Matrix-assisted laser desorption/ionization-ion mobility separation-mass spectrometry imaging of vinblastine in whole body tissue sections

During early-stage drug development, drug and metabolite distribution studies are carried out in animal tissues using a range of techniques, particularly whole body autoradiography (WBA). While widely employed, WBA has a number of limitations, including the following: expensive synthesis of radiolabeled drugs and analyte specificity and identification. WBA only images the radiolabel. MALDI MSI has been shown previously to be advantageous for imaging the distribution of a range of drugs and metabolites in whole body sections. Ion mobility separation (IMS) adds a further separation step to imaging experiments; demonstrated here is MALDI-IMS-MS whole body imaging of rats dosed at 6 mg/kg i.v. with an anticancer drug, vinblastine and shown is the distribution of the precursor ion m/z 811.4 and several product ions including m/z 793, 751, 733, 719, 691, 649, 524, and 355. The distribution of vinblastine within the ventricles of the brain is also depicted. Clearly demonstrated in these data are the removal of interfering isobaric ions within the images of m/z 811.4 and also of the transition m/z 811-751, resulting in a higher confidence in the imaging data. Within this work, IMS has shown to be advantageous in both MS and MS/MS imaging experiments by separating vinblastine from an endogenous isobaric lipid.     

Use of Linear Free Energy Relationships (LFERs) to Elucidate the Mechanisms of Reaction of a γ-Methyl-β-alkynyl and an ortho-Substituted Aryl Chloroformate Ester

The specific rates of solvolysis of 2-butyn-1-yl-chloroformate (1) and 2-methoxyphenyl chloroformate (2) are studied at 25.0 °C in a series of binary aqueousorganic mixtures. The rates of reaction obtained are then analyzed using the extended Grunwald-Winstein (G-W) equation and the results are compared to previously published G-W analyses for phenyl chloroformate (3), propargyl chloroformate (4), p-methoxyphenyl choroformate (5), and p-nitrophenyl chloroformate (6). For 1, the results indicate that dual side-by-side addition-elimination and ionization pathways are occurring in some highly ionizing solvents due to the presence of the electron-donating γ-methyl group. For 2, the analyses indicate that the dominant mechanism is a bimolecular one where the formation of a tetrahedral intermediate is rate-determining.     

Extra-terrestrial life in the European Space Agency's Cosmic Vision plan and beyond

Our exciting time allows us to contemplate the moment in the not-too-distant future when we can detect the presence of life on worlds orbiting stars other than our Sun. It will not be easy and will require the development and use of the very latest technologies. It also very probably demands deployment in space of relevant instrumentation in order to carry out these investigations. The European Space Agency has been involved in the studies and development of the required technologies for more than a decade and is currently formulating a roadmap for how to achieve the ultimate detection of signs of life as we know it on terrestrial exoplanets. The major elements of the roadmap consist of the following. First, the search for and detection of terrestrial exoplanets. Here, some progress has been made recently and is reported in this paper. Second, the more and more detailed study of the physical characteristics of such exoplanets. Finally, the search for biomarkers--indicators of biological activity--that can be observed at interstellar distances. The last is probably one of the most difficult problems ever contemplated by observational astronomy.     

Analysis of the inhibition of food spoilage yeasts by vanillin

The antimicrobial potential of vanillin, the major component of vanilla flavour, was examined against the growth of three yeasts associated with food spoilage, Saccharomyces cerevisiae, Zygosaccharomyces bailii and Zygosaccharomyces rouxii. Minimum inhibitory concentration (MIC) values of 21, 20 and 13 mM vanillin were determined for the three yeast strains, respectively. The observed inhibition was found to be biostatic. During fermentation, the bioconversion of sub-MIC levels of vanillin in the culture medium was demonstrated. The major bioconversion product was identified as vanillyl alcohol, however low levels of vanillic acid were also detected. Neither the vanillyl alcohol nor the vanillic acid was found to be antagonistic to yeast cell growth. The results indicate the importance of the aldehyde moiety in the vanillin structure regarding its antimicrobial activity and that the bioconversion of vanillin could be advantageous for the yeasts, but only at levels below MIC. These bioconversion activities, presumably catalysed by non-specific dehydrogenases, were shown to be expressed constitutively. It was observed that increased vanillin concentrations inhibited its own bioconversion suggesting that the activity required intact cells with metabolic capacity.     

A preliminary study on the effect of germination on saponin content and composition of lentils and chickpeas

Two cultivars of chickpeas (Cicer arietinum) and one cultivar of lentils (Lens culinaris) were subjected to germination in the dark for 6 days at 20°C. Soyasaponin VI, also known as soyasaponinβg, a DDMP- (2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one-) conjugated form of soyasaponin I, was the only saponin detected in both the unprocessed and germinated seed. No significant changes in saponin content were observed for chickpeas or lentils after a 6-day germination.     

Dissolution of various sources of gypsum in aqueous solutions and in soil

The dissolution of six sources of gypsum in water and 0.01 M CaCl₂ was examined in the presence and absence of soil. The gypsum samples included: analytical grade (AR), three sources of flue-gas desulphurisation (FGD) gypsum, phosphogypsum (PG), and mined gypsum (MG). Dissolution in aqueous solutions was monitored by measuring the concentration of calcium (Ca²⁺) and sulphate (SO) ions. In soils which adsorb small amounts of SO^?2₄, dissolution was estimated from the increase in the concentration of Ca²⁺ and SO in gypsum-treated soil over the control soil. However, in soils which adsorb significant amounts of SO, measurement of solution SO concentration underestimates the extent of dissolution. Gypsum dissolution was larger in water (15.20 mmol litre^?1) than in 0.01 M CaCl₂ (11.12 mmol litre^?1), and this was attributed to the Ca²⁺ common-ion effect. The rate of dissolution decreased in the order: AR > FGD > PG > MG. Dissolution was 2 to 10 times faster for powdered (< 500 .m) gypsum than for the discs obtained by pelletising. The differences in the rate of dissolution between the gypsum sources and between powder and disc samples were related to both surface area and the presence of CaCO₃, impurity. The rate of dissolution was 3 to 8 times faster in the presence than in the absence of soil. Whereas the dissolution of gypsum in the presence of soil followed first order reaction kinetics, it followed second order kinetics in the absence of soil. This difference in reaction kinetics resulted from the continuous removal of Ca2+ and SO by the soil.     

Design and synthesis of conformationally constrained cyclophilin inhibitors showing a cyclosporin-A phenotype in C. elegans

Cyclophilin A (CypA) is a member of the immunophilin family of proteins and receptor for the immunosuppressant drug cyclosporin A (CsA). Here we describe the design and synthesis of a new class of small-molecule inhibitors for CypA that are based upon a dimedone template. Electrospray mass spectrometry is utilised as an initial screen to quantify the protein affinity of the ligands. Active inhibitors and fluorescently labelled derivatives are then used as chemical probes for investigating the biological role of cyclophilins in the nematode Caenorhabditis elegans.     

Treatment of an Iron-rich ARD Using Waste Carbonate Rock: Bench-Scale Reactor Test Results

The treatment of acid rock drainage (ARD) places extraordinary financial burdens on governments and companies worldwide, and an improved efficiency in treatment by as little as 1% can save many millions of dollars in rehabilitation. We investigated a system for treating Fe-rich ARD using a three-stage reactor design. In the first reaction cell, Fe-rich ARD was partially neutralised using rapid periodic carbonate resuspension with a rotating axial mixer. This was followed by an air-sparged oxidation chamber and then a second reaction cell, with more carbonate periodically resuspended until a pH of 6.3 was reached, which was followed by a settlement chamber. This reactor design has a high capacity for neutralisation, with an efficiency of ≈70% of acidity neutralised by the acid neutralising capacity (g of CaCO₃ equivalent) added to the reactor. Axial mixers were tested because of their low-energy requirements and their high reliability. The intermediate chamber effectively removes Fe by oxidising Fe(II) to Fe(III). Given the amount of acidity neutralised, the sludge volume produced was low compared to other technologies, providing further potential savings in sludge handling. Waste carbonate rock proved to be an effective neutralising agent, even though it was about 60% dolomite and 40% magnesite, with minor calcite, and despite the fact that magnesite has substantially slower dissolution kinetics compared to the more dominant dolomite. The mixed waste carbonates were capable of raising the pH sufficiently to reduce the heavy metal loadings in Fe-rich ARD by more than two orders of magnitude. The final settlement stage of the process was shown to be essential for metal precipitation, for the carry-over of fine carbonates, and CO₂ loss. This was associated with a rise in pH, from 6.3 to 7.5. In addition, residual slow-reacting magnesite from the mixed carbonate remains in the sludge from the first reactor and provides acid buffering capacity within the sludge, which is commonly lacking in the ARD neutralisation sludge of other systems.