Multiple Proton Research Articles

The Relationship Between Segmental Motions, Hydration and Overall Mass Transport in Pfsas

A great many membranes have been studied for use in fuel cells and other electrochemical devices. Prominent amongst these are the perfluorosulfonic acids, including Nafion as an archetype and materials prepared by Dow (later others) and 3M presented over time. Generally, similar mass transport (conductivity and water transport) phenomena have been observed, with high transport rates closely tied to high levels of hydration. However, maintaining high hydration of the membrane by maintaining an environment of high relative humidity requires system level measures that represent parasitic losses. Achieving high conductivity with less hydration requires more substantial understanding and then control of the transport mechanisms involved at low water content. There are clear differences in the behavior of materials at low and high hydration, with a line of demarcation at hydration levels of ca. 5 or 6 waters per sulfonate. Above this level, the water in the membrane is more continuous across multiple pores and protons move in an environment that increasing resembles that in aqueous solutions as hydration levels increase. Below this level, such factors as the acidity of the sulfonic acid, the mobility of water within the first or second hydration spheres of the sulfonate and proton and possibly sidechain movements in the polymer all have been suggested to play roles in the transport processes. In this contribution, we will explore various processes in the low water content regime. For a series of PFSAs, we will gather experimental information to reveal the approximate rate of side chain motion, use vibrational spectroscopy and related methods to provide an in-depth view into the hydration of ions and water interactions in the membrane and present information on the energetics of hydration. These will be synthesized into an experimentally supported picture allowing us to assess the relative importance of the motions of anions, cations and water molecules in determining transport in PFSAs at RH < 50% under different conditions.

N-Heterocyclic carbene ligands bearing a naphthoquinone appendage: Synthesis and coordination chemistry

Many biochemical transformations for small molecule functionalisation depend on the temporal delivery of multiple protons and electrons. For this purpose, Nature elegantly combines transition metals with redox-active cofactors. In a biomimetic spirit, we report on the synthesis and coordination chemistry of an N-heterocyclic carbene ligand bearing a naphthoquinone moiety NHC 1. Both the silver and palladium complexes [Ag(μ-Cl)(NHC 1)]22 and [Pd(η3-allyl)(NHC 1)Cl] 5 were characterized by X-ray crystallography. Cyclic voltammetry of the metal complexes suggest that redox events occur both on the naphthoquinone and on the metal for the iridium and ruthenium complexes.

Label-free in vivo molecular imaging of underglycosylated mucin-1 expression in tumour cells.

Alterations in mucin expression and glycosylation are associated with cancer development. Underglycosylated mucin-1 (uMUC1) is overexpressed in most malignant adenocarcinomas of epithelial origin (for example, colon, breast and ovarian cancer). Its counterpart MUC1 is a large polymer rich in glycans containing multiple exchangeable OH protons, which is readily detectable by chemical exchange saturation transfer (CEST) MRI. We show here that deglycosylation of MUC1 results in >75% reduction in CEST signal. Three uMUC1+ human malignant cancer cell lines overexpressing uMUC1 (BT20, HT29 and LS174T) show a significantly lower CEST signal compared with the benign human epithelial cell line MCF10A and the uMUC1− tumour cell line U87. Furthermore, we demonstrate that in vivo CEST MRI is able to make a distinction between LS174T and U87 tumour cells implanted in the mouse brain. These results suggest that the mucCEST MRI signal can be used as a label-free surrogate marker to non-invasively assess mucin glycosylation and tumour malignancy.

Quantitative description of radiofrequency (RF) power-based ratiometric chemical exchange saturation transfer (CEST) pH imaging.

Chemical exchange saturation transfer (CEST) MRI holds great promise for the imaging of pH. However, routine CEST measurement varies not only with the pH-dependent chemical exchange rate, but also with CEST agent concentration, providing pH-weighted information. Conventional ratiometric CEST imaging normalizes the confounding concentration factor by analyzing the relative CEST effect from different exchangeable groups, requiring CEST agents with multiple chemically distinguishable labile proton sites. Recently, a radiofrequency (RF) power-based ratiometric CEST MRI approach has been developed for concentration-independent pH MRI using CEST agents with a single exchangeable group. To facilitate quantification and optimization of the new ratiometric analysis, we quantified the RF power-based ratiometric CEST ratio (rCESTR) and derived its signal-to-noise and contrast-to-noise ratios. Using creatine as a representative CEST agent containing a single exchangeable site, our study demonstrated that optimized RF power-based ratiometric analysis provides good pH sensitivity. We showed that rCESTR follows a base-catalyzed exchange relationship with pH independent of creatine concentration. The pH accuracy of RF power-based ratiometric MRI was within 0.15-0.20 pH units. Furthermore, the absolute exchange rate can be obtained from the proposed ratiometric analysis. To summarize, RF power-based ratiometric CEST analysis provides concentration-independent pH-sensitive imaging and complements conventional multiple labile proton group-based ratiometric CEST analysis.

Excited-state multiple proton transfer depending on the acidity and basicity of mediating alcohols in 7-azaindole-(ROH)2 (R = H, CH3) complexes: a theoretical study.

Long-range proton transfer plays an important role in many chemical and biological phenomena. It has recently been reported that the rate of excited-state multiple proton transfer depends on the acidity and basicity of mediating alcohols in the H-bonded wire. The excited-state triple proton transfer in 7-azaindole complexes through cyclic H-bonded wires was theoretically studied to investigate rates depending on the mediating alcohols. This study showed that the acidity and basicity of alcohols collectively functioned to assist proton transfers depending on the paths; the proton transfers of protolytic and solvolytic paths were assisted by the pull-behind effect and the push-ahead effect, respectively. Both proton-donating and accepting abilities of alcohols in the H-bonded wire can accumulate to help proton transfer, and the strong acidity and basicity of the alcohols with relatively small structural changes in the wire have larger impacts on reducing the activation energies than those of alcohols that trigger proton transfer.

Proton-coupled electron transfer chemistry of hangman macrocycles: Hydrogen and oxygen evolution reactions

The splitting of water into its constituent elements is an important solar fuels conversion reaction for the storage of renewable energy. For each of the half reactions of the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER), multiple protons and electrons must be coupled to avoid high-energy intermediates. To understand the mechanistic details of the PCET chemistry that underpins HER and OER, we have designed hangman porphyrin and corrole catalysts. In these hangman constructs, a pendant acid/base functionality within the secondary coordination sphere is "hung" above the macrocyclic redox platform on which substrate binds. The two critical thermodynamic properties of a PCET event, the redox potential and pKa may be tuned with the macrocycle and hanging group, respectively. This review outlines the synthesis of these catalysts, as well as the examination of the PCET kinetics of hydrogen and oxygen evolution by the hangman catalysts. The insights provided by these systems provide a guide for the design of future HER and OER catalysts that use a secondary coordination sphere to manage PCET.

The excited-state multiple proton transfer mechanism of the 7-hydroxyquinoline–(CH3OH)3cluster

Two proposed competitive types of multiple excited-state proton transfer take place along the intermolecular hydrogen-bond for 7-hydroxyquinoline–(CH3OH)3.

Jet energy measurement and its systematic uncertainty in proton-proton collisions at [Formula: see text]TeV with the ATLAS detector.

The jet energy scale (JES) and its systematic uncertainty are determined for jets measured with the ATLAS detector using proton–proton collision data with a centre-of-mass energy of sqrt{s}=7 TeV corresponding to an integrated luminosity of 4.7 ,,text{ fb }^{-1}. Jets are reconstructed from energy deposits forming topological clusters of calorimeter cells using the anti-k_{t} algorithm with distance parameters R=0.4 or R=0.6, and are calibrated using MC simulations. A residual JES correction is applied to account for differences between data and MC simulations. This correction and its systematic uncertainty are estimated using a combination of in situ techniques exploiting the transverse momentum balance between a jet and a reference object such as a photon or a Z boson, for {20} le p_{mathrm {T}}^mathrm {jet}<{1000}, ~mathrm{GeV } and pseudorapidities |eta |<{4.5}. The effect of multiple proton–proton interactions is corrected for, and an uncertainty is evaluated using in situ techniques. The smallest JES uncertainty of less than 1 % is found in the central calorimeter region (|eta |<{1.2}) for jets with {55} le p_{mathrm {T}}^mathrm {jet}<{500}, ~mathrm{GeV }. For central jets at lower p_{mathrm {T}}, the uncertainty is about 3 %. A consistent JES estimate is found using measurements of the calorimeter response of single hadrons in proton–proton collisions and test-beam data, which also provide the estimate for p_{mathrm {T}}^mathrm {jet}> 1 TeV. The calibration of forward jets is derived from dijet p_{mathrm {T}} balance measurements. The resulting uncertainty reaches its largest value of 6 % for low-p_{mathrm {T}} jets at |eta |=4.5. Additional JES uncertainties due to specific event topologies, such as close-by jets or selections of event samples with an enhanced content of jets originating from light quarks or gluons, are also discussed. The magnitude of these uncertainties depends on the event sample used in a given physics analysis, but typically amounts to 0.5–3 %.

Evidence for hydrogen-bonded ammonia wire influencing the ESMPT process of the 7-hydroxy-4-methylcoumarin·(NH3)3 cluster

The different types of excited-state hydrogen-bonded dynamics mechanisms orderly provide two driving forces for the excited-state multiple proton transfer (ESMPT) reaction of the 7H4MC·(NH3)3 cluster.

A biomimetic phenol substituent effect on the reaction of a dimethylplatinum(ii) complex with oxygen: proton coupled electron transfer and multiple proton relay.

The complex [PtMe2({κ(2)-N,N-RN[double bond, length as m-dash]CH-2-C5H4N})] reacts with oxygen in acetone solution to give the platinum(iv) complex [Pt(OH)Me2{κ(3)-N,N,O-RNH-CH(2-C5H4N)(CH[double bond, length as m-dash]CMeO)}], when R = 2-C6H4OH, but not when R = Ph. It has been suggested that the phenol substituent plays two key biomimetic roles; firstly, in proton coupled electron transfer reactions in the activation of oxygen and hydroperoxide groups and, secondly, in proton relay from a methyl group of the coordinated acetone.

Multiple proton relay routes in the reaction mechanism of RNAP II: assessing the effect of structural model.

RNA polymerase II catalyzes the nucleotidyl transfer reaction for messenger RNA synthesis in eukaryotes. Two crystal structures of this system have been resolved, each with its own defects in the coordination sphere of Mg(2+) (A) resulting from chemical modifications. We have used both structures and also a novel hybrid of the two that allows a better exploration of the parts of configuration space that reflect substrate-enzyme interactions. MD and QM/MM calculations have been performed, the latter with the semiempirical AM1/d-PhoT method, calibrated against density functional theory. Reaction path scans in 1-D provided insights about the role of Mg(2+) (A) which turns out to be more structural than catalytic. In contrast, 1-D scans of the incorporation of the nucleotidyl group yielded barriers that were much too high, necessitating the use of 2-D reaction coordinates. Three different proton acceptors for the initial reaction step were examined. For those models based on the two PDB structures the 2-D scans continued to yield very high barriers, indicating that the reaction is unlikely to proceed from these configurations. On the other hand, two hybrid models, chosen from the early and late parts of a 12 ns molecular dynamics simulation yielded greatly reduced barriers in the range of ∼ 17 to ∼ 27 kcal/mol for the three proton acceptors, as compared to the experimental estimate of 18 kcal/mol. The final step, release of pyrophosphate, was found to be facile. Our overall mechanism involves only active site residues or water without the need for external reactive agents such as the hydroxide ion previously proposed.

Role of tautomerism in RNA biochemistry.

Heterocyclic nucleic acid bases and their analogs can adopt multiple tautomeric forms due to the presence of multiple solvent-exchangeable protons. In DNA, spontaneous formation of minor tautomers has been speculated to contribute to mutagenic mispairings during DNA replication, whereas in RNA, minor tautomeric forms have been proposed to enhance the structural and functional diversity of RNA enzymes and aptamers. This review summarizes the role of tautomerism in RNA biochemistry, specifically focusing on the role of tautomerism in catalysis of small self-cleaving ribozymes and recognition of ligand analogs by riboswitches. Considering that the presence of multiple tautomers of nucleic acid bases is a rare occurrence, and that tautomers typically interconvert on a fast time scale, methods for studying rapid tautomerism in the context of nucleic acids under biologically relevant aqueous conditions are also discussed.

Oxidative uncoupling in cysteine dioxygenase is gated by a proton-sensitive intermediate.

Cysteine dioxygenase (CDO) is a non-heme mononuclear iron enzyme that catalyzes the O2-dependent oxidation of l-cysteine (Cys) to produce cysteine sulfinic acid (CSA). This enzyme catalyzes the first committed step in Cys catabolism; thus, it is central to mammalian sulfur metabolism and redox homeostasis. Ironically, despite nearly 45 years of continued research on CDO, essentially no information has been reported with respect to its kinetic mechanism. In this work, the timing of chemical steps in the CDO kinetic mechanism is investigated by pH/pD-dependent steady-state kinetics and solvent isotope effects on kcat, kcat/KM, and (O2/CSA) coupling. Normal solvent kinetic isotope effects of 1.45 ± 0.05 and 2.0 ± 0.1 are observed in kcat-pL and kcat/KM-pL profiles, respectively. Proton inventory experiments within the pL-independent region (pL 8.5) suggest multiple solvent-exchangeable protons in flight for both kcat and kcat/KM data. The influence of solvent viscosity was also investigated to probe non-chemical steps and to verify that the apparent isotope effects were not attributable to increased solvent viscosity of D2O reactions relative to H2O. Although solvent viscosity did have a modest influence on kcat and kcat/KM, the response is not sufficient to account for the observed solvent isotope effects. This suggests that product release is only partially rate-limiting for CDO catalysis. Most crucially, proton inventory of (O2/CSA) coupling indicates that a proton-sensitive transition state directly follows O2 activation. Thus, protonation of a transient species preceding Cys oxidation is gated by protons in flight. This behavior provides valuable insight into the kinetically masked transients generated during catalysis.

Three-way cooperativity in d8 metal complexes with ligands displaying chemical and redox non-innocence.

Reversible proton- and electron-transfer steps are crucial for various chemical transformations. The electron-reservoir behavior of redox non-innocent ligands and the proton-reservoir behavior of chemically non-innocent ligands can be cooperatively utilized for substrate bond activation. Although site-decoupled proton- and electron-transfer steps are often found in enzymatic systems, generating model metal complexes with these properties remains challenging. To tackle this issue, we present herein complexes [(cod-H)M(μ-L(2-)) M(cod-H)] (M = Pt(II), [1] or Pd(II), [2], cod = 1,5-cyclooctadiene, H2L = 2,5-di-[2,6-(diisopropyl)anilino]-1,4-benzoquinone), in which cod acts as a proton reservoir, and L(2-) as an electron reservoir. Protonation of [2] leads to an unusual tetranuclear complex. However, [1] can be stepwise reversibly protonated with up to two protons on the cod-H ligands, and the protonated forms can be stepwise reversibly reduced with up to two electrons on the L(2-) ligand. The doubly protonated form of [1] is also shown to react with OMe(-) leading to an activation of the cod ligands. The site-decoupled proton and electron reservoir sources work in tandem in a three-way cooperative process that results in the transfer of two electrons and two protons to a substrate leading to its double reduction and protonation. These results will possibly provide new insights into developing catalysts for multiple proton- and electron-transfer reactions by using metal complexes of non-innocent ligands.

Excited-state proton-transfer reactions of 7-azaindole with water, ammonia and mixed water–ammonia: microsolvated dynamics simulation

Dynamics simulations of excited-state multiple proton transfer (ESMPT) reactions in 7-azaindole (7AI) with ammonia, mixed water–ammonia, and water molecules were investigated by quantum dynamics simulations in the first-excited state using RI-ADC(2)/SVP-SV(P) in the gas phase. 7AI(WW), 7AI(WA), 7AI(AW) and 7AI(AA) clusters (W, water and A, ammonia) show very high probability of the excited-state triple proton transfer (ESTPT) occurrence in ranges from 20% for 7AI(WA) to 60% for 7AI(AW), respectively. Furthermore, 7AI(AW) clusters with ammonia placed near N–H of 7AI has the highest probability among other isomers. In 7AI with three molecules of bridged-planar of water, ammonia and mixed water–ammonia clusters, the excited-state quadruple proton transfer reactions occur ineffectively and rearrangement of hydrogen-bonded network on solvents also takes place prior to either ESTPT or excited-state double proton transfer. The role played by mixed-solvent is revealed with replacing H2O with NH3 in which the ESMPT is found to be more efficient corresponding to lower barrier in the excited state. The preferential number of solvent surrounding 7AI that facilitates the proton transfer process is two for methanol and water but this preferential number for ammonia is one.Highlights: (i) replacing H2O with NH3 assists ESPT corresponding to lower barrier in the excited state; (ii) the ESMPT time of 7AI with mixed water–ammonia is in the sub-picosecond timescale; (iii) the PT tends to be concerted process with at least one ammonia, but synchronous without ammonia.

Exceptional Isotopic‐Substitution Effect: Breakdown of Collective Proton Tunneling in Hexagonal Ice due to Partial Deuteration

AbstractMultiple proton transfer controls many chemical reactions in hydrogen‐bonded networks. However, in contrast to well‐understood single proton transfer, the mechanisms of correlated proton transfer and of correlated proton tunneling in particular have remained largely elusive. Herein, fully quantized ab initio simulations are used to investigate H/D isotopic‐substitution effects on the mechanism of the collective tunneling of six protons within proton‐ordered cyclic water hexamers that are contained in proton‐disordered ice, a prototypical hydrogen‐bonded network. At the transition state, isotopic substitution leads to a Zundel‐like complex, [HO⋅⋅⋅D⋅⋅⋅OH], which localizes ionic defects and thus inhibits perfectly correlated proton tunneling. These insights into fundamental aspects of collective proton tunneling not only rationalize recent neutron‐scattering experiments, but also stimulate investigations into multiple proton transfer in hydrogen‐bonded networks much beyond ice.

Exceptional isotopic-substitution effect: breakdown of collective proton tunneling in hexagonal ice due to partial deuteration.

Multiple proton transfer controls many chemical reactions in hydrogen-bonded networks. However, in contrast to well-understood single proton transfer, the mechanisms of correlated proton transfer and of correlated proton tunneling in particular have remained largely elusive. Herein, fully quantized ab initio simulations are used to investigate H/D isotopic-substitution effects on the mechanism of the collective tunneling of six protons within proton-ordered cyclic water hexamers that are contained in proton-disordered ice, a prototypical hydrogen-bonded network. At the transition state, isotopic substitution leads to a Zundel-like complex, [HO⋅⋅⋅D⋅⋅⋅OH], which localizes ionic defects and thus inhibits perfectly correlated proton tunneling. These insights into fundamental aspects of collective proton tunneling not only rationalize recent neutron-scattering experiments, but also stimulate investigations into multiple proton transfer in hydrogen-bonded networks much beyond ice.

Efficient Electrochemical Reduction of CO2 to Formic Acid

Fossil fuels comprise more than 80% of global energy sources because of their availability, versatility, and high energy density. However, their continued use at this level is accompanied by an unchecked accumulation of atmospheric CO2. An attractive alternative is to develop a scalable synthesis of carbon-containing products (formic acid, methane, methanol, and ethanol) using renewable energy, H2O, and CO2 at room temperature and atmospheric pressure. An efficient catalyst must mediate multiple electron and proton transfers to CO2 for the reduction of CO2 in the presence of H2O, and selectively produce one of many possible products. Researchers over the past three decades have identified several materials (e.g., semiconducting metal oxides) that are capable of reducing CO2 electrochemically in aqueous solutions, but none are efficient and stable enough for practical use due to the large overpotential (>0.7 V) required for CO2 reduction to outcompete H2O reduction. The energy level of the conduction band of semiconducting materials such as Cu2O or CuO cannot contain the sufficient reduction potential of CO2 to formic acid (HCOOH). In this regard, we are going to present our recent progress on the efficient CO2 reduction to formic acid by using bipolar WO3/Cu-CuO nanowires hybrid electrodes with low overpotential.

Quantification of iopamidol multi-site chemical exchange properties for ratiometric chemical exchange saturation transfer (CEST) imaging of pH

pH-sensitive chemical exchange saturation transfer (CEST) MRI holds great promise for in vivo applications. However, the CEST effect depends on not only exchange rate and hence pH, but also on the contrast agent concentration, which must be determined independently for pH quantification. Ratiometric CEST MRI normalizes the concentration effect by comparing CEST measurements of multiple labile protons to simplify pH determination. Iopamidol, a commonly used x-ray contrast agent, has been explored as a ratiometric CEST agent for imaging pH. However, iopamidol CEST properties have not been solved, determination of which is important for optimization and quantification of iopamidol pH imaging. Our study numerically solved iopamidol multi-site pH-dependent chemical exchange properties. We found that iopamidol CEST MRI is suitable for measuring pH between 6 and 7.5 despite that T1 and T2 measurements varied substantially with pH and concentration. The pH MRI precision decreased with pH and concentration. The standard deviation of pH determined from MRI was 0.2 and 0.4 pH unit for 40 and 20 mM iopamidol solution of pH 6, and it improved to be less than 0.1 unit for pH above 7. Moreover, we determined base-catalyzed chemical exchange for 2-hydrooxypropanamido (ksw = 1.2*10pH−4.1) and amide (ksw = 1.2*10pH−4.6) protons that are statistically different from each other (P < 0.01, ANCOVA), understanding of which should help guide in vivo translation of iopamidol pH imaging.

Catalytic strategy used by the myosin motor to hydrolyze ATP.

Myosin is a molecular motor responsible for biological motions such as muscle contraction and intracellular cargo transport, for which it hydrolyzes adenosine 5'-triphosphate (ATP). Early steps of the mechanism by which myosin catalyzes ATP hydrolysis have been investigated, but still missing are the structure of the final ADP·inorganic phosphate (Pi) product and the complete pathway leading to it. Here, a comprehensive description of the catalytic strategy of myosin is formulated, based on combined quantum-classical molecular mechanics calculations. A full exploration of catalytic pathways was performed and a final product structure was found that is consistent with all experiments. Molecular movies of the relevant pathways show the different reorganizations of the H-bond network that lead to the final product, whose γ-phosphate is not in the previously reported HPγO4(2-) state, but in the H2PγO4(-) state. The simulations reveal that the catalytic strategy of myosin employs a three-pronged tactic: (i) Stabilization of the γ-phosphate of ATP in a dissociated metaphosphate (PγO3(-)) state. (ii) Polarization of the attacking water molecule, to abstract a proton from that water. (iii) Formation of multiple proton wires in the active site, for efficient transfer of the abstracted proton to various product precursors. The specific role played in this strategy by each of the three loops enclosing ATP is identified unambiguously. It explains how the precise timing of the ATPase activation during the force generating cycle is achieved in myosin. The catalytic strategy described here for myosin is likely to be very similar in most nucleotide hydrolyzing enzymes.