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Journal of Bioenergetics and... Apr 2022In his Transmembrane Electrostatically Localized Proton hypothesis (TELP), James W. Lee has modeled the bioenergetic membrane as a simple capacitor. According to this... (Review)
Review
In his Transmembrane Electrostatically Localized Proton hypothesis (TELP), James W. Lee has modeled the bioenergetic membrane as a simple capacitor. According to this model, the surface concentration of protons is completely independent of proton concentration in the bulk phase, and is linearly proportional to the transmembrane potential. Such a proportionality runs counter to the results of experimental measurements, molecular dynamics simulations, and electrostatics calculations. We show that the TELP model dramatically overestimates the surface concentration of protons, and we discuss the electrostatic reasons why a simple capacitor is not an appropriate model for the bioenergetic membrane.
Topics: Energy Metabolism; Hydrogen-Ion Concentration; Membrane Potentials; Protons
PubMed: 35190945
DOI: 10.1007/s10863-022-09931-w -
Journal of the American Chemical Society Jun 2022Real-time monitoring of strain/stress in polymers is a big challenge to date. Herein, we for the first time report an ESIPT (excited-state intramolecular proton...
Real-time monitoring of strain/stress in polymers is a big challenge to date. Herein, we for the first time report an ESIPT (excited-state intramolecular proton transfer)-based mechanochromic mechanophore (MM). The synthesis of target MM PhMz-4OH [(2-hydroxyphenyl)benzimidazole with four aliphatic hydroxyls] is quite facile. PhMz-4OH possesses characteristic dual emissions, and its ESIPT activity is greatly affected by steric hindrance. Then, PhMz-4OH was covalently linked into polyurethane chains (PhMz-4OH@PU). Upon stretching, the PhMz-4OH@PU films showed fluorescence color change and spectral variation with the increase in enol emission and blueshift of keto emission due to the force-induced torsion of the dihedral angle between the proton donor and the proton acceptor. The PhMz-4OH@PU films with high mechanophore concentrations (>0.36 mol %) might undergo a two-stage force-responsive process, including torsion of the dihedral angle via force-induced disaggregation and direct chain-transduced force-induced torsion of the dihedral angle. The intensity ratio of enol emission to keto emission (/) shows a quantitative correlation with elongation, and real-time strain sensing is achieved. PhMz-4OH is a successful type II MM (without covalent bond scission) and displays high sensitivity and excellent reversibility to stress. Two control structures PhMz-NH and PhMz-2OH were also embedded into PU but no spectral or color changes were detected, further confirming that mechanochromism of PhMz-4OH@PU films arises from the chain-transduced force. Density function theory (DFT) calculation was performed to study the force-tuned ESIPT process theoretically and rationalize the experimental results. This study might lay the foundation for real-time stress/strain sensing in practical applications.
Topics: Polymers; Protons
PubMed: 35617457
DOI: 10.1021/jacs.2c03056 -
ELife Oct 2021Ligand-gated ion channels conduct currents in response to chemical stimuli, mediating electrochemical signaling in neurons and other excitable cells. For many channels,...
Ligand-gated ion channels conduct currents in response to chemical stimuli, mediating electrochemical signaling in neurons and other excitable cells. For many channels, the details of gating remain unclear, partly due to limited structural data and simulation timescales. Here, we used enhanced sampling to simulate the pH-gated channel GLIC, and construct Markov state models (MSMs) of gating. Consistent with new functional recordings, we report in oocytes, our analysis revealed differential effects of protonation and mutation on free-energy wells. Clustering of closed- versus open-like states enabled estimation of open probabilities and transition rates, while higher-order clustering affirmed conformational trends in gating. Furthermore, our models uncovered state- and protonation-dependent symmetrization. This demonstrates the applicability of MSMs to map energetic and conformational transitions between ion-channel functional states, and how they reproduce shifts upon activation or mutation, with implications for modeling neuronal function and developing state-selective drugs.
Topics: Animals; Ligand-Gated Ion Channels; Markov Chains; Nuclear Pore; Protons; Xenopus laevis
PubMed: 34652272
DOI: 10.7554/eLife.68369 -
International Journal of Molecular... Nov 2022Organic molecules with excited-state intramolecular proton transfer (ESIPT) and thermally activated delayed fluorescence (TADF) properties have great potential for...
Organic molecules with excited-state intramolecular proton transfer (ESIPT) and thermally activated delayed fluorescence (TADF) properties have great potential for realizing efficient organic light-emitting diodes (OLEDs). Furthermore, 2,2'-bipyridine-3,3'-diol (BP(OH)) is a typical molecule with ESIPT and TADF properties. Previously, the double ESIPT state was proved to be a luminescent state, and the T state plays a dominant role in TADF for the molecule. Nevertheless, whether BP(OH) undergoes a double or single ESIPT process is controversial. Since different ESIPT channels will bring different TADF mechanisms, the previously proposed TADF mechanism based on the double ESIPT structure for BP(OH) needs to be reconsidered. Herein, reduced density gradient, potential energy surface, IR spectra and exited-state hydrogen-bond dynamics computations confirm that BP(OH) undergoes the barrierless single ESIPT process rather than the double ESIPT process with a barrier. Moreover, based on the single ESIPT structure, we calculated spin-orbit coupling matrix elements, nonradiative rates and electron-hole distributions. These results disclose that the T state plays a predominant role in TADF. Our investigation provides a better understanding on the TADF mechanism in hydrogen-bonded molecular systems and the interaction between ESIPT and TADF, which further provides a reference for developing efficient OLEDs.
Topics: Protons; Alcohols; Proton Therapy; Hydrogen Bonding
PubMed: 36430447
DOI: 10.3390/ijms232213969 -
Journal of the American Chemical Society Jun 2023[NiFe]-hydrogenases catalyze the reversible cleavage of H into two protons and two electrons at the inorganic heterobimetallic NiFe center of the enzyme. Their catalytic...
[NiFe]-hydrogenases catalyze the reversible cleavage of H into two protons and two electrons at the inorganic heterobimetallic NiFe center of the enzyme. Their catalytic cycle involves at least four intermediates, some of which are still under debate. While the core reaction, including H/H binding, takes place at the inorganic cofactor, a major challenge lies in identifying those amino acid residues that contribute to the reactivity and how they stabilize (short-lived) intermediate states. Using cryogenic infrared and electron paramagnetic resonance spectroscopy on the regulatory [NiFe]-hydrogenase from , a model enzyme for the analysis of catalytic intermediates, we deciphered the structural basis of the hitherto elusive Ni-L intermediates. We unveiled the protonation states of a proton-accepting glutamate and a Ni-bound cysteine residue in the Ni-L1, Ni-L2, and the hydride-binding Ni-C intermediates as well as previously unknown conformational changes of amino acid residues in proximity of the bimetallic active site. As such, this study unravels the complexity of the Ni-L intermediate and reveals the importance of the protein scaffold in fine-tuning proton and electron dynamics in [NiFe]-hydrogenase.
Topics: Protons; Hydrogenase; Catalysis; Catalytic Domain; Glutamic Acid; Oxidation-Reduction
PubMed: 37328284
DOI: 10.1021/jacs.3c01625 -
Brain Injury Jun 2021: Patients in intensive care units with traumatic brain injuries (TBI) frequently present acid-base abnormalities and coagulability disorders, which complicate their...
: Patients in intensive care units with traumatic brain injuries (TBI) frequently present acid-base abnormalities and coagulability disorders, which complicate their condition.: To identify protonation through simulations of molecules involved in the process of coagulation in standard laboratory tests.: Ten patients with TBI were selected from the intensive care unit in addition to ten "healthy control subjects", and another nine patients as "disease control subjects"; the latter being a comparative group, corresponding to subjects with diabetes mellitus 2 (DM2). Fibrinogen, FVII, FVIII, FIX, FX, and D-dimer in the presence of acidification were evaluated in 20 healthy subjects in order to compare clinical results with molecular dynamics (MD), and to explain proton interactions and coagulation molecules.: The TBI group presented a slight, non-significant increase in D-dimer; but this was not present in "disease control subjects". Levels of fibrinogen, FVII, FIX, FX, and D-dimer were affected in the presence of acidification. We observed that various specific residues of coagulation factors "trap" ions.: Protonation of tissue factor and factor VIIa may favor anticoagulant mechanisms, and protonation does not affect ligand binding sites of GPIIb/IIIa (PAC1) suggesting other causes for the low affinity to PAC1.
Topics: Blood Coagulation; Brain Injuries, Traumatic; Humans; Molecular Dynamics Simulation; Protons
PubMed: 33678100
DOI: 10.1080/02699052.2021.1895312 -
Journal of the American Society For... Apr 2020Gas phase modification in ESI-MS can significantly alter the charge state distribution of small peptides and proteins. The preceding paper presented a systematic...
Gas phase modification in ESI-MS can significantly alter the charge state distribution of small peptides and proteins. The preceding paper presented a systematic experimental study on this topic using Substance P and proposed a charge retention/charge depletion mechanism, explaining different gas- and liquid-phase modifications [Thinius et al. 2020, 10.1021/jasms.9b00044]. In this work, we aim to support this rational by theoretical investigations on the proton transfer processes from (multiply) charged analytes toward solvent clusters. As model systems we use small (di)amines as analytes and methanol (MeOH) and acetonitrile (ACN) as gas phase modifiers. The calculations are supported by a set of experiments using (di)amines, to bridge the gap between the present model system and Substance P used in the preceding study. Upon calculation of the thermochemical stability as well as the proton transfer pathways, we find that both ACN and MeOH form stable adduct clusters at the protonation site. MeOH can form large clusters through a chain of H-bridges, eventually lowering the barriers for proton transfer to an extent that charge transfer from the analyte to the MeOH cluster becomes feasible. ACN, however, cannot form H-bridged structures due to its aprotic nature. Hence, the charge is retained at the original protonation site, i.e., the analyte. The investigation confirms the proposed charge retention/charge depletion model. Thus, adding aprotic solvent vapors to the gas phase of an ESI source more likely yields higher charge states than using protic compounds.
Topics: Acetonitriles; Diamines; Gases; Lysine; Methanol; Models, Chemical; Protons; Spectrometry, Mass, Electrospray Ionization
PubMed: 32150409
DOI: 10.1021/jasms.9b00045 -
Journal of the American Chemical Society May 2023Channelrhodopsins (ChRs) are light-gated ion channels and central optogenetic tools that can control neuronal activity with high temporal resolution at the single-cell...
Channelrhodopsins (ChRs) are light-gated ion channels and central optogenetic tools that can control neuronal activity with high temporal resolution at the single-cell level. Although their application in optogenetics has rapidly progressed, it is unsolved how their channels open and close. ChRs transport ions through a series of interlocking elementary processes that occur over a broad time scale of subpicoseconds to seconds. During these processes, the retinal chromophore functions as a channel regulatory domain and transfers the optical input as local structural changes to the channel operating domain, the helices, leading to channel gating. Thus, the core question on channel gating dynamics is how the retinal chromophore structure changes throughout the photocycle and what rate-limits the kinetics. Here, we investigated the structural changes in the retinal chromophore of canonical ChR, C1C2, in all photointermediates using time-resolved resonance Raman spectroscopy. Moreover, to reveal the rate-limiting factors of the photocycle and channel gating, we measured the kinetic isotope effect of all photoreaction processes using laser flash photolysis and laser patch clamp, respectively. Spectroscopic and electrophysiological results provided the following understanding of the channel gating: the retinal chromophore highly twists upon the retinal Schiff base (RSB) deprotonation, causing the surrounding helices to move and open the channel. The ion-conducting pathway includes the RSB, where inflowing water mediates the proton to the deprotonated RSB. The twisting of the retinal chromophore relaxes upon the RSB reprotonation, which closes the channel. The RSB reprotonation rate-limits the channel closing.
Topics: Channelrhodopsins; Ion Channels; Electrophysiological Phenomena; Protons; Light
PubMed: 37129501
DOI: 10.1021/jacs.3c01879 -
The Science of the Total Environment Nov 2021Fuel cells (FCs) are a chemical fuel device which can directly convert chemical energy into electrical energy, also known as electrochemical generator. Proton exchange... (Review)
Review
Fuel cells (FCs) are a chemical fuel device which can directly convert chemical energy into electrical energy, also known as electrochemical generator. Proton exchange membrane fuel cells (PEMFCs) are one of the most appealing FC systems that have been broadly developed in recent years. Due to the poor conductivity of electrolyte membrane used in traditional PEMFC, its operation at higher temperature is greatly limited. The incorporation of ionic liquids (ILs) which is widely regarded as a greener alternative compared to traditional solvents in the proton exchange membrane electrolyte shows great potential in high temperature PEMFCs (HT-PEMFCs). This review provides insights in the latest progress of utilizing ILs as an electrochemical electrolyte in PEMFCs. Besides, electrolyte membranes that are constructed by ILs combined with polybenzimidazole (PBI) have many benefits such as better thermal stability, improved mechanical properties, and higher proton conductivity. The current review aims to investigate the newest development and existing issues of ILs research in electrolyte and material selection, system fabrication method, synthesis of ILs, and experimental techniques. The evaluation of life cycle analysis, commercialization, and greenness of ILs are also discussed. Hence, this review provides insights to material scientists and develops interest of wider community, promoting the use of ILs to meet energy challenges.
Topics: Electrolytes; Ionic Liquids; Membranes, Artificial; Protons; Technology
PubMed: 34328982
DOI: 10.1016/j.scitotenv.2021.148705 -
Journal of the American Chemical Society Aug 2022The unique four-level photocycle characteristics of excited-state intramolecular proton transfer (ESIPT) materials enable population inversion and large spectral...
The unique four-level photocycle characteristics of excited-state intramolecular proton transfer (ESIPT) materials enable population inversion and large spectral separation between absorption and emission through their respective enol and keto forms. This leads to minimal or no self-absorption losses, a favorable feature in acting as an optical gain medium. While conventional ESIPT materials with an enol-keto tautomerism process are widely known, zwitterionic ESIPT materials, particularly those with high photoluminescence, are scarce. Facilitated by the synthesis and characterization of a new family of 2-hydroxyphenyl benzothiazole (HBT) with fluorene substituents, and , we herein report the first efficient zwitterionic ESIPT lasing material (). The zwitterionic ESIPT not only shows a remarkably low solid-state amplified spontaneous emission (ASE) threshold of 5.3 μJ/cm with an ASE peak at 609 nm but also exhibits high ASE photostability. Coupled with its substantially large Stokes shift (≈236 nm ≈10,390 cm) and an extremely small overlap of excited-state absorption with ASE emission, comprehensive density functional theory (DFT) and time-dependent DFT studies reveal the zwitterionic characteristics of . In opposition to conventional ESIPT with π-delocalized tautomerism as observed in analogue and parent HBT, instead shows charge redistribution in the proton transfer through the fluorene conjugation. This structural motif provides a design tactic in the innovation of new zwitterionic ESIPT materials for efficient light amplification in red and longer-wavelength emission.
Topics: Fluorenes; Protons
PubMed: 35862745
DOI: 10.1021/jacs.2c02163