Proton Transfer Mechanism Research Articles

Surface Confinement of Finite-Size Water Droplets for SO3 Hydrolysis Reaction Revealed by Molecular Dynamics Simulations Based on a Machine Learning Force Field

As an important source for sulfuric acid in the atmosphere, hydrolysis of sulfur trioxide (SO3) takes place with water clusters of sizes from several molecules to several nanometers, resulting in various final products, including neutral (H2SO4)-(H2O) clusters and ionic (HSO4)--(H3O)+ clusters. The diverse products may be due to the ability of proton transfer and the formation of hydrated ions for water cluster of finite sizes, especially the sub-micrometer ones. However, the detailed molecular-level mechanism is still unclear due to the lack of available characterization and simulations tools. Here, we developed a quantum chemistry-level machine learning (ML) model to simulate the hydrolysis of SO3 with water clusters of sizes up to nanometers. The simulation results demonstrate diverse reaction paths taking place between SO3 and water clusters of different sizes. Generally, neutral (H2SO4)-(H2O) clusters are preferred by water clusters of ultra-small size, and a loop structure-mediated mechanism with SO3(H2O)n≤4 structures and a non-loop structure-mediated mechanism with structure relaxation are observed. As the water cluster size increases to (H2O)8, a (HSO4)--(H3O)+ ion-pair product emerges; and the Eigen-Zundel ion conversion-like proton transfer mechanism takes place and stabilizes the ion pairs. As the water cluster sizes further increase beyond several nanometers ((H2O)n≥32), the (SO4)2-[(H3O)+]2 ion-pair product appears. The reason could be that the surface of these water clusters is large enough to screen Coulomb repulsion between two tri-coordinated ion-pair complexes. These findings would provide new perspectives for understanding SO3 hydrolysis in the real atmosphere and sulfuric acid chemistry in atmospheric aerosols.

Mechanism of Asparagine-Mediated Proton Transfer in Photosynthetic Reaction Centers.

In photosynthetic reaction centers from purple bacteria (PbRCs), light-induced charge separation leads to the reduction of the terminal electron acceptor quinone, QB. The reduction of QB to QB•- is followed by protonation via Asp-L213 and Ser-L223 in PbRC from Rhodobacter sphaeroides. However, Asp-L213 is replaced with nontitratable Asn-L222 and Asn-L213 in PbRCs from Thermochromatium tepidum and Blastochloris viridis, respectively. Here, we investigated the energetics of proton transfer along the asparagine-involved H-bond network using a quantum mechanical/molecular mechanical approach. The potential energy profile for the H-bond between H3O+ and the carbonyl O site of Asn-L222 shows that the proton is predominantly localized at the Asn-L222 moiety in the T. tepidum PbRC protein environment, easily forming the enol species. The release of the proton from the amide -NH2 site toward Ser-L232 via tautomerization suffers from the energy barrier. Upon reorientation of Asn-L222, the enol -OH site forms a short low-barrier H-bond with Ser-L232, facilitating protonation of QB•- in a Grotthuss-like mechanism. This is a basis of how asparagine or glutamine side chains function as acceptors/donors in proton transfer pathways.

A Handy Chemical Sensor Based on Benzaldehyde and Imidazo[1,2-a]pyridine Mixture for Naked-eye Colorimetric and Fluorescent Detection of F.

Upon the Schiff base condensation reaction of imidazo[1,2-a]pyridine-2-carbohydrazide and 2,5-dihydroxybenzaldehyde, a bimodal colorimetric and fluorescent chemosensor 1o for assaying fluoride (F-) in DMSO was synthesized. The characterization of 1o structure was obtained by 1H NMR, 13C NMR and MS.The structure of 1o was characterized by 1H NMR, 13C NMR and MS. Under the presence of various anions, 1o could be applied for naked-eye and fluorescent detection of F- (naked eye: colorless to yellow; fluorescence: dark to green) and displayed promising performance, such as high selectivity and sensitivity, as well as a low detection limit. Upon calculation, the detection limit of chemosensor 1o for F- was 193.5nM, which is well below the allowed maximum value of F- (1.5mg/L) by WHO. As the intermolecular proton transfer mechanism induced "turn-on" fluorescent signal and naked-eye color change of F- to 1o through deprotonation effect, which was confirmed by Job's plot curve, mass spectrometry and 1H NMR titration. Alternatively, the chemosensor 1o can be effectively manufactured into test strips to detect fluoride in solid state, which is user-friendly with no additional equipment required.

Probing radical versus proton migration in the aniline cation with IRMPD spectroscopy

Intramolecular radical and proton migration in the gas phase are important processes driving the dissociation reactions underlying common tandem mass spectrometry processes, such as collision-induced and electron-induced dissociation reactions (CID and ExD). Mechanistic insights in these processes requires experiments that probe the molecular structures of ions along the reaction pathways, usually combined with quantum-chemical calculations. The combination of ion trap mass spectrometry with IR laser spectroscopy, pioneered among others by Dieter Gerlich, provides a particularly effective method to explore details of the ion structures. In this work, we employ infrared multiple-photon dissociation (IRMPD) spectroscopy and density functional theory (DFT) calculations to probe the reactant and product ion structures of a homolytic bond cleavage reaction. First, we employ IRMPD spectroscopy to establish that protonation of the 4-bromoaniline precursor occurs on the amine moiety and then that C-Br homolytic cleavage produces the π-radical cation of aniline. Transition-state calculations are performed to compare the various pathways that connect reactant and product ions, including both proton and radical transfer mechanisms.

Molecular insight into the GaP(110)-water interface using machine learning accelerated molecular dynamics

GaP has been shown to be a promising photoelectrocatalyst for selective CO2 reduction to methanol. Due to the relevance of the interface structure to important processes such as electron/proton transfer, a detailed understanding of the GaP(110)-water interfacial structure is of great importance. Ab initio molecular dynamics (AIMD) can be used for obtaining the microscopic information of the interfacial structure. However, the GaP(110)-water interface cannot converge to an equilibrated structure at the time scale of the AIMD simulation. In this work, we perform the machine learning accelerated molecular dynamics (MLMD) to overcome the difficulty of insufficient sampling by AIMD. With the help of MLMD, we unravel the microscopic information of the structure of the GaP(110)-water interface, and obtain a deeper understanding of the mechanisms of proton transfer at the GaP(110)-water interface, which will pave the way for gaining valuable insights into photoelectrocatalytic mechanisms and improving the performance of photoelectrochemical cells.

A benzoxazole-based turn-on fluorosensor for rapid and sensitive detection of sarin surrogate, diethylchlorophosphate

A benzoxazole-based fluorosensor (IMP) has been synthesized and employed for the selective and sensitive detection of sarin surrogate, diethylchlorophosphate (DCP) in solution, and gas phase, respectively. Remarkable turn-on fluorescence is observed due to the introduction of DCP in the solution of IMP because of inhibition of the intramolecular charge transfer process and disruption of the excited state intramolecular proton transfer (ESIPT) mechanism. The synthesized IMP-based fluorescence sensor exhibits excellent selectivity, high sensitivity, and a wide linear range of 15–60 μM with a detection limit of 44 nM. Low-intense to highly intensified visible violet color could be seen by the naked eye under a portable 365 nm UV lamp due to the addition of DCP in the solution of IMP. IMP-stained paper strips-based test kit experiment has been demonstrated to detect traces of DCP in stockpiles of related analytes. A dip-stick experiment for the detection of DCP vapor has also been demonstrated. The effectiveness of IMP in detecting DCP established that it might be used as a signal tool for real sample analysis.

Observing Aqueous Proton-Uptake Reactions Triggered by Light.

Proton-transfer reactions in water are essential to chemistry and biology. Earlier studies reported on aqueous proton-transfer mechanisms by observing light-triggered reactions of strong (photo)acids and weak bases. Similar studies on strong (photo)base-weak acid reactions would also be of interest because earlier theoretical works found evidence for mechanistic differences between aqueous H+ and OH- transfer. In this work, we study the reaction of actinoquinol, a water-soluble strong photobase, with the water solvent and the weak acid succinimide. We find that in aqueous solutions containing succinimide, the proton-transfer reaction proceeds via two parallel and competing reaction channels. In the first channel, actinoquinol extracts a proton from water, after which the newly generated hydroxide ion is scavenged by succinimide. In the second channel, succinimide forms a hydrogen-bonded complex with actinoquinol and the proton is transferred directly. Interestingly, we do not observe proton conduction in water-separated actinoquinol-succinimide complexes, which makes the newly studied strong base-weak acid reaction essentially different from previously studied strong acid-weak base reactions.

A Multiple Proton Transfer Mechanism for the Charging Step of the Aminoacylation Reaction at the Active Site of Aspartyl tRNA Synthetase.

Aspartyl-tRNA synthetase catalyzes the attachment of aspartic acid to its cognate tRNA by the aminoacylation reaction during the initiation of the protein biosynthesis process. In the second step of the aminoacylation reaction, known as the charging step, the aspartate moiety is transferred from aspartyl-adenylate to the 3'-OH of A76 of tRNA through a proton transfer process. We have investigated different pathways for the charging step through three separate QM/MM simulations combined with the enhanced sampling method of well-sliced metadynamics and found out the most feasible pathway for the reaction at the active site of the enzyme. In the charging reaction, both the phosphate group and the ammonium group after deprotonation can potentially act as a base for proton transfer in the substrate-assisted mechanism. We have considered three possible mechanisms involving different pathways of proton transfer, and only one of them is determined to be enzymatically feasible. The free energy landscape along reaction coordinates where the phosphate group acts as the general base showed that, in the absence of water, the barrier height is 52.6 kcal/mol. The free energy barrier is reduced to 39.7 kcal/mol when the active site water molecules are also treated quantum mechanically, thus allowing a water mediated proton transfer. The charging reaction involving the ammonium group of the aspartyl adenylate is found to follow a path where first a proton from the ammonium group moves to a water in the vicinity forming a hydronium ion (H3O+) and NH2 group. The hydronium ion subsequently passes the proton to the Asp233 residue, thus minimizing the chance of back proton transfer from hydronium to the NH2 group. The neutral NH2 group subsequently takes the proton from the O3' of A76 with a free energy barrier of 10.7 kcal/mol. In the next step, the deprotonated O3' makes a nucleophilic attack to the carbonyl carbon forming a tetrahedral transition state with a free energy barrier of 24.8 kcal/mol. Thus, the present work shows that the charging step proceeds through a multiple proton transfer mechanism where the amino group formed after deprotonation acts as the base to capture a proton from O3' of A76 rather than the phosphate group. The current study also shows the important role played by Asp233 in the proton transfer process.

An ESIPT-based NIR-fluorescent probe for exosome labeling and in situ imaging

Exosomes play significant roles in physiological and tumorigenic processes and it is desirable to visualize and track the exosomes. Herein, a novel amphiphilic fluorescent probe HBT-Exo based on excited-state intramolecular proton transfer (ESIPT) mechanism is reported for exosome-labeling. Its ESIPT characteristics were confirmed by both theory calculation and experimental observation, which enable the probe to show a large Stokes shift as well as near-infrared (NIR) keto-form emission. HBT-Exo displayed excellent biocompatibility and remarkable efficiency for exosome-labeling in gastric cancer cells. Furthermore, the labeled exosomes were successfully applied for the real-time in situ imaging in mouse models.

Thermodynamic Insights into MgBr2-Mediated Glucose Interconversion to Fructose Undertaking Multiple Reaction Pathways by Applying the Macro- and Micro-Kinetic Principles

While many reports on the kinetics and mechanism of glucose isomerization to fructose via a chemical pathway have been published, thermodynamic insights into the interconversion reaction are rarely reported. Here, we report the temperature-dependent characteristics of the cation- and anion-mediated glucose conversion to fructose. The counter ions of MgBr2 enabled the reaction via different pathways in water; e.g., Mg2+ influenced the reaction by undertaking the 1,2-hydride shift mechanism and accounted for up to 50% of the conversion. However, the counter ion (Br–) promoted the conversion via the proton transfer mechanism, which contributed to the remaining 50%, based on the results of the isotopic labeling experiments. This selective transformation (32% wt fructose yield and 76% selectivity) aided by MgBr2 is attributed to the formation of a weak water shell around Mg2+ (due to a lower ratio of MgBr2 to water), which permitted the cation to expose its catalytic activity and affected the administering activity by Br–, which induces maximum side reactions. By applying the principles of transition-state Eyring and Marcus theories to the elementary steps involving a proton transfer and electron transfer, respectively, the temperature-dependent characteristics of the corresponding pathways were determined. The Eyring model exhibited a linear trend in the ln(k/T) vs 1/T plot with an activation energy barrier of 70.25 kJ/mol (comparable to the value of the collision-based Arrhenius model). The semi-classical Marcus model disclosed that the hydride shift is a normal electron transfer rate based on the localization of kET in the λ< -ΔGo >0 region.

Thermal-Response Proton Conduction in Schiff Base-Incorporated Metal-Organic Framework Hybrid Membranes under Low Humidity Based on the Excited-State Intramolecular Proton Transfer Mechanism.

Stimulus-responsive proton conduction materials have attracted enormous interest as a new kind of "smart material". It is desirable to develop the appropriate stimulus signal and high proton-conducting materials with an excellent proton-conducting switch ratio (γ), but it remains a great challenge. Here, it can be found for the first time that 4-((2-hydroxybenzylidene)amino)benzenesulfonic acid (HBABSA) has obvious thermal isomerization when porous solids act as matrixes at the ambient temperatures, which is different from that in the crystalline state at 77 K. Therefore, we proposed a host-guest metal-organic framework (MOF) composite, namely, MOF-808 incorporated with HBABSA (HBABSA@MOF-808), which has a proton-conducting switch ratio (γ) of 16 between 338 and 343 K due to the thermally induced isomerization of HBABSA molecules in the MOF pores. The strong binding between the keto-type HBABSA and MOF at the relatively low temperatures can efficiently suppress the proton conduction, while the enol-type one provides more mobile protons for conduction at the high temperatures due to the excited-state intramolecular proton transfer mechanism. Further, the HBABSA@MOF-808 as a filler is blended into polyvinyl alcohol and poly(2-acrylamide-2-methyl-1-propane sulfonic acid) to form hybrid membranes. The hybrid membrane with the highest content of the MOF composite displays a high proton conductivity of 5.57 × 10-3 S·cm-1 under 353 K and 57% RH along with a good switch ratio of 5.4. The development of thermal-response proton-conducting MOF materials is opening up a unique pathway for remote control, thermal sensing, intelligent batteries, and other fields.

A 4-aminophthalimide derive smart molecule for sequential detection of aluminum ions and picric acid

A fluorosensor derived from 4-aminophthalimide,((E)-5-((2-hydroxybenzylidene) amino) isoindoline-1, 3-dione, HID) working with excited state intramolecular proton transfer (ESIPT) mechanism is synthesized and employed for the selective recognition of aluminum(Al3+) ions and picric acid (PA) based on ‘off–on-off’ fluorescence mechanism. The sensor HID shows a turn-on fluorescence response towards Al3+ ions in 10 % (v/v) DMSO/H2O with a rapid response time (2 min) and exceptional sensitivity (LOD = 0.56 μM). The binding constant (K) of HID with Al3+ ions is estimated to be 1.32 × 108 M−2. The 1:2 stoichiometries of the complex between HID and Al3+ ions are confirmed through Job’s plot and 1H NMR spectral analysis. Al3+ chelated HID complex is further employed to detect explosive nitroaromatic compounds, especially PA. Furthermore, using these two chemically encoded inputs, viz. Al3+ and PA and corresponding optical output, we have constructed the INHIBIT molecular logic gate. The HID chemosensor and Al3+ chelated HID complex are also applied to map Al3+ ions and PA in the living cell. The HID chemosensor and Al3+ chelated HID complex's performance toward detecting Al3+ ions and PA demonstrates that they might be used as a signaling tool for the analysis of biological and environmental samples.

Comparison of classical and ab initio simulations of hydronium and aqueous proton transfer.

Proton transfer represents the simplest chemical reaction, yet it is still typically not accounted for in standard biomolecular simulations. Here we compare an ab initio molecular dynamics (MD) simulation trajectory of an excess proton in water to classical MD trajectories of hydronium in TIP3P water. We characterize the structural differences between them and correlate these with the energy gap upon instant proton transfer, which is much higher in the classical simulations. One structural difference is in the tilt angle of the waters that accept an h-bond from hydronium, which is too large in TIP3P. This can be largely alleviated by use of the TIP5P model, whose lone pairs orient the water molecule properly. Other discrepancies include a lower number of h-bonds and a less favorable second solvation shell geometry in classical MD, which is likely due to lack of polarization. The identification of these structural differences paves the way toward classical MD simulations that can more closely mimic ab initio trajectories. We also present efforts to develop a classical model for hydroxide that reproduces ab initio solvation structure and proton transfer mechanism.

Elucidation of the mechanism and the free energy of a Morita-Baylis-Hillman type reaction catalyzed by enzymes using transition path sampling.

Transition path sampling (TPS) is a Monte-Carlo importance sampling technique in the space of trajectories which is used to elucidate transition states, reaction coordinates and kinetic parameters of complex biomolecular reactions. Within TPS an ensemble of truly dynamic reactive trajectories are obtained with a Monte-Carlo type acceptance criterion in combination with the shooting and shifting algorithms. To sample the equilibrium properties such as free energies, the inclusion of non-reactive trajectories in the TPS ensemble is essential since these trajectories sample the long lived reactant and product states. With a modified acceptance criterion and in combination with a window based sampling algorithm, TPS can be used to obtain unbiased free energy profiles for chemical reactions that are catalyzed by enzymes. Here we use TPS to study the proton transfer mechanism and the corresponding reaction free energy of enzymes (MBHases) that catalyze a Morita-Baylis-Hillman (MBH) type reaction. These enzymes were developed through directed evolution and we aim to map the quantum mechanical tunneling (QMT) contribution in the proton transfer mechanism to laboratory evolution of the MBHases to determine the role played by QMT to rate improvements of evolved variants. The calculated free energies would also provide insights into the role of QMT in the reaction mechanism as the width and height of the free energy barrier determines the importance of the QMT contributions.

The proton transfer mechanism of the Ras GTPases, the effect of the GTPase activating protein, and oncogenic mutations.

Ras-positive cancer constitutes a major challenge for medical treatment. Ras is a central protein in the RAF/MAPK signaling pathway and mutational hot spot residues Gly12, Gly13 and Gln61 constitute the majority of oncogenic mutations which are associated with detrimental clinical prognosis. To target the aberrant signaling by directly interfering with the Ras activity, one must have a thorough understanding of the mechanism of GTP hydrolysis. We employed ab initio calculations and QM/MM enhanced sampling methods to study the possible pathways, with a particular focus on the proton transfer steps. One important requirement for a feasible mechanism is to be consistent with the activating role of the GTPase activating protein (GAP) as well as the disabling nature of key oncogenic mutations of the Ras. Our model successfully recovers the GAP activation and the decreased rate of hydrolysis in Ras mutants. The thus obtained data on the mechanism can be the foundation of a virtual screening procedure designed to find ways of modulating mutant Ras activity.

Spectral signatures of excess-proton waiting and transfer-path dynamics.

Signatures of solvated excess protons in infrared difference absorption spectra, such as the continuum band between the water bend and stretch bands, have been experimentally known for a long time and have recently been used to analyze protonation dynamics in photoactive proteins. However, the theoretical basis for linking spectral signatures with the microscopic proton-transfer mechanism so far relied on normal-mode analysis. We analyze the excess-proton dynamics in ab initio molecular-dynamics simulations of aqueous hydrochloric acid solutions by trajectory-decomposition techniques. The continuum band in the 2000 cm−1 to 3000 cm−1 range is shown to be due to normal-mode oscillations of temporary H3O+ complexes. An additional prominent peak at 400 cm−1 reports on the coupling of excess-proton motion to the relative vibrations of the two flanking water molecules. The actual proton transfer between two water molecules, which for large water separations involves crossing of a barrier and thus is not a normal mode, is characterized by two time scales: Firstly, the waiting time for transfer to occur in the range of 200 fs to 300 fs, which leads to a broad weak shoulder around 100 cm−1, consistent with our experimental THz spectra. Secondly, the mean duration of a transfer event of about 14 fs, which produces a rather well-defined spectral contribution around 1200 cm−1 and agrees in location and width with previous experimental mid-infrared spectra.

Transverse electronic transport properties of single DNA nucleobase pairs between different electrode materials

Detection of gene mutation through electronic transport properties measurements is an attractive research topic. For this purpose, we computed the current–voltage characteristics of adenine-thymine and guanine-cytosine nucleobase pairs, using a combination method of density-functional theory with non-equilibrium Green’s function. Gene mutation was also simulated by structural change in nucleobase pairs by a double proton transfer mechanism. Four different metal electrodes were tested. Comparing the results, nucleobase pairs between platinum surfaces showed distinct electronic transport properties. Such as reverse rectifying direction and negative differential resistance behaviors. The discrepancy can be explained from series of electronic and structural analyses. All these results made identification of structural changes in individual DNA nucleobase pairs possible.

QM-cluster model study of CO2 hydration mechanisms in metal-substituted human carbonic anhydrase II

Human carbonic anhydrase (CA) metalloenzymes utilize a Zn2+-containing active site to catalyze the interconversion of carbon dioxide to bicarbonate. The Zn2+ ion may be replaced with other divalent transition metals, though the catalytic efficiency of the enzyme will be reduced. In this work, quantum mechanical cluster models of the active site are used to map the reaction profile for the hydration mechanism of carbon dioxide. The Lipscomb proton transfer and Lindskog rotation mechanisms were examined for the native Zn2+-enzyme along with variants where the metal was substituted with Cd2+, Ni2+, Fe2+, and Fe3+. The findings highlight the impact the metal coordination geometry has on the reaction profile. The results also suggest Fe2+, which is the functional metal for a prototypical CA of an anaerobic bacterium, might also be functional for human CA if cultured within an anaerobic environment.

A phthalimide-based turn on fluorosensor for selective and rapid detection of G-series nerve agent’s mimics

Organophosphorus-based nerve agents are extremely toxic. Their use in terrorist attacks and wars has caused increased interest in developing simple, portable, displayable, and authentic methods for detecting these lethal substances. In this article, we have designed and synthesized a fluorosenor (HBAI) derived from 4-aminophthalimide moiety that exhibits high selectivity and sensitivity towards G-series nerve agent mimics in their solution and gas phases, respectively. HBAI shows significant fluorescence response to DCP and DCNP that induced noticeable bare eye color changes under a 365 nm UV light irradiation. The detection limit of HBAI for DCP and DCNP has been established in the order of 10-7 M and 10-6 M, respectively. The sensing mechanism for the probe HBAI has been elucidated by time-resolved photoluminescence decay analysis and 1H NMR titration experiment. The significant photoluminescence enhancement is mainly found for disrupting the excited state intramolecular proton transfer (ESIPT) mechanism because of the phosphorylation process. However, for the practical utility of HBAI, a test kit employing Whatman-41 filter paper has been fabricated as a portable and displayable photonic device for on-site detection of G-series nerve agents. Also, a dip-stick method has been demonstrated to identify the vapor of G-series nerve agents mimic.

Photoacid Dynamics in the Green Fluorescent Protein.

The photoacid dynamics of fluorescent proteins include both electronic excited- and ground-state mechanisms of proton transfer. The associated characteristic timescales of these reactions range over many orders of magnitude, and the tunneling, barrier crossing, and relevant thermodynamics have in certain cases been linked to coherent nuclear motion. We review the literature and summarize the experiments and theory that demonstrate proton tunneling in the electronic ground state of the green fluorescent protein (GFP). We also discuss the excited-state proton-transfer reaction of GFP that takes place on the picosecond timescale. Although this reaction has been investigated using several vibrational spectroscopic methods, the interpretation remains unsettled. We discuss recent advances as well as remaining questions, in particular those related to the vibrational mode couplings that involve low-frequency modulations of chromophore vibrations on the timescale of proton transfer.