Exploring the Effects of the Photochromic Response and Crystallization on the Local Structure of Noncrystalline Niobium Oxide.

Niobium oxide (Nb2O5) is a versatile semiconductor material with photochromic properties. This study investigates the local structure of noncrystalline, short-range-ordered niobium oxide synthesized via a sol-gel method. X-ray atomic pair distribution function analysis unravels the structural arrangements within the noncrystalline materials at a local scale. In the following, in situ scattering and diffraction experiments elucidate the heat-induced structure transformation of the amorphous material into crystalline TT-Nb2O5 at 550 °C. In addition, the effect of photocatalytic conditions on the structure of the material was investigated by exposing the short-range-ordered and crystalline materials to ultraviolet light, resulting in a reversible color change from white to dark brown or blue. This photochromic response is due to the reversible elongation of the nearest Nb-O neighbors, as shown by local structure analysis based on in situ PDF analyses. Optical band gap calculations based on the ultraviolet-visible spectra collected for both the short-range-ordered and crystalline materials show that the band gap values reduced for the darkened materials return to their initial state after bleaching. Furthermore, electron energy loss spectroscopy reveals the reduction of Nb5+ to Nb4+ centers as a persistent effect. The study establishes a correlation between the band gap and the structure of niobium oxide, providing insights into the structure-performance relation at the atomic level.

The Chemistry of Spinel Ferrite Nanoparticle Nucleation, Crystallization, and Growth.

The nucleation, crystallization, and growth mechanisms of MnFe2O4, CoFe2O4, NiFe2O4, and ZnFe2O4 nanocrystallites prepared from coprecipitated transition metal (TM) hydroxide precursors treated at sub-, near-, and supercritical hydrothermal conditions have been studied by in situ X-ray total scattering (TS) with pair distribution function (PDF) analysis, and in situ synchrotron powder X-ray diffraction (PXRD) with Rietveld analysis. The in situ TS experiments were carried out on 0.6 M TM hydroxide precursors prepared from aqueous metal chloride solutions using 24.5% NH4OH as the precipitating base. The PDF analysis reveals equivalent nucleation processes for the four spinel ferrite compounds under the studied hydrothermal conditions, where the TMs form edge-sharing octahedrally coordinated hydroxide units (monomers/dimers and in some cases trimers) in the aqueous precursor, which upon hydrothermal treatment nucleate through linking by tetrahedrally coordinated TMs. The in situ PXRD experiments were carried out on 1.2 M TM hydroxide precursors prepared from aqueous metal nitrate solutions using 16 M NaOH as the precipitating base. The crystallization and growth of the nanocrystallites were found to progress via different processes depending on the specific TMs and synthesis temperatures. The PXRD data show that MnFe2O4 and CoFe2O4 nanocrystallites rapidly grow (typically <1 min) to equilibrium sizes of 20-25 nm and 10-12 nm, respectively, regardless of applied temperature in the 170-420 °C range, indicating limited possibility of targeted size control. However, varying the reaction time (0-30 min) and temperature (150-400 °C) allows different sizes to be obtained for NiFe2O4 (3-30 nm) and ZnFe2O4 (3-12 nm) nanocrystallites. The mechanisms controlling the crystallization and growth (nucleation, growth by diffusion, Ostwald ripening, etc.) were examined by qualitative analysis of the evolution in refined scale factor (proportional to extent of crystallization) and mean crystallite volume (proportional to extent of growth). Interestingly, lower kinetic barriers are observed for the formation of the mixed spinels (MnFe2O4 and CoFe2O4) compared to the inverse (NiFe2O4) and normal (ZnFe2O4) spinel structured compounds, suggesting that the energy barrier for formation may be lowered when the TMs have no site preference.

In situ synchrotron X-ray total scattering measurements and analysis of colloidal CsPbX3 nanocrystals during flow synthesis.

In situ X-ray scattering measurements of CsPbX3 (X = Cl, Br, I) nanocrystal formation and halide exchange at NSLS-II beamlines were performed in an automated flow reactor. Total scattering measurements were performed at the 28-ID-2 (XPD) beamline and small-angle X-ray scattering at the 16-ID (LiX) beamline. Nanocrystal structural parameters of interest, including size, size distribution and atomic structure, were extracted from modeling the total scattering data. The results highlight the potential of these beamlines and the measurement protocols described in this study for studying dynamic processes of colloidal nanocrystal synthesis in solution with timescales on the order of seconds.

Pharmaceutical Development Challenges in a Beyond Rule of Five Prodrug: Case Study of ABBV-167, Phosphate Prodrug of Venetoclax.

ABBV-167, a phosphate prodrug of BCL-2 inhibitor venetoclax, was recently progressed into the clinic as an alternative means of reducing pill burden for patients in high-dose indications. The dramatically enhanced aqueous solubility of ABBV-167 allowed for high drug loading within a crystalline tablet and, when administered in phase I clinical study, conferred venetoclax exposure commensurate with the equivalent dose administered as an amorphous solid dispersion. In enabling the progression into the clinic, we performed a comprehensive evaluation of the CMC development aspects of this beyond the rule of five (bRo5) prodrug. Adding a phosphate moiety resulted in excessively complex chemical speciation and solid form landscapes with significant physical-chemical stability liabilities. A combination of experimental and computational methods including microelectron diffraction (MicroED), total scattering, tablet colorimetry, finite element, and molecular dynamics modeling were used to understand CMC developability across drug substance and product manufacture and storage. The prodrug's chemical structural characteristics and loose crystal packing were found to be responsible for the loss of crystallinity during its manufacturing, which in turn led to high solid-state chemical reactivity and poor shelf life stability. The ABBV-167 case exemplifies key CMC development challenges for complex chemical matter such as bRo5 phosphate prodrugs with significant ramifications during drug substance and drug product manufacturing and storage.

A reactor for time-resolved X-ray studies of nucleation and growth during solvothermal synthesis.

Understanding the nucleation and growth mechanisms of nanocrystals under hydro- and solvothermal conditions is key to tailoring functional nanomaterials. High-energy and high-flux synchrotron radiation is ideal for characterization by powder X-ray diffraction and X-ray total scattering in real time. Different versions of batch-type cell reactors have been employed in this work, exploiting the robustness of polyimide-coated fused quartz tubes with an inner diameter of 0.7 mm, as they can withstand pressures up to 250 bar and temperatures up to 723 K for several hours. Reported here are recent developments of the in situ setups available for general users on the P21.1 beamline at PETRA III and the DanMAX beamline at MAX IV to study nucleation and growth phenomena in solvothermal synthesis. It is shown that data suitable for both reciprocal-space Rietveld refinement and direct-space pair distribution function refinement can be obtained on a timescale of 4 ms.

Sub-second pair distribution function using a broad bandwidth monochromator.

Here the use of a broad energy bandwidth monochromator, i.e. a pair of B4C/W multilayer mirrors (MLMs), is demonstrated for X-ray total scattering (TS) measurements and pair distribution function (PDF) analysis. Data are collected both on powder samples and from metal oxo clusters in aqueous solution at various concentrations. A comparison between the MLM PDFs and those obtained using a standard Si(111) double-crystal monochromator shows that the measurements yield MLM PDFs of high quality which are suitable for structure refinement. Moreover, the effects of time resolution and concentration on the quality of the resulting PDFs of the metal oxo clusters are investigated. PDFs of heptamolybdate clusters and tungsten α-Keggin clusters from X-ray TS data were obtained with a time resolution down to 3 ms and still showed a similar level of Fourier ripples to PDFs obtained from 1 s measurements. This type of measurement could thus open up faster time-resolved TS and PDF studies.

An Amorphous Phase Precedes Crystallization: Unraveling the Colloidal Synthesis of Zirconium Oxide Nanocrystals.

One can nowadays readily generate monodisperse colloidal nanocrystals, but the underlying mechanism of nucleation and growth is still a matter of intense debate. Here, we combine X-ray pair distribution function (PDF) analysis, small-angle X-ray scattering (SAXS), nuclear magnetic resonance (NMR), and transmission electron microscopy (TEM) to investigate the nucleation and growth of zirconia nanocrystals from zirconium chloride and zirconium isopropoxide at 340 °C, in the presence of surfactant (tri-n-octylphosphine oxide). Through E1 elimination, precursor conversion leads to the formation of small amorphous particles (less than 2 nm in diameter). Over the course of the reaction, the total particle concentration decreases while the concentration of nanocrystals stays constant after a sudden increase (nucleation). Kinetic modeling suggests that amorphous particles nucleate into nanocrystals through a second order process and they are also the source of nanocrystal growth. There is no evidence for a soluble monomer. The nonclassical nucleation is related to a precursor decomposition rate that is an order of magnitude higher than the observed crystallization rate. Using different zirconium precursors (e.g., ZrBr4 or Zr(OtBu)4), we can tune the precursor decomposition rate and thus control the nanocrystal size. We expect these findings to help researchers in the further development of colloidal syntheses.

An inclined detector geometry for improved X-ray total scattering measurements.

X-ray total scattering measurements are implemented using a digital flat-panel area detector in an inclined geometry and compared with the traditional geometry. The traditional geometry is defined here by the incident X-ray beam impinging on and normal to the center-most pixel of a detector. The inclined geometry is defined here by a detector at a pitch angle α, set to 15° in this case, bisected by the vertical scattering plane. The detector is positioned such that the incident X-ray beam strikes the pixels along the bottom edge and 90° scattered X-rays impinge on the pixels along the top edge. The geometric attributes of the inclined geometry translate into multiple benefits, such as an extension of the measurable scattering range to 90°, a 47% increase in the accessible magnitudes of the reciprocal-space vector Q and a leveling of the dynamic range in the measured total scattering pattern. As a result, a sixfold improvement in signal-to-noise ratios is observed at higher scattering angles, enabling up to a 36-fold reduction in acquisition time. Additionally, the extent of applied modification functions is reduced, decreasing the magnitude of termination ripples and improving the real-space resolution of the pair distribution function G(r). Taken all together, these factors indicate that the inclined geometry produces higher quality data than the traditional geometry, usable for simultaneous Rietveld refinement and total scattering studies.

Total scattering measurements at the Australian Synchrotron Powder Diffraction beamline: capabilities and limitations.

This study describes the capabilities and limitations of carrying out total scattering experiments on the Powder Diffraction (PD) beamline at the Australian Synchrotron, ANSTO. A maximum instrument momentum transfer of 19 Å-1 can be achieved if the data are collected at 21 keV. The results detail how the pair distribution function (PDF) is affected by Qmax, absorption and counting time duration at the PD beamline, and refined structural parameters exemplify how the PDF is affected by these parameters. There are considerations when performing total scattering experiments at the PD beamline, including (1) samples need to be stable during data collection, (2) highly absorbing samples with a µR > 1 always require dilution and (3) only correlation length differences >0.35 Šmay be resolved. A case study comparing the PDF atom-atom correlation lengths with EXAFS-derived radial distances of Ni and Pt nanocrystals is also presented, which shows good agreement between the two techniques. The results here can be used as a guide for researchers considering total scattering experiments at the PD beamline or similarly setup beamlines.

Extended q-Range X-Ray Scattering Reveals High-Resolution Structural Details of Biomacromolecules in Aqueous Solutions.

We communicate a feasibility study for high-resolution structural characterization of biomacromolecules in aqueous solution from X-ray scattering experiments measured over a range of scattering vectors (q) that is approximately two orders of magnitude wider than used previously for such systems. Scattering data with such an extended q-range enables the recovery of the underlying real-space atomic pair distribution function, which facilitates structure determination. We demonstrate the potential of this method for biomacromolecules using several types of cyclodextrins (CD) as model systems. We successfully identified deviations of the tilting angles for the glycosidic units in CDs in aqueous solutions relative to their values in the crystalline forms of these molecules. Such level of structural detail is inaccessible from standard small angle scattering measurements. Our results call for further exploration of ultra-wide-angle X-ray scattering measurements for biomacromolecules.

Lorentz factor for time-of-flight neutron Bragg and total scattering.

The three fundamental origins of the Lorentz factor for neutron time-of-flight powder diffraction are revisited. A detailed derivation of the Lorentz factor is presented in the context of diffuse scattering modelling in reciprocal space when perfect periodicity is assumed, and the total scattering pattern is constructed in its discrete form - the factor in this case becomes 1/Q2 (or d2). Discussion is also presented with respect to practical data reduction where a vanadium measurement is usually taken as the normalization factor (to account for various factors such as detector efficiency), and it is shown that the existence of the Lorentz factor is independent of such a normalization process.

Temperature-dependent anisotropy in the bond lengths of UO2as a result of phonon-induced atomic correlations.

Previous experiments on cubic UO2have suggested that the temperature dependences of the nearest-neighbour U-O and U-U distances aredifferent. We have acquired total-scattering neutron diffraction patterns out toQ = 23.5 Å-1for50

Pressure cells for in situ neutron total scattering: time and real-space resolution during deuterium absorption.

In situ gas-loading sample holders for two-dimensionally arranged detectors in time-of-flight neutron total scattering experiments have been developed to investigate atomic arrangements during deuterium absorption using time and real-space resolution. A single-crystal sapphire container was developed that allows conditions of 473 K and 10 MPa hydrogen gas pressure. High-resolution transient measurements detected deuterium absorption by palladium that proceeded within a few seconds. A double-layered container with thick- and thin-walled vanadium allowed conditions of 423 K and 10 MPa hydrogen gas pressure. The deuterium occupation sites of a lanthanum-nickel-aluminium alloy are discussed in detail on the basis of real-space high-resolution data obtained from in situ neutron scattering measurements and reverse Monte Carlo structural modeling.

On single-crystal total scattering data reduction and correction protocols for analysis in direct space. Corrigendum.

The name of the third author of the article by Koch et al. [Acta Cryst. (2021). A77, 611-636] is corrected.

Effects of Grain Refinement and Thermal Aging on Atomic Scale Local Structures of Ultra-Fine Explosives by X-ray Total Scattering.

The atomic scale local structures affect the initiation performance of ultra-fine explosives according to the stimulation results of hot spot formation. However, the experimental characterization of local structures in ultra-fine explosives has been rarely reported, due to the difficulty in application of characterization methods having both high resolution in and small damage to unstable organic explosive materials. In this work, X-ray total scattering was explored to investigate the atomic scale local distortion of two widely applicable ultra-fine explosives, LLM-105 and HNS. The experimental spectra of atomic pair distribution function (PDF) derived from scattering results were fitted by assuming rigid ring structures in molecules. The effects of grain refinement and thermal aging on the atomic scale local structure were investigated, and the changes in both the length of covalent bonds have been identified. Results indicate that by decreasing the particle size of LLM-105 and HNS from hundreds of microns to hundreds of nanometers, the crystal structures remain, whereas the molecular configuration slightly changes and the degree of structural disorder increases. For example, the average length of covalent bonds in LLM-105 reduces from 1.25 Å to 1.15 Å, whereas that in HNS increases from 1.25 Å to 1.30 Å, which is possibly related to the incomplete crystallization process and internal stress. After thermal aging of ultra-fine LLM-105 and HNS, the degree of structural disorder decreases, and the distortion in molecules formed in the synthesis process gradually healed. The average length of covalent bonds in LLM-105 increases from 1.15 Å to 1.27 Å, whereas that in HNS reduces from 1.30 Å to 1.20 Å. The possible reason is that the atomic vibration in the molecule intensifies during the heat aging treatment, and the internal stress was released through changes in molecular configuration, and thus the atomic scale distortion gradually heals. The characterization method and findings in local structures obtained in this work may pave the path to deeply understand the relationship between the defects and performance of ultra-fine explosives.

Structure and Surface Relaxation of CeO2 Nanoparticles Unveiled by Combining Real and Reciprocal Space Total Scattering Analysis.

We present a combined real and reciprocal space structural and microstructural characterization of CeO2 nanoparticles (NPs) exhibiting different crystallite sizes; ~3 nm CeO2 NPs were produced by an inverse micellae wet synthetic path and then annealed at different temperatures. X-ray total scattering data were analyzed by combining real-space-based Pair Distribution Function analysis and the reciprocal-space-based Debye Scattering Equation method with atomistic models. Subtle atomic-scale relaxations occur at the nanocrystal surface. The structural analysis was corroborated by ab initio DFT and force field calculations; micro-Raman and electron spin resonance added important insights to the NPs' defective structure. The combination of the above techniques suggests a core-shell like structure of ultrasmall NPs. These exhibit an expanded outer shell having a defective fluorite structure, while the inner shell is similar to the bulk structure. The presence of partially reduced O2-δ species testifies to the high surface activity of the NPs. On increasing the annealing temperature, the particle dimensions increase, limiting disorder as a consequence of the progressive surface-to-volume ratio reduction.

Adaptive Cation Pillar Effects Achieving High Capacity in Li-Rich Layered Oxide, Li2 MnO3 -LiMeO2 (Me = Ni, Co, Mn).

Intensive research is underway to further enhance the performance of lithium-ion batteries (LIBs). To increase the capacity of positive electrode materials, Li-rich layered oxides (LLO) are attracting attention but have not yet been put to practical use. The structural mechanisms through which LLO materials exhibit higher capacity than conventional materials remain unclear because their disordered phases make it difficult to obtain structural information by conventional analysis. The X-ray total scattering analysis reveals a disordered structure consisting of metal ions in octahedral and tetrahedral sites of Li layers as a result of cation mixing after the extraction of Li ions. Metal ions in octahedral sites act as rigid pillars. The metal ions move to the tetrahedral site of the Li layer, which functions as a Li-layer pillar during Li extraction, and returns to the metal site during Li insertion, facilitating Li diffusion as an adaptive pillar. Adaptive pillars are the specific structural features that differ from those of the conventional layered materials, and their effects are responsible for the high capacity of LLO materials. An essential understanding of the pillar effects will contribute to design guidelines for intercalation-type positive electrodes for next-generation LIBs.

Neutron Total Scattering Investigation of the Dissolution Mechanism of Trehalose in Alkali/Urea Aqueous Solution.

The atomic picture of cellulose dissolution in alkali/urea aqueous solution is still not clear. To reveal it, we use trehalose as the model molecule and total scattering as the main tool. Three kinds of alkali solution, i.e., LiOH, NaOH and KOH are compared. The most probable all-atom structures of the solution are thus obtained. The hydration shell of trehalose has a layered structure. The smaller alkali ions can penetrate into the glucose rings around oxygen atoms to form the first hydration layer. The larger urea molecules interact with hydroxide groups to form complexations. Then, the electronegative complexation can form the second hydration layer around alkali ions via electrostatic interaction. Therefore, the solubility of alkali aqueous solution for cellulose decreases with the alkali cation radius, i.e., LiOH > NaOH > KOH. Our findings are helpful for designing better green solvents for cellulose.

Investigating pair distribution function use in analysis of nanocrystalline hydroxyapatite and carbonate-substituted hydroxyapatite.

Hydroxyapatite (HA) is a complex material, which is often nanocrystalline when found within a biological setting. This work has directly compared the structural characteristics derived from data collected using a conventional laboratory-based X-ray diffractometer with those collected from a dedicated pair distribution function (PDF) beamline at Diamond Light Source. In particular, the application of PDF analysis methods to carbonated HA is evaluated. 20 synthetic samples were measured using both X-ray diffraction (XRD) and PDFs. Both Rietveld refinement (of laboratory XRD data) and real-space refinement (of PDF data) were used to analyse all samples. The results of Rietveld and real-space refinements were compared to evaluate their application to crystalline and nanocrystalline hydroxyapatite. Significant relationships were observed between real-space refinement parameters and increasing carbonate substitution. Understanding the local order of synthetic hydroxyapatite can benefit several fields, including both biomedical and clinical settings.

Phase behaviour of ammonium bromide-d4under high pressure and low temperature; an average and local structure study.

We revisit the pressure-induced order-disorder transition between phases II and IV in ammonium bromide-d4using neutron diffraction measurements to characterise both the average and local structures. We identify a very sluggish transition that does not proceed to full conversion and local structure correlations indicate a slight preference for ammonium cation ordering along ⟨110⟩ crystallographic directions, as pressure is increased. Simultaneous cooling below ambient temperature appears to facilitate the pressure-induced transition. Variable-temperature, ambient-pressure measurements across the IV → III → II transitions show slower conversion than previously observed, and that phase III exhibits metastability above ambient temperature.