page_title: Kinetic isotope effect
section_title: Isotope-ratio mass spectrometry
hierarchical_section_title: Kinetic isotope effect / Experiments / Kinetic isotope effect measurement at natural abundance / Isotope-ratio mass spectrometry
caption_attribution_description: English: 34S isotope effect on sulfate ester hydrolysis reaction scheme
context_page_description: In physical organic chemistry, a kinetic isotope effect 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 and the heavy isotopically substituted reactants:
  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, 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.
context_section_description: High precision isotope-ratio mass spectrometry (IRMS) is another method for measuring kinetic fractionation of isotopes for natural abundance KIE measurements. Widlanski and coworkers demonstrated ³⁴
  S
   KIE at natural abundance measurements for the hydrolysis of sulfate monoesters. Their observation of a large KIE suggests S-O bond cleavage is rate controlling and likely rules out an associate reaction mechanism.
  The major limitation for determining KIE's at natural abundance using IRMS is the required site selective degradation without isotopic fractionation into an analyzable small molecule, a non-trivial task.
caption: 34S isotope effect on sulfate ester hydrolysis reaction
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