Dystrophic calcinosis: structural and morphological composition, and evaluation of ethylenediaminetetraacetic acid ('EDTA') for potential local treatment.

BACKGROUND: To perform a detailed morphological analysis of the inorganic portion of two different clinical presentations of calcium-based deposits retrieved from subjects with SSc and identify a chemical dissolution of these deposits suitable for clinical use. METHODS: Chemical analysis using Fourier Transform IR spectroscopy ('FTIR'), Raman microscopy, Powder X-Ray Diffraction ('PXRD'), and Transmission Electron Microscopy ('TEM') was undertaken of two distinct types of calcinosis deposits: paste and stone. Calcinosis sample titration with ethylenediaminetetraacetic acid ('EDTA') assessed the concentration at which the EDTA dissolved the calcinosis deposits in vitro. RESULTS: FTIR spectra of the samples displayed peaks characteristic of hydroxyapatite, where signals attributable to the phosphate and carbonate ions were all identified. Polymorph characterization using Raman spectra were identical to a hydroxyapatite reference while the PXRD and electron diffraction patterns conclusively identified the mineral present as hydroxyapatite. TEM analysis showed differences of morphology between the samples. Rounded particles from stone samples were up to a few micron in size, while needle-like crystals from paste samples reached up to 0.5 µm in length. Calcium phosphate deposits were effectively dissolved with 3% aqueous solutions of EDTA, in vitro. Complete dissolution of both types of deposit was achieved in approximately 30 min using a molar ratio of EDTA/HAp of ≈ 300. CONCLUSIONS: Stone and paste calcium-based deposits both comprise hydroxyapatite, but the constituent crystals vary in size and morphology. Hydroxyapatite is the only crystalline polymorph present in the SSc-related calcinosis deposits. Hydroxyapatite can be dissolved in vitro using a dosage of EDTA considered safe for clinical application. Further research is required to establish the optimal medium to develop the medical product, determine the protocol for clinical application, and to assess the effectiveness of EDTA for local treatment of dystrophic calcinosis.

Micron-sized biogenic and synthetic hollow mineral spheres occlude additives within single crystals.

Incorporating additives within host single crystals is an effective strategy for producing composite materials with tunable mechanical, magnetic and optical properties. The type of guest materials that can be occluded can be limited, however, as incorporation is a complex process depending on many factors including binding of the additive to the crystal surface, the rate of crystal growth and the stability of the additives in the crystallisation solution. In particular, the size of occluded guests has been restricted to a few angstroms - as for single molecules - to a few hundred nanometers - as for polymer vesicles and particles. Here, we present a synthetic approach for occluding micrometer-scale objects, including high-complexity unicellular organisms and synthetic hollow calcite spheres within calcite single crystals. Both of these objects can transport functional additives, including organic molecules and nanoparticles that would not otherwise occlude within calcite. Therefore, this method constitutes a generic approach using calcite as a delivery system for active compounds, while providing them with effective protection against environmental factors that could cause degradation.

Disordered Filaments Mediate the Fibrillogenesis of Type I Collagen in Solution.

Collagen type I is one of the major structural proteins in mammals, providing tissues such as cornea, tendon, bone, skin, and dentin with mechanical stability, strength, and toughness. Collagen fibrils are composed of collagen molecules arranged in a quarter-stagger array that gives rise to a periodicity of 67 nm along the fibril axis, with a 30 nm overlap zone and a 37 nm gap zone. The formation of such highly organized fibrils is a self-assembly process where electrostatic and hydrophobic interactions play a critical role in determining the staggering of the molecules with 67 nm periodicity. While collagen self-assembly has been extensively studied, not much is known about the mechanism, and in particular, the nature of the nuclei that initially form, the different stages of the aggregation process, and how the organization of the molecules into fibrils arises. By combining time-resolved cryo-transmission electron microscopy with molecular dynamics simulations, we show that collagen assembly is a multistep process in which the molecules first form filaments which self-organize into fibrils with a disordered structure. The appearance of the D-band periodicity is gradual and starts with the alignment of adjacent filaments at the N-terminal end of the molecules, first leading to bands with a periodicity of 67 nm and then to the formation of gap and overlap regions.

Effect of Ag Co-catalyst on TiO2-Cu2O nanocomposites structure and apparent visible photocatalytic activity.

Although Cu2O is a commonly used narrow band gap semiconductor to fabricate visible response photocatalysts, up to date there are only a few reports on Ag co-catalysed TiO2-Cu2O nanocomposites. Herein we report a facile wet chemical synthesis approach to prepare TiO2-Ag-Cu2O ternary hybrid nanomaterials. Uniquely, both the effect of Ag content and the synthesis sequence of Ag deposition step was investigated on the visible decoloration rate. The crystal structure, morphology, optical and dark adsorption properties of the nanostructures were characterized by XRD, SEM, TEM and diffuse reflectance, respectively. Due to the mixed indirect and direct nature of the nanocomposites, the band gap estimation was performed by using both Tauc plot and differential reflectance model. The dark adsorption properties of catalysts could be typically well-approximated by pseudo-second order kinetics, while TiO2-Ag(5%)-Cu2O catalyst cannot be described by standard models due to a delayed adsorption behaviour observed in the first 50 min. The apparent visible activities followed pseudo-zero order kinetics. It was found that TiO2-Ag(3%)-Cu2O catalyst exhibited the highest rate constant which was ca. two times as high as that of the binary TiO2-Cu2O catalyst. The synthesis sequence of the Ag deposition step significantly altered the material properties which resulted in different dark adsorption and apparent visible activities.

ß-Chitin Nanofibril Self-Assembly in Aqueous Environments.

Chitin is one of the most studied biopolymers but the understanding of how it assembles from molecules to microfibers is still limited. Organisms are able to assemble chitin with precise control over polymorphism, texture, and final morphology. The produced hierarchical structure leads to materials with outstanding mechanical properties. In this study, the self-assembly in aqueous solutions of ß-chitin nanofibrils, as far as possible similar to their native state, is investigated. These nanofibrils increase their tendency to self-assemble in fibers, up to millimetric length and ≈10 µm thickness, with the pH increasing from 3 to 8, forming loosely organized bundles as observed using cryo-transmission electron microscopy. The knowledge from this study contributes to the understanding of the self-assembly process that follows chitin once extruded from cells in living organisms. Moreover, it describes a model system which can be used to investigate how other biomolecules can affect the self-assembly of chitin nanofibrils.

Amino Acid Assisted Incorporation of Dye Molecules within Calcite Crystals.

Biomineralisation processes invariably occur in the presence of multiple organic additives, which act in combination to give exceptional control over structures and properties. However, few synthetic studies have investigated the cooperative effects of soluble additives. This work addresses this challenge and focuses on the combined effects of amino acids and coloured dye molecules. The experiments demonstrate that strongly coloured calcite crystals only form in the presence of Brilliant Blue R (BBR) and four of the seventeen soluble amino acids, as compared with almost colourless crystals using the dye alone. The active amino acids are identified as those which themselves effectively occlude in calcite, suggesting a mechanism where they can act as chaperones for individual molecules or even aggregates of dyes molecules. These results provide new insight into crystal-additive interactions and suggest a novel strategy for generating materials with target properties.

Solid-State Transformation of Amorphous Calcium Carbonate to Aragonite Captured by CryoTEM.

Early-stage reaction mechanisms for aragonite-promoting systems are relatively unknown compared to the more thermodynamically stable calcium carbonate polymorph, calcite. Using cryoTEM and SEM, the early reaction stages taking place during aragonite formation were identified in a highly supersaturated solution using an alcohol-water solvent, and an overall particle attachment growth mechanism was described for the system. In vitro evidence is provided for the solid-state transformation of amorphous calcium carbonate to aragonite, demonstrating the co-existence of both amorphous and crystalline material within the same aragonite needle. This supports non-classical formation of aragonite within both a synthetic and biological context.

Bio-inspired synthetic approaches: from hierarchical, hybrid supramolecular assemblies to CaCO3-based microspheres.

A bio-inspired synthetic approach to unprecedented hybrid supramolecular assemblies [Ca(Me2hda)(H2O)3]·H2O (1) and [Ca(C12hda)(H2O)2]·H2O (2), that are stabilized by iminodiacetate-substituted organic ligands is reported. The results of the single-crystal X-ray analysis of 1 further allowed the use of electron microscopy to verify the supramolecular structure of the fibrous assemblies of 2 that incorporate extended alkyl-substituted ligand derivatives. 2 reveals interesting features that distinguish these soft structures from purely inorganic, brittle materials: meshes of nanobelts transform on solid supports to form homogeneous films covering extended, micro-sized areas. The use of the reported ligand system as a habit modifier for CaCO3 results in hierarchical calcite aggregates. The structure-influencing effects of the ligands and their supramolecular assemblies promote the formation of calcite disks that tessellate into hollow microspheres that contain distinctive openings.

Biomineralization of a titanium-modified hydroxyapatite semiconductor on conductive wool fibers.

Metal ions are frequently incorporated into crystalline materials to improve their electrochemical properties and to confer new physicochemical properties. Naturally-occurring phosphate apatite, which is formed geologically and in biomineralization processes, has extensive potential applications and is therefore an attractive functional material. In this study, we generate a novel building block for flexible optoelectronics using bio-inspired methods to deposit a layer of photoactive titanium-modified hydroxyapatite (TiHA) nanoparticles (NPs) on conductive polypyrrole(PPy)-coated wool yarns. The titanium concentration in the reaction solution was varied between 8-50 mol% with respect to the phosphorous, which led to titanate ions replacing phosphate in the hydroxyapatite lattice at levels up to 17 mol%. PPy was separately deposited on wool yarns by oxidative polymerization, using two dopants: (i) anthraquinone-2,6-disulfonic acid to increase the conductivity of the PPy layer and (ii) pyroglutamic acid, to reduce the resistivity of the wool yarns and to promote the heterogeneous nucleation of the TiHA NPs. A specific titanium concentration (25 mol% wrt P) was used to endow the TiHA NPs on the PPy-coated fibers with a desirable band gap value of 3.68 eV, and a specific surface area of 146 m2 g-1. This is the first time that a thin film of a wide-band gap semiconductor has been deposited on natural fibers to create a fiber-based building block that can be used to manufacture flexible electronic devices.

3D visualization of additive occlusion and tunable full-spectrum fluorescence in calcite.

From biomineralization to synthesis, organic additives provide an effective means of controlling crystallization processes. There is growing evidence that these additives are often occluded within the crystal lattice. This promises an elegant means of creating nanocomposites and tuning physical properties. Here we use the incorporation of sulfonated fluorescent dyes to gain new understanding of additive occlusion in calcite (CaCO3), and to link morphological changes to occlusion mechanisms. We demonstrate that these additives are incorporated within specific zones, as defined by the growth conditions, and show how occlusion can govern changes in crystal shape. Fluorescence spectroscopy and lifetime imaging microscopy also show that the dyes experience unique local environments within different zones. Our strategy is then extended to simultaneously incorporate mixtures of dyes, whose fluorescence cascade creates calcite nanoparticles that fluoresce white. This offers a simple strategy for generating biocompatible and stable fluorescent nanoparticles whose output can be tuned as required.

Homologous size-extension of hybrid vanadate capsules - solid state structures, solution stability and surface deposition.

The dimensions and cavity sizes of the molecular capsules with the general formula [V10O18L4](10-) can be controlled modularly through the nature of the bifunctional, rigid organophosphonate ligands L(1) and L(2) (L(1) = bis(4-phosphonatophenyl)ethyne and L(2) = bis(4-phosphonatophenyl)butadiyne); the solution stability of the molecular entities as demonstrated by ESI-MS studies permits their assembly on the Au(111) surface on a sub-monolayer scale giving rise to a 2D supramolecular structure that is comparable to the packing arrangements of the capsules in the crystal structures.

A facile "bottom-up" approach to prepare free-standing nano-films based on manganese coordination clusters.

We present herein a novel method to prepare free-standing Dried Foam Films (DFFs) whereby individual polynuclear manganese complexes cover quantitatively the holes of micro-grids; the fabricated, homogeneous films have a cross-sectional thickness of only ca. 5 nm and are characterised by high mechanical stability.

Supramolecular approaches to metal-organic gels using 'Chevrel-type' coordination clusters as building units.

A novel hexanuclear {Mn(6)} coordination complex with octahedral topology has been prepared and was subsequently used as a building unit for the construction of coordination polymers and metal-organic gels; the latter exhibit thixotropic behavior and reversible sol-gel phase transitions.

N-Cyclo-pentyl-N-(3-oxo-2,3-dihydro-1H-inden-1-yl)acetamide.

The title mol-ecule, C(16)H(19)NO(2), consists of an indane moiety, which is connected through an N atom to an acetamide group and a cyclo-pentane ring. The N atom adopts planar triangular geometry. Inter-molecular inter-actions, such as π-π stacking or hydrogen bonding, were not observed.

{4,6-Bis[(E)-1-methyl-2-(pyridin-2-yl-methyl-idene)hydrazinyl]pyrimidine-κN,N',N''}dichloridomanganese(II).

In the title compound, [MnCl(2)(C(18)H(18)N(8))], the geometry around the Mn(II) centre is distorted square-pyramidal. In the crystal structure, mol-ecules pack via weak C-H⋯N and C-H⋯Cl inter-actions.

{4,6-Bis[(E)-1-methyl-2-(pyridin-2-yl-methyl-idene-κN)hydrazinyl-κN]pyrimidine-κN}dichloridocopper(II) methanol disolvate monohydrate.

The title compound, [CuCl(2)(C(18)H(18)N(8))]·2CH(3)OH·H(2)O, contains a penta-coordinated Cu(II) atom bonded to the tridentate 4,6-bis-[(E)-1-methyl-2-(pyridin-2-yl-methyl-idene)hydrazin-yl]pyrimidine ligand and two Cl atoms. The geometry around the Cu(II) atom is distorted square-pyramidal. The mol-ecules pack in the crystal structure via O-H⋯Cl, O-H⋯N, C-H⋯Cl and C-H⋯O hydrogen bonds, C-H⋯π and π-π inter-actions [centroid-centroid distances of the pyrimidine-pyridine and pyridine-pyridine inter-actions are 3.750 (3) and 3.850 (3) Å, respectively], forming sheet-like assemblies.