Kinetic isotope effects

1. Sahaya Asirvatham

2. lAn element is identified by its symbol, mass number,
and atomic number.
lThe atomic number is the number of protons in the
nucleus while the mass number is the total number of
protons and neutrons in the nucleus.
lIsotopes are two atoms of the same element that have
the same number of protons but different numbers of
neutrons. Isotopes are specified by the mass number.

3. Why Kinetic Isotope effect???
Traditional kinetics studies do not provide
information as to what bonds are broken/formed
and changes in hybridization that occur during the
rate limiting step of a reaction.
Isotope effects can provide this information.
Substituting one iosotope for another at or near an
atom at which bonds are breaking or re-hybridizing
typically leads to a change in the rate of the
reaction.

4. Kinetic Isotope Effects
The kinetic isotope effect (KIE) is a
phenomenon associated with isotopically
substituted molecules exhibiting different
reaction rates.

5. Differences in the properties which arise from the
difference in mass are called as isotope effect.
Rates of reactions are measurable different for the
process in which E-H & E-D bonds are broken,
made or rearranged (E – another element).
The detection of this kinetic isotope effect help to
support a proposed reaction mechanism of many
chemical reactions.

6. The isotope effect is expressed as a ratio of rate
constants:
The rate constant for the reaction with the natural
abundance isotope over the rate constant for the
reaction with the altered isotope.
For H/D substitutions: kH/kD

7. The magnitude of the IE gives information about
reaction mechanism:
If kH/KD = 1, the bond where substitution has
occured is not changing during the chemical
reaction (RDS)
OR The IE is negligible to be measured
If kH/KD > 1, the IE is Normal IE
If kH/KD < 1, the IE is Inverse IE

8. Primary kinetic isotope effects
A Primary Kinetic Isotope effect may
be found when a bond to the
Isotopically labelled atom is being
formed or broken.

9. Origin of Primary Kinetic Isotope Effects
The origins of isotope effects is the difference in the
frequencies of various Vibrational modes of a
molecule, arising when one isotope is substituted for
another.
Different type of bond in a molecule have different
frequency.

10. Vibrational frequancy of a molecule is calculated by
using the formula:
Where Mr = Reduced mass
The VF is directly proportional to FORCE constant
‘k’ and inversely proportional to the mass of the
atom.

11. As deuterium is heavier than hydrogen the VF of
C-H bond will be more as compared to C-D bond.
Energy for bond breaking is directly proportional to
VF
Thus energy for C-H bond will be less as compared
to C-D bond.

12. Vibrational energy which is calculated at
ambient temperature for bond is called Zero
Point energy (ZPE)
Zero Point energy (ZPE) can be stated as,

13. Example
lDehydrohalogenation reaction
lWithout isotope:
lCH3-CH2-CH2-Br CH3-CH=CH2
lWithout isotope:
lCH3-CD2-CH2-Br CH3-CD=CH2
NaOC2H5
C2H5OH
NaOC2H5
C2H5OH
kH/kD= 6.7

14. Secondary Kinetic Isotope Effects
lWhen the IE is attributed to a REHYBRIDIZATION or when IE
arises from substitution remote/away from the bond
undergoinig reaction it is reffered to as Secondary IE.
lα or β secondary isotope effects: based on whether the
isotope is on a position α or β to the bond that is changing.

15. In Secondary IE we consider change in Hybridization of
Carbon atom.
As the hybridization state of carbon changes the VF of C-
H and C-D bond will change
When C-H bond involving an sp3 hybridized carbon is
changing to a bond involving an sp2 hybridized carbon
the vibrational modes changes.
C-H bond strengths decrease in the order sp > sp2 > sp3
Hybridization Changes

16. Consider the in-plane and out-of-plane bending motions for sp3 and sp2
hybridized carbons, along with the associated IR frequencies.
The in-plane and out-of-plane bends for an sp3 hybridized carbon are
degenerate.
However, the in-plane bend is a much stiffer motion for the sp2 hybridized
carbon than is the out-of-plane bend ---- because of Steric Hindrance

17. This large difference in force constant for the out-of-plane bend
of an sp3 hybrid vs sp2 hybrid leads to -----
Significant difference in ZPE differences between C-H and C-D
bonds in reactions that involve rehybridization between sp3 and
sp2.
Therefore, it is this bending mode that leads to a measurable
Secondary Isotope Effect.