Primary KIEs

Some species have a large number of exchangeable hydrogens. Thus, metal ions with many coordinated water molecules will become completely deuterated in D20. For example, Co(H20) + becomes Co(D20) +. If there were a 2 percent secondary kie per bond, it would be amplified to (1.02)12 or 1.27. It would not be a simple matter to demonstrate the operation of a primary kie in such a system because of this, given the p/f difference between the two metal ions and the general effects of the solvent change. 

Both the 12C/13C primary KIE and the 14N/15N secondary KIE have been determined (Table 4-2) [19, 20], with the immediate adjacent atoms about the isotopic substitution site quantized as well. To our knowledge, we are not aware of any such simulations prior to our work for a condensed phase reaction with converged secondary heavy isotope effects. This demonstrates the applicability and accuracy of the PI-FEP/UM method. 

All the 14C primary KIE data above and the C(4) and C(6) secondary deuterium KIEs have been fitted to BEBOVIB modeling calculations and it has been deduced that, in the transition state of the reaction of 234a, 70-80% bond breaking and 20% bond making occurs, while for 234b both bond breaking and bond formation amount to 30-40%. 

The second explanation was suggested by Kurz and Frieden. Because the masses of the leaving group (the hydride) and the isotopes generating the secondary a-deuterium KIE are comparable, it may be possible that bending motion of the a-hydrogen (deuterium) is part of the reaction coordinate motion. In these circumstances, the large observed KIE is not purely secondary but is the product of a secondary and a primary KIE. 

The size of heavy atom KIEs is usually considered to be normal (larger than unity) when the total bonding at the labeled atom is decreasing in the TS and inverse (less than unity) when the bonding is increasing. This is true of course, but an equally or even more important factor that determines the size of a primary KIE is the dynamic character of the TS the KIE is larger if the labeled atom is involved to a greater extent in the reaction-coordinate motion. The importance of the reaction-coordinate contribution has been well... 

Figure 15.2 The dominant contribution to a primary KIE is the differential loss of zero-point vibrational energy in the reaction coordinate when an isotopically substituted bond is broken. Because the light isotopomer has a higher vibrational frequency, it has more ZPVE, and a lower potential energy of activation (thus primary isotope effects expressed as ught/ heavy are essentially always greater than 1). Effects from other normal modes are ignored in this diagram (cf. Figure 15.3)...

To a rough approximation, then, in the limit of a fully broken bond i primary KIE is... 

Secondary KIEs are also typically much smaller than primary KIEs, because the isotopi-cally substituted modes arc not lost in the TS structure (see Figure 15.3). In addition. 

D KIE of 6.35 has been observed in the oxidation of a-deuteriomandelic acid by pyri-dinium bromochromate to the corresponding oxo acid. The analysis of the D KIE indicated that the reaction involves a symmetric transition state443. The oxidations of phosphinic and phosphorous acids by pyridinium bromochromate exhibits a substantial primary deuterium KIE444. The hydroxyacids, glycolic, lactic, mandelic and malic acids are oxidized by pyridinium hydrobromide perbromide in acetic acid-water mixtures to oxo acids445. The primary KIE in the oxidation of a-deuteriomandelic acid is kn/kn = 5.07, and it does not exhibit a solvent isotope effect. A mechanism involving hydride ion transfer to the oxidant has been proposed445. 

A Sizable primary KIE s have been observed in the gas-phase thermal decomposition of 2,2-dimethyl-4-phenyl but-3-enoic acid528,529, consistent with a synchronous mechanism via a six-membered cyclic ideal TS, 462. Recently531 the mechanism of thermal decarboxylation of 461 and its derivatives HR1C=CR2CH2COOH (R1 and R2 = H, F, Me, Et and Cl) has been studied again530,531 from the theoretical point of view by ctb initio MO calculations and a twisted chair six-membered cyclic TS (463) has been constructed. 

C Kinetic isotope effects (KIEs) of a xylose reductase-catalysed cinnamalde-hyde reduction have been determined by 13C NMR using competition reactions with reactants at natural 13C abundance. The primary KIEs indicated that the chemical reaction steps are only partly rate limiting during reduction of aromatic aldehydes and slow steps occur outside the catalytic sequence. The aldo-keto reductase-catalysed... 

Another more general comment on the interplay of KIE and SE is indicated. Primary KIEs associated with hydrogen migrations depend on the intrinsic structural details of the key step of bond activation where ring sizes and steric constraints of the intermediates can be regarded as minor perturbations. In contrast, the local details of the TSs are more or less identical for transfer of di-astereotopic H(D) atoms while conformational aspects of the backbone play a pivotal role. Therefore, KIEs and SEs provide complementary information on the reactions observed. With respect to the level of sophistication of contemporary ab initio methods, an explicit computational treatment of the KIEs and SEs in one of the above systems is therefore desirable. 

Mechanistic studies of alkoxide-promoted dehydrohalogenations of C6H5CH2CH2X and various derivatives YC6H4CHX CH2X and YC6H4CHX CHp2X (where X = Br, Cl, or F and X = Br or Cl) have been extended to include MeO /MeOH-promoted dehydrohalogenations of (8a-c) and interpreted with reference to Scheme 1 The Arrhenius behaviour of the primary KIEs, = 3.40, 3.49, 2.19 and... 

The density functional theory calculations of primary KIE and secondary deuterium kinetic isotope effects (SKIE) did not reproduce satisfactorily all the experimentally determined KIE and deuterium (4,4- H2)- and 6,6- H2-SKIE, though the non-local DFT methods provide transition state energies on a par with correlated molecular orbital theory. ... 

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