Kinetic isotope effects, use

Abstract The statistical thermodynamic theory of isotope effects on chemical equilibrium constants is developed in detail. The extension of the method to treat kinetic isotope effects using the transition state model is briefly described. 

The chapter starts with a brief review of thermodynamic principles as they apply to the concept of the chemical equilibrium. That section is followed by a short review of the use of statistical thermodynamics for the numerical calculation of thermodynamic equilibrium constants in terms of the chemical potential (often designated as (i). Lastly, this statistical mechanical development is applied to the calculation of isotope effects on equilibrium constants, and then extended to treat kinetic isotope effects using the transition state model. These applications will concentrate on equilibrium constants in the ideal gas phase with the molecules considered in the rigid rotor, harmonic oscillator approximation. 

Seymom-, S.L. and Klinman, J.P. (2002). Comparison of rates and kinetic isotope effects using PEG-modified variants and glycoforms of glucose oxidase the relationship of modification of the protein envelope to C-H activation and turmeUng. Biochemistry 41, 8747-8758... 

Human type II inosine monophosphate dehydrogenase catalyses NAD-dependent conversion of inosine monophosphate (IMP) into xanthosine monophosphate (XMP) measurements of the primary kinetic isotope effect using [ H]IMP suggest that both substrates (IMP and NAD) can dissociate from the enzyme-substrate complex therefore, the kinetic mechanism is not ordered. NMR studies indicate hydride transfer to the B or pro-S face of the nicotinamide ring of NAD, while kinetic studies suggest... 

Apparent activation energies and kinetic isotope effects using the reaction order approach... 

Theoretical calculations of the kinetic isotope effect using Bigeleisen and Wolfs-berg s formulation were made both with and without a tunnel correction. Theoretical force constants were evaluated from Sato surfaces fit to the Ar-... 

The low kinetic isotope effect using A-rr/-deuteromethyl-9-t-butylacridane indicated that a hydrogen-atom abstraction was not operative in this case. 

Kinetic isotope effects using CH3OH and CH3OD show that the O-H bond is at least partially involved in the rate-limiting step. TPD experiments with pure Cu°, pure ZnO, and the catalyst Cu/ZnO showed that methanol can be activated by both ZnO and copper. On the ZnO surface, methanol can form intermediates, which in the presence of copper might react and desorb more easily probably via a reverse spillover process. The isotopic product distribution of H2, HD, D2,H20, HDO and D2O in the... 

Figure 7.6. Multiple hydrogen kinetic isotope effects used to diagnose a concerted versus stepw/ise mechanisms.

On the mechanism of D-amino add oxidase. Structure/linear free energy correlations and deuterium kinetic isotope effects using substituted phenylglydnes,... 

A few processes reported in the literature have been interpreted as binuclear H2 reductive elimination Irom 17-electron hydride complexes. This process requires, of course, the formation of 16-electron products or intermediates, unless it is preceded by coordination of a 2-electron donor to afford 19-electron complexes which then undergoes the reductive elimination process. In most cases, however, mechanistic studies e.g. rate law determinations, kinetic isotope effects, use of different solvents, etc.) in support of this proposal have not been carried out. In particular, in no case can the observed process be unambiguously distinguished from a disproportionation process. Proof of the viability of a truly bimolecular one-electron reductive elimination process from 17-electron hydride complexes requires, in our opinion, additional investigations. 

Kinetic isotope effects using CH3OH and CH3OD show that the O-H bond is at least partially involved in the rate limiting step. TPD... 

The rate equation for solvent isotope effects with more complex bisubstrate mechanisms may be derived in the same way as was described in Section 173.3 for the kinetic isotope effects, using the corresponding nomenclature. 

Cheah, M.H., Millar, A.H., Myers, R.C., Day, D.A., Roth, J., Hillier, W, Badger, M.R. (2014) Online Oxygen Kinetic Isotope Effects Using Membrane Inlet Mass Spectrometry Can Differentiate between Oxidases for Mechanistic Studies and Calculation of Their Contributions to Oxygen Consumption in Whole Tissues. Anal. Chem. 86 5171-5178. 

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