Proton Transfer Pathways Research Articles

Activation mechanism of hydrogen peroxide by a divanadium–substituted polyoxometalate [γ–PV2W10O38(μ–OH)2]3–: A computational study

In the present paper, the reaction mechanism corresponding to activation of hydrogen peroxide (H2O2) by a divanadium–substituted polyoxometalate (POM) [γ–PV2W10O38(μ–OH)2]3– (I) to form catalytic active species, peroxo complex [γ–PV2W10O38(μ-η2,η2–O2)]3– (III), was studied by using the density functional theory (DFT) calculations method with B3LYP functional. The results indicate that coordination of H2O2 to I proceeds via a vanadium–center–assisted proton transfer pathway to remove the first water molecule and form a hydroperoxy intermediate [γ–PV2W10O38(μ–OH) (μ–OOH)]3– (II). And intermediate II occurs through three successive water–assisted proton transfer steps to remove the second water molecule and finally forms catalytic active species. The calculated overall energy profiles show that coordination of H2O2 to vanadium center requires a proton transfer barrier of about 24 kcal mol−1. A detailed comparison of molecular geometries and electronic structure shows that the catalytic active species has a very interesting structural feature, where a superoxide radical (O2−) was embedded into two vanadium centers, and may be a potential nucleophile. The unique withdrawing electron properties and flexible bonding ability of the γ–Keggin–type POM ligand contribute to the formation of O2− radical. The tunable alternate arrangement of W–O bond series in γ–Keggin–type POM ligand contributes to the flexibility of the γ–Keggin–type POM ligand. Meanwhile, our DFT calculations show a good performance of B3LYP-gauge-independent atomic orbital (IGAIM) method for the calculation of 1H NMR parameters of divanadium-substituted phosphotungstate.

Engineering Proton Transfer in Photosynthetic Oxygen Evolution: Chloride, Nitrate, and Trehalose Reorganize a Hydrogen-Bonding Network.

Photosystem II oxidizes water at a Mn4CaO5 cluster. Oxygen evolution is accompanied by proton release through a 35 Å hydrogen-bonding network to the lumen. The mechanism of this proton-transfer reaction is not known, but the reaction is dependent on chloride. Here, vibrational spectroscopy defines the functional properties of the proton-transfer network using chloride, bromide, and nitrate as perturbative agents. As assessed by peptide C═O frequencies, bromide substitution yields a spectral Stark shift because of its increase in ionic radius. Nitrate substitution leads to more complex spectral changes, consistent with an overall increase in hydrogen-bonding interactions with the peptide backbone. The effects are similar to spectral changes previously documented in site-directed mutations in a putative lumenal pathway. Importantly, the effects of nitrate are reversed by the osmolyte, trehalose. Trehalose is known to alter hydrogen-bonding interactions in proteins. Trehalose addition also reverses a shift in an internal hydronium ion signal, consistent with an alteration in its p Ka value and a change in the basicity of bound nitrate. The spectra provide evidence that the proton-transfer pathway contains peptide carbonyl groups, internal water, a hydronium ion, and amino acid side chains. These experiments also show that the proton-transfer pathway functionally adapts to changes in electric field, p Ka, and hydrogen bonding and thereby optimizes proton transfer to the lumen.

Comprehensive performance enhancement of polybenzimidazole based high temperature proton exchange membranes by doping with a novel intercalated proton conductor

On the study of high temperature proton exchange membrane (HTPEM), the trade-off between proton conductivity and physico-chemical property (such as mechanical strength, dimensional stability and methanol resistance) remained a main obstacle for comprehensive performance enhancement. To address this issue, novel HTPEM was prepared by doping phosphotungstic acid intercalated ferric sulfophenyl phosphate (FeSPP-PWA) into polybenzimidazole (PBI) via hot pressed method. Intense hydrogen bonding network was built between PBI and FeSPP-PWA, rendering construction of proton channels and reinforcement of physico-chemical property. As a novel proton conductor, FeSPP-PWA facilitated formation of efficient proton transfer pathway. The layered morphology and inorganic intrinsity of FeSPP-PWA also improved the mechanical and dimensional stability while reducing the methanol permeability of the PBI/FeSPP-PWA membranes. The composite membrane exhibited good thermal stability up to 200 °C. The proton conductivity of PBI/FeSPP-PWA (30 wt%) reached 110 mS cm−1 at 170 °C and 100% RH, and was 69.3 mS cm−1 at 180 °C and 50% RH. The PBI/FeSPP-PWA also showed low methanol permeability and high membrane selectivity for application in direct methanol fuel cells.

Excited-State Proton Transfer Mechanism of 2,6-Diazaindoles·(H2O) n ( n = 2-4) Clusters.

This paper identified a new excited-state proton transfer (ESPT) mechanism for 2,6-diazaindoles (2,6-DAI) in aqueous (H2O) solution based on time-dependent density functional theory. The calculated results show that the excited-state three proton transfer reaction cannot occur because the 2,6-DAI with two water molecules do not form hydrogen bond wires; this finding was different from those reported in previous experiments (Chung et al. J. Am. Chem. Soc. 2017, 139, 6396-6402). 2,6-DAI with three water molecules form 2,6-DAI·(H2O)3 clusters, whereas 2,6-DAI with four water molecules form 2,6-DAI·(H2O)4 cluster. These clusters participate in the ESPT reaction. To determine the ESPT mechanism of 2,6-DAI·(H2O)3 and 2,6-DAI·(H2O)4 clusters, we constructed the potential energy curves of S1 and S0 states. The results confirmed the simultaneous presence of both 2,6-DAI·(H2O)3 and 2,6-DAI·(H2O)4 clusters and only one proton transfer pathway. By calculating the transition states of 2,6-DAI·(H2O)3 and 2,6-DAI·(H2O)4 clusters, we found that the ESPT reaction is a consistent mechanism. Our work investigated the number of water molecules involved in the ESPT and paved the way to further study the intermolecular hydrogen bonding interactions in the biological field.

Excited-State Proton Transfer in Thiazolo-[4, 5-d]thiazo Heterocyclic Systems and the Geometry Alterations' Effect on Photophysical Characters: A Theoretical Study.

Thiazolo-[4,5- d]-thiazo-frame (tztz) compounds are important heteroaromatic organic systems, which recently became a subject of several studies in the field of organic electronics and organic photovoltaics. The most important physical nature of these systems is reported to be an equilibrium between enol and keto forms following excited-state proton transfer. This process originates from a flat trend of the S1 PE (potential energy) profile along the proton transfer coordinate. In the present work, we determined and interpreted the excited-state proton transfer and photophysical nature of these systems extensively by means of the MP2/CC2 and CASSCF theoretical approaches. Also, the effects of amine (-NH2) and cyano (-CN) substitutions were taken into account comprehensively by considering the transition energies and proton transfer pathways of the resulting tztz derivatives. It has been predicted that the physical nature of the excited-state intramolecular proton transfer, as the main character of these systems, is being affected significantly by substitutions. For all of the considered tztz derivatives, a conical intersection (CI) between ground and the S1 excited state was predicted. This CI makes the considered species capable to be responsible for photochromism and photoswitching as well.

Pseudomonas aeruginosa overexpression system of nitric oxide reductase for in vivo and in vitro mutational analyses

Membrane-integrated nitric oxide reductase (NOR) reduces nitric oxide (NO) to nitrous oxide (N2O) with protons and electrons. This process is essential for the elimination of the cytotoxic NO that is produced from nitrite (NO2−) during microbial denitrification. A structure-guided mutagenesis of NOR is required to elucidate the mechanism for NOR-catalyzed NO reduction. We have already solved the crystal structure of cytochrome c-dependent NOR (cNOR) from Pseudomonas aeruginosa. In this study, we then constructed its expression system using cNOR-gene deficient and wild-type strains for further functional study. Characterizing the variants of the five conserved Glu residues located around the heme/non-heme iron active center allowed us to establish how the anaerobic growth rate of cNOR-deficient strains expressing cNOR variants correlates with the in vitro enzymatic activity of the variants. Since bacterial strains require active cNOR to eliminate cytotoxic NO and to survive under denitrification conditions, the anaerobic growth rate of a strain with a cNOR variant is a good indicator of NO decomposition capability of the variants and a marker for the screening of functionally important residues without protein purification. Using this in vivo screening system, we examined the residues lining the putative proton transfer pathways for NO reduction in cNOR, and found that the catalytic protons are likely transferred through the Glu57 located at the periplasmic protein surface. The homologous cNOR expression system developed here is an invaluable tool for facile identification of crucial residues in vivo, and for further in vitro functional and structural studies.

Characterization of the quinol-dependent nitric oxide reductase from the pathogen Neisseria meningitidis, an electrogenic enzyme

Bacterial nitric oxide reductases (NORs) catalyse the reduction of NO to N2O and H2O. NORs are found either in denitrification chains, or in pathogens where their primary role is detoxification of NO produced by the immune defense of the host. Although NORs belong to the heme-copper oxidase superfamily, comprising proton-pumping O2-reducing enzymes, the best studied NORs, cNORs (cytochrome c-dependent), are non-electrogenic. Here, we focus on another type of NOR, qNOR (quinol-dependent). Recombinant qNOR from Neisseria meningitidis, a human pathogen, purified from Escherichia coli, showed high catalytic activity and spectroscopic properties largely similar to cNORs. However, in contrast to cNOR, liposome-reconstituted qNOR showed respiratory control ratios above two, indicating that NO reduction by qNOR was electrogenic. Further, we determined a 4.5 Å crystal structure of the N. meningitidis qNOR, allowing exploration of a potential proton transfer pathway from the cytoplasm by mutagenesis. Most mutations had little effect on the activity, however the E-498 variants were largely inactive, while the corresponding substitution in cNOR was previously shown not to induce significant effects. We thus suggest that, contrary to cNOR, the N. meningitidis qNOR uses cytoplasmic protons for NO reduction. Our results allow possible routes for protons to be discussed.

Benchmark ab Initio Characterization of the Complex Potential Energy Surfaces of the X- + NH2Y [X, Y = F, Cl, Br, I] Reactions.

We report a comprehensive high-level explicitly correlated ab initio study on the X- + NH2Y [X,Y = F, Cl, Br, I] reactions characterizing the stationary points of the SN2 (Y- + NH2X) and proton-transfer (HX + NHY-) pathways as well as the reaction enthalpies of various endothermic additional product channels such as H- + NHXY, XY- + NH2, XY + NH2-, and XHY- + NH. Benchmark structures and harmonic vibrational frequencies are obtained at the CCSD(T)-F12b/aug-cc-pVTZ(-PP) level of theory, followed by CCSD(T)-F12b/aug-cc-pVnZ(-PP) [n = Q and 5] and core correlation energy computations. In the entrance and exit channels we find two equivalent hydrogen-bonded C1 minima, X-···HH'NY and X-···H'HNY connected by a Cs first-order saddle point, X-···H2NY, as well as a halogen-bonded front-side complex, X-···YNH2. SN2 reactions can proceed via back-side attack Walden inversion and front-side attack retention pathways characterized by first-order saddle points, submerged [X-NH2-Y]- and high-energy [H2NXY]-, respectively. Product-like stationary points below the HX + NHY- asymptotes are involved in the proton-transfer processes.

Effect of Microheterogeneity of Different Aqueous Binary Mixtures on the Proton Transfer Dynamics of [2,2'-Bipyridyl]-3,3'-diol: A Femtosecond Fluorescence Upconversion Study.

In this article, we have investigated the excited-state intramolecular double proton transfer dynamics of [2,2′-bipyridyl]-3,3′-diol, BP(OH)2, in three alcohol–water binary mixtures, namely, ethanol (EtOH)–water, n-propanol (PrOH)–water, tert-butyl alcohol (TBA)–water, and dimethyl sulfoxide (DMSO)–water utilizing the femtosecond fluorescence upconversion technique. We have found that in alcohol–water binary mixtures the proton transfer (PT) pathway of BP(OH)2 is sequential and the anomalous slowdown in PT dynamics is observed in mole fraction (χ) ranges χEtOH = 0.04–0.07, χEtOH = 0.23–0.28, χPrOH = 0.17–0.30, χTBA = 0.12–0.21, and χTBA = 0.40–0.46. Our study sheds light on the involvement of water network in the PT dynamics. Reduction in water accessibility due to the involvement of water molecules in cluster formation results in hindered PT dynamics, and this retardation is more for the TBA–water binary mixture compared to that for the other two mixtures. Additionally, we have found two anomalous regions for the DMSO–water binary mixture in ranges χDMSO = 0.12–0.16 and χDMSO = 0.26–0.34. However, most interestingly, beyond χDMSO = 0.40, we do not find any growth component in the femtosecond fluorescence upconversion trace, which may be due to the change in the PT mechanism from a sequential water-mediated pathway to a concerted intramolecular pathway.

CNT@polydopamine embedded mixed matrix membranes for high-rate and long-life vanadium flow batteries

Developing low-cost and high selectivity membranes is critical for vanadium flow batteries (VFB) energy storage system. Among several potential candidates, sulfonated poly(ether ether ketone) (SPEEK) membrane is most promising, yet its proton conductivity and durability are still insufficient to meet the needs of practical applications. Here we report the preparation of a mussel-inspired polydopamine coated carbon nanotube embedded SPEEK mixed matrix membrane (S/CNT@PDA MMM) and its successful application in VFB. The acid-base interface interaction between the SPEEK matrix and the CNT@PDA filler is beneficial to construct additional proton transfer pathway as well as improve the mechanical property of the S/CNT@PDA MMM. Compared to pristine SPEEK membrane, the S/CNT@PDA MMM demonstrates higher proton conductivity, superior proton to vanadium ion selectivity and significantly enhanced stability. As a result, the VFB assembled with the S/CNT@PDA MMM exhibits greatly improved rate performance compared with the benchmark Nafion 115 membrane, and reaches the peak power density of 580mWcm−2 at 650mAcm−2. Moreover, the S/CNT@PDA MMM shows super long-term stability over 1000 cycles at 200mAcm−2, and wide temperature adaptability from − 20°C to 50°C, indicating the great potential of this MMM for practical application in VFB.

D1-Asn-298 in photosystem II is involved in a hydrogen-bond network near the redox-active tyrosine YZ for proton exit during water oxidation

In photosynthetic water oxidation, two water molecules are converted into one oxygen molecule and four protons at the Mn4CaO5 cluster in photosystem II (PSII) via the S-state cycle. Efficient proton exit from the catalytic site to the lumen is essential for this process. However, the exit pathways of individual protons through the PSII proteins remain to be identified. In this study, we examined the involvement of a hydrogen-bond network near the redox-active tyrosine YZ in proton transfer during the S-state cycle. We focused on spectroscopic analyses of a site-directed variant of D1-Asn-298, a residue involved in a hydrogen-bond network near YZ We found that the D1-N298A mutant of Synechocystis sp. PCC 6803 exhibits an O2 evolution activity of ∼10% of the wild-type. D1-N298A and the wild-type D1 had very similar features of thermoluminescence glow curves and of an FTIR difference spectrum upon YZ oxidation, suggesting that the hydrogen-bonded structure of YZ and electron transfer from the Mn4CaO5 cluster to YZ were little affected by substitution. In the D1-N298A mutant, however, the flash-number dependence of delayed luminescence showed a monotonic increase without oscillation, and FTIR difference spectra of the S-state cycle indicated partial and significant inhibition of the S2 → S3 and S3 → S0 transitions, respectively. These results suggest that the D1-N298A substitution inhibits the proton transfer processes in the S2 → S3 and S3 → S0 transitions. This in turn indicates that the hydrogen-bond network near YZ can be functional as a proton transfer pathway during photosynthetic water oxidation.

Ionic liquid grafted graphene oxide composite to create proton transfer pathways in polymer electrolyte membrane

For the synthesis of polymer electrolyte membrane (PEM), high ionic conductivity and stability are the key challenge. This paper deals with the preparation of polymer electrolyte membranes based on ionic liquid (IL) functionalized graphene oxide (GO) and sulfonated polyether sulfone (SPES). Using a simple solution casting technique, composite membranes have been prepared possessing good physicochemical properties and mechanical stability. Methanol crossover resistance have been measured across the composite membranes and found to be low for IG- 05 membrane (0.53×10−7cm2s−1) with the selectivity of 7.99×105. Composite IG- 05 membrane also exhibit high ionic conductivity of 7.27×10−2S.cm−1 which is around 66% higher than that of SPES membrane.

Insights into functions of the H channel of cytochrome c oxidase from atomistic molecular dynamics simulations

Proton pumping A-type cytochrome c oxidase (CcO) terminates the respiratory chains of mitochondria and many bacteria. Three possible proton transfer pathways (D, K, and H channels) have been identified based on structural, functional, and mutational data. Whereas the D channel provides the route for all pumped protons in bacterial A-type CcOs, studies of bovine mitochondrial CcO have led to suggestions that its H channel instead provides this route. Here, we have studied H-channel function by performing atomistic molecular dynamics simulations on the entire, as well as core, structure of bovine CcO in a lipid-solvent environment. The majority of residues in the H channel do not undergo large conformational fluctuations. Its upper and middle regions have adequate hydration and H-bonding residues to form potential proton-conducting channels, and Asp51 exhibits conformational fluctuations that have been observed crystallographically. In contrast, throughout the simulations, we do not observe transient water networks that could support proton transfer from the N phase toward heme a via neutral His413, regardless of a labile H bond between Ser382 and the hydroxyethylfarnesyl group of heme a In fact, the region around His413 only became sufficiently hydrated when His413 was fixed in its protonated imidazolium state, but its calculated pKa is too low for this to provide the means to create a proton transfer pathway. Our simulations show that the electric dipole moment of residues around heme a changes with the redox state, hence suggesting that the H channel could play a more general role as a dielectric well.

Influence of Proton Acceptors on the Proton-Coupled Electron Transfer Reaction Kinetics of a Ruthenium-Tyrosine Complex.

A polypyridyl ruthenium complex with fluorinated bipyridine ligands and a covalently bound tyrosine moiety was synthesized, and its photo-induced proton-coupled electron transfer (PCET) reactivity in acetonitrile was investigated with transient absorption spectroscopy. Using flash-quench methodology with methyl viologen as an oxidative quencher, a Ru3+ species is generated that is capable of initiating the intramolecular PCET oxidation of the tyrosine moiety. Using a series of substituted pyridine bases, the reaction kinetics were found to vary as a function of proton acceptor concentration and identity, with no significant H/D kinetic isotope effect. Through analysis of the kinetics traces and comparison to a control complex without the tyrosine moiety, PCET reactivity was found to proceed through an equilibrium electron transfer followed by proton transfer (ET-PT) pathway in which irreversible deprotonation of the tyrosine radical cation shifts the ET equilibrium, conferring a base dependence on the reaction. Comprehensive kinetics modeling allowed for deconvolution of complex kinetics and determination of rate constants for each elementary step. Across the five pyridine bases explored, spanning a range of 4.2 pKa units, a linear free-energy relationship was found for the proton transfer rate constant with a slope of 0.32. These findings highlight the influence that proton transfer driving force exerts on PCET reaction kinetics.

Tuning Intrinsic and Extrinsic Proton Conduction in Metal-Organic Frameworks by the Lanthanide Contraction.

Seven isomorphous lanthanide metal-organic frameworks in the PCMOF-5 family, [Ln(H5L)(H2O)n](H2O) (L = 1,2,4,5-tetrakis(phosphonomethyl)benzene, Ln = La, Ce, Pr, Nd, Sm, Eu, Gd) have been synthesized and characterized. This family contains 1-D water-filled channels lined with free hydrogen phosphonate groups and gives a very low activation energy pathway for proton transfer. The lanthanide contraction was employed to systematically vary the unit cell dimensions and tune the proton conducting pathways. LeBail fitting of the crystalline series shows that the crystallographic a-axis, along the channel, can be varied in increments less than 0.02 Å correspondingly shortening the proton transfer pathway. The proton conductivities for the La and Pr complexes were roughly an order of magnitude higher than other members of the series (10-3 S cm-1 versus 10-4 S cm-1). Single crystal structures of the high and low conducting members of the series (La, Pr for high and Ce for low) affirm the structural similarities extend beyond the unit cell parameters to positions of free acid groups and included water molecules. Scanning electron microscopy reveals marked differences in particle size of the different members of the Ln series owing to lattice strain effects induced by changing the lanthanide. Notably, the high conducting La and Pr complexes have the largest particle sizes. This result contradicts any notion that degradation of the MOF at grain boundaries is enabling the observed conductivity as proton conduction dominated by extrinsic pathways would be enabled by small particles (i.e., the La and Pr complexes would be the worst conductors). Proton conductivity measurements of a ball milled sample of the La complex corroborate this result.

Cavity hydration dynamics in cytochrome c oxidase and functional implications

Cytochrome c oxidase (CcO) is a transmembrane protein that uses the free energy of O2 reduction to generate the proton concentration gradient across the membrane. The regulation of competitive proton transfer pathways has been established to be essential to the vectorial transport efficiency of CcO, yet the underlying mechanism at the molecular level remains lacking. Recent studies have highlighted the potential importance of hydration-level change in an internal cavity that connects the proton entrance channel, the site of O2 reduction, and the putative proton exit route. In this work, we use atomistic molecular dynamics simulations to investigate the energetics and timescales associated with the volume fluctuation and hydration-level change in this central cavity. Extensive unrestrained molecular dynamics simulations (accumulatively [Formula: see text]4 [Formula: see text]s) and free energy computations for different chemical states of CcO support a model in which the volume and hydration level of the cavity are regulated by the protonation state of a propionate group of heme a3 and, to a lesser degree, the redox state of heme a and protonation state of Glu286. Markov-state model analysis of [Formula: see text]2-[Formula: see text]s trajectories suggests that hydration-level change occurs on the timescale of 100-200 ns before the proton-loading site is protonated. The computed energetic and kinetic features for the cavity wetting transition suggest that reversible hydration-level change of the cavity can indeed be a key factor that regulates the branching of proton transfer events and therefore contributes to the vectorial efficiency of proton transport.

Synergistic Conductivity Effect in a Proton Sources-Coupled Metal–Organic Framework

A water-stable metal–organic framework (MOF)-based composite, H2SO4@MIL-101-SO3H, configured with functionalized sulfonate groups bound to the polymeric backbone and nonvolatile strong acid H2SO4 encapsulated into pores, is demonstrated as a superior proton-conducting material, owing to the resultant multiple proton-transfer pathways. This solid material exhibits a superprotonic conductivity of 1.82 S cm–1 (70 °C, 90% RH) that is comparable to that of other excellent MOF-based proton conductors reported thus far. More importantly, the splendid conductivity (0.92 × 10–2 S cm–1, −40 °C) of the title material achieves an enormous improvement compared with that of all proton-conducting systems demonstrated at subzero temperatures.

Sulfonated Ti3C2Tx to construct proton transfer pathways in polymer electrolyte membrane for enhanced conduction

Here, Ti3C2Tx sheets, a representative of MXenes, with lamellar structure and hydrophilic surface are prepared, and then functionalized with sulfonated polyelectrolyte brushes (Ti3C2Tx-SO3H) through a facile surface-initiated precipitation-polymerization. The Ti3C2Tx-SO3H is then utilized as a new nanofiller to fabricate hybrid proton exchange membrane, where both acidic sulfonated poly (ether ether ketone) (SPEEK) and basic chitosan (CS) are employed as polymer matrixes. The resultant hybrid membranes are systematically characterized and measured including their microstructures, water uptake and proton conduction properties. The results demonstrate that using the sulfonated polyelectrolyte brushes, Ti3C2Tx-SO3H sheets construct efficient proton transfer pathways and connect the inherent conduction channels/paths in polymer phase. This significantly enhances the proton conduction of polymer membrane including SPEEK membrane and CS membrane, under both hydrated condition and anhydrous condition. Particularly, the incorporation of 10 wt.% Ti3C2Tx-SO3H readily offers 144% and 66% increase in proton conductivity, respectively, to SPEEK membrane and CS membrane under hydrated condition. Furthermore, the hybrid membranes achieve improved thermal and mechanical stabilities. These results herald further advances to preparing functionalized MXenes and their relevant hybrid materials with enhanced performances.

Thermal decomposition mechanisms of 1H-1,2,4-triazole derivatives: A theoretical study

The onset temperatures (TDSC) of 1H-1,2,4-triazole (1Htri), 3-methyl-1Htri (1Htri-CH3), and 3-amino-1Htri (1Htri-NH2) have been determined by sealed cell differential scanning calorimetry (SC-DSC), and molecular orbital calculations (MO) were performed to clarify the thermal decomposition mechanism and stability criteria of the decomposition pathways. The TDSC values of 1Htri, 1Htri-CH3, and 1Htri-NH2 were determined by the change in the energy of the thermal decomposition pathway model of intramolecular proton transfer combined with bond cleavage. The determined TDSC values are 297 °C for 1Htri, 114 °C for 1Hti-CH3, and 289 °C for 1Htri-NH2. These results agree well with the measured TDSC values of 338 °C for 1Htri, 172 °C for 1Hti-CH3, and 293 °C for 1Htri-NH2. The results reveal that our approach using the thermal decomposition pathways of intramolecular proton transfer combined with bond cleavage of 1Htri, 1Htri-CH3, and 1Htri-NH2 could expand and control application of these compounds.

Role of water and protein dynamics in proton pumping by respiratory complex I

Membrane bound respiratory complex I is the key enzyme in the respiratory chains of bacteria and mitochondria, and couples the reduction of quinone to the pumping of protons across the membrane. Recently solved crystal or electron microscopy structures of bacterial and mitochondrial complexes have provided significant insights into the electron and proton transfer pathways. However, due to large spatial separation between the electron and proton transfer routes, the molecular mechanism of coupling remains unclear. Here, based on atomistic molecular dynamics simulations performed on the entire structure of complex I from Thermus thermophilus, we studied the hydration of the quinone-binding site and the membrane-bound subunits. The data from simulations show rapid diffusion of water molecules in the protein interior, and formation of hydrated regions in the three antiporter-type subunits. An unexpected water-protein based connectivity between the middle of the Q-tunnel and the fourth proton channel is also observed. The protonation-state dependent dynamics of key acidic residues in the Nqo8 subunit suggest that the latter may be linked to redox-coupled proton pumping in complex I. We propose that in complex I the proton and electron transfer paths are not entirely separate, instead the nature of coupling may in part be ‘direct’.