1,10-phenanthrolin-1-ium 2-carboxy-4,5-dichlorobenzoate

In the structure of the 1:1 proton-transfer compound of 1,10-phenanthroline with 4,5-dichlorophthalic acid, C12H9N2+ C8H3Cl2O4-, determined at 130 K, the 1,10-phenanthroline cation and the hydrogen 4,5-dichlorophthalate anion associate through a single N-H...O(carboxyl) hydrogen bond giving discrete units which have no extension except through a number of weak cation C-H...O(anion) associations and weak cation--anion aromatic ring pi-pi interactions [minimum centroid separation, 3.6815(12)A]. The anions are essentially planar [maximum deviation 0.214(1)A (a carboxyl O)] with the syn-related H atom of the carboxyl group forming a short intramolecular O-H...O(carboxyl) hydrogen bond.

Zero- one- and two-dimensional hydrogen-bonded structures in the 1:1 proton-transfer compounds of 4,5-dichlorophthalic acid with the monocyclic heteroaromatic Lewis bases 2-aminopyrimidine, nicotinamide and isonicotinamide

The structures of the anhydrous 1:1 proton-transfer compounds of 4,5-dichlorophthalic acid (DCPA) with the monocyclic heteroaromatic Lewis bases 2-aminopyrimidine, 3-(aminocarboxy) pyridine (nicotinamide) and 4-(aminocarbonyl) pyridine (isonicotinamide), namely 2-aminopyrimidinium 2-carboxy-4,5-dichlorobenzoate C4H6N3+ C8H3Cl2O4- (I), 3-(aminocarbonyl) pyridinium 2-carboxy-4,5-dichlorobenzoate C6H7N2O+ C8H3Cl2O4- (II) and the unusual salt adduct 4-(aminocarbonyl) pyridinium 2-carboxy-4,5-dichlorobenzoate 2-carboxymethyl-4,5-dichlorobenzoic acid (1/1/1) C6H7N2O+ C8H3Cl2O4-.C9H6Cl2O4 (III) have been determined at 130 K. Compound (I) forms discrete centrosymmetric hydrogen-bonded cyclic bis(cation--anion) units having both R2/2(8) and R2/1(4) N-H...O interactions. In compound (II) the primary N-H...O linked cation--anion units are extended into a two-dimensional sheet structure via amide-carboxyl and amide-carbonyl N-H...O interactions. The structure of (III) reveals the presence of an unusual and unexpected self-synthesized methyl monoester of the acid as an adduct molecule giving one-dimensional hydrogen-bonded chains. In all three structures the hydrogen phthalate anions are

Development of a colorimetric assay for heparanase activity suitable for kinetic analysis and inhibitor screening

The role that heparanase plays during metastasis and angiogenesis in tumors makes it an attractive target for cancer therapeutics. Despite this enzyme’s significance, most of the assays developed to measure its activity are complex. Moreover, they usually rely on labeling variable preparations of the natural substrate heparan sulfate, making comparisons across studies precarious. To overcome these problems, we have developed a convenient assay based on the cleavage of the synthetic heparin oligosaccharide fondaparinux. The assay measures the appearance of the disaccharide product of heparanase-catalyzed fondaparinux cleavage colorimetrically using the tetrazolium salt WST-1. Because this assay has a homogeneous substrate with a single point of cleavage, the kinetics of the enzyme can be reliably characterized, giving a Km of 46 μM and a kcat of 3.5 s−1 with fondaparinux as substrate. The inhibition of heparanase by the published inhibitor, PI-88, was also studied, and a Ki of 7.9 nM was determined. The simplicity and robustness of this method, should, not only greatly assist routine assay of heparanase activity but also could be adapted for high-throughput screening of compound libraries, with the data generated being directly comparable across studies.

An Improved Synthetic Route to the Potent Angiogenesis Inhibitor Benzyl Manα(1→3)-Manα(1→3)-Manα(1→3)-Manα(1→2)-Man Hexadecasulfate

An improved synthetic route to α(1→3)/α(1→2)-linked mannooligosaccharides has been developed and applied to a more efficient preparation of the potent anti-angiogenic sulfated pentasaccharide, benzyl Manα(1→3)-Manα(1→3)-Manα(1→3)-Manα(1→2)-Man hexadecasulfate, using only two monosaccharide building blocks. Of particular note are improvements in the preparation of both building blocks and a simpler, final deprotection strategy. The route also provides common intermediates for the introduction of aglycones other than benzyl, either at the building block stage or after oligosaccharide assembly. The anti-angiogenic activity of the synthesized target compound was confirmed via the rat aortic assay.

Proton-transfer versus nontransfer in compounds of the diazo-dye precursor 4-(phenyldiazenyl) aniline (aniline yellow) with strong organic acids: the 5-sulfosalicylate and the dichroic benzenesulfonate salts, and the 1:2 adduct with 3,5-dinitrobenzoic

The structures of two 1:1 proton-transfer red-black dye compounds formed by reaction of aniline yellow [4-(phenyldiazenyl)aniline] with 5-sulfosalicylic acid and benzenesulfonic acid, and a 1:2 nontransfer adduct compound with 3,5-dinitrobenzoic acid have been determined at either 130 or 200 K. The compounds are 2-(4-aminophenyl)-1-phenylhydrazin-1-ium 3-carboxy-4-hydroxybenzenesulfonate methanol solvate, C12H12N3+.C7H5O6S-.CH3OH (I), 2-(4-aminophenyl)-1-hydrazin-1-ium 4-(phenydiazinyl)anilinium bis(benzenesulfonate), 2C12H12N3+.2C6H5O3S-, (II) and 4-(phenyldiazenyl)aniline-3,5-dinitrobenzoic acid (1/2) C12H11N3.2C~7~H~4~N~2~O~6~, (III). In compound (I) the diaxenyl rather than the aniline group of aniline yellow is protonated and this group subsequently akes part in a primary hydrogen-bonding interaction with a sulfonate O-atom acceptor, producing overall a three-dimensional framework structure. A feature of the hydrogen bonding in (I) is a peripheral edge-on cation-anion association involving aromatic C--H...O hydrogen bonds, giving a conjoint R1/2(6)R1/2(7)R2/1(4)motif. In the dichroic crystals of (II), one of the two aniline yellow species in the asymmetric unit is diazenyl-group protonated while in the other the aniline group is protonated. Both of these groups form hydrogen bonds with sulfonate O-atom acceptors and thee, together with other associations give a one-dimensional chain structure. In compound (III), rather than proton-transfer, there is a preferential formation of a classic R2/2(8) cyclic head-to-head hydrogen-bonded carboxylic acid homodimer between the two 3,5-dinitrobenzoic acid molecules, which in association with the aniline yellow molecule that is disordered across a crystallographic inversion centre, result in an overall two-dimensional ribbon structure. This work has shown the correlation between structure and observed colour in crystalline aniline yellow compounds, illustrated graphically in the dichroic benzenesulfonate compound.

Fingerprint analysis of eucommia bark by LC-DAD and LC-MS with the aid of chemometrics

Chromatographic fingerprints of 46 Eucommia Bark samples were obtained by liquid chromatography-diode array detector (LC-DAD). These samples were collected from eight provinces in China, with different geographical locations, and climates. Seven common LC peaks that could be used for fingerprinting this common popular traditional Chinese medicine were found, and six were identified as substituted resinols (4 compounds), geniposidic acid and chlorogenic acid by LC-MS. Principal components analysis (PCA) indicated that samples from the Sichuan, Hubei, Shanxi and Anhui—the SHSA provinces, clustered together. The other objects from the four provinces, Guizhou, Jiangxi, Gansu and Henan, were discriminated and widely scattered on the biplot in four province clusters. The SHSA provinces are geographically close together while the others are spread out. Thus, such results suggested that the composition of the Eucommia Bark samples was dependent on their geographic location and environment. In general, the basis for discrimination on the PCA biplot from the original 46 objects× 7 variables data matrix was the same as that for the SHSA subset (36 × 7 matrix). The seven marker compound loading vectors grouped into three sets: (1) three closely correlating substituted resinol compounds and chlorogenic acid; (2) the fourth resinol compound identified by the OCH3 substituent in the R4 position, and an unknown compound; and (3) the geniposidic acid, which was independent of the set 1 variables, and which negatively correlated with the set 2 ones above. These observations from the PCA biplot were supported by hierarchical cluster analysis, and indicated that Eucommia Bark preparations may be successfully compared with the use of the HPLC responses from the seven marker compounds and chemometric methods such as PCA and the complementary hierarchical cluster analysis (HCA).

4-(2-hydroxyethyl)anilinium 3-carboxy-4-hydroxybenzenesulfonate monohydrate

In the structure of the title compound C8H12NO+ C7H5O6S- . H2O, from the reaction of 2-(4-aminophenyl)ethanol with 5-sulfosalicylic acid, the cations form head-to-tail hydrogen-bonded chains through C1/1(9) anilinium N+-H...O(hydroxyl} interactions while the anions also form similar but C1/1(8)-linked chains through carboxylic acid O-..O(sulfonate) interactions. The chains inter-associate through a number of N-H...O and O-H...O bridging interactions giving a two-dimensional array in the ab plane.

Inhibition of myeloperoxidase-mediated hypochlorous acid production by nitroxides

Tissue damage resulting from the extracellular production of HOCl (hypochlorous acid) by the MPO (myeloperoxidase)-hydrogen peroxide-chloride system of activated phagocytes is implicated as a key event in the progression of a number of human inflammatory diseases. Consequently, there is considerable interest in the development of therapeutically useful MPO inhibitors. Nitroxides are well established antioxidant compounds of low toxicity that can attenuate oxidative damage in animal models of inflammatory disease. They are believed to exert protective effects principally by acting as superoxide dismutase mimetics or radical scavengers. However, we show here that nitroxides can also potently inhibit MPO-mediated HOCl production, with the nitroxide 4-aminoTEMPO inhibiting HOCl production by MPO and by neutrophils with IC50 values of approx. 1 and 6 μM respectively. Structure–activity relationships were determined for a range of aliphatic and aromatic nitroxides, and inhibition of oxidative damage to two biologically-important protein targets (albumin and perlecan) are demonstrated. Inhibition was shown to involve one-electron oxidation of the nitroxides by the compound I form of MPO and accumulation of compound II. Haem destruction was also observed with some nitroxides. Inhibition of neutrophil HOCl production by nitroxides was antagonized by neutrophil-derived superoxide, with this attributed to superoxide-mediated reduction of compound II. This effect was marginal with 4-aminoTEMPO, probably due to the efficient superoxide dismutase-mimetic activity of this nitroxide. Overall, these data indicate that nitroxides have considerable promise as therapeutic agents for the inhibition of MPO-mediated damage in inflammatory diseases.

Seismic performance of brick infilled RC frame structures in low and medium rise buildings in Bhutan

The construction of reinforced concrete buildings with unreinforced infill is common practice even in seismically active country such as Bhutan, which is located in high seismic region of Eastern Himalaya. All buildings constructed prior 1998 were constructed without seismic provisions while those constructed after this period adopted seismic codes of neighbouring country, India. However, the codes have limited information on the design of infilled structures besides having differences in architectural requirements which may compound the structural problems. Although the influence of infill on the reinforced concrete framed structures is known, the present seismic codes do not consider it due to the lack of sufficient information. Time history analyses were performed to study the influence of infill on the performance of concrete framed structures. Important parameters were considered and the results presented in a manner that can be used by practitioners. The results show that the influence of infill on the structural performance is significant. The structural responses such as fundamental period, roof displacement, inter-storey drift ratio, stresses in infill wall and structural member forces of beams and column generally reduce, with incorporation of infill wall. The structures designed and constructed with or without seismic provision perform in a similar manner if the infills of high strength are used.

A sequencing approach for creating new train timetables

Train scheduling is a complex and time consuming task of vital importance. To schedule trains more accurately and efficiently than permitted by current techniques a novel hybrid job shop approach has been proposed and implemented. Unique characteristics of train scheduling are first incorporated into a disjunctive graph model of train operations. A constructive algorithm that utilises this model is then developed. The constructive algorithm is a general procedure that constructs a schedule using insertion, backtracking and dynamic route selection mechanisms. It provides a significant search capability and is valid for any objective criteria. Simulated Annealing and Local Search meta-heuristic improvement algorithms are also adapted and extended. An important feature of these approaches is a new compound perturbation operator that consists of many unitary moves that allows trains to be shifted feasibly and more easily within the solution. A numerical investigation and case study is provided and demonstrates that high quality solutions are obtainable on real sized applications.

Reading and writing PE-files with PERWAPI

PERWAPI is a component for reading and writing .NET PE-files. The name is a compound acronym for Program Executable – Reader/Writer – Application Programming Interface. The code was written by one of us (Diane Corney) with some contributions from some of the early users of the tool. PERWAPI is a managed component, written entirely in safe C#. The design of the writer part of the component is loosely based on Diane Corney’s previous PEAPI component. It is open source software, and is released under a “FreeBSD-like” license. The source may be downloaded from “http://plas.fit.qut.edu.au/perwapi/” As of the date of this document the code has facilities for reading and writing PEfiles compatible with the latest (beta-2) release of the ”Whidbey” version of .NET, that is, the Visual Studio 2005 framework. An invocation option allows earlier versions of the framework to be targeted.

Peripheral ocular monochromatic aberrations

Aberrations affect image quality of the eye away from the line of sight as well as along it. High amounts of lower order aberrations are found in the peripheral visual field and higher order aberrations change away from the centre of the visual field. Peripheral resolution is poorer than that in central vision, but peripheral vision is important for movement and detection tasks (for example driving) which are adversely affected by poor peripheral image quality. Any physiological process or intervention that affects axial image quality will affect peripheral image quality as well. The aim of this study was to investigate the effects of accommodation, myopia, age, and refractive interventions of orthokeratology, laser in situ keratomileusis and intraocular lens implantation on the peripheral aberrations of the eye. This is the first systematic investigation of peripheral aberrations in a variety of subject groups. Peripheral aberrations can be measured either by rotating a measuring instrument relative to the eye or rotating the eye relative to the instrument. I used the latter as it is much easier to do. To rule out effects of eye rotation on peripheral aberrations, I investigated the effects of eye rotation on axial and peripheral cycloplegic refraction using an open field autorefractor. For axial refraction, the subjects fixated at a target straight ahead, while their heads were rotated by ±30º with a compensatory eye rotation to view the target. For peripheral refraction, the subjects rotated their eyes to fixate on targets out to ±34° along the horizontal visual field, followed by measurements in which they rotated their heads such that the eyes stayed in the primary position relative to the head while fixating at the peripheral targets. Oblique viewing did not affect axial or peripheral refraction. Therefore it is not critical, within the range of viewing angles studied, if axial and peripheral refractions are measured with rotation of the eye relative to the instrument or rotation of the instrument relative to the eye. Peripheral aberrations were measured using a commercial Hartmann-Shack aberrometer. A number of hardware and software changes were made. The 1.4 mm range limiting aperture was replaced by a larger aperture (2.5 mm) to ensure all the light from peripheral parts of the pupil reached the instrument detector even when aberrations were high such as those occur in peripheral vision. The power of the super luminescent diode source was increased to improve detection of spots passing through the peripheral pupil. A beam splitter was placed between the subjects and the aberrometer, through which they viewed an array of targets on a wall or projected on a screen in a 6 row x 7 column matrix of points covering a visual field of 42 x 32. In peripheral vision, the pupil of the eye appears elliptical rather than circular; data were analysed off-line using custom software to determine peripheral aberrations. All analyses in the study were conducted for 5.0 mm pupils. Influence of accommodation on peripheral aberrations was investigated in young emmetropic subjects by presenting fixation targets at 25 cm and 3 m (4.0 D and 0.3 D accommodative demands, respectively). Increase in accommodation did not affect the patterns of any aberrations across the field, but there was overall negative shift in spherical aberration across the visual field of 0.10 ± 0.01m. Subsequent studies were conducted with the targets at a 1.2 m distance. Young emmetropes, young myopes and older emmetropes exhibited similar patterns of astigmatism and coma across the visual field. However, the rate of change of coma across the field was higher in young myopes than young emmetropes and was highest in older emmetropes amongst the three groups. Spherical aberration showed an overall decrease in myopes and increase in older emmetropes across the field, as compared to young emmetropes. Orthokeratology, spherical IOL implantation and LASIK altered peripheral higher order aberrations considerably, especially spherical aberration. Spherical IOL implantation resulted in an overall increase in spherical aberration across the field. Orthokeratology and LASIK reversed the direction of change in coma across the field. Orthokeratology corrected peripheral relative hypermetropia through correcting myopia in the central visual field. Theoretical ray tracing demonstrated that changes in aberrations due to orthokeratology and LASIK can be explained by the induced changes in radius of curvature and asphericity of the cornea. This investigation has shown that peripheral aberrations can be measured with reasonable accuracy with eye rotation relative to the instrument. Peripheral aberrations are affected by accommodation, myopia, age, orthokeratology, spherical intraocular lens implantation and laser in situ keratomileusis. These factors affect the magnitudes and patterns of most aberrations considerably (especially coma and spherical aberration) across the studied visual field. The changes in aberrations across the field may influence peripheral detection and motion perception. However, further research is required to investigate how the changes in aberrations influence peripheral detection and motion perception and consequently peripheral vision task performance.

4-Hydroxy-4,4-diphenylbutan-2-one

The mol­ecules of the title compound, C16H16O2, display an intra­molecular O—HO hydrogen bond between the hydroxyl donor and the ketone acceptor. Inter­molecular C—Hπ inter­actions connect adjacent mol­ecules into chains that propagate parallel to the ac diagonal. The chains are arranged in sheets, and mol­ecules in adjacent sheets inter­act via inter­molecular O—HO hydrogen bonds.

Reading and writing PE-files with PERWAPI

PERWAPI is a component for reading and writing .NET PE-files. The name is a compound acronym for Program Executable – Reader/Writer – Application Programming Interface. The code was written by one of us (Diane Corney) with some contributions from some of the early users of the tool. PERWAPI is a managed component, written entirely in safe C#. The design of the writer part of the component is loosely based on Diane Corney’s previous PEAPI component. It is open source software, and is released under a “FreeBSD-like” license. The source may be downloaded from “http://perwapi.codeplex.com”. As of the date of this document the code has facilities for reading and writing PEfiles compatible with the V2 or later frameworks.

Isopropylaminium 2-carboxy-4, 5-dichlorobenzoate

In the structure of the 1:1 proton-transfer compound of isopropylamine with 4,5-dichlorophthalic acid, C3H10N+·C8H3Cl2O4-, the three cation H-atom donors associate with three separate carboxyl O-atom anion acceptors, giving conjoint cyclic R44(12), R44(16) hydrogen-bonding cation-anion interactions in a one-dimensional ribbon structure. In the anions, the carboxyl groups lie slightly out of the plane of the benzene ring [maximum deviations = 0.439 (1) for a carboxylic acid O atom and 0.433 (1) Å for a carboxylate O atom]. However, the syn-related proton of the carboxylic acid group forms the common short intramolecular O-HOcarboxyl hydrogen bond.