The <Emphasis Type="Italic">Saunders-Bell</Emphasis> Analysis of Tunnel Effects in Reactions with Kinetic Isotope Effects

Summary. The primary kinetic isotope effects of deuterium were investigated in 22 hydrogen and deuterium transfer reactions, including enzymatic and nonenzymatic hydride transfer reactions, elimination reactions, and reactions catalyzed by enzymes lipooxygenase, amine dehydrogenase, and methylmalonyl-CoA mutase. In each case, the Saunders-Bell analysis was applied to calculate the tunnel effects and the corresponding thermodynamic parameters. The Saunders-Bell analysis was effective in 14 cases out of 22. A high degree of correlation was found between the barrier factor, the tunnel factor, and the entropy factor among all reactions studied. From this, a general relationship between the three factors was derived, based on the Saunders-Bell analysis of the Bell equation; the Saunders-Bell analysis is valid within certain limits of the barrier factor. This general relationship is universally valid for all hydrogen/deuterium transfer reactions in nature with moderate tunneling, when the Saunders-Bell analysis applies.     

取代基对有机金属铼化合物中分子内α-氢转移反应势垒的影响

使用B3LYP方法研究了有机铼化合物R³R⁵(NHR⁴)Re(＝CHR¹)(＝NR²)中分子内α-氢转移反应, 探讨了不同取代基对α-氢转移反应势垒的影响. 研究发现, 可以通过改变取代基来影响过渡金属Re有机化合物中的α-氢转移反应. R¹位置的取代基为Me或CMe₃时, 可以较大程度降低α-氢转移反应的势垒. R²为H时, α-氢转移反应势垒最低. R³和R⁵位置为SiH₃时的反应势垒最低. R⁴为CMe₃时, α-氢转移反应势垒最低. 研究结果还表明, 取代基对于反应势垒的影响有加和性.     

Multicomponent QM study on the reaction of HOSO + NO2 with H2O: Nuclear quantum effect on structure and reaction energy profile

The hydrogen transfer reaction in the reaction of HOSO + NO₂ with and without H₂O have been investigated using multicomponent quantum-mechanics method, which can directly take nuclear quantum effect (NQE) of light nuclei into account. For the case of the reaction without H₂O, our calculation reveals that the reaction leading to trans-HONO is preferred. For the reaction with H₂O, water-non-mediated and water-mediated (hydrogen-relay) hydrogen transfer mechanism are investigated. The NQE of hydrogen nucleus lowers the relative energy of the stationary point structures and reduces the activation barrier of the reactions. The largest stabilization is found in the transition state structure of the hydrogen-relay type reaction. H/D isotope effects for the reactions are also analyzed. In particular, H/D isotope effect on the activation barrier is analyzed in detail with the aid of the active strain model.     

The ‘preference factor’ and isotope effect in the loss of hydrogen or deuterium from labeled toluenes

Metastable ion decompositions involving the loss of hydrogen and deuterium from partially deuterated toluene ions were studied using a double focusing mass spectrometer. The electric sector voltage was adjusted so that the only ions transmitted were those which lost a particular fraction of their kinetic energy in decompositions taking place in front of the electric sector. Transitions involving loss of mass 1 or mass 2 from the molecular ions of toluene-α-d₃ and toluene-2,3,4,5,6-d₅ were studied. The results showed that in these slow reactions, the ‘preference factor’ defined as the ratio of the probability of loss of a hydrogen atom from a side-chain position to loss of a hydrogen atom from a ring position was 1.00. The ‘isotope factor,’ defined as the ratio of the probability of loss of a hydrogen atom from any position to that for the loss of a deuterium atom from the same position was found to be 3·50.     

Unusual deuterium isotope effects in 13C NMR spectra of trans-stilbene

A detailed analysis of the ¹³C NMR spectra of trans-stilbene and ten deuteriated trans-stilbenes has been undertaken. Some unusual deuterium isotope effects on carbon–hydrogen spin–spin coupling constants could not be explained by the ordinary primary and secondary isotope effects. The positive and negative changes of ⁿJ(CH) were interpreted in terms of a steric effect, the vibrational influence of the C? D bond and the para-effect induced by deuterium. In this respect, deuterium behaves as a real substituent with electronic properties different from those of hydrogen. The deuterium isotope effects on ¹³C NMR chemical shifts and carbon–deuterium coupling constants have also been determined.     

Large Isotope Effects in Organometallic Chemistry

The kinetic isotope effect (KIE) is key to understanding reaction mechanisms in many areas of chemistry and chemical biology, including organometallic chemistry. This ratio of rate constants, k_H/k_D, typically falls between 1–7. However, KIEs up to 105 have been reported, and can even be so large that reactivity with deuterium is unobserved. We collect here examples of large KIEs across organometallic chemistry, in catalytic and stoichiometric reactions, along with their mechanistic interpretations. Large KIEs occur in proton transfer reactions such as protonation of organometallic complexes and clusters, protonolysis of metal–carbon bonds, and dihydrogen reactivity. C−H activation reactions with large KIEs occur with late and early transition metals, photogenerated intermediates, and abstraction by metal-oxo complexes. We categorize the mechanistic interpretations of large KIEs into the following three types: (a) proton tunneling, (b) compound effects from multiple steps, and (c) semi-classical effects on a single step. This comprehensive collection of large KIEs in organometallics provides context for future mechanistic interpretation.     

Effects of strong inter-hydrogen bond dynamical couplings in the polarized IR spectra of adipic acid crystals

This paper presents the results of the re-investigation of polarized IR spectra of adipic acid and of its d₂, d₈ and d₁₀ deuterium derivative crystals. The spectra were measured at 77 K by a transmission method using polarized light for two different crystalline faces. Theoretical analysis concerned linear dichroic effects and H/D isotopic effects observed in the spectra of the hydrogen and deuterium bonds in adipic acid crystals at the frequency ranges of the ν_O–H and the ν_O–D bands. The two-branch fine structure pattern of the ν_O–H and ν_O–D bands and the basic linear dichroic effects characterizing them were ascribed to the vibronic mechanism of vibrational dipole selection rule breaking for IR transitions in centrosymmetric hydrogen bond dimers. It was proved that for isotopically diluted crystalline samples of adipic acid, a non-random distribution of protons and deuterons occurs in the dimers (H/D isotopic “self-organization” effect). This effect results from the dynamical co-operative interactions involving the dimeric hydrogen bonds.     

An Interfacial View of Cation Effects on Electrocatalysis Systems

The identity of alkali metal cations in the electrolyte of electrocatalysis systems has been recently introduced as a crucial factor to tailor the kinetics and Faradaic efficiency of many electrocatalytic reactions. In this Minireview, we have summarized the recent advances in the molecular-level understanding of cation effects on relevant electrocatalytic processes such as hydrogen evolution (HER), oxygen evolution (OER), and CO₂ electroreduction (CO₂RR) reactions. The discussion covers the effects of electrolyte cations on interfacial electric fields, structural organization of interfacial water molecules, blocking the catalytic active sites, stabilization or destabilization of intermediates, and interfacial pHs. These cation-induced interfacial phenomena have been reported to impact the performance (activity, selectivity, and stability) of electrochemical reactions collaboratively or independently. We describe that although there is almost a general agreement on the relationship between the size of alkali cations and the activities of HER, OER, and CO₂RR, however, the mechanism by which the performance of these electrocatalytic reactions is influenced by alkali metal cations is still in debate.     

Theoretical Study of Structure,Energetic, Hydrogen Bonds Strength and Intramolecular Proton Transfer of 2‐(2‐R (ROH,NH2, SH) Phenyl (or Pyridyl)) Benzoxazoles (or Benzothiazoles)

The ground‐ and excited‐state intramolecular proton transfer processes of 2‐(2‐R (R?OH, NH₂, SH) phenyl (or pyridyl)) benzoxazoles (or benzothiazoles) are investigated by the DFT methods. The calculated results indicate that in the ground state there is a high correlation (R=0.9950) between the proton transfer barrier and the intramolecular hydrogen bonds (IMHB) strength. The increase of the strength of IMHB in the proton transfer processes leads to a larger barrier contributions. Intramolecular proton transfer process pathway is along with the minimal difference of change value in the IMHB angle. In the excited‐state, there is a similar relationship between the IMHB and the barrier.     

N-Cα bond cleavage of the peptide backbone via hydrogen abstraction

The specific cleavage of N-C_α bonds on the peptide backbone to form the so-called ‘c’ and ‘z + 2’ products, which can be used for the rapid determination of protein amino-acid sequences, has been examined to clarify the mechanism(s) that occur during hydrogen abstraction induced by bombardment with 337-nm laser photons in matrix-assisted laser desorption/ionization (MALDI) method. Intramolecular hydrogen abstraction, which results from the hydrogen(s) on the C_α or C_β carbon, did not occur with a deuterium-labeled dodecapeptide. To confirm a proposition that intermolecular hydrogen abstraction occurs between the peptide and the MALDI matrix, a deuterium dodecapeptide embedded in a deuterium 2,5-dihydroxybenzoic acid matrix at a molar ratio of 1:7000 was analyzed. The resulting deuterium c product ions suggested that c ions form via intermolecular hydrogen abstraction, although the results obtained did not deny any other possibilities such as intramolecular transfer of labile hydrogen. A mechanism for the N-C_α bond cleavage has been proposed that the formation of hypervalent radical species and subsequent prompt bond cleavages occur. The proposed mechanism successfully rationalizes the formation of both the z + 2 and the c product ions.     

Two-dimensional vibrational analysis of the Lippincott-Schröder potential for OHO,NHO and NHN hydrogen bonds and the deuterium isotope effect

Two-dimensional vibrational analyses [i.e. crude adiabatic approximation, SCF approximation and variational method (crude adiabatic basis function)] are performed on the hydrogen bond systems consisting of the Lippincott-Schröder potentials for the OHO, NHO and NHN bonds. The OHO and NHN systems are supposed to be linear and the bent structure is considered for the NHO system. The frequency shift for the hydrogen bond length variation and its deuterium substitution effects are in good agreement with experiment. The anomalies in the frequency ratio ν_OH/ν_OD at an O—O distance of 2.5 Å, and in the interminimum distance shift on deuteration at 2.5 Å are well explained as the difference of double minimum behavior between the vibrational states of proton and deuterium. It is also shown that the Lippincott-Schröder model for the OHO system supplies the general features for proton tunneling, proton delocalization beyond the barrier and other type processes in hydrogen bonds.     

Deuterium isotope effects on 13C NMR chemical shifts of some α-(2-hydroxyaryl)-N-phenylnitrones (Schiff base N-oxides)

The deuterium isotope effect on the ¹³C NMR chemical shifts of some α-2-hydroxyaryl-N-phenylnitrones (Schiff base N-oxides) was studied. The existence of an intramolecular hydrogen bond with the proton localized on the phenolic oxygen atom was evidenced. Exceptionally large isotope effects ΔC-2(D) and ΔC-α(D) suggest that the substitution of the proton of the OH group by deuterium leads to a weakening of the hydrogen bond and some conformational changes in the molecule. This conclusion was drawn on the basis of a comparison of the deuterium isotope effects of Schiff base N-oxides and parent Schiff bases. Copyright © 2001 John Wiley & Sons, Ltd.     

Rate-promoting vibrations and coupled hydrogen-electron transfer reactions in the condensed phase: a model for enzymatic catalysis

A model is presented for coupled hydrogen-electron transfer reactions in condensed phase in the presence of a rate promoting vibration. Large kinetic isotope effects (KIEs) are found when the hydrogen is substituted with deuterium. While these KIEs are essentially temperature independent, reaction rates do exhibit temperature dependence. These findings agree with recent experimental data for various enzyme-catalyzed reactions, such as the amine dehydrogenases and soybean lipoxygenase. Consistent with earlier results, turning off the promoting vibration results in an increased KIE. Increasing the barrier height increases the KIE, while increasing the rate of electron transfer decreases it. These results are discussed in light of other views of vibrationally enhanced tunneling in enzymes.     

Isomeric Effect on H/D Exchange of Resveratrol Studied by NMR Spectroscopy

Resveratrol (3,5,4′‐trihydroxylstilbene), a phytoalexin in response to injury or fungal attack, is found in grapes and other food products. It has been well documented that the compound has beneficial effects as hypolipidemic, anticancer, antiviral, neuroprotective, antiaging, and anti‐inflammatory natural active principle. It was observed that both trans‐ and cis‐resveratrols undergo hydrogen‐deuterium (H/D) exchange at H‐2,6 and H‐4 positions of the A‐ring. The exchange rates were determined by ¹H NMR spectroscopy. The results reveal that the exchange rates are configuration and pH dependent. Derivative of 2‐O‐β‐D‐glucoside can significantly speed up the H/D exchange reactions for both isomers. The trans‐resveratrol experiences faster H/D exchanging than the cis‐resveratrol. Such isomeric effect is possibly due to the factor that the trans‐resveratrol is in favor of forming larger/super conjugative system and has less spatial interference. Theoretical calculation shows that electronegativity at these positions is in the order of H‐2,6>H‐4, which is in consistent with the exchange rates observed by NMR. The results may be of help in understanding the properties of resveratrol, and in analysis of resveratrol in natural products or body fluids using mass spectroscopy that occasionally requires stable deuterium isotope labeling.     

A Semi-Empirical Model of the Energy Barrier of Proton Transfer Reactions

The energy barrier in proton transfer reactions is described by a Johnston-type equation (1) (n = order of bond to be broken). The barrier model is discussed in terms of free energies. The V_i values are free energies of ionic cleavage in aqueous solution of the X? H and Y? H bonds; they are computed from eqns. (4c) and (4d). The values of p₁ and p₂ affect curvature (absence or presence of maximum) and symmetry of the barrier. It is postulated that pi is a typical constant of the reacting bond and can be transferred from one transition state to another. With the aid of eqn. (1) and its first derivative, values of pi and n_m (bond order at maximum of barrier) can be based on quantities determined experimentally, Δ≠ and ΔG. For O? H bonds, pi ≈ 1.0. For C? H bonds pi is larger than 1.0 and depends on the structure of the carbanionic moiety (influence of resonance and inductive effects). As there cannot be a maximum if p₁ = p₂ = 1.0, the suggested model of the barrier leads to a better understanding why proton transfer must be ‘fast’ in some reactions and ‘slow’ in others. The computed values of n_m may be utilized to gain some insight into the nature of the transition states; they supply a basis for the discussion of primary hydrogen isotope effects.     

The tunneling dynamics of the low temperature H exchange reactions

A simple method for calculating of the tunneling linear hydrogen atom exchange reaction is proposed for heavy reactants Its main feature is the competing of two sniall probabilities of a sufficientiv close reactant approaching and of H transfer. The good accuracy and the validity of the whole tunnel dynamics picture are confirmed by the numerical results obtained bv the classical S-matrix method modified for strongly exothermic reactions. The study of temperature dependences and isotopic effects of the linear H exchange reactions with a number of typical potential energy surfaces yields for the reaction barrier a value significantly higher than that given by simple one-dimensional barrier penetrability calculations.     

钐(II)类卡宾CH3SmCH2I与乙烯环丙烷化反应及溶剂化效应的理论研究

用密度泛函B3LYP方法研究了过渡金属钐类卡宾与乙烯的环丙烷化反应的机理. 对钐类卡宾试剂CH₃SmCH₂I和CH₂CH₂反应的反应物、中间体、过渡态和产物构型的全部结构几何参数进行了优化, 并计算了THF溶液的溶剂化效应, 用内禀反应坐标(IRC)计算和频率分析方法, 对过渡态进行了验证. 结果表明: CH₃SmCH₂I与CH₂CH₂环丙烷化反应按亚甲基转移机理(通道A)和卡宾金属化机理(通道B)都可以进行, 与锂类卡宾的反应机理相同, 通道A比通道B反应的势垒降低了14.65 kJ/mol. 溶剂化效应使通道B比通道A的反应势垒大幅度提高, 更有利于反应沿通道A进行, 而不利于通道B.     

Kinetics of the interaction of ketyl and semiquinone radicals with dioxygen. Concerted electron and proton transfer involving ketyl and semiquinone radicals

Kinetics of the interaction of ketyl and neutral semiquinone radicals with dioxygen was studied by the flash photolysis technique. The reactivity of neutral semiquinone radicals in the transfer of a hydrogen atom to O₂ is lower than that of ketyl radicals and increases as the reduction ability of the radicals increases, which give evidence for the charge transfer from the radicals to O₂ in the transition state of the reaction. The deuterium kinetic isotope effect of the reaction (up to 2.6) suggests considerable weakening of the O−H bond of the seminquinone radical in the transition state. A cyclic structure of the transition state similar to that in the reactions of ketyl radicals with hydrogen atom acceptors is proposed. In aprotic volvents, solvation has essentially no effect on the reactivity of neutral anthrasemiquinone radicals up to solvent nucleophilicityB≈240. In solvents with higher nucleophilicity and in protic solvents, their reactivity drops sharply. Hydrogen atom transfer reactions involving ketyl and neutral semiquinone radicals are shown to involve concerted electron and proton transfers, and to have transition states in which the partial transfer of an electron and a proton from the ketyl or semiquinone radical to an acceptor occurs. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1131–1137, June, 1997.     

Deuterium isotope effects on 15N chemical shifts of double Schiff bases in the solid state and solution

The proton transfer equilibrium in a series of double Schiff base derivatives of trans‐1,2‐diaminocyclohexane in solution and the solid state was studied by means of ¹⁵N NMR spectroscopy and analysis of the deuterium isotope effect on the chemical shifts Δ¹⁵N(D). The presence of a proton transfer equilibrium in the N‐2‐hydroxynaphthylidene moieties of the Schiff bases studied in the solid state at room temperature was evidenced. The results confirmed the interrelation of the two hydrogen bonds in double Schiff base derivatives of trans‐1,2‐diaminocyclohexane. Copyright © 2003 John Wiley & Sons, Ltd.     

Tunneling Assists the 1,2‐Hydrogen Shift in N‐Heterocyclic Carbenes

At room temperature, 1,2‐hydrogen‐transfer reactions of N‐heterocyclic carbenes, like the imidazol‐2‐ylidene to give imidazole is shown to occurr almost entirely (>90 %) by quantum mechanical tunneling (QMT). At 60 K in an Ar matrix, for the 2, 3‐dihydrothiazol‐2‐ylidene→thiazole transformation, QMT is shown to increase the rate about 10⁵ times. Calculations including small‐curvature tunneling show that the barrier for intermolecular 1,2‐hydrogen‐transfer reaction is small, and QMT leads to a reduced rate of the forward reaction because of nonclassical reflections even at room temperature. A small barrier also leads to smaller kinetic isotope effects because of efficient QMT by both H and D. QMT does not always lead to faster reactions or larger KIE values, particularly when the barrier is small.