Inverse secondary KIE

Figure 15.3 Secondary KIEs are associated with normal modes other than the reaction coordinate, one of which is shown in this diagram. The heavy and light vibrational frequencies both change on going from the reactant (R) to the TS structure ( ) because in this example the mode is tighter in the TS structure, the difference between the heavy and light ZPVEs increases, and this causes the potential energy of activation to be larger for the light isotopomer than the heavy one (an example of an inverse secondary KIE). In a real many-atom system there are potentially a large number of modes that will contribute to the secondary KIE. some in a normal fashion and some in an inverse fashion...

Bruner and Horenstein observed a very large inverse -secondary KIE = 0.944 in a reaction catalyzed by a(2 — 6) sialyltransferase (equation 4)." This result demonstrates that, unlike non-enzymatic reactions, there is not necessarily any distance dependence on secondary KIEs in enzymatic reactions enzymes commonly use binding interactions remote from the reaction site to promote catalysis. 

The calculations were performed at the semiempirical level using AMI parametrization. The results for the methyl chloride reaction (Table 8) supported Williams earlier findings for the methylammonium ion-ammonia reaction (p. 147) and the results by Wolfe and Kim in that the inverse secondary a-deuterium KIE arose from an increase in the C —H stretching force constants which accompanied the change from sp3 hybridization at the a-carbon in the reactant to the spMike hybridization in the transition state. More important, however, were the observations that (i) the total KIE is dominated by the vibrational (ZPE) component of the KIE with which it correlates linearly, and (ii) that the inverse contribution from the C —H(D) stretching vibrations is almost constant for all the reactions. Ibis suggests that the contribution from the other vibrations, i.e. the rest in Table 8, determines the magnitude of the KIE. In fact, Barnes and Williams stated that the... 

While it is difficult to rule out an inductive contribution to the secondary a-deuterium KIEs in these Menshutkin SN2 reactions, the steric origin of these KIEs is clearly indicated by the inverse secondary a-deuterium KIEs found in an extensive study of the SN2 Menshutkin reactions between substituted... 

Kaplan and Thornton (1967) also concluded that the secondary deuterium KIEs found in these SN2 reactions were not inductive in origin. Although the large inverse secondary deuterium KIE (kH/kD = 0.883 0.008) found in the... 

A value of ku/kD = 1.07 per /3-D was observed when the deuteriums were on the bridge at C-12 [5] and the dihedral angle between the p-orbital of the carbocation and the Cp—H bonds was approximately 30° and hyperconjuga-tion could occur. When [6] was used, the dihedral angle was 90° and there was no overlap between the empty p-orbital of the carbocation and the Cp—H bonds i.e. no hyperconjugation could occur and only a small inverse, inductive KIE, kH/fcD = 0.99, was observed. This study and other studies by Shiner and co-workers (Shiner, 1970b) have established that the maximum secondary /3-deuterium KIE in any system is observed when the dihedral angle is either 0° or 180°, i.e. where the overlap between the Cp—H and the p-orbital on the... 

A large inverse secondary deuterium KIE of 0.64 was observed in acetic acid at 25°C when the perdeutero (d2o) compound was the deuterated substrate. This large inverse deuterium KIE was attributed to the KIE for the rate-determining formation of the bromonium ion (62). Although a portion of this KIE is undoubtedly due to the inductive effect (deuterium is more electron-donating than hydrogen and the deuterated bromonium ion would... 

Scheme 3) a large inverse secondary deuterium KIE is observed both in the presence, and in the absence, of added bromide ion. However, in acetic acid, the KIE becomes even more inverse as the concentration of bromide ion increases, i.e. it decreases from kH/kD = 0.64 to a minimum of 0.55 as the bromide ion concentration increases from zero to 0.04 mol dm-3 (Table 44). In methanol, on the other hand, the inverse secondary deuterium KIE of 0.56 0.04 is effectively independent of bromide ion concentration. 

The inductive effect of the donating C—D bonds to the observed large inverse secondary deuterium isotope effect has not been given proper consideration but treated as a rather minor component superimposed on the important steric component caused by larger amplitudes of vibrations of C—H bonds than those of the C—D bonds. 14C KIE have not been studied in this reaction. The C2, C V. C3 , C3, endo hydrogens are separated only by 2.11 A, substantially less than van der Waals radii (2 x 1.2 A)404. 

The activation energy of the concerted mechanism is only 3-7 kcalmoD lower than that for the first step of the stepwise mechanism. However, the geometries of the two transition states are dissimilar, one bond being formed in the stepwise structure while two bonds are formed in the concerted case, and this leads to different KIEs. The secondary KIEs calculated for concerted TS (terminal hydrogens) are always inverse (and vary from 0.93 to 0.99, depending on the position and the level of theory), in agreement with expectations for sp to sp hybridization changes. The most reliable values are 3% and... 

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