31] The use of isotope effects to determine transition-state structure for enzymic reactions

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Isotope effects have been used for a long time to determine the structures of transition states for chemical reactions. Such analysis is made easier by the fact that the chemical reaction being looked at is often the sole rate-limiting step. There are two kinds of isotope effects: primary and secondary. A primary isotope effect results from substitution of a heavy atom in a position where a total bond cleavage (or bond formation) occurs. Conversely, secondary isotope effects result from isotopic substitution in a position where no bonds are made or broken, but there is a change in the strength of the bonding during the reaction (or to be precise, the bonding in the transition state differs from that in the reactant). Primary and secondary isotope effects are often treated as separate phenomena, because with deuterium the primary ones tend to be much larger than the secondary ones. There are different isotope effects on V and on V/K for each reactant, and it is not always easy to determine the intrinsic isotope effect on the bond-breaking step, which is the value that gives information on the structure of the transition state. This chapter reviews the status of techniques for determining intrinsic isotope effects and discusses the interpretation of these values in terms of transition-state structure.