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Chemosphere Jun 2024The processes leading to high levels of arsenic (As), iron (Fe), and manganese (Mn) in groundwater, in a naturally reducing aquifer at a controlled municipal landfill...
The processes leading to high levels of arsenic (As), iron (Fe), and manganese (Mn) in groundwater, in a naturally reducing aquifer at a controlled municipal landfill site, are investigated. The challenge is to distinguish the natural water-rock interaction processes, that allow these substances to dissolve in groundwater, from direct pollution or enhanced dissolution of hydroxides as undesired consequences of the anthropic activities above. Ordinary groundwater monitoring of physical-chemical parameters and inorganic compounds (major and trace elements) was complemented by environmental isotopes of groundwater (tritium, deuterium, oxygen-18 and carbon-13) and dissolved gases (carbon-13 of methane and carbon dioxide and carbon-14 of methane). Pearson/Spearman correlation indices, as well as Principal Component Analysis (PCA), were used to determine the main correlations among variables. The concurrent presence of As, Fe and CH, as reported in similar anoxic environments, suggests that anaerobic oxidation of methane could drive the reductive dissolution of As-rich Fe(III)(hydro)oxides. Manganese is more sensitive to carbon dioxide, possibly due to a decrease in pH which accelerates the dissolution of Mn-oxides. Finally, we found that tritium and deuterium, which have been used for decades as leachate tracer in groundwater, may be subject to false positives due to the reuse of water recovered from leachate treatment (which has the same isotopic signature of leachate) within the plants, to comply with the requirements of the circular economy. The integration of the environmental isotope analysis into the traditional monitoring approach can effectively support the comprehension of processes. However, this strategy needs to be complemented by a good conceptual hydrogeological model and expert evaluation to avoid misinterpretations.
PubMed: 38901701
DOI: 10.1016/j.chemosphere.2024.142657 -
Paired Electrolysis Enables Reductive Heck Coupling of Unactivated (Hetero)Aryl Halides and Alkenes.Angewandte Chemie (International Ed. in... Jun 2024The formation of carbon-carbon (C-C) bonds is a cornerstone of organic synthesis. Among various methods to construct Csp2-Csp3 bonds, the reductive Heck reaction between...
The formation of carbon-carbon (C-C) bonds is a cornerstone of organic synthesis. Among various methods to construct Csp2-Csp3 bonds, the reductive Heck reaction between (hetero)aryl halides and alkenes stands out due to its potential efficiency and broad substrate availability. However, traditional reductive Heck reactions are limited by the use of precious metal catalysts and/or limited aryl halide and alkene compatibility. Here, we present an electrochemically mediated, metal- and catalyst-free reductive Heck reaction that tolerates both unactivated (hetero)aryl halides and diverse alkenes such as vinyl boronates and silanes. Detailed electrochemical and deuterium-labeling studies support that this transformation likely proceeds through a paired electrolysis pathway, in which acid generated by the oxidation of N,N-diisopropylethylamine (DIPEA) at the anode intercepts an alkyl carbanion formed after radical-polar crossover at the cathode. As such, this approach offers a sustainable method for the construction of Csp2-Csp3 bonds from (hetero)aryl halides and alkenes, paving the way for the development of other electrochemically mediated olefin difunctionalization reactions.
PubMed: 38900083
DOI: 10.1002/anie.202408834 -
ACS Pharmacology & Translational Science Jun 2024Photopharmacology is a powerful approach to investigate biological processes and overcomes the common therapeutic challenges in drug development. Enhancing the...
Photopharmacology is a powerful approach to investigate biological processes and overcomes the common therapeutic challenges in drug development. Enhancing the photopharmacology properties of photoswitches contributes to extend their applications. Deuteration, a tiny structural modification, makes it possible to improve the photopharmacology and photophysical properties of prototype compounds, avoiding extra complex chemical changes or constructing multicomponent systems. In this work, we developed a series of D-labeled azobenzenes to expand the azobenzene photoswitchable library and introduced the D-labeled azobenzene unit into the photoagonist of α7 nicotinic acetylcholine receptors (α7 nAChRs) to investigate the effects of deuteration in photopharmacology. Spectral data indicated that deuteration maintained most of the photophysical properties of azobenzenes. The D-labeled photoagonist exhibited good control of the activity of α7 nAChRs than the prototype photoagonist. These results confirmed that deuteration is a promising strategy to improve the photopharmacological properties.
PubMed: 38898952
DOI: 10.1021/acsptsci.4c00058 -
BioRxiv : the Preprint Server For... Jun 2024The synthesis and degradation rates of proteins form an essential component of gene expression control. Heavy water labeling has been used in conjunction with mass...
UNLABELLED
The synthesis and degradation rates of proteins form an essential component of gene expression control. Heavy water labeling has been used in conjunction with mass spectrometry to measure protein turnover rates, but the optimal analytical approaches to derive turnover rates from the isotopomer patterns of deuterium labeled peptides continue to be a subject of research. Here we describe a method, which comprises a reverse lookup of numerically approximated peptide isotope envelopes, coupled to the selection of optimal isotopomer pairs based on peptide sequence, to calculate the molar fraction of new peptide synthesis in heavy water labeling mass spectrometry experiments. We validated this approach using an experimental calibration curve comprising mixtures of fully unlabeled and fully labeled proteomes. We then re-analyzed 17 proteome-wide turnover experiments from four mouse organs, and showed that the method increases the coverage of well-fitted peptides in protein turnover experiments by 25-82%. The method is implemented in the Riana software tool for protein turnover analysis, and may avail ongoing efforts to study the synthesis and degradation kinetics of proteins in animals on a proteome-wide scale.
WHAT’S NEW
We describe a reverse lookup method to calculate the molar fraction of new synthesis from numerically approximated peptide isotopomer profiles in heavy water labeling mass spectrometry experiments. Using an experimental calibration curve comprising mixtures of fully unlabeled and fully labeled proteomes at various proportions, we show that this method provides a straightforward way to calculate the proportion of new proteins in a protein pool from arbitrarily chosen isotopomer ratios. We next analyzed which of the isotopomer pairs within the peptide isotope envelope yielded isotopomer time courses that fit most closely to kinetic models, and found that the identity of the isotopomer pair depends partially on the number of deuterium accessible labeling sites of the peptide. We next derived a strategy to automatically select the isotopomer pairs to calculate turnover rates based on peptide sequence, and showed that this increases the coverage of existing proteome-wide turnover experiments in multiple data sets of the mouse heart, liver, kidney, and skeletal muscle by up to 25-82%.
PubMed: 38895333
DOI: 10.1101/2024.06.04.597043 -
Materials (Basel, Switzerland) May 2024The WMoTaNbV alloy has shown promise for applications as a solid state hydrogen storage material. It absorbs significant quantities of H directly from the atmosphere,...
The WMoTaNbV alloy has shown promise for applications as a solid state hydrogen storage material. It absorbs significant quantities of H directly from the atmosphere, trapping it with high energy. In this work, the dynamics of the absorption of hydrogen isotopes are studied by determining the activation energy for the solubility and the solution enthalpy of H in the WMoTaNbV alloy. The activation energy was studied by heating samples in a H atmosphere at temperatures ranging from 20 °C to 400 °C and comparing the amounts of absorbed H. The solution activation energy EA of H was determined to be EA=0.22±0.02 eV (21.2 ± 1.9 kJ/mol). The performed density functional theory calculations revealed that the neighbouring host atoms strongly influenced the solution enthalpy, leading to a range of theoretical values from -0.40 eV to 0.29 eV (-38.6 kJ/mol to 28.0 kJ/mol).
PubMed: 38893838
DOI: 10.3390/ma17112574 -
Molecules (Basel, Switzerland) Jun 2024The origin of nuclear magnetic shielding in diamagnetic molecules is discussed, pointing out various contributions to the shielding from electrons and the effects of... (Review)
Review
The origin of nuclear magnetic shielding in diamagnetic molecules is discussed, pointing out various contributions to the shielding from electrons and the effects of intra- and intermolecular interactions. In NMR practice, chemical shifts are determined first as the measure of shielding in observed samples. The descriptions of shielding and chemical shifts are not fully consistent. Gas phase studies permit the withdrawal of intermolecular contributions from shielding and obtaining the magnetic shielding data in isolated molecules. The shielding determination in molecules is possible using at least three methods delivering the reference shielding standards for selected nuclei. The known shielding of one magnetic nucleus can be transferred to other nuclei if the appropriate nuclear magnetic moments are available with satisfactory accuracy. It is possible to determine the nuclear magnetic dipole moments using the most advanced ab initio shielding calculations jointly with the NMR frequencies measurements for small-sized isolated molecules. Helium-3 gas is postulated as all the molecules' primary and universal reference standard of shielding. It can be easily applied using common deuterium lock solvents as the secondary reference standards. The measurements of absolute shielding are available for everyone with the use of standard NMR spectrometers.
PubMed: 38893492
DOI: 10.3390/molecules29112617 -
Bulletin of Experimental Biology and... Jun 2024Anemia is the most widespread hematological disease, therefore the search for new approaches to erythropoiesis regulation in the body remains an extremely urgent...
Anemia is the most widespread hematological disease, therefore the search for new approaches to erythropoiesis regulation in the body remains an extremely urgent problem. We studied the effect of long-term reduction of deuterium level in the internal milieu of the body on hemoglobin production and parameters of erythropoiesis in sexually mature male Wistar rats. The animals consumed water with deuterium content decreased to 10 ppm for 2 months. After 1 month, an increase of hemoglobin synthesis in erythrocytes was detected, and after 2 months we observed intensification of erythropoiesis. Since the observed processes occurred in healthy animals with initially normal indices of hematopoiesis, the obtained data allow us to consider the reduction of deuterium level in the internal milieu of the body as a factor of erythropoiesis regulation and a possible option of its alternative non-pharmacological regulators.
PubMed: 38890210
DOI: 10.1007/s10517-024-06117-9 -
Journal of Chromatography. A Jun 2024Hydrogen/deuterium (H/D) isotope effects are not unusual in chromatography and such phenomena have been observed in both gas- and liquid-phase separations. Despite the...
Separation of isotopologues of amphetamine with various degree of deuteration on achiral and polysaccharide-based chiral columns in high-performance liquid chromatography.
Hydrogen/deuterium (H/D) isotope effects are not unusual in chromatography and such phenomena have been observed in both gas- and liquid-phase separations. Despite the numerous reports on this topic, the understanding of mechanisms and the underlying noncovalent interactions at play remains rather challenging. In our recent study, we reported baseline separation of isotopologoues of some amphetamine (AMP) derivatives on achiral and polysaccharide-based chiral columns, as well as some correlations between the degree of separation of enantiomers and isotopologues on (the same) polysaccharide-based chiral column(s). Following our previous findings on isotope effects in high-performance liquid chromatography, we report herein a comparative study on the isotope effects observed with AMP and methamphetamine (MET). The impact of some pivotal factors such as the number of deuterium atoms part of AMP isotopologues, the structure of its isotopomers, the chemical structure of the achiral and chiral stationary phases used in this study, and the use of methanol- vs acetonitrile-containing mobile phases on the isotope effects was examined and discussed. Quantitative correlations between the observed isotope effects and the enantioselectivity of the chiral columns used are also shortly discussed. Furthermore, considering the chromatographic results as benchmark experimental data, we attempted to elucidate the molecular bases of the observed phenomena using quantum mechanics calculations.
PubMed: 38889581
DOI: 10.1016/j.chroma.2024.465062 -
The Review of Scientific Instruments Jun 2024The nuclear imaging system at the National Ignition Facility (NIF) is a crucial diagnostic for determining the geometry of inertial confinement fusion implosions. The...
The nuclear imaging system at the National Ignition Facility (NIF) is a crucial diagnostic for determining the geometry of inertial confinement fusion implosions. The geometry is reconstructed from a neutron aperture image via a set of reconstruction algorithms using an iterative Bayesian inference approach. An important step in these reconstruction algorithms is finding the fusion source location within the camera field-of-view. Currently, source localization is achieved via an iterative optimization algorithm. In this paper, we introduce a machine learning approach for source localization. Specifically, we train a convolutional neural network to predict source locations given a neutron aperture image. We show that this approach decreases computation time by several orders of magnitude compared to the current optimization-based source localization while achieving similar accuracy on both synthetic data and a collection of recent NIF deuterium-tritium shots.
PubMed: 38888398
DOI: 10.1063/5.0205472 -
Protein Science : a Publication of the... Jul 2024Adeno-associated virus (AAV), a widely used gene therapy vector, is a small, nonenveloped virus that contains a single-stranded DNA genome with a maximum length of...
Adeno-associated virus (AAV), a widely used gene therapy vector, is a small, nonenveloped virus that contains a single-stranded DNA genome with a maximum length of 4.7 kb. Despite extensive biophysical and structural characterization, many aspects of AAV functions remain elusive. This knowledge gap is primarily due to a lack of structurally resolved dynamic information and the absence of structural coverage of functionally critical segments on the AAV capsid. Here, we developed a protocol to study AAV structural dynamics by hydrogen-deuterium exchange mass spectrometry (HDX-MS), a powerful method for monitoring protein structure stability and dynamics in solution. We performed HDX-MS measurements on AAVs without or with different DNA payloads of different sizes, and obtained detailed dynamic information on the entire AAV sequence including the two functionally important segments not previously structurally characterized. The unique N terminus of the capsid protein VP1 (VP1u) was found to adopt a highly dynamic and unstable conformation with low HDX protection across the entire region, whereas the presence of a DNA payload increased its protection. The VP1 and VP2 shared region (VP1/2) showed no measurable protection, with or without DNA. Differential HDX between empty and full capsid samples allowed us to identify potential new DNA-capsid interaction sites located primarily around the five-fold channel, which differ from the three-fold pocket binding site previously identified. Our HDX-MS method for characterizing AAV structural dynamics opens a new way for future efforts to understand AAV structure-function relationships and engineer next-generation AAV vectors with improved gene delivery properties.
Topics: Dependovirus; Capsid Proteins; Genetic Vectors; Genetic Therapy; Capsid; Hydrogen Deuterium Exchange-Mass Spectrometry; Protein Stability; Humans; Protein Conformation; Models, Molecular
PubMed: 38888268
DOI: 10.1002/pro.5074