Kinetic isotope effects transition state structures

SECONDARY a-DEUTERIUM KINETIC ISOTOPE EFFECT AND THE STRUCTURE OF FERROCENYLMETHYL CARBOCATION TYPE TRANSITION STATE... 

Today a good understanding of transition state structure can be obtained through a combination of experimental measurements of kinetic isotope effects (KIE) and computational chemistry methods (Schramm, 1998). The basis for the KIE approach is that incorporation of a heavy isotope, at a specific atom in a substrate molecule, will affect the enzymatic reaction rate to an extent that is correlated with the change in bond vibrational environment for that atom, in going from the ground state to the... 

Deuterium kinetic isotope effects, secondary, and transition state structure, 31,143 Diazo compounds, aliphatic, reactions with acids, 5, 331... 

The physical organic chemistry of very high-spin polyradicals, 40, 153 Thermodynamic stabilities of carbocations, 37, 57 Topochemical phenomena in solid-slate chemistry, 15, 63 Transition state analysis using multiple kinetic isotope effects, 37, 239 Transition state structure, crystallographic approaches to, 29, 87 Transition state structure, in solution, effective charge and 27, 1... 

Using kinetic isotope effects to determine the structure of the transition states of SN2 reactions, 41, 219... 

Secondary Deuterium Kinetic Isotope Effects and Transition State Structure... 

Secondary a-deuterium kinetic isotope effects (KIEs) have been widely used to determine the mechanism of SN reactions and to elucidate the structure of their transition states (Shiner, 1970a Westaway, 1987a). Some of the significant studies illustrating these principles are presented in this section. 

The nucleophile in the S.v2 reactions between benzyldimethylphenylammonium nitrate and sodium para-substituted thiophenoxides in methanol at 20 °C (equation 42) can exist as a free thiophenoxide ion or as a solvent-separated ion-pair complex (equation 43)62,63. The secondary alpha deuterium and primary leaving group nitrogen kinetic isotope effects for these Sjv2 reactions were determined to learn how a substituent on the nucleophile affects the structure of the S.v2 transition state for the free ion and ion-pair reactions64. 

TABLE 17. The secondary alpha deuterium and primary leaving group nitrogen kinetic isotope effects and the relative transition state structures for the ion-pair S 2 reactions between sodium thiophenoxide and benzyldimethylphenylammonium nitrate in DMF at different ionic strengths at 0°C... 

The principal goal of most studies of kinetic isotope effects on enzymatic reactions is to deduce intrinsic rate constants, which, in turn, can be correlated with the geometric features, that is the structure, of the corresponding transition states. Formal kinetics provides several options for reaching this goal. For example, as we have seen above, changes in concentration can diminish the commitment to the point where the KIE experimental value corresponds directly to the intrinsic kinetic... 

Equation 11.74 allows for an explicit solution for all five unknowns. The intrinsic values obtained are listed in Table 11.2 together with the experimental ones. In addition to these intrinsic values of kinetic isotope effects to be used in further analysis of the transition state structure, the commitments were calculated as Cf = 0.8 0.3 and cr = 0.5 0.3. 

T-secondary isotope effect can be determined. As recounted in the last item of Chart 3, such effects are expected to be measures of transition-state structure. If the transition state closely resembled reactants, then no change in the force field at the isotopic center would occur as the reactant state is converted to the transition state and the -secondary kinetic isotope effect should be 1.00. If the transition state closely resembled products, then the transition-state force field at the isotopic center would be very similar to that in the product state, and the a-secondary kinetic isotope effect should be equal to the equilibrium isotope effect, shown by Cook, Blanchard, and Cleland to be 1.13. Between these limits, the kinetic isotope effect should change monotonically from 1.00 to 1.13. 

The kinetic isotope effect has its origin in force constant changes occurring at an isotopically substituted position as the react2mt is converted into an activated complex. Hence it provides information about the transition state in the solvolysis reaction, but not necessarily about the stmcture of possible intermediates. This limits the utility of information drawn from isotope studies in resolving the structure of ions under stabilizing conditions. 

In 1998, Hasanayn and Streitwieser reported the kinetics and isotope effects of the Aldol-Tishchenko reaction . They studied the reaction between lithium enolates of isobu-tyrophenone and two molecule of beuzaldehyde, which results iu the formation of a 1,3-diol monoester after protonation (Figure 28). They analyzed several aspects of this mechanism experimentally. Ab initio molecular orbital calculatious ou models are used to study the equilibrium and transition state structures. The spectroscopic properties of the lithium enolate of p-(phenylsulfonyl) isobutyrophenone (LiSIBP) have allowed kinetic study of the reaction. The computed equilibrium and transition state structures for the compounds in the sequence of reactions in Figure 28 are given along with the computed reaction barriers and energy in Figure 29 and Table 6. 

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