Proton Transfer Research Articles

Photochemical coupling reaction of phenacyl benzoate with acetone to form 1,4‐dicarbonyl compound enabled by charge transfer

AbstractPhotolysis of phenacyl benzoates tethered with a phenol or anisole in acetone resulted in the formation of 1,4‐dicarbonyl compounds, coupling products of the phenacyl moiety with acetone. The reaction occurs via electron and/or proton transfer from a triplet exciplex, leading to the formation of a phenacyl radical, which then adds to the enol form of acetone. The reaction also occurs in intermolecular fashion with external electron donors.

Towards a universal method for middle-down analysis of antibodies via proton transfer charge reduction-Orbitrap mass spectrometry.

Modern mass spectrometry technology allows for extensive sequencing of the ~ 25kDa subunits of monoclonal antibodies (mAbs) produced by IdeS proteolysis followed by disulfide bond reduction, an approach known as middle-down mass spectrometry (MD MS). However, the spectral congestion of tandem mass spectra of large polypeptides dramatically complicates fragment ion assignment. Here, we report the development and benchmark of an MD MS strategy based on the combination of different ion fragmentation techniques with proton transfer charge reduction (PTCR) to simplify the gas-phase sequencing of mAb subunits. Applied on the liquid chromatography time scale using an Orbitrap Tribrid mass spectrometer, PTCR produces easy-to-interpret mass spectra with limited ion signal overlap. We demonstrate that the accurate estimation of the number of charges submitted to the Orbitrap mass analyzer after PTCR allows for the detection of charge-reduced product ions over a wide mass-over-charge (m/z) window with low parts per million m/z accuracy. Therefore, PTCR-based MD MS analysis increases not only sequence coverage, number of uniquely identified fragments, and number of assigned complementary ion pairs, but also the general confidence in the assignment of subunit fragments. This data acquisition method can be readily applied to any class of mAbs without an apparent need for optimization, and benefits from the high resolving power of the Orbitrap mass analyzer to return sequence coverage of individual subunits exceeding 80% in a single run, and > 90% when just two experiments are combined.

The application value of support vector machine model based on multimodal MRI in predicting IDH-1mutation and Ki-67 expression in glioma

PurposeTo investigate the application value of support vector machine (SVM) model based on diffusion-weighted imaging (DWI), dynamic contrast-enhanced (DCE) and amide proton transfer- weighted (APTW) imaging in predicting isocitrate dehydrogenase 1(IDH-1) mutation and Ki-67 expression in glioma.MethodsThe DWI, DCE and APTW images of 309 patients with glioma confirmed by pathology were retrospectively analyzed and divided into the IDH-1 group (IDH-1(+) group and IDH-1(-) group) and Ki-67 group (low expression group (Ki-67 ≤ 10%) and high expression group (Ki-67 > 10%)). All cases were divided into the training set, and validation set according to the ratio of 7:3. The training set was used to select features and establish machine learning models. The SVM model was established with the data after feature selection. Four single sequence models and one combined model were established in IDH-1 group and Ki-67 group. The receiver operator characteristic (ROC) curve was used to evaluate the diagnostic performance of the model. Validation set data was used for further validation.ResultsBoth in the IDH-1 group and Ki-67 group, the combined model had better predictive efficiency than single sequence model, although the single sequence model had a better predictive efficiency. In the Ki-67 group, the combined model was built from six selected radiomics features, and the AUC were 0.965 and 0.931 in the training and validation sets, respectively. In the IDH-1 group, the combined model was built from four selected radiomics features, and the AUC were 0.997 and 0.967 in the training and validation sets, respectively.ConclusionThe radiomics model established by DWI, DCE and APTW images could be used to detect IDH-1 mutation and Ki-67 expression in glioma patients before surgery. The prediction performance of the radiomics model based on the combination sequence was better than that of the single sequence model.

Incorporation of ESIPT into pillar[5]arene for solid-state dual emission responsive to n-hexane vapor

Abstract Pillar[5]arene is a promising macrocyclic receptor of a chemical sensor showing shape-selective encapsulation of neutral molecules into the cavity, but the poor fluorescence properties remain a challenge. Herein, we report a pillar[5]arene coupled with 2-(2-hydroxyphenyl)benzoxazole (HBO), which displays bright fluorescence in both solution and the solid state. Owing to the excited-state intramolecular proton transfer (ESIPT) in the HBO moiety, greatly improved fluorescence is observed for the pillar[5]arene derivative in CHCl3 (Φlum = 11%) and powder form (Φlum = 25%). Moreover, the emission color changes from light green to blue when the powder sample is exposed to n-hexane vapor. The color change derives from variable dual emission via ESIPT and excimer-forming pathways, as suggested by fluorescence lifetime measurements at different wavelengths. Powder x-ray diffraction indicates that increased crystallinity and a small alteration in the solid-state structure leads to visible fluorescent chromism upon vapor encapsulation.

Interaction between reacetylated chitosan and albumin in alcalescent media

Interaction of chitosan and its derivatives with proteins of animal blood at blood pH relevant conditions is of a particular interest for construction of antimicrobial chitosan/protein-based drug delivery systems. In this work, the interaction of a series of N-reacetylated oligochitosans (RA-CHI) having Mw of 10–12 kDa and differing in the degree of acetylation (DA 19, 24, and 40 %) with bovine serum albumin (BSA) in alkalescent media is described in first. It is shown that RA-CHI forms soluble complexes with BSA in solutions with pH 7.4 and a low ionic strength. Light scattering study shows that soluble RA-CHI complexes have spherical form with the radius of about 100 nm. Circular dichroism, fluorescent spectroscopy, and micro-IR spectroscopy studies show that the secondary structure of BSA in soluble complexes remain intact. Isothermal titration calorimetry of RA-CHI with DA 24 % and BSA mixing in the buffers with different ionization heats reveals a significant contribution of electrostatic forces to the binding process and an additional ionization of chitosan due to the proton transfer from the buffer substance. An increase of ionic strength to the blood relevant value 0.15 M suppresses the binding. It is shown that application of RA-CHI with higher DA value leads to a decrease in the affinity of RA-CHI to BSA and an alteration of the interaction mechanism. The finding opens an opportunity to the application of N-reacetylated chitosan derivatives in the complex systems compatible with blood plasma proteins.

Bio-metal organic framework functionalized nanofibers as efficient proton-conducting for proton exchange membrane

A membrane with a low methanol permeability and high proton conductivity (σp) is essential for the effective operation of a direct methanol-based fuel cell. Herein, a bio-metal organic framework was prepared with natural α-amino acids as ligands and then combined with hydrolyzed polyacrylonitrile (PAN) nanofibers (AA-MOF@PAN). The resulting nanocomposite membranes were subsequently integrated into a Nafion matrix (AA-MOF@PAN/Nafion). The –NH2 groups on AA-MOF@PAN interact with –SO3H groups on Nafion, forming long-range acid-base pairs along the interface between the matrix and nanofibers. This interaction creates abundant proton-conducting sites for proton exchange membrane. Notably, the AA-MOF@PAN-4h/Nafion membrane demonstrated an exceptional proton conductivity (σp) of 0.25 S cm−1 and a higher power density of 117.61 mW cm−2 compared to the recast Nafion membrane. This study offers valuable insights into the three-dimensional ordered design of a natural α-amino acids as a proton transfer sites and highlighting their potential applications in proton exchange membranes.

On the link between the reaction force constant and conceptual DFT.

The reaction force constant ( ), introduced by Professor Alejandro Toro-Labbé, plays a pivotal role in characterizing the reaction pathway by assessing the curvature of the potential energy profile along the intrinsic reaction coordinate. This study establishes a novel link between and the reactivity descriptors of conceptual density functional theory (c-DFT). Specifically, we derive expressions that relate the reaction force constant to nuclear softness and variations in chemical potential. Our findings indicate that regions of the reaction pathway where is negative match with significant electronic structure rearrangements, while positive regions match mostly with geometric rearrangements. This correlation between and c-DFT reactivity descriptors enhances our understanding of the underlying forces driving chemical reactions and offers new perspectives for analyzing reaction mechanisms. The internal reaction path for the proton transfer in SNOH, chemical potential, and nuclear softness were computed using DFT with B3LYP exchange-correlation functional and 6-311++G(d,2p) basis set.

Photochemistry of a proton relay – system with triple fluorescence

The excited state of proton transfer and the dynamics of the excited states of three 3-carboxy substituted bis-salicylidenes (H4L1-3) have been studied by combining steady state and time-resolved absorption and emission methods, and with quantum chemical calculations. The 3-carboxy substituted bis-salicylidenes contain two coupled intramolecular hydrogen bonds of the OH…OH…N type. This system has two proton transfer sites. The compounds have excitation – dependent emission and a high sensitivity to the solvent polarity. ESIPT and deprotonation result in the co-existence of enol, keto, anionic and zwitterionic species with or without quinoid structure, whose emission bands are located from the blue to the yellowish-green region. The photophysical processes in the nano-to-microseconds timescale have been linked to the intermolecular interactions with the solvent, where hydrogen bonding leads to the formation of a cyclic 1:2 solute − solvent complex. Transient absorption spectroscopy revealed that the generation of charged structures of H4L1-3 occurs through a solvent-assisted proton transfer along the chain of two solvent molecules, which act as a proton-relay system. The computational study of the energy profiles and of the enol-to-keto tautomerization with explicit solvent molecules has been performed for the first time for this kind of ESIPT system.

A ‘Turn-on’ fluorogenic probe for selective and specific detection of Hg(II) ions

Mercury (Hg2+) and its associated compounds have drawn serious concern from the scientific communities for their extreme toxicity to human beings. The present article introduced a chromone-benzoxazole embracing an effective fluorogenic probe, (E)-3-(((4-(benzo[d]oxazol-2-yl) phenyl) imino) methyl)-2-methoxy-2H-chromen-4-ol (BPMC) for selective and specific detection of Hg2+ ions having detection and quantification limit in the µM range. A significant photoluminescence enhancement has been observed from BPMC solution (water-DMSO mixture, 50 % v/v) displaying low to highly intense blue-violet photoluminescence under a 365 nm UV lamp due to the inhibition of intramolecular charge transfer (ICT) and excited state intramolecular proton transfer (ESIPT) processes involved in BPMC. Furthermore, to achieve on-site detection of Hg2+ ions and investigate the practical utility of our developed probe, we have fabricated a BPMC-stained paper-strips-based test kit and demonstrated its practical effectiveness for on-spot detection. The details of the detection mechanism have been revealed through 1H NMR, FT-IR, and high-resolution mass spectrometric analysis. The present report evokes a broader perspective for tailoring ICT and ESIPT-based chromo-fluorogenic probes to accelerate their real-world application and environmental monitoring.

Transforming Element Sulfur to High Performance Closed-Loop Recyclable Polymer via Proton Transfer Enabled Anionic Hybrid Copolymerization.

The utilization of sulfur has been a global issue. Copolymerization of element sulfur (S8) with other monomers is a promising route to convert it to useful materials but is limited by the comonomers. Here, we report anionic hybrid copolymerization of S8 with acrylate and epoxide at room temperature, where S8 does not copolymerize with epoxide in the absence of acrylate. Yet, the proton transfer from the methyne in acrylate to the oxygen anion enables the ring-opening of the cyclic comonomer and hence the copolymerization. The cyclic comonomers can be expanded to lactone and cyclic carbonate. Specifically, the copolymer of S8 with bisphenl A diglycidyl ether and diacrylate displays mechanical properties comparable to those of most common plastics, namely, it has ultimate tensile strength as high as 60.8 MPa and Young's modulus up to 680 MPa. It also exhibits high UV resistance and good transparency. Particularly, it has excellent UV-induced self-healing, reprocessability and closed-loop recyclability due to the abundant dynamic S-S bonds and ester groups. This study provides an efficient strategy to turn element sulfur into closed-loop recyclable polymer with high mechanical and optical performances.

A 3D open-framework amino acid templated cerium phosphite-oxalate showing proton conductive property

Using L-histidine as template, a three-dimensional (3D) open-framework cerium phosphite-oxalate, Ce2(H2O)2(H2PO3)2(C2O4)3·C6H11N3O2·H2O (1), has been synthesized under hydrothermal condition. Interestingly, it is the first example of lanthanide phosphite-oxalate with amino acid as the template. Compound 1 shows 3D framework with 8-, 12- and 20-ring channels and has a mog Moganite topology. A large amount of free water molecules and histidine cations are located in the channels of 1, which are favorable to the efficient proton transfer. Correspondingly, compound 1 displays temperature and humidity dependent proton conductivity with the highest value of 3.67 × 10−4 S cm−1 at 75 °C and 98 % RH.

Complexity-Building Exhaustive Dearomatization of Benzenoid Aromatics within an ESIPT-Initiated Three-Step Photochemical Cascade.

Dearomative cycloadditions offer rapid access to complex 3D molecular architectures, commonly via a sp2-to-sp3 rehybridization of two atoms of an aromatic ring. Here we report that the 6e π-system of a benzenoid aromatic pendant could be exhaustively depleted within a single photochemical cascade. An implementation of this approach involves the initial dearomative [4+2] cycloaddition of the Exited State Intramolecular Proton Transfer (ESIPT)-generated azaxylylene, followed by two consecutive [2+2] cycloadditions of auxiliary π moieties strategically positioned in the photoprecursor. Such photochemical cascade fully dearomatizes the benzenoid aromatic ring, saturating all six sp2 atoms to yield a complex sp3-rich scaffold with high control of its 3D molecular shape, rendering it a robust platform for rapid systematic mapping of underexplored chemical space. Significant growth of molecular complexity - starting with a modular synthesis of photoprecursors from readily available building blocks - is quantified by Böttcher score calculations.

Color-tunable and white circularly polarized luminescence through confining guests into chiral MOFs.

Herein, chiral metal-organic frameworks (MOFs), DCF-20 and LCF-20, were utilized as matrices for both chirality transfer and energy transfer. HBT1@MOFs and HBT2@MOFs emit excitation-dependent circularly polarized luminescence (CPL) due to excited-state intramolecular proton transfer (ESIPT). HBT1/C152/NIR@MOFs exhibit full-color and white CPL. The luminescence dissymmetry factors (glum) were significantly increased, benefiting from the efficient chirality space transfer and high luminescence efficiency.

Nonadiabatic Hydrogen Tunneling Dynamics for Multiple Proton Transfer Processes with Generalized Nuclear-Electronic Orbital Multistate Density Functional Theory.

Proton transfer and hydrogen tunneling play key roles in many processes of chemical and biological importance. The generalized nuclear-electronic orbital multistate density functional theory (NEO-MSDFT) method was developed in order to capture hydrogen tunneling effects in systems involving the transfer and tunneling of one or more protons. The generalized NEO-MSDFT method treats the transferring protons quantum mechanically on the same level as the electrons and obtains the delocalized vibronic states associated with hydrogen tunneling by mixing localized NEO-DFT states in a nonorthogonal configuration interaction scheme. Herein, we present the derivation and implementation of analytical gradients for the generalized NEO-MSDFT vibronic state energies and the nonadiabatic coupling vectors between these vibronic states. We use this methodology to perform adiabatic and nonadiabatic dynamics simulations of the double proton transfer reactions in the formic acid dimer and the heterodimer of formamidine and formic acid. The generalized NEO-MSDFT method is shown to capture the strongly coupled synchronous or asynchronous tunneling of the two protons in these processes. Inclusion of vibronically nonadiabatic effects is found to significantly impact the double proton transfer dynamics. This work lays the foundation for a variety of nonadiabatic dynamics simulations of multiple proton transfer systems, such as proton relays and hydrogen-bonding networks.

Theoretical insights into rotary mechanism of MotAB in the bacterial flagellar motor

Many bacteria enable locomotion by rotating their flagellum. It has been suggested that this rotation is realized by the rotary motion of the stator unit, MotAB, which is driven by proton transfer across the membrane. Recent cryo-electron microscopy studies have revealed a 5:2 MotAB configuration, in which a MotB dimer is encircled by a ring-shaped MotA pentamer. Although the structure implicates the rotary motion of the MotA wheel around the MotB axle, the molecular mechanisms of rotary motion and how they are coupled with proton transfer across the membrane remain elusive. In this study, we built a structure-based computational model for Campylobacter jejuni MotAB, conducted comprehensive protonation-state-dependent molecular dynamics simulations, and revealed a plausible proton-transfer-coupled rotation pathway. The model assumes rotation-dependent proton transfer, in which proton uptake from the periplasmic side to the conserved aspartic acid in MotB is followed by proton hopping to the MotA proton-carrying site, followed by proton export to the CP. We suggest that, by maintaining two of the proton-carrying sites of MotA in the deprotonated state, the MotA pentamer robustly rotates by ∼36° per proton transfer across the membrane. Our results provide a structure-based mechanistic model of the rotary motion of MotAB in bacterial flagellar motors and provide insights into various ion-driven rotary molecular motors.

An effective strategy to enhance phosphoric acid retention and proton conductivity stability: Construction of proton transfer channels with starch rather than H3PO4

To enhance the phosphoric acid (PA) retention as well as maintain high proton conductivity of phosphoric acid doped proton exchange membranes at high temperature, we successfully design a series of phosphoric acid doped biobased composite membranes by incorporation of starch and graphene oxide (GO) into poly arylene ether ketones (PAEK). Proton transfer channels should be mainly built through dense hydrogen bonds formed from massive oxygen-containing groups of starch mainchain, which is confirmed by Molecular dynamics (MD) simulation, FT-IR and XRD analysis. The dense hydrogen-bond structure could construct fast proton transfer channels with extreme low doping level (0.00484 molH3PO4). The excellent PA retention properties with almost unchanged proton conductivity at high temperature (200 °C) for 600 min indicates that PA molecules are firmly fixed into membranes. Thus, in this study, we suggest a novel strategy for stablizing proton conductivity at high temperature and improving PA retention properties of PA doped membranes, which is building dense hydrogen-bond structure with low PA doping level.Based on the results in this study and the Grotthuss proton transfer mechanism, dense hydrogen-bonds from oxygen-containing groups in polymer backbones should be more stable than hydrogen-bonds from massive H3PO4 molecules with high acid doping levels to promote proton conduction.

Unidirectional photoisomerisation in a dual channel proton transfer molecule rhodamine B based Schiff Base: A ratiometric pH sensor

In this article we have presented the synthesis, characterisation and spectral study of a newly designed fluorophore, (E)-2-((3-(benzo[d]oxazol-2-yl)-5-bromo-2-hydroxybenzylidene)amino)-3′,6′-bis(diethylamino)spiro [isoindoline-1,9′-xanthen]-3-one (RHHBO) which has two possible six member intramolecular hydrogen bonded networks capable for dual channels proton transfer reaction − one towards the N atom of oxazole moiety and the other towards the N atom of rhodamine moity. Details steady state and time resolved spectral analysis of RHHBO and a comparison of spectral features of control compounds 2-(2-hydroxyphenyl)benzoxazole (HBO), (E)-4-bromo-2-(hydrazonomethyl)phenol (HBN) and (E)-2-((5-bromo-2-hydroxybenzylidene)amino)-3′,6′-bis(diethylamino)spiro[isoindoline-1,9′-xanthen]-3-one (RH) having only single proton transfer site reveal that excited state intramolecular proton transfer (ESIPT) in RHHBO occurs towards the rhodamine side but not towards the oxazole side. Interestingly, RHHBO shows different fluorescence colour in acidic and basic medium and hence can be used ratiometric emission based pH sensor.

Proton Transport Scenarios in Sulfuric Acid Explored via Ab Initio Molecular Dynamics Simulations.

Sulfuric acid (H2SO4), a highly reactive reagent containing intrinsic protonic charge carriers, has been studied via ab initio molecular dynamics simulations. Specifically, we explore the solvation shell structure of the protonic defects, H1SO4- and H3SO4+, as well as the underlying proton transport mechanisms in both the neat and hydrated H2SO4 solutions. Our findings reveal a significant contraction of the dynamic hydrogen-bonded network around the protonic defects, which resembles features seen in water. The simulations provide estimates of the structural relaxation time scales for proton release from both the covalent O-H bonds (∼23 ps) and the hydrogen bonds (∼0.4 ps). In contrast to water, our analysis of the proton transfer scenarios in sulfuric acid reveals correlated events mediated by the formation of longer (up to four) hydrogen-bonded Grotthuss chains.

Air pollution from unconventional oil and gas development in the Eagle Ford Shale

Unconventional oil and gas development (UOGD) has experienced substantial growth in recent years with currently unconstrained impacts on air quality. In this work, we describe ambient aerosol and gas-phase measurements during spring 2021 to examine air quality in the Eagle Ford Shale (EFS), a region in southeast Texas with thousands of UOGD wells. NOx, O3, H2S, PM1, and several VOCs were measured at concentrations above expected levels for non-urban regions. Hydrocarbon measurements from gas chromatography (GC) and proton transfer reaction (PTR) mass spectrometry show periodic high concentrations of variable compositions consisting of both saturated and unsaturated (polycyclic and/or aromatic) hydrocarbons, including larger (C > 10) unsaturated hydrocarbons that are often not quantified by GC measurements but are still present at substantial concentrations and relevant for air quality. Hydrocarbon VOCs are expected pollutants from anthropogenic activity and, based on ratios of i-pentane to n-pentane, xylene to benzene, and toluene to benzene, measured VOC ratios were characteristic of UOGD activity. Wind data and back-trajectory analyses show that air predominantly arrived from the S/SE, consistent with UOGD sources as well as shipping emissions from the Gulf of Mexico impacting air quality in the EFS. Analysis of diurnal trends at the site show hydrocarbon and NOx accumulation overnight and highlight diurnal differences in oxidative conditions, with important implications for both SOA and O3 formation. UOGD emissions impact the air quality in Karnes City and more broadly the EFS as well as the nearby urban area of San Antonio, which struggles to meet national air quality standards set by the Environmental Protection Agency.

Enriching productive mutational paths accelerates enzyme evolution.

Darwinian evolution has given rise to all the enzymes that enable life on Earth. Mimicking natural selection, scientists have learned to tailor these biocatalysts through recursive cycles of mutation, selection and amplification, often relying on screening large protein libraries to productively modulate the complex interplay between protein structure, dynamics and function. Here we show that by removing destabilizing mutations at the library design stage and taking advantage of recent advances in gene synthesis, we can accelerate the evolution of a computationally designed enzyme. In only five rounds of evolution, we generated a Kemp eliminase-an enzymatic model system for proton transfer from carbon-that accelerates the proton abstraction step >108-fold over the uncatalyzed reaction. Recombining the resulting variant with a previously evolved Kemp eliminase HG3.17, which exhibits similar activity but differs by 29 substitutions, allowed us to chart the topography of the designer enzyme's fitness landscape, highlighting that a given protein scaffold can accommodate several, equally viable solutions to a specific catalytic problem.