Difference Between Primary and Secondary Kinetic Isotope Effect

The key difference between primary and secondary kinetic isotope effect is that primary isotope effect describes the isotopic substitution at the broken bond whereas secondary isotope effect describes the isotopic substitution at the bond adjacent to the broken bond.

Kinetic isotope effect or KIE refers to the change in the reaction rate of a chemical reaction upon substitution of an isotope. Here, an atom in a reactant is replaced by its isotope so the reaction rate would be different from the initial rate. Then we can determine a value for KIE by dividing rate constant for the reaction involving the light isotopically substituted reactant from the rate constant for the reaction involving the heavy isotopically substituted reactant. Therefore, KIE larger than 1 is considered as normal kinetic isotopic effect while KIE less than 1 is considered as an inverse kinetic isotopic effect.

1. Overview and Key Difference
2. What is Primary Kinetic Isotope Effect
3. What is Secondary Kinetic Isotope Effect
4. Side by Side Comparison – Primary vs Secondary Kinetic Isotope Effect in Tabular Form
5. Summary

What is Primary Kinetic Isotope Effect?

Primary kinetic isotope effect is the change of reaction rate due to isotopic substitution at the site of bond breaking. Here, this substitution is in the bond-breaking stage at the rate-determining step of the reaction. Therefore, this type of isotopic effect is indicative of bond breaking or bond-forming to the isotope at the rate-limiting step.

For nucleophilic substitution reactions, the primary kinetic isotope effect is applied for leaving groups, nucleophiles and alpha-carbon at which the substitution occurs. This type of kinetic effect is less sensitive than an ideal KIE. This is due to the contribution of non-vibrational factors.

What is Secondary Kinetic Isotope Effect?

Secondary kinetic isotope effect is the change of the rate of a reaction due to isotopic substitutions at a site other than the bond-breaking site. In other words, it indicates that no bond to the isotopically labelled atom is broken or formed. Like primary kinetic effect, this also takes place in the rate-determining step. There are three types of secondary kinetic effects named as alpha, beta and gamma effect.

Difference Between Primary and Secondary Kinetic Isotope Effect

Figure 01: Nucleophilic Substitution with Molecules having Hydrogen Replaced by Deuterium

Unlike primary KIE, secondary KIE tends to be much smaller. However, this type of KIE is still very useful in elucidating reaction mechanisms because per Deuterium atoms, the secondary KIE is considerably large. Apart from that, the magnitude of secondary kinetic isotopic effects is determined by vibrational factors.

What is the Difference Between Primary and Secondary Kinetic Isotope Effect?

Kinetic isotope effect or KIE refers to the change in the reaction rate of a chemical reaction upon substitution of an isotope. The key difference between primary and secondary kinetic isotope effect is that the primary isotope effect describes the isotopic substitution at the broken bond, whereas the secondary isotope effect describes the isotopic substitution at the adjacent bond to the broken bond. Further, unlike primary KIE, the secondary KIE tends to be much smaller.

Moreover, the magnitude of secondary kinetic isotopic effects is determined by vibrational factors while the primary kinetic isotopic effect is less sensitive due to the non-vibrational factors.

Below infographic summarizes the difference between primary and secondary kinetic isotope effect.

Summary – Primary vs Secondary Kinetic Isotope Effect

Reference:

1. “Kinetic Isotope Effect.” Wikipedia, Wikimedia Foundation, 8 Nov. 2019, Available here.
2. “Kinetic Isotope Effects.” Chemistry LibreTexts, Libretexts, 5 June 2019, Available here.