Editing Kinetic isotope effect (section)

== Background ==
KIE is considered one of the most essential and sensitive tools for studying reaction mechanisms, the knowledge of which allows improvement of the desirable qualities of said reactions. For example, KIEs can be used to reveal whether a [[nucleophilic substitution]] reaction follows a [[unimolecular]] (S{{sub|N}}1) or [[bimolecular]] (S{{sub|N}}2) pathway.

In the reaction of [[methyl bromide]] and [[cyanide]] (shown in the introduction), the observed methyl carbon KIE is 1.082, a small effect which indicates an S{{sub|N}}2 mechanism in which the C-Br bond is formed as the C-CN bond is broken. For S{{sub|N}}1 reactions in which the leaving group leaves first to form a trivalent carbon transition state, the KIE is close to the maximum observed value for a secondary KIE (SKIE, see below) of 1.22.<ref name="Westaway1">{{cite journal|last=Westaway|first=Kenneth C. | name-list-style = vanc |title=Using kinetic isotope effects to determine the structure of the transition states of S{{sub|N}}2 reactions|journal=Advances in Physical Organic Chemistry|year=2006|volume=41|pages=217–273|doi=10.1016/S0065-3160(06)41004-2|isbn=978-0-12-033541-1 }}</ref> Depending on the pathway, different strategies may be used to stabilize the [[transition state]] of the [[rate-determining step]] of the reaction and improve the [[reaction rate]] and selectivity, which are important for industrial applications.

[[File:Kinetic isotope effect (reaction mechanism) (2).png|center]]

Isotopic rate changes are most pronounced when the relative [[mass]] change is greatest, since the effect is related to vibrational frequencies of the affected bonds. Thus, replacing normal [[hydrogen]] ({{sup|1}}H) with its isotope [[deuterium]] (D or {{sup|2}}H), doubles the mass; whereas in replacing [[carbon-12]] with [[carbon-13]], the mass increases by only 8%. The rate of a reaction involving a C–{{sup|1}}H bond is typically 6–10x faster than with a C–{{sup|2}}H bond, whereas a {{sup|12}}C reaction is only 4% faster than the corresponding {{sup|13}}C reaction;<ref name="Laidler_1987" />{{rp|445}} even though, in both cases, the isotope is one atomic mass unit (amu) ([[Dalton (unit)|dalton]]) heavier.

Isotopic substitution can modify the reaction rate in a variety of ways. In many cases, the rate difference can be rationalized by noting that the mass of an atom affects the [[molecular vibration|vibrational frequency]] of the [[chemical bond]] that it forms, even if the [[potential energy surface]] for the reaction is nearly identical. Heavier isotopes will ([[classical physics|classically]]) lead to lower vibration frequencies, or, viewed [[quantum mechanics|quantum mechanically]], have lower [[Zero-point energy#The uncertainty principle|zero-point energy]] (ZPE). With a lower ZPE, more energy must be supplied to break the bond, resulting in a higher [[activation energy]] for bond cleavage, which in turn lowers the measured rate (see, for example, the [[Arrhenius equation]]).<ref name="Atkins" /><ref name="Laidler_1987" />{{rp|427}}