Kinetic Isotope
운동 동위원소

Kinetic Isotope(운동 동위원소)란 무엇입니까?

Kinetic Isotope 운동 동위원소 - Kinetic isotope-labelling experiments—performed in an operando differential electrochemical mass spectrometry capillary flow cell with millisecond time resolution—showed an unexpected enhanced production of C2H4, with a yield increase of almost 50%, from a cross-coupled 12CO2–13CO reactive pathway. ^[1]

rate determining step 비율 결정 단계

Kinetic isotope effects suggested that the hydride transfer is involved in the rate-determining step. ^[1] The radical interrupting experiment suggested a radical process, while the kinetic isotope effect (KIE) showed that the C-H cleavage likely was not involved in the rate-determining step. ^[2] The kinetic isotope studies indicate that the cleavage of OH bond in H2O molecules is the rate-determining step (RDS). ^[3] Kinetic isotope effect experiments confirm the participation of hydrogen transfer in the rate-determining step of both the reduction of O2 and H2O2. ^[4] The measured and computed inverse deuterium kinetic isotope effect supports the C-C bond-formation step as the rate-determining step. ^[5] Through a series of 12C/13C and 1H/2H kinetic isotope effect studies, the rate-determining step for the polymerization was determined to be the formation of the metallacyclobutane ring. ^[6] Neighbored carbon atoms in pyridinic N species are responsible for facilitating the rate-determining step process clarified by kinetic isotope effects, in situ NMR, in situ ATR-IR and theoretical calculation. ^[7] Consistent with the kinetic isotope effect reported experimentally, the α-hydride elimination is calculated to be the rate-determining step with an overall activation free energy of ∼24 kcal/mol. ^[8]
운동 동위원소 효과는 수소화물 전달이 속도 결정 단계와 관련되어 있음을 시사했습니다. ^[1] 급진적 방해 실험은 급진적 과정을 제안한 반면, 동위원소 효과(KIE)는 C-H 절단이 속도 결정 단계에 관여하지 않았을 가능성이 있음을 보여주었습니다. ^[2] nan ^[3] nan ^[4] nan ^[5] nan ^[6] nan ^[7] nan ^[8]

rate limiting step 속도 제한 단계

Kinetic isotope effects revealed C-H activation as the rate-limiting step. ^[1] Distinct from most other catalysts, the kinetic isotope effect (KIE) study revealed that the protonation step of the Fe-CO2 adduct is not involved in the rate-limiting step. ^[2] The H/D kinetic isotope effect in N298A PSII was relatively small, revealing that water transfer is a rate-limiting step in this mutant. ^[3] Hammett analysis and the kinetic isotope effect indicated that the hydride elimination by Au24Clx was the rate-limiting step with an apparent activation energy of 56 ± 3 kJ/mol, whereas the oxygen pressure dependence of the reaction kinetics suggested the involvement of hydrogen abstraction by coadsorbed O2 as a faster process. ^[4] The kinetic isotope experiments indicate that the C-H bond cleavage is the rate-limiting step. ^[5] Mechanistic studies, including kinetic isotope effects, showed that the allenic C(sp3)-H bond cleavage is the rate-limiting step. ^[6] We find that the rate-limiting step is C-H bond activation that occurs via a concerted metalation deprotonation mechanism, which is consistent with Guin's experimental kinetic isotope effect observations. ^[7]
운동 동위 원소 효과는 속도 제한 단계로 C-H 활성화를 나타냅니다. ^[1] 대부분의 다른 촉매와 달리, 동위원소 효과(KIE) 연구는 Fe-CO2 부가물의 양성자화 단계가 속도 제한 단계에 관여하지 않는 것으로 나타났습니다. ^[2] N298A 광계2에서 H/D 운동 동위원소 효과는 상대적으로 작았고, 이는 물 전달이 이 돌연변이체에서 속도 제한 단계임을 나타냅니다. ^[3] nan ^[4] nan ^[5] nan ^[6] nan ^[7]

density functional theory 밀도 함수 이론

Notably, studies on the kinetic isotope effects in combination with density functional theory (DFT)-computations completely exclude the involvement of a previously proposed β-hydride elimination in the catalytic cycle, revealing that the chlorine atom transfer process is the key catalytic turnover step. ^[1] studied the formation of hydrogen peroxide from hydrogen and oxygen on palladium nanoparticles by measuring the kinetic isotope effect and performing density functional theory simulations in aqueous and organic solvents. ^[2] Mechanistic experiments, including kinetic isotope effect measurements and density functional theory (DFT) calculations, suggest a rate-determining [1,5]-hydride transfer during the transformation of the intermediate propargylamine to the final allene. ^[3] studied the formation of hydrogen peroxide from hydrogen and oxygen on palladium nanoparticles by measuring the kinetic isotope effect and performing density functional theory simulations in aqueous and organic solvents. ^[4] Studies included surface reaction modeling using Density-Functional Theory, experimental performance, H-NMR spectroscopy, and deuterium kinetic isotope effect. ^[5] This result was supported by stoichiometric Cr(V) kinetics, 13C kinetic isotope effects, and density functional theory (DFT) calculations. ^[6]
특히, 밀도 기능 이론(DFT) 계산과 결합된 운동 동위원소 효과에 대한 연구는 이전에 제안된 β-수소화물 제거가 촉매 주기에 관여하는 것을 완전히 배제하여 염소 원자 이동 과정이 핵심 촉매 전환 단계임을 보여줍니다. ^[1] 동위 원소 효과를 측정하고 수성 및 유기 용매에서 밀도 기능 이론 시뮬레이션을 수행하여 팔라듐 나노 입자에서 수소와 산소로부터 과산화수소의 형성을 연구했습니다. ^[2] nan ^[3] nan ^[4] nan ^[5] nan ^[6]

Deuterium Kinetic Isotope 중수소 동위원소

Here, a combination of a variety of computational chemistry tools and experimental methods, including quantum mechanical (QM) calculations, molecular dynamic simulations, progress curve analysis, and deuterium kinetic isotope effect (KIE) experiments, are utilized to comprehensively study the mechanism of inactivation of GABA-AT by CPP-115 and OV329 and account for their experimentally obtained global kinetic parameters kinact and KI. ^[1] A considerable primary deuterium kinetic isotope effect for the bromination of 2 indicates that the rate-limiting stage is B-H bond breakage. ^[2] Psychrophilic HBDH primary deuterium kinetic isotope effects on kcat (Dkcat) and kSTO (DkSTO) decrease at lower temperatures, suggesting more efficient hydride transfer relative to other steps as the temperature decreases. ^[3] That this large substrate deuterium kinetic isotope effect has no impact on the EF:RO partition ratio implies that the same ferryl intermediate cannot be on the EF pathway; the pathways must diverge earlier. ^[4] The introduction of sulfur ligands weakens the Fe[double bond, length as m-dash]O bond and enhances the oxidative reactivity of the FeIV[double bond, length as m-dash]O unit with a diminished deuterium kinetic isotope effect, thereby providing a compelling rationale for nature's use of the cis-thiolate ligated oxoiron(iv) motif in key metabolic transformations. ^[5] Solvent deuterium kinetic isotope effects and the effect of methanol on cephalosporin turnover showed that for both E and E', kcat is limited by deacylation of an acyl-enzyme intermediate rather than by enzyme isomerization. ^[6] The measured and computed inverse deuterium kinetic isotope effect supports the C-C bond-formation step as the rate-determining step. ^[7] 0 kcal mol-1 and a deuterium kinetic isotope effect of 1. ^[8] Studies included surface reaction modeling using Density-Functional Theory, experimental performance, H-NMR spectroscopy, and deuterium kinetic isotope effect. ^[9] To observe quantum effects in the electrode processes, the hydrogen/deuterium kinetic isotope effect constant ratio (≡KH/D) was measured in various conditions. ^[10] Sensitivity of anticlumping to 13C and deuterium kinetic isotope effects (KIEs) are tested for methane generation. ^[11] A significant primary deuterium kinetic isotope effect (KIE) for bromo-de-protonation is measured indicating proton removal is rate limiting, as confirmed by computed DFT models. ^[12] The deuterium kinetic isotope effect has been known for a period of 40 years, but it is only relatively recently that new drug entities (NDEs) incorporating deuterium demonstrating beneficial pharmacokinetics, pharmacodynamics, and toxicology have arrived to market. ^[13] Thus, this theoretical analysis predicts that inverted region behavior could be observed for systems with asymmetric double well potentials characteristic of hydrogen-bonded systems and that the hydrogen/deuterium kinetic isotope effect will approach unity and could even become inverse in this region due to the oscillatory nature of the highly excited vibrational wavefunctions. ^[14]
여기서 양자 역학(QM) 계산, 분자 역학 시뮬레이션, 진행 곡선 분석, 중수소 운동 동위원소 효과(KIE) 실험을 포함한 다양한 전산 화학 도구와 실험 방법의 조합을 활용하여 비활성화 메커니즘을 종합적으로 연구합니다. CPP-115 및 OV329에 의한 GABA-AT 및 실험적으로 얻은 전체 운동 매개변수 kinact 및 KI를 설명합니다. ^[1] 2의 브롬화에 대한 상당한 1차 중수소 운동 동위원소 효과는 속도 제한 단계가 B-H 결합 파손임을 나타냅니다. ^[2] nan ^[3] nan ^[4] nan ^[5] nan ^[6] nan ^[7] nan ^[8] nan ^[9] nan ^[10] nan ^[11] nan ^[12] nan ^[13] nan ^[14]

Inverse Kinetic Isotope 역운동동위원소

An inverse kinetic isotope effect of k(H3O+)/k(D3O+) = 0. ^[1] An inverse kinetic isotope effect (k(H₃O⁺)/k(D₃O⁺) = 0. ^[2] An inverse kinetic isotope effect of k(H₃O⁺)/k(D₃O⁺ = 0. ^[3] There exists an inverse kinetic isotope effect at temperatures from 150 to 1500 K. ^[4] Under all treatments, an inverse kinetic isotope effect of −19. ^[5] Further studies on the isotope effect and inverse kinetic isotope effect are required from different perspectives; in particular, our results support one of the competing mechanisms of olfaction, in which molecular shape (size) is important in the process. ^[6] These resonances, which are more important for H than for D , increase the low-temperature diffusivity of both isotopologues, but prevent the inverse kinetic isotope effect reported for similar nanostructured systems. ^[7] An inverse kinetic isotope effect is observed; ND3 reacts faster than NH3. ^[8]
k(H3O+)/k(D3O+) = 0의 역 동위원소 효과. ^[1] 역 동위원소 효과(<i>k</i>(H₃O⁺)/<i>k</i>(D<sub>3< /sub>O⁺) = 0. ^[2] nan ^[3] nan ^[4] nan ^[5] nan ^[6] nan ^[7] nan ^[8]

Large Kinetic Isotope 큰 동위원소

In recent years, many experiments have shown large kinetic isotope effects (KIEs) for hydrogen transfer reactions in condensed phases as evidence of strong quantum tunneling effects. ^[1] The large kinetic isotope effect (KIE) of kH/kD=5. ^[2] We report a large kinetic isotope effect (KIE) for intramolecular charge transport in π-conjugated oligophenyleneimine (OPI) molecules connected to Au electrodes. ^[3] The loss of a Cl atom from metastable CH2Cl2+ in the mass-analyzed ion kinetic energy experiment is characterized by a borderline zero kinetic energy release and large kinetic isotope effects on chlorine and hydrogen. ^[4] We show that Ca isotopes can be used to constrain crystal growth rates in volcanic systems and confirm that large kinetic isotope effects can arise during plagioclase crystallization in natural phenocrystic, orbicular, and experimental samples. ^[5] Based on the observation of the linear correlation of the logarithm of the second rate constant (log k2′) and the bond dissociation energy (BDE, kcal mol−1) of alkyl hydrocarbons along with a large kinetic isotope effect (KIE = 8. ^[6] We identify a large kinetic isotope effect for the replacement of the transferring hydrogen atom by deuterium. ^[7]
최근 몇 년 동안 많은 실험에서 강력한 양자 터널링 효과의 증거로 응축상의 수소 전달 반응에 대한 큰 운동 동위원소 효과(KIE)가 나타났습니다. ^[1] kH/kD=5의 큰 동위원소 효과(KIE). ^[2] nan ^[3] nan ^[4] nan ^[5] nan ^[6] nan ^[7]

Primary Kinetic Isotope 1차 동위원소

28 × 10-1 M-1 s-1, -135 °C, 2-MeTHF) with a primary kinetic isotope effect of kH/kD = 5. ^[1] Recent study of structural effects on primary kinetic isotope effects (1° KIEs) of H-transfer reactions in enzymes and solution revealed that a more rigid reaction system gave rise to a weaker temperature dependence of 1° KIEs, i. ^[2] This reaction shows a primary kinetic isotope effect (KIE = 4. ^[3] Over the past few years, deuterium-labeled drugs have been extensively studied for the improvement of ADME (absorption, distribution, metabolism, excretion) properties of existing bioactive molecules as a consequence of the primary kinetic isotope effect. ^[4] The data presented herein suggest a mechanism involving two subsequent equilibrium isotope effects in combination with a primary kinetic isotope effect. ^[5] The kinetic studies with the catalyst Pt1Co1NP@dendrimer involve in particular a primary kinetic isotope effect kD/kH=3. ^[6]
28 × 10-1 M-1 s-1, -135 °C, 2-MeTHF) kH/kD = 5의 1차 동위원소 효과가 있습니다. ^[1] 효소 및 용액에서 H-전달 반응의 1차 동위원소 효과(1° KIE)에 대한 구조적 효과에 대한 최근 연구는 더 단단한 반응 시스템이 1° KIE의 약한 온도 의존성을 야기한다는 것을 밝혀냈습니다. ^[2] nan ^[3] nan ^[4] nan ^[5] nan ^[6]

13c Kinetic Isotope 13c 동위원소

A practical approach is introduced for the rapid determination of 13C kinetic isotope effects that utilizes a "designed" reactant with two identical reaction sites. ^[1] 13C kinetic isotope effects (KIEs) for the photoredox-promoted [2 + 2] cycloaddition of enones were determined in homocoupling and heterocoupling examples. ^[2] Natural abundance 13C kinetic isotope effects provide quantitative information about the transition-state structures of two key elementary steps in the catalytic cycle, transmetallation and oxidative addition. ^[3] The 12C/13C kinetic isotope effect is 1. ^[4] This result was supported by stoichiometric Cr(V) kinetics, 13C kinetic isotope effects, and density functional theory (DFT) calculations. ^[5]
2개의 동일한 반응 부위가 있는 "설계된" 반응물을 활용하는 13C 동위원소 효과의 신속한 결정을 위한 실용적인 접근 방식이 도입되었습니다. ^[1] 에논의 광산화환원 촉진 [2 + 2] 고리화 첨가에 대한 13C 운동 동위원소 효과(KIE)는 동종결합 및 이종결합 예에서 결정되었습니다. ^[2] nan ^[3] nan ^[4] nan ^[5]

Apparent Kinetic Isotope 겉보기 운동 동위원소

The apparent kinetic isotope effect of carbon (AKIEC) was different between BDE-47 and BDE-153 in single exposure, whilst identical in combined exposure, indicating the similar degradation mechanism for BDE-47 and BDE-153 in co-exposure condition. ^[1] Carbon and hydrogen apparent kinetic isotope effects (AKIEs) obtained from •OH reactions with DEP supported the hypothesis of C-H bond cleavage. ^[2] 3‰ was obtained for α-HCH using Rayleigh model, which is equivalent to an apparent kinetic isotope effect (AKIEC) value of 1. ^[3] Though rate constants varied, N and C apparent kinetic isotope effects (AKIEs) remained consistent across all experiments (averaged values of 15N-AKIE = 1. ^[4] Investigation of the apparent kinetic isotope effects (AKIEs) expected for cleavage of a CCl bond showed an important masking of the intrinsic isotope fractionation. ^[5]
탄소의 겉보기 운동 동위원소 효과(AKIEC)는 단일 노출에서 BDE-47과 BDE-153 간에 달랐지만 결합 노출에서는 동일하여 동시 노출 조건에서 BDE-47과 BDE-153에 대한 유사한 분해 메커니즘을 나타냅니다. ^[1] DEP와 OH 반응에서 얻은 탄소 및 수소 겉보기 운동 동위원소 효과(AKIE)는 C-H 결합 절단의 가설을 뒷받침합니다. ^[2] nan ^[3] nan ^[4] nan ^[5]

Solvent Kinetic Isotope 용매 동위원소

Solvent kinetic isotope effects reveal that proton transfer is not rate-limiting for inhibition of Y122· of E. ^[1] A significant solvent kinetic isotope effect (KIE) of 1. ^[2] Solvent kinetic isotope effect indicates that the pendant imidazole groups attack the phosphorus atom to form a phosphorylated polymeric intermediate that is rapidly hydrolyzed, allowing for the catalyst regeneration. ^[3] These findings are supported by solvent kinetic isotope effect experiments, which show that proton transfer from the FAD N5‐atom is rate limiting in the absence of a substrate, however, is significantly less rate limiting in the presence of Orn and or Lys. ^[4]
용매 운동 동위원소 효과는 양성자 전달이 E의 Y122· 억제에 대한 속도 제한이 아님을 보여줍니다. ^[1] 1의 유의미한 용매 동위원소 효과(KIE). ^[2] nan ^[3] nan ^[4]

Dependent Kinetic Isotope 의존 동위원소

, a Marcus plot), construction of Eyring plots, and temperature-dependent kinetic isotope effect (KIE) measurements. ^[1] Calculation of temperature-dependent kinetic isotope effects (KIE) in enzymes presents a significant theoretical challenge. ^[2] Secondary processes, including thermochemical sulfate reduction (TSR) and diffusion, result in an enrichment of the gases in 13C and 2H due to mass-dependent kinetic isotope effect. ^[3]
, Marcus 플롯), Eyring 플롯의 구성 및 온도 의존적 ​​운동 동위원소 효과(KIE) 측정. ^[1] 효소에서 온도 의존적 ​​동위원소 효과(KIE)의 계산은 상당한 이론적 도전을 제시합니다. ^[2] nan ^[3]

D Kinetic Isotope D 동위원소

6), and generates a Co(III)−OH moiety (Co6(III)−OH), as proven by transient absorption spectroscopy; (ii) at pH>pKa, the Co6(II)−OH→RuIII(bpy)3 3+ ET occurs via bimolecular kinetics, with a rate constant k close to the diffusion limit and dependent on the ionic strength of the medium, consistent with reaction between charged species; (iii) at pH electron transfer (CPET) where water assists the transfer of the proton, as proven by the absence of effect of buffer base concentrations on the rate of the ET and by a H/D kinetic isotope in a range of 1. ^[1] The H/D kinetic isotope effect in N298A PSII was relatively small, revealing that water transfer is a rate-limiting step in this mutant. ^[2] d5-ethoxyl radical with 2,6-lutidine and 4-phenylpyridine show that both reactions exhibit primary H/D kinetic isotope effects for the hydrogen (deuterium) atom transfer reactions. ^[3]
6) 과도 흡수 분광법에 의해 입증된 바와 같이 Co(III)-OH 부분(Co6(III)-OH)을 생성합니다. (ii) pH>pKa에서 Co6(II)-OH→RuIII(bpy)3 3+ ET는 이분자 역학을 통해 발생하며, 속도 상수 k는 확산 한계에 가깝고 매질의 이온 강도에 따라 일관성이 있습니다. 하전된 종 사이의 반응으로; (iii) pH <pKa에서 이 과정은 Co6(II)-OH2→Co6(III)-OH 변환을 포함하고 물이 다음과 같이 양성자의 이동을 돕는 다중 위치, 공동 양성자 전자 이동(CPET)을 통해 진행됩니다. 완충 염기 농도가 ET의 속도에 미치는 영향의 부재와 1 범위의 H/D 동위원소에 의해 입증되었습니다. ^[1] N298A 광계2에서 H/D 운동 동위원소 효과는 상대적으로 작았고, 이는 물 전달이 이 돌연변이체에서 속도 제한 단계임을 나타냅니다. ^[2] nan ^[3]

Observed Kinetic Isotope

The microscopic rate constants that govern an enzymatic reaction are only directly measured under certain experimental set-ups, such as stopped flow, quenched flow, or temperature-jump assays; the majority of enzymology proceeds from steady state conditions which leads to a set of more easily–observable parameters such as kcat, KM, and observed Kinetic Isotope Effects (Dkcat). ^[1] In the kinetic analysis on the C-H oxidation, we observed kinetic isotope effects (KIEs) on the C-H oxidation with use of deuterated substrates and remarkably large solvent KIE (sKIE) in D2O. ^[2]
효소 반응을 제어하는 ​​미시적 속도 상수는 정지된 흐름, 급냉된 흐름 또는 온도 점프 분석과 같은 특정 실험 설정 하에서만 직접 측정됩니다. 대부분의 효소학은 kcat, KM 및 관찰된 동적 동위원소 효과(Dkcat)와 같이 보다 쉽게 ​​관찰할 수 있는 매개변수 세트로 이어지는 정상 상태 조건에서 진행됩니다. ^[1] nan ^[2]

2h Kinetic Isotope

Through a series of 12C/13C and 1H/2H kinetic isotope effect studies, the rate-determining step for the polymerization was determined to be the formation of the metallacyclobutane ring. ^[1] We have evaluated the role of hydride tunneling in a thermostable variant of this enzyme (17X-PTDH) by measuring the temperature dependence of the primary 2H kinetic isotope effects (KIEs) between 5 °C and 45 °C. ^[2]

Strong Kinetic Isotope

Several layers affected by significant prior calcite precipitation under a dry climate display strong kinetic isotope influences: positive δ18O and negative Δ47 deviations. ^[1] The results show that while S2tYZ•/QA•– recombination can be described as pure electron transfer occurring in the Marcus inverted region, the S2t → S2 reversion depends on proton rearrangement and exhibits a strong kinetic isotope effect. ^[2]
건조한 기후에서 상당한 이전 방해석 강수의 영향을 받은 여러 층은 강한 운동 동위원소 영향을 나타냅니다: 양의 δ18O 및 음의 Δ47 편차. ^[1] nan ^[2]

Enzyme Kinetic Isotope 효소 동위원소

An early report on deuterium-labeled Escherichia coli alkaline phosphatase (AP) showed an unusually large enzyme kinetic isotope effect on kcat. ^[1] Discovery of natural inverse heavy enzyme kinetic isotope effects reveals new principles of coupled protein dynamics. ^[2]
중수소로 표지된 대장균 알칼리성 인산분해효소(AP)에 대한 초기 보고서는 kcat에 대한 비정상적으로 큰 효소 운동 동위원소 효과를 보여주었습니다. ^[1] 천연 역중효소 운동 동위원소 효과의 발견은 결합된 단백질 역학의 새로운 원리를 드러냅니다. ^[2]

Chlorine Kinetic Isotope 염소 동위원소

Chlorine kinetic isotope effects and equilibrium isotope effects vary in stepwise chlorination reactions, leading to inconsistent chlorine isotope ratios on different reaction positions of products, which results in non-binomial chlorine isotopologue distributions of the products. ^[1] Although all substrates showed normal apparent carbon/chlorine kinetic isotope effects (C-/Cl-AKIE >1), the putative inverse C-AKIE of nondechlorinated pathways was suggested by 13C depletion of the average carbon isotope composition of PCB138 and corresponding dechlorinated products in MeOH/H2O, which might originate from the magnetic isotope effect. ^[2]
염소 운동 동위원소 효과와 평형 동위원소 효과는 단계적 염소화 반응에서 다양하여 제품의 서로 다른 반응 위치에서 염소 동위원소 비율이 일관되지 않아 제품의 비이항 염소 동위원소 분포가 발생합니다. ^[1] 모든 기질이 정상적인 겉보기 탄소/염소 운동 동위원소 효과를 나타내었지만(C-/Cl-AKIE >1), 비탈염소 경로의 추정 역 C-AKIE는 PCB138의 평균 탄소 동위원소 조성 및 상응하는 탈염소 생성물의 13C 고갈에 의해 제안되었습니다. 자기 동위원소 효과에서 기인할 수 있는 MeOH/H2O. ^[2]

kinetic isotope effect 운동 동위원소 효과

28 × 10-1 M-1 s-1, -135 °C, 2-MeTHF) with a primary kinetic isotope effect of kH/kD = 5. ^[1] The replacement process resulted in obvious kinetic isotope effect, in which pyrites are possessed in extreme negative Fe isotopic composition (~−4‰). ^[2] An early report on deuterium-labeled Escherichia coli alkaline phosphatase (AP) showed an unusually large enzyme kinetic isotope effect on kcat. ^[3] Chemically deuterated cellulose fiber was expected to provide novel applications due to its spectral, biological, and kinetic isotope effect. ^[4] An inverse kinetic isotope effect of k(H3O+)/k(D3O+) = 0. ^[5] An inverse kinetic isotope effect (k(H₃O⁺)/k(D₃O⁺) = 0. ^[6] Kinetic isotope effects revealed C-H activation as the rate-limiting step.