Search

Cytochrome c oxidase (CcO) is a transmembrane protein complex that reduces molecular oxygen to water while translocating protons across the mitochondrial membrane. Changes in the redox states of its cofactors trigger both O2 reduction and vectorial proton transfer, which includes a proton-loading site, yet unidentified. In this work, we exploited carbon monoxide (CO) as a vibrational Stark effect (VSE) probe at the binuclear center of CcO from Rhodobacter sphaeroides. The CO stretching frequency was monitored as a function of the electrical potential, using Fourier transform infrared (FTIR) absorption spectroelectrochemistry. We observed three different redox states (R4CO, R2CO, and O), determined their midpoint potential, and compared the resulting electric field to electrostatic calculations. A change in the local electric field strength of +2.9 MV/cm was derived, which was induced by the redox transition from R4CO to R2CO. We performed potential jump experiments to accumulate the R2CO and R4CO species and studied the FTIR difference spectra in the protein fingerprint region. The comparison of the experimental and computational results reveals that the key glutamic acid residue E286 is protonated in the observed states, and that its hydrogen-bonding environment is disturbed upon the redox transition of heme a3. Our experiments also suggest propionate A of heme a3 changing its protonation state in concert with the redox state of a second cofactor, heme a. This supports the role of propionic acid side chains as part of the proton-loading site.

Nuclear quantum effects (NQEs) are known to impact a number of features associated with chemical reactivity and physicochemical properties, particularly for light atoms and at low temperatures. In the imaginary time path integral formalism, each atom is mapped onto a “ring polymer” whose spread is related to the quantum mechanical uncertainty in the particle’s position, i.e., its thermal wavelength. A number of metrics have previously been used to investigate and characterize this spread and explain effects arising from quantum delocalization, zero-point energy, and tunneling. Many of these shape metrics consider just the instantaneous structure of the ring polymers. However, given the significant interest in methods such as centroid molecular dynamics and ring polymer molecular dynamics that link the molecular dynamics of these ring polymers to real time properties, there exists significant opportunity to exploit metrics that also allow for the study of the fluctuations of the atom delocalization in time. Here we consider the ring polymer delocalization from the perspective of computational topology, specifically persistent homology, which describes the 3-dimensional arrangement of point cloud data, (i.e. atomic positions). We employ the Betti sequence probability distribution to define the ensemble of shapes adopted by the ring polymer. The Wasserstein distances of Betti sequences adjacent in time are used to characterize fluctuations in shape, where the Fourier transform and associated principal components provides added information differentiating atoms with different NQEs based on their dynamic properties. We demonstrate this methodology on two representative systems, a glassy system consisting of two atom types with dramatically different de Broglie thermal wavelengths, and ab initio molecular dynamics simulation of an aqueous 4 M HCl solution where the H-atoms are differentiated based on their participation in proton transfer reactions.

The transfer of electrons and protons is compared. Electron transfer over long distances is possible through a series of relays. The range of proton transfer is an order of magnitude less than for electrons but it may be directed along hydrogen bonds.

Two kinds of Schiff bases, 85 samples of N‐(benzylidene)‐anilines (ZBAY) and 83 samples of N‐(phenyl‐ethylene)‐anilines (ZAPEY), were used as model compounds, in which the ZBAY contains 13 compounds with 2‐OH and the ZAPEY contains 35 compounds with 2‐OH (synthesized by this work). The quantitative correlation analysis ultraviolet absorption spectra of ZBAY and ZAPEY were performed, and the effect of intramolecular hydrogen bond on their wave number vmax (cm−1) of the maximum absorption wavelength λmax (nm) was investigated. The results show that (a) the factors affecting the vmax of ZBAY and ZAPEY are roughly the same, but their intensities are different. (b) The vmax move caused by intramolecular hydrogen bond is all red shift for both ZBAY and ZAPEY, but the red shift value (2,381) of the ZBAY is more than twice than that (850) of ZAPEY. (c) The effect of intramolecular hydrogen bond on vmax is only dominated by the parent structure unit of Schiff base, rather than the substituents in the molecule. For those compounds with the same parent structure unit, their red shift values of vmax are at fixed value, but their red shift values of λmax are unequal. Generally, the red shift value caused by the intramolecular hydrogen bond is larger for the compound with a larger λmax value. The above observed phenomena are discussed from the view of molecular coplanarity. [ABSTRACT FROM AUTHOR]

Proton transfer processes mediate many organic reactions. How to realize stereochemical control of this process has always been a challenging topic in the field of asymmetric catalysis. In this study, N-(diphenyl-methyl)-1-phenylethan-1-imine (Schiff base derived from 2,2-diphenylethan-1-amine and acetophenone) was used as substrate, and different near neutral solvents and various chiral metal complex catalysts were used to carry out photoinduced C=N double bond transfer in the substrate under irradiation with a mercury ultraviolet lamp. The double bond transfer in the substrate molecule was highly selective. Solvents containing strong electronegative atoms like oxygen and chlorine, such as alcohols, aldehydes, and carbon tetrachloride, were more effective than other solvents under high light intensity. The 1,3-proton transfer process involves photo-excitation of the Schiff base and coordination of the latter to the central metal atom of the chiral catalyst, so that the substrate molecule is placed in a stable chiral environment to form a transition state. The strongly electro-negative atom of the near-neutral solvent attracts the active α-hydrogen from the excited Schiff base molecule to form a negatively charged delocalized π-bond structure. The subsequent proton addition yields more stable molec-ular structure to complete the selective proton transfer process. Among the examined chiral catalysts, divalent tin porphyrin was the most effective, and the product yield and enantiomeric excess were 98% and 91.49%, respectively. The described photoinduced C=N double bond transfer in N-(diphenylmethyl)-1-phenyl-ethan-1-imine is characterized by mild conditions (room temperature), high stereoselectivity, and simple operation. [ABSTRACT FROM AUTHOR]

Reversible photoacids have been widely used in different areas for control of proton‐driven processes with light. Previously reported reversible photoacids rely on thermal relaxation to return to the low‐acidity ground state. Herein we report a photoacid that can be switched between low‐acidity and high‐acidity states by different wavelengths of light. The photoacid can be converted into a high‐acidity metastable state by 470 nm irradiation. The thermal relaxation of the metastable state is very slow and its half‐life in DMSO is 55 h. Irradiation with 365 nm light quickly induced the reverse reaction and reached a photostationary state. UV/Vis absorption spectra of the forward and reverse processes induced by 470 nm and 365 nm irradiation, respectively, have well‐matched isosbestic points. No decomposition was observed after the photoacid was switched by the two wavelengths of light for many cycles. Reversible patterning with both writing and erasing steps performed with light was demonstrated using a polymer thin film containing the photoacid and chlorophenol red as the proton acceptor. [ABSTRACT FROM AUTHOR]

To investigate substitution effects on excited-state intermolecular proton transfer (ESPT) reactions as well as acidity of proton donating fragments in the ground state, we synthesized substituted anthracen-2-yl-3-phenylurea derivatives that form a hydrogen bonds with acetate anions and undergo ESPT reaction. Fluorescence lifetime measurements and their kinetic analyses revealed that the trifluoromethyl group on the phenyl ring as an electron-withdrawing group caused a slow ESPT reaction despite an increase in the acidity of the N–H fragment in the ground state. In contrast, the methoxy group as a donating group leads to a fast ESPT reaction despite a reduction of the acidity of the N–H fragment in the ground state. These effects of substituents on ESPT reaction are due to their influence on the charge transfer reaction, which occurs from the N–H fragment to the anthryl ring to increase the acidity of N–H followed by ESPT reaction, over the urea unit by a combination of resonance and inductive effects. These opposing effects of substituents on the acidity of the urea unit in the ground and excited states provide an important insight in balancing the reactivity of proton transfer reaction in both the excited and ground states. [ABSTRACT FROM AUTHOR]

Solid-state NMR spectroscopy is used to study the proton transfer from aqueous sulfuric-acid solution to coal of early metamorphic stages and to SKN-2K porous carbon sorbent (the carbonized copolymer of 2-methyl-5-vinylpyridine and divinylbenzene). The proton transfer to a spherical polymer granule or a coal membrane is determined by electrolyte diffusion in the solid. In SKN-2K porous sorbent, the diffusion coefficient of sulfuric acid is 1 × 10–8 m2/s. When the electrolyte flux is perpendicular to the membrane plane, the diffusion coefficient of sulfuric acid is 1 × 10–13 m2/s. [ABSTRACT FROM AUTHOR]

The regularities of intermolecular proton transfer from β-substituted porphyrazines to dimethylsulfoxide, cyclic and acyclic nitrogen-containing bases in inert solvents are considered. We found that the process rates are unusually low. We showed that the acidic properties of a porphyrazine macrocycle, the proton-acceptor ability of a base, and the dielectric constant of the environment influence the kinetic parameters of acid–base interaction. The structure and the stability of proton transfer complexes of porphyrazines are discussed. [ABSTRACT FROM AUTHOR]

Quinone cyanine 9 (QCy9) is one of the strongest photoacids known to date. The origin of "super"‐photoacidity was investigated via time‐resolved fluorescence (TF) with high time resolution to accurately resolve the ultrafast dynamics of the excited‐state proton transfer (ESPT) to solvent. The ESPT of QCy9 in water is found to proceed fully by two ultrafast time constants of 40 fs (65 %) and 200 fs (35 %). More importantly, the initially created base form of QCy9 in the excited state undergoes a significant dynamic red shift of over 2700 cm−1 by solvation. We suggest that the entirely ultrafast reaction rate and the massive solvation of the conjugate base could make QCy9 a particularly strong photoacid. Quantum chemical calculations show that structural diversity leads to the nonexponential behavior of the ESPT dynamics. [ABSTRACT FROM AUTHOR]

The intra‐molecular proton transfer of octahydrotriborate, [B3H8]−, is discovered by density functional theory (DFT) computational studies; such a transfer can largely impact its dehydrogenation pathways. The DFT calculation results further disclose the generation of another triborane intermediate product, B3H9, which is formed via inter‐molecular proton transfer from [NH4]+ to [B3H8]−. Additionally, this intermediate product is unstable and can release hydrogen easily, as the corresponding energy barrier via this pathway is only 12.0 kcal mol−1. Such a relative energy is much lower than that of the routinely raised pathway, which mainly depends on the dihydrogen interaction between the B−Hδ− and N−Hδ+. This new mechanism is able to explain several experimental observations involving the dehydrogenation of NH4B3H8. Moreover, the detailed dehydrogenations of NH4B3H8 in different states are also studied, and the role of chemical environment during dehydrogenation is demonstrated. [ABSTRACT FROM AUTHOR]

Density functional theory (DFT) calculations were carried out for reactions forming (A) phenolphthalein and (B) fluorescein. M06‐2X/6‐311G** and M06‐2X/6‐311++G(2d,p) with SCRF=PCM were applied to the search for elementary processes. Reactant models are (A) phthalic anhydride + (phenol)2 + H2SO4 and (B) phthalic anhydride + (resorcinol)2 + H2SO4, respectively. For (A), the acid catalyzed ortho and para phenol additions to phthalic anhydride were compared. While the ortho addition is more favorable than the para one, the ortho adduct involves the strong O2(HO)S–O−....H–O hydrogen bond and the reaction progress was blocked. In the para route, five elementary processes were obtained to arrive at the product, phenolphthalein. For (B), there are two reaction channels from the phenolphthalein‐like intermediate. The first channel is the direct H2O elimination to the lactoid tautomer of fluorescein. This channel has the significantly large activation energy and is unlikely. The second one includes three intermediates with the open form of the γ‐butyrolactone ring. Nine elementary processes were obtained for the fluorescein formation. A carbocation intermediate was found to be the key one for affording three tautomers (quinoid, zwitterionic, and lactoid) of fluorescein. [ABSTRACT FROM AUTHOR]

Recently, the successful incorporation of artificial base pairs in genetics has made a significant progress in synthetic biology. The present work reports the proton transfer and photoisomerization of unnatural base pair ZP, which is synthesized from the pyrimidine analog 6-amino-5-nitro-3-(1-β-D-2′-deoxyribo-furanosyl)-2 (1H)-pyridone (Z) and paired with its Watson-Crick complement, the purine analog 2-amino-8-(1′-β-D-2′- deoxyribofuranosyl)-imidazo[1,2-a]-1,3,5-triazin-4(8H)-one (P). To explain the mechanism of proton transfer process, we constructed the relaxed potential energy surfaces (PESs) linking the different tautomers in both gas phase and solution. Our results show that the double proton transfer in the gas phase occurs in a concerted way both in S0 and S1 states, while the stepwise mechanism becomes more favorable in solution. The solvent effect can promote the single proton transfer, which undergoes a lower energy barrier in S1 state due to the strengthened hydrogen bond. In contrast to the excited state ultrafast deactivation process of the natural bases, there is no conical intersection between S0 and S1 states along the proton transfer coordinate to activate the decay mechanism in ZP. Of particular relevance to the photophysical properties, charge-transfer character is obviously related to the nitro rotation in S1 state. We characterized the molecular vibration effect on the electronic properties, which reveals the electronic excitation can be tuned by the rotation-induced structural distortion accompanied with the electron localization on nitro group.

Carbonic anhydrases (CAs) are a family of ubiquitous metal enzymes catalyzing the reversible conversion of CO2 and H2O to HCO3− with the release of a proton. They play an important role in pH regulation and in the balance of body fluids and are involved in several functions such as homeostasis regulation and cellular respiration. For these reasons, they have been studied as targets for the development of agents for treating several pathologies. CA inhibitors have been used in therapy for a long time, especially as diuretics and for the treatment of glaucoma, and are being investigated for application in other pathologies including obesity, cancer, and epilepsy. On the contrary, CAs activators are still poorly studied. They are proposed to act as additional (other than histidine) proton shuttles in the rate-limiting step of the CA catalytic cycle, which is the generation of the active hydroxylated enzyme. Recent studies highlight the involvement of CAs activation in brain processes essential for the transmission of neuronal signals, suggesting CAs activation might represent a potential therapeutic approach for the treatment of Alzheimer’s disease and other conditions characterized by memory impairment and cognitive problems. Actually, some compounds able to activate CAs have been identified and proposed to potentially resolve problems related to neurodegeneration. This review reports on the primary literature regarding the potential of CA activators for treating neurodegeneration-related diseases.

The proton transfer from carbon to a chloride ion and the proton transfer to a molecule of water promoted by chloride ions in the acid-catalyzed formation of hydroxamic acids from aldehydes and substituted nitrosobenzenes in mixed solvents have been proposed based on experimental and theoretical investigations. The formation of uncommon contact ion pairs consisting of the nitrosocarbinolic cation intermediate and a chloride anion, followed by the proton transfer from a C-H moiety of the cation intermediate, has been proposed. The influence of chloride on the proton transfer to a water molecule of the solvent-separated nitrosocarbinolic-cation–chloride ion pair was investigated too. The insights are based on the obtained kinetic and other evidence with regard to (1) influences of chloride anions on the observed reaction rates and primary kinetic isotope effects (PKIE) in the reaction; (2) the observed variation of the PKIE-s and rates of the reaction when perchlorate anions are present along with the chloride ions; and (3) the consideration of a model of the nitrosocarbinolic-cation-intermediate—chloride ion pair and transition structure for the proposed proton transfers based on the ab initio calculations.

Water plays a central role in chemistry and biology by mediating the interactionsbetween molecules, altering energy levels of solvated species, modifying potentialenergy profiles along reaction coordinates, and facilitating efficient proton transportthrough ion channels and interfaces. This study investigates proton transfer in amodel system comprising dry and microhydrated clusters of nucleobases. With massspectrometry and tunable vacuum ultraviolet (VUV) synchrotron radiation, we showthat water shuts down ionization-induced proton transfer between nucleobases, whichis very efficient in dry clusters. Instead, a new pathway opens up in which protonatednucleobases are generated by proton transfer from the ionized water molecule andelimination of a hydroxyl radical. Electronic structure calculations reveal that theshape of the potential energy profile along the proton transfer coordinate dependsstrongly on the character of the molecular orbital from which the electron is removed,i.e., the proton transfer from water to nucleobases is barrierless when an ionized statelocalized on water is accessed. The computed energetics of proton transfer is inexcellent agreement with the experimental appearance energies. Possible adiabaticpassage on the ground electronic state of the ionized system, while energeticallyaccessible at lower energies, is not efficient. Thus, proton transfer is controlledelectronically, by the character of the ionized state, rather than statistically, bysimple energy considerations.

Slow multi-proton coupled electron transfer kinetics and unexpected desorption of intermediates severely hinder the selectivity of CO 2 methanation. In this work, a one-stone-two-bird strategy of pumping protons and improving adsorption configuration/capability enabled by electron localization is developed to be highly efficient for CH 4 electrosynthesis over Cu single atoms anchored on bismuth vacancies of BiVO 4 (Bi 1-x VO 4 ─Cu), with superior kinetic isotope effect and high CH 4 Faraday efficiency (92%), far outperforming state-of-the-art electrocatalysts for CO 2 methanation. Control experiments and theoretical calculations reveal that the bismuth vacancies (V Bi ) not only act as active sites for H 2 O dissociation but also induce electron transfer toward Cu single-atom sites. The V Bi -induced electron localization pumps *H from V Bi sites to Cu single atoms, significantly promoting the generation and stabilization of the pivotal intermediate (*CHO) for highly selective CH 4 electrosynthesis. The metal vacancies as new initiators show enormous potential in the proton transfer-involved hydrogenative conversion processes., (© 2024 Wiley‐VCH GmbH.)

The Cu-O-Cu core has been proposed as a potential site for methane oxidation in particulate methane monooxygenase. In this work, we used density functional theory (DFT) to design a mixed-valent Cu III -O-Cu II species from an experimentally known peroxo-dicopper complex supported by N-donor ligands containing phenolic groups. We found that the transfer of two-protons and two-electrons from phenolic groups to peroxo-dicopper core takes place, which results to the formation of a bis-μ-hydroxo-dicopper core. The bis-μ-hydroxo-dicopper core converts to a mixed-valent Cu III -O-Cu II core with the removal of a water molecule. The orbital and spin density analyses unravel the mixed-valent nature of Cu III -O-Cu II . We further investigated the reactivity of this mixed-valent core for aliphatic C-H hydroxylation. Our study unveiled that mixed-valent Cu III -O-Cu II core follows a hydrogen atom transfer mechanism for C-H activation. An in-situ generated water molecule plays an important role in C-H hydroxylation by acting as a proton transfer bridge between carbon and oxygen. Furthermore, to assess the relevance of a mixed-valent Cu III -O-Cu II core, we investigated aliphatic C-H activation by a symmetrical Cu II -O-Cu II core. DFT results show that the mixed-valent Cu III -O-Cu II core is more reactive toward the C-H bond than the symmetrical Cu II -O-Cu II core., (© 2024 Wiley-VCH GmbH.)

Covalent organic frameworks (COFs) offer a desirable platform to explore multichoromophoric arrays for photocatalytic conversion. Symmetric arrangement of choromophoric modules over π-extended frameworks enhances exciton delocalization while impairing excitation density and accordingly photochemical reactivity. Herein, a photoisomerization-driven strategy is proposed to break the excited-state symmetry of ketoenamine-linked COFs with multichoromophoric arrays. Incorporating electron-withdrawing benzothiadiazole facilitates the ultrafast excited-state intramolecular proton transfer (ESIPT) from enamine to keto within 140 fs, resulting in partially enolized COF isomers. The hybrid linkages containing imine and enamine bonds at the node of framework alter the symmetry of electronic structure and enforce the photoinduced charge separation. Increasing the imine-to-enamine ratio further promotes the electron transferred number in a long range, thereby affording the optimum photocatalytic hydrogen evolution rate. This work put forward an ESIPT-induced photoisomerization to build a symmetry-breaking COF with weakened exciton effect and enhanced photochemical reactivity., (© 2023 Wiley-VCH GmbH.)

Transaminase is a key enzyme for amino acid metabolism, which reversibly catalyzes the transamination reaction with the help of PLP (pyridoxal 5'-phosphate) as its cofactor. Here we have investigated the mechanism and free energy landscape of the transamination reaction involving the aspartate transaminase (AspTase) enzyme and aspartate-PLP (Asp-PLP) complex using QM/MM simulation and metadynamics methods. The reaction is found to follow a stepwise mechanism where the active site residue Lys258 acts as a base to shuttle a proton from a-carbon (CA) to imine carbon (C4A) of the PLP-Asp Schiff base. In the first step, the Lys258 abstracts the CA proton of the substrate leading to the formation of a carbanionic intermediate which is followed by the reprotonation of the Asp-PLP Schiff base at C4A atom by Lys258. It is found that the free energy barrier for the proton abstraction by Lys258 and that for the reprotonation are 17.85 and 3.57 kcal/mol, respectively. The carbanionic intermediate is 7.14 kcal/mol higher in energy than the reactant. Hence, the first step acts as the rate limiting step. The present calculations also show that the Lys258 residue undergoes a conformational change after the first step of transamination reaction and becomes proximal to C4A atom of the Asp-PLP Schiff base to favor the second step. The active site residues Tyr70* and Gly38 anchor the Lys258 in proper position and orientation during the first step of the reaction and stabilize the positive charge over Lys258 generated at the intermediate step. [ABSTRACT FROM AUTHOR]

Lewis base catalyzed electrophilic aromatic halogenation using N‐halosuccinimides (NsX; X=Cl, Br, I) under mild conditions has attracted much attention, but the detailed mechanism remains elusive. Using the aniline MesNH2 and anisole PhOMe as the typical base catalyst and aromatic substrate, respectively, a novel mechanism is revealed by extensive DFT calculations. The autogenic protonation of imine XMes=NH (via Mes=NH+ mediated dimerization of MesNH2) is crucial to initialize the electrophilic halonium X+ transfer to nucleophilic substrates. It is shown that the aniline MesNH2 and more basic imine XMes=NH may act as efficient halonium X+ and proton H+ shuttles, respectively, connected by the arenium XMesNH2+. Non‐coordinating MesNH3+ salts are suggested as efficient catalyst for electrophilic iodination. Without suitable stabilization of the highly basic anion Ns−, the generally accepted concept of Lewis base catalyst as simple X+ shuttle will never work efficiently due to a high thermodynamic barrier. In general, autogenic or additional acid additives should be used for more efficient Lewis base catalyzed halogenation. [ABSTRACT FROM AUTHOR]

We compute the proton transfer rates to a range of volatile organic compounds (VOCs) related to cork taint in wine. These rates are useful to support quantification in proton‐transfer‐reaction mass spectrometry (PTR‐MS) and in selected‐ion flow‐tube mass spectrometry (SIFT‐MS). We apply the average dipole orientation theory and the parameterized trajectory method to evaluate the rate coefficients for proton transfer occurring in ion–molecule collision, from both H3O+ and NH 4+ to the VOCs. The main input ingredients for these methods are the electric dipole moment and polarizability of the VOC molecules, which we evaluate by means of quantum chemical calculations based on density functional theory. We provide new data for proton transfer rate coefficients of compounds responsible for cork taint and off‐flavor in wine such as chloroanisoles, bromoanisoles, methylisoborneol, guaiacol, and terpenes. [ABSTRACT FROM AUTHOR]

Tunable soft ionization coupled to mass spectroscopy is a powerful method toinvestigate isolated molecules, complexes and clusters and their spectroscopy anddynamics.[1-4] Fundamental studies of photoionization processes of biomoleculesprovide information about electronic structure of these systems. Furthermoredeterminations of ionization energies and other properties of biomolecules in the gasphase are not trivial, and these experiments provide a platform to generate these data.We have developed a thermal vaporization technique coupled with supersonicmolecular beams that provides a gentle way to transport these species into the gasphase. Judicious combination of source gas and temperature allows for formation ofdimers and higher clusters of the DNA bases. The focus of this particular work is on theeffects of non-covalent interactions, i.e., hydrogen bonding, stacking, and electrostaticinteractions, on the ionization energies and proton transfer of individual biomolecules,their complexes and upon micro-hydration by water.[1, 5-9]We have performed experimental and theoretical characterization of thephotoionization dynamics of gas-phase uracil and 1,3-methyluracil dimers usingmolecular beams coupled with synchrotron radiation at the Chemical DynamicsBeamline[10] located at the Advanced Light Source and the experimental details arevisualized here. This allowed us to observe the proton transfer in 1,3-dimethyluracildimers, a system with pi stacking geometry and with no hydrogen bonds[1]. Molecularbeams provide a very convenient and efficient way to isolate the sample of interestfrom environmental perturbations which in return allows accurate comparison withelectronic structure calculations[11, 12]. By tuning the photon energy from thesynchrotron, a photoionization efficiency (PIE) curve can be plotted which informs usabout the cationic electronic states. These values can then be compared to theoreticalmodels and calculations and in turn, explain in detail the electronic structure anddynamics of the investigated species [1, 3].

Understanding the mechanism of proton pumping requires a detailed description of the energetics and sequence of events associated with the proton transfers, and of how proton transfer couples to conformational rearrangements of the protein. Here, we discuss our recent advances in using computer simulations to understand how bacteriorhodopsin pumps protons. We emphasize the importance of accurately describing the retinal geometry and the location of water molecules.

This study aims to study the conformation, the hydrogen bond network, and the stabilities of all the possible intermolecular interactions in phosphorylated nata de coco membrane with water (NDCF-(H2O)n, n = 1-5). Analysis of natural bond orbital (NBO) was performed to measure the relative strength of the hydrogen bonding interactions, charge transfer, particularly the interactions of n-σ * O-H and to take into account the effect on the stabilities of the molecular structure. All calculation were performed using density functional theory (DFT) method, at B3LYP functional level of theory and 6-311 G** basis set. The charge transfer between the lone pair of a proton acceptor to the anti-bonding orbital of the proton donor provides the substantial to the stabilization of the hydrogen bonds. Interaction between NDCF and (H2O)5 was strongest with the stabilization energy of 37.73 kcal/mol, that indicate the ease of donating lone pair electrons. The contributions of each hydrogen bond to the stability of the complex have been analyzed.

Human carbonic anhydrase II (hCA II) is a zinc metalloenzyme that catalyzes the reversible hydration/dehydration of CO2/HCO3−. Although hCA II has been extensively studied to investigate the proton-transfer process that occurs in the active site, its underlying mechanism is still not fully understood. Here, ultrahigh-resolution crystallographic structures of hCA II cryocooled under CO2 pressures of 7.0 and 2.5 atm are presented. The structures reveal new intermediate solvent states of hCA II that provide crystallographic snapshots during the restoration of the proton-transfer water network in the active site. Specifically, a new intermediate water (WI′) is observed next to the previously observed intermediate water WI, and they are both stabilized by the five water molecules at the entrance to the active site (the entrance conduit). Based on these structures, a water network-restructuring mechanism is proposed, which takes place at the active site after the nucleophilic attack of OH− on CO2. This mechanism explains how the zinc-bound water (WZn) and W1 are replenished, which are directly responsible for the reconnection of the His64-mediated proton-transfer water network. This study provides the first `physical' glimpse of how a water reservoir flows into the hCA II active site during its catalytic activity.

Four human (h) carbonic anhydrase isoforms (CA, EC 4.2.1.1), hCA I, II, IV, and VII, were investigated for their activation profile with piperazines belonging to various classes, such as N-aryl-, N-alkyl-, N-acyl-piperazines as well as 2,4-disubstituted derivatives. As the activation mechanism involves participation of the activator in the proton shuttling between the zinc-coordinated water molecule and the external milieu, these derivatives possessing diverse basicity and different scaffolds were appropriate for being investigated as CA activators (CAAs). Most of these derivatives showed CA activating properties against hCA I, II, and VII (cytosolic isoforms) but were devoid of activity against the membrane-associated hCA IV. For hCA I, the KAs were in the range of 32.6–131 µM; for hCA II of 16.2–116 µM, and for hCA VII of 17.1–131 µM. The structure-activity relationship was intricate and not easy to rationalize, but the most effective activators were 1-(2-piperidinyl)-piperazine (KA of 16.2 µM for hCA II), 2-benzyl-piperazine (KA of 17.1 µM for hCA VII), and 1-(3-benzylpiperazin-1-yl)propan-1-one (KA of 32.6 µM for hCA I). As CAAs may have interesting pharmacologic applications in cognition and for artificial tissue engineering, investigation of new classes of activators may be crucial for this relatively new research field.

Six tripeptides incorporating acidic amino acid residues were prepared for investigation as activators of β- and γ-carbonic anhydrases (CAs, EC 4.2.1.1) from the pathogenic bacteria Vibrio cholerae, Mycobacterium tuberculosis, and Burkholderia pseudomallei. The primary amino acid residues that are involved in the catalytic mechanisms of these CA classes are poorly understood, although glutamic acid residues near the active site appear to be involved. The tripeptides that contain Glu or Asp residues can effectively activate VchCAβ and VchCAγ (enzymes from V. cholerae), Rv3273 CA (mtCA3, a β-CA from M. tuberculosis) and BpsCAγ (γ-CA from B. pseudomallei) at 0.21–18.1 µM levels. The position of the acidic residues in the peptide sequences can significantly affect bioactivity. For three of the enzymes, tripeptides were identified that are more effective activators than both l-Glu and l-Asp. The tripeptides are also relatively selective because they do not activate prototypical α-CAs (human carbonic anhydrases I and II). Because the role of CA activators in the pathogenicity and life cycles of these infectious bacteria are poorly understood, this study provides new molecular probes to explore such processes.

In the title organic salt, C17H20F2N3O3+·C8H4FO4−, proton transfer leads to one protonated lomefloxacin molecule (HLf+) and one 3-carboxy-5-fluorobenzoate (5-F-Hip−) anion in the asymmetric unit. The HLf+ cation is bent, with a dihedral angle of 38.3 (1)° between the quinoline ring and the piperazinium moiety. In the crystal, two kinds of N—H...O and O—H...O hydrogen-bonded chains cross-link each other to produce a three-dimensional network structure that is additionally stabilized by weak C—H...O and C—H...F hydrogen bonds, as well as π–π interactions. The methyl group attached to the piperazinium ring is disordered over two sets of sites [refined ratio: 0.645 (5):0.335 (5)], indicating the presence of both enantiomers of the cation in the structure.

In this study, the interactions of ESIPT fluorescent lipophile-based benzazoles with bovine serum albumin (BSA) were studied and their binding affinity was evaluated. In phosphate-buffered saline (PBS) solution these compounds produce absorption maxima in the UV region and a main fluorescence emission with a large Stokes shift in the blue–green regions due to a proton transfer process in the excited state. The interactions of the benzazoles with BSA were studied using UV-Vis absorption and steady-state fluorescence spectroscopy. The observed spectral quenching of BSA indicates that these compounds could bind to BSA through a strong binding affinity afforded by a static quenching mechanism (Kq~1012 L·mol−1·s−1). The docking simulations indicate that compounds 13 and 16 bind closely to Trp134 in domain I, adopting similar binding poses and interactions. On the other hand, compounds 12, 14, 15, and 17 were bound between domains I and III and did not directly interact with Trp134.

The mechanism of isomerization of hydroxyacetone to 2‐hydroxypropanal is studied within the framework of reaction force analysis at the M06‐2X/6‐311++G(d,p) level of theory. Three unique pathways are considered: (a) a step‐wise mechanism that proceeds through the formation of the Z‐isomer of their shared enediol intermediate, (b) a step‐wise mechanism that forms the E‐isomer of the enediol, and (c) a concerted pathway that bypasses the enediol intermediate. Energy calculations show that the concerted pathway has the lowest activation energy barrier at 45.7 kcal mol−1. The reaction force, chemical potential, and reaction electronic flux are calculated for each reaction to characterize electronic changes throughout the mechanism. The reaction force constant is calculated in order to investigate the synchronous/asynchronous nature of the concerted intramolecular proton transfers involved. Additional characterization of synchronicity is provided by calculating the bond fragility spectrum for each mechanism. [ABSTRACT FROM AUTHOR]

A proton–electron coupling system, exhibiting unique bistability or multistability of the protonated state, is an attractive target for developing new switchable materials based on proton dynamics. Herein, we present an iron(II) hydrazone crystalline compound, which displays the stepwise transition and bistability of proton transfer at the crystal level. These phenomena are realized through the coupling with spin transition. Although the multi‐step transition with hysteresis has been observed in various systems, the corresponding behavior of proton transfer has not been reported in crystalline systems; thus, the described iron(II) complex is the first example. Furthermore, because proton transfer occurs only in one of the two ligands and π electrons redistribute in it, the dipole moment of the iron(II) complexes changes with the proton transfer, wherein the total dipole moment in the crystal was canceled out owing to the antiferroelectric‐like arrangement. [ABSTRACT FROM AUTHOR]

The Grothus like hydrogen motion in the inter‐conversion of classical to non‐classical conformation of protonated acetylene is studied in the purview of the electronic structure perspective. The reorganization of electrons during the proton transfer is explored by means of the changes in structural features, partial charges, natural bond orbital and normal mode analysis following an intrinsic reaction coordinate (IRC) connecting classical and non‐classical structures. It is found that conversion of classical to non‐classical structures along the IRC occurs due to the charge donation to the vacant non‐bonding p‐orbital of a sp hybridized carbon from the adjacent C–H σ ‐bond which facilitates the delocalization of electron and leads to gain in stabilization energy. This interaction continues till post transition state, gradually weakens and is finally decomposed to two non‐bonding orbitals, one p‐orbital on sp2 carbon and one s‐orbital on migrating hydrogen. From this point, the migrating hydrogen in turn accepts and donates electrons simultaneously from the p‐orbital on sp2 carbon and non‐bonding p‐orbital of sp hybridized carbon, respectively, to finally arrive at the non‐classical structure. [ABSTRACT FROM AUTHOR]

The synthesis is described of a luminescent furophenanthraquinone derivative, 9‐methoxyphenanthro[4,3‐b]furan‐4,5‐dione (MPFD). The biological importance of tetracyclic furophenanthraquinones was considered and the tunable luminescence of MPFD in different solvents was studied to explore the nature of the specific interactions between MPFD and solvents. Observation of dual emission bands and identical nature of the fluorescence excitation spectra of MPFD monitored at the emission wavelength in polar solvents indicated the formation of two different types of species in the excited state, probably due to proton transfer from the solvent to MPFD. Luminescence intensity due to anionic species was found to be increased and the corresponding peak was red shifted with increase in the proton‐donating ability of the solvents, acting as an acid with respect to MPFD. Availability of more acidic protons in the solvent facilitated this phenomenon occurring in the excited state. MPFD also interacted with halogen‐containing solvents by forming electron donor–acceptor charge transfer (CT) complexes. This CT complex formation was dependent on the number of chlorine atoms; the position of the corresponding luminescence band varied with the polarity of the solvent. Extent of the CT increased with increase in the number of chlorine atoms in the dichloro, trichloro and tetrachloro solvents, whereas the luminescence peak due to the CT complex was found to be blue shifted with decrease in solvent polarity. Interaction of the synthesized bioactive MPFD with different solvents deserves biological importance as proton transfer and CT play pivotal roles in biology. [ABSTRACT FROM AUTHOR]

The dynamics of excited‐state double proton transfer (ESDPT) depending on hydrogen bonding of water molecules to the mediating water were studied at the TD‐M06‐2X/6‐31+G(d, p) level. The additional H‐bonding accepting (aW) or donating (dW) water had an effect on the mechanism of ESDPT. The double proton transfer occurred in an asynchronous but concerted protolysis or solvolysis pattern dependence on the aW or dW, respectively. The aW or dW stabilized the corresponding protolysis or solvolysis mechanism, respectively. The extra aW and dW would increase the asynchronicity of proton transfer. The bridging water in ESDPT process needed only one single H‐bond accepting or donating solvent molecule relying on the protolysis or solvolysis mechanism energetically. The specific vibrational modes in the 7AIW‐aW, 7AIW‐dW, and 7AIW‐aW‐dW complexes red‐shifted due to aW or dW. [ABSTRACT FROM AUTHOR]

The S‐adenosyl methionine (SAM)‐dependent methyltransferases attach a methyl group to the deprotonated methyl lysine using SAM as a donor. An intriguing, yet unanswered, question is how the deprotonation takes place. PRDM9 with well‐defined enzyme activity is a good representative of the methyltransferase family to study the deprotonation and subsequently the methyl transfer. Our study has found that the pKa of Tyr357 is low enough to make it an ideal candidate for proton abstraction from the methyl lysine. The partially deprontonated Tyr357 is able to change its H‐bond pattern thus bridging two proton tunneling states and providing a cascading proton transfer. We have uncovered a new catalytic mechanism for the deprotonation of the methyl lysine in methyltransferases. [ABSTRACT FROM AUTHOR]

Copyright of Zeitschrift für Physikalische Chemie is the property of De Gruyter and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Education & Science is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Nitrogen (N2) fixation to produce bio‐available ammonia (NH3) is essential to all life but is a challenging transformation to catalyze owing to the chemical inertness of N2. Transition metals can, however, bind N2 and activate it for functionalization. Significant opportunities remain in developing robust and efficient transition metal catalysts for the N2 reduction reaction (N2RR). One opportunity to target in catalyst design concerns the stabilization of transition metal diazenido species (M‐NNH) that result from the first N2 functionalization step. Well‐characterized M‐NNH species remain very rare, likely a consequence of their low N–H bond dissociation free energies (BDFEs). In this essay, we discuss the relationship between the BDFEN–H of a given M‐NNH species to the observed overpotential and selectivity for N2RR catalysis with that catalyst system. We note that developing strategies to either increase the N–H BDFEs of M‐NNH species, or to avoid M‐NNH intermediates altogether, are potential routes to improved N2RR efficiency. [ABSTRACT FROM AUTHOR]

Here, we propose an experimental methodology based on femtosecond‐resolved fluorescence spectroscopy to measure the hydrogen (H)‐bond free energy of water at protein surfaces under isothermal conditions. A demonstration was conducted by installing a non‐canonical isostere of tryptophan (7‐azatryptophan) at the surface of a coiled‐coil protein to exploit the photoinduced proton transfer of its chromophoric moiety, 7‐azaindole. The H‐bond free energy of this biological water was evaluated by comparing the rates of proton transfer, sensitive to the hydration environment, at the protein surface and in bulk water, and it was found to be higher than that of bulk water by 0.4 kcal mol−1. The free‐energy difference is dominated by the entropic cost in the H‐bond network among water molecules at the hydrophilic and charged protein surface. Our study opens a door to accessing the energetics and dynamics of local biological water to give insight into its roles in protein structure and function. [ABSTRACT FROM AUTHOR]

In redox metalloenzymes, the process of electron transfer often involves the concerted movement of a proton. These processes are referred to as proton-coupled electron transfer, and they underpin a wide variety of biological processes, including respiration, energy conversion, photosynthesis, and metalloenzyme catalysis. The mechanisms of proton delivery are incompletely understood, in part due to an absence of information on exact proton locations and hydrogen bonding structures in a bona fide metalloenzyme proton pathway. Here, we present a 2.1-Å neutron crystal structure of the complex formed between a redox metalloenzyme (ascorbate peroxidase) and its reducing substrate (ascorbate). In the neutron structure of the complex, the protonation states of the electron/proton donor (ascorbate) and all of the residues involved in the electron/proton transfer pathway are directly observed. This information sheds light on possible proton movements during heme-catalyzed oxygen activation, as well as on ascorbate oxidation. [ABSTRACT FROM AUTHOR]

A large jump of proton transfer rates across solid‐to‐solid interfaces by inserting an ultrathin amorphous silica layer into stacked metal oxide nanolayers is discovered using electrochemical impedance spectroscopy and Fourier‐transform infrared reflection absorption spectroscopy (FT‐IRRAS). The triple stacked nanolayers of Co3O4, SiO2, and TiO2 prepared by atomic layer deposition (ALD) enable a proton flux of 2400 ± 60 s−1 nm−2 (pH 4, room temperature), while a single TiO2 (5 nm) layer exhibits a threefold lower flux of 830 s−1 nm−2. Based on FT‐IRRAS measurements, this remarkable enhancement is proposed to originate from the sandwiched silica layer forming interfacial SiOTi and SiOCo linkages to TiO2 and Co3O4 nanolayers, respectively, with the O bridges providing fast H+ hopping pathways across the solid‐to‐solid interfaces. Together with the complete O2 impermeability of a 2 nm ALD‐grown SiO2 layer, the high flux for proton transport across multi‐stack metal oxide layers opens up the integration of incompatible catalytic environments to form functional nanoscale assemblies such as artificial photosystems for CO2 reduction by H2O. [ABSTRACT FROM AUTHOR]