Hydrogen Exchange Research Articles

Solution NMR assignments and structure for the dimeric kinesin neck domain.

Kinesin is a motor protein, comprised of two heavy and two light chains that transports cargo along the cytoskeletal microtubule filament network. The heavy chain has a neck domain connecting the ATPase motor head responsible for walking along microtubules, with the stalk and subsequent tail domains that bind cargo. The neck domain consists of a coiled coli homodimer with about five heptad repeats, preceded by a linker region that joins to the ATPase head. Here we report 1H, 15N, and 13C NMR assignments and a solution structure for the kinesin neck domain from rat isoform Kif5c. The calculation of the NMR structure of the homodimer was facilitated by unambiguously assigning sidechain NOEs between heptad a and d positions to interchain contacts, since these positions are too far apart to give sidechain contacts in the monomers. The dimeric coiled coil NMR structure is similar to the previously described X-ray structure, whereas the linker region is disordered in solution but contains a short segment with β-strand propensity- the β-linker. Only the coiled coil is protected from solvent exchange, with ∆G values for hydrogen exchange on the order of 4-6kcal/mol. The high stability of the hydrogen-bonded α-helical structure makes it unlikely that unzippering of the coiled coil is involved in kinesin walking. Rather, the linker region serves as a flexible hinge between the kinesin head and neck.

Protein dynamics govern the oxyferrous state lifetime of an artificial oxygen transport protein

It has long been known that the alteration of protein side chains that occlude or expose the heme cofactor to water can greatly affect the stability of the oxyferrous heme state. Here, we demonstrate that the rate of dynamically driven water penetration into the core of an artificial oxygen transport protein also correlates with oxyferrous state lifetime by reducing global dynamics, without altering the structure of the active site, via the simple linking of the two monomers in a homodimeric artificial oxygen transport protein using a glycine-rich loop. The tethering of these two helices does not significantly affect the active site structure, pentacoordinate heme-binding affinity, reduction potential, or gaseous ligand affinity. It does, however, significantly reduce the hydration of the protein core, as demonstrated by resonance Raman spectroscopy, backbone amide hydrogen exchange, and pKa shifts in buried histidine side chains. This further destabilizes the charge-buried entatic state and nearly triples the oxyferrous state lifetime. These data are the first direct evidence that dynamically driven water penetration is a rate-limiting step in the oxidation of these complexes. It furthermore demonstrates that structural rigidity that limits water penetration is a critical design feature in metalloenzyme construction and provides an explanation for both the failures and successes of earlier attempts to create oxygen-binding proteins.

Synergistic effects in the co-pyrolysis of thermoset epoxy resin and biomass on kinetics and product distribution

With the rapid growth of wind power, batteries, and aerospace industries, sustainable disposal of thermoset plastics has become a long-term concern. However, pyrolysis, a highly promising solution for this issue, has seen limited studied on thermoset plastics. Drawing inspiration from the synergistic interactions observed between thermoplastics and biomass, this study explored the co-pyrolysis of a thermoset epoxy resin, diglycidyl ether of bisphenol A, cured with 4,4′-Diaminodiphenylmethane, with ash-free biomass pseudo-components (cellulose, lignin, and xylan) using thermogravimetry and Py-GC/MS. The results revealed distinctive synergistic effects in Epoxy-Cellulose and Epoxy-Lignin mixtures, delaying the onset and hastening the conclusion of weight loss. This was accompanied by increased activation energies, assessed through the Friedman and Kissinger-Akahira-Sunose methods, as well as higher char yields. Conversely, in Epoxy-Xylan, synergistic effects led to reduced activation energy across most α values, resulting in a lower onset temperature and a heightened maximum rate of mixture degradation. Regarding product distribution, all three pseudo-components, particularly lignin, enhanced the selectivity of bisphenol A. Additionally, cellulose and xylan altered the kinetics of N–C and C(N)–C(OH) bond cleavage, reducing the amount and altering the distribution of 2-B-N compounds (compounds featuring two benzene rings and nitrogen). Conversely, the presence of resin reduced the volatiles from cellulose and xylan, promoting phenol-type products and –H and alkylene side chains while diminishing guaiacol-type products and alkyl side chains. Three mechanisms were proposed to elucidate these observed synergistic effects: catalytic effects of –OH groups from biomass pseudo-components, hydrogen exchange or hydrogen bonding between resin-derived nitrogen and biomass-derived oxygen-containing functional groups, and radical reactions. These insights into the co-pyrolysis of biomass and cured epoxy resin can inform the selection of suitable feedstocks for various applications.

Hydrogen Transport and Evolution in Ni-MH Batteries by Neutron Imaging.

Efficiency losses due to side reactions are one of the main challenges in battery development. Despite providing valuable insights, the results of standard analysis on the individual components cannot be simply extrapolated to the full operating system. Therefore, non-destructive, and high resolution approaches that allow the investigation of the full system are desired. Herein, we combined neutron radiography and tomography with electrical monitoring of the state of charge of commercial Ni-mischmetal hydride batteries, to track the exchange and transport of hydrogen under operating conditions. This non-destructive approach allowed both the quantification of the hydrogen distribution in the electrodes in 4D, and the distinction between the electrochemically exchanged hydrogen and the hydrogen gas pressure generated by side reactions, as a function of the applied potential and current. One of the most counter-intuitive observation is that the generation of hydrogen gas during discharge depends on the charging state of the battery. The results presented provide critical new insights in the mechanisms governing the electrochemical processes during Nimischmetal hydride battery operation, and also pave the way for the extrapolation of this approach to the investigation of state-of-the-art Li-ions batteries.

Sodium-glucose Cotransporter 2 Inhibitors and Pathological Myocardial Hypertrophy.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new type of oral hypoglycemic drugs that exert a hypoglycemic effect by blocking the reabsorption of glucose in the proximal renal tubules, thus promoting the excretion of glucose from urine. Their hypoglycemic effect is not dependent on insulin. Increasing data shows that SGLT2 inhibitors improve cardiovascular outcomes in patients with type 2 diabetes. Previous studies have demonstrated that SGLT2 inhibitors can reduce pathological myocardial hypertrophy with or without diabetes, but the exact mechanism remains to be elucidated. To clarify the relationship between SGLT2 inhibitors and pathological myocardial hypertrophy, with a view to providing a reference for the future treatment thereof, this study reviewed the possible mechanisms of SGLT2 inhibitors in attenuating pathological myocardial hypertrophy. We focused specifically on the mechanisms in terms of inflammation, oxidative stress, myocardial fibrosis, mitochondrial function, epicardial lipids, endothelial function, insulin resistance, cardiac hydrogen and sodium exchange, and autophagy.

Hydrogen Exchange and Diffusion Kinetics at Elevated Temperatures in Proton-Conducting Solid Oxide Materials

Storage of purified hydrogen is one of the central challenges in addressing climate change and reducing our reliance on fossil fuels for energy conversion and storage, and therefore there is a global surge in research and development concerning hydrogen purification and storage. In this regard, we are studying proton conduction in solid oxide materials at elevated temperatures for applications in hydrogen separation and compression membranes. Hydrogen compression is the most recommended method to store hydrogen for automotive applications as it allows an increase in the hydrogen volumetric energy density.Traditionally the protonic conductivity in these materials is measured by indirect methods. For example, conductivity measurements in mixed gas atmospheres, comparing for example dry N2 with humidified N2, thereby allowing the contribution of protons to be evaluated. In this study, we for the first time report the evaluation of protonic conductivity in BaZr1-xCexY0.2O3−δ, BaZr0.1Ce0.7Y0.2–xYbxO3–δ and Ba7Nb4MoO20 by direct measurements afforded by the Isotope Exchange Depth Profiling technique with deuterium labelling. We also report the kinetics of H/D transport through the bulk materials and across metal-ceramic interfaces with a particular interest in the behaviour of the interface between the key Pd/Pd alloy catalyst component and the hydrogen-transporting oxide ceramic material. The transport and interface behaviour information will be of significance in designing hydrogen separation and compression membranes. Figure 1

SARS-CoV-2 fusion peptide sculpting of a membrane with insertion of charged and polar groups

The fusion peptide of SARS-CoV-2 spike is essential for infection. How this charged and hydrophobic domain occupies and affects membranes needs clarification. Its depth in zwitterionic, bilayered micelles at pH 5 (resembling late endosomes) was measured by paramagnetic NMR relaxation enhancements used to bias molecular dynamics simulations. Asp830 inserted deeply, along with Lys825 or Lys835. Protonation of Asp830 appeared to enhance agreement of simulated and NMR-measured depths. While the fusion peptide occupied a leaflet of the DMPC bilayer, the opposite leaflet invaginated with influx of water and choline head groups in around Asp830 and bilayer-inserted polar side chains. NMR-detected hydrogen exchange found corroborating hydration of the backbone of Thr827-Phe833 inserted deeply in bicelles. Pinching of the membrane at the inserted charge and the intramembrane hydration of polar groups agree with theory. Formation of corridors of hydrated, inward-turned head groups was accompanied by flip-flop of head groups. Potential roles of the defects are discussed.

Utilizing hydrogen exchange measurements to drive small molecules into cryptic protein binding sites

Utilizing hydrogen exchange measurements to drive small molecules into cryptic protein binding sites

Transient conformations in the unliganded FK506 binding domain of FKBP51 correspond to two distinct inhibitor-bound states

Members of the FK506-binding protein (FKBP) family regulate a range of important physiological processes. Unfortunately, current therapeutics such as FK506 and rapamycin exhibit only modest selectivity among these functionally distinct proteins. Recent progress in developing selective inhibitors has been reported for FKBP51 and FKBP52, which act as mutual antagonists in the regulation of steroid hormone signaling. Two structurally similar inhibitors yield distinct protein conformations at the binding site. Localized conformational transition in the binding site of the unliganded FK1 domain of FKBP51 is suppressed by a K58T mutation that also suppresses the binding of these inhibitors. Here, it is shown that the changes in amide hydrogen exchange kinetics arising from this K58T substitution are largely localized to this structural region. Accurate determination of the hydroxide-catalyzed exchange rate constants in both the wildtype and K58T variant proteins impose strong constraints upon the pattern of amide exchange reactivities within either a single or a pair of transient conformations that could give rise to the differences between these two sets of measured rate constants. Poisson-Boltzmann continuum dielectric calculations provide moderately accurate predictions of the structure-dependent hydrogen exchange reactivity for solvent-exposed protein backbone amides. Applying such calculations to the local protein conformations observed in the two inhibitor-bound FKBP51 domains demonstrated that the experimentally determined exchange rate constants for the wildtype domain are robustly predicted by a population-weighted sum of the experimental hydrogen exchange reactivity of the K58T variant and the predicted exchange reactivities in model conformations derived from the two inhibitor-bound protein structures.

Understanding lanthanum effects on the structure and properties of LaxY1−xMgNi4 hydrogen storage alloys

This study mainly concentrated on investigating the effects on the crystal structure, hydrogen storage, and electrochemical properties of LaxY1−xMgNi4 (x = 0, 0.25, and 0.5) alloys. The refined X-ray diffraction patterns reveal the substitution by La results in a change in the phase composition and abundance of the compound and an increase in the lattice constants. La can increase the maximum hydrogen absorption capacity while decreasing the hydrogen absorption and desorption plateaus. However, increasing the La content leads to incomplete hydrogen desorption. In electrochemistry, La addition can improve the activation property, while the electrodes with higher Y content show better cycling stability. The La0 25Y0.75MgNi4 alloy exhibits a maximum capacity for discharge of ∼400 mAh g−1 @10 mA g−1. Its superior electrochemical kinetic performance is attributed to a higher hydrogen diffusion coefficient and exchange current density. Therefore, by optimizing the La content, the tested alloys' hydrogen storage, and electrochemical performance can be improved.

Hydrogen/Deuterium Exchange in Ambrox Could Improve the Long-Term Scent and Shelf Life of Perfumes

Ambrox is a marine natural compound with a delicious ambergris-type scent widely used in fine perfumery. The increase in the long-term scent and shelf life of perfumes has become a paramount endeavor in the fragrance industry. To the best of our knowledge, the exchange of hydrogen by deuterium to decrease the volatility of the constituents of a perfume has not yet been investigated. In this article, we propose this new use of deuteration to synthesize deuterated ambrox in order to decrease its volatility and improve the long-term scent and extend the shelf-life of perfumes.

Study of hydrogen exchange between the Zr–1%Nb alloy and the gaseous ambient through the oxidized surface under ion and atomic irradiation

In the article, a hydrogen exchange between the Zr–1%Nb alloy (E110) and the gas ambient was experimentally studied when the samples were irradiated with deuterium and argon plasma ions. It has been established that, upon irradiation with deuterium plasma ions with an energy of E = 650 eV/at, the enhanced absorption of deuterium exceeds the release of hydrogen initially contained in the samples, which leads to their loading with hydrogen isotopes. Adding 30 at.% oxygen to the plasma-forming gas or raising the sample temperature from T = 450 K to T = 600 K, significantly reduces the content of hydrogen isotopes in the sample. Based on the aggregate data obtained by atomic and ion irradiation, a mechanism of hydrogen exchange between zirconium alloy and gas ambient is proposed. The process includes three stages: reactions on the oxidized surface of the zirconium alloy (surface hydroxylation and formation of water molecules); reactions at the metal-oxide interface; transfer of hydrogen isotopes through the surface oxide layer in both directions due to hopping between neighboring oxygen ions. Surface reactions caused by irradiation of atoms and ions trigger the hydrogen exchange. The proposed model agrees with the experimental data on the irradiation of the E110 alloy with atoms and ions of hydrogen isotopes.

Transformation of waste battery cathode material LiMn2O4 into efficient ultra-low temperature NH3-SCR catalyst: Proton exchange synergistic vanadium modification

It is essential to develop the catalyst for NH3-SCR with excellent performance at ultra-low temperature (≤150 °C), and resource recycling is another important part of environmental protection. Based on the principle of environmental friendliness, the LiMn2O4, one of the waste battery cathode materials, was successfully modified into a novel high-value catalyst for ultra-low temperature NH3-SCR through hydrogen ion exchange and two-dimensional vanadic oxide modification. The optimized LiMn2O4-0.5V-10H catalyst performed the best balance of NOx conversion and N2 selectivity, with activity reaching 96 % at 150 °C and N2 selectivity exceeding 70 % at ultra-low temperature. Due to the unique three-dimensional network structural characteristics of LiMn2O4 spinel, hydrogen exchange could exchange Li+ from the lattice and increase surface acidity; and a small amount of two-dimensional vanadic oxide loading could appropriately regulate redox ability and increase acidic sites. The in-situ DRIFTS results still showed that the L-H and E-R mechanisms coexisted during the reaction. Moreover, combining first-principles calculations and in-situ DRIFTS, the dual modification of H and V could enhance the adsorption of NH3 on the surface of LiMn2O4 but weaken the adsorption of NO, and promote the decomposition of nitrites while inhibit the formation of surface nitrate species, which was the core reason for the improvement of N2 selectivity. The modification mode in this work was simple and inexpensive, which provided a new idea for the high-value utilization of waste batteries and the design of NOx purification catalyst at ultra-low temperature.

Theoretical understanding of two-dimensional boridenes M4/3B2 for hydrogen evolution

Layered boridenes M4/3B2 have been experimentally validated as a rising two-dimensional (2D) material family. Herein, we investigate nine kinds of 2D M4/3B2 (M = Ti, Zr, Hf, V, Nb, Ta, Cr, Mo, and W) toward their structural stabilities, electronic properties, and hydrogen evolution performances based on density functional theory (DFT) calculations. Our results show that except for Cr4/3B2, other 2D M4/3B2 materials are dynamically and kinetically stable and are promising for synthesis and application in hydrogen production. Metallic Ti4/3B2 and Ta4/3B2 monolayers are easily oxidized in aqueous environments as ideal platforms with optimal hydrogen adsorption free energies and exchange current densities around the peak of the activity volcano. Our work provides a systematic guideline for the application of the 2D M4/3B2 family in HER and reveals their underlying electronic origins.

Bacterial chemoreceptor signaling complexes control kinase activity by stabilizing the catalytic domain of CheA

Motile bacteria have a chemotaxis system that enables them to sense their environment and direct their swimming toward favorable conditions. Chemotaxis involves a signaling process in which ligand binding to the extracellular domain of the chemoreceptor alters the activity of the histidine kinase, CheA, bound ~300 Å away to the distal cytoplasmic tip of the receptor, to initiate a phosphorylation cascade that controls flagellar rotation. The cytoplasmic domain of the receptor is thought to propagate this signal via changes in dynamics and/or stability, but it is unclear how these changes modulate the kinase activity of CheA. To address this question, we have used hydrogen deuterium exchange mass spectrometry to probe the structure and dynamics of CheA within functional signaling complexes of the Escherichia coli aspartate receptor cytoplasmic fragment, CheA, and CheW. Our results reveal that stabilization of the P4 catalytic domain of CheA correlates with kinase activation. Furthermore, differences in activation of the kinase that occur during sensory adaptation depend on receptor destabilization of the P3 dimerization domain of CheA. Finally, hydrogen exchange properties of the P1 domain that bears the phosphorylated histidine identify the dimer interface of P1/P1' in the CheA dimer and support an ordered sequential binding mechanism of catalysis, in which dimeric P1/P1' has productive interactions with P4 only upon nucleotide binding. Thus stabilization/destabilization of domains is a key element of the mechanism of modulating CheA kinase activity in chemotaxis, and may play a role in the control of other kinases.

Quantum Dynamical Investigation of Dihydrogen-Hydride Exchange in a Transition-Metal Polyhydride Complex.

The ongoing shift toward clean, sustainable energy is a primary driving force behind hydrogen fuel research. Safe and effective storage of hydrogen is a major challenge (particularly for mobile applications) and requires a detailed understanding of the atomic level interactions of hydrogen with its host materials. The light mass of hydrogen, however, implies that quantum effects are important, so a quantum dynamical treatment is required to properly account for these effects in computational simulations. As one such example, we describe herein the hydrogen exchange dynamics between a hydride and a dihydrogen ligand in the [FeH(H2)(PH3)4]+ model complex. A global three-dimensional (3D) potential energy surface (PES) was constructed by fitting to and interpolating from a discrete set of grid points computed using density functional theory; exact quantum dynamical calculations were then carried out on the 3D PES using discrete variable representation basis sets. Energy levels and their quantum tunneling splittings were computed up to 3000 cm-1 above the ground state. Within that energy range, all three fundamentals have been identified using wave function plots, as well as the first three overtones of the exchange (reaction coordinate) motion and several of its combination bands. From the tunneling splittings, the Boltzmann-averaged tunneling rates were computed. The Arrhenius plot of the total exchange rate shows a clear transition around 150 K, below which the activation energy is essentially zero and above which it is less than half of the electronic structure barrier. This indicates that exchange rates are governed by quantum tunneling throughout the relevant temperature range with the low-temperature regime dominated by a single quantum (ground) state. This work is the first-ever fully quantum dynamical study to investigate the hydrogen exchange dynamics between hydride and dihydrogen ligands coordinated to a transition-metal complex.

2D Hemiporphyrazine: A new nanoporous material

Crystalline microporous materials are solids formed by interconnected pores of less than 2 nm in size. Typically, they possess large surface areas desirable for versatile applications such as catalysis, gas adsorption, and energy storage. In the present work, we propose a new porphyrin-based 2D nanoporous crystal, named 2D Porphyrazine (2DP), which is formed by topological assembling H$_{5}$C$_{13}$N$_{4}$ porphyrins. We have considered its monolayer, bi-layer, and molecular crystal (bulk) arrangements. We carried out DFT calculations to investigate 2DP structural and electronic properties. Results show that 2DP is a very stable structure with a direct bandgap of 0.65 eV and significant optical absorption in the visible range. 2DP exhibited satisfactory affinity to lithium atoms. Simulations also showed the existence of proton transfer between nitrogen atoms. It is the first report on the site-specific hydrogen exchange process in 2D crystals.

NMR detection and conformational dependence of two, three, and four-bond isotope shifts due to deuteration of backbone amides.

NMR isotope shifts occur due to small differences in nuclear shielding when nearby atoms are different isotopes. For molecules dissolved in 1:1 H2O:D2O, the resulting mixture of N-H and N-D isotopes leads to a small splitting of resonances from adjacent nuclei. We used multidimensional NMR to measure isotope shifts for the proteins CUS-3iD and CspA. We observed four-bond 4∆N(ND) isotope shifts in high-resolution 2D 15N-TROSY experiments of the perdeuterated proteins that correlate with the torsional angle psi. Three-bond 3∆C'(ND) isotope shifts detected in H(N)CO spectra correlate with the intraresidue H-O distance, and to a lesser extent with the dihedral angle phi. The conformational dependence of the isotope shifts agree with those previously reported in the literature. Both the 4∆N(ND) and 3∆C'(ND) isotope shifts are sensitive to distances between the atoms giving rise to the isotope shifts and the atoms experiencing the splitting, however, these distances are strongly correlated with backbone dihedral angles making it difficult to resolve distance from stereochemical contributions to the isotope shift. H(NCA)CO spectra were used to measure two-bond 2∆C'(ND) isotope shifts and [D]/[H] fractionation factors. Neither parameter showed significant differences for hydrogen-bonded sites, or changes over a 25° temperature range, suggesting they are not sensitive to hydrogen bonding. Finally, the quartet that arises from the combination of 2∆C'(ND) and 3∆C'(ND) isotope shifts in H(CA)CO spectra was used to measure synchronized hydrogen exchange for the sequence neighbors A315-S316 in the protein CUS-3iD. In many of our experiments we observed minor resonances due to the 10% D2O used for the sample deuterium lock, indicating isotope shifts can be a source of spectral heterogeneity in standard NMR experiments. We suggest that applications ofisotope shifts such as conformational analysis and correlated hydrogen exchange could benefit from the larger magnetic fields becoming available.

Determining Reaction Paths by Evaluating Kinetic Isotopic Effects with Density Functional Theory: Example of Methane Thermogenesis

This study demonstrates the determination of reaction pathways by evaluating the carbon kinetic isotopic effect and interpreting isotopic fractionations based on quantum chemical calculations. The reaction under investigation is methane thermogenesis from the decomposition of kerogen, which is a geochemical reaction under temperatures below 150 °C and lasts for tens of millions of years. Investigating its mechanism requires theoretical simulations because lab experiments at practical time-lengths require elevated temperatures, which introduce unwanted side reactions. Density functional theory and kinetic simulations were conducted on isotopic fractionations with the use of two possible pathways (free-radical versus carbonium), and the results were compared to field data sets. Different molecular sizes of kerogen were investigated to account for the hindrance of translation and rotation in modeling a reactant in the solid phase. Both pathways have low reaction barriers, implying that the reaction rates are limited by the concentration of active species (hydrated protons and free radicals). The results support the carbonium pathway and rule out the free-radical pathway as the 13CH4 from the latter would be 30‰ more depleted than the observed data. Additionally, simulations were conducted on hydrocarbon isotope fractionation of the carbonium pathway with consideration of hydrogen exchange between methane and water, successively reproducing the observed abundances of deuterium-containing isotopologues (13CH3D, 13CH3D, and 12CH2D2).

Global Hydrogen and Synfuel Exchanges in an Emission-Free Energy System

This study investigates the global allocation of hydrogen and synfuels in order to achieve the well below 2 °C, preferably 1.5 °C target set in the Paris Agreement. For this purpose, TIMES Integrated Assessment Model (TIAM), a global energy system model is used. In order to investigate global hydrogen and synfuel flows, cost potential curves are aggregated and implemented into TIAM, as well as demand technologies for the end use sectors. Furthermore, hydrogen and synfuel trades are established using liquid hydrogen transport (LH2), and both new and existing technologies for synfuels are implemented. To represent a wide range of possible future events, four different scenarios are considered with different characteristics of climate and security of supply policies. The results show that in the case of climate policy, the renewable energies need tremendous expansion. The final energy consumption is shifting towards the direct use of electricity, while certain demand technologies (e.g., aviation and international shipping) require hydrogen and synfuels for full decarbonization. Due to different security of supply policies, the global allocation of hydrogen and synfuel production and exports is shifting, while the 1.5 °C target remains feasible in the different climate policy scenarios. Considering climate policy, Middle East Asia is the preferred region for hydrogen export. For synfuel production, several regions are competitive, including Middle East Asia, Mexico, Africa, South America and Australia. In the case of security of supply policies, Middle East Asia is sharing the export volume with Africa, while only minor changes can be seen in the synfuel supply.