Kinetic isotope effect

${\displaystyle {\begin{matrix}\\{\ce {{CN^{-}}+{^{12}CH3-Br}->[k_{12}]{^{12}CH3-CN}+Br^{-}}}\\{\ce {{CN^{-}}+{^{13}CH3-Br}->[k_{13}]{^{13}CH3-CN}+Br^{-}}}\\{}\end{matrix}}\qquad {\text{KIE}}={\frac {k_{12}}{k_{13}}}=1.082\pm 0.008}$

An example of KIE. In the reaction of methyl bromide with cyanide, the KIE of the carbon in the methyl group was found to be 1.082 ± 0.008.^[1][2]

In physical organic chemistry, a kinetic isotope effect (KIE) is the change in the reaction rate of a chemical reaction when one of the atoms in the reactants is replaced by one of its isotopes.^[3] Formally, it is the ratio of rate constants for the reactions involving the light (k_L) and the heavy (k_H) isotopically substituted reactants (isotopologues): KIE = k_L/k_H.

This change in reaction rate is a quantum effect that occurs mainly because heavier isotopologues have lower vibrational frequencies than their lighter counterparts. In most cases, this implies a greater energy input needed for heavier isotopologues to reach the transition state (or, in rare cases, dissociation limit), and therefore, a slower reaction rate. The study of KIEs can help elucidate reaction mechanisms, and is occasionally exploited in drug development to improve unfavorable pharmacokinetics by protecting metabolically vulnerable C-H bonds.