12C/13C kinetic isotope effects

Figure 7 12C/13C Kinetic isotopic effect in asymmetric dihydroxylation using (DHQD)2PDZ.

Kinetic evidence implicates a pre-association mechanism for catalysis that supports decarboxylation involving reversible formation of a complex of C02 and the carbanionic product.50 The catalyst is able to accelerate the reaction by competing for the carbanion. Such a situation would routinely be available in an enzyme active site.37 The complex cannot be observed spectroscopically because of its short lifetime and low concentration. However, catalysis after C C bond-breaking should alter the observed 12C/13C kinetic isotope effects (CKIE). 

Table 4-2. Computed and experimental primary 12C/13C and secondary 14N/15N kinetic isotope effects for the decarboxylation of N-methyl picolinate at 25 °C in water...

Corey et al. investigated the kinetic isotopic effect (KIE) in asymmetric dihydroxylation. 12C/13C KIE was measured for the dihydroxylation of styrene, p-nitrostyrene, and 4-methoxy-benzoate (Figure 7).197 The observed similar 12C/13C isotopic effect of two olefinic carbons... 

An S-12C bond breaks a little faster than an S-13C bond in a nucleophilic displacement reaction. This primary kinetic isotope effect (KIE)3a 3b/31a-d is usually discussed first for breakage of a C-H bond. 

One of the important mechanistic uses of isotopic substitution is that it can selectively affect different steps in a stepwise mechanism and so help resolve mechanisms and pathways. For example, in reactions where there is hydride transfer coupled to C—C bond formation, the measurement of both 13C/12C and D/H kinetic isotope effects can distinguish whether the steps are concerted or stepwise. Consider, for example, the oxidative decarboxylation of malate catalyzed by the malic enzyme, which could occur either via an intermediate mechanism (2.81) or in a concerted mechanism (2.82).59... 

As logical as this diagnostic method is, one needs to recognized its lack of absolute applicability The observed magnitude of the kinetic isotopic effect is not great, and the aforementioned statement of independence of electron affinity from the increase in the molecular mass of the substrate is not obvious. This postulate should be proven in each case. Benzophenone, taken as an isotopic mixture of 12C=0 and 13C=0 gives a mixture of anion radicals with a decreased proportion of 13C=0 isotomer when reduced with potassium in HMPA (G.R. Stevenson, Reiter, Espe, Bartmess 1987). In effect, this means that for the heavier isotopomer of benzophenone, the electron affinity is smaller. 

Other kinetic isotope effects are known but they are very small D is twice as heavy as H but 13C only slightly heavier than 12C. 

These are primary factors that explain the more important differences in I3C content more subtle variations however may be observed and depend essentially on the existence of 13C/12C kinetic isotope effects (KIE). 

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