Kinetic Isotope Effects

From quantum mechanics it can be shown that increasing the mass of an atom bonded in a molecule increases the energy between ground and transition states. In other words, the bond with the heavier atom is less easily broken. The rate of reaction of C-D bonds is often four to eight times slower than the reaction of C-H bonds, but it can vary widely, depending upon the bond type. Use can be made of this difference in studying the mechanism of biochemical reactions. For example, in the formation of a double bond in stearic acid (Figure 3.6), by labelling either C-9 or C-10 with two deuterium atoms each, it is found that the rate of formation of oleic acid decreases sharply with deuterium on C-9, showing that the slow, rate-determining step is the breaking of a C-H (or C-D) bond on carbon atom number 9.

Stereochemistry can similarly be studied by deuterium labelling of the pro-R hydrogens on C-9 and C-10 of stearic acid and showing that these are both lost by a ^«-elimination to give oleic acid. This is how the stereochemistry given in Figure 3.8 was determined. Similarly our knowledge of the stereochemistry of alcohol oxidation with NAD+, and carbonyl reduction with NADH comes from deuterium labelling (Figure 2.8).

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