ABSTRACT
I. Introduction ...................................................................................................................... 975
II. Zero-Point Energy Effects and Hydrogen Bonds ............................................................ 977
A. Classification of Hydrogen Bond Types.................................................................. 977
B. NMR Chemical Shifts of Strong Hydrogen Bonds................................................. 978
C. Isotope Effects on Physical Parameters................................................................... 979
1. Isotope Effects on Vibrational Frequencies...................................................... 979
2. Isotope Effects on Chemical Shifts of LBHBs................................................. 980
3. D/H Fractionation Factors................................................................................. 981
D. Strengths of Hydrogen Bonds.................................................................................. 981
III. Low-Barrier Hydrogen Bonds in Enzymes ..................................................................... 982
A. Serine Proteases ....................................................................................................... 982
B. Cholinesterases......................................................................................................... 985
C. D
-3-Ketosteroid Isomerase ..................................................................................... 986
IV. Role of Low-Barrier Hydrogen Bonds in the Actions of Enzymes................................ 987
A. Serine Proteases and Esterases ................................................................................ 987
B. D
-3-Ketosteroid Isomerase ..................................................................................... 990
C. Other Enzymes ......................................................................................................... 990
Acknowledgments ........................................................................................................................ 990
References..................................................................................................................................... 990
In this article, the focus will be on the importance of zero-point vibrational energy effects in the
characterization of low-barrier hydrogen bonds (LBHBs). The most widely studied zero point-
phenomena are kinetic-isotope effects. The observation of a kinetic-isotope effect identifies a
rate-limiting step in a complex reaction mechanism, and the magnitude of the effect includes
information about the structure of the activated complex or transition state. The theory of KIEs is
well developed, and the observation of experimental deviations from theory in deuterium or tritium
KIEs can give clues to the possible involvement of quantum mechanical tunneling in hydrogen
transfer mechanisms. The classical theory of KIEs is centered on the kinetic consequences of zero-
point vibrational energy differences between isotopes of an atom undergoing a chemical change.
However, zero point effects also figure prominently in other phenomena, including the isotope
effects on the physical properties of hydrogen bonds.
