Proton-coupled electron transfer in soybean lipoxygenase

The proton-coupled electron transfer reaction catalyzed by soybean lipoxygenase-1 is studied with a multistate continuum theory that represents the transferring hydrogen nucleus as a quantum mechanical wave function. The inner-sphere reorganization energy of the iron cofactor is calculated with density functional theory, and the outer-sphere reorganization energy of the protein is calculated with the frequency-resolved cavity model for conformations obtained with docking simulations. Both classical and quantum mechanical treatments of the proton donor-acceptor vibrational motion are presented. The temperature dependence of the calculated rates and kinetic isotope effects is in agreement with the experimental data. The weak temperature dependence of the rates is due to the relatively small free energy barrier arising from a balance between the reorganization energy and the reaction free energy. The unusually high deuterium kinetic isotope effect of 81 is due to the small overlap of the reactant and product proton vibrational wave functions and the dominance of the lowest energy reactant and product vibronic states in the tunneling process. The temperature dependence of the kinetic isotope effect is strongly influenced by the proton donor-acceptor distance with the dominant contribution to the overall rate. This dominant proton donor-acceptor distance is significantly smaller than the equilibrium donor-acceptor distance and is determined by a balance between the larger coupling and the smaller Boltzmann probability as the distance decreases. Thus, the proton donor-acceptor vibrational motion plays a vital role in decreasing the dominant donor-acceptor distance relative to its equilibrium value to facilitate the proton-coupled electron transfer reaction.     

Dipole–reaction field interaction model for the solvent reorganization energy and its application to the benzoquinone–benzoquinone anion radical system

 Based on the spherical cavity approximation and the Onsager model, a dipole–reaction field interaction model has been proposed to elucidate the solvent reorganization energy of electron transfer (ET). This treatment only needs the cavity radius and the solute dipole moment in the evaluation of the solvent reorganization energy, and fits spherelike systems well. As an application, the ET reaction between p-benzoquinone and its anion radical has been investigated. The inner reorganization energy has been calculated at the level of MP2/6–31+G, and the solvent reorganization energies of different conformations have been evaluated by using the self-consistent reaction field approach at the HF/6–31+G level. Discussions have been made on the cavity radii and the values are found to be reasonable when compared with the experimental ones of some analogous intramolecular ET reactions. The ET matrix element has been determined on the basis of the two-state model. The fact that the value of the ET matrix element is about 10 times larger than RT indicates that this ET reaction can be treated as an adiabatic one. By invoking the classical Marcus ET model, a value of 4.9 × 10⁷M⁻¹s⁻¹ was obtained for the second-order rate constant, and it agrees quite well with the experimental one. Received: 19 October 2001 / Accepted: 17 January 2002 / Published online: 3 May 2002     

Solvent reorganization of electron transitions in viscous solvents

We develop a model of electron transfer reactions at conditions of nonergodicity when the time of solvent relaxation crosses the observation time window set up by the reaction rate. Solvent reorganization energy of intramolecular electron transfer in a charge-transfer molecule dissolved in water and acetonitrile is studied by molecular dynamics simulations at varying temperatures. We observe a sharp decrease of the reorganization energy at a temperature identified as the temperature of structural arrest due to cage effect, as discussed by the mode-coupling theory. This temperature also marks the onset of the enhancement of translational diffusion relative to rotational relaxation signaling the breakdown of the Stokes-Einstein relation. The change in the reorganization energy at the transition temperature reflects the dynamical arrest of the slow, collective relaxation of the solvent related to the relaxation of the solvent dipolar polarization. An analytical theory proposed to describe this effect agrees well with both the simulations and experimental Stokes shift data. The theory is applied to the analysis of charge-transfer kinetics in a low-temperature glass former. We show that the reorganization energy is substantially lower than its equilibrium value for the low-temperature portion of the data. The theory predicts the possibility of discontinuous changes in the dependence of the electron transfer rate on the free energy gap when the reaction switches between ergodic and nonergodic regimes.     

A kinetic study of the electron-transfer reaction of the phthalimide-N-oxyl radical (PINO) with ferrocenes

A kinetic study of the one-electron oxidation of a series of ferrocenes (FcX: X = H, CO2Et, CONH2, CH2CN, CH2OH, Et, and Me2) by PINO generated in CH3CN by reaction of N-hydroxyphthalimide (NHPI) with the cumyloxyl radical produced by 355 nm laser flash photolysis of dicumyl peroxide has been carried out. Ferrocenium cations were formed, and the reaction rate was determined by following the decay of PINO radical at 380 nm as a function of the FcX concentration. Rate constants were very sensitive to the oxidation potential of the substrates and exhibited a good fit with the Marcus equation, from which a lambda value of 38.3 kcal mol(-1) was calculated for the reorganization energy required in the PINO/ferrocenes electron-transfer process. Knowing the ferrocene/ferrocenium self-exchange reorganization energy it was possible to calculate a value of 49.1 kcal mol(-1) for the PINO/PINO- self-exchange reaction in CH3CN. Moreover, from the Marcus cross relation and the self-exchange rates of ferrocene and dimethylferrocene, the intrinsic reactivity of PINO in electron-transfer reactions has been calculated as 7.6 x 10(2) M(-1) s(-1). The implications of these values and the comparison with the electron-transfer self-exchange reorganization energies of peroxyl radicals are briefly discussed.     

Skeletal reorganization of enynes to 1-vinylcycloalkenes catalyzed by GaCl(3)

The skeletal reorganization of enynes is achieved by the presence of GaCl3 as the catalyst. This reaction demonstrates the first example of the skeletal reorganization of enynes catalyzed by typical metal complexes. The process is simple and provides a diverse range of enynes in good to high yields. The reaction of enynes bearing a monosubstituent at the terminal olefinic carbon proceeds in a stereospecific manner with respect to the geometry of the olefin moiety. Enynes, bearing two substituents at the olefinic terminal carbon, undergo an efficient skeletal reorganization, these substrates having been known to be unsuitable substrates for the skeletal reorganization of enynes.     

Adiabatic and non-adiabatic concerted proton-electron transfers. Temperature effects in the oxidation of intramolecularly hydrogen-bonded phenols

The one-electron electrochemical and homogeneous oxidations of two closely similar aminophenols that undergo a concerted proton-electron transfer reaction, in which the phenolic proton is transferred to the nitrogen atom in concert with electron transfer, are taken as examples to test procedures that allow the separate determination of the degree of adiabaticity and the reorganization energy of the reaction. The Marcus (or Marcus-Hush-Levich) formalism is applicable in both cases, but not necessarily in its adiabatic version. Linearization of the activation-driving force laws simplifies the treatment of the kinetic data, notably allowing the use of Arrhenius plots to treat the temperature dependence of the rate constant. A correct estimation of the adiabaticity and reorganization energy requires the determination of the variation of the driving force with temperature. Application of these procedures led to the conclusion that, unlike previous reports, the homogeneous reaction is non-adiabatic, with a transmission coefficient of the order of 0.005, and that the self-exchange reorganization energy is about 1 eV lower than previously estimated. With such systems, the intramolecular reorganization energy, although sizable, is in fact rather modest, being only slightly larger than that for the outer-sphere electron transfer that produced the cation radical. The electrochemical reaction is, in contrast, adiabatic, as revealed by the temperature dependence of its standard rate constant obtained from cyclic voltammetric experiments. This difference in behavior is deemed to derive from the effect of the strong electric field within which the electrochemical reaction takes place, stabilizing a zwitterionic form of the reactant (in which the proton has been transferred from oxygen to nitrogen). Taking this difference in adiabaticity into account, the magnitudes of the reorganization energies of the two reactions appear to be quite compatible with one another, as revealed by an analysis of the solvent and intramolecular contributions in both cases.     

Skeletal reorganization of enynes catalyzed by InCl3

[reaction: see text] The skeletal reorganization of enynes is achieved by the presence of InCl(3) as the catalyst. The reaction of enynes having a terminal acetylenic moiety proceeds in a stereospecific manner to give 1-vinylcycloalkenes. The reaction of enynes containing an alkyl group on the acetylenic terminal carbon resulted in a new type of skeletal reorganization to give 1-allylcycloalkenes, formation of which involves a double cleavage of the C-C double bond and the triple bond.     

Crucial role of protein flexibility in formation of a stable reaction transition state in an α-amylase catalysis

Conformational flexibility of proteins provides enzymes with high catalytic activity. Although the conformational flexibility is known to be pivotal for the ligand binding and release, its role in the chemical reaction process of the reactive substrate remains unclear. We determined a transition state of an enzymatic reaction in a psychrophilic α-amylase by a hybrid molecular simulation that allows one to identify the optimal chemical state in an extensive conformational ensemble of protein. The molecular simulation uncovered that formation of the reaction transition state accompanies a large and slow movement of a loop adjacent to the catalytic site. Free energy calculations revealed that, although catalytic electrostatic potentials on the reactive moiety are formed by local and fast reorganization around the catalytic site, reorganization of the large and slow movement of the loop significantly contributes to reduction of the free energy barrier by stabilizing the local reorganization.     

细菌光合反应中心Q~A和Q~B间电子转移反应的量子化学研究

用量子化学半经验的AM1和密度泛函DFT(BELYP/6-31G(d))方法分别优化了质体醌MQ1(Q~A)、泛醌UQ1(Q~B)及其阳离子自由基的结构。用Nelsen方法计算了电子转移反应MQ1-UQ1→MQ1UQ^-~1的内重组能λi。用线性反应坐标方法构造了该电子转移反应的双势阱,两透热势能面在反应坐标R≈0.30处相交。对该电子转移体系进行闭壳层的单点计算,并用Koopmans定理计算了体系的分裂能△,得到△随线性反应坐标R的变化关系。结果表明,在R=0.342处△有一极小值,从而得到该电子转移反应的电子转移矩阵元Vrp,并由此确定了反应的过渡态。在此基础上,用两球模型计算了反应的溶剂重组能λ0。本文还计算了该电子转移反应的活化自由能△G。最后,根据Marcus电子转移理论计算了该反应的速率常数ket为5.93×10^4s^-^1,由此得到该反应的半衰期与文献报道的结果一致。     

苯硝化反应中电子转移反应重组能的计算

提出了重组能的量子化学算法,在用CISD/6-31G基组水平上,得到苯硝化反应中反应物及过渡态的结构.并计算了各自交换电子转移反应以及交叉电子转移反应的重组能,同实验重组能进行了比较.计算用了Gaussian 94程序.从重组能的角度分析了苯硝化反应.结果表明,对于NO2++NO2→NO2+NO2+的自交换电子转移反应,重组能较大,结论为: 在芳烃硝化反应中,存在以NO2+为氧化剂的电子转移步骤的可能性很小,而从动力学的角度上,用NO+作反应的氧化剂更有可能.     

Theoretical study on electron transfer in biological systems (III)

Iritramolwular electron transfer of nlctal-containing spiro π-electron system was studied by AM1 method in the MOPAC-ET program developed by the present group. The results indicated that with the increasing of the outer electric field F, the activation energy of the reaction decreased. When F reaches a certain threshold value, the activation energy barrirr becomcs zero and the rate of reaction achieves the largest value. The results also indicated that electron transfer matrix elements V_AB and reorganization energy λ were not obviously affected by outer electric field while the exothermicity ΔE was directly proportional to it.     

Theoretical modeling of enzyme catalytic power: analysis of "cratic" and electrostatic factors in catechol O-methyltransferase

A comparative theoretical study of a bimolecular reaction in aqueous solution and catalyzed by the enzyme catechol O-methyltransferase (COMT) has been carried out by a combination of two hybrid QM/MM techniques: statistical simulation methods and internal energy minimizations. In contrast to previous studies by other workers, we have located and characterized transition structures for the reaction in the enzyme active site, in water and in a vacuum, and our potential of mean force calculations are based upon reaction coordinates obtained from features of the potential energy surfaces in the condensed media, not from the gas phase. The AM1/CHARMM calculated free energy of activation for the reaction of S-adenosyl methionine (SAM) with catecholate catalyzed by COMT is 15 kcal mol(-1) lower the AM1/TIP3P free-energy barrier for the reaction of the trimethylsulfonium cation with the catecholate anion in water at 300 K, in agreement with previous estimates. The thermodynamically preferred form of the reactants in the uncatalyzed model reaction in water is a solvent-separated ion pair (SSIP). Conversion of the SSIP into a contact ion pair, with a structure resembling that of the Michaelis complex (MC) for the reaction in the COMT active site, is unfavorable by 7 kcal mol(-1), largely due to reorganization of the solvent. We have considered alternative ways to estimate the so-called "cratic" free energy for bringing the reactant species together in the correct orientation for reaction but conclude that direct evaluation of the free energy of association by means of molecular dynamics simulation with a simple standard-state correction is probably the best approach. The latter correction allows for the fact that the size of the unit cell employed with the periodic boundary simulations does not correspond to the standard state concentration of 1 M. Consideration of MC-like species allows a helpful decomposition of the catalytic effect into preorganization and reorganization phases. In the preorganization phase, the substrates are brought together into the MC-like species, either in water or in the enzyme active site. In the reorganization phase, the roles of the enzymic and aqueous environments may be compared directly because reorganization of the substrate is about the same in both cases. Analysis of the electric field along the reaction coordinate demonstrates that in water the TS is destabilized with respect to the MC-like species because the polarity of the solute diminishes and consequently the reaction field is also decreased. In the enzyme, the electric field is mainly a permanent field and consequently there is only a small reorganization of the environment. Therefore, destabilization of the TS is lower than in solution, and the activation barrier is smaller.     

溶液中M(H_2O)_6~(2+/3+)(M=V,Cr,Mn,Fe,Co)自交换电子转移体系内层重组能和活化能的理论研究

通过建立电子转移过程的活化模型和重组模型,提出了用量子化学从头算方法研究电子转移过程内层重组能和活化能的新方法．在ＵＭＰ２／６－３１１Ｇ水平上获得了５对过渡金属水合离子体系Ｍ（Ｈ２Ｏ）２＋／３＋６（Ｍ＝Ｖ,Ｃｒ,Ｍｎ,Ｆｅ,Ｃｏ）自交换反应的内层重组能和活化能,获得了与Ｍａｒｃｕｓ电子转移理论相一致的结果     

Theoretical Study of the Inner/sphere Reorganization Energy and Activation Energy of Self/exchange Electron Transfer Reaction for M(H2O)26+/3+ (M=V, Cr, Mn, Fe and Co) Systems

通过建立电子转移过程的活化模型和重组模型, 提出了用量子化学从头算方法研究电子转移过程内层重组能和活化能的新方法. 在UMP26/311G水平上获得了5对过渡金属水合离子体系M(H     

Studies of the inner reorganization energies of the cation radicals of 1,4-bis(dimethylamino)benzene, 9,10-bis(dimethylamino)anthracene, and 3,6-bis(dimethylamino)durene by photoelectron spectroscopy and reinterpretation of the mechanism of the electrochemical oxidation of the parent diamines

The inner reorganization energy of the cation radical of 1,4-bis(dimethylamino)benzene, 1, has been determined to be 0.72 +/- 0.02 eV by means of gas-phase photoelectron spectroscopy (PES). PES studies of 9,10-bis(dimethylamino)anthracene, 2, and 3,6-bis(dimethylamino)durene, 3, demonstrate that their reorganization energies are smaller than that of 1. The effect of lowering the inner reorganization energy on the rate constant for an electrochemical electron-transfer reaction is to increase the electron-transfer rate constant, k(s). However, voltammetric studies of the two-electron oxidation of 2 and 3 indicate that the values of k(s) for each step are smaller than those for 1, in contradistinction to the measured differences in reorganization energies. The voltammetric studies of 2 and 3 were reinterpreted according to a mechanism in which each step of oxidation was written as a two-step process, electron transfer with a small inner reorganization energy plus a chemical step of structural change. The agreement of simulations according to this mechanism with the experimental data was excellent. The new reaction scheme eliminated some suspicious features previously obtained with an analysis where electron transfer and structural change were considered to be concerted. In particular, all electron-transfer coefficients (alpha) were close to one-half, whereas the earlier treatment produced values of alpha much larger or smaller than one-half.     

Energetically driven reorganization of a modified catalytic surface under reaction conditions

The compositional and structural rearrangements at the catalyst surface during chemical reactions are issues of great importance for understanding and modeling the catalytic processes. Low-energy electron microscopy and photoelectron spectromicroscopy studies of the real-space structure and composition of a Au-modified Rh(110) surface during water formation reveal reorganization processes due to Au mass transport triggered by the propagating reaction fronts. The temporal evolution of the surface reaction results in a 'patterned' surface consisting of separated Au-rich and Au-poor phases with different oxygen coverage, Rh surface structure, and reactivity. The experimental results are complemented by ab initio electronic-structure calculations of the O and Au adsorption phases, which demonstrate that the reorganization of the Au adlayer by the propagating reaction fronts is an energetically driven process. Our findings suggest that reaction-induced spatial inhomogeneity in the surface composition and structure is a common feature of metal catalysts modified with adatoms which become mobile under reaction conditions.     

Determination of a large reorganization energy barrier for hydride abstraction by glucose oxidase

Glucose oxidase mediates the aerobic oxidation of simple sugars to lactones using a noncovalently bound flavin cofactor. The chemical mechanism of this reaction has been uncertain for many years. Here it is shown, using enzymes reconstituted with chemically modified cofactors, that sugar oxidation most likely occurs by concerted hydride (H-) abstraction. Studies of the kinetics and thermodynamics together with the application of Marcus theory reveal a large reorganization energy barrier. The magnitude of this intrinsic contribution appears characteristic of H- transfer in proteins and in solution. The observation that neither the thermodynamics nor reorganization energy is significantly altered in the glucose oxidase active site raises questions concerning how the redox reaction may be catalyzed.     

The dependence of the electrochemical charge-transfer coefficient on the electrode potential: Study of the Fe(CN)63−/Fe(CN)64− redox reaction on polycrystalline Au electrode in KF solutions

The kinetics of the Fe(CN)₆^3?/Fe(CN)₆^4? redox reaction on a polycrystalline gold electrode in KF solutions was studied by the potential step method. It was found that the apparent rate constant of this reaction changes approximately linearly with the KF concentration and that the apparent charge-transfer coefficient is a linear function of the electrode potential. The experimental results, which were analyzed considering the formation of ion pairs between the reactant and potassium cations and also considering the effect of the double layer can be interpreted on the basis of the quantum theory of the electron-transfer reaction through a bridge activated complex. The value of the reorganization energy of the classic subsystem λ=(0.47±0.06) eV calculated from our results is comparable with the λ value derived from the results of other authors.     

Activation entropy of electron transfer reactions

We report microscopic calculations of free energies and entropies for intramolecular electron transfer reactions. The calculation algorithm combines the atomistic geometry and charge distribution of a molecular solute obtained from quantum calculations with the microscopic polarization response of a polar solvent expressed in terms of its polarization structure factors. The procedure is tested on a donor–acceptor complex in which ruthenium donor and cobalt acceptor sites are linked by a four-proline polypeptide. The reorganization energies and reaction energy gaps are calculated as a function of temperature by using structure factors obtained from our analytical procedure and from computer simulations. Good agreement between two procedures and with direct computer simulations of the reorganization energy is achieved. The microscopic algorithm is compared to the dielectric continuum calculations. We found that the strong dependence of the reorganization energy on the solvent refractive index predicted by continuum models is not supported by the microscopic theory. Also, the reorganization and overall solvation entropies are substantially larger in the microscopic theory compared to continuum models.     

Theoretical Study on Electron Transfer Matrix Element in Oxidation of α—Amino Carbon—Centered Radical by O2

As a successive work of our previous paper,^1the electron transfer matrix element(Vrp)in the oxidation of the simplified model molecule of α-amino carbon-centered radical by O2 has been investigated with ab initio calculation at the level of UHF/6-31 G**.Based on the optimized geometries of the reactgant and the ion-pair complex obtained previously,the reaction heat and the iuner reorganization energy have been obtained by constructing the potential energy curves of reactant and product states considering the solvent effect with the conductor-like screening model(COSMO).The solvent reorganization energy has been estimated using Lippert-Mataga relationship.The calculated results show that the value of Vrp is several times larger than that of RT,which means that the model reaction is an adiabatic one.Theoretical investigation indicates that the solvent effect on the direct electron transfer (ET) process of oxidation of α-amino carbon-centered radical by oxygen is remarkable.