Dynamic barriers and tunneling. New views of hydrogen transfer in enzyme reactions
J. P. Klinman
Department of Chemistry and Department of Molecular
and Cell Biology,
University of California, Berkeley, CA 94720, USA
Abstract: Hydrogen-transfer processes
are expected to show appreciable quantum mechanical behavior. Intensive
investigations of enzymes under their physiological conditions show
this to be true in practically every example investigated. Initially,
tunneling was treated either as a tunneling correction [cf. Bell, The
Tunnel Effect in Chemistry, Chapman & Hall, New
York, (l980)], or as corner-cutting [Truhlar et al., J. Chem. Phys.
100, 12771 (l996)]. This worked well as long as the observed properties
could be explained by “corrections” to transition-state
theory. However, over the past several years, enzymatic behaviors have
been observed that are so deviant as to lie outside of transition-state
theory. This phenomenon is discussed in the context of the enzyme, soybean
lipoxygenase. An environmentally coupled
hydrogen-tunneling model is presented that derives from the treatments
of Kuznetsov and Ullstrup [Can. J. Chem. 77, 689 (l999)], and
includes heavy-atom reorganization (temperature-dependent and largely
isotope-independent), together with heavy-atom gating (temperature-
and isotope-dependent). This treatment can explain a wide range of behaviors
and leads to a new view of the origin of kinetic isotope effects in
hydrogen-transfer reactions. These properties link enzyme fluctuations
to the hydrogen-transfer reaction coordinate, making a quantum view
of H-transfer necessarily a dynamic view of catalysis.
*Plenary lectures presented at the 16th International Conference on Physical Organic Chemistry (ICPOC-16): Structure and Mechanism in Organic Chemistry,San Diego, California, USA, 4�9 August 2002. Other presentations are published in this issue, pp. 541�630.
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