bluuebunny/crossref_metadata_2025 huggingface dataset:
Reversible De-/Rehydration Process in Paroxetine Hydrobromide
Authors: Carvalho-Jr Paulo , Ellena Javier , Ayala Alejandro
Published: November 2015

Paroxetine (PRX) is an antidepressant widely used in depression treatment for decades. The anhydrous and hemidrate chloride forms have been used in pharmaceutical formulations. During their developing a discussion associated with its physical forms and the complex hydration/dehydration behavior involving these phases were established. To improve our understanding of this issue we investigate the crystal structure of paroxetine bromide hemidrate, (PRX+.Br-).H2O, as a model for understanding the stability anhydrous/hemihydrate paroxetine arrangements and the nature of the intermolecular interaction of water within the crystal lattice by single crystal X-ray diffraction experiments. A combination of complementary characterization techniques were also used including Differential Scanning Calorimetry (DSC), thermogravimetric analysis (TGA), Hot Stage microscopy and solubility measurements. As expected the paroxetine bromide hemidrate, (PRX+.Br-).H2O, is isostructural with the paroxetine chloride hemidrate, (PRX+.Cl-).H2O. As in that case, the crystal packing of (PRX+.Br-).H2O is stabilized by strong NH2+...O and NH2+...Br hydrogen bonds which forms infinite channels along the b axis. The water and bromide anions are located along these channels. The DSC/TGA analysis for (PRX+.Br-).H2O show an endothermic desolvation process with an onset temperature of 77.09 °C, that is not present in the paroxetine chloride hemidrate DSC curve. This process leaves to a paroxetine anhydrous bromide crystal structure that is isomorphic to the anhydrous chloride one. However, this structure is spontaneously rehydrated at ambient atmosphere. This rehydration phenomenon probe the stability of paroxetine hemihydrate arrangement, since (PRX+.Br-) is slightly more soluble that its hydrate form. As opposed to chloride hemidrate, the rehydration of paroxetine bromide only involves a rearrangement of the water molecule within the cavities.
Insights into hydrate formation and stability of morphinanes
Authors: Braun Doris , Griesser Ulrich
Published: November 2015

The formation of multi-component crystals with water (hydrates) is a widespread phenomenon among organic molecules. Hydrate formation is of high practical relevance for industrially used materials, as it affects their physicochemical properties. [1,2] To exclude water or moisture in industrial processes is often difficult. Therefore knowledge about the existence and stability of hydrates and the understanding and control of the anhydrate/hydrate balance is mandatory for avoiding manufacturing problems. In order to improve our understanding of hydrate formation we selected representative substances (morphine, codeine, ethylmorphine) from a class of molecules (morphinanes), which are prone to crystallize along with water. Stable hydrates of both, free bases and HCl salts, have been observed in this important class of drug compounds. This allowed us to investigate the influence of different functional groups, the role of water and the Cl– counterion on the structure and properties of these morphinanes. A crystallization screen on the six compounds considerably extended the total number of known solid forms from twelve [3] to 17 and the number of crystal structures from five to twelve. Anhydrous polymorphs were detected for all compounds except ethylmorphine (one anhydrate) and its HCl salt (no anhydrate). The relative stabilities of the hydrated and anhydrous forms differ considerably, which was evaluated by moisture sorption studies and thermal analytical experiments. Two different hydrates, a tri- and dihydrate, were found for morphine HCl. In the free bases, the substituents define the number of hydrogen bond donor groups and lead to differences in the sterical hindrance around polar groups, influencing the intermolecular interactions, packing and stability. Hydrate formation results in higher dimensional hydrogen bond networks, whereas salt formation decreases the packing variability of the structures among the different compounds. Calorimetric measurements and lattice energy calculations were employed to estimate the heat of hydrate/anhydrate phase transformation, showing an enthalpic stabilization of the hydrates over the anhydrates. The combination of a variety of experimental techniques with computational modelling allowed us to generate sufficient kinetic, thermodynamic and structural information to understand the principles of hydrate formation of morphinanes.
Structure and thermal analysis of amino acids
Authors: Athmani Hamza , Benali-Cherif Nourreedine
Published: November 2015

The twenty amino acids are chemical compounds having two functional groups (carboxyl:-COOH, amine:-NH2) and an asymmetric carbon (except glycine). They are amphoteric and can exist as zwitterion. Because of the reactivity of amino acids (esterification, amidation, N-alkylisation, N-arylation, protonation), and their conformation (aliphatic, aromatic) chemical, properties (acid, base, and / or hydroxylated, solubility), and physical properties (absorbance, NLO), our laboratory contribute to the study (synthesis and X ray single crystal structures) of new organic-inorganic hybrid compounds which allows to the development of materials with novel properties [1-3]. Our work is also based on the relationship between the thermal decomposition of amino acids and their chemical structures, dozens compounds were selected and the results of the DTA, TG and DTG thermal decomposition was performed by several methods. Diffraction results are used for the identification of degradation mechanisms of the chemical structure, the stability of the compound studied and the anticipation of possible syntheses of hybrid compounds.
High pressure studies of L-Serine-L-Ascorbic acid co-crystal
Authors: Arkhipov Sergey , Zakharov Boris , Boldyreva Elena
Published: November 2015

"Experiments for studying crystalline materials under extreme conditions are a powerful tool for investigating ""structure-property"" relationships. They also give information on the behavior of hydrogen bonds and are important both for materials science and crystal engineering. In addition, many processes in the living organisms are also related to mechanical stress. One of the most interesting tasks is to identify factors which influence the stability of a structure, or a part of the structure, at high pressure. Experiments on the systematic study of compounds in a wide range of pressures allow us to accumulate data that can be used to solve this problem. For a more complete picture, the mixed crystals of the selected compound are studied. Investigation of mixed crystals and cocrystals of interest can be compared with the crystals of individual compounds. We have chosen the structure of L-serine - L-ascorbic acid to be compared with those of L-serine and L-ascorbic acids for such a study. Phase transitions were previously reported to be induced by increasing pressure in both L-serine [1] and L-ascorbic acid [2]; moreover, the structure of L-serine was followed at multiple pressures by single-crystal and powder X-ray diffraction[3]. L-serine – L-ascorbic acid co-crystal was studied in the pressure range 0-5.4 GPa (at multiple points at every 0.5-0.7 GPa) by single-crystal X-ray diffraction and Raman spectroscopy. A phase transition has been detected and some rearrangement in the network of hydrogen bonds was observed. The high pressure data were compared with those for the individual structures of the L-serine and L-ascorbic acid. This work was supported by RFBR (grants 12–03-31541, 14-03-31866, 13-03-92704, 14-03-00902 ), Ministry of Science and Education of Russia and Russian Academy of Sciences."
Trapping liquid drugs inside crystals
Authors: Bacchi Alessia , Capucci Davide , Pelagatti Paolo
Published: November 2015

The objective of this work is to embed liquid or volatile pharmaceuticals inside crystalline materials, in order to tune their delivery properties in medicine or agrochemistry, and to explore new regulatory and intellectual properties issues. Liquid or volatile formulations of active pharmaceutical ingredients (APIs) are intrinsically less stable and durable than solid forms; in fact most drugs are formulated as solid dosage because they tend to be stable, reproducible, and amenable to purification. Most drugs and agrochemicals are manufactured and distributed as crystalline materials, and their action involves the delivery of the active molecule by a solubilization process either in the body or on the environment. However some important compounds for the human health or for the environment occur as liquids at room temperature. The formation of co-crystals has been demonstrated as a means of tuning solubility properties of solid phases, and therefore it is widely investigated by companies and by solid state scientists especially in the fields of pharmaceuticals, agrochemicals, pigments, dyestuffs, foods, and explosives. In spite of this extremely high interest towards co-crystallization as a tool to alter solubility, practically no emphasis has been paid to using it as a means to stabilize volatile or labile or low-melting products. In this work we trap and stabilize volatile and liquid APIs and agrochemicals in crystalline matrices by engineering suitable co-crystals. These new materials alter the physic state of the active ingredients allowing to expand the phase space accessible to manufacturing and delivery. We have defined a benchmark of molecules relevant to human health and environment that have been combined with suitable partners according to the well known methods of crystal engineering in order to obtain cocrystals. The first successful results will be discussed; the Figure shows a cocrystal of propofol, a worldwide use anesthetic.
Solid-state assembly of metal-organic architectures
Authors: Friscic Tomislav
Published: November 2015

"Chemical reactions induced or sustained by mechanical force (mechanochemistry) have attracted considerable interest as a means to achieve cleaner and ""greener"" solvent-free synthesis of molecules and materials. Such reactions also provide an opportunity to explore molecular recognition and self-assembly without the interfering effects of bulk solvents, such as solubility, complexation with solvent, or solvolysis.[1] This presentation will highlight our recent exploration of solvent-free chemistry as a means to understand the assembly, templating and the collapse of porous metal-organic structures. First, the recently developed methodology for real-time, in situ monitoring of mechanochemical reactions will be presented,[2] which uses highly penetrating synchrotron radiation to directly observe chemical and structural transformations during mechanical milling. By using this methodology it was possible, for the first time, to illuminate the mechanisms of metal-organic framework formation by milling, and observe new, fleeting intermediate phases. The second part of the presentation will focus on 'accelerated aging"", a simple, diffusion-controlled and catalytically-accelerated methodology for the transformation of inert metal oxides into metal-organic architectures under the conditions mimicking those of geological mineral ""weathering"".[3] This solvent-free and low-energy technique provides reactant generality not yet demonstrated in mechanosynthesis, and allows the transformations of diverse transition, main group and lanthanide metal oxides, into 2- and 3-dimensional metal-organic architectures. The applications of accelerated aging in the clean synthesis of metal-organic frameworks and low-energy, solvent-free mineral separation will be discussed."
Relaxor ferroelectrics materials under high pressure
Authors: Liu Arthur Haozhe , Wang Lisa Luhong , Kong Lingping
Published: November 2015

The rich phase diagrams from both relaxor and normal ferroelectrics under high pressure, stimulate us to study the pressure effect on the relaxor-PbTiO3 (PT) systems, to check whether the high pressure cubic structure will turn to low symmetry structure upon strong compression is the common behaviors for relaxor ferroelectrics materials. Furthermore, a complete phase diagram study of pressure-temperature effect on structure will allow us to explore the limitation on applications of relaxor-PT material devices under harsh environment involving in high pressure and high temperature conditions. Structure evolution and phase transition of several solid solution ferroelectrics, such as Pb(YbNb)O3-PT (PYN-PT), have been studied using in situ synchrotron X-ray diffraction (XRD) and Raman spectroscopy techniques under high pressure and high temperature conditions. XRD results show pressure induced phase transitions to a cubic phase, while the persistence of Raman spectroscopy in the full pressure range indicates its local distortion. A pressure-temperature phase diagram is further constructed to determine the stability region of the ferroelectric phase. The results provide useful guidance for the applications of this kind of high Curie temperature ferroelectric crystal under extreme conditions, and extra clue to synthesis of ferroelectric materials with tailored properties.
Application of 3D-RISM to Water Placement
Authors: Truchon Jean-Francois , Williams Chris , Drummond Michael , Labute Paul
Published: November 2015

Increasingly there is significant interest in understanding the behavior of water as it relates to ligand-receptor interactions. Ligand affinity and specificity appear to be influenced by the action of water molecules on the solvated ligand-receptor complex. As such, the ability to predict the location of water molecules is of significant importance. Here we apply 3D-RISM to elucidate the placement of water molecules given the solute 3D coordinates. A sum-of-Gaussians techniques is used to infer the water sites from the particle density calculated from 3D-RISM. The results of several computational experiments will be presented and discussed.
Charge density studies on 1:1 co-crystals of ethenzamide and saccharin
Authors: Mapp Lucy , Pitak Mateusz , Coles Simon , Aitipamula Srinivasulu
Published: November 2015

The study of multi-component crystals, as well as the phenomenon of polymorphism, both have relevance to crystal engineering. Obtaining a specific polymorph is crucial as different polymorphs usually exhibit different physical and chemical properties and often the origin of this behaviour is unknown. This is especially important in the pharmaceutical industry. Herein, we present results of comparative studies of an analgesic drug, ethenzamide and its co-crystals with saccharin. The co-crystalisation of ethenzamide (2-ethoxybenzamide, EA) with saccharin (1,1-dioxo-,1,2-benzothiazol-3-one, SAC) with a 1:1 stoichiometric ratio resulted in two polymorphic forms of the co-crystal. Form I crystallises in the triclinic P-1 space group, whereas form II crystallises in monoclinic space group P21/n. Previous crystal structure analyses on forms I and II revealed that in both polymorphs the primary carboxy-amide-imide heterosynthon is the same, however the secondary level of interactions which extends the hydrogen bond network is different. Form I consists of extended linear tapes via N-H···O hydrogen bonds, whereas form II is composed of stacks of tetrameric motifs including N-H···O hydrogen bonds and C-H···O interactions. These two forms of EA-SAC can be classified as synthon polymorphs at a secondary level of hydrogen bonding [1]. In our approach an accurate, high resolution charge density distribution analysis has been carried out to obtain greater insight into the electronic structures of both types of the EA-SAC co-crystals and relate differences in electronic distribution with their polymorphic behaviour. To describe the nature and role of inter and intra-molecular interactions in a quantitative manner, the Hansen-Coppens formalism [2] and Bader's AIM theory [3] approach have been applied.
Detection of vancancies by using XAS, is it possible? The case of ZnO
Authors: Guglieri Clara , Céspedes Eva , Prieto Carlos , Chaboy Jesús
Published: November 2015

The occurrence of high temperature ferromagnetism (HTFM) in transition-metal-doped ZnO systems has attracted much attention in the last years. In particular, the Mn–Zn–O system has been widely studied and large efforts have been aimed at finding Curie temperatures above room temperature (RT). However the origin of that magnetic behaviour has not been explained yet. While doubts rise about the role of the 3d cations, several types of defects, such as oxygen and zinc vacancies, as well as hydrogen, oxygen and zinc interstitials, have been proposed by different authors to induce HTFM [1]. Aiming at determine the exact type of defect that causes the HTFM in these systems several experimental tools, such as x-ray absorption spectroscopy, have been applied. However, based on similar experimental spectra, different authors report opposing conclusions regarding the nature of defects involved in the observed HTFM [2,3]. These results pose serious doubts about the real capability of XAS to determine the presence of vacancies in these systems and, consequently, to shed light on the origin of the magnetism in these systems. Here we report a XANES study at both Mn and Zn K-edges in Zn(0.95)Mn(0.05)O thin films prepared with different sputtering gases (pure Ar, Ar/N2 and Ar/O2). We have studied the local order around Mn in the films, by means of ab initio XANES calculations. During this study, a special emphasis has been paid to determine the role played by both vacancies and structural distortions associated with the substitution of Zn by Mn in the ZnO host. Our results indicate that XANES is not sensitive to the presence of randomly distributed vacancies. On the contrary, the observed modifications of the XANES spectra are associated with the structural distortion around Mn sites, which rules the magnetic behaviour of these Mn:ZnO thin films in terms of the different sputtering gases involved in the preparation.
How my Experiences at the MRC-LMB led to the Structure of the Ribosome
Authors: Steitz Thomas
Published: November 2015

Max Perutz's Dunham Lectures at Harvard in 1963, in which he showed the first atomic structure of a protein (myoglobin) that anyone in the room had ever seen, led to my working on the structure of carboxypeptidase A (CPA) (in the Lipscomb lab) before going to the MRC LMB in Cambridge. "Rapid" data collection on CPA in the mid-1960s was 5,000 reflections in a week, and now obtaining 2.7 Å resolution data on crystals with two 70S ribosomes in the asymmetric unit takes 5 minutes. Importantly, the LMB promoted creative and novel science because of its cooperative, interactive atmosphere where everyone interacted in the hall or over coffee, lunch or tea. This influenced how I have carried out science over the subsequent years. In the canteen, Crick, Brenner, Perutz, etc., would be interacting and talking with postdocs and students about asking important questions and solving scientific problems. It was a great place to learn, develop and use the most advanced methods in protein crystallography and apply them to explore the most interesting and significant questions in molecular biology. The importance of integrating structure and function in our research goals was made clear. My interactions in the Cambridge LMB led me to pursue the structural basis for understanding Crick's Central Dogma of Molecular Biology – DNA makes DNA makes RNA makes proteins. This resulted in our ultimately determining the structures of the ribosome and its various complexes.
Structure determination of submicron-sized porous materials by EM and XRD
Authors: Sun Junliang
Published: November 2015

Structure determination of submicron-sized porous materials is always a great challenge for widening their industrial application. There are a few reasons for this challenge, such as 1) their big unit cell dimensions cause serious peak overlapping in powder X-ray diffraction (PXRD); 2) typical disordered guest molecules in the big portion of pores lower the resolution; 3) their relatively low stability prevents an easy application of high resolution transmission electron microscope image (HRTEM) and STEM techniques. PXRD and electron diffraction (ED) techniques are complimentary for the structure determination of such materials. The PXRD technique gives very accurate intensities and the major difficulty for the structure determination from PXRD is the peak overlapping while there is almost no peak overlapping in ED since the single-crystal-like ED patterns can be obtained from nano-sized crystals. For the ED techniques, the intensities suffer severely from dynamical effects which make it less reliable for the structure determination in many cases. The combination of them can overcome both shortcomings and solve most difficulties in the structure determination of submicron-sized porous materials. Here we will use a few examples to demonstrate how this combination facilitates the structure determination, such as ITQ-37, PKU-16, PKU-3, ITQ51.
Analysis of Sr3-xCa1+xMn2CoO9 combining electron, X-ray and neutron diffraction
Authors: Boullay Philippe , Pérez Olivier , Raveau Bernard , Motin Seikh , Vincent Caignaert
Published: November 2015

The AxBX3 hexagonal perovskite-type compounds exhibit interesting magnetic properties such as complex magnetism or random spin chain magnetism[1,2]. Their structures are built up from infinite [BO3] chains consisting of alternating octahedral and trigonal prismatic units, separated by A infinite chains. Sr3-xCa1+xMn2CoO9 are belonging to this family of materials. X-ray powder diffraction patterns are collected for different Sr3-xCa1+xMn2CoO9 samples with different x values. Pattern matching analysis with the SG P-3 and the following cell parameters a=b=9.490(1)Å c=3xc'=3x2.57=7.732(1)Å reveals problematic groups of reflections; these reflections are shifted from one pattern to another one and, moreover, have positions preventing their indexation. Owing to the lack of spatial resolution and peaks overlapping in the powder data, the understanding of the present problem is quite impossible. Electron Diffraction Tomography (EDT) combined with Precession Electron Diffraction (PED) has been used for exploring the reciprocal space of the Sr3-xCa1+xMn2CoO9, x=0 sample. The slight deviations observed from the rational 1/3 c'* value is in agreement with the existence of aperiodicities. The structure of this family of materials has been then described using the super space formalism as a composite structure. The structural model is determined from the PED data integrated with PETS[2]; the first and second sublattices are referring to (Mn,Co)O3 and (Ca,Sr) structural parts respectively. This model is confirmed by the refinement of the X-ray powder diffraction data. Powder neutron diffraction data were then collected at PSI for different temperatures and different Sr3-xCa1+xMn2CoO9 samples. Using the previously refined model, a Co/Mn ordering is revealed thanks to the neutron scattering lengths of these two elements (see fig1). Finally, the treatment of the antiferromagnetic behavior observed bellow 25K is performed in the 4d approach using Jana2006[3].
Applying the Structure Correlation Principle to retro Diels Alder Reactions
Authors: Pool Brett , Goh Rachel , Roth-Barton Jesse , White Jonathan
Published: November 2015

The early stages of molecular rearrangements are often apparent in the crystal structures of molecules susceptible to that rearrangement. For example, if a particular bond is broken, or if a particular group migrates during the rearrangement, then deviations of bond distances and angles from their `standard values' along the reaction coordinate are often observed. This is the structure correlation principle,1 which holds provided the molecule exists in the ground state, in a geometry, which is similar to the transition state geometry for the reaction. In this geometry the frontier orbitals whose interactions facilitate the reaction, can mix in the ground state. This paper discusses the application of this principle to pericyclic fragmentation reactions related to the retro Diels Alder reaction, using low temperature X-ray structural analysis of a range of model substrates. The substrates can be classified on the basis of this data into three groups: (i) those that undergo a synchronous retro Diels Alder reaction, (2) those that undergo an asynchronous retro Diels Alder reaction, and (3) those that react via a 2-step process. Examples of molecules falling into these three categories are given below.
Control of Photochromism in Crystalline-State in Dual Photoisomeric Complexes
Authors: Sekine Akiko , Yamazaki Yuta , Johmoto Kohei , Uekusa Hidehiro
Published: November 2015

Photochromic materials have attracted attention in recent years, however, in situ control of the photochromic reactivities still challenging. In order to realize dynamic control of photochromic property in crystal, we designed and created new dual photoisomeric type cobaloxime complexes, in which the reactivity of photochromic ligand changes by contact with surrounding photoreactive ligands. In this study, salicylideneaniline derivatives (SAP) are used as photochromic ligands, and the relationships between their photochromic reactivity and structural changes induced by crystalline-state photoisomerization of alkyl group of cobaloxime complex were investigated. As a salicylideneaniline (SAP) type cobaloxime complex, (3-cyanopropyl)(N-(3,5-di-tert-butylsalicylidene)-3-aminopyridine)cobaloxime was successfully synthesized. In the crystal, the SAP moiety which had a twisted conformation (dihedral angle of rings, 30.0(6)0)showed the photochromism upon UV irradiation. Also the 3-1 photoisomerization of the 3-cyanopropyl group in the cobaloxime moiety occurred with retention of the single-crystal form upon visible light irradiation. After crystalline-state 3-1 photoisomerization of the alkyl group by visible light, the photochromic property was examined to show the lifetime of colored species became significantly longer than before the reaction. It would be explained that the reaction cavity around the SAP moiety was modified by solid-state photoisomerization of alkyl group of the surrounding cobaloxime complexes, which successfully enabled the control of the photochromism. Moreover, other several derivatives are investigated similarly and their results were discussed together.
Serotonin in different compounds: crystallographic and computational insight
Authors: Rychkov Denis , Boldyreva Elena , Kovalskii Viktor , Hunter Steven , Pulham Colin , Morrison Carole
Published: November 2015

Biologically active substances are in the focus of pharmaceutical and chemical research. Serotonin, one of the most common neurotransmitters, is widely studied in relation to its effect on humans from cellular to neurological levels. Although serotonin plays a key role in some biological processes, its chemistry and crystallography are not sufficiently understood. The aim of the present study was to crystallize serotonin adipate and creatinine sulfate monohydrate, determine their crystal structures, and analyze them in a comparison with other previously known serotonin crystal structures. Special attention was paid to the interrelation between the molecular conformation and crystalline environment. This issue was addressed using crystallographic and computational chemistry (DFT-D, MD) approaches. In our research was shown that the crystal structure of the creatinine sulfate complex significantly differs from what was previously determined. The conformation of serotonin in the new structure differs from serotonin conformations in all other known complexes, as well as from the most stable conformation, predicted by the adiabatic conformational analysis using quantum chemical calculations (DFT, MP) in different phases. This work has explicitly shown the influence of different interactions on serotonin molecular conformation in the crystalline state, described from a crystallographic and theoretical point of view. It has been previously demonstrated that salt formation in the presence of different anions produces variation in pharmacological, therapeutic and physic-chemical properties. This study has shown that alterations of the anion affects the molecular geometry of the bioactive substance and invite further investigation to rationalize the geometry changes. The work was supported by the RFBR Grants No.14-03-31866, 13-03-92704, Russian Ministry of Science and Education and RAS, Siberian Supercomputer Center SB RAS Integration Grant No.130, Edinburgh Compute and Data Facility
Se-N chemistry: Revisiting an old molecule in the design of novel compounds
Authors: Lock Nina , Matussek Julia , Stalke Dietmar
Published: November 2015

Chalcogenide chemistry is rich and diverse: The large variety of molecular sulfur and selenium compounds can be ascribed to their multiple stable oxidation states and large radius enabling high coordination. Sulfur-nitrogen chemistry is thoroughly explored and well-understood; polyimido sulfur species S(NR)n with charge m- (n = 2, 3, 4; m = 0, 2) are analogues of SOn molecules (with charge: m-) in which oxygen has been replaced by isovalent NR imido groups [1]. These compounds have been studied in depth and have been demonstrated to be versatile ligand systems which form multifaceted potentially catalytic metal complexes and compounds with lithium organics [2]. Selenium-nitrogen chemistry is comparatively less developed than sulfur-nitrogen chemistry despite of significant contributions to the field [3]. This may be ascribed to the rich redox chemistry of selenium in addition to its ability to polymerize, unfortunately none of these properties are easily controlled. A crucial parameter in the development of sulfur-nitrogen chemistry is attributed to the access to sulfur diimides S(NR)2 and sulfur triimides S(NR)3. Therefore, our starting point in exploring new directions of selenium-nitrogen chemistry was to revisit Se(NtBu)2 (tBu = tertbutyl), which has been used as ligand for metal complexes, but also discussed in large detail with respect to structural geometry and stability. Herein, we are presenting a study of selenium-nitrogen chemistry based on Se(NtBu)2.
Pressure tunablity in ReX4based SMMs; A magnetostructural study
Authors: Woodall Christopher , Lillo Francisco Jose Martinez , Míšek Martin , Prescimone Alessandro , Allan Dave , Brechin Euan , Kamenev Konstantin , Parsons Simon
Published: November 2015

Since the discovery of Single-Molecule Magnets (SMMs) in 1993 there has been extensive interest in understanding, developing and tuning the nature of magnetic interactions within SMMs with the intention of gaining greater insight into the nature of these interactions.[1] Typically this is done synthetically using variations in ligand geometry and co-ordination environment to vary magnetic behaviour. More recently it has been demonstrated that high hydrostatic pressure are also an effective mechanism for "tuning" properties such as magnetic susceptibility in a variety of SMMs.[2] The number of studies utilising high hydrostatic pressure to investigate molecular magnetism is extremely limited due to their inherent difficulty however we report a new study investigating the pressure tunabilty of Re(IV) based SMMs. 4d and 5d metal ions such as Re are of interest due their enhanced magnetic exchanges relative to their 3d analogues and Re(IV) based complexes are of particular interest. Previous studies into [ReX6]2-(X = Cl, Br and I) anions demonstrate significant antiferromagnetic coupling, not transmitted through chemical interactions but rather through weak Re-X...X interactions in the solid state which may be easily perturbed at high pressure. [3] Therefore we report an investigation into the tunability of magnetic susceptibility in a variety of [ReX4] based compounds using high pressure magnetic susceptibility measurements and correlate the results with structure observations taken from high pressure single crystal X-ray diffraction experiments. The effects of the removal of solvent trapped in the lattice using temperature and vacuum and the corresponding effect on magnetic behaviour and chemical structure are also reported.
A quick laboratory X-ray reflectometer for time-resolved observations
Authors: Kamezawa Chika , Voegeli Wolfgang , Hishinuma Wakari , Arakawa Etsuo , Matsushita Tadashi , Yano Yohko
Published: November 2015

The measurement of the X-ray reflectivity curve is a widely used method to obtain structural information about thin films, surfaces and interfaces. With conventional instruments, the reflectivity curve is measured sequentially for a range of incident angles, which takes a long time. A recently developed method using white synchrotron radiation can measure the whole curve at once [1, 2]. In this contribution, the adaption of this method to a laboratory characteristic X-ray source is presented. This will make it possible to do time-resolved or high-throughput measurements using standard laboratory sources. The basic idea of our method is to focus the divergent X-ray beam emitted from a point source with either a doubly-curved Si crystal monochromator or a bent-twisted Si crystal monochromator [1]. Instead of using the whole beam, however, only the fan-shaped beam from a diagonal line on the monochromator is focused onto the sample. This is realized by placing an inclined slit before the monochoromator. The beam reflected from the sample forms a line on a two-dimensional pixel array detector. For each horizontal position on the detector, the incident angle onto the sample, and therefore the momentum transfer, is different. The reflectivity curve for a range of momentum transfers can therefore be measured with a single detector exposure without moving the sample, monochromator or detector. Reflectivity curves from a silicon wafer sample measured by our method are compared with the conventional angle scan method in the figure. The reflectivity down to 10 to the -7th power can be obtained, because the background can be subtracted from the measured intensity. We will show an example of time-resolved (10 s) measurements of specular X-ray reflectivity curves. We will also discuss the momentum transfer range that can be measured simultaneously and factors limiting the resolution of the method.
Self-ordering on vicinal surfaces studied by 3D GISAXS measurements
Authors: Matringe Caroline , Thune Elsa , Guinebretière René , Babonneau David
Published: November 2015

Nanostructured systems made of islands deposited onto oxide surfaces have both fundamental and technological interests and are used in the field of electronic, linear or non-linear optic, and optoelectronic. The final properties of these systems depend on the shape and the size of nanoparticles and also on their organization. On this general framework, we aim at producing self-organized nanostructures using vicinal surfaces [1],[2]. Vicinal surfaces are obtained by cutting a single crystal with a small deviation of the surface normal with respect to a crystallographic plane leading to a surface with terraces separated by steps. Suitable templates for the growth of self-organized nanostructures are created thanks to the re-arrangement of the steps during thermal treatment (step bunching). Different types of nanostructured surfaces can be elaborated and used as templates since the substrates exhibit a one-dimensional (1D) or two-dimensional (2D) periodic patterns (fig. 1a). The surface morphology and the periodicity can be tuned with the thermal treatment parameters (i.e. annealing time, temperature and atmosphere) and also with the sample parameters (i.e. miscut and azimuthal angles). Ordered stepped oxide surfaces are characterized ex-situ after each treatment on a laboratory scale by Atomic Force Microscopy (AFM), which provide a direct image of the surface morphology (step height, step curvature, terrace width...) over a small probed area (a few µm2). Quantitative analysis of the surface morphology has been studied by grazing incidence small angle scattering using a specific set-up implemented recently onto the BM02 beamline at ESRF (Grenoble, France). Prior to the SAXS measurements, the samples were strictly oriented according to the primary beam direction using a 3-axis sample holder. 3D reciprocal space maps around the (000) node were then recorded onto a 2D pixel detector through 3600rotation of the samples around the azimuthal angle. Modelling of 2D sections of the (000) reciprocal space node were realized using the FitGISAXS software [3]. Typical experimental and calculated maps are reported fig. 1b and 1c. We demonstrate that the 2D ordered surface is consistent with a rectangular centred periodic lattice decorated by truncated tetrahedrons (see fig. 1d).
Realtime X-ray reflectometry to see changes at buried interfaces
Authors: Sakurai Kenji , Mizusawa Mari , Stoev Krassimir
Published: November 2015

X-ray reflectometry is powerful in determining internal structure of multilayered thin films, such as thickness and density of each layer, as well as the roughness of surface and interfaces [1]. The measurement requires some precise angular scans near the critical angle with monochromatic parallel X-rays, and therefore it has not been thought that the technique is basically suitable to see changes. However, even without any angular scans, it is possible to obtain essentially the same data by using wide angular dispersion of the incident X-ray beam. The principle is basically known as Naudon's pioneering concept [2]. The system has been improved further by employing a monochroator, which was not used by Naudon's work. A multilayer monochromator was placed at very narrow limited space between a rotating anode X-ray source and the sample stage [3]. Use of a fast Si strip detector also contributed to improve the time-resolution. One can obtain an X-ray reflectivity curve with 4.5 decades even in 1 sec. It is possible to measure the curve down to 10-6, if 20 sec accumulation is allowed. Another advantage of the present instrument is fairly wide angular divergence, which ensures simultaneous data collection for 2 deg range. One of our recent successful applications of this method is the measurement of thermal expansion factor of the polymer thin film. It was also possible to see melting and freezing surfaces. In the presentation, such practical application will be demonstrated, in addition to the detailed description of our instruments.
Local Symmetry Breaking in the High Temperature Regime of SnTe
Authors: Knox Kevin , Bozin Emil , Malliakas Christos , Kanatzidis Mercouri , Billinge Simon
Published: November 2015

The term emphanisis [1] has been coined to define the appearance of local off-centering displacements of ions from a high-symmetry ground state on warming, as recently discovered in PbTe [2]. Such a phenomenon is unusual because, in the canonical view of structural transformations, a low-symmetry ground state evolves into a higher symmetry state on warming. Although it is not uncommon for remnants of a low-symmetry phase to appear as spatial fluctuations at high temperature, the emergence of a locally broken symmetry state from a high symmetry ground state is quite rare. Emphanisis may be behind some long-known, but poorly understood anomalies seen in the lead chalcogenides. However, the origin and nature of emphanisis are still the subject of controversy. Several explanations for emphanisis have been suggested, including a simple response to an underlying anharmonic potential [3], a dynamic ferroelectric-like off-centering [2], and a temperature-dependent competition between ionicity and covalency [1], but an understanding remains elusive. In this talk I will report on atomic pair distribution function (PDF) measurements of the lead-free compound SnTe, which is isostructural to PbTe at high T but with a ferroelectric phase below Tc ~ 100K. Our data show that SnTe also exhibits an emphanitic response, but with an onset temperature well above Tc and a symmetry that is distinct from that of the ferroelectric phase. Taken together these results suggests that the emphanitic and ferroelectric responses are quite distinct.
The crystal structure of the active domain of AAPP, a powerful anti-coagulant, in complex with an antibody
Authors: Sugiyama Kanako , Iyori Mitsuhiro , Sawaguchi Asuka , Akashi Satoko , Tame Jeremy , Yoshida Shigeto , Park Sam-Yong
Published: November 2015

Blood clotting is a vitally important process that must be carefully regulated to prevent blood loss on one hand and thrombosis on the other. Severe injury and hemophilia may be treated with pro-coagulants, whereas risk of obstructive clotting or embolism may be reduced with anti-coagulants. Anti-coagulants are an extremely important class of drug, one of the most widely used types of medication, but there remains a pressing need for novel treatments however as present drugs such as warfarin have significant drawbacks. Nature provides a number of examples of anti-coagulant proteins produced by blood-sucking animals, which may provide templates for the development of new small molecules with similar physiological effects. We have therefore studied an Anopheles anti-platelet protein (AAPP) from a malaria vector mosquito, and report its crystal structure in complex with an antibody. Overall the protein is extremely sensitive to proteolysis, but the crystal structure reveals a stable domain built from two helices and a turn, which corresponds to the functional region. The antibody raised against AAPP prevents it from binding collagen. Our work therefore opens new avenues to the development of both novel small molecule anti-clotting agents and anti-malarials.
Structural & biochemical study of peroxiredoxin from Candidatus liberibacter asiaticus
Authors: Singh Anamika , Kumar Pravindra , Kumar Sharma Ashwani
Published: November 2015

Candidatus Liberibacter asiaticus is a fastidious prokaryotic α-proteobacterium that has not been cultured as yet. It is the causative agent of Citrus Huanglongbing (HLB) is a disease that infects citrus plants causing huge losses to the citrus industry. The plants employ a variety of defense mechanisms to combat the pathogen attack which mainly involves the formation of reactive oxygen species (ROS) mainly hydrogen peroxide, peroxynitrite and organic hydroperoxides. The microbe on the other hand has antioxidant proteins that counter the reactive oxygen species. Peroxiredoxin (Prx) which is known to play a crucial role in peroxide detoxification is a super family of one of such antioxidant proteins. In this work, we have determined the crystal structure of Bacterioferritin Comigratory Protein (BCP) that belongs to 1-Cys Prx enzyme having peroxidatic/sulfenic acid cysteine (C-47) but lacks the resolving cysteine. Furthermore, we are investigating structural aspects to gain insight into the binding of different peroxide substrates at the active site. Site directed mutagenesis has been done to introduce the non-conserved resolving cysteine to study its effect on peroxidase activity in both wild type and mutant form. Biochemically, both BCP 1-cys and BCP 2-cys have shown peroxidase activity. DNA protection activity against oxidative damage and cell-line based assays has implicated its protective role towards the hypoxic condition of cells. Hence, the protein becomes a lucrative target for ligands which might be potential antimicrobials.
Virtual Screening of Histone Lysine Demethylase(JMJD2) identifies new inhibitors
Authors: Korczynska Magdalena , Le Daniel , Gregori-Puigjané Elisabet , Younger Noah , Krojer Tobias , Tumber Anthony , Oppermann Udo , Galonić Fujimori Danica , Shoichet Brian
Published: November 2015

The JmjC domain-containing proteins are hydroxylases that confer posttranslational modifications on histone tails, by removing methylation marks on methylated lysine residues. This serves to either promote or repress gene transcription. The JMJD2A-D family members include the enzyme Jumonji domain 2C (JMJD2C), which specifically demethylates di- and trimethylated histone H3 at Lys 9 or Lys 36.[1] Dysregulation of JMJD2C has been implicated in prostate, colonic, and breast cancer as the demethylase can modify the expression levels of oncogenes.[2] The goal of the present study was to identify potent and selective small-molecule inhibitors of JMJD2C, to be used as chemical biology tools to further investigate the role of JMJD2C in cell proliferation and survival. Using high-resolution crystal structures of the JMJD2 subfamily members as templates, we have performed a small molecule virtual docking screen. From the ~3 million molecules that were docked, this experiment identified 21 compounds as possible leads. These compounds were tested against JMJD2C in enzymatic assays and here we report an overall hit rate of 76%, with 8 compounds demonstrating an IC50 of 176μM to 1.18μM. A molecule containing a salicylate core was selected as a candidate for optimization and thus far we have completed several rounds of iterative target-specific compound docking, hybrid molecule design, compound synthesis and in vitro characterization. Notably, our method demonstrated a substantial increase in potency when we linked two docked fragments together and further derivatized this new scaffold, through which we have successfully derived a 65nM inhibitor of JMJD2C. A compound representing the inhibitor scaffold has been co-crystallized with JMJD2A to a resolution of 2.4 Å. In the crystal structure each asymmetric unit contains two JMJD2A monomers, each bound to a single inhibitor molecule. This complex-structure superposes well with the docked pose for the hybrid series of compounds. We are now focusing our efforts on identifying an inhibitor that is selective for the JMJD2 family over other JmjC domain-containing proteins.
Structural basis for the peptidoglycan recognition by Helicobacter pylori Csd4
Authors: Kim Hyoun Sook , Han Byung Woo , Lee Byung Il , Suh Se Won
Published: November 2015

Helicobacter pylori infection causes a variety of gastrointestinal diseases including peptic ulcers and gastric cancer. The colonization of this bacterium in the gastric mucosa is required for the survival in the stomach. Its colonization of the gastric mucosa of human stomach depends on its motility, which is facilitated by the helical cell shape. In H. pylori, crosslinking relaxation or trimming of peptidoglycan muropeptide affects the helical shape. Among several cell shape-determining peptidoglycan hydrolases identified in H. pylori, Csd4 is a Zn2+-dependent D,L-carboxypeptidase that cleaves the bond between the γ-D-Glu and mDAP bond of the uncrosslinked tripeptide of peptidoglycan (L-Ala-γ-D-Glu-mDAP) to produce L-Ala-γ-D-Glu dipeptide and mDAP, promoting the helical cell shape. Inhibition of D,L-carboxypeptidase activity of Csd4 may represent a novel therapeutic approach. We report here the crystal structures of H. pylori Csd4 in three different states: the ligand-free form, the substrate-bound form, and the product-bound form. H. pylori Csd4 consists of three domains: an N-terminal D,L-carboxypeptidase domain, a novel β-barrel domain, and a C-terminal immunoglobulin-like domain. Our ligand-bound structures provide structural basis of peptidoglycan recognition by D,L-carboxypeptidase. H. pylori Csd4 recognizes primarily the terminal mDAP of the tripeptide substrate and undergoes a significant structural change upon binding either mDAP or mDAP-containing tripeptide.