Cation Adaptive Structures Based on Manganese Cyanide Prussian Blue Analogues: Application of Powder Diffraction Data to Solve Complex, Unprecedented Stoichiometries and New Structure Types.

A Mn(II) salt and A+ CN- under anaerobic conditions react to form 2-D and 3-D extended structured compounds of Am MnII n (CN)m+2n stoichiometry. Here, the creation and characterization of this large family of compounds, for example AMnII 3 (CN)7 , A2 MnII 3 (CN)8 , A2 MnII 5 (CN)12 , A3 MnII 5 (CN)13 , and A2 MnII [MnII (CN)6 ], where A represents alkali and tetraalkylammonium cations, is reviewed. Cs2 MnII [MnII (CN)6 ] has the typical Prussian blue face centered cubic unit cell. However, the other alkali salts are monoclinic or rhombohedral. This is in accord with smaller alkali cation radii creating void space that is minimized by increasing the van der Waals stabilization energy by reducing ∠Mn-N≡C, which, strengthens the magnetic coupling and increases the magnetic ordering temperatures. This is attributed to the non-rigidity of the framework structure due the significant ionic character associated with the high-spin MnII sites. For larger tetraalkylammonium cations, the high-spin Mn sites lack sufficient electrostatic A+ ⋅⋅⋅NC stabilization and form unexpected 4- and 5-coordinated Mn sites within a flexible, extended framework around the cation; hence, the size, shape, and charge of the cation dictate the unprecedented stoichio-metry and unpredictable cation adaptive structures. Antiferromagnetic coupling between adjacent MnII sites leads to ferrimagnetic ordering, but in some cases antiferromagnetic coupling of ferrimagnetic layers are compensated and synthetic antiferromagnets are observed. The magnetic ordering temperatures for ferrimagnetic A2 MnII [MnII (CN)6 ] with both octahedral high- and low-spin MnII sites increase with decreasing ∠Mn-N≡C. The crystal structures for all of the extended structured materials were obtained by powder diffraction.

Glycosides of Nadifloxacin-Synthesis and Antibacterial Activities against Methicillin-Resistant Staphylococcus aureus.

The increase in the number of bacteria that are resistant to multiple antibiotics poses a serious clinical problem that threatens the health of humans worldwide. Nadifloxacin (1) is a highly potent antibacterial agent with broad-spectrum activity. However, its poor aqueous solubility has limited its use to topical applications. To increase its solubility, it was glycosylated herein to form a range of trans-linked (3a-e) and cis-linked (7a,b) glycosides, each of which was prepared and purified to afford single anomers. The seven glycoside derivatives (3a-e, 7a,b) were examined for potency against eight strains of S. aureus, four of which were methicillin-resistant. Although less potent than free nadifloxacin (1), the α-L-arabinofuransoside (3a) was effective against all strains that were tested (minimum inhibitory concentrations of 1-8 µg/mL compared to 0.1-0.25 µg/mL for nadifloxacin), demonstrating the potential of this glycoside as an antibacterial agent. Estimation of Log P as well as observations made during preparation of these compounds reveal that the solubilities of the glycosides were greatly improved compared with nadifloxacin (1), raising the prospect of its use in oral applications.

Time series study of the sales of non-subsidised contraceptives in Kenya at times of public sector shortage: implications for future sustainability.

This paper describes volume trends of non-subsidised contraceptive commodities (NSCC) in Kenya between 2016-2019. We hypothesise that if non-subsidised contraceptive commodities volumes increased at times of public sector shortage then then we might hope for a similar response should public sector supplies reduce in response to an expected decline in donor funding. We find that non-subsidised contraceptive commodities contribute only 2% of total volume, and that these volumes are dominated by emergency contraceptives (EC) and combined oral contraceptives (COC). EC and COC volumes increased significantly during the 2017 nurses' strike, but not during those periods when the Kenya Medical Supplies Authority (KEMSA) was out of stock. Increases in NSCC volumes were not of sufficient size, however, to compensate for the decline in public sector volumes. In short it appears that the market for NSCC is small and constrained. We recommend that further research is needed to understand why distributors of NSCCs are not able to take advantage of continuing public sector supply shortages.

A Molecular Compound for Highly Selective Purification of Ethylene.

Purification of C2 H4 from an C2 H4 /C2 H6 mixture is one of the most challenging separation processes, which is achieved mainly through energy-intensive, cryogenic distillation in industry. Sustainable, non-distillation methods are highly desired as alternatives. We discovered that the fluorinated bis(pyrazolyl)borate ligand supported copper(I) complex {[(CF3 )2 Bp]Cu}3 has features very desirable in an olefin-paraffin separation material. It binds ethylene exclusively over ethane generating [(CF3 )2 Bp]Cu(C2 H4 ). This molecular compound exhibits extremely high and record ideal adsorbed solution theory (IAST) C2 H4 /C2 H6 gas separation selectivity, affording high purity (>99.5 %) ethylene that can be readily desorbed from separation columns. In-situ PXRD provides a "live" picture of the reversible conversion between [(CF3 )2 Bp]Cu(C2 H4 ) and the ethylene-free sorbent in the solid-state, driven by the presence or removal of C2 H4 . Molecular structures of trinuclear {[(CF3 )2 Bp]Cu}3 and mononuclear [(CF3 )2 Bp]Cu(C2 H4 ) are also presented.

Circulating tumour DNA analysis to direct therapy in advanced breast cancer (plasmaMATCH): a multicentre, multicohort, phase 2a, platform trial.

BACKGROUND: Circulating tumour DNA (ctDNA) testing might provide a current assessment of the genomic profile of advanced cancer, without the need to repeat tumour biopsy. We aimed to assess the accuracy of ctDNA testing in advanced breast cancer and the ability of ctDNA testing to select patients for mutation-directed therapy. METHODS: We did an open-label, multicohort, phase 2a, platform trial of ctDNA testing in 18 UK hospitals. Participants were women (aged ≥18 years) with histologically confirmed advanced breast cancer and an Eastern Cooperative Oncology Group performance status 0-2. Patients had completed at least one previous line of treatment for advanced breast cancer or relapsed within 12 months of neoadjuvant or adjuvant chemotherapy. Patients were recruited into four parallel treatment cohorts matched to mutations identified in ctDNA: cohort A comprised patients with ESR1 mutations (treated with intramuscular extended-dose fulvestrant 500 mg); cohort B comprised patients with HER2 mutations (treated with oral neratinib 240 mg, and if oestrogen receptor-positive with intramuscular standard-dose fulvestrant); cohort C comprised patients with AKT1 mutations and oestrogen receptor-positive cancer (treated with oral capivasertib 400 mg plus intramuscular standard-dose fulvestrant); and cohort D comprised patients with AKT1 mutations and oestrogen receptor-negative cancer or PTEN mutation (treated with oral capivasertib 480 mg). Each cohort had a primary endpoint of confirmed objective response rate. For cohort A, 13 or more responses among 78 evaluable patients were required to infer activity and three or more among 16 were required for cohorts B, C, and D. Recruitment to all cohorts is complete and long-term follow-up is ongoing. This trial is registered with ClinicalTrials.gov, NCT03182634; the European Clinical Trials database, EudraCT2015-003735-36; and the ISRCTN registry, ISRCTN16945804. FINDINGS: Between Dec 21, 2016, and April 26, 2019, 1051 patients registered for the study, with ctDNA results available for 1034 patients. Agreement between ctDNA digital PCR and targeted sequencing was 96-99% (n=800, kappa 0·89-0·93). Sensitivity of digital PCR ctDNA testing for mutations identified in tissue sequencing was 93% (95% CI 83-98) overall and 98% (87-100) with contemporaneous biopsies. In all cohorts, combined median follow-up was 14·4 months (IQR 7·0-23·7). Cohorts B and C met or exceeded the target number of responses, with five (25% [95% CI 9-49]) of 20 patients in cohort B and four (22% [6-48]) of 18 patients in cohort C having a response. Cohorts A and D did not reach the target number of responses, with six (8% [95% CI 3-17]) of 74 in cohort A and two (11% [1-33]) of 19 patients in cohort D having a response. The most common grade 3-4 adverse events were raised gamma-glutamyltransferase (13 [16%] of 80 patients; cohort A); diarrhoea (four [25%] of 20; cohort B); fatigue (four [22%] of 18; cohort C); and rash (five [26%] of 19; cohort D). 17 serious adverse reactions occurred in 11 patients, and there was one treatment-related death caused by grade 4 dyspnoea (in cohort C). INTERPRETATION: ctDNA testing offers accurate, rapid genotyping that enables the selection of mutation-directed therapies for patients with breast cancer, with sufficient clinical validity for adoption into routine clinical practice. Our results demonstrate clinically relevant activity of targeted therapies against rare HER2 and AKT1 mutations, confirming these mutations could be targetable for breast cancer treatment. FUNDING: Cancer Research UK, AstraZeneca, and Puma Biotechnology.

Universal A-Cation Splitting in LiNbO3-Type Structure Driven by Intrapositional Multivalent Coupling.

Understanding the electric dipole switching in multiferroic materials requires deep insight of the atomic-scale local structure evolution to reveal the ferroelectric mechanism, which remains unclear and lacks a solid experimental indicator in high-pressure prepared LiNbO3-type polar magnets. Here, we report the discovery of Zn-ion splitting in LiNbO3-type Zn2FeNbO6 established by multiple diffraction techniques. The coexistence of a high-temperature paraelectric-like phase in the polar Zn2FeNbO6 lattice motivated us to revisit other high-pressure prepared LiNbO3-type A2BB'O6 compounds. The A-site atomic splitting (∼1.0-1.2 Šbetween the split-atom pair) in B/B'-mixed Zn2FeTaO6 and O/N-mixed ZnTaO2N is verified by both powder X-ray diffraction structural refinements and high angle annular dark field scanning transmission electron microscopy images, but is absent in single-B-site ZnSnO3. Theoretical calculations are in good agreement with experimental results and suggest that this kind of A-site splitting also exists in the B-site mixed Mn-analogues, Mn2FeMO6 (M = Nb, Ta) and anion-mixed MnTaO2N, where the smaller A-site splitting (∼0.2 Šatomic displacement) is attributed to magnetic interactions and bonding between A and B cations. These findings reveal universal A-site splitting in LiNbO3-type structures with mixed multivalent B/B', or anionic sites, and the splitting-atomic displacement can be strongly suppressed by magnetic interactions and/or hybridization of valence bands between d electrons of the A- and B-site cations.

First-in-human study of the PARP/tankyrase inhibitor E7449 in patients with advanced solid tumours and evaluation of a novel drug-response predictor.

BACKGROUND: This phase 1 study examined the safety, maximum-tolerated dose (MTD) and antitumour activity of E7449, a novel PARP 1/2 and tankyrase 1/2 inhibitor. METHODS: E7449 was orally administered once daily in 28-day cycles to patients with advanced solid tumours (50-800-mg doses). Archival tumour samples from consenting patients were evaluated for the expression of 414 genes in a biomarker panel (2X-121 drug-response predictor [DRP]) found to be predictive of the response to E7449 in cell lines. RESULTS: Forty-one patients were enrolled (13 pancreatic, 5 ovarian, 4 each with breast, lung or colorectal cancer and 11 with other tumour types). The most common grade ≥3 treatment-related adverse event was fatigue (n = 7, 17.1%). Five patients experienced a dose-limiting toxicity (fatigue, n = 4, 800 mg; anaphylaxis, n = 1, 600 mg) for an MTD of 600 mg. E7449 exhibited antitumour activity in solid tumours, including 2 partial responses (PRs), and stable disease (SD) in 13 patients, which was durable (>23 weeks) for 8 patients. In 13 patients, the 2X-121 DRP identified those achieving PR and durable SD. E7449 showed good tolerability, promising antitumour activity and significant concentration-dependent PARP inhibition following 50-800-mg oral dosing. CONCLUSION: The results support further clinical investigation of E7449 and its associated biomarker 2X-121 DRP. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov code: NCT01618136.

Sales of anti-cancer medicines; China, Indonesia, Kazakhstan, Malaysia, Philippines and Thailand.

OBJECTIVE: To assess sales of anti-cancer medicines in the 2017 World Health Organization's WHO Model list of essential medicines in China, Indonesia, Kazakhstan, Malaysia, Philippines and Thailand from 2007 (2008 for Kazakhstan and Malaysia) to 2017. METHODS: We extracted sales volume data for 39 anti-cancer medicines from the IQVIA database. We divided the total quantity sold by the reference defined daily dose to estimate the total number of defined daily doses sold, per country per year, for three types of anti-cancer therapies (traditional chemotherapy, targeted therapy and endocrine therapy). We adjusted these data by the number of new cancer cases in each country for each year. FINDINGS: We observed an increase in sales across all types of anti-cancer therapies in all countries. The largest number of defined daily doses of traditional chemotherapy per new cancer case was sold in Thailand; however, the largest relative increase per new cancer case occurred in Indonesia (9.48-fold). The largest absolute and relative increases in sales of defined daily doses of targeted therapies per new cancer case occurred in Kazakhstan. Malaysia sold the largest number of adjusted defined daily doses of endocrine therapies in 2017, while China and Indonesia more than doubled their adjusted sales volumes between 2007 and 2017. CONCLUSION: The use of sales data can fill an important knowledge gap in the use of anti-cancer medicines, particularly during periods of insurance coverage expansion. Combined with other data, sales volume data can help to monitor efforts to improve equitable access to essential medicines.

Ferrimagnetic Ordering and Anomalous Stoichiometry Observed for the Cubic, Extended 3D Prussian Blue Analogues (NEt3 Me)2 MnII 5 (CN)12 and (NEt2 Me2 )2 MnII 5 (CN)12 : A Cation-Adaptive Structure.

The reactions of MnII (O2 CCH3 )2 with NEt3 Me+ CN- and NEt2 Me2 + CN- form (NEt3 Me)2 MnII 5 (CN)12 (1) and (NEt2 Me2 )2 MnII 5 (CN)12 (2), respectively. Structure model-building and Rietveld refinement of high-resolution synchrotron powder diffraction data revealed a cubic [a=24.0093 Š(1), 23.8804 Š(2)] 3D extended structural motif with adjacent tetrahedral and octahedral MnII sites in a 3:2 ratio. Each tetrahedral MnII site is surrounded by four low-spin octahedral MnII sites, and each octahedral MnII site is surrounded by six high-spin tetrahedral MnII sites; adjacent sites are antiferromagnetically coupled in 3D. Compensation does not occur, and magnetic ordering as a ferrimagnet is observed at Tc =13 K for 2 based on the temperature at which remnant magnetization, Mr (T)→0. The hysteresis has an unusual constricted shape with inflection points around 50 and 1.2 kOe with a 5 K coercivity of 16 Oe and remnant magnetization, Mr , of 2050 emuOe mol-1 . The unusual structure and stoichiometry are attributed to the very ionic nature of the high-spin N-bonded MnII ion, which enables the maximization of the attractive van der Waals interactions through minimization of void space via a reduced ∠ MnNC. This results in an additional example of the Ax MnII y (CN)x+2y (x=0, y=1; x=1, y=3; x=2, y=1; x=2, y=2; x=2, y=3; x=3, y=5; and x=4, y=1) family of compounds possessing an unprecedented stoichiometry and lattice motif that are cation adaptive structured materials.

Anomalous Stoichiometry, 3-D Bridged Triangular/Pentagonal Layered Structured Artificial Antiferromagnet for the Prussian Blue Analogue A3MnII5(CN)13 (A = NMe4, NEtMe3). A Cation Adaptive Structure.

The size of the organic cation dictates both the composition and the extended 3-D structure for hybrid organic/inorganic Prussian blue analogues (PBAs) of A aMnII b(CN) a+2 b (A = cation) stoichiometry. Alkali PBAs are typically cubic with both MC6 and M'N6 octahedral coordination sites and the alkali cation content depends on the M and M' oxidation states. The reaction of MnII(O2CCH3)2 and A+CN- (A = NMe4, NEtMe3) forms a hydrated material of A3MnII5(CN)13 composition. A3MnII5(CN)13 forms a complex, 3-D extended structural motif with octahedral and rarely observed square pyramidal and trigonal bipyramidal MnII sites with a single layer motif of three pentagonal and one triangular fused rings. A complex pattern of MnIICN chains bridge the layers. (NMe4)3MnII5(CN)13 possesses one low-spin octahedral and four high-spin pentacoordinate MnII sites and orders as an antiferromagnet at 11 K due to the layers being bridged and antiferromagnetically coupled by the nonmagnetic cyanides. These are rare examples of intrinsic, chemically prepared and controlled artificial antiferromagnets and have the advantage of having controlled uniform spacing between the layers as they are not physically prepared via deposition methods. A3Mn5(CN)13 (A = NMe4, NEtMe3) along with [NEt4]2MnII3(CN)8, [NEt4]MnII3(CN)7, and Mn(CN)2 form stoichiometrically related A aMnII b(CN) a+2 b ( a = 0, b = 1; a = 2, b = 3; a = 1, b = 3; and a = 3, b = 5) series possessing unprecedented stoichiometries and lattice motifs. These unusual structures and stoichiometries are attributed to the very ionic nature of the high-spin N-bonded MnII ion that enables the maximization of the attractive van der Waals interactions via minimization of void space via a reduced ∠MnNC. This A aMnII b(CN) a+2 b family of compounds are referred to as being cation adaptive in which size and shape dictate both the stoichiometry and structure.

Anomalous Stoichiometry and Antiferromagnetic Ordering for the Extended Hydroxymanganese(II) Cubes/Hexacyanometalate-Based 3D-Structured [MnII 4 (OH)4 ][MnII (CN)6 ](OH2 )6 ⋠H2 O.

The reaction of MnII (O2 CMe)2 and NaCN or LiCN in water forms a light green insoluble material. Structural solution and Rietveld refinement of high-resolution synchrotron powder diffraction data for this unprecedented, complicated compound of previously unknown composition revealed a new alkali-free ordered structural motif with [MnII 4 (µ3 -OH)4 ]4+ cubes and octahedral [MnII (CN)6 ]4- ions interconnected in 3D by MnII -N≡C-MnII linkages. The composition is {[MnII (OH2 )3 ][MnII (OH2 )]3 }(µ3 -OH)4 ][MnII (µ-CN)2 (CN)4 ]⋅H2 O=[MnII 4 (µ3 -OH)4 (OH2 )6 ][MnII (µ-CN)2 (CN)4 ]⋅H2 O, which is further simplified to [Mn4 (OH)4 ][Mn(CN)6 ](OH2 )7 (1). 1 has four high-spin (S=5/2) MnII sites that are antiferromagnetically coupled within the cube and are antiferromagnetically coupled to six low-spin (S=1/2) octahedral [MnII (CN)6 ]4- ions. Above 40 K the magnetic susceptibility, χ(T), can be fitted to the Curie-Weiss expression, χ ∝(T-θ)-1 , with θ=-13.4 K, indicative of significant antiferromagnetic coupling and 1 orders as an antiferromagnet at Tc =7.8 K.

Hydrating the Bispropionate Notch in Malaria Pigment: A New Structural Motif in the Iron(III)(deuteroporphyrin) Dimer.

Treating deuterohemin, chloro(deuteroporphyrinato)iron(III), with a non-coordinating base in DMSO/methanol allows for the isolation of [(deuteroporphyrinato)iron(III)]2 , deuterohematin anhydride (DHA), an analogue of malaria pigment, the natural product of heme detoxification by malaria. The structure of DHA obtained from this solvent system has been solved by X-ray powder diffraction analysis and displays many similarities, yet important structural differences, to malaria pigment. Most notably, a water molecule of solvation occupies a notch created by the propionate side chains and stabilizes a markedly bent propionate ligand coordinated with a long Fe-O bond, and a carboxylate cluster associated with water molecules is generated. Together, these features account for its increased solubility and more open structure, with an increased porphyrin-porphyrin separation. The IR spectroscopic signature associated with this structure also accounts for the strong IR band at 1587 cm-1 seen for many amorphous preparations of synthetic malaria pigment, and it is proposed that stabilizing these structures may be a new objective for antimalarial drugs. The important role of the vinyl substituents in this biochemistry is further demonstrated by the structure of deuterohemin obtained by single-crystal X-ray diffraction analysis.

A new approach to gathering pharmaceutical market data to support policy implementation and access to medicines: as demonstrated by malaria medicines in Zambia.

BACKGROUND: The steady supply of quality, affordable medicines is a pillar of a functioning health system. In addition to the public sector, the private, mission and not-for-profit sectors often serve a large part of the population in Africa. However, while there is generally systematic recording of public sector supply of medicines, detailed, systematic and reliable national market data including these non-public sectors are not commonly available in most countries in Africa. Understanding the total market is a missing part of the access puzzle: without this information, policy makers and health practitioners are not able to fully measure the impact of interventions, measure access to effective products, or fully evaluate the rational use of medicines. This article reports on a unique innovation which provides routine, national-level data on the total pharmaceuticals market, through a system which can be replicated elsewhere. It demonstrates how national-level market data contribute to the evidence base for policies on access to essential medicines, using the Zambian anti-malarial medicines market as a case study. METHODS: A new, routine national database on pharmaceutical market size and structure was established through a multi-partner collaboration. Information was extracted from import authorizations and allows for information on local manufacture. Data included value and volume of products as well as pack details, manufacturer and importer. The system was continually updated: data for this analysis were extracted for 6 years: 2009-2014 inclusive. Data were analysed using Microsoft Excel and validated against other sources including donor procurement data. Analysis included public and private sector markets. The policy relevance was demonstrated through analysis of four aspects of national policies on access and rational use of malaria medicines: (i) volume of product relative to disease burden; (ii) distribution by sector relative to treatment-seeking; (iii) consistency of products with respect to national policy guidelines; (iv) market concentration as a proxy for security of supply. RESULTS: The system developed provides the first accurate, systematic data on the breakdown of a national pharmaceutical market in an African context. The total value of the anti-malarials market in Zambia, including all sectors, was USD 5.5-6 million. This included 22 different molecules or combinations, produced by 56 different manufacturers, with 142 different permutations of molecule/manufacturer/strength. Such data provide a complementary mechanism to confirm key trends in malaria treatment and control in Zambia: (i) sufficient supply relative to disease burden, (ii) value and volume of the private/non-profit sector; 29%-2% of market value and 17%-2% of market volume (from 2009 to 2014), (iii) dominance of the 3 molecules recommended in the national treatment guidelines; and (iv) an evidence-base for national discussions on medicines quality, security of supply and rationale use. The system extracts information on all medicines and therefore could be used to analyse other therapeutic classes. Data have been used for several policy purposes, notably by ZAMRA to monitor the quality of products in Zambia, monitoring implementation of WHO Resolutions on artemisinin monotherapy as well as monitoring trends in product choice across sectors. CONCLUSION: Routine data are important for researchers and policy makers alike. This study shows how medicines data can be systematically gathered at national level-comprising range, volume and value in the public, private and not-for-profit sectors-to monitor more detailed trends in the market and allows triangulation of supply-side data against other sources. This systematic approach can contribute significantly to support access to medicines, monitor treatment and public health policies and create healthy markets. It can be used to monitor changes between therapeutic areas, for example the impact of improved malaria treatment on the use of antibiotics in the context of anti-microbial resistance monitoring. As data contain commercially confidential information, appropriate safeguards should be put in place to balance public health and commercial interests.

Structure and Magnetic Behavior of Layered Honeycomb Tellurates, BiM(III)TeO6 (M = Cr, Mn, Fe).

New layered honeycomb tellurates, BiM(III)TeO6 (M = Cr, Mn, Fe) were synthesized and characterized. BiM(III)TeO6 (M = Cr, Fe) species crystallize in a trigonal space group, P3̅1c (No. 163), of edge-sharing M3+/Te6+O6 octahedra, which form honeycomb-like double layers in the ab plane with Bi3+ cations located between the layers. Interestingly, the structure of BiMnTeO6 is similar to those of the Cr/Fe analogues, but with monoclinic space group, P21/c (No. 14), attributed to the strong Jahn-Teller distortion of Mn3+ cations. The crystal structure of BiM(III)TeO6 is a superstructure of PbSb2O6-related materials (ABB'O6). The Cr3+ and Fe3+ cations are ordered 80% and 90%, respectively, while the Mn3+ ions are completely ordered on the B-site of the ABB'O6 structure. BiCrTeO6 shows a broad antiferromagnetic transition (AFM) at ∼17 K with a Weiss temperature (θ) of -59.85 K, while BiFeTeO6 and BiMnTeO6 show sharp AFM transitions at ∼11 K with θ of -27.56 K and at ∼9.5 K with θ of -17.57 K, respectively. These differences in the magnetic behavior are ascribed to the different concentration of magnetic nearest versus next-nearest neighbor interactions of magnetic cations due to the relative differences in the extent of M/Te ordering.

Combined Theoretical and in Situ Scattering Strategies for Optimized Discovery and Recovery of High-Pressure Phases: A Case Study of the GaN-Nb2O5 System.

The application of pressure in solid-state synthesis provides a route for the creation of new and exciting materials. However, the onerous nature of high-pressure techniques limits their utility in materials discovery. The systematic search for novel oxynitrides-semiconductors for photocatalytic overall water splitting-is a representative case where quench high-pressure synthesis is useful and necessary in order to obtain target compounds. We utilize state of the art crystal structure prediction theory (USPEX) and in situ synchrotron-based X-ray scattering to speed up the discovery and optimization of novel compounds using high-pressure synthesis. Using this approach, two novel oxynitride phases were discovered in the GaN-Nb2O5 system. The (Nb2O5)0.84:(NbO2)0.32:(GaN)0.82 rutile structured phase was formed at 1 GPa and 900 °C and gradually transformed to a α-PbO2-related structure above 2.8 GPa and 1000 °C. The low-pressure rutile type phase was found to have a direct optical band gap of 0.84 eV and an indirect gap of 0.51 eV.

Ba3(Cr0.97(1)Te0.03(1))2TeO9: in Search of Jahn-Teller Distorted Cr(II) Oxide.

A novel 6H-type hexagonal perovskite Ba3(Cr0.97(1)Te0.03(1))2TeO9 was prepared at high pressure (6 GPa) and temperature (1773 K). Both transmission electron microscopy and synchrotron powder X-ray diffraction data demonstrate that Ba3(Cr0.97(1)Te0.03(1))2TeO9 crystallizes in P63/mmc with face-shared (Cr0.97(1)Te0.03(1))O6 octahedral pairs interconnected with TeO6 octahedra via corner-sharing. Structure analysis shows a mixed Cr2+/Cr3+ valence state with ∼10% Cr2+. The existence of Cr2+ in Ba3(Cr2+0.10(1)Cr3+0.87(1)Te6+0.03)2TeO9 is further evidenced by X-ray absorption near-edge spectroscopy. Magnetic properties measurements show a paramagnetic response down to 4 K and a small glassy-state curvature at low temperature. In this work, the octahedral Cr2+O6 component is stabilized in an oxide material for the first time; the expected Jahn-Teller distortion of high-spin (d4) Cr2+ is not found, which is attributed to the small proportion of Cr2+ (∼10%) and the face-sharing arrangement of CrO6 octahedral pairs, which structurally disfavor axial distortion.

Pb2MnTeO6 Double Perovskite: An Antipolar Anti-ferromagnet.

Pb2MnTeO6, a new double perovskite, was synthesized. Its crystal structure was determined by synchrotron X-ray and powder neutron diffraction. Pb2MnTeO6 is monoclinic (I2/m) at room temperature with a regular arrangement of all the cations in their polyhedra. However, when the temperature is lowered to ∼120 K it undergoes a phase transition from I2/m to C2/c structure. This transition is accompanied by a displacement of the Pb atoms from the center of their polyhedra due to the 6s(2) lone-pair electrons, together with a surprising off-centering of Mn(2+) (d(5)) magnetic cations. This strong first-order phase transition is also evidenced by specific heat, dielectric, Raman, and infrared spectroscopy measurements. The magnetic characterizations indicate an anti-ferromagnetic (AFM) order below TN ≈ 20 K; analysis of powder neutron diffraction data confirms the magnetic structure with propagation vector k = (0 1 0) and collinear AFM spins. The observed jump in dielectric permittivity near ∼150 K implies possible anti-ferroelectric behavior; however, the absence of switching suggests that Pb2MnTeO6 can only be antipolar. First-principle calculations confirmed that the crystal and magnetic structures determined are locally stable and that anti-ferroelectric switching is unlikely to be observed in Pb2MnTeO6.

Antiferromagnetism in a Family of S = 1 Square Lattice Coordination Polymers NiX2(pyz)2 (X = Cl, Br, I, NCS; pyz = Pyrazine).

The crystal structures of NiX2(pyz)2 (X = Cl (1), Br (2), I (3), and NCS (4)) were determined by synchrotron X-ray powder diffraction. All four compounds consist of two-dimensional (2D) square arrays self-assembled from octahedral NiN4X2 units that are bridged by pyz ligands. The 2D layered motifs displayed by 1-4 are relevant to bifluoride-bridged [Ni(HF2)(pyz)2]EF6 (E = P, Sb), which also possess the same 2D layers. In contrast, terminal X ligands occupy axial positions in 1-4 and cause a staggered packing of adjacent layers. Long-range antiferromagnetic (AFM) order occurs below 1.5 (Cl), 1.9 (Br and NCS), and 2.5 K (I) as determined by heat capacity and muon-spin relaxation. The single-ion anisotropy and g factor of 2, 3, and 4 were measured by electron-spin resonance with no evidence for zero-field splitting (ZFS) being observed. The magnetism of 1-4 spans the spectrum from quasi-two-dimensional (2D) to three-dimensional (3D) antiferromagnetism. Nearly identical results and thermodynamic features were obtained for 2 and 4 as shown by pulsed-field magnetization, magnetic susceptibility, as well as their Néel temperatures. Magnetization curves for 2 and 4 calculated by quantum Monte Carlo simulation also show excellent agreement with the pulsed-field data. Compound 3 is characterized as a 3D AFM with the interlayer interaction (J⊥) being slightly stronger than the intralayer interaction along Ni-pyz-Ni segments (J(pyz)) within the two-dimensional [Ni(pyz)2](2+) square planes. Regardless of X, J(pyz) is similar for the four compounds and is roughly 1 K.

Low-Temperature Cationic Rearrangement in a Bulk Metal Oxide.

Cationic rearrangement is a compelling strategy for producing desirable physical properties by atomic-scale manipulation. However, activating ionic diffusion typically requires high temperature, and in some cases also high pressure in bulk oxide materials. Herein, we present the cationic rearrangement in bulk Mn2 FeMoO6 at unparalleled low temperatures of 150-300 (o) C. The irreversible ionic motion at ambient pressure, as evidenced by real-time powder synchrotron X-ray and neutron diffraction, and second harmonic generation, leads to a transition from a Ni3 TeO6 -type to an ordered-ilmenite structure, and dramatic changes of the electrical and magnetic properties. This work demonstrates a remarkable cationic rearrangement, with corresponding large changes in the physical properties in a bulk oxide at unprecedented low temperatures.

Longitudinal trends and cross-sectional analysis of English national hospital antibacterial use over 5 years (2008-13): working towards hospital prescribing quality measures.

OBJECTIVES: There is global concern that antimicrobial resistance is a major threat to healthcare. Antimicrobial use is a primary driver of resistance but little information exists about the variation in antimicrobial use in individual hospitals in England over time or comparative use between hospitals. The objective of this study was to collate, analyse and report issue data from pharmacy records of 158 National Health Service (NHS) acute hospitals. METHODS: This was a cohort study of inpatient antibacterial use in acute hospitals in England analysed over 5 years through a data warehouse from IMS Health, a leading provider of information, services and technology for the healthcare industry. Around 98% of NHS hospitals were included in a country with a population of 50 million residents. RESULTS: There was a dramatic change in the usage of different groups of antibacterials between 2009 and 2013 with a marked reduction in the use of first-generation cephalosporins by 24.7% and second-generation cephalosporins by 41%, but little change in the use of third-generation cephalosporins (+5.7%) and fluoroquinolones (+1.6%). In contrast, use of co-amoxiclav, carbapenems and piperacillin/tazobactam increased by 60.1%, 61.4% and 94.8%, respectively. There was wide variation in the total and relative amounts of antibacterials used between individual hospitals. CONCLUSIONS: Longitudinal analysis of antibacterial use demonstrated remarkable changes in NHS hospitals, probably reflecting governmental and professional guidance to mitigate the risk of Clostridium difficile infection. The wide variation in usage between individual hospitals suggests potential for quality improvement and benchmarking. Quality measures of optimal hospital antimicrobial prescribing need urgent development and validation to support antimicrobial stewardship initiatives.