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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 Medical Radiation Sciences Apr 2024Australia has taken a collaborative nationally networked approach to achieve particle therapy capability. This supports the under-construction proton therapy facility in... (Review)
Review
Australia has taken a collaborative nationally networked approach to achieve particle therapy capability. This supports the under-construction proton therapy facility in Adelaide, other potential proton centres and an under-evaluation proposal for a hybrid carbon ion and proton centre in western Sydney. A wide-ranging overview is presented of the rationale for carbon ion radiation therapy, applying observations to the case for an Australian facility and to the clinical and research potential from such a national centre.
Topics: Protons; Australia; Heavy Ion Radiotherapy; Proton Therapy; Ions
PubMed: 38061984
DOI: 10.1002/jmrs.744 -
Journal of the American Chemical Society Sep 2022In this research article, we describe a 4H/4e electron-coupled-proton buffer (ECPB) based on Cu and a redox-active ligand. The protonated/reduced ECPB (complex : ),...
In this research article, we describe a 4H/4e electron-coupled-proton buffer (ECPB) based on Cu and a redox-active ligand. The protonated/reduced ECPB (complex : ), consisting of Cu with 2 equiv of the ligand (LH: 1,1'-(4,5-dimethoxy-1,2-phenylene)bis(3-(-butyl)urea)), reacted with H/e acceptors such as O to generate the deprotonated/oxidized ECPB. The resulting compound, (complex : ), was characterized by X-ray diffraction analysis, nuclear magnetic resonance (H-NMR), and density functional theory, and it is electronically described as a cuprous bis(benzoquinonediimine) species. The stoichiometric 4H/4e reduction of was carried out with H/e donors to generate (Cu and 2 equiv of LH) and the corresponding oxidation products. The ECPB system catalyzed the 4H/4e reduction of O to HO and the dehydrogenation of organic substrates in a decoupled (oxidations and reductions are separated in time and space) and a coupled fashion (oxidations and reductions coincide in time and space). Mechanistic analysis revealed that upon reductive protonation of and oxidative deprotonation of , fast disproportionation reactions regenerate complexes and in a stoichiometric fashion to maintain the ECPB equilibrium.
Topics: Copper; Electrons; Ligands; Oxidation-Reduction; Protons; Urea
PubMed: 36083845
DOI: 10.1021/jacs.2c05454 -
Scientific Reports Aug 2018The H, K-ATPase (HKA) uses ATP to pump protons into the gastric lumen against a million-fold proton concentration gradient while counter-transporting K from the lumen....
The H, K-ATPase (HKA) uses ATP to pump protons into the gastric lumen against a million-fold proton concentration gradient while counter-transporting K from the lumen. The mechanism of release of a proton into a highly acidic stomach environment, and the subsequent binding of a K ion necessitates a network of protonable residues and dynamically changing protonation states in the cation binding pocket dominated by five acidic amino acid residues E343, E795, E820, D824, and D942. We perform molecular dynamics simulations of spontaneous K binding to all possible protonation combinations of the acidic amino acids and carry out free energy calculations to determine the optimal protonation state of the luminal-open EP state of the pump which is ready to bind luminal K. A dynamic pK correlation analysis reveals the likelihood of proton transfer events within the cation binding pocket. In agreement with in-vitro measurements, we find that E795 is likely to be protonated, and that E820 is at the center of the proton transfer network in the luminal-open EP state. The acidic residues D942 and D824 are likely to remain protonated, and the proton redistribution occurs predominantly amongst the glutamate residues exposed to the lumen. The analysis also shows that a lower number of K ions bind at lower pH, modeled by a higher number of protons in the cation binding pocket, in agreement with the 'transport stoichiometry variation' hypothesis.
Topics: Animals; Binding Sites; H(+)-K(+)-Exchanging ATPase; HEK293 Cells; Humans; Models, Molecular; Mutant Proteins; Potassium; Protein Conformation; Protons; Swine; Thermodynamics
PubMed: 30143663
DOI: 10.1038/s41598-018-30885-w -
IUBMB Life Jan 2014Escherichia coli possesses four [NiFe]-hydrogenases that catalyze the reversible redox reaction of 2H(+) + 2e(-) ↔ H2. These enzymes together have the potential to... (Review)
Review
Escherichia coli possesses four [NiFe]-hydrogenases that catalyze the reversible redox reaction of 2H(+) + 2e(-) ↔ H2. These enzymes together have the potential to form a hydrogen cycle across the membrane. Their activity, operational direction, and interaction with each other depend on the fermentation substrate and particularly pH. The enzymes producing H2 are likely able to translocate protons through the membrane. Moreover, the activity of some of these enzymes is dependent on the F0 F1 -ATPase, thus linking a proton cycle with the cycling of hydrogen. These two cycles are suggested to have a primary basic role in modulating the cell's energetics during mixed-acid fermentation, particularly in response to pH. Nevertheless, the mechanisms underlying the physical interactions between these enzyme complexes, as well as how this is controlled, are still not clearly understood. Here, we present a synopsis of the potential impact of proton-hydrogen cycling in fermentative bioenergetics.
Topics: Bacteria; Energy Metabolism; Fermentation; Hydrogen; Proton-Motive Force; Protons
PubMed: 24501007
DOI: 10.1002/iub.1236 -
Annual Review of Biophysics 2013Posttranslational modification is an evolutionarily conserved mechanism for regulating protein activity, binding affinity, and stability. Compared with established... (Review)
Review
Posttranslational modification is an evolutionarily conserved mechanism for regulating protein activity, binding affinity, and stability. Compared with established posttranslational modifications such as phosphorylation or ubiquitination, posttranslational modification by protons within physiological pH ranges is a less recognized mechanism for regulating protein function. By changing the charge of amino acid side chains, posttranslational modification by protons can drive dynamic changes in protein conformation and function. Addition and removal of a proton is rapid and reversible and, in contrast to most other posttranslational modifications, does not require an enzyme. Signaling specificity is achieved by only a minority of sites in proteins titrating within the physiological pH range. Here, we examine the structural mechanisms and functional consequences of proton posttranslational modification of pH-sensing proteins regulating different cellular processes.
Topics: Animals; Disease; Eukaryotic Cells; Humans; Hydrogen-Ion Concentration; Prokaryotic Cells; Protein Conformation; Protein Processing, Post-Translational; Protons
PubMed: 23451893
DOI: 10.1146/annurev-biophys-050511-102349 -
FEBS Letters May 2010Mitochondrial uncoupling proteins (UCPs) are pure anion uniporters, which mediate fatty acid (FA) uniport leading to FA cycling. Protonated FAs then flip-flop back... (Review)
Review
Mitochondrial uncoupling proteins (UCPs) are pure anion uniporters, which mediate fatty acid (FA) uniport leading to FA cycling. Protonated FAs then flip-flop back across the lipid bilayer. An existence of pure proton channel in UCPs is excluded by the equivalent flux-voltage dependencies for uniport of FAs and halide anions, which are best described by the Eyring barrier variant with a single energy well in the middle of two peaks. Experiments with FAs unable to flip and alkylsulfonates also support this view. Phylogenetically, UCPs took advantage of the common FA-uncoupling function of SLC25 family carriers and dropped their solute transport function.
Topics: Animals; Electrophoresis; Humans; Ion Channels; Mitochondrial Proteins; Models, Biological; Protons; Uncoupling Protein 1
PubMed: 20206627
DOI: 10.1016/j.febslet.2010.02.068 -
The Journal of Physiology Jan 2021Acid-sensing ion channels (ASICs) are a class of trimeric cation-selective ion channels activated by changes in pH within the physiological range. They are widely... (Review)
Review
Acid-sensing ion channels (ASICs) are a class of trimeric cation-selective ion channels activated by changes in pH within the physiological range. They are widely expressed in the central and peripheral nervous systems where they participate in a range of physiological and pathophysiological situations such as learning and memory, pain sensation, fear and anxiety, substance abuse and cell death. ASICs are localized to cell bodies and dendrites, including the postsynaptic density, and within the last 5 years several examples of proton-evoked ASIC excitatory postsynaptic currents have emerged. Thus, ASICs have become bona fide neurotransmitter-gated ion channels, activated by the smallest neurotransmitter possible: protons. Here we review how protons are thought to drive the conformational changes associated with ASIC activation and desensitization. In particular, we weigh the evidence for and against the so-called 'acidic pocket' being a vital proton sensor and discuss the emerging role of the β11-12 linker as a desensitization switch or 'molecular clutch'. We also examine how proton-induced conformational changes pose unique challenges to classical molecular dynamics simulations, as well as some possible solutions. Given the emergence of new methodologies and structures, the coming years will probably see many advances in the study of acid-sensing ion channels.
Topics: Acid Sensing Ion Channels; Hydrogen-Ion Concentration; Protons
PubMed: 32306405
DOI: 10.1113/JP278707 -
International Journal of Molecular... Jun 2023Cytochrome c Oxidase (CcO), a membrane protein of the respiratory chain, pumps protons against an electrochemical gradient by using the energy of oxygen reduction to...
Cytochrome c Oxidase (CcO), a membrane protein of the respiratory chain, pumps protons against an electrochemical gradient by using the energy of oxygen reduction to water. The ("chemical") protons required for this reaction and those pumped are taken up via two distinct channels, named D-channel and K-channel, in a step-wise and highly regulated fashion. In the reductive phase of the catalytic cycle, both channels transport protons so that the pumped proton passes the D-channel before the "chemical" proton has crossed the K-channel. By performing molecular dynamics simulations of CcO in the O→E redox state (after the arrival of the first reducing electron) with various combinations of protonation states of the D- and K-channels, we analysed the effect of protonation on the two channels. In agreement with previous work, the amount of water observed in the D-channel was significantly higher when the terminal residue E286 was not (yet) protonated than when the proton arrived at this end of the D-channel and E286 was neutral. Since a sufficient number of water molecules in the channel is necessary for proton transport, this can be understood as E286 facilitating its own protonation. K-channel hydration shows an even higher dependence on the location of the excess proton in the K-channel. Also in agreement with previous work, the K-channel exhibits a very low hydration level that likely hinders proton transfer when the excess proton is located in the lower part of the K-channel, that is, on the N-side of S365. Once the proton has passed S365 (towards the reaction site, the bi-nuclear centre (BNC)), the amount of water in the K-channel provides hydrogen-bond connectivity that renders proton transfer up to Y288 at the BNC feasible. No significant direct effect of the protonation state of one channel on the hydration level, hydrogen-bond connectivity, or interactions between protein residues in the other channel could be observed, rendering proton conductivity in the two channels independent of each other. Regulation of the order of proton uptake and proton passage in the two channels such that the "chemical" proton leaves its channel last must, therefore, be achieved by other means of communication, such as the location of the reducing electron.
Topics: Electron Transport Complex IV; Protons; Electron Transport; Oxidation-Reduction; Water; Rhodobacter sphaeroides
PubMed: 37445646
DOI: 10.3390/ijms241310464 -
Current Pharmaceutical Design 2013In this review we discuss the role of protonation states in receptor-ligand interactions, providing experimental evidences and computational predictions that complex... (Review)
Review
In this review we discuss the role of protonation states in receptor-ligand interactions, providing experimental evidences and computational predictions that complex formation may involve titratable groups with unusual pKa's and that protonation states frequently change from unbound to bound states. These protonation changes result in proton uptake/release, which in turn causes the pH-dependence of the binding. Indeed, experimental data strongly suggest that almost any binding is pH-dependent and to be correctly modeled, the protonation states must be properly assigned prior to and after the binding. One may accurately predict the protonation states when provided with the structures of the unbound proteins and their complex; however, the modeling becomes much more complicated if the bound state has to be predicted in a docking protocol or if the structures of either bound or unbound receptor-ligand are not available. The major challenges that arise in these situations are the coupling between binding and protonation states, and the conformational changes induced by the binding and ionization states of titratable groups. In addition, any assessment of the protonation state, either before or after binding, must refer to the pH of binding, which is frequently unknown. Thus, even if the pKa's of ionizable groups can be correctly assigned for both unbound and bound state, without knowing the experimental pH one cannot assign the corresponding protonation states, and consequently one cannot calculate the resulting proton uptake/release. It is pointed out, that while experimental pH may not be the physiological pH and binding may involve proton uptake/release, there is a tendency that the native receptor-ligand complexes have evolved toward specific either subcellular or tissue characteristic pH at which the proton uptake/release is either minimal or absent.
Topics: Ligands; Models, Molecular; Protein Binding; Protons; Receptors, Cell Surface
PubMed: 23170880
DOI: 10.2174/1381612811319230004