Equilibrium isotope effect for

In 1983, Huskey and Schowen tested the coupled-motion hypothesis and showed it to be inadequate in its purest form to account for the results. If, however, tunneling along the reaction coordinate were included along with coupled motion, then not only was the exaltation of the secondary isotope effects explained but also several other unusual feamres of the data as well. Fig. 4 shows the model used and the results. The calculated equilibrium isotope effect for the NCMH model (the models employed are defined in Fig. 4) was 1.069 (this value fails to agree with the measured value of 1.13 because of the general simplicity of the model and particularly defects in the force field). If the coupled-motion hypothesis were correct, then sufficient coupling, as measured by the secondary/primary reaction-coordinate amplimde ratio should generate secondary isotope effects that... 

TABLE 9.1 Equilibrium Isotope Effects for Converting 02 to rj1-Superoxide (02 ) Structures... 

Lewis BE, Schramm VL (2003) Binding equilibrium isotope effects for glucose at the catalytic domain of human brain hexokinase. J. Am. Chem. Soc. 125 4785-4798... 

TABLE 4. Kinetic and equilibrium isotope effects for the reaction of benzaldehyde with various organolithium reagents12... 

Isotope effects result from changes in the stiffness of bonding of isotopic atoms. Kinetic isotope effects reflect differences between reactant and transition state, and equilibrium isotope effects come from differences between reactant and product. Equilibrium isotope effects are easily measured experimentally, and they can also be calculated from the force fields derived for small molecules from vibrational frequencies. They are commonly expressed as fractionation factors, which are equilibrium isotope effects for exchange of isotope with a reference molecule such as water or ammonia. Tables of fractionation factors are in Refs. (96) and (98) and further values are in Ref. (99). 

This phenomenon was first discovered with formate dehydrogenase, where the secondary deuterium isotope effect at C-4 of the nucleotide was 1.23, even though the equilibrium isotope effect for the reduction of NAD is 0.89... 

Tabie 1 Intramolecular equilibrium Isotope effects for M-H to a-CHx exchange reactions... 

Recent calculations of the conformational equilibrium isotope effect for [65] using a scaled quantum mechanical 3-21 G force field are in qualitative accord with the experiment and confirm the zero point energy origin of the effect (Williams, 1986). 

The proton spectrum (100 MHz, — 125°C) of the monodeuteriated cation is in accord with this conclusion. The same spectrum was observed as for the unlabelled cation except for the reduced intensity of the peak for the averaged hydrogens on C-l/C-2 (Saunders et al., 1973). In the C nmr spectrum of the cation with one dideuteriomethylene group, the undeuter-iated methylene carbon peak was found shifted 0.94 ppm downfield from the methylene peak in the nonlabelled cation. This shift must be caused by an equilibrium isotope effect for either one of the proposed structures [113] or [114] but the direction of this equilibrium isotope effect could not be correlated to the structures because the shift difference A of the averaged methylene groups is not accessible from nmr spectra in solution. 

---