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High-oxidation-state group 6 metal alkylidenes have been dominated by imido and oxo ligands. Here, the first neutral tungsten sulfido alkylidene and cationic tungsten sulfido alkylidene N-heterocyc...

Covalent organic frameworks (COFs) with a pore size beyond 5 nm are still rarely seen in this emerging field. Besides obvious complications such as the elaborated synthesis of large linkers with sufficient solubility, more subtle challenges regarding large-pore COF synthesis, including pore occlusion and collapse, prevail. Here we present two isoreticular series of large-pore imine COFs with pore sizes up to 5.8 nm and correlate the interlayer interactions with the structure and thermal behavior of the COFs. By adjusting interlayer interactions through the incorporation of methoxy groups acting as pore-directing "anchors", different stacking modes can be accessed, resulting in modified stacking polytypes and, hence, effective pore sizes. A strong correlation between stacking energy toward highly ordered, nearly eclipsed structures, higher structural integrity during thermal stress, and a novel, thermally induced phase transition of stacking modes in COFs was found, which sheds light on viable design strategies for increased structural control and stability in large-pore COFs.

We compare three methods for quantitatively distinguishing the location of noble metal (NM) particles in mesopores from those found on the external support surface. MCM-41 and SBA-15 with NM located in mesopores or on the external surface were prepared and characterized by TEM. 31 P MAS NMR spectroscopy was used to quantify arylphosphines in complexes with NM. Phosphine/NM ratios drop from 2.0 to 0.2 when increasing the probe diameter from 1.08 to 1.54 nm. The reaction between NM and triphenylphosphine (TPP) within 3.0 nm MCM-41 pores takes due to confinement effects multiple weeks. In contrast, external NM react with TPP instantly. A promising method is filling the pores by using the pore volume impregnation technique with tetraethylorthosilicate (TEOS). TPP loading revealed that 66 % of NMs are located on the external surface of MCM-41. The pore filling method can be used in association with any probe molecule, also for the quantification of acid sites.

The recent wave of detections of interstellar aromatic molecules has sparked interest in the chemical behaviour of aromatic molecules under astrophysical conditions. In most cases, these detections have been made through chemically related molecules, called proxies, that implicitly indicate the presence of a parent molecule. In this study, we present the results of the theoretical evaluation of the hydrogenation reactions of different aromatic molecules (benzene, pyridine, pyrrole, furan, thiophene, silabenzene, and phosphorine). The viability of these reactions allows us to evaluate the resilience of these molecules to the most important reducing agent in the interstellar medium, the hydrogen atom (H). All significant reactions are exothermic and most of them present activation barriers, which are, in several cases, overcome by quantum tunnelling. Instanton reaction rate constants are provided between 50 and 500 K. For the most efficiently formed radicals, a second hydrogenation step has been studied. We propose that hydrogenated derivatives of furan and pyrrole, especially 2,3-dihydropyrrole, 2,5-dihydropyrrole, 2,3-dihydrofuran, and 2,5-dihydrofuran, are promising candidates for future interstellar detections.

For the fatigue life of thin-walled components, not only fatigue crack initiation, but also crack growth is decisive. The phase-field method for fracture is a powerful tool to simulate arbitrary crack phenomena. Recently, it has been applied to fatigue fracture. Those models pose an alternative to classical fracture-mechanical approaches for fatigue life estimation. In the first part of this paper, the parameters of a phase-field fatigue model are calibrated and its predictions are compared to results of fatigue crack growth experiments of aluminium sheet material. In the second part, compressive residual stresses are introduced into the components with the help of laser shock peening. It is shown that those residual stresses influence the crack growth rate by retarding and accelerating the crack. In order to study these fatigue mechanisms numerically, a simple strategy to incorporate residual stresses in the phase-field fatigue model is presented and tested with experiments. The study shows that the approach can reproduce the effects of the residual stresses on the crack growth rate.

Enantiopure secondary alcohols are fundamental high‐value synthetic building blocks. One of the most attractive ways to get access to this compound class is the catalytic hydroboration. We describe a new concept for this reaction type that allowed for exceptional catalytic turnover numbers (up to 15 400), which were increased by around 1.5–3 orders of magnitude compared to the most active catalysts previously reported. In our concept an aprotic ammonium halide moiety cooperates with an oxophilic Lewis acid within the same catalyst molecule. Control experiments reveal that both catalytic centers are essential for the observed activity. Kinetic, spectroscopic and computational studies show that the hydride transfer is rate limiting and proceeds via a concerted mechanism, in which hydride at Boron is continuously displaced by iodide, reminiscent to an SN2 reaction. The catalyst, which is accessible in high yields in few steps, was found to be stable during catalysis, readily recyclable and could be reused 10 times still efficiently working., A new concept for asymmetric hydroboration of ketones is shown, in which an ammonium halide initiates a hydride transfer to a Lewis acid activated ketone. Advantages of the bifunctional catalyst include remarkable turnover numbers (up to 15 400, 50 ppm catalyst) and high enantioselectivity. The catalyst was recycled 10 times still providing high efficiency. Mechanistic and DFT studies confirm the cooperative mechanism.

The charge delocalization between the N-heterocyclic carbene (NHC) and the metal in cationic molybdenum imido alkylidene NHC mono(nonafluoro-tert-butoxide) complexes has been studied for different ...

Polycyclic aromatic hydrocarbons (PAHs) constitute an essential family of compounds in interstellar (ISM) and circumstellar (CSM) media. Recently, formation routes for the corresponding polycyclic aromatic phosphorus heterocycles (PAPHs) in astrophysical environments have been proposed. In order to contribute to a better understanding of the phosphorus chemistry in the ISM, infrared (IR) spectra and selected properties of PAPHs were computed at the density functional theory level for neutral, cationic, and anionic species. Our results reveal that several protonated PAPHs do not have planar backbones, and all species have permanent dipole moments between 2D and 4D. Closed-shell PAPHs have similar ionization potentials compared to the parent PAHs, below the Lyman threshold limit. In addition, all PAPHs show positive electron affinities higher than those of PAHs. Protonation preferably occurs on the heteroatom but with lower proton affinities than those of the corresponding nitrogen analogues (polycyclic aromatic nitrogen heterocycles). In general, neutral species have similar IR spectra profile with the most intense bands around 800 cm−1 (12.5 μm) related to C−H wagging. Charge and protonation affect the IR spectra mainly by decreasing the intensities of these modes and increasing the ones between 1000 (10.0 μm) and 1800 cm−1 (5.6 μm). The P−H stretching appears in a different spectral region, between 2300 (4.3 μm) and 2700 cm−1 (3.7 μm). Our results are discussed in the context of distinct sources where PAHs and phosphorus are detected. PAPHs, in particular the coronene derivatives, can contribute to the unidentified infrared emission band at 6.2 μm.

Atom probe tomography allows us to measure the three-dimensional composition of materials with up to atomic resolution by evaporating the material using high electric fields. Initially developed for metals, it is increasingly used for covalently bound structures. To aid the interpretation of the obtained fragmentation pattern, we modeled the fragmentation and desorption of self-assembled monolayers of thiolate molecules on a gold surface in strong electrostatic fields using density functional theory. We used a cluster model and a periodic model of amino-undecanethiolate, NH

The influence of nuclearity and charge of chiral Rh diene complexes on the activity and enantioselectivity in catalytic asymmetric 1,2-additions of organoboron reagents to N-tosylimines and 1,4-add...

DFT calculations were carried out to explore all relevant pathways for the ring-closing metathesis (RCM) reaction of a cationic molybdenum imido alkylidene N-heterocyclic carbene (NHC) catalyst wit...

Summary Background Patients with inflammatory diseases, such as rheumatoid arthritis, often receive glucocorticoids, but long-term use can produce adverse effects. Evidence from randomised controlled trials to guide tapering of oral glucocorticoids is scarce. We investigated a scheme for tapering oral glucocorticoids compared with continuing low-dose oral glucocorticoids in patients with rheumatoid arthritis. Methods The Steroid EliMination In Rheumatoid Arthritis (SEMIRA) trial was a double-blind, multicentre, two parallel-arm, randomised controlled trial done at 39 centres from six countries (France, Germany, Italy, Russia, Serbia, and Tunisia). Adult patients with rheumatoid arthritis receiving tocilizumab and glucocorticoids 5–15 mg per day for 24 weeks or more were eligible for inclusion if they had received prednisone 5 mg per day for 4 weeks or more and had stable low disease activaity, confirmed by a Disease Activity Score for 28 joints–erythrocyte sedimentation rate (DAS28-ESR) of 3·2 or less 4–6 weeks before and on the day of randomisation. Patients were randomly assigned 1:1 to either continue masked prednisone 5 mg per day for 24 weeks or to taper masked prednisone reaching 0 mg per day at week 16. All patients received tocilizumab (162 mg subcutaneously every week or 8 mg/kg intravenously every 4 weeks) with or without csDMARDs maintained at stable doses during the entire 24-week study. The primary outcome was the difference in mean DAS28-ESR change from baseline to week 24, with a difference of more than 0·6 defined as clinically relevant between the continued-prednisone group and the tapered-prednisone group. The trial is registered with ClinicalTrials.gov , NCT02573012 . Findings Between Oct 21, 2015, and June 9, 2017, 421 patients were screened and 259 (200 [77%] women and 59 [23%] men) were recruited onto the trial. In all 128 patients assigned to the continued-prednisone regimen, disease activity control was superior to that in all 131 patients assigned to the tapered-prednisone regimen; the estimated mean change in DAS28-ESR from baseline to week 24 was 0·54 (95% CI 0·35–0·73) with tapered prednisone and −0·08 (–0·27 to 0·12) with continued prednisone (difference 0·61 [0·35–0·88]; p Interpretation In patients who achieved low disease activity with tocilizumab and at least 24 weeks of glucocorticoid treatment, continuing glucocorticoids at 5 mg per day for 24 weeks provided safe and better disease control than tapering glucocorticoids, although two-thirds of patients were able to safely taper their glucocorticoid dose. Funding F Hoffmann-La Roche.

Background Persistence is a key criterion for the risk assessment of chemicals. In degradation tests, microbial biodegradation of labeled test chemicals leads to the incorporation of the label in microbial biomass, resulting in biogenic non-extractable residues (bioNER), which are not considered as harmful in persistence assessment. The amount of bioNER can be estimated using the Microbial Turnover to Biomass (MTB) model. MTB estimates the biomass growth during productive degradation of a compound from theoretical growth yield and CO2-formation and gives an upper and a lower value for bioNER formation. Results We collected experimental data in order to test accuracy and precision of this estimation method. In total, 16 experimental studies were found in literature where bioNER was experimentally quantified. Hereof, 13 studies used the amount of label recovered from total amino acid (tAA) content as proxy for bioNER. Unfortunately, the comparison with experimental data was difficult due to the variety of employed methods. A conversion factor is required to extrapolate from tAA on bioNER, and this factor may vary during the experiment and between experiments. The bioNER formation for all compounds tested was calculated with the MTB method, and the outcome was compared to measured tAA as proxy for bioNER. The relation between predicted and measured bioNER was significant, but no better correlation was obtained than with CO2 to tAA. The mean absolute error of the prediction (low MTB versus tAA) was 5% (unit applied label, %aL). Large deviations between experimentally determined bioNER and the calculated result for some compounds may indicate problems in the experimental determination of bioNER. Conclusions MTB thus provides a robust model for determining of the potential amounts of biomass and bioNER formed from the degradation of organic chemicals.

A new type of electrolyte salt based on a weakly coordinating anion (Na-PPB) for RT Na-SPAN batteries has been developed. Na-PPB was synthesized in bulk via a one-pot reaction. NMR spectroscopy reveals high purity of the salt and stability even under ambient atmospheric conditions. Single-crystal X-ray analysis confirmed the molecular structure of Na-PPB with Na+ coordinated by one DME molecule. The electrolyte containing Na-PPB with PC + 10 wt% FEC showed high oxidative stability on Al current collector exceeding 5.5 V. In a Na-SPAN cell, the Na-PPB electrolyte allows for an initial and final discharge capacity (500 cycles) of 1140 mAh/gsulfur and 965 mAh/gsulfur respectively, obtained at 2C (3.35 A/gsulfur). The excellent electrochemical performance and good chemical stability of Na-PPB offers access to the design of novel electrolyte salts for RT Na-SPAN batteries.

Optical surfaces are achieving increasingly complex shapes which brings out challenges to functionalize them conformally for improved performance. Besides, plastic optics pose a great challenge on coating technologies due to their large coefficient of thermal expansion and poor adhesion of functional coatings. Here, the potential of plasma enhanced atomic layer deposition (PEALD) technique to develop uniform and 3D-conformal films on polycarbonate (PC) (Makrolon) planar and dome substrates has been explored. It enables to grow conformal Al2O3, TiO2 and SiO2 films on steeply curved PC substrates. Moreover, we demonstrate an 11-layer antireflection (AR) coating reaching about 0.2% reflection at 905 nm wavelength on the entire outer surface of several PC domes along with a consistent optical performance on the inner surface. The adhesion and environmental stability tests according to ISO-9211-04 resulted in promising adhesive and environmentally durable films on PC dome optics. These results suggest a possible way to grow uniform, dense, conformal, and stable optical coatings on sensitive polymer PC substrates for desired optical applications.

Microemulsions provide a unique opportunity to tailor the polarity and liquid confinement in asymmetric catalysis via nanoscale polar and nonpolar domains separated by a surfactant film. For chiral diene Rh complexes, the influence of counterion and surfactant film on the catalytic activity and enantioselectivity remained elusive. To explore this issue chiral norbornadiene Rh(X) complexes (X=OTf, OTs, OAc, PO2F2) were synthesized and characterized by X-ray crystallography and theoretical calculations. These complexes were used in Rh-catalyzed 1,2-additions of phenylboroxine to N-tosylimine in microemulsions stabilized either exclusively by n-octyl-beta-D-glucopyranoside (C(8)G(1)) or a C(8)G(1)-film doped with anionic or cationic surfactants (AOT, SDS and DTAB). The Rh(OAc) complex showed the largest dependence on the composition of the microemulsion, yielding up to 59 % (90 %ee) for the surfactant film doped with 5 wt% of AOT as compared to 52 % (58 %ee) for neat C(8)G(1) at constant surfactant concentration. Larger domains, determined by SAXS analysis, enabled further increase in yield and selectivity while the reaction rate almost remained constant according to kinetic studies.

Covalent organic frameworks (COFs) with a pore size beyond 5 nm are still rarely seen in this emerging field. Besides obvious complications like the elaborated synthesis of large linkers with sufficient solubility, more subtle challenges regarding large-pore COF synthesis, including pore occlusion and collapse, prevail. Here we present two isoreticular series of large-pore imine COFs with pore sizes up to 5.8 nm and correlate the interlayer-interactions with the structure and thermal behavior of the COFs. By adjusting interlayer-interactionsthroughthe incorporation of methoxy groups acting as pore-directing “anchors”, different stacking modes can be accessed, resulting in modified stacking polytypes and, hence, effective pore sizes. A strong correlation between stacking energy towards highly ordered, nearly-eclipsed structures, higher structural integrity during thermal stress, and a novel, thermally induced phase transition of stacking modes in COFs was found, which sheds light on viable design strategies for increased structural control and stability in large-pore COFs.

Overcoming the detrimental effects of sweet spots during crystallization is an important step to improve the quantitative abilities of matrix‐assisted laser desorption/ionization (MALDI) mass spectrometry. In this study, we introduce MALDI targets, which exhibit a channel design to reduce sweet spot phenomena and improve reproducibility. The size of the channels was 3.0 mm in length, 0.35 mm in depth, and 0.40 mm in width, adjusted to the width of the implemented laser beam. For sample deposition, the matrix/sample mixture was homogenously deposited into the channels using capillary action. To demonstrate the proof‐of‐principle, the novel plates were used for the quantification of acetyl‐L‐carnitine in human blood plasma using a combined standard addition and isotope dilution method. The results showed that the reproducibility of acetyl‐L‐carnitine detection was highly improved over a conventional MALDI‐MS assay, with RSD values of less than 5.9% in comparison with 15.6% using the regular MALDI method. The limits of quantification using the new plates were lowered approximately two‐fold in comparison with a standard rastering approach on a smooth stainless‐steel plate. Matrix effects were also assessed and shown to be negligible. The new assay was subsequently applied to the quantification of acetyl‐L‐carnitine in human plasma samples.

New tungsten and molybdenum alkylidyne complexes bearing mono-, bi-, and tridentate N-heterocyclic carbenes (NHCs) have been synthesized. Formation of unprecedented structures in complexes bearing ...

We implemented a gradient-based algorithm for finding minimum energy paths (MEPs) using Gaussian process regression (GPR). A subsequent search for transition states can be performed very fast. We describe the algorithm in detail and compare its performance to the nudged elastic band (NEB) method in 27 test systems. Additionally, three different possibilities for an initial guess of the path are evaluated. We found the new optimizer to considerably decrease the number of required energy and gradient evaluations.

Soil carbon transformation and sequestration have received significant interest in recent years due to a growing need for quantitating its role in mitigating climate change. Even though our understanding of the nature of soil organic matter has recently been substantially revised, fundamental uncertainty remains about the quantitative importance of microbial necromass as part of persistent organic matter. Addressing this uncertainty has been hampered by the absence of quantitative assessments whether microbial matter makes up the majority of the persistent carbon in soil. Direct quantitation of microbial necromass in soil is very challenging because of an overlapping molecular signature with nonmicrobial organic carbon. Here, we use a comprehensive analysis of existing biomarker amino sugar data published between 1996 and 2018, combined with novel appropriation using an ecological systems approach, elemental carbon-nitrogen stoichiometry, and biomarker scaling, to demonstrate a suit of strategies for quantitating the contribution of microbe-derived carbon to the topsoil organic carbon reservoir in global temperate agricultural, grassland, and forest ecosystems. We show that microbial necromass can make up more than half of soil organic carbon. Hence, we suggest that next-generation field management requires promoting microbial biomass formation and necromass preservation to maintain healthy soils, ecosystems, and climate. Our analyses have important implications for improving current climate and carbon models, and helping develop management practices and policies.

Many organic co-solutes are known to stabilize or to destabilize native structures of proteins or DNA. Most of these effects can be explained by co-solute binding or exclusion mechanisms. A beneficial approach to study the underlying principles relies on the computation of Kirkwood–Buff integrals, which can be also used to derive detailed expressions for transfer free energies and changes of the chemical equilibrium between the unfolded and the native states. In this article, we use the framework of Kirkwood–Buff theory in order to study the influence of ectoine on the stability of short DNA hairpins. Our results highlight a strong binding of ectoine, which reveals a pronounced destabilization of DNA in good agreement with experimental findings.

Formylglycine generating enzyme is a copper and oxygen-dependent protein, which catalyzes C–H activation, namely the transformation of peptidyl cysteine to formylglycine. No crystal structures of the enzyme containing copper were published so far. Here, we show by combinations of density functional theory with force fields in the QM/MM approach how copper can be incorporated in the enzyme based on two crystal structures containing Ag(I) and Cd(II) in place of Cu(I) and Cu(II). While we find a linear coordination for Cu(I) and a distorted octahedral environment for Cu(II) we also find the possibility of tetrahedral coordinations in both cases. This structural flexibility may allow the enzyme to catalyze the redox process and accommodate copper in both oxidation states.

The proton affinity (PA) of a range of structurally different N-heterocycles with an exocyclic double bond (= N-heterocyclic olefins, NHOs) has been determined using DFT calculations on the BLYP/def2-TZVPP level. It was found that NHOs belong to the upper end of the superbasicity scale, covering PA values from 262 to 296 kcal/mol. Different types of NHOs are compared with each other and with frequently employed organocatalysts. To boost PA, (a) the ability to delocalize the positive charge and (b) steric pressure/ring strain which can be relieved after protonation were identified as key tuning parameters. Importantly, by analyzing PA alongside partial charges and molecular electrostatic potentials, it is shown that an increase of double bond polarization is not a necessary prerequisite for high PA. In contrast, the more basic, more sterically congested NHOs minimize unfavorable interactions by partly pyramidalyzing the nitrogen atoms, rendering the olefinic bond less electron rich and less polarized. These findings are in excellent agreement with experimental evidence on NHO catalysis, not only providing guidelines for a more rational design regarding PA/basicity but also suggesting that NHOs could be specifically tailored toward either nucleophilic or base-type reaction pathways.

In the mid-1950s, Bert Lester Vallee and his colleague Marvin Margoshes discovered a molecule referred to today as metallothionein (MT). Meanwhile, MTs have been shown to be common in many biological organisms. Despite their prevalence, however, it remains unclear to date what exactly MTs do and how they contribute to the biological function of an organism or organ. We investigate why biochemical research has not yet been able to pinpoint the function(s) of MTs. We shall systematically examine both the discovery of and recent research on Dr. Vallee’s beloved family of MT proteins utilizing tools from philosophy of science. Our analysis highlights that Vallee’s initial work exhibited features prototypical of a developing research tradition: it was upward-looking, exploratory, and utilized mere interactions. Since the 1960s, MT research has increasingly become intervention- and hypothesis-based while it remained largely upward-looking in character. Whilst there is no reason to think that upward-looking research cannot successfully yield structure-function mappings, it has not yet been successful in the case of MTs. Thus, we suggest it might be time to change track and consider other research strategies looking into the evolution of MTs. Recent studies in mollusks render research in this direction worthy of pursuit.

Pesticides in agricultural surface water runoff cause a major threat to freshwater systems. Installation of filter systems or constructed wetlands in areas of preferential run-off is a possible measure for pesticides abatement. To develop such systems, combinations of filter materials suitable for retention of both hydrophilic and hydrophobic organic pesticides were tested for pesticide removal in planted microcosms. The retention of six pesticides frequently detected in surface waters (bentazone, MCPA, metalaxyl, propiconazole, pencycuron, and imidacloprid) was evaluated in unplanted and planted pot experiments with novel bed material mixtures consisting of pumice, vermiculite, water super-absorbent polymer (SAP) for retention of ionic and water soluble pesticides, and synthetic hydrophobic wool for adsorption of hydrophobic pesticides. The novel materials were compared to soil with high organic matter content. The highest retention of the pesticides was observed in the soil, with a considerable translocation of pesticides into the plants, and low leaching potential, in particular for the hydrophobic compounds. However, due to the high retention of pesticides in soil, environmental risks related to their long term mobilization cannot be excluded. Mixtures of pumice and vermiculite with SAP resulted in high retention of i) water and ii) both hydrophilic and hydrophobic pesticides but with much lower leaching potential compared to the mineral systems without SAP. Mixtures of such materials may provide near natural treatment options in riparian strips and also for treatment of rainwater runoff without the need for water containment systems.

We report new computational and experimental evidence of an efficient and astrochemically relevant formation route to formaldehyde (H$_2$CO). This simplest carbonylic compound is central to the formation of complex organics in cold interstellar clouds, and is generally regarded to be formed by the hydrogenation of solid-state carbon monoxide. We demonstrate H$_2$CO formation via the reaction of carbon atoms with amorphous solid water. Crucial to our proposed mechanism is a concerted proton transfer catalyzed by the water hydrogen bonding network. Consequently, the reactions $^3$C + H$_2$O -> $^3$HCOH and $^1$HCOH -> $^1$H$_2$CO can take place with low or without barriers, contrary to the high-barrier traditional internal hydrogen migration. These low barriers or absence thereof explain the very small kinetic isotope effect in our experiments when comparing the formation of H$_2$CO to D$_2$CO. Our results reconcile the disagreement found in the literature on the reaction route: C + H$_2$O -> H$_2$CO., Accepted for publication in JPCL

The mixed lineage leukemia 3 or MLL3 is the enzyme in charge of the writing of an epigenetic mark through the methylation of lysine 4 from the N-terminal domain of histone 3 and its deregulation has been related to several cancer lines. An interesting feature of this enzyme comes from its regulation mechanism, which involves its binding to an activating dimer before it can be catalytically functional. Once the trimer is formed, the reaction mechanism proceeds through the deprotonation of the lysine followed by the methyl-transfer reaction. Here we present a detailed exploration of the activation mechanism through a QM/MM approach focusing on both steps of the reaction, aiming to provide new insights into the deprotonation process and the role of the catalytic machinery in the methyl-transfer reaction. Our finding suggests that the source of the activation mechanism comes from conformational restriction mediated by the formation of a network of salt-bridges between MLL3 and one of the activating subunits, which restricts and stabilizes the positioning of several residues relevant for the catalysis. New insights into the deprotonation mechanism of lysine are provided, identifying a valine residue as crucial in the positioning of the water molecule in charge of the process. Finally, a tyrosine residue was found to assist the methyl transfer from SAM to the target lysine., Fondo Nacional de Desarrollo Científico, Tecnológico y de Innovación Tecnológica

We calculated reaction rate constants including atom tunneling for the hydrogen abstraction reaction CH3OH+H -> CH2OH+H2 with the instanton method. The potential energy was fitted by a neural network, that was trained to UCCSD(T)-F12/VTZ-F12 data. Bimolecular gas-phase rate constants were calculated using microcanonic instanton theory. All H/D isotope patterns on the CH3 group and the incoming H atom are studied. Unimolecular reaction rate constants, representing the reaction on a surface, down to 30 K, are presented for all isotope patterns. At 30 K they range from 4100 for the replacement of the abstracted H by D to ~ 8 for the replacement of the abstracting H to about 2--6 for secondary KIEs. The $^\text{12}$C/$^\text{13}$C kinetic isotope effect is 1.08 at 30 K, while the $^\text{16}$O/$^\text{18}$O kinetic isotope effect is vanishingly small. A simple kinetic surface model using these data predicts high abundances of the deuterated forms of methanol.

Taurine/α-ketoglutarate dioxygenase is one of the most studied α-ketoglutarate-dependent dioxygenases (αKGDs), involved in several biotechnological applications. We investigated the key step in the catalytic cycle of the αKGDs, the hydrogen transfer process, by a quantum mechanics/molecular mechanics approach (B3LYP/CHARMM22). Analysis of the charge and spin densities during the reaction demonstrates that a concerted mechanism takes place, where the H atom transfer happens simultaneously with the electron transfer from taurine to the Fe═O cofactor. We found the quantum tunneling of the hydrogen atom to increase the rate constant by a factor of 40 at 5 °C. As a consequence, a quite high kinetic isotope effect close to 60 is obtained, which is consistent with the experimental value.

Numerical optimization of the manufacturing process of hybrid lightweight struc- tures consisting of fiber-reinforced plastics (FRP) is of high importance. It can reduce the time to market and can also avoid the production of costly prototypes. To model the considered thermoforming process, the temperature dependent defor- mation mechanisms have to be characterized and modeled within a finite element framework. An industry-oriented approach based on the parameterization of a mate- rial model implemented in LS-DYNA is introduced. The accordingly parameterized material model for the FRP is eventually applied in the simulation of thermoforming processes to show the influence of process and material parameters on the forming behavior of the thermoplastic prepreg.

International audience; Aluminum (Al) can be taken up from food, packaging, or the environment and thus reaches the human gastrointestinal tract. Its toxic potential after oral uptake is still discussed. The fate of different solid and ionic Al species during the passage through the digestive tract is the focus of this research, as well as the cellular effects caused by these different Al species. The present study combines the physicochemical processing of three recently studied Al species (metallic Al0, mineral Al2O3, and soluble AlCl3) in artificial digestion fluids with in vitro cell systems for the human intestinal barrier. Inductively coupled plasma mass spectrometry (ICP-MS) and small-angle X-ray scattering (SAXS) methods were used to characterize the Al species in the artificial digestion fluids and in cell culture medium for proliferating and differentiated intestinal Caco-2 cells. Cytotoxicity testing and cellular impedance measurements were applied to address the effects of digested Al species on cell viability and cell proliferation. Microarray-based transcriptome analyses and quantitative real-time PCR were conducted to obtain a deeper insight into cellular mechanisms of action and generated indications for cellular oxidative stress and an influence on xenobiotic metabolism, connected with alterations in associated signaling pathways. These cellular responses, which were predominantly caused by formerly ionic Al species and only at very high concentrations, were not impacted by artificial digestion. A two-directional conversion of Al between ionic species and solid particles occurred throughout all segments of the gastrointestinal tract, as evidenced by the presence of nanoscaled particles. Nevertheless, this presence did not increase the toxicity of the respective Al species.

The hexapeptide hIAPP22–27 (NFGAIL) is known as a crucial amyloid core sequence of the human islet amyloid polypeptide (hIAPP) whose aggregates can be used to better understand the wild‐type hIAPP′s toxicity to β‐cell death. In amyloid research, the role of hydrophobic and aromatic‐aromatic interactions as potential driving forces during the aggregation process is controversially discussed not only in case of NFGAIL, but also for amyloidogenic peptides in general. We have used halogenation of the aromatic residue as a strategy to modulate hydrophobic and aromatic‐aromatic interactions and prepared a library of NFGAIL variants containing fluorinated and iodinated phenylalanine analogues. We used thioflavin T staining, transmission electron microscopy (TEM) and small‐angle X‐ray scattering (SAXS) to study the impact of side‐chain halogenation on NFGAIL amyloid formation kinetics. Our data revealed a synergy between aggregation behavior and hydrophobicity of the phenylalanine residue. This study introduces systematic fluorination as a toolbox to further investigate the nature of the amyloid self‐assembly process., F for formation: This study introduces systematic fluorination as a tool to investigate the nature of amyloid formation as shown for the model peptide NFGAIL. Modulation of hydrophobicity and the σ‐framework of the Phe residue trough fluorine and iodine led to different amyloid folding kinetics. TEM and SAXS studies revealed the presence of amyloid fibrils.

The approval of chemicals for placing on the market is subject to various regulations in many countries. Regulations often require the assessment of the environmental fate in simulation tests using isotope labels for facilitated analysis. Such tests simulate the turnover of a chemical in complex environmental systems such as soils, water-sediment or wastewater treatment systems. Non-extractable residues (NER) are formed during the turnover of organic chemicals in solid matrices. NER are the ‘black box’ in current risk assessments of organic chemicals since their chemical composition is largely unknown. NER can result from sorption of the parent compound or its primary transformation products to the solid matrix; this leads to xenobiotic NER formation (considered as ‘hidden hazard’). However, microbial biomass formed during microbial biodegradation of chemicals can also contribute substantially to NER formation (biogenic NER; considered as ‘safe sink’ of no environmental concern). Biogenic NER thus need to be distinguished from the toxic xenobiotic NER in improved risk assessments and registration procedures of chemicals. The formation and the analytics of NER have so far only been phenomenologically described. This chapter describes the general microbial degradation processes of organic chemicals and summarizes the state of the art on NER analytics with particular focus on biogenic NER. Knowledge gaps in the NER analytics and suggestions for improvement are presented.

Quantum mechanical tunneling of atoms is increasingly found to play an important role in many chemical transformations. Experimentally, atom-tunneling can be indirectly detected by temperature-independent rate constants at low temperature or by enhanced kinetic isotope effects. On the contrary, using computational investigations the influence of tunneling on the reaction rates can directly be monitored. The tunnel effect, for example, changes reaction paths and branching ratios, enables chemical reactions in an astrochemical environment that would be impossible by thermal transition, and influences biochemical processes.