QMX: A versatile environment for hybrid calculations applied to the grafting of Al2Cl3Me3 on a silica surface

We present a new software to easily perform QM:MM and QM:QM' calculations called QMX. It follows the subtraction scheme and it is implemented in the Atomic Simulation Environment (ASE). Special attention is paid to couple molecular calculations with periodic boundaries approaches. QMX inherits the flexibility and versatility of the ASE package: any combination of methods namely force field, semiempirical, first principle, and ab initio, can be used as hybrid potential energy surface (PES). Its ease of use is demonstrated by considering the adsorption of Al₂Cl₃Me₃ on silica surface and by combining different levels of theory (from standard DFT to MP2 calculations) for the so‐called High Level cluster with standard PW91 density functional theory calculations for the Low Level environment. It is shown that the High Level cluster must contain the silanol group close to the aluminum atoms. The bridging adsorption is favored by 58 kJ mol^?1 at the MP2:PW91 level with respect to the terminal position. Using large clusters at the MP2:PW91 level, it is shown that PW91 calculations are sufficient for structure optimization but that embedded methods are required for accurate energy profiles. © 2013 Wiley Periodicals, Inc.     

Development of an automated dual‐mode supercritical fluid chromatography and reversed‐phase liquid chromatography mass‐directed purification system for small‐molecule drug discovery

We report the development of a dual‐mode mass‐directed supercritical fluid chromatography and reversed‐phase liquid chromatography purification system. The addition of a third pump allows for flexible mobile phase control between the two techniques, and enables operation of either chromatography mode within minutes by activation of a set of switching valves on a single system. Software control, fluidic pathways, interface to the mass spectrometer, and fraction collection have been modified for compatibility between both separation methods. The conditioning solvent and tuning parameters for the mass spectrometer were adjusted to achieve an ideal signal trace in either mode with good linearity (r² > 0.970) over a range of concentrations and minimal noise for accurate peak detection and isolation. The registration success rate is 90% and overall sample recovery for either technique is 80?90%. Combining two orthogonal separation and purification modes in one single system has improved the purification throughput of complex mixtures and has been a valuable, cost‐saving tool in our laboratory.     

Discovery and validation of urinary exposure markers for different plant foods by untargeted metabolomics

While metabolomics is increasingly used to investigate the food metabolome and identify new markers of food exposure, limited attention has been given to the validation of such markers. The main objectives of the present study were to (1) discover potential food exposure markers (PEMs) for a range of plant foods in a study setting with a mixed dietary background and (2) validate PEMs found in a previous meal study. Three-day weighed dietary records and 24-h urine samples were collected three times during a 6-month parallel intervention study from 107 subjects randomized to two distinct dietary patterns. An untargeted UPLC-qTOF-MS metabolomics analysis was performed on the urine samples, and all features detected underwent strict data analyses, including an iterative paired t test and sensitivity and specificity analyses for foods. A total of 22 unique PEMs were identified that covered 7 out of 40 investigated food groups (strawberry, cabbages, beetroot, walnut, citrus, green beans and chocolate). The PEMs reflected foods with a distinct composition rather than foods eaten more frequently or in larger amounts. We found that 23 % of the PEMs found in a previous meal study were also valid in the present intervention study. The study demonstrates that it is possible to discover and validate PEMs for several foods and food classes in an intervention study with a mixed dietary background, despite the large variability in such a dataset. Final validation of PEMs for intake of foods should be performed by quantitative analysis.

Uncertainty measurement for automated macro program-processed quantitative proton NMR spectra

The evaluation of a fully automated quantitative proton nuclear magnetic resonance spectroscopy (qNMR) processing program, including the determination of its processing uncertainty, and the calculations of the combined uncertainty of the qNMR result, is presented with details on the use of a trimmed purity average. Quantitative NMR spectra (1359) were collected over a 4-month period on various concentrations of pseudoephedrine HCl dissolved in D₂O (0.0610 to 93.60 mg/mL) containing maleic acid (the internal standard) to yield signal-to-noise ratios ranging from 3 to 72,000 for analyte integral regions. The resulting 5436 purities exhibited a normal distribution about the best estimate of the true value. The median absolute deviation (MAD) statistical method was used to obtain a model of uncertainty relative to the signal-to-noise of the analyte’s integral peaks. The model was then tested using different concentrations of known purity chloroquine diphosphate. qNMR results of numerous illicit heroin HCl samples were compared to those obtained by capillary electrophoresis. Graphical Abstract

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Single versus poly-crystalline layered oxide cathode materials for solid-state battery applications - a short review article

The recent developments in the application of single-crystalline (SC) cathode materials in solid-state batteries are discussed in this mini-review. The characteristics of SC and poly-crystalline (PC) cathode materials are explored, with emphasis on the kinetic and mechanical properties. The critical factors influencing their performance in liquid electrolyte and solid-state battery cells are investigated. Finally, the advantages and disadvantages of both morphologies are discussed and considerations to ensure a fair comparison between SC and PC cathodes in different systems are raised.     

Characterization of Functional Groups in Estuarine Dissolved Organic Matter by DNP-enhanced 15N and 13C Solid-State NMR

Estuaries are key ecosystems with unique biodiversity and are of high economic importance. Along the estuaries, variations in environmental parameters, such as salinity and light penetration, can modify the characteristics of dissolved organic matter (DOM). Nevertheless, there is still limited information about the atomic-level transformations of DOM in this ecosystem. Solid-state NMR spectroscopy provides unique insights into the nature of functional groups in DOM. A major limitation of this technique is its lack of sensivity, which results in experimental time of tens of hours for the acquisition of ¹³C NMR spectra and generally precludes the observation of ¹⁵N nuclei for DOM. We show here how the sensitivity of solid-state NMR experiments on DOM of Seine estuary can be enhanced using dynamic nuclear polarization (DNP) under magic-angle spinning. This technique allows the acquisition of ¹³C NMR spectra of these samples in few minutes, instead of hours for conventional solid-state NMR. Both conventional and DNP-enhanced ¹³C NMR spectra indicate that the ¹³C local environments in DOM are not strongly modified along the Seine estuary. Furthermore, the sensitivity gain provided by the DNP allows the detection of ¹⁵N NMR signal of DOM, in spite of the low nitrogen content. These spectra reveal that the majority of nitrogen is in the amide form in these DOM samples and show an increased disorder around these amide groups near the mouth of the Seine.     

Red Blood Cell Stiffness and Adhesion Are Species-Specific Properties Strongly Affected by Temperature and Medium Changes in Single Cell Force Spectroscopy

Besides human red blood cells (RBC), a standard model used in AFM-single cell force spectroscopy (SCFS), little is known about apparent Young’s modulus (Ea) or adhesion of animal RBCs displaying distinct cellular features. To close this knowledge gap, we probed chicken, horse, camel, and human fetal RBCs and compared data with human adults serving as a repository for future studies. Additionally, we assessed how measurements are affected under physiological conditions (species-specific temperature in autologous plasma vs. 25 °C in aqueous NaCl solution). In all RBC types, Ea decreased with increasing temperature irrespective of the suspension medium. In mammalian RBCs, adhesion increased with elevated temperatures and scaled with reported membrane sialic acid concentrations. In chicken only adhesion decreased with higher temperature, which we attribute to the lower AE-1 concentration allowing more membrane undulations. Ea decreased further in plasma at every test temperature, and adhesion was completely abolished, pointing to functional cell enlargement by adsorption of plasma components. This halo elevated RBC size by several hundreds of nanometers, blunted the thermal input, and will affect the coupling of RBCs with the flowing plasma. The study evidences the presence of a RBC surface layer and discusses the tremendous effects when RBCs are probed at physiological conditions.     

Pharmacological modulation of functional connectivity: the correlation structure underlying the phMRI response to d-amphetamine modified by selective dopamine D3 receptor antagonist SB277011A

Pharmacological MRI (phMRI) experiments utilise fMRI time series methods to map the central effect of pharmaceutical compounds. The typical univariate maps may, however, integrate the effects of several different neurotransmitter systems or underlying mechanisms. The results may thus be spatially and/or mechanistically nonspecific. Intersubject correlation analysis based on the phMRI response amplitude can more directly identify patterns of functional connectivity underlying the central effects of an acutely administered compound. In this article, we extend this approach to experiments where the effects of one compound in modulating the response to another are of interest. Specifically, we show a modulation of the correlation structure of a probe compound (d-amphetamine) by pretreatment with the selective dopamine D3 receptor antagonist SB277011A in the rat. The strongest modifications in the correlation patterns occurred in connection with the ventral tegmental area, the source of mesolimbic dopamine projections and a key substrate in the reward system.