Structural Studies of Analgesics and Their Interactions. V.* The Crystal and Molecular Structure of Metamizol Monohydrate

Metamizol, Na[Ct3H16N3045], C13H16N304S-Na +, a sulphonyl derivative of amidopyrine, is perhaps the most widely used non-narcotic analgetic and antiinflammatory pyrazolone derivative. The monohydrate of the compound crystallizes in the monoclinic space group P2Jc with eight molecules in a unit cell of dimensions a = 9.143 (3), b = 49.50 (2), c = 7.314 (2)/k and fl = 90.9 (1) °. The structure was solved by direct methods and refined to an R value of 0.080 for 4466 observed reflections. The two crystallographically independent molecules in the structure have similar dimensions. The elongated molecules are hydrophobic at one end and hydrophilic at the other with the middle portion partly hydrophobic and partly hydrophilic. The pyrazolone group in the structure has dimensions similar to those found in uncomplexed antipyrine and amidopyrine. The crystal structure can be described as consisting of double layers of metamizol molecules stacked perpendicular to the b axis. The adjacent double layers are separated by a layer of Naions and water molecules.

Structural Investigations on Poly(4-hydroxy-L-proline). 2. Physicochemical Studies

We report experimental studies which confirm our prediction, namely that the ordered structure of poly(hydroxypro1ine) in solution corresponds to a left-handed helical structure with intrachain hydrogen bonds. The CD studies show that the poly(hydroxypro1ine) molecule has essentially the same conformation in aqueous solution and in the film obtained subsequently by evaporation. X-ray diffraction patterns of the sample in this form (B form) have been recorded at different relative humidities. The patterns recorded at relative humidities over 66% can be interpreted in terms of a helical structure with intrachain hydrogen bonds. These results lead us to conclude that the ordered conformation of poly(hydroxypro1ine) in solution is form B and not form A. This offers a simple explanation for the greater stability of the poly(hydroxypro1ine) helix in solution as compared to the poly(pro1ine) form I1 helix and also for the absence of mutarotation for poly(hydroxypro1ine).

Structural Investigations on Poly(4-hydroxy-L-proline). 1. Theoretical Studies

Model building studies on poly(hydroxypro1ine) indicate that in addition to the well-known helical structure of form A, a left-handed helical structure with trans peptide units and with h = 2.86 A and n = 2.67 (i.e., 8 residues in 3 turns) is also possible. In this structure which is shown to be in agreement with X-ray data of the form B in the next paper, the y-hydroxyl group of an (i + 1)th Hyp residue is hydrogen bonded to the carbonyl oxygen of an (i - 1)th residue. The possibility of a structure with cis peptide units is ruled out. It is shown that both forms A and B are equally favorable from considerations of intramolecular energies. Since form B is further stabilized by intrachain hydrogen bonds, we believe that this is likely to be the ordered conformation for poly(hydroxypro1ine) in water.

Structural and functional studies of Bacillus stearothermophilus serine hydroxymethyl transferase: the role of N341, Y60 and F351 in tetrahydrofolate binding.

SHMT (serine hydoxymethyltransferase), a type I pyridoxal 5'-phosphate-dependent enzyme, catalyses the conversion of L-serine and THF (tetrahydrofolate) into glycine and 5,10 -methylene THE SHMT also catalyses several THF-independent side reactions such as cleavage of P-hydroxy amino acids, trans-amination, racemization and decarboxylation. In the present study, the residues Asn(341), Tyr(60) and Phe(351), which are likely to influence THF binding, were mutated to alanine, alanine and glycine respectively, to elucidate the role of these residues in THF-dependent and -independent reactions catalysed by SHMT. The N341A and Y60A bsSHMT (Bacillus stearothermophilus SHMT) mutants were inactive for the THF-dependent activity, while the mutations had no effect on THF-independent activity. However, mutation of Phe(351) to glycine did not have any effect oil either of the activities. The crystal structures of the glycine binary complexes of the mutants showed that N341A bsSHMT forms an external aldimine as in bsSHMT, whereas Y60A and F351G bsSHMTs exist as a Mixture of internal/external aldimine and gem-diamine forms. Crystal structures of all of the three Mutants obtained in the presence of L-allo-threonine were similar to the respective glycine binary complexes. The structure of the ternary complex of F351G bsSHMT with glycine and FTHF (5-formyl THF) showed that the monoglutamate side chain of FTHF is ordered in both the subunits of the asymmetric unit, unlike in the wild-type bsSHMT. The present studies demonstrate that the residues Asn(341) and Tyr(60) are pivotal for the binding of THF/FTHF, whereas Phe(351) is responsible for the asymmetric binding of FTHF in the two subunits of the dimer.

Synthesis, spectral and structural studies on metal complexes of Schiff bases involving vitamin B6 and histamine

Six metal complexes of Schiff bases involving Vitamin B6 and the decarboxylated amino acid histamine have been synthesised and characterized. Crystal structures have been determined for [CuL1(H2O)Br]-NO31(L1= pyridoxylidenehistamine) and [Cu2L22(NO3)2]·6H2O 2(L2= 5′-phosphopyridoxylidenehistaminate). The crystal structure of complex 1[space group P[1 with combining macron], a= 8.161(2), b= 10.368(2), c= 11.110(2)Å, α= 105.18(1), β= 102.12(1), γ= 72.10(1)° and Z= 2; R= 0.072, R′= 0.083] consists of square-pyramidally co-ordinated copper with the tridentate Schiff base in the zwitterionic form, whereas in 2[space group P[1 with combining macron], a= 8.727(1), b= 10.308(1), c= 12.845(2)Å, α= 110.00(1), β= 78.94(1), γ= 114.35(1)° and Z= 1; R= 0.035, R′= 0.034] the copper has the same co-ordination geometry but the tetradentate Schiff-base ligand exists as a monoanion. The conformational parameters deduced from such structures are important for understanding the stereochemical aspects of Vitamin B6-catalysed model reactions involving histidine.

Synthetic, spectroscopic, magnetic, and x-ray structural studies on a vitamin B6-amino acid Schiff base complex, aqua(5'-phosphopyridoxylidenetyrosinato)copper(II) tetrahydrate

A Schiff base metal complex, [Cu(II)(PLP-DL-tyrosinato)(H2O)].4H2O (PLP = pyridoxal phosphate), with the molecular formula CuC17O13N2H27P has been prepared and characterized by magnetic, spectral, and X-ray structural studies. The compound crystallizes in the triclinic space group P1BAR with a = 8.616 (2) angstrom, b = 11.843 (3) angstrom, c = 12.177 (3) angstrom, alpha = 103.40 (2)degrees, beta = 112.32 (2)degrees, gamma = 76.50 (1)degrees, and Z = 2. The structure was solved by the heavy-atom method and refined by least-squares techniques to a final R value of 0.057 for 3132 independent reflections. The coordination geometry around Cu(II) is distorted square pyramidal with phenolic oxygen, imino nitrogen, and carboxylate oxygen from the Schiff base ligand and water oxygen as basal donor atoms. The axial site is occupied by a phosphate oxygen from a neighboring molecule, thus resulting in a one-dimensional polymer. The structure reveals pi-pi interaction of the aromatic side chain of the amino acid with the pyridoxal pi system. A comparative study is made of this complex with similar Schiff base complexes. The variable-temperature magnetic behavior of this compound shows a weak antiferromagnetic interaction.

Vain hätapua? : Taloudellinen avustaminen diakoniatyön professionaalisen itseymmärryksen ilmentäjänä

Financial Help Alone? Financial help as an exponent of professional diaconal work One essential form of helping people in the Evangelical Lutheran Church s diaconal work is providing economic aid. It can be seen as work which is in accordance with the spirit of the Church Order (4:3). One of the tasks of diaconal work, determined by the Church Order, is to help those whose distress is the greatest and who have no other source of help. This financial support has become a permanent and essential working method, which has also created tension of various kinds. Financial support has been criticized, especially when the support has been used to fill a gap in the social services provided by the government. It has been argued that diaconal work has been forced to take on responsibility for tasks that belong to the welfare state. The tensions involved in the financial support of diaconal work do not only concern the patching up and supplementing of the deficiencies in the welfare state s services but also the question of diaconal workers self-understanding of financial support and how it relates to their professionalism. In this thesis, I examine the experiences and visions diaconal workers have concerning financial support in their work with clients. The viewpoint of my work is the diaconal workers own experiences and interpretations of the meaning of financial support in customer service. In the articles of my thesis, I examined the meanings that diaconal workers gave to financial support in the aspects of work motivation, empowerment, expertise and tensions. The research material of my articles consists of three different data, which are theme interviews from diaconal workers, a survey from diaconal workers of Espoo and a diaconal barometer of 2009. I have analysed the theme interviews and the survey using qualitative content analysis. The results of my articles showed that diaconal workers motivation in tasks concerning economic aid was sustained by the nature and spiritual aspects of support activities. Work that supported empowerment through financial assistance meant influencing the client s personal life, community and local ties and structural circumstances of the surrounding society. Diaconal workers expertise in financial support work can be characterised as horizontal, which means that the expertise was built on acknowledging the client s dignity, the uniqueness of the client s life situation and listening to the client s own voice. Diaconal workers were also experts in community and area-based work. The tensions in financial support work are linked to its unofficial and undefined role in the field of social welfare and the inability of other aiding parties to respond to their duties. The results of my thesis on the experiences and visions of financial support reveal that it is multilateral and multidimensional. Diaconal workers used financial support to help the clients, taking into account their individual, communal, social and spiritual context. The professionalism of this financial support is reflectively related to the client s need of help and the spontaneity and unexpectedness of the situation. Support work was deeply bound to diaconal workers experiences of spirituality as the basic value in their work, the foundation of their idea of humanity and their method of helping others. In different tasks of financial support diaconal workers balanced between traditional, individual client work based on caritas and working methods which are based on supporting the individual s empowerment and active citizenship, as in postmodern social work. Diaconal workers experiences of financial support illustrated the transition or turning point in the professionalism of diaconal work, which involves finding one s own, stronger and clearer professional identity than earlier with respect to other helpers in society. Creating a unique identity is part of the empowerment process of diaconal work, in which it must define its professional role by itself. In postmodern pluralism and the fragmented context of diaconal activities, the question arose as to whether the spiritual traditions and traditional values of diaconal work support the modifications and adaptations needed in new, unpredictable situations. Diaconal work is said to be fast to react, able to predict changes and adapt to those changes. To preserve its sensitive reactive ability, also in the complex postmodern world, it must retain its own views and orientations. Otherwise, the distinctive values and traditions of diaconal work might sustain static diaconal work, employee-centeredness and a smug attitude when defining beneficiaries and needs, which highlights the paternalism of diaconal work. Such paternalism may complicate the progress of working methods which are based on empowerment and citizenship.

Biochemical and structural characterization of recombinant hyoscyamine 6 beta-hydroxylase from Datura metel L.

Hyoscyamine 6 beta-hydroxylase (H6H; EC 1.14.11.11), an important enzyme in the biosynthesis of tropane alkaloids, catalyzes the hydroxylation of hyoscyamine to give 6 beta-hydroxyhyoscyamine and its epoxidation in the biosynthetic pathway leading to scopolamine. Datura metel produces scopolamine as the predominant tropane alkaloid. The cDNA encoding H6H from D. mete! (DmH6H) was cloned, heterologously expressed and biochemically characterized. The purified recombinant His-tagged H6H from D. mete! (DmrH6H) was capable of converting hyoscyamine to scopolamine. The functionally expressed DmrH6H was confirmed by HPLC and ESI-MS verification of the products, 6 beta-hydroxyhyoscyamine and its derivative, scopolamine; the DmrH6H epoxidase activity was low compared to the hydroxylase activity. The K-m values for both the substrates, hyoscyamine and 2-oxoglutarate, were 50 mu M each. The CD (circular dichroism) spectrum of the DmrH6H indicated a preponderance of alpha-helicity in the secondary structure. From the fluorescence studies, Stern-Volmer constants for hyoscyamine and 2-oxoglutarate were found to be 0.14 M-1 and 0.56 M-1, respectively. These data suggested that the binding of the substrates, hyoscyamine and 2-oxoglutarate, to the enzyme induced significant conformational changes. (C) 2010 Elsevier Masson SAS. All rights reserved.

Deformation and structural densification in Al2O3-Y2O3 glass

In this article, we examine the unusual plastic deformation under uniaxial compression of an Al2O3-15 mol % Y2O3 (A15Y) glass synthesized by a wet chemical route At a low temperature of 650-725 degrees C, plastic deformation of this glass is largely non-viscous through shear instabilities In contrast deformation near the crystallization temperature (850 degrees C) occurs homogeneously with work hardening and with a monotonic increase in the true density of the glass by 10-12% accompanied by an increase in hardness (H) and elastic modulus (E) of up to 100% We hypothesize a phenomenon of molecular densification of the amorphous structure through a hierarchy of multiple phases, analogous to density- or entropy-driven amorphous to-amorphous phase transitions (polyamorphism) These results suggest that the present method of preparation and the unusual behavior can trigger a search for many more systems that display such behavior (C) 2010 Acta Materialia Inc Published by Elsevier Ltd All rights reserved

Structural features of B-DNA dodecamer crystal structures: Influence of crystal packing versus base sequence

We have analyzed the set of inter and intra base pair parameters for each dinucleotide step in single crystal structures of dodecamers, solved at high and medium resolution and all crystallized in P2(1)2(1)2(1) space group. The objective was to identify whether all the structures which have either the Drew-Dickerson (DD) sequence d[CGCGAATTCGCG] with some base modification or related sequence (non-DD), would display the same sequence dependent structural variability about its palindromic sequence, despite the molecule being bent at one end because of similar crystal lattice packing effect. Most of the local doublet parameters for base pairs steps G2-C3 and G10-C11 positions, symmetrically situated about the lateral twofold, were significantly correlated between themselves. In non-DD sequences, significant correlations between these positional parameters were absent. The different range of local step parameter values at each sequence position contributed to the gross feature of smooth helix axis bending in all structures. The base pair parameters in some of the positions, for medium resolution DD sequence, were quite unlike the high-resolution set and encompassed a higher range of values. Twist and slide are the two main parameters that show wider conformational range for the middle region of non-DD sequence structures in comparison to DD sequence structures. On the contrary, the minor and major groove features bear good resemblance between DD and non-DD sequence crystal structure datasets. The sugar-phosphate backbone torsion angles are similar in all structures, in sharp contrast to base pair parameter variation for high and low resolution DD and non-DD sequence structures, consisting of unusual (epsilon =g(-), xi =t) B-II conformation at the 10(th) position of the dodecamer sequence. Thus examining DD and non-DD sequence structures packed in the same crystal lattice arrangement, we infer that inter and intra base pair parameters are as symmetrically equivalent in its value as the symmetry related step for the palindromic DD sequence about lateral two-fold axis. This feature would lead us to agree with the conclusion that DNA conformation is not substantially affected by end-to-end or lateral inter-molecular interaction due to crystal lattice packing effect. Non-DD sequence structures acquire step parameter values which reflect the altered sequence at each of the dodecamer sequence position in the orthorhombic lattice while showing similar gross features of DD sequence structures

Structural Relationships in 2,3-Bis-n-decyloxyanthracene and 12-Hydroxystearic Acid Molecular Gels and Aerogels Processed in Supercritical CO2

Supercritical carbon dioxide is used to prepare aerogels of two reference molecular organogelators, 2,3-bis-n-decyloxyanthracene (DDOA) (luminescent molecule) and 12-hydroxystearic acid (HSA). Electron microscopy reveals the fibrillar morphology of the aggregates generated by the protocol. SAXS and SANS measurements show that DDOA aerogels are crystalline materials exhibiting three morphs: (1) arrangements of the crystalline solid (2D p6m), (2) a second hexagonal morph slightly more compact, and (3) a packing specific of the fibers in the gel. Aggregates specific of the aerogel (volume fraction being typically phi approximate to 0.60) are developed over larger distances (similar to 1000 angstrom) and bear fewer defaults and residual strains than aggregates in the crystalline and gel phases. Porod, Scherrer and Debye-Bueche analyses of the scattering data have been performed. The first five diffraction peaks show small variations in position and intensity assigned to the variation of the number of fibers and their degree of vicinity within hexagonal bundles of the related SAFIN according to the Oster model. Conclusions are supported by the guidelines offered by the analysis of the situation in HSA aerogels for which the diffraction pattern can be described by two coexisting lamellar-like arrangements. The porosity of the aerogel, as measured by its specific surface extracted from the scattering invariant analysis, is only 1.8 times less than that of the swollen gel and is characteristic of a very porous material.

Structural morphology of acoustically levitated and heated nanosilica droplet

We study the vaporization and precipitation dynamics of a nanosilica encapsulated water droplet by levitating it acoustically and heating it with a CO2 laser. For all concentrations, we observe three phases: solvent evaporation, surface agglomeration, and precipitation leading to bowl or ring shaped structures. At higher concentrations, ring reorientation and rotation are seen consistently. The surface temperature from an infrared camera is seen to be dependent on the final geometrical shape of the droplet and its rotation induced by the acoustic field of the levitator. With nonuniform particle distribution, these structures can experience rupture which modifies the droplet rotational speed. (C) 2010 American Institute of Physics. doi:10.1063/1.3493178]