Molecular modelling studies of binding of DACD derivatives into G-Quadruplex DNA: comparison of force field and quantum polarized ligand docking methods

The DNA G-qadruplexes are one of the targets being actively explored for anti-cancer therapy by inhibiting them through small molecules. This computational study was conducted to predict the binding strengths and orientations of a set of novel dimethyl-amino-ethyl-acridine (DACA) analogues that are designed and synthesized in our laboratory, but did not diffract in Synchrotron light.Thecrystal structure of DNA G-Quadruplex(TGGGGT)4(PDB: 1O0K) was used as target for their binding properties in our studies.We used both the force field (FF) and QM/MM derived atomic charge schemes simultaneously for comparing the predictions of drug binding modes and their energetics. This study evaluates the comparative performance of fixed point charge based Glide XP docking and the quantum polarized ligand docking schemes. These results will provide insights on the effects of including or ignoring the drug-receptor interfacial polarization events in molecular docking simulations, which in turn, will aid the rational selection of computational methods at different levels of theory in future drug design programs. Plenty of molecular modelling tools and methods currently exist for modelling drug-receptor or protein-protein, or DNA-protein interactionssat different levels of complexities.Yet, the capasity of such tools to describevarious physico-chemical propertiesmore accuratelyis the next step ahead in currentresearch.Especially, the usage of most accurate methods in quantum mechanics(QM) is severely restricted by theirtedious nature. Though the usage of massively parallel super computing environments resulted in a tremendous improvement in molecular mechanics (MM) calculations like molecular dynamics,they are still capable of dealing with only a couple of tens to hundreds of atoms for QM methods. One such efficient strategy that utilizes thepowers of both MM and QM are the QM/MM hybrid methods. Lately, attempts have been directed towards the goal of deploying several different QM methods for betterment of force field based simulations, but with practical restrictions in place. One of such methods utilizes the inclusion of charge polarization events at the drug-receptor interface, that is not explicitly present in the MM FF.

Reversible thermal transition of polydiacetylene based on KTTKS collagen sequence

Here we explore the physico-chemical properties of a peptide amphiphile obtained by chemical conjugation of the collagenstimulating peptide KTTKS with 10,12-pentacosadiynoic acid which photopolymerizes as a stable and extended polydiacetylene. We investigate the self-assembly of this new polymer and rationalize its peculiar behavior in terms of a thermal conformational transition. Surprisingly, this polymer shows a thermal transition associated with a non-cooperative increase in b-sheet content at high temperature.

Nanoscale zerovalent iron alters soil bacterial community structure and inhibits chloroaromatic biodegradation potential in Aroclor 1242-contaminated soil

Nanoscale zerovalent iron (nZVI) has potential for the remediation of organochlorine-contaminated environments. Environmental safety concerns associated with in situ deployment of nZVI include potential negative impacts on indigenous microbes whose biodegradative functions could contribute to contaminant remediation. With respect to a two-step polychlorinated biphenyl remediation scenario comprising nZVI dechlorination followed by aerobic biodegradation, we examined the effect of polyacrylic acid (PAA)-coated nZVI (mean diameter = 12.5 nm) applied at 10 g nZVI kg−1 to Aroclor-1242 contaminated and uncontaminated soil over 28 days. nZVI had a limited effect on Aroclor congener profiles, but, either directly or indirectly via changes to soil physico-chemical conditions (pH, Eh), nZVI addition caused perturbation to soil bacterial community composition, and reduced the activity of chloroaromatic mineralizing microorganisms. We conclude that nZVI addition has the potential to inhibit microbial functions that could be important for PCB remediation strategies combining nZVI treatment and biodegradation.

Synthesis, characterization, crystal structure, and DNA-binding of ruthenium(II) complexes of heterocyclic nitrogen ligands resulting from a benzimidazole-based quinazoline derivative

The reaction of cis-[RuCl2(dmso)(4)] with [6-(2-pyridinyl)-5,6-dihydrobenzimidazo[1,2-c] quinazoline] (L) afforded in pure form a blue ruthenium(II) complex, [Ru(L-1)(2)] (1), where the original L changed to [2-(1H-benzoimidazol-2-yl)-phenyl]-pyridin-2-ylmethylene-amine (HL1). Treatment of RuCl3 center dot 3H(2)O with L in dry tetrahydrofuran in inert atmosphere led to a green ruthenium(II) complex, trans-[RuCl2(L-2)(2)] (2), where L was oxidized in situ to the neutral species 6-pyridin-yl-benzo[4,5]imidazo[1,2-c] quinazoline (L-2). Complex 2 was also obtained from the reaction of RuCl3 center dot 3H(2)O with L-2 in dry ethanol. Complexes 1 and 2 have been characterized by physico-chemical and spectroscopic tools, and 1 has been structurally characterized by single-crystal X-ray crystallography. The electrochemical behavior of the complexes shows the Ru(III)/Ru(II) couple at different potentials with quasi-reversible voltammograms. The interaction of these complexes with calf thymus DNA by using absorption and emission spectral studies allowed determination of the binding constant K-b and the linear Stern-Volmer quenching constant K-SV

The impact of climate change on the treatability of dissolved organic matter (DOM) in upland water supplies: A UK perspective

Climate change in the UK is expected to cause increases in temperatures, altered precipitation patterns and more frequent and extreme weather events. In this review we discuss climate effects on dissolved organic matter (DOM), how altered DOM and water physico-chemical properties will affect treatment processes and assess the utility of techniques used to remove DOM and monitor water quality. A critical analysis of the literature has been undertaken with a focus on catchment drivers of DOM character, removal of DOM via coagulation and the formation of disinfectant by-products (DBPs). We suggest that: (1) upland catchments recovering from acidification will continue to produce more DOM with a greater hydrophobic fraction as solubility controls decrease; (2) greater seasonality in DOM export is likely in future due to altered precipitation patterns; (3) changes in species diversity and water properties could encourage algal blooms; and (4) that land management and vegetative changes may have significant effects on DOM export and treatability but require further research. Increases in DBPs may occur where catchments have high influence from peatlands or where algal blooms become an issue. To increase resilience to variable DOM quantity and character we suggest that one or more of the following steps are undertaken at the treatment works: a) ‘enhanced coagulation’ optimised for DOM removal; b) switching from aluminium to ferric coagulants and/or incorporating coagulant aids; c) use of magnetic ion-exchange (MIEX) pre-coagulation; and d) activated carbon filtration post-coagulation. Fluorescence and UV absorbance techniques are highlighted as potential methods for low-cost, rapid on-line process optimisation to improve DOM removal and minimise DBPs.

Effect of seasonal variation on the composition and properties of raw milk destined for processing in the UK

The composition and physical properties of raw milk from a commercial herd were studied over a one year period in order to understand how best to utilise milk for processing throughout the year. Protein and fat levels demonstrated seasonal trends, while minerals and many physical properties displayed considerable variations, which were apparently unrelated to season. However, rennet clotting time, ethanol stability and foaming ability were subject to seasonal variation. Many significant interrelationships in physico-chemical properties were found. It is clear that the milk supply may be more suited to the manufacture of different products at different times of the year or even on a day to day basis. Subsequent studies will report on variation in production and quality of products manufactured from the same milk samples described in the current study and will thus highlight potential advantages of seasonal processing of raw milk.

Atmospheric chemistry and physics in the atmosphere of a developed megacity (London): an overview of the REPARTEE experiment and its conclusions

The REgents PARk and Tower Environmental Experiment (REPARTEE) comprised two campaigns in London in October 2006 and October/November 2007. The experiment design involved measurements at a heavily trafficked roadside site, two urban background sites and an elevated site at 160–190 m above ground on the BT Tower, supplemented in the second campaign by Doppler lidar measurements of atmospheric vertical structure. A wide range of measurements of airborne particle physical metrics and chemical composition were made as well as measurements of a considerable range of gas phase species and the fluxes of both particulate and gas phase substances. Significant findings include (a) demonstration of the evaporation of traffic-generated nanoparticles during both horizontal and vertical atmospheric transport; (b) generation of a large base of information on the fluxes of nanoparticles, accumulation mode particles and specific chemical components of the aerosol and a range of gas phase species, as well as the elucidation of key processes and comparison with emissions inventories; (c) quantification of vertical gradients in selected aerosol and trace gas species which has demonstrated the important role of regional transport in influencing concentrations of sulphate, nitrate and secondary organic compounds within the atmosphere of London; (d) generation of new data on the atmospheric structure and turbulence above London, including the estimation of mixed layer depths; (e) provision of new data on trace gas dispersion in the urban atmosphere through the release of purposeful tracers; (f) the determination of spatial differences in aerosol particle size distributions and their interpretation in terms of sources and physico-chemical transformations; (g) studies of the nocturnal oxidation of nitrogen oxides and of the diurnal behaviour of nitrate aerosol in the urban atmosphere, and (h) new information on the chemical composition and source apportionment of particulate matter size fractions in the atmosphere of London derived both from bulk chemical analysis and aerosol mass spectrometry with two instrument types.

Towards a unified approach for the determination of the bioaccessibility of organic pollutants

Bioaccessibility studies have been widely used as a research tool to determine the potential human exposure to ingested contaminants. More recently they have been practically applied for soil borne toxic elements. This paper reviews the application of bioaccessibility tests across a range of organic pollutants and contaminated matrices. Important factors are reported to be: the physiological relevance of the test, the components in the gut media, the size fraction chosen for the test and whether it contains a sorptive sink. The bioaccessibility is also a function of the composition of the matrix (e.g. organic carbon content of soils) and the physico-chemical characteristics of the pollutant under test. Despite the widespread use of these tests, there are a large number of formats used and very few validation studies with animal models. We propose a unified format for a bioaccessibility test for organic pollutants. The robustness of this test should first be confirmed through inter laboratory comparison, then tested in-vivo.

Long-term conditioning of soil by plantation eucalypts and pines does not affect growth of the native jarrah tree

Plant species can condition the physico-chemical and biological properties of soil in ways that modify plant growth via plant–soil feedback (PSF). Plant growth can be positively affected, negatively affected or neutrally affected by soil conditioning by the same or other plant species. Soil conditioning by other plant species has particular relevance to ecological restoration of historic ecosystems because sites set aside for restoration are often conditioned by other, potentially non-native, plant species. We investigated changes in properties of jarrah forest soils after long-term (35 years) conditioning by pines (Pinus radiata), Sydney blue gums (Eucalyptus saligna), both non-native, plantation trees, and jarrah (Eucalyptus marginata; dominant native tree). Then, we tested the influence of the conditioned soils on the growth of jarrah seedlings. Blue gums and pines similarly conditioned the physico-chemical properties of soils, which differed from soil conditioning caused by jarrah. Especially important were the differences in conditioning of the properties C:N ratio, pH, and available K. The two eucalypt species similarly conditioned the biological properties of soil (i.e. community level physiological profile, numbers of fungal-feeding nematodes, omnivorous nematodes, and nematode channel ratio), and these differed from conditioning caused by pines. Species-specific conditioning of soil did not translate into differences in the amounts of biomass produced by jarrah seedlings and a neutral PSF was observed. In summary, we found that decades of soil conditioning by non-native plantation trees did not influence the growth of jarrah seedlings and will therefore not limit restoration of jarrah following the removal of the plantation trees.

Terrestrial exposure of oilfield flowline additives diminish soil structural stability and remediative microbial function

Onshore oil production pipelines are major installations in the petroleum industry, stretching many thousands of kilometres worldwide which also contain flowline additives. The current study focuses on the effect of the flowline additives on soil physico-chemical and biological properties and quantified the impact using resilience and resistance indices. Our findings are the first to highlight deleterious effect of flowline additives by altering some fundamental soil properties, including a complete loss of structural integrity of the impacted soil and a reduced capacity to degrade hydrocarbons mainly due to: (i) phosphonate salts (in scale inhibitor) prevented accumulation of scale in pipelines but also disrupted soil physical structure; (ii) glutaraldehyde (in biocides) which repressed microbial activity in the pipeline and reduced hydrocarbon degradation in soil upon environmental exposure; (iii) the combinatory effects of these two chemicals synergistically caused severe soil structural collapse and disruption of microbial degradation of petroleum hydrocarbons.

Production of milk foams by steam injection: the effects of steam pressure and nozzle design

Foam properties depend on the physico-chemical characteristics of the continuous phase, the method of production and process conditions employed; however the preparation of barista-style milk foams in coffee shops by injection of steam uses milk as its main ingredient which limits the control of foam properties by changing the biochemical characteristics of the continuous phase. Therefore, the control of process conditions and nozzle design are the only ways available to produce foams with diverse properties. Milk foams were produced employing different steam pressures (100-280 kPa gauge) and nozzle designs (ejector, plunging-jet and confined-jet nozzles). The foamability of milk, and the stability, bubble size and texture of the foams were investigated. Variations in steam pressure and nozzle design changed the hydrodynamic conditions during foam production, resulting in foams having a range of properties. Steam pressure influenced foam characteristics, although the net effect depended on the nozzle design used. These results suggest that, in addition to the physicochemical determinants of milk, the foam properties can also be controlled by changing the steam pressure and nozzle design.