Page 37 - Visions of the Future Chemistry and Life Science

26 M. J. SUTCLIFFE AND N. S. SCRUTTON

Paradoxically, reaction rates (as with transition state theory) are still highly
dependent on temperature. This observation is inconsistent with a pure
‘ground state’ tunnelling reaction, since the probability of tunnelling (and
thus rate of reaction) is a function of barrier width, but is independent of
temperature. This apparent paradox is resolved by taking into account the
temperature-dependent natural breathing of enzyme molecules which dis-
torts the structure of the protein to produce the geometry required for
nuclear tunnelling (achieved by reducing the width of the barrier between
reactants and products, thus increasing the probability of tunnelling). In
this dynamic view of enzyme catalysis, it is thus the width – and not the
height (as with transition state theory) – of the energy barrier that controls
the reaction rate.
The important criterion thus becomes the ability of the enzyme to
distort and thereby reduce barrier width, and not stabilisation of the tran-
sition state with concomitant reduction in barrier height (activation
energy). We now describe theoretical approaches to enzymatic catalysis
that have led to the development of dynamic barrier (width) tunnelling the-
ories for hydrogen transfer. Indeed, enzymatic hydrogen tunnelling can be
treated conceptually in a similar way to the well-established quantum the-
ories for electron transfer in proteins.

2.2 Enzyme catalysis in the classical world
In the classical world (and biochemistry textbooks), transition state theory
has been used extensively to model enzyme catalysis. The basic premise of
transition state theory is that the reaction converting reactants (e.g. A–H
B) to products (e.g. A B–H) is treated as a two-step reaction over a static
‡
potential energy barrier (Figure 2.1). In Figure 2.1, [A . . . H . . . B] is the transi-
tion state, which can interconvert reversibly with the reactants (A–H B).
However, formation of the products (A B–H) from the transition state is an
irreversible step.
Transition state theory has been useful in providing a rationale for the
so-called ‘kinetic isotope effect’. The kinetic isotope effect is used by enzy-
mologists to probe various aspects of mechanism. Importantly, measured
kinetic isotope effects have also been used to monitor if non-classical beha-
viour is a feature of enzyme-catalysed hydrogen transfer reactions. The
kinetic isotope effect arises because of the differential reactivity of, for
example, a C–H (protium), a C–D (deuterium) and a C–T (tritium) bond.