Editing Kinetic isotope effect (section)

=== Other examples ===
Since KIEs arise from differences in isotopic mass, the largest observable KIEs are associated with substitution of {{sup|1}}H with {{sup|2}}H (2× increase in mass) or {{sup|3}}H (3× increase in mass). KIEs from isotopic mass ratios can be as large as 36.4 using muons. They have produced the lightest "hydrogen" atom, {{sup|0.11}}H (0.113 amu), in which an electron orbits a positive muon (μ{{sup|+}}) "nucleus" that has a mass of 206 electrons. They have also prepared the heaviest "hydrogen" atom by replacing one electron in [[helium]] with a negative muon μ{{sup|−}} to form Heμ (mass 4.116 amu). Since μ{{sup|−}} is much heavier than an electron, it orbits much closer to the nucleus, effectively shielding one proton, making Heμ behave as {{sup|4.1}}H. With these [[exotic atom]]s, the reaction of H with {{sup|1}}H{{sub|2}} was investigated. Rate constants from reacting the lightest and the heaviest hydrogen analogs with {{sup|1}}H{{sub|2}} were then used to calculate ''k''{{sub|0.11}}/''k''{{sub|4.1}}, in which there is a 36.4× difference in isotopic mass. For this reaction, isotopic substitution happens to produce an IKIE, and the authors report a KIE as low as 1.74×10{{sup|−4}}, the smallest KIE ever reported.<ref>{{cite journal | vauthors = Fleming DG, Arseneau DJ, Sukhorukov O, Brewer JH, Mielke SL, Schatz GC, Garrett BC, Peterson KA, Truhlar DG | title = Kinetic isotope effects for the reactions of muonic helium and muonium with H2 | journal = Science | volume = 331 | issue = 6016 | pages = 448–50 | date = January 2011 | pmid = 21273484 | doi = 10.1126/science.1199421 | bibcode = 2011Sci...331..448F | s2cid = 206530683 }}</ref>

The KIE leads to a specific distribution of {{sup|2}}H in natural products, depending on the route they were synthesized in nature. By NMR spectroscopy, it is therefore easy to detect whether the alcohol in wine was fermented from [[glucose]], or from illicitly added [[saccharose]].

Another [[reaction mechanism]] that was elucidated using the KIE is [[halogenation]] of [[toluene]]:<ref>{{cite journal
 | vauthors = Wiberg KB, Slaugh LH
 |year=1958
 |title=The Deuterium Isotope Effect in the Side Chain Halogenation of Toluene
 |journal=[[Journal of the American Chemical Society]]
 |volume=80 |issue=12 |pages=3033–3039
 |doi=10.1021/ja01545a034
|bibcode=1958JAChS..80.3033W
 }}</ref>

:[[File:KineticIsotopeEffectHalogenation.png|400px|KIE in halogenation of toluene]]

In this particular "intramolecular KIE" study, a benzylic hydrogen undergoes [[radical substitution]] by bromine using [[N-Bromosuccinimide|''N''-bromosuccinimide]] as the brominating agent. It was found that PhCH{{sub|3}} brominates 4.86x faster than PhC{{sup|2}}H{{sub|3}} (PhCD{{sub|3}}). A large KIE of 5.56 is associated with the reaction of [[ketone]]s with [[bromine]] and [[sodium hydroxide]].<ref>{{cite journal
 | vauthors = Lynch RA, Vincenti SP, Lin YT, Smucker LD, Subba Rao SC
 |year=1972
 |title=Anomalous kinetic hydrogen isotope effects on the rate of ionization of some dialkyl substituted ketones
 |journal=[[Journal of the American Chemical Society]]
 |volume=94 |issue=24 |pages=8351–8356
 |doi=10.1021/ja00779a012
|bibcode=1972JAChS..94.8351L
 }}</ref>

:[[File:KineticIsotopeEffectEnolateFormation.png|500px|KIE in bromination of ketone]]

In this reaction the rate-limiting step is formation of the [[enolate]] by deprotonation of the ketone. In this study the KIE is calculated from the [[reaction rate constant]]s for regular 2,4-dimethyl-3-pentanone and its deuterated isomer by [[optical density]] measurements.

In asymmetric catalysis, there are rare cases where a KIE manifests as a significant difference in the enantioselectivity observed for a deuterated substrate compared to a non-deuterated one. One example was reported by Toste and coworkers, in which a deuterated substrate produced an enantioselectivity of 83% ee, compared to 93% ee for the undeuterated substrate. The effect was taken to corroborate additional inter- and intramolecular competition KIE data that suggested cleavage of the C-H/D bond in the enantiodetermining step.<ref>{{cite journal | vauthors = Zi W, Wang YM, Toste FD | title = An in situ directing group strategy for chiral anion phase-transfer fluorination of allylic alcohols | journal = Journal of the American Chemical Society | volume = 136 | issue = 37 | pages = 12864–7 | date = September 2014 | pmid = 25203796 | pmc = 4183625 | doi = 10.1021/ja507468u | bibcode = 2014JAChS.13612864Z }}</ref>

[[File:EnantioselectivityKIE.png|frameless|700x700px]]