Ensemble‐Averaged QM/MM Kinetic Isotope Effects for the SN2 Reaction of Cyanide Anions with Chloroethane in DMSO Solution

The existence of solvent fluctuations leads to populations of reactant‐state (RS) and transition‐state (TS) configurations and implies that property calculations must include appropriate averaging over distributions of values for individual configurations. Average kinetic isotope effects 〈KIE〉 for NC^?+EtCl→NCEt+Cl^? in DMSO solution at 30 °C are best obtained as the ratio 〈f_RS〉/〈f_TS〉 of isotopic partition function ratios separately averaged over all RS and TS configurations. In this way the hybrid AM1/OPLS‐AA potential yields 〈KIE〉 values for all six isotopic substitutions (2° α‐²H₂, 2° β‐²H₃, α‐¹¹C/¹⁴C, leaving group ³⁷Cl, and nucleophile ¹³C and ¹⁵N) for this reaction in the correct direction as measured experimentally. These thermally‐averaged calculated KIEs may be compared meaningfully with experiment, and only one of them differs in magnitude from the experimental value by more than one standard deviation from the mean. This success contrasts with previous KIE calculations based upon traditional methods without averaging. The isotopic partition function ratios are best evaluated using all (internal) vibrational and (external) librational frequencies obtained from Hessians determined for subsets of atoms, relaxed to local minima or saddle points, within frozen solvent environments of structures sampled along molecular dynamics trajectories for RS and TS. The current method may perfectly well be implemented with other QM or QM/MM methods, and thus provides a useful tool for investigating KIEs in relation to studies of chemical reaction mechanisms in solution or catalyzed by enzymes.     

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.     

Substrate‐Dependent H/D Kinetic Isotope Effects and the Role of the Di(μ‐oxo)diiron(IV) Core in Soluble Methane Monooxygenase: A Theoretical Study

Soluble methane monooxygenase (sMMO) is an enzyme that converts alkanes to alcohols using a di(μ‐oxo)diiron(IV) intermediate Q at the active site. Very large kinetic isotope effects (KIEs) indicative of significant tunneling are observed for the hydrogen transfer (H‐transfer) of CH₄ and CH₃CN; however, a relatively small KIE is observed for CH₃NO₂. The detailed mechanism of the enzymatic H‐transfer responsible for the diverse range of KIEs is not yet fully understood. In this study, variational transition‐state theory including the multidimensional tunneling approximation is used to calculate rate constants to predict KIEs based on the quantum‐mechanically generated intrinsic reaction coordinates of the H‐transfer by the di(μ‐oxo)diiron(IV) complex. The results of our study reveal that the role of the di(μ‐oxo)diiron(IV) core and the H‐transfer mechanism are dependent on the substrate. For CH₄, substrate binding induces an electron transfer from the oxygen to one Fe^IV center, which in turn makes the μ‐O ligand more electrophilic and assists the H‐transfer by abstracting an electron from the C?H σ orbital. For CH₃CN, the reduction of Fe^IV to Fe^III occurs gradually with substrate binding and H‐transfer. The charge density and electrophilicity of the μ‐O ligand hardly change upon substrate binding; however, for CH₃NO₂, there seems to be no electron movement from μ‐O to Fe^IV during the H‐transfer. Thus, the μ‐O ligand appears to abstract a proton without an electron from the C?H σ orbital. The calculated KIEs for CH₄, CH₃CN, and CH₃NO₂ are 24.4, 49.0, and 8.27, respectively, at 293 K, in remarkably good agreement with the experimental values. This study reveals that diverse KIE values originate mainly from tunneling to the same di(μ‐oxo)diiron(IV) core for all substrates, and demonstrate that the reaction dynamics are essential for reproducing experimental results and understanding the role of the diiron core for methane oxidation in sMMO.     

Theoretical prediction on the thermal stability of cyclic ozone and strong oxygen tunneling

Dual-level dynamics calculation with variational transition state theory including multidimensional tunneling has been performed on the isomerization reaction of cyclic ozone → normal (open) ozone, which was believed to be the stability-determining reaction of the elusive cyclic ozone molecule under thermal condition. The high-level potential energy surface data were obtained from the calculation using the MRCISD+Q theory with the aug-cc-pVQZ basis set, while the low-level reaction path information was obtained using the hybrid density functional theory B3LYP with the cc-pVTZ basis set. The calculated results showed very significant tunneling effects below 300 K (a factor of ～200 at 300 K and over 10(7) at 200 K). Because of the strong tunneling effects and the potential energy surface crossing of the 1A(1) and 1A(2) states, the isomerization reactions were found to be significantly faster than previously believed. The half-life of the cyclic ozone was estimated only ～10 s at 200 K and ～70 s below 100 K, which might partly explain the unsuccessful attempts for its experimental identification. The kinetic isotope effects (KIEs) for various (18)O substitution reactions were also calculated as a function of temperature and were as high as 10 at very low temperature. Because of the large KIEs, the experimental identification of the cyclic (18)O(3) seems more promising.     

Intermolecular insertion of an N,N-heterocyclic carbene into a nonacidic C-H bond: Kinetics, mechanism and catalysis by (K-HMDS)2 (HMDS = Hexamethyldisilazide)

The reaction of 2‐[¹³C]‐1‐ethyl‐3‐isopropyl‐3,4,5,6‐tetrahydropyrimidin‐1‐ium hexafluorophosphate ([¹³C₁]‐ 1 ‐PF₆) with a slight excess (1.03 equiv) of dimeric potassium hexamethyldisilazide (“(K‐HMDS)₂”) in toluene generates 2‐[¹³C]‐3‐ethyl‐1‐isopropyl‐3,4,5,6‐tetrahydropyrimid‐2‐ylidene ([¹³C₁]‐ 2 ). The hindered meta‐stable N,N‐heterocyclic carbene [¹³C₁]‐ 2 thus generated undergoes a slow but quantitative reaction with toluene (the solvent) to generate the aminal 2‐[¹³C]‐2‐benzyl‐3‐ethyl‐1‐isopropylhexahydropyrimidine ([¹³C₁]‐ 14 ) through formal C? H insertion of C(2) (the “carbene carbon”) at the toluene methyl group. Despite a significant pK_a mismatch (ΔpK_a 1 ⁺ and toluene estimated to be ca. 16 in DMSO) the reaction shows all the characteristics of a deprotonation mechanism, the reaction rate being strongly dependent on the toluene para substituent (ρ=4.8(±0.3)), and displaying substantial and rate‐limiting primary (k_H/k_D=4.2(±0.6)) and secondary (k_H/k_D=1.18(±0.08)) kinetic isotope effects on the deuteration of the toluene methyl group. The reaction is catalysed by K‐HMDS, but proceeds without cross over between toluene methyl protons and does not involve an HMDS anion acting as base to generate a benzyl anion. Detailed analysis of the reaction kinetics/kinetic isotope effects demonstrates that a pseudo‐first‐order decay in 2 arises from a first‐order dependence on 2 , a first‐order dependence on toluene (in large excess) and, in the catalytic manifold, a complex noninteger dependence on the K‐HMDS dimer. The rate is not satisfactorily predicted by equations based on the Brønsted salt‐effect catalysis law. However, the rate can be satisfactorily predicted by a mole‐fraction‐weighted net rate constant: ?d[ 2 ]/dt=({x ₂ k_uncat}+{(1?x ₂ ) k_cat})[ 2 ]¹[toluene]¹, in which x ₂ is determined by a standard bimolecular complexation equilibrium term. The association constant (K_a) for rapid equilibrium–complexation of 2 with (K‐HMDS)₂ to form [ 2 (K‐HMDS)₂] is extracted by nonlinear regression of the ¹³C NMR shift of C(2) in [¹³C₁]‐ 2 versus [(K‐HMDS)₂] yielding: K_a=62(±7) M ^?1; δ_C(2) in 2 =237.0 ppm; δ_C(2) in [ 2 (K‐HMDS)₂]=226.8 ppm. It is thus concluded that there is discrete, albeit inefficient, molecular catalysis through the 1:1 carbene/(K‐HMDS)₂ complex [ 2 (K‐HMDS)₂], which is found to react with toluene more rapidly than free 2 by a factor of 3.4 (=k_cat/k_uncat). The greater reactivity of the complex [ 2 (K‐HMDS)₂] over the free carbene ( 2 ) may arise from local Brønsted salt‐effect catalysis by the (K‐HMDS)₂ liberated in the solvent cage upon reaction with toluene.     

Kinetic isotope effects calculated with the instanton method

The ring-opening reaction of the cyclopropylcarbinyl radical proceeds via heavy-atom tunneling at low temperature. We used instanton theory to calculate tunneling rates and kinetic isotope effects with on-the-fly calculation of energies by density functional theory (B3LYP). The accuracy was verified by explicitly correlated coupled-cluster calculations (UCCSD(T)-F12). At cryogenic temperatures, we found protium/deuterium KIEs up to 13 and inverse KIEs down to 0.2. We also studied an intramolecular tautomerization reaction. A simple and computationally efficient method is proposed to calculate KIEs with the instanton method: the instanton path is assumed to be independent of the atomic masses. This results in surprisingly good estimates of the KIEs for the cyclopropylcarbinyl radical and for the secondary KIEs of the tautomerization. Challenges and capabilities of the instanton method for calculating KIEs are discussed.     

Understanding the Mechanisms of Unusually Fast HH,CH,and CC Bond Reductive Eliminations from Gold(III) Complexes

Carbon–carbon bond reductive elimination from gold(III) complexes are known to be very slow and require high temperatures. Recently, Toste and co‐workers have demonstrated extremely rapid C?C reductive elimination from cis‐[AuPPh₃(4‐F‐C₆H₄)₂Cl] even at low temperatures. We have performed DFT calculations to understand the mechanistic pathway for these novel reductive elimination reactions. Direct dynamics calculations inclusive of quantum mechanical tunneling showed significant contribution of heavy‐atom tunneling (>25 %) at the experimental reaction temperatures. In the absence of any competing side reactions, such as phosphine exchange/dissociation, the complex cis‐[Au(PPh₃)₂(4‐F‐C₆H₄)₂]⁺ was shown to undergo ultrafast reductive elimination. Calculations also revealed very facile, concerted mechanisms for H?H, C?H, and C?C bond reductive elimination from a range of neutral and cationic gold(III) centers, except for the coupling of sp³ carbon atoms. Metal–carbon bond strengths in the transition states that originate from attractive orbital interactions control the feasibility of a concerted reductive elimination mechanism. Calculations for the formation of methane from complex cis‐[AuPPh₃(H)CH₃]⁺ predict that at ?52 °C, about 82 % of the reaction occurs by hydrogen‐atom tunneling. Tunneling leads to subtle effects on the reaction rates, such as large primary kinetic isotope effects (KIE) and a strong violation of the rule of the geometric mean of the primary and secondary KIEs.     

Combined QM/MM and path integral simulations of kinetic isotope effects in the proton transfer reaction between nitroethane and acetate ion in water

An integrated Feynman path integral-free energy perturbation and umbrella sampling (PI-FEP/UM) method has been used to investigate the kinetic isotope effects (KIEs) in the proton transfer reaction between nitroethane and acetate ion in water. In the present study, both nuclear and electronic quantum effects are explicitly treated for the reacting system. The nuclear quantum effects are represented by bisection sampling centroid path integral simulations, while the potential energy surface is described by a combined quantum mechanical and molecular mechanical (QM/MM) potential. The accuracy essential for computing KIEs is achieved by a FEP technique that transforms the mass of a light isotope into a heavy one, which is equivalent to the perturbation of the coordinates for the path integral quasiparticle in the bisection sampling scheme. The PI-FEP/UM method is applied to the proton abstraction of nitroethane by acetate ion in water through molecular dynamics simulations. The rule of the geometric mean and the Swain-Schaad exponents for various isotopic substitutions at the primary and secondary sites have been examined. The computed total deuterium KIEs are in accord with experiments. It is found that the mixed isotopic Swain-Schaad exponents are very close to the semiclassical limits, suggesting that tunneling effects do not significantly affect this property for the reaction between nitroethane and acetate ion in aqueous solution.     

Carbon-13 kinetic isotope effects in the decarbonylations of lactic acid containing13C at the natural abundance level

The¹³C kinetic isotope fractionation in the decarbonylation of lactic acid of natural isotopic composition by sulfuric acid has been studied in the temperature range of 20–80°C. The¹³C₍₁₎ isotope separation in the decarbonylation of lactic acid by concentrated sulfuric acid depends strongly on the temperature above 40°C. Below this temperature the¹³C isotope effect in the decarbonylation of lactic acid by concentrated sulfuric acid is normal similarly as has been found inthe decarbonylation of lactic [1-¹⁴C] acid. The experimental values of k(¹²C)/k(¹³C) ratios of isotopic rate constants for¹²C and¹³C are close to, but slightly higher than theoretical¹³C-kinetic isotope effects calculated (neglecting tunneling) under the asumption that the C₍₁₎-OH bond is broken in the rate-controlling step of the dehydration reaction. Dilution of concentrated sulfuric acid with water up to 1.4 molar (H₂O)/(H₂SO₄) ratio caused the increase of the¹³C isotope fractionation from 1.0273 found in concentrated sulfuric acid at 80.5°C to 1.0536±0.0008 (at 80.6°C). A discussion of the abnormally high temperature dependence of¹⁴C and¹³C isotope fractionation in this reaction and the discussion of the problem of relative¹⁴C/¹³C kinetic isotope effects is given.     

Investigating Inner-Sphere Reorganization via Secondary Kinetic Isotope Effects in the C-H Cleavage Reaction Catalyzed by Soybean Lipoxygenase: Tunneling in the Substrate Backbone as Well as the Transferred Hydrogen

This work describes the application of NMR to the measurement of secondary deuterium (2° (2)H) and carbon-13 ((13)C) kinetic isotope effects (KIEs) at positions 9-13 within the substrate linoleic acid (LA) of soybean lipoxygenase-1. The KIEs have been measured using LA labeled with either protium (11,11-h2-LA) or deuterium (11,11-d2-LA) at the reactive C11 position, which has been previously shown to yield a primary deuterium isotope effect of ca. 80. The conditions of measurement yield the intrinsic 2° (2)H and (13)C KIEs on k(cat)/K(m) directly for 11,11-d2-LA, whereas the values for the 2° (2)H KIEs for 11,11-h2-LA are obtained after correction for a kinetic commitment. The pattern of the resulting 2° (2)H and (13)C isotope effects reveals values that lie far above those predicted from changes in local force constants. Additionally, many of the experimental values cannot be modeled by electronic effects, torsional strain, or the simple inclusion of a tunneling correction to the rate. Although previous studies have shown the importance of extensive tunneling for cleavage of the primary hydrogen at C11 of LA, the present findings can only be interpreted by extending the conclusion of nonclassical behavior to the secondary hydrogens and carbons that flank the position undergoing C-H bond cleavage. A quantum mechanical method introduced by Buhks et al. [J. Phys. Chem. 1981, 85, 3763] to model the inner-sphere reorganization that accompanies electron transfer has been shown to be able to reproduce the scale of the 2° (2)H KIEs.     

Computational studies on the mechanism and kinetics of Cl reaction with C2H5I

The dual‐level direct kinetics method has been used to investigate the multichannel reactions of C₂H₅I + Cl. Three hydrogen abstraction channels and one displacement process are found for the title reaction. The calculation indicates that the hydrogen abstraction from ? CH₂? group is the dominant reaction channel, and the displacement process may be negligible because of the high barrier. The rate constants for individual reaction channels are calculated by the improved canonical variational transition‐state theory with small‐curvature tunneling correction over the temperature range of 220–1500 K. Our results show that the tunneling correction plays an important role in the rate constant calculation in the low‐temperature range. Agreement between the calculated and experimental data available is good. The Arrhenius expression k(T) = 2.33 × 10^?16 T^1.83 exp(?185.01/T) over a wide temperature range is obtained. Furthermore, the kinetic isotope effects for the reaction C₂H₅I + Cl are estimated so as to provide theoretical estimation for future laboratory investigation. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010     

Fast Heavy‐Atom Tunneling in Trifluoroacetyl Nitrene

Chemical reactions involving quantum mechanical tunneling (QMT) increasingly attract the attention of scientists. In contrast to the hydrogen‐tunneling as frequently observed in chemistry and biology, tunneling solely by heavy atoms is rare. Herein, we report heavy‐atom tunneling in trifluoroacetyl nitrene, CF₃C(O)N. The carbonyl nitrene CF₃C(O)N in the triplet ground state was generated in cryogenic matrices by laser (193 or 266 nm) photolysis of CF₃C(O)N₃ and characterized by IR and EPR spectroscopy. In contrast to the theoretically predicted activation barriers (>10 kcal mol⁻¹), CF₃C(O)N undergoes rapid rearrangement into CF₃NCO with half‐life times of less than 10 min and unprecedentedly large ¹⁴N/¹⁵N kinetic isotope effects (1.18–1.33) in solid Ar, Ne, and N₂ matrices even at 2.8 K. The tunneling disappearance of CF₃C(O)N becomes much slower in the chemically active toluene and in 2‐methyltetrahydrofuran at 5 K.     

Catalytic Mechanism of a Heme and Tyrosyl Radical-Containing Fatty Acid α-(Di)oxygenase

The steady-state catalytic mechanism of a fatty acid α-(di)oxygenase is examined, revealing that a persistent tyrosyl radical (Tyr379(?)) effects O(2) insertion into C(α)-H bonds of fatty acids. The initiating C(α)-H homolysis step is characterized by apparent rate constants and deuterium kinetic isotope effects (KIEs) that increase hyperbolically upon raising the concentration of O(2). These results are consistent with H(?) tunneling, transitioning from a reversible to an irreversible regime. The limiting deuterium KIEs increase from ～30 to 120 as the fatty acid chain is shortened from that of the native substrate. In addition, activation barriers increase in a manner that reflects decreased fatty acid binding affinities. Anaerobic isotope exchange experiments provide compelling evidence that Tyr379(?) initiates catalysis by H(?) abstraction. C(α)-H homolysis is kinetically driven by O(2) trapping of the α-carbon radical and reduction of a putative peroxyl radical intermediate to a 2(R)-hydroperoxide product. These findings add to a body of work which establishes large-scale hydrogen tunneling in proteins. This particular example is novel because it involves a protein-derived amino acid radical.     

Experimental and theoretical multiple kinetic isotope effects for an SN2 reaction. An attempt to determine transition-state structure and the ability of theoretical methods to predict experimental kinetic isotope effects

The secondary alpha-deuterium, the secondary beta-deuterium, the chlorine leaving-group, the nucleophile secondary nitrogen, the nucleophile (12)C/(13)C carbon, and the (11)C/(14)C alpha-carbon kinetic isotope effects (KIEs) and activation parameters have been measured for the S(N)2 reaction between tetrabutylammonium cyanide and ethyl chloride in DMSO at 30 degrees C. Then, thirty-nine readily available different theoretical methods, both including and excluding solvent, were used to calculate the structure of the transition state, the activation energy, and the kinetic isotope effects for the reaction. A comparison of the experimental and theoretical results by using semiempirical, ab initio, and density functional theory methods has shown that the density functional methods are most successful in calculating the experimental isotope effects. With two exceptions, including solvent in the calculation does not improve the fit with the experimental KIEs. Finally, none of the transition states and force constants obtained from the theoretical methods was able to predict all six of the KIEs found by experiment. Moreover, none of the calculated transition structures, which are all early and loose, agree with the late (product-like) transition-state structure suggested by interpreting the experimental KIEs.     

A Spectroscopic Overview of Intramolecular Hydrogen Bonds of NH…O,S,N Type

Intramolecular NH…O,S,N interactions in non-tautomeric systems are reviewed in a broad range of compounds covering a variety of NH donors and hydrogen bond acceptors. ¹H chemical shifts of NH donors are good tools to study intramolecular hydrogen bonding. However in some cases they have to be corrected for ring current effects. Deuterium isotope effects on ¹³C and ¹⁵N chemical shifts and primary isotope effects are usually used to judge the strength of hydrogen bonds. Primary isotope effects are investigated in a new range of magnitudes. Isotope ratios of NH stretching frequencies, νNH/ND, are revisited. Hydrogen bond energies are reviewed and two-bond deuterium isotope effects on ¹³C chemical shifts are investigated as a possible means of estimating hydrogen bond energies.     

Solvent as a Probe of Active Site Motion and Chemistry during the Hydrogen Tunnelling Reaction in Morphinone Reductase

The reductive half‐reaction of morphinone reductase involves a hydride transfer from enzyme‐bound β‐nicotinamide adenine dinucleotide (NADH) to a flavin mononucleotide (FMN). We have previously demonstrated that this step proceeds via a quantum mechanical tunnelling mechanism. Herein, we probe the effect of the solvent on the active site chemistry. The pK_a of the reduced FMN N1 is 7.4±0.7, based on the pH‐dependence of the FMN midpoint potential. We rule out that protonation of the reduced FMN N1 is coupled to the preceding H‐transfer as both the rate and temperature‐dependence of the reaction are insensitive to changes in solution pH above and below this pK_a. Further, the solvent kinetic isotope effect is ～1.0 and both the 1° and 2° KIEs are insensitive to solution pH. The effect of the solvent’s dielectric constant is investigated and the rate of H‐transfer is found to be unaffected by changes in the dielectric constant between ～60 and 80. We suggest that, while there is crystallographic evidence for some water in the active site, the putative promoting motion involved in the H‐tunnelling reaction is insensitive to such changes.     

The Kinetic Isotope Effect as a Probe of Spin Crossover in the CH Activation of Methane by the FeO+ Cation

Two‐state reactivity (TSR) is often used to explain the reaction of transition‐metal–oxo reagents in the bare form or in the complex form. The evidence of the TSR model typically comes from quantum‐mechanical calculations for energy profiles with a spin crossover in the rate‐limiting step. To prove the TSR concept, kinetic profiles for C? H activation by the FeO⁺ cation were explored. A direct dynamics approach was used to generate potential energy surfaces of the sextet and quartet H‐transfers and rate constants and kinetic isotope effects (KIEs) were calculated using variational transition‐state theory including multidimensional tunneling. The minimum energy crossing point with very large spin–orbit coupling matrix element was very close to the intrinsic reaction paths of both sextet and quartet H‐transfers. Excellent agreement with experiments were obtained when the sextet reactant and quartet transition state were used with a spin crossover, which strongly support the TSR model.     

Four‐bond deuterium isotope effects on the chemical shifts of amide nitrogens in proteins

An approach towards precision NMR measurements of four‐bond deuterium isotope effects on the chemical shifts of backbone amide nitrogen nuclei in proteins is described. Three types of four‐bond ¹⁵ N deuterium isotope effects are distinguished depending on the site of proton‐to‐deuterium substitution: ⁴ΔN(N_i‐1D), ⁴ΔN(N_i+1D) and ⁴ΔN(C_β,i‐1D). All the three types of isotope shifts are quantified in the (partially) deuterated protein ubiquitin. The ⁴ΔN(N_i+1D) and ⁴ΔN(C_β,i‐1D) effects are by far the largest in magnitude and vary between 16 and 75 ppb and ?18 and 46 ppb, respectively. A semi‐quantitative correlation between experimental ⁴ΔN(N_i+1D) and ⁴ΔN(C_β,i‐1D) values and the distances between nitrogen nuclei and the sites of ¹H‐to‐D substitution is noted. The largest isotope shifts in both cases correspond to the shortest inter‐nuclear distances. Copyright © 2013 John Wiley & Sons, Ltd.     

Hydrogen-Atom Tunneling in Metaphosphorous Acid

Metaphosphorous acid (HOPO), a key intermediate in phosphorus chemistry, has been generated in syn- and anti-conformations in the gas phase by high-vacuum flash pyrolysis (HVFP) of a molecular precursor ethoxyphosphinidene oxide (EtOPO→C₂H₄+HOPO) at ca. 1000 K and subsequently trapped in an N₂-matrix at 2.8 K. Unlike the two conformers of the nitrogen analogue HONO, the anti-conformer of HOPO undergoes spontaneous rotamerization at 2.8 K via hydrogen-atom tunneling (HAT) with noticeable kinetic isotope effects for H/D (>10⁴ for DOPO) and ¹⁶O/¹⁸O (1.19 for H¹⁸OPO and 1.06 for HOP¹⁸O) in N₂-matrices.     

Aqueous Oxidations Started by TiO2 Photoinduced Holes Can Be a Rate‐Determining Step

In aqueous TiO₂ photocatalytic hydroxylation of weakly polar aromatics, a series of inverse H/D KIEs of 0.7–0.8 were observed, which is different than the normal H/D kinetic isotope effects (KIEs) usually observed for polar aromatics. This result indicated that the oxidation started by photo‐induced h_vb⁺ can be the rate‐determining step.