On-road ultrafine particle concentration in the M5 East road tunnel, Sydney, Australia

The human health effects following exposure to ultrafine (<100nm) particles (UFPs) produced by fuel combustion, while not completely understood, are generally regarded as detrimental. Road tunnels have emerged as locations where maximum exposure to these particles may occur for the vehicle occupants using them. This study aimed to quantify and investigate the determinants of UFP concentrations in the 4km twin-bore (eastbound and westbound) M5 East tunnel in Sydney, Australia. Sampling was undertaken using a condensation particle counter (CPC) mounted in a vehicle traversing both tunnel bores at various times of day from May through July, 2006. Supplementary measurements were conducted in February, 2008. Over three hundred transects of the tunnel were performed, and these were distributed evenly between the bores. Additional comparative measurements were conducted on a mixed route comprising major roads and shorter tunnels, all within Sydney. Individual trip average UFP concentrations in the M5 East tunnel bores ranged from 5.53 × 104 p cm-3 to 5.95 × 106 p cm-3. Data were sorted by hour of capture, and hourly median trip average (HMA) UFP concentrations ranged from 7.81 × 104 p cm-3 to 1.73 × 106 p cm-3. Hourly median UFP concentrations measured on the mixed route were between 3.71 × 104 p cm-3 and 1.55 × 105 p cm-3. Hourly heavy diesel vehicle (HDV) traffic volume was a very good determinant of UFP concentration in the eastbound tunnel bore (R2 = 0.87), but much less so in the westbound bore (R2 = 0.26). In both bores, the volume of passenger vehicles (i.e. unleaded gasoline-powered vehicles) was a significantly poorer determinant of particle concentration. When compared with similar studies reported previously, the measurements described here were among the highest recorded concentrations, which further highlights the contribution road tunnels may make to the overall UFP exposure of vehicle occupants.

Increase in particle number emissions from motor vehicles due to interruption of steady traffic flow

We assess the increase in particle number emissions from motor vehicles driving at steady speed when forced to stop and accelerate from rest. Considering the example of a signalized pedestrian crossing on a two-way single-lane urban road, we use a complex line source method to calculate the total emissions produced by a specific number and mix of light petrol cars and diesel passenger buses and show that the total emissions during a red light is significantly higher than during the time when the light remains green. Replacing two cars with one bus increased the emissions by over an order of magnitude. Considering these large differences, we conclude that the importance attached to particle number emissions in traffic management policies be reassessed in the future.

2,4-Diodoaniline

The structure of the title compound C6H6I2N shows a weak intermolecular amine-amine N--H...N hydrogen-bonding interaction giving a helical chain which extends along the axis. An intramolecular N-H...I hydrogen bond is also observed.

Sodium 2-nitrocinnamate dihydrate: a one-dimensional hydrogen-bonded coordination polymer

The title compound catena-poly[aqua-mu3-2-nitrocinnamato], [Na(C9H6NO4)(H2O)2]n, the sodium salt of trans-2-nitrocinnamic acid, is a one-dimensional coordination polymer based on six-coordinate octahedral NaO6 centres comprising three facially-related monodentate carboxylate O-atom donors from separate ligands (all bridging)[Na-O, 2.4370(13)-2.5046(13)A] and three water molecules (two bridging, one monodentate) [Na-O, 2.3782(13)-2.4404(17)A]. The structure is also stabilized by intra-chain water-O-H...O(carboxylate) and O-H...O(nitro) hydrogen bonds.

4-(2-Hydroxyethyl) anilinium 3,5-dinitrobenzoate

In the title compound, C8H12NO+ C7H3N2O6-, the anilinium and hydroxyl protons of the cation result in N-H...O, N-H..(O,O) and O-H...O hydrogen-bonding interactions with carboxylate O atom acceptors, forming a two-dimensional network structure. An intermolecular C-H...O interaction is also present.

8-Ammonionaphthalene-2-sulfonate monohydrate : the zwitterionic hydrate of 1,7-Cleve's acid

The structure of 8-amino-2-naphthalenesulfonic acid monohydrate (1,7-Cleve's acid hydrate), C10H9NO3S.H2O, shows the presence of a sulfonate-aminium group zwitterion, both groups and the water molecule of solvation giving cyclic R3/3(8) intermolecular hydrogen-bonding interactions forming chains which extend down a axis of the unit cell. Additional peripheral associations, including weak aromatic ring pi-pi interactions [centroid-centroid distance 3.6299(15)A], result in a two-dimensional sheet structure.

4-Chloroanilinium 2-carboxy-4,5-dichlorobenzoate

The structure of the 1:1 proton-transfer compound of 4-chloroaniline with 4,5-dichlorophthalic acid (DCPA), viz. C6H7ClN+ C8H3Cl2O4-, has been determined at 130 K. The non-planar hydrogen phthalate anions and the 4-chloroanilinium cations form two-dimensional O-H...O and N-H...O hydrogen-bonded substructures which have no peripheral extension. Between the sheets there are weak \p--\p associations between alternating cation--anion aromatic ring systems [shortest centroid separation, 3.735(4)A].

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

Synthesis of a heparan sulfate mimetic disaccharide with a conformationally locked residue from a common intermediate

A simple mimetic of a heparan sulfate disaccharide sequence that binds to the growth factors FGF-1 and FGF-2 was synthesized by coupling a 2-azido-2-deoxy-D-glucosyl trichloroacetimidate donor with a 1,6-anhydro-2-azido-2-deoxy--D-glucose acceptor. Both the donor and acceptor were obtained from a common intermediate readily obtained from D-glucal. Molecular docking calculations showed that the predicted locations of the disaccharide sulfo groups in the binding site of FGF-1 and FGF-2 are similar to the positions observed for co-crystallized heparin-derived oligosaccharides obtained from published crystal structures.

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.

The PG500 series : novel heparan sulfate mimetics as potent angiogenesis and heparanase inhibitors for cancer therapy

Heparan sulfate mimetics, which we have called the PG500 series, have been developed to target the inhibition of both angiogenesis and heparanase activity. This series extends the technology underpinning PI-88, a mixture of highly sulfated oligosaccharides which reached Phase III clinical development for hepatocellular carcinoma. Advances in the chemistry of the PG500 series provide numerous advantages over PI-88. These new compounds are fully sulfated, single entity oligosaccharides attached to a lipophilic moiety, which have been optimized for drug development. The rational design of these compounds has led to vast improvements in potency compared to PI-88, based on in vitro angiogenesis assays and in vivo tumor models. Based on these and other data, PG545 has been selected as the lead clinical candidate for oncology and is currently undergoing formal preclinical development as a novel treatment for advanced cancer.

Unusual hydrate stabilization in the two-dimensional layered structure of quinacrinium bis(2-carboxy-4,5-dichlorobenzoate) tetrahydrate, a proton-transfer compound of the drug quinacrine

The crystal structure of the hydrated proton-transfer compound of the drug quinacrine [rac-N'-(6-chloro-2-methoxyacridin-9-yl)-N,N-diethylpentane-1,4-diamine] with 4,5-dichlorophthalic acid, C23H32ClN3O2+ . 2(C8H3Cl2O4-).4H2O (I), has been determined at 200 K. The four labile water molecules of solvation form discrete ...O--H...O--H... hydrogen-bonded chains parallel to the quinacrine side chain, the two N--H groups of which act as hydrogen-bond donors for two of the water acceptor molecules. The other water molecules, as well as the acridinium H atom, also form hydrogen bonds with the two anion species and extend the structure into two-dimensional sheets. Between these sheets there are also weak cation--anion and anion--anion pi-pi aromatic ring interactions. This structure represents only the third example of a simple quinacrine derivative for which structural data are available but differs from the other two in that it is unstable in the X-ray beam due to efflorescence, probably associated with the destruction of the unusual four-membered water chain structures.

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.