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. Formally, it is the ratio of rate constants for the reactions involving the light (k) and the heavy (k) isotopically substituted reactants (isotopologues):
This change in reaction rate is a quantum mechanical effect that primarily results from heavier isotopologues having lower vibrational frequencies compared to their lighter counterparts. In most cases, this implies a greater energetic input needed for heavier isotopologues to reach the transition state (or, in rare cases, the dissociation limit), and consequently, a slower reaction rate.  The study of kinetic isotope effects can help the elucidation of the reaction mechanism of certain chemical reactions and is occasionally exploited in drug development to improve unfavorable pharmacokinetics by protecting metabolically vulnerable C-H bonds.