纯水溶液中的氢键交换反应路径

利用分子动力学模拟方法对纯水溶液的氢键转化动力学性质进行了深入的微观探讨,溶液中非氢键构型为寿命较短(0.1～0.2 ps)的过渡态构型,我们发现氢键交换通过两种过渡构型完成,氢键角度扭曲激发后与氢键第一壳层水分子沿路径1交换,氢键径向拉伸激发后与氢键第二壳层水分子沿路径2交换,过渡态路径的选择具有温度依赖性.氢键转化需在旧氢键受体氢键过量和新氢键受体氢键不足,同时满足交换反应空间结构要求下才能完成.氢键交换反应对水分子平动和转动行为起着决定作用.     

Dissociation mechanism of acetic acid in water

The reaction mechanism for acetic acid dissociation in aqueous solution has been investigated by combining the metadynamics method with transition path sampling (TPS). By using collective variables that describe not only the deprotonation of the acid but also the solvation state of the hydronium ion and its distance from the acetate, a reactive trajectory in which stable separated ions were produced was obtained. More transition trajectories were sampled by using the TPS technique, taking the metadynamics trajectory as the initial trajectory. Two different dissociation reaction pathways were determined, one driven by the breaking of an H-bond formed by the water molecule in contact with the hydroxyl and involving the formation of a metastable contact ion pair and the other characterized by a direct transfer of the proton to the solution through an unstable Zundel-ion-like intermediate.     

Orientational relaxation dynamics in aqueous ionic solution: polarization-selective two-dimensional infrared study of angular jump-exchange dynamics in aqueous 6M NaClO4

The dynamics of hydrogen bond (H-bond) formation and dissociation depend intimately on the dynamics of water rotation. We have used polarization resolved ultrafast two-dimensional infrared (2DIR) spectroscopy to investigate the rotational dynamics of deuterated hydroxyl groups (OD) in a solution of 6M NaClO(4) dissolved in isotopically mixed water. Aqueous 6M NaClO(4) has two peaks in the OD stretching region, one associated with hydroxyl groups that donate a H-bond to another water molecule (OD(W)) and one associated with hydroxyl groups that donate a H-bond to a perchlorate anion (OD(P)). Two-dimensional IR spectroscopy temporally resolves the equilibrium inter conversion of these spectrally distinct H-bond configurations, while polarization-selective 2DIR allows us to access the orientational motions associated with this chemical exchange. We have developed a general jump-exchange kinetic theory to model angular jumps associated with chemical exchange events. We use this to model polarization-selective 2DIR spectra and pump-probe anisotropy measurements. We determine the H-bond exchange induced jump angle to be 49 ± 5° and the H-bond exchange rate to be 6 ± 1 ps. Additionally, the separation of the 2DIR signal into contributions that have or have not undergone H-bond exchange allows us to directly determine the orientational dynamics of the OD(W) and the OD(P) configurations without contributions from the exchanged population. This proves to be important because the orientational relaxation dynamics of the populations that have undergone a H-bond exchange differ significantly from the populations that remain in one H-bond configuration. We have determined the slow orientational relaxation time constant to be 6.0 ± 1 ps for the OD(W) configuration and 8.3 ± 1 ps for the OD(P) configuration. We conclude from these measurements that the orientational dynamics of hydroxyl groups in distinct H-bond configurations do differ, but not significantly.     

Direct observation and control of hydrogen-bond dynamics using low-temperature scanning tunneling microscopy

Hydrogen(H)-bond dynamics are involved in many elementary processes in chemistry and biology. Because of its fundamental importance, a variety of experimental and theoretical approaches have been employed to study the dynamics in gas, liquid, solid phases, and their interfaces. This review describes the recent progress of direct observation and control of H-bond dynamics in several model systems on a metal surface by using low-temperature scanning tunneling microscopy (STM). General aspects of H-bond dynamics and the experimental methods are briefly described in chapter 1 and 2. In the subsequent four chapters, I present direct observation of an H-bond exchange reaction within a single water dimer (chapter 3), a symmetric H bond (chapter 4) and H-atom relay reactions (chapter 5) within water–hydroxyl complexes, and an intramolecular H-atom transfer reaction (tautomerization) within a single porphycene molecule (chapter 6). These results provide novel microscopic insights into H-bond dynamics at the single-molecule level, and highlight significant impact on the process from quantum effects, namely tunneling and zero-point vibration, resulting from the small mass of H atom. Additionally, local environmental effect on H-bond dynamics is also examined by using atom/molecule manipulation with the STM.     

Competitive hydrolytic and elimination mechanisms in the urease catalyzed decomposition of urea

We present a high-level quantum chemical study of possible elimination reaction mechanisms associated with the catalytic decomposition of urea at the binuclear nickel active site cluster of urease. Stable intermediates and transition state structures have been identified along several possible reaction pathways. The computed results are compared with those reported by Suarez et al. for the hydrolytic catalyzed decomposition. On the basis of these comparative studies, we propose a monodentate coordination of urea in the active site from which both the elimination and hydrolytic pathways can decompose urea into CO2 and NH3. This observation is counter to what has been experimentally suggested based on the exogenous observation of carbamic acid (the reaction product from the hydrolysis pathway). However, this does not address what has occurred at the active site of urease prior to product release. On the basis of our computed results, the observation that urea prefers the elimination channel in aqueous solution and on the observation of Lippard and co-workers of an elimination reaction channel in a urease biomimetic model, we propose that the elimination channel needs to be re-examined as a viable reaction channel in urease.     

On the role of the conserved aspartate in the hydrolysis of the phosphocysteine intermediate of the low molecular weight tyrosine phosphatase

The usual rate-determining step in the catalytic mechanism of the low molecular weight tyrosine phosphatases involves the hydrolysis of a phosphocysteine intermediate. To explain this hydrolysis, general base-catalyzed attack of water by the anion of a conserved aspartic acid has sometimes been invoked. However, experimental measurements of solvent deuterium kinetic isotope effects for this enzyme do not reveal a rate-limiting proton transfer accompanying dephosphorylation. Moreover, base activation of water is difficult to reconcile with the known gas-phase proton affinities and solution phase pK(a)'s of aspartic acid and water. Alternatively, hydrolysis could proceed by a direct nucleophilic attack by a water molecule. To understand the hydrolysis mechanism, we have used high-level density functional methods of quantum chemistry combined with continuum electrostatics models of the protein and the solvent. Our calculations do not support a catalytic activation of water by the aspartate. Instead, they indicate that the water oxygen directly attacks the phosphorus, with the aspartate residue acting as a H-bond acceptor. In the transition state, the water protons are still bound to the oxygen. Beyond the transition state, the barrier to proton transfer to the base is greatly diminished; the aspartate can abstract a proton only after the transition state, a result consistent with experimental solvent isotope effects for this enzyme and with established precedents for phosphomonoester hydrolysis.     

The mechanism of formamide hydrolysis in water from ab initio calculations and simulations

The neutral hydrolysis of formamide in water is a suitable reference to quantify the efficiency of proteolytic enzymes. However, experimental data for this reaction has only very recently been obtained and the kinetic constant determined experimentally is significantly higher than that predicted by previous theoretical estimations. In this work, we have investigated in detail the possible mechanisms of this reaction. Several solvent models have been considered that represent a considerable improvement on those used in previous studies. Density functional and ab initio calculations have been carried out on a system which explicitly includes the first solvation shell of the formamide molecule. Its interaction with the bulk has been treated with the aid of a dielectric continuum model. Molecular dynamics simulations at the combined density functional/molecular mechanics level have been carried out in parallel to better understand the structure of the reaction intermediates in aqueous solution. Overall, the most favored mechanism predicted by our study involves two reaction steps. In the first step, the carbonyl group of the formamide molecule is hydrated to form a diol intermediate. The corresponding transition structure involves two water molecules. From this intermediate, a water-assisted proton transfer occurs from one of the hydroxy groups to the amino group. This reaction step may lead either to the formation of a new reaction intermediate with a marked zwitterionic character or to dissociation of the system into ammonia and formic acid. The zwitterionic intermediate dissociates quite easily but its lifetime is not negligible and it could play a role in the hydrolysis of substituted amides or peptides. The predicted pseudo-first-order kinetic constant for the rate-limiting step (the first step) of the hydrolysis reaction at 25 degrees C (3.9x10(-10) s(-1)) is in excellent agreement with experimental data (1.1x10(-10) s(-1)).     

The Energy of Interaction between Water Monolayer and Carbon Surface and the Determination of H-Bond Energy from the Isotherms of Water Desorption by Organic Molecules into an Aqueous Solution

It is proven that, when passing from a liquid into an adsorption phase on a carbon surface, the maximal number of H-bonds between water molecules decreases from four to three because of the screening of one unpaired electron of the oxygen atom of an adsorbed water molecule by aromatic rings of the carbon surface. An energy gain equal to the energy of one H-bond arises upon water desorption by organic molecules adsorbed from an aqueous solution. The ratio between the number of H-bonds of a group of water molecules, which is displaced into a solution by one organic molecule, in the solution and in the adsorption phase is independent of the number of molecules in this group and is, on the average, equal to 2.038 for all possible structures of H-bonds in both phases. The allowance for this ratio in the isotherm of water desorption into a solution and the introduction of a coefficient, which depends on the relative water content ( ) in the adsorption phase, in the form of into the equation of the desorption isotherm make it possible to determine the balance of the change in the Gibbs energy at the desorption equilibrium and the standard Gibbs energy = –1.76 kJ/mol of water desorption into a solution from a carbon surface. This value determined by an independent method is = –1.79 kJ/mol; i.e., both values are close to each other. The RTlnf energy of the additional H-bond, which is formed between water molecules upon passing from the adsorption phase into the solution, is found by the extrapolation of the isotherms of water desorption by molecules of several benzene derivatives. This energy ranges from 9.13 to 9.24 kJ/mol, thus corresponding to the energy of one H-bond, as measured by IR spectroscopy and NMR.     

pH-Sensitive Oscillatory Motion of a Urease Motor on the Urea Aqueous Phase

A self-propelled object coupled with an enzyme reaction between urease and urea was investigated at the air/aqueous interface. A plastic object that was fixed to a urease-immobilized filter paper was used as a self-propelled object, termed a urease motor, placed on an aqueous urea solution. The driving force of the urease motor is the difference in the surface tension around the object. Oscillatory motion or no motion was triggered depending on the initial pH of the urea solution. Both the frequency and maximum speed of the oscillatory motion varied depending on the initial pH of the water phase. The mechanisms underlying the oscillatory motion and no motion were discussed in relation to the bell-shaped enzyme activity of urease in the enzyme reaction and the surface tension around the urease motor.     

Alkaline hydrolysis of ethylene phosphate: an ab initio study by supermolecule model and polarizable continuum approach

The alkaline hydrolysis reaction of ethylene phosphate (EP) has been investigated using a supermolecule model, in which several explicit water molecules are included. The structures and single-point energies for all of the stationary points are calculated in the gas phase and in solution at the B3LYP/6-31++G(df,p) and MP2/6-311++G(df,2p) levels. The effect of water bulk solvent is introduced by the polarizable continuum model (PCM). Water attack and hydroxide attack pathways are taken into account for the alkaline hydrolysis of EP. An associative mechanism is observed for both of the two pathways with a kinetically insignificant intermediate. The water attack pathway involves a water molecule attacking and a proton transfer from the attacking water to the hydroxide in the first step, followed by an endocyclic bond cleavage to the leaving group. While in the first step of the hydroxide attack pathway the nucleophile is the hydroxide anion. The calculated barriers in aqueous solution for the water attack and hydroxide attack pathways are all about 22 kcal/mol. The excellent agreement between the calculated and observed values demonstrates that both of the two pathways are possible for the alkaline hydrolysis of EP.     

Mechanistic Study on the Ozone‐Mercury Reaction and the Effect of Water and Water Dimer Molecules

The thermodynamics and mechanism of the reaction of elemental mercury with ozone has been studied computationally. The effect of water and water dimer molecules on the reaction has also been investigated. For dry reaction, we obtained two pathways and geometry optimization, atoms in molecules analysis and vibrational frequencies of all component of reaction have been used for confirming of reaction mechanism. Thermodynamic variable of reaction has been calculated. For the reaction in the presence of the water, our studies focus on ozone‐mercury complex reaction with water and water dimer and obtained the mechanism of reactions. Comparison of wet and dry reaction shows the energy profile of reaction decreases with water molecule correspond to experimental prediction. Calculated thermodynamic variable of all reaction shows the Gibbs free energy of reaction decreases with the number of water molecule.     

Transition states for glucopyranose interconversion

Glucose is a central molecule in biology and chemistry, and the anomerization reaction has been studied for more than 150 years. Transition-state structure is the last impediment to an in-depth understanding of its solution chemistry. We have measured kinetic isotope effects on the rate constants for approach of alpha-glucopyranose to its equilibrium with beta-glucopyranose, and these were converted into unidirectional kinetic isotope effects using equilibrium isotope effects. Saturation transfer 13C NMR spectroscopy has yielded the relative free energies of the transition states for the ring-opening and ring-closing reactions, and both transition states contribute to the experimental kinetic isotope effects. Both transition states of the anomerization process have been modeled with high-level computational theory with constraints from the primary, secondary, and solvent kinetic isotope effects. We have found the transition states for anomerization, and we have also concluded that it is forbidden for the water molecule to form a hydrogen bond bridge to both OH1 and O5 of glucose simultaneously in either transition state.     

Enzymatic catalysis of urea decomposition: elimination or hydrolysis?

We present a high-level quantum chemical study of possible reaction mechanisms associated with the catalytic decomposition of urea by a bioinorganic mimetic of the dinickel active site of urease. We chose the phthalazine-dinickel complexes of Lippard and co-workers, because these mimetics have been shown to hydrolytically degrade urea. High-level quantum chemical methodologies were utilized to identify stable intermediates and transition-state structures along several possible reaction pathways. The computed results were then used to further analyze what may occur in the active site of urease. Valuable information on the latter has been extracted from experimental data, computational approaches, and unpublished molecular dynamics simulations. On the basis of these comparative studies, we propose that both the elimination and hydrolytic pathways may compete for urea decomposition in the active site of urease.     

Role of structural water molecule in HIV protease-inhibitor complexes: a QM/MM study

Structural water molecule 301 found at the interface of HIV protease-inhibitor complexes function as a hydrogen bond (H-bond) donor to carbonyl groups of the inhibitor as well as H-bond acceptor to amide/amine groups of the flap region of the protease. In this study, six systems of HIV protease-inhibitor complexes were analyzed, which have the presence of this "conserved" structural water molecule using a two-layer QM/MM ONIOM method. The combination of QM/MM and QM method enabled the calculation of strain energies of the bound ligands as well as the determination of their binding energies in the ligand-water and ligand-water-protease complexes. Although the ligand experiences considerable strain in the protein bound structure, the H-bond interactions through the structural water overcomes this strain effect to give a net stability in the range of 16-24 kcal/mol. For instance, in 1HIV system, the strain energy of the ligand was 12.2 kcal/mol, whereas the binding energy associated with the structural water molecule was 20.8 kcal/mol. In most of the cases, the calculated binding energy of structural water molecule showed the same trend as that of the experimental binding free energy values. Further, the classical MD simulations carried out on 1HVL system with and without structural water 301 showed that this conserved water molecule enhances the H-bond dynamics occurring at the Asp-bound active site region of the protease-inhibitor system, and therefore it will have a direct influence on the mechanism of drug action.     

Determination of Michaelis-Menten parameters obtained from isothermal flow calorimetric data

Recent papers have reported [Thermochim. Acta 399 (2003) 63; Thermochim. Acta, in press] the results of a preliminary inter/intra laboratory study into the suitability of the base-catalysed hydrolysis of methyl paraben as a test and reference reaction for isothermal flow-through calorimeters. It was shown that this reaction can be used to investigate the flow characteristics of the instrument being used. It has also allowed, for the first time, the calculation of accurate values for the rate constant and for the enthalpy change, ΔH (hereafter H (enthalpy) for simplicity) of reaction directly from the calorimetric data, free from assumption. These findings have been extended to permit the direct determination of Michaelis-Menten based kinetic parameters from calorimetric data again free from assumption (except that the system conforms to Michaelis-Menten kinetic theory). This paper describes the method used for such an analysis and reports the results of a preliminary study on the urea/urease enzymatic system.     

Effect of thermosensitive matrix-phase transition on urease-catalyzed urea hydrolysis

Temperature dependencies of kinetic and equilibrium parameters of urea hydrolysis catalyzed by native urease and the urease immobilized in a thermosensitive poly-N-isopropylacrylamide gel have been studied. The swelling ratio of the collapsed urease-containing gel is shown to increase in the presence of urea. Below a lower critical solution temperature (LCST) of the polymer, the immobilized u reaseactually has thesame catalytic properties as the native enzyme. At temperatures above LCST, the observed catalytic activity of the immobilized enzyme depends chiefly not only on the thermoreversible matrix state, but also on gel water content.     

Monolayers of salen derivatives as catalytic planes for alkene oxidation in water

Monolayers at the gas/water interface have been used as an adjustable catalytic system in which the molecular density may be modified. Mn(III)-salen complexes bearing perfluoroalkyl substituents have been organized as a Langmuir film on an aqueous subphase containing a urea/hydrogen peroxide adduct (UHP, the oxidant) and cinnamyl alcohol (the substrate). The catalytic activity of the monolayer for the epoxidation of the alkene dissolved in water has been demonstrated and the reaction kinetic investigated. For a constant area per molecule of catalyst, the reaction rate exhibits first-order dependence on oxidant concentration and zero-order dependence on alkene concentration, in agreement with the reaction orders reported for Mn(III)-salen-catalyzed epoxidation reactions carried out in solution. Furthermore, kinetic experiments suggest an enhanced activity of the catalysts assembled in a Langmuir film relative to that observed in bulk reaction. Finally, varying the molecular density of the catalyst at the gas/water interface highlights an important dependence of the catalytic activity of the layer with the mean molecular area. A strong increase of the catalytic properties of the monolayer was observed for a mean molecular area of 140-145 A2, an increase which was supposedly related to a modification of the Mn(III)-salen complex orientation at the interface upon compression. This hypothesis was supported by PM-IRRAS (polarization modulation infrared reflection adsorption spectroscopy) experiments performed in situ on the monolayer. Such results demonstrate that a soft and adjustable molecular system like a Langmuir film can be used to better understand the reactivity in various heterogeneous and/or pseudohomogeneous (such as those based on dendrimers) catalytic systems.     

Intermediates and kinetics for phenol gasification in supercritical water

We processed phenol with supercritical water in a series of experiments, which systematically varied the temperature, water density, reactant concentration, and reaction time. Both the gas and liquid phases were analyzed post-reaction using gas chromatographic techniques, which identified and quantified the reaction intermediates and products, including H(2), CO, CH(4), and CO(2) in the gas phase and twenty different compounds--mainly polycyclic aromatic hydrocarbons--in the liquid phase. Many of these liquid phase compounds were identified for the first time and could pose environmental risks. Higher temperatures promoted gasification and resulted in a product gas rich in H(2) and CH(4) (33% and 29%, respectively, at 700 °C), but char yields increased as well. We implicated dibenzofuran and other identified phenolic dimers as precursor molecules for char formation pathways, which can be driven by free radical polymerization at high temperatures. Examination of the trends in conversion as a function of initial water and phenol concentrations revealed competing effects, and these informed the kinetic modeling of phenol disappearance. Two different reaction pathways emerged from the kinetic modeling: one in which rate ∝ [phenol](1.73)[water](-16.60) and the other in which rate ∝ [phenol](0.92)[water](1.39). These pathways may correspond to pyrolysis, which dominates when there is abundant phenol and little water, and hydrothermal reactions, which dominate in excess water. This result confirms that supercritical water gasification of phenol does not simply follow first-order kinetics, as previous efforts to model phenol disappearance had assumed.     

H-bond relays in proton-coupled electron transfers. Oxidation of a phenol concerted with proton transport to a distal base through an OH relay

Four molecules comprising a phenol moiety and a distal pyridine base connected by an intermediary H-bonding and an H-bonded alcohol group have been synthesized and their electrochemistry has been investigated by means of cyclic voltammetry. The molecules differ by the substituent at the alcohol functional carbon and by methyl groups on the pyridine. The reaction follows a concerted proton-electron transfer pathway as confirmed by the observation of a significant H/D kinetic isotope effect in all four cases. The standard rate constants characterizing each of the four compounds are analyzed in terms of reorganization energy and pre-exponential factor. Intramolecular and solvent reorganization energies appear as practically constant in the series, in which a previously investigated aminophenol is included, whereas significantly different pre-exponential factors are observed. That the latter, which is a measure of the efficiency of proton tunneling concerted with electron transfer, be substantially smaller with the H-bond relay molecules than with the aminophenol is related to the fact that two protons are moved in the first case instead of one in the second. Within the H-bond relay molecules, the pre-exponential factor varies with the substituent present at the alcohol functional carbon in the order CF(3) > H > CH(3), presumably as the result of a fine tuning of the balance between the H-bond accepting and H-bond donating properties of the central OH group. The kinetic H/D kinetic isotope effect increases accordingly in the same order.