X-ray crystallographic study of DNA duplex cross-linking: simultaneous binding to two d(CGTACG)(2) molecules by a bis(9-aminoacridine-4-carboxamide) derivative

Acridine-4-carboxamides form a class of known DNA mono-intercalating agents that exhibit cytotoxic activity against tumour cell lines due to their ability to inhibit topoisomerases. Previous studies of bis-acridine derivatives have yielded equivocal results regarding the minimum length of linker necessary between the two acridine chromophores to allow bis-intercalation of duplex DNA. We report here the 1.7 angstrom resolution X-ray crystal structure of a six-carbon-linked bis(acridine-4-carboxamide) ligand bound to d(CGTACG)(2) molecules by non-covalent duplex cross-linking. The asymmetric unit consists of one DNA duplex containing an intercalated acridine-4-carboxamide chromophore at each of the two CG steps. The other half of each ligand is bound to another DNA molecule in a symmetry-related manner, with the alkyl linker threading through the minor grooves. The two crystallographically independent ligand molecules adopt distinct side chain interactions, forming hydrogen bonds to either O6 or N7 on the major groove face of guanine, in contrast to the semi-disordered state of mono-intercalators bound to the same DNA molecule. The complex described here provides the first structural evidence for the non-covalent cross-linking of DNA by a small molecule ligand and suggests a possible explanation for the inconsistent behaviour of six-carbon linked bis-acridines in previous assays of DNA bis-intercalation.

Vibrations in the B-4 rhombic structure

A double minimum six-dimensional Potential energy surface (PES) is determined in symmetry coordinates for the most stable rhombic (D-2h) B-4 isomer in its (1)A(g) electronic ground state by fitting to energies calculated ab initio. The PES exhibits a barrier to the D-4h square structure of 255 cm(-1). The vibrational levels (J=0) are calculated variationally using an approach which involves the Watson kinetic energy operator expressed in normal coordinates. The pattern of about 65 vibrational levels up to 1600 cm-1 for all stable isotopomers is analyzed. Analogous to the inversion in ammonia-like molecules, the rhombus rearrangements lead to splittings of the vibrational levels. In B-4 it is the B-1g (D-4h mode which distorts the square molecule to its planar rhombic form. The anharmonic fundamental vibrational transitions of B-11(4) are calculated to be (splittings in parentheses): G(O) = 2352(22) cm(-1), v(1)(A(1g)) - 1136(24) cm(-1,) v(2)(B-1g)=209(144) cm(-1) v(3)(B-2g)=1198(19)cm(-1), v(4)(B-2u) = 271(24) cm(-1), and v(5) (E-u) = 1030( 166) cm(-1) (D-4h notation). Their variations in all stable isotoporners were investigated. Due to the presence of strong anharmonic resonances between the B-1g in-plane distortion and the B-2u, out-of-plane bending modes. the hiaher overtones and combination levels are difficult to assign unequivocally. (C) 2005 American Institute of Physics.

Intercalation of diiodine molecules in cis-Ru(bpy)(2)Cl-2

Reaction of diiodine with cis-Ru(bpy)(2)Cl-2 in methanol at room temperature yields a thermally stable intercalate cis-Ru(bpy)(2)Cl-2 center dot 1.7I(2) (1) which has been characterised by X-ray crystallography. Iodine is leeched from 1 as it reacts with acetone at room temperature. (C) 2005 Elsevier B.V. All rights reserved.

Mesoporous concentric magnetic FePt core-shells nanoparticle with functionalized surfaces for capturing metal ions and DNA molecules

It is demonstrated that monodisperse magnetic FePt nanoparticle can be engineered into a protective dense silica layer, followed by concentric outer mesoporous silica layers with tailored -SH, -SO3H and -NH2 surface groups, these new materials can be used to capture heavy metal ions and DNA molecules from solution specifically by their internal or/and external functionalised surfaces by magnetic means.

Selective catalytic oxidation of alkylaromatic molecules by nanosize water droplets containing Co2+ species in supercritical carbon dioxide fluid

Stabilized nano-sized water droplet carrying water-soluble Co2+ species is employed as a new catalyst system for the oxidation of the alkyl aromatics in the presence of a fluorinated surfactant. This stable system contains no labile C-H structure and can facilitate excellent mixing of catalytic Co(II)/NaBr species, hydrocarbon substrates and oxygen in supercritical carbon dioxide fluid, which is demonstrated to be an excellent alternative solvent system to acetic acid or nitric acid for air oxidation of a number of alkyl aromatic hydrocarbons using Co(II) species at mild conditions. As a result, potential advantages of this 'greener' catalytic method including safer operation, easier separation and purification, higher catalytic activity with selectivity and without using corrosive or oxidation unstable solvent are therefore envisaged.

Flavonoids: antioxidants or signalling molecules?

Many studies are accumulating that report the neuroprotective, cardioprotective, and chemopreventive actions of dietary flavonoids. While there has been a major focus on the antioxidant properties, there is an emerging view that flavonoids, and their in vivo metabolites, do not act as conventional hydrogen-donating antioxidants but may exert modulatory actions in cells through actions at protein kinase and lipid kinase signalling pathways. Flavonoids, and more recently their metabolites, have been reported to act at phosphoinositide 3-kinase (PI 3-kinase), Akt/protein kinase B (Akt/PKB), tyrosine kinases, protein kinase C (PKC), and mitogen activated protein kinase (MAP kinase) signalling cascades. Inhibitory or stimulatory actions at these pathways are likely to affect cellular function profoundly by altering the phosphorylation state of target molecules and by modulating gene expression. A clear understanding of the mechanisms of action of flavonoids, either as antioxidants or modulators of cell signalling, and the influence of their metabolism on these properties are key to the evaluation of these potent biomolecules as anticancer agents, cardioprotectants, and inhibitors of neurodegeneration (C) 2004 Elsevier Inc. All rights reserved.

Expressions and activities of cell cycle regulatory molecules during the transition from myocyte hyperplasia to hypertrophy

The role of cell cycle dependent molecules in controlling the switch from cardiac myocyte hyperplasia to hypertrophy remains unclear, although in the rat this process occurs between day 3 and 4 after birth. In this study we have determined (1) cell cycle profiles by fluorescence activated cell sorting (FACS); and (2) expressions, co-expressions and activities of a number of cyclins, cyclin-dependent kinases (CDKs) and CDK inhibitors by reverse transcriptase-polymerase chain reaction (RT-PCR), immunoblotting andin vitrokinase assays in freshly isolated rat cardiac myocytes obtained from 2, 3, 4 and 5-day-old animals. The percentage of myocytes found in the S phase of the cell cycle decreased significantly during the transition from hyperplasia to hypertrophy (5.5, 3.5, 2.3 and 1.9% of cells in 2-, 3-, 4- and 5-day-old myocytes, respectively,P<0.05), concomitant with a significant increase in the percentage of G0/G1phase cells. At the molecular level, the expressions and activities of G1/S and G2/M phase acting cyclins and CDKs were downregulated significantly during the transition from hyperplasia to hypertrophy, whereas the expressions and activities of G1phase acting cyclins and CDKs were upregulated significantly during this transition. In addition, p21CIP1- and p27KIP1- associated CDK kinase activities remained relatively constant when histone H1 was used as a substrate, whereas phosphorylation of the retinoblastoma protein was upregulated significantly during the transition from hyperplasia to hypertrophy. Thus, there is a progressive and significant G0/G1phase blockade during the transition from myocyte hyperplasia to hypertrophy. Whilst CDK2 and cdc2 may be pivotal in the withdrawal of cardiac myocytes from the cell cycle, CDK4 and CDK6 may be critical for maintaining hypertrophic growth of the myocyte during development.

Chiral molecules on surfaces

chiral molecules can modify surfaces in many ways. Long-range chiral structures can be induced by local chirality, which can act as templates stereo-directing other molecules. Such templates are either based on the arrangement of molecules alone or involve reconstruction of the substrate suface. Stereo-direction can also be achieved buy direct local interaction between chiral moleculesx. Even the adsorption of achiral molecules onto achiral surfaces can induce local chirality due to a reduction ofsymmetry in the presence of the surface. Intrinsically chiral metal and oxide surfaces can act as templates for enantioselective adsorption and surface reactions without any surface modification.

Effects of ammonia treatment and undegradable protein supplementation on nutrient digestion of sheep fed on wheat straw based diets.

A study was conducted to investigate the effects of wheat straw ammonisation and supplementation with a rumen undegradable protein (UDP) source on nutrient digestion and nitrogen balance by lambs while diets were supplemented with kibbled carob pods as energy source. Ammonisation increased the crude protein content of wheat straw by nearly 100% and decreased the contents of neutral detergent fibre and acid detergent fibre by 7% and 1.7% respectively. Treating the straw with ammonia resulted in significant (P<0.01) increase in nitrogen (N) intake and intakes of organic matter (OM) and dry matter (DM) tended toward significance (P<0.1). The UDP source had no effect (P>0.05) on DM and OM intakes but resulted in an increase (P<0.05) of N intakes. Both, ammonization and UDP supplementation increased (P<0.01) the DM, OM and N digestibility. In conclusion, the results of this study suggest that ammonisation and UDP supplementation is a practical dietary manipulation option to improve the nutritional status of ruminants fed on roughage-based diets.

The effect of dopant molecules on the molecular order of electrically-conducting films of polypyrrole

X-ray scattering curves have been measured for a range of electrochemically-prepared conducting polypyrrole films employing a variety of counterions in aqueous solutions. Films containing counterions based on aromatic rings exhibit an anisotropic molecular organization. The degree of anisotropy is enhanced through the use of highly planar counterions. The electrical conductivity of such films is also improved if the charge/volume ratio of the counterion is maintained at a high level. Polypyrrole films prepared using ‘spherically’ shaped counterions such as SO42− do not display such anisotropic molecular organizations, and exhibit lower electrical conductivities. The competing structural roles of the counterions within these molecular composites are discussed.

Diffraction from thermotropic copolyester molecules

Analytical expressions for the meridional scattering from highly oriented random copolyesters are presented. These procedures are utilised in developing the relationship of the features in the diffraction pattern to compositions and relative lengths of the constituent monomer units. The difference between the scattering patterns for random and block copolymers are discussed. The theory is applied to an example of a liquid crystal froming random copolyester.

Effluent quality and ammonia emissions from out-wintering pads in England, Wales and Ireland

Out-wintering pads offer a reduced cost system for wintering cattle, minimising damage to pasture, providing animal welfare and production benefits, and generate, potentially, a more manageable effluent and lower ammonia emissions. The objectives of the present study were (i) to contribute to improved understanding of the factors impacting on effluent quality, ammonia emissions and animal welfare via observations on four farm-based out-wintering pads (ComOWPs) in England, Wales and Ireland and more detailed studies undertaken on four experimental OWPs (ExpOWPs) constructed at Rothamsted Research North Wyke, Devon, England and (ii) to corroborate the effluent quality data from both the ComOWPs and the ExpOWPs, with findings in the literature. Woodchip size, feeding management and area allowance were the treatment factors applied on the ExpOWPs. These three factors were randomised across the four ExpOWPs, over four 6–7 week periods. Effluent quality from the ExpOWPs was sampled frequently in a flow proportional way and analysed for total N (TN); total P (TP); total solids (TS); ammonium-N (NH4+-N); nitrate-N (NO3−-N). Beef cattle were periodically weighed for determination of live weight gain (LWG). An approximate nitrogen balance was calculated as a means of understanding its partitioning and fate during and after the ExpOWPs use. Effluent quality from the ComOWPs was sampled frequently, also in a flow-proportional way, and analysed for TN, TP, TS, NH4+-N, NO3−-N, total K and COD. Effluent quality data from the ExpOWPs showed no significant differences (P > 0.05) between treatments, with average concentrations of 1095 mg l−1, and 806 mg l−1, for TN and NH4+-N, respectively. Average effluent concentrations from the ComOWPs were 356 mg l−1 TN and 124 mg l−1 NH4+-N. Ammonia emissions from the ExpOWPs showed no significant differences (P > 0.05) between the treatments, with average mean emission rates of 2.5 g m−2 d−1 NH3-N, respectively. A positive correlation was established between NH3-N emission rate and wind speed. Emission rates from the ComOWPs ranged from 0.7 to 1.6 g m−2 d−1 NH3-N. Average daily LWG on the ExpOWPs was 1.33 kg steer−1 d−1. The effluent from both the ComOWPs and ExpOWPs were more similar with dirty water and of consistently lower strength than beef cattle slurry, as supported by findings in the literature, and therefore, it is suggested to be subject to the regulatory requirements of dirty water rather than slurry.

The reaction between silylene and ammonia: some gas-phase kinetic and quantum chemical studies

Time-resolved kinetic studies of the reaction of silylene, SiH2, generated by 193 nm laser flash photolysis of silacyclopent-3-ene, have been carried out in the presence of ammonia, NH3. Second order kinetics were observed. The reaction was studied in the gas phase at 10 Torr total pressure in SF6 bath gas at each of the three temperatures, 299, 340 and 400 K. The second order rate constants (laser pulse energy of 60 mJ/pulse) fitted the Arrhenius equation: log(k/cm3 molecule-1 s-1) = (-10.37 ± 0.17) + (0.36 ± 1.12 kJ mol-1)/RTln10 Experiments at other pressures showed that these rate constants were unaffected by pressure in the range 10-100 Torr, but showed small decreases in value at 3 and 1 Torr. There was also a weak intensity dependence, with rate constants decreasing at laser pulse energies of 30 mJ/pulse. Ab initio calculations at the G3 level of theory, show that SiH2 + NH3 should form an initial adduct (donor-acceptor complex), but that energy barriers are too great for further reaction of the adduct. This implies that SiH2 + NH3 should be a pressure dependent association reaction. The experimental data are inconsistent with this and we conclude that SiH2 decays are better explained by reaction of SiH2 with the amino radical, NH2, formed by photodissociation of NH3 at 193 nm. The mechanism of this previously unstudied reaction is discussed.