bluuebunny/crossref_metadata_2025 huggingface dataset:
CCP4: a resource for macromolecular crystallography
Authors: Ballard Charles , Keegan Ronan , Krissinel Eugene , Lebedev Andrey , Uski Ville , Waterman David , Wojdyr Marcin
Published: November 2015

CCP4 has been serving the software needs of the protein crystallography community for more than 30 years. In this time the CCP4 Suite of software has been refined through contributions from some of the leading developers in the field of protein crystallographic software and the feedback of both expert and novice users. Today it is a highly comprehensive suite, providing tools and packages covering all aspects from data collection through to structure deposition. Here we will present details of the latest release series of the Suite, version 6.4. This release brings updates to many of the key elements in the Suite. The most obvious of these is the integration of the rolling updates mechanism. This is used to distribute timely fixes, update existing programs and introduce new functionality to users of the suite. Recent updates have seen updates to major programs such as phaser and imosflm/mosflm, and the introduction of a major overhaul of the Experimental Phasing pipeline Crank. An overview is given of the operation behind the updates and releases, including the jhbuild system, repositories and testing, the availability of nightly builds, and work towards the next major release of CCP4. This will see the integration of the CCP4MG package, along with preparations for the introduction of the long awaited CCP4i2.
Tetraphenylphosphonium Salts for Small Molecule Capture
Authors: Robertson Katherine , Murphy Luke , Clyburne Jason
Published: November 2015

Tetraphenylphosphonium salts are useful tools for capturing (and crystallizing) small molecules. The packing of the cations in such salts leads to channels or cavities suitable for trapping of the small molecule by the anion. For example, we have prepared the complex salts [PPh4][SO2X] (X = Cl, Br, I) through the exposure of solutions of [PPh4]X to an atmosphere of SO2. Churakov et al. have reported the preparation of [PPh4]X·nH2O2 (X = Cl, Br; n = 0.98–1.90) after trapping hydrogen peroxide using the precursor halide salts (1). Envisioning a similar result, a concentrated solution of [PPh4]CN·xH2O was exposed to an atmosphere of CO2. Colourless crystals were isolated and characterised as [PPh4][NCCO2] using crystallographic and spectroscopic techniques. The packing of the ions in the product, in the tetragonal space group I-4, is similar to that observed in many other simple [PPh4]X salts, where X = Br, I, SCN, OCN, N(CN)2, etc. Solution of the crystal structure was complicated by the high symmetry and disorder in the anion, with only three unique atoms being necessary for its characterization. Thus the utility of our chosen cation can also become a hindrance. Crystals can usually be grown and data obtained but structure solution is not a certainty. For example, the structures of [PPh4]CN·xH2O have not been reported, likely because of the rapid spinning of the anions in the cation framework, even though they are hydrogen bonded to the water which is clearly visible. Similarly, we have data collected for the products from a number of related reactions, [PPh4][CN]·xH2O + PhC(O)F, [PPh4]F + SO2, [PPh4]X (X = Cl, Br, I, CN, N3) + CS2, and can clearly identify the cation in the unit cell. However, elucidation of the structures of the anions has not been possible. It is hoped that this presentation will engender discussion of possible solutions to the observed disorder problems.
Tetrakis(μ-2-phenylacetato-κ2O:O′) bis{(DMSO κO′)]copper(II)}(Cu-Cu)]
Authors: Benslimane Meriem , Kheira Redjel Yasmine , Denes Georges , Merazig Hocine
Published: November 2015

Carboxylate groups may interact as bridging ligands with divalent transition metals present in biological environments, thereby altering the bioavailability of drugs. Moreover, it is well known that many complexes of divalent transition metals are capable of catalyzing the hydrolysis of RNA (Stem et al., 1990; Kimura, 1994). The coordination chemistry of Cu2+ complexes bridged by phenylacetate has been reported. We have found only two reports of a dinuclear Co2+ complexes, namely tetrakis (phenylacetato)bis[(quinoline-N)-cobalt(II)](Cui et al.,1999),μ-aqua-κ2O:O-di-μ-phenylacetato-κ4O:O′-bis[(1,10-phenanthroline-κ2N,N′) (phenyl acetato-κO)cobalt(II)](Kong et al., 2005) and dinuclear Cu2+ complex, namely tetrakis (phenylacetato)bis-[(N,N-dimethylformamide)copper(II)], in which all phenylacetate groups are in bidendate bridging modes. In this presentation, the crystal structure of a new dimeric complex obtained by reaction of phenylacetic acid with copper(II) acetate is described. Each Cu(II) atom is six-coordinated by five O atoms from carboxylate groups of the phenylacetate and DMSO ligands and is completed by a Cu-Cu bond in a strongly distorted octahedral coordination, in which an inversion center is located at the mid-point of the Cu-Cu bond with a Cu...Cu distance of 2.6321(4) Å. This is longer than the 2.251(2)Å distance found in the polymeric complex [Cu2(C8H7O2)4]n. However, it is similar to the 2.6414(8) Å and 2.6261(8)Å distances found in the complex [Cu2(C8H7O2)4(C3H7NO)2] (Kong et al., 2005). The Cu-O phenylacetate bond length lies in the range 1.9644(14) to 1.9734 (14) Å and the Cu-ODMSO bond length is 2.1319(13) Å.
Crankshaft chains of LEP cations as a solution to the cation size misfit
Authors: Makovicky Emil , Topa Dan
Published: November 2015

In Pb-As and Pb-Sb sulfosalts, columns of large coordination prisms of Pb combine with intervening slabs of As- or/and Sb coordination polyhedra. The LEP of these elements dictate the configurations resembling SnS (especially for As) or inflated PbS (especially for Sb). The size misfit of cation polyhedra forces the short As-S and Sb-S bonds to form crankshaft chains. In the homologues with thicker slabs, parallel crankshaft chains and incorporation of Pb in the slabs compensate for the misfit. In the low homologues, N = 3 for sartorite series and N = 4 for andorites, the misfit becomes critical and requires special arrangements. In sartorite (~PbAs2S4), two subsets of parallel short crankshaft chains in a slab are (approximately) mirror-related via two contacts. One contact has a missing S atom with valence compensation by Tl; the other one differs between the two structurally analyzed varieties, sartorite (9a) [1] and sartorite (11a) [new], which are type structures for two homologous subseries: (13a; 9a;5a) and (15a;11a;7a;3a). Structures of andorites VI and IV(~PbAgSb3S6) [2,3], and arsenquatrandorite [new] allow to construct a predictive scheme of zig-zag crankshaft chain arrangement. The 4c superstructure of andorite (IV) contains simple zig-zag sequences of As3S7 chains; in 6c andorite (VI) parallel and perpendicular chains alternate. Andorite (VI) unites, in one slab, two different stackings of perpendicular chains which are present, as separate 3c intervals, in two adjacent slabs in andorite (IV). An additional 1c interval gives the 4c structure. Further varieties, such as 10c roshchinite, are derived from these unit sequences. The fourfold varieties either have slight surplus of Pb or As replaces a part of Sb (arsenquatrandorite).
Synthesis and Structure determination of a new interrupted zeolite PKU-14
Authors: Liang Jie , Su Jie , Wang Ying , Inge A. Ken , Zou Xiao , Lin Jian , Sun Jun
Published: November 2015

Zeolites have been extensively studied over many years due to their widely applications in catalysis, ion exchange, adsorption, and separation.[1] Knowing the structure of zeolite is important for understanding their properties and predicting possible applications of such materials. Structure determination of zeolites has remains challenging, as submicro- and nano-sized crystals are often obtained. Here, we elucidate a novel germanate-based zeolite PKU-14 with a 3D 12*12*12-ring channel system. The structure was solved by combing high-resolution PXRD, rotation electron diffraction method, NMR and IR spectroscopy. Ordered Ge4O4 vacancies inside the [46612] cages has been found in PKU-14, where a unique water dimer was located at the vacancies and played a structure-directing role.
Crystal structure analysis of LiN(DxH1-x)4SO4by neutron diffraction
Authors: Kim Shin Ae , Lee Chang-Hee
Published: November 2015

The crystal structure of Li(ND4)SO4 was analysed by neutron diffraction method. The crystal is a partially deuterated Li(NH4)SO4 and one of the ferroelectric materials with hydrogen atoms. The crystal is orthorhombic at room temperature with lattice parameters of a=5.2773(5) Å, b=9.124(2) Å, c=8.772(1) Å and Z=4. Neutron intensity data were collected on the Four-Circle Diffractometer (FCD) at HANARO in Korea Atomic Energy Research Institute. The structure was refined by full-matrix least-square to final R value of 0.049 for 745 observed reflections by neutron diffraction. All atomic positions of four hydrogen atoms at NH4 and the occupation factors of D and H were refined. From these results we obtained the average chemical structure of this sample, LiND3.05H0.95SO4. Five years later, neutron intensity data were collected and analysed once more with same crystal. The crystal is orthorhombic but with different lattice parameters, or hexagonal. We will report and discuss these results in this presentation.
Radiation Damage in Chemical Crystallography
Authors: Horton Peter , Coles Simon , Pitak Mateusz , Tizzard Graham , Wilson Claire
Published: November 2015

Although crystals suffering radiation damage is a well-known and studied phenomena for macromolecular crystallography[1], as far as we are aware there appears to be no such published work relating to chemical crystallography. However, there are numerous anecdotal accounts of disintegrating crystals and resolution progressively dropping off that have been ascribed to radiation damage. Since the start of operations on the small molecule synchrotron beamline I19[2] at Diamond Light Source, there have been multiple comments from several users observing sample damage in the beam. The UK National Crystallography Service[3] handles a wide variety of samples and a number of these have experienced radiation damage. In order to understand the causes and symptoms of this effect in greater detail some controlled experiments were performed. A series of experiments were conducted on crystals that were known to undergo radiation damage in order to determine some quantification of the effect. Additionally the aim is to understand what one might be able to do to mitigate against the damage caused and determine whether the effects observed are similar to those of macromolecular crystallography. The effects of varying the collection temperature, overall dose, dose rate and wavelength of X-ray used were all tested and normalised for each sample. Samples where radiation damage has been observed were chosen and were also required to be air stable and preferably not suffer from solvent loss, in order to minimize problems of non-reproducibility. Those chosen to probe this effect were: 1. A gold complex – has potential to suffer heavily from absorption effects. 2. A nickel complex with significant solvent water – this could to some extent mimic the behaviour exhibited by proteins. 3. A small organic compound – an example of unexpected decay. The poster will summarise the results of these experiments and contrast them with data collected on a high intensity rotating anode laboratory source.
Experimental and DFT studies of Mtpnm
Authors: Akbal Tufan , Agˇar Erbil , Gümüş Sümeyye , Erdönmez Ahmet
Published: November 2015

Experimental and DFT studies of (Z)-N-[3- Methoxy -5-(trifluormethyl) phenyl]-1-(5- nitrothiophene -2- yl)methanamine Tufan Akbala, , Erbil Agˇarb, Sümeyye Gümüşb and Ahmet Erdönmeza aDepartment of Physics, Ondokuz Mayıs University, Samsun, Turkey . b Department of Chemistry Ondokuz Mayıs University, Samsun, Turkey E-mail: erdonmez@omu.edu.tr The title molecule, C13H12N2O3F3S, is nonplanar with an interplanar angle of 23.94(23)0 between the benzene and thiophene rings. In the crystal there exist only weak intermolecular C–H...O interactions and π...π interactions between the benzene rings and thiophene rings [centroid–centroid distance= 4.892(3) A0]. The length of the C9=N2 double bond is 1.2534 A0. This value agrees well with the analogous bond reported elsewhere. [1,2]. The theoretical calculations were performed with Gaussian03W software. In calculations, the stable structure geometries of the isolated molecules in the gas phase was investigated under the framework of Density Functional Theory (DFT). In order to find the stable molecular geometries, the global minimum scanning were performed on the potential energy surfaces and some properties of molecules such as charge densities, dipole moments and frontier orbitals (HOMO and LUMO) from B3LYP/6-31G(d) calculations. REFERENCES: [1] Akbal T., Agˇar E., Erdönmez A., 2012. Acta Cryst. E68, 2673. [2] Aygün M., Işık Ş., Öcal N., Nawaz T.M., Kaban Ş. & Büyükgüngör O., 1998. Acta Cryst. C54, 527-529. Keywords: tautomerism, crystal and molecular structure, density functional theory(DFT) studies
Utilising Crystallographic Data to Better Design Solid Forms
Authors: Dix Ina , Woollam Grahame , Chan Stephen
Published: November 2015

Understanding crystalline forms in the pharmaceutical industry is very essential as the majority of small molecule drugs are delivered to patients in a crystalline state. Chemical and physical solid-state properties of an active pharmaceutical ingredient (API) such as stability, solubility, reactivity and bioavailability can be influenced by the formation of salts, anhydrous forms, hydrates, solvates, polymorphs and cocrystals. It is clear therefore, that an insight into molecular arrangements including existing interactions is required for effective drug development. The status quo to obtain experimental three-dimensional solid-state information is by x-ray structure analysis. One clear advantage of this method is its wide spread use due to the relative ease of use in a standard analytical laboratory and cost (compared for example to neutron diffraction). The Cambridge Structural Database (CSD) [1] consolidates the information of hundreds and thousands of determined crystal structures and offers plenty of opportunities to investigate solid-state properties more in detail. In order to exploit the readily available knowledge, a variety of informatics tools such as Full Interaction Maps (FIMS) [2] or Hydrogen Bond Propensity (HBP) [3] calculations were developed within the Crystal Form Consortium (http://cfc.ccdc.cam.ac.uk), a collaboration of people from leading industrial companies and experts from the CCDC. We will present how the CSD knowledge in combination with informatics tools can support effective drug development in a pharmaceutical environment.
When crystallography can use help from tin-119 Mössbauer spectroscopy
Authors: Denes Georges , Madamba M. Cecilia , Merazig Hocine , Muntasar Abdualhafed
Published: November 2015

Crystallography, the most powerful method for obtaining structural data, can benefit from help from other techniques. In this work, 119Sn Mössbauer spectroscopy was used to assist crystallography, for finding the tin(II) positions in the unit-cell and determine a tin(II) coordination in agreement with both the diffraction data and the tin electronic structure. Even high quality single crystal data do not guarantee that the right solution will be obtained. A first attempt at the structure of α–SnF2 yielded the tin positions with very reasonable R and Rw residuals, 0.23-0.25. However, the fluorine positions could not be found (Bergerhoff, 1962). After many other attempts, the full crystal structure was finally solved 14 years later (R.C. McDonald et al. 1976). The difference in the tin position with the initial solution (1962) was that, in the latter, half of the tin atoms were on special sites, however, the tin sublattice was identical. Because the tin sites in the initial solution gave very reasonable residuals, 14 years of hopeless efforts were wasted. The presentation will show that this could have been avoided using 119Sn Mössbauer spectroscopy. This was possible since the spectrum had already been recorded (A.J.F. Boyle et al., 1962). Mössbauer spectroscopy can also help determine the tin coordination, when combined with powder diffraction data, in case of disordered structures. The presence of tin(II), disordered with a metal ion in cubic coordination, when diffraction shows there is no lattice distortion and no superstructure, suggests that tin has also a cubic coordination. This would require the tin lone pair to be non-stereoactive; however Mössbauer spectroscopy shows it is stereoactive.
The New wwPDB Deposition and Annotation System
Authors: Westbrook John , Feng Zukang , Gore Swanand , Lawson Cathy , Oldfield Tom , Quesada Martha , Sen Sanchayita , Velankar Sameer , Yang Huanwang , Young Jasmine
Published: November 2015

In anticipation of continued growth in the number, size and complexity of the structures that are being studied and deposited in the PDB and EMDB, the Worldwide Protein Data Bank (wwPDB) has developed a new system for deposition and annotation of structural data. The new wwPDB Deposition & Annotation (D&A) system offers a single entry point for depositors from around the world to deposit X-ray, NMR, 3DEM data, receive detailed validation feedback, and preview annotations, all prior to submission. The system will assign not only PDB identifiers upon submission, but also EMDB and BMRB identifiers for 3DEM and NMR data, respectively. Furthermore, the new system is used at all wwPDB processing sites around the globe. After deposition, wwPDB annotators use the system for sequence annotation, ligand annotation, additional structure analysis and validation, and review. Validation functionality implements recommendations from the wwPDB X-ray Validation Task Force and produces a structure validation report for depositor review and submission to scientific journals. Depositors will have the option to use the new system or one of the legacy deposition tools (ADIT, AutoDep) through the end of 2014. At that time, the legacy tools will stop accepting new entries, and will only be available for a limited period of time to complete in-progress deposition sessions. An important feature of the new deposition system is its ability to accept and produce data in PDBx/mmCIF format, which has no limitations in the size or complexity of structures that can be represented. The PDBx/mmCIF Working Group, consisting of software developers from CCP4, Global Phasing Ltd., Phenix, and the wwPDB, have adapted structure determination software packages to produce PDBx/mmCIF format files suitable for deposition. The new wwPDB deposition and annotation will produce more consistent and higher quality archive entries, and will improve the efficiency and throughput of deposition and annotation. The modular design of the system will facilitate incorporating new functionalities and support for hybrid and other methods in the future. wwPDB members are RCSB PDB (supported by NSF, NIH, and DOE), PDBe (EMBL-EBI, Wellcome Trust, BBSRC, NIGMS, and EU), PDBj (NBDC-JST) and BMRB (NLM).
The role of Ndc10 in budding yeast kinetochore establishment
Authors: Perriches Thibaud , Singleton Martin
Published: November 2015

The kinetochore is a large assembly of protein that connects sister chromatids to the mitotic spindle during mitosis. It both transmits microtubule (MT) tension and controls the mitotic checkpoint. The kinetochore forms onto the centromere (CEN), a chromosomal locus classified in two groups varying dramatically in composition. In the vast majority of eukaryotes, regional CENs are long arrays of repetitive non-conserved DNA hosting multiple MTs nucleation. On the contrary, in a small group of yeast related to S.cerevisae, point CENs are characterised by a conserved short sequence hosting a single MT. Despite this difference, all CENs share a similar establishment mechanism relying on the loading of the CENP-A histone-like protein by the chaperone Scm3. This mechanism is ambiguous in regional CENs, whereas in point CENs it solely relies on the CBF3 complex binding to the centromeric DNA elements III (CDEIII). CDEIII is point CEN most conserved sequence and point mutants show totally impaired kinetochore formation. CBF3 is composed by the essential Ndc10, Cep3, Ctf13, and Skp1. Ctf13 and Skp1 link the CBF3 formation to the cell cycle, whereas Cep3 and Ndc10 bind to the CEN. Before our study, Ndc10's role was speculative but it was known that its primary function is to recruit CENP-A after S-phase through interaction with the histone chaperone Scm3. In this study, we have solved the X-ray structure of Ndc10 N-terminal domain (NTD) at 1.9 Å resolution. Unexpectedly, Ndc10 NTD fold belongs to the tyrosine recombinase/α-integrase family, which alters DNA structure through a conserved catalytic tyrosine. Interestingly, Ndc10 has lost the catalytic tyrosine but, as we suspect, might alter the CEN DNA winding, something possibly critical for CENP-A loading. By analysing the recombinase fold and by mutating key residues, we described Ndc10 NTD DNA-binding motifs. This finding offers new insights into kinetochore evolution and the adaptation of a well-studied protein fold to a novel role.
Structural basis for the interaction of HSP90 with R2TP and TTT complexes
Authors: Pal Mohinder , Morgan Marc , Phelps Sarah , Roe Mark , Parry-Morris Sarah , Downs Jessica , Polier Sigrun , Pearl Laurence , Prodromou Chrisostomos
Published: November 2015

Assembly and regulation of snoRNPs, RNA polymerases, PI3-kinase-like kinases and the chromatin remodelling complexes, depends on both the TTT complex (Tel2-Tti1-Tti2) and the R2TP complex (Rvb1-Rvb2-Tah1-Pih1p in yeast and RuvBL1-RuvBL2-RPAP3-Pih1D1 in metazoa), which provide the direct connection to Hsp90. Previous studies have shown that the R2TP complex recruits client proteins to Hsp90 for their folding and assembly. In this study, we have determined the crystal structures of three complexes: Hsp90-Tah1-Pih1p, Hsp90-Tah1, Hsp90-RPAP3 (TPR1 and TPR2 domains of RPAP3, each in complex with Hsp90). Tah1 was shown to have an unusual TPR domain, composed of only five α-helices instead of the more usual six or seven. As expected, Tah1 TPR domain binds to the conserved MEEVD motif at the C-terminus of HSP90. In contrast, the C-terminal region of Tah1 is unstructured in the apo form but wraps around the CS domain of Pih1p, thus becoming ordered in the complex, and bridging the interaction between Hsp90 and Pih1p. We show a different modus operandii of Tah1-Hsp90 binding in yeast relative to RPAP3-Hsp90 interactions in metazoa. Finally, we present the crystal structure of the Pih domain of Pih1D1 bound to a phosphopeptide of Tel2 that reveals a novel phosphopeptide-binding domain specific for a subset of CK2 phosphorylation sites. Together these structures define the basis by which the R2TP complex connects the Hsp90 chaperone system to the TTT complex.
Molecular details of sugar biosynthesis in mycobacteria
Authors: Fraga Joana , Silva Alexandra , Maranha Ana , Mendes Vitor , Alarico Susana , Empadinhas Nuno , Pereira Pedro , Macedo-Ribeiro Sandra
Published: November 2015

Despite the research efforts of decades, Mycobacterium tuberculosis is still in the origin of 1.3 million deaths annually (WHO, Tuberculosis, 2013) and is estimated to infect 2 billion people worldwide. The currently available antimicrobial therapies are aimed at only a few molecular targets and the growing number of strains resistant to multiple drugs drives an urgent need for the identification of novel pathways and new points for therapeutic intervention. Although the sequence of the M. tuberculosis genome has been known for more than a decade, there is still no function assigned to many of its genes. Among M. tuberculosis ORFs with known function, more than 1% encode enzymes involved in glycosidic bond synthesis. Since the increased resilience of M. tuberculosis is, to a great extent, due to its complex, polysaccharide/lipid-rich and thus unusually impermeable cell wall, we became interested on the functional and structural characterization of mycobacterial enzymes involved in biosynthetic pathways for cell wall components. Over the last few years, we have carried out the functional and structural characterization of novel enzymes in the sugar biosynthesis metabolic routes from thermostable and mesostable mycobacteria [1-3]. Recently, we characterized functionally two enzymes from M. vanbalenii and M. hassiacum whose orthologs in M. tuberculosis are essential for growth, and determined their three-dimensional structures to high resolution (1.2-1.5 Å), allowing the thorough elucidation of their intricate nucleotide and sugar specificities. These experimental molecular models will be presented as examples of frameworks for the rational design of novel anti-mycobacterial drug leads. (Funded by national funds through FCT and by EU-FEDER funding through COMPETE (grants FCOMP-01-0124-FEDER-014321, FCOMP-01-0124-FEDER-014187, FCOMP-01-0124-FEDER-028359) and through ON.2-O Novo Norte, under QREN (grant NORTE-07-0124-000002 - Host-Pathogen Interactions).
Nitric oxide synthase and possible redox partners in Bacillus cereus
Authors: Lofstad Marie , Hersleth Hans-Petter , Røhr Åsmund , Hammerstad Marta , Andersson K.
Published: November 2015

Nitric oxide synthase (NOS), a BH4-dependent heme-enzyme, is the only enzyme that specifically produces NO in mammals. NO is produced by the NOS homodimer in two multistep reaction cycles involving electron transfer from a reducing domain to the heme active site. The importance of NO in mammals is due to its function in signalling, vasodilation and immune response. Some bacterial species also contain NOS-encoding genes, but these bacterial NOSs are differently organized – they contain no reducing domain – and their functions and mechanism are not fully resolved [1]. Bacterial NOSs are potential drug targets, because of their role in protection against antibiotics and oxidative stress in some pathogenic bacterial species (e.g. Bacillus anthracis) [2]. Flavodoxins (Flds) have been shown to be relevant redox partners for bacterial NOSs [3], but the specificity of the interaction between NOS and Flds remains poorly understood. We have investigated the NOS protein system in Bacillus cereus, whose genome encodes NOS and two Flds, by combining crystallographic and spectroscopic methods. So far the structures of the two Flds have been solved to 0.98 Å and 2.75 Å resolution, while NOS has been solved to 2.9 Å resolution. An important part of the study has been to investigate the effect of synchrotron X-ray radiation on the oxidation state and structure of the Flds, due to their radiation sensitive cofactor flavin mononucleotide (FMN). The high-resolution (0.98 Å), oxidized structure of one Fld indicates that X-rays induce structural changes around the FMN cofactor. Another important part of the study has been to gain further insight into the specificity and flexibility of the interactions between ferredoxin/flavodoxin-NADP+ reductases, Flds and NOS in Bacillus cereus, as well as the possible mechanism of bacterial NOSs.
Enzymatic hydrolysis of the β–β amide linkage in poly-β-aspartate
Authors: Hisano Tamao , Hiraishi Tomohiro , Minami Kosuke , Masuda Eriko , Abe Hideki , Maeda Mizuo , Shiro Yoshitsugu
Published: November 2015

Polyaspartate is a biodegradable and water-soluble polymer, and an important material as an alternative to polyacrylate. Polyacrylate is widely used as a builder of detergents, pigment dispersant, cosmetic moisturizer, water treatment agents (scale preventive, metal corrosion preventive), water absorptive polymer of disposable diaper, and so on, and are likely accumulated in the environment. Replacement of the polymer by biodegradable polyaspartate should reduce the accumulation and therefore environmental pollution. Thermally synthesized polyaspartate contains both α- and β-amide linkages. Recently, three bacterial enzymes that degrade polyaspartate have been isolated and characterized. An enzyme from Pedobacter sp. KP-2 specifically catalyzes the hydrolysis of the β–β-amide linkage in the polymer. The enzyme is a monomeric periplasmic protein, and the mature form contains 265 amino acid residues with a molecular weight of about 30,000. To understand the mechanisms underlying the interactions with the polymer substrate and hydrolysis of the β–β amide linkage, we set out the crystallographic study of the enzyme. We succeeded in crystallization of the enzyme by vapor-diffusion using polyethylene glycol 4,000. Crystals belonged to orthorhombic space group C222. Addition of cobalt salt in the mother liquor altered the space group of crystals to P6422 and greatly improved the diffraction quality. Data sets for native and mutant enzymes were collected to a resolution of 1.9 Å at SPring-8, Japan. Phases were calculated by cobalt-SAD. The obtained structure represented an α/β hydrolase fold which is often observed for a large number of serine esterases such as lipase and PHB depolymerase. Residues Ser125, Asp193, and His248 were within hydrogen bonding interactions, forming a catalytic triad. Structures of subsites 1 and 2 for binding of monomer units of the polymer were determined for the mutant enzyme complexed with an oligomer substrate. The monomer unit bound to subsite 1 was in extensive hydrogen bond interactions with residues including arginine. Though overall structural similar between the enzyme and PHB depolymerase from Penicillium funiculosum, residues that may interact with polymer substrates were totally different.
Structure factor measurement by 3-beam convergent beam electron diffraction
Authors: Guo Yueming , Nakashima Philip , Etheridge Joanne
Published: November 2015

It has been shown mathematically that both the magnitudes and 3-phase invariants of the structure factors of a centrosymmetric crystal can be expressed explicitly in terms of the distances to specific features in the 3-beam convergent beam electron diffraction (CBED) pattern [1].This theoretical inversion can be implemented experimentally, enabling direct observations of 3-phase invariants and the approximate measurement of structure factor magnitudes. This method then enables a different approach to crystal structure determination, which is based on the observation of phases, rather than the measurement of amplitudes. It has been shown that by inspection of just a few phases using 3-beam CBED patterns, centrosymmetric crystal structures can be determined directly to picometre precision without the need to measure magnitudes [2]. Here, we will explore a different approach for measuring structure factor magnitudes from 3-beam CBED patterns. It has been demonstrated that the relative structure factor magnitudes can be determined directly from the ratio of the intensity distributions along specific lines within the CBED discs [3]. We will investigate the potential of using this approach for the relatively fast measurement of approximate structure factor magnitudes from nano-scale volumes of crystals.
Structure prediction of N-heteroacenes as potential organic semiconductors
Authors: Campbell Josh , Day Graeme
Published: November 2015

Organic electronics offer exciting new alternatives to traditional inorganic devices based on advantages such as lower cost, ease of manufacture and flexibility. Small molecule semiconductors such as pentacene and rubrene are the focus of intense research due to performance approaching that of inorganic semiconductors. Charge transfer in polyaromatic hydrocarbons (PAHs) relies on the degree of π-conjugation and overlap of the π-systems of neighbouring molecules in the solid state. Small changes in the intermolecular interactions can lead to important changes in crystal packing and electronic properties. Thus, functionalization of PAHs is often used to improve their packing in the solid state. The addition of electronegative atoms into the ring system of pentacene has been proposed for improving stability while retaining attractive properties. [1] N-heteroacenes result from the substitution of nitrogen into the arene ring structure. The resulting potential for weak hydrogen bonding could direct coplanar molecular arrangements, sheet formation and favourable π-overlap for charge transport. Theoretical studies [2] have been carried out showing promising properties at the molecular level. As of yet no analysis of the solid state of these molecules has been performed to investigate how this substitution affects the packing and electronic properties. Here, we present the results of crystal structure prediction studies and calculation of charge transport properties aimed at understanding the influence of nitrogen substitution on the crystal packing of N-heteropentacenes and their performance as semiconducting materials.
Modeling molecular crystals with fragment-based electronic structure techniques
Authors: Beran Gregory
Published: November 2015

"A proper theoretical description of molecular crystal packing requires a uniformly high-quality treatment of the diverse intra- and intermolecular interactions. Fragment-based electronic structure methods enable the application of accurate electronic structure approaches to chemically interesting molecular crystals by decomposing the total crystal energy into the sum of many smaller ""fragment"" calculations. In this talk, we will discuss (1) the hybrid quantum/classical fragment based approach we have developed for molecular crystal problems, (2) state-of-the-art electronic structure approaches for treating the individual fragments with the requisite accuracy and acceptable computational effort, and (3) applications of these techniques to interesting molecular crystal problems."
Structural change of the TiO2(110) surface in the hydrophilic reaction
Authors: Shirasawa Tetsuroh , Voegeli Wolfgang , Arakawa Etsuo , Iwami Ryutaro , Kamezawa Chinatsu , Takahashi Toshio , Matsushita Tadashi
Published: November 2015

Photocatalysis of titanium dioxides has been extensively studied in the past. Especially, after the discovery of the UV-light induced hydrophobic-hydrophilic transition of the rutile-TiO2(110) surface in the late of 1990's [1], the number of photochemistry-related publications increased dramatically over the last decade to the extent that ~2400 related papers were published in 2008, in which ~80% of the papers involve the TiO2-related materials. The remarkable research activity arises from the potential applications of the photo-induced wettability control such as anti-fog coatings or self-cleaning coatings. However, despite the intensive study, the mechanism of the hydrophilic reaction is not completely clarified yet, mainly due to the lack of the detailed information of the atomic-scale surface structure. We have studied the surface structural change by means of surface X-ray diffraction. By using the recently developed time-resolved x-ray crystal truncation rod (CTR) scattering measurement [2] and the static measurement for the hydrophobic and hydrophilic surfaces, we confirmed that (i) the surface roughness increases during the reaction probably due to the desorption of the surface oxygen atoms and (ii) an ordered water molecular layer formed on the hydrophobic surface disappears in the hydrophilic surface. Considering the previous reports which show the increase of hydrogen bond density in the hydrophilic surface, we suggest that the ill-ordered surface of the hydrophilic phase allows a larger number of water molecules to adsorb by making a hydrogen-bond network.
Probing the spatial distribution of counterions in charged soft matter by ASAXS
Authors: Sztucki Michael , Lotze Gudrun , Narayanan Theyencheri
Published: November 2015

The precise knowledge of spatial distribution of counterions is a key ingredient for the better understanding of the microstructure and interactions in charged soft matter systems such as polyelectrolytes, proteins, surfactant micelles, membranes, DNA, etc. Quantitative Anomalous Small-Angle X-ray Scattering (ASAXS) can elucidate this unique information provided that an atomic absorption edge of the counterions is accessible within the available X-ray energy range of measurements [1]. Recent advances in instrumentation and data reduction have made ASAXS a suitable method for the quantitative characterization of the charge distribution in a variety of soft matter systems [2]. The emphasis has been to derive the weak self-term in the partial intensities and the Fourier transform of this term yields the spatial distribution of counterions. Furthermore, quantitative analysis of the two ASAXS partial intensities could reveal unique information about the counterion concentration fluctuations in the system [1]. This presentation will give an overview of experimental facilities available for ASAXS studies at the ESRF. The virtue of this method will be illustrated by a comparative study of surfactant micellar systems of alkyltrimethyl ammonium bromide with varying length of alkyl chains from 12 to 16. The scattered intensities from these systems display spectacular changes when the incident energy is varied near the K atomic absorption edge of Br which allowed us to derive the profile of counterions with high accuracy [2]. Furthermore, a comparison of the partial intensities of the macroions and counterions, and their cross-term reveal semi-quantitative agreement with computed partial scattering functions by molecular dynamics simulations [3]. Finally, results from recent ASAXS studies of counterion distribution around DNA and comparison with Poisson-Boltzmann cell model will be presented.
Hydration and Dehydration Transformation Mechanism of Cefaclor Pseudopolymorphs
Authors: Toyoshima Ryosuke , Sekine Akiko , Uekusa Hidehiro
Published: November 2015

Hydration/dehydration phase transitions of active pharmaceutical ingredients (API) are often accompanied with changes of physicochemical properties, such as solubility, stability, and bioavailability. Therefore, three dimensional structural investigation of the hydration / dehydration mechanism of API is important for pharmaceutical research and development. By relative humidity control, Cefaclor hydrate crystal dehydrates non-stoichiometrically from dihydrate to anhydrous form A. Unexpectedly, its monohydrate form transformed into new 1.9 hydrate by slurry treatment (methanol / water) which dehydrated into another anhydrous form B through hemihydrate by heating. In this study, these hydration and dehydration presudo-polymorphic transitions of Cefaclor are investigated by the crystal structure analyses. Crystal structures of anhydrous and partially dehydrated forms were determined by structure determination from powder diffraction data technique because such dehydration phase transitions were resulted in a disintegration of single crystal form. In the first dehydration route, hydrates and the anhydrous form A have similar crystal structure, which is referred as `isomorphic desolvation'. Interestingly, the anhydrous form A has void spaces which corresponds to the water molecule position in the hydrate form. Thus, in hydration / dehydration phase transitions, water molecules move in and out of the void without changing the crystal structures, and the anhydrous form A can hydrate even in low R.H. condition. In the second route, the 1.9 hydrate, hemihydrate and the anhydrate form B have three crystallographically independent molecules forming similar T-shape building block pattern. There are tunnel spaces along b axis between the blocks. In the hydration / dehydration process, the blocks slide each other to open and close the channel. This mechanism explains another non-stoichiometric dehydration in this route.
Celecoxib cocrystal polymorphs†
Authors: Bolla Geetha , Mittapalli Sudhir , Nangia Ashwini
Published: November 2015

Celecoxib (CEL) is a well-known nonsteroidal anti-inflammatory drug (NSAID) and selectively used from the cocxib family. It is a specific COX-2 inhibitor for pain and inflammation without inhibiting COX-1. A major downside of this popular NSAID is its poor aqueous solubility (9 mg L–1), which limits bioavailability (40%). Several methods were attempted in recent past to overcome solubility issues of the drug. A metastable form-IV showed four times greater solubility and improved bioavailability compared to commercial CEL form-III. Cocrystal of CEL with nicotinamide (CEL–NIC) is reported, but it rapidly dissociates to form-III.[1] Cocrystals of the CEL were screened in this study to improve the poor aqueous solubility and bioavailability through crystal engineering approach of supramolecular synthons.[2] Cyclic syn-carboxamides (with five to eight member ring lactams) produced cocrystals of CEL with different supramolecular synthons were reported.[3] Among them valerolactam (VLM) gave trimorphic cocrystals which showed synthons of sulfonamide/syn carboxamide functional groups (dimer and catemer) others gave only single form exclusively. The alteration of the coformer ring size offers crystal engineering approach to form sulfonamide-syn carboxamide supramolecular synthons sustained by SO2N–H···H–N–C=O hydrogen bonds. Binary systems including trimorphic cocrystals were characterized by FT-IR, PXRD, DSC and Hirshfeld surface analysis and finally confirmed by single crystal X-ray diffraction. Solubility and dissolution study of all the cocrystals and API carried out in 50% EtOH-water medium. Interestingly, we found there is a correlation between Hirshfeld surface analysis of F···H, O···H with the cocrystals stability following the order CEL–VLM-I>CEL–CPR>CEL–VLM-II (39.8>38.1>34.5%). The 2D finger print Hirshfeld % follows the stability order of the trimorphic cocrystals examined.
Phase transitions in efavirenz induced by mechanical activation
Authors: Oliveira Alcemira , Ayala Alejandro
Published: November 2015

Efavirenz,(S)-6-chloro-4(cyclopropylethynyl)-1,4-dihydro-4-(trifluoromethyl)-2H-3,1-benzoxazin-2-one, is a anti HIV agent belonging to the class of the non-nucleoside reverse transcriptase inhibitors, which is used in combination with other protease inhibitors or nucleoside reverse transcriptase inhibitors. Several polymorphs were reported in patents and scientific publications, being form I the thermodynamically most stable and the selected for commercial formulations. Mechanochemistry has emerged as an experimental methodology to efficiently and rapidly screen for new solid forms of a pharmaceutical active ingredient. These methods include neat and drop assisted grinding have been successfully applied to produce solvates, polymorphs, salts and cocrystals. In this contribution, we investigate the structural stability of efavirenz under mechanochemistry conditions. Room temperature and cryogenic neat and drop assisted grinding were applied to induce new crystalline forms, which were characterized by x-ray powder diffraction, vibrational spectroscopy and thermal analysis. The mechanism involved in these transformations were also investigated and discussed.
Structure Determination of Molecular Solids from Powder X-ray Diffraction Data
Authors: Harris Kenneth
Published: November 2015

Structure determination of organic molecular solids from powder X-ray diffraction (XRD) data [1] is nowadays carried out extensively by researchers in both academia and industry, and the development of new methodology in this field has made particularly significant impact in the pharmaceuticals industry within the last 20 years or so. However, although software for carrying out each stage of the procedure for structure determination from powder XRD data is now readily accessible and relatively straightforward to use, it is essential that the results from such structure determination calculations are subjected to careful scrutiny to confirm that the final structure obtained is actually correct. In this regard, it can be particularly advantageous to augment the analysis of the powder XRD data and to assist the scrutiny of the structural results by considering complementary structural information derived from other experimental and computational techniques. Techniques that can be particularly valuable in this regard include solid-state NMR spectroscopy, energy calculations (either on individual molecules or periodic crystal structures), vibrational spectroscopies, and techniques of thermal analysis (e.g. DSC and TGA). The lecture will give an overview of the current "state of the art" in the structure determination of organic materials from powder XRD data, giving emphasis [2,3] to the opportunities to enhance the structure determination process by making use of information derived from other experimental (especially solid-state NMR) and computational techniques. Recent results will be presented, with emphasis on raising issues of relevance to research on pharmaceutical materials.
Skyrmions in Multiferroic Insulator
Authors: Seki Shinichiro
Published: November 2015

Magnetic skyrmion is a topologically stable particle-like object, which appears as nanometer-scale vortex-like spin texture in a chiral-lattice magnet [1]. In metallic materials (MnSi, FeGe, Fe1-xCoxSi etc), electrons moving through skyrmion spin texture gain a nontrivial quantum Berry phase, which provides topological force to the underlying spin texture and enables the current-induced manipulation of magnetic skyrmion [2]. Such electric controllability, in addition to the particle-like nature, is a promising advantage for potential spintronic device applications. Recently, we newly discovered that skyrmions appear also in an insulating chiral-lattice magnet Cu2OSeO3 [3]. We find that the skyrmions in insulator can magnetically induce electric polarization through the relativistic spin-orbit interaction, which implies possible manipulation of the skyrmion by external electric field without loss of joule heating. The present finding of multiferroic skyrmion may pave a new route toward the engineering of novel magnetoelectric devices with high energy efficiency. In this talk, our recent attempts to drive skyrmions by external field are also introduced.
Magnetic structures and anisotropic excitations in Tb2Ti2O7spin liquid
Authors: Mirebeau Isabelle , Petit Sylvain , Robert Julien , Guitteny Solene , Gukasov Arsen , Bonville Pierre , Sazonov Andrew , Decorse Claudia
Published: November 2015

Geometrical frustration in the pyrochlore lattice of corner sharing tetrahedra yields exotic short range ordered ground states known as spin liquids or spin ices. Among them, Tb2Ti2O7 spin liquid (also called quantum spin ice) remains the most mysterious, in spite of 15 years of intense investigation. Our recent single crystal experiments using neutron diffraction and inelastic scattering down to 50 mK yield new insight on this question. By applying a high magnetic field along a [111] anisotropy axis [1], the Tb moments reorient gradually without showing the magnetization plateau observed in classical spin ices. Quantitative comparison with mean field calculation supports a dynamical symmetry breaking akin to a dynamic Jahn-Teller distortion, preserving the overall cubic symmetry. In the non-Kramers Tb ion this induce a quantum mixing of the wave-functions of the ground state crystal field doublet enabling the formation of a spin liquid, viewed as a non-magnetic two-singlet ground state in this mean-field picture [2]. The spin lattice coupling also shows up in the spin fluctuations in zero field [3]. Dispersive excitations emerge from pinch-points in the reciprocal space, with anisotropic spectral weight. This is the first evidence of them in a disordered ground state. They reveal the breaking of some conservation law ruling the relative orientations of the fluctuating magnetic moments in a given tetrahedron, as for the monopole excitations in classical spin ices. The algebraic character of the correlations shows that Tb2Ti2O7 ground state is akin to a Coulomb phase. Finally, the first excited crystal field level and an acoustic phonon mode interact, repelling each other. The whole results show that the magnetoelastic coupling is a key feature to understand the surprising spin liquid ground state. They call for an interaction between quadrupolar moments, whose Jahn-Teller distortion is the first (single site) approximation.