, 18, 2740). C-13 chemical shift anisotropy (CSA) patterns measured by a 2D C-13 CSA/isotropic shift correlation SSNMR were well reproduced by the chemical shift tensor obtained by the ab initio calculation for the former model. The approach presented here is likely to be applicable to other chemically modified graphenes and graphite-based systems