Reduction of β-VOPO4 [1] by moist hydrogen leads to two new metastable polymorphs of VPO4 ("m1" and "m2"). Two structure models for VPO4-m1 are proposed. The first one is based on the crystal structure of β-VOPO4. The second one is related to the crystal structures of the Lipscombite/Lazulite structure family, namely β-V2OPO4 and V4O3(PO4)3. Both structure models consist of PO4 tetrahedra sharing corners with square planar VO4 units. To the best of our knowledge this is the first example for V3+ in square-planar coordination by oxygen. Geometry optimization without symmetry constraints (PBE functional [2]) VPO4-m1 led to another new metastable polymorph of VPO4. The predicted structure consists of VO4 tetrahedra corner sharing with PO4 tetrahedra forming a 3D network. The second metastable phase VPO4-m2 is isotypic to FeIIFeIII(VIVO)(P2O7)(PO4) [3]. DFT calculation (PBE functional [2]) allowed relaxation of the structure of VPO4-m2. Considering the interatomic distances obtained from DFT calculation the oxidatation states are V3+/V3+/V3+ instead of V2+/V3+/V4+. The average oxidation state of vanadium in VPO4-m2 is also V3+ which is suggested by the sealed tube experiments.

We report a powerful new technique: hyphenating synchrotron X-ray powder diffraction (XRD) with differential scanning calorimetry (DSC). This is achieved with a simple modification to a standard laboratory DSC instrument, in contrast to previous reports which have involved extensive and complex modifications to a DSC to mount it in the synchrotron beam. The high-energy X-rays of the synchrotron permit the recording of powder diffraction patterns in as little as 2 s, meaning that thermally induced phase changes can be accurately quantified and additional insight on the nature of phase transitions obtained. Such detailed knowledge cannot be gained from existing laboratory XRD instruments, since much longer collection times are required. We demonstrate the power of our approach with two model systems, glutaric acid and sulfathiazole, both of which show enantiotropic polymorphism. The phase transformations between the low and high temperature polymorphs are revealed to be direct solid-solid processes, and sequential refinement against the diffraction patterns obtained permits phase fractions at each temperature to be calculated and unit cell parameters to be accurately quantified as a function of temperature. The combination of XRD and DSC has further allowed us to identify mixtures of phases which appeared phase-pure by DSC.

The formation of the layered double hydroxide [Cu 2 Cr(OH) 6 ]ClÁyH 2 O from the reaction between CuO and aqueous CrCl 3 Á6H 2 O was explored using synchrotron X-ray diffraction and ex situ analyses. The use of hard X-rays permitted time-resolved in situ studies to be performed as the reaction proceeded under a range of conditions. Additional information was obtained from ex situ experiments in which aliquots of the reaction mixture were removed, quenched, and subsequently analysed by laboratory X-ray diffraction, IR, UV-visible, and atomic emission spectroscopies. On the basis of these data, it is proposed that the reaction involves three steps. First, the solid CuO starting material is hydrolysed to give Cu(OH) 2 chains, releasing Cu 2+ ions into solution. The Cu hydroxide chains subsequently condense with aqueous Cr 3+ species, Cl À ions and water molecules to give a hydrated form of the LDH. This material then extrudes some water to form a phase with a reduced interlayer spacing.

Identifying effective disease modifying therapies for neurological diseases remains an important challenge in drug discovery and development. Drug repurposing attempts to determine new indications for pre-existing compounds and represents a major opportunity to address this clinically unmet need. It is potentially more cost effective and time efficient than de novo drug development and has yielded notable successes in neurological disorders.However, across all medical disciplines only 30% of repurposed drugs, and 10% of novel candidate molecules, gain market approval. One potentially significant contributor towards this limited success rate is an incomplete knowledge of the exposure-response relationships for the compounds of interest, and how these relate to the new indication, prior to commencing a new trial. We will provide an overview of the current approach to early stage drug repurposing and consider the issues contributing to inconclusive, or possibly falsely negative, Phase II and III trial outcomes in neurological diseases by including examples that illustrate the limitations of empirical evidence generation without a strong scientific basis for the dose rationale. We conclude with a framework suggesting a translational, iterative approach that integrates pharmacological, pharmaceutical and clinical expertise towards preclinical and early clinical drug development. This ensures appropriate dosing regimen, route of administration, and/or formulation are selected for the new indication before their evaluation in prospective clinical trials. Abbreviations: ALS = amyotrophic lateral sclerosis; EMA = European Medicines Agency; FDA = US Food and Drug Administration; FIH = first-in-human; GCP = good clinical practice; GLP = good laboratory practice; GMP = good manufacturing practice; IMP = investigational medicinal product; MAD = multiple ascending dose; MDS = Myelodysplastic Syndrome;