Heavy atom motions and tunneling in hydrogen transfer reactions: the importance of the pre-tunneling state

Arrhenius curves of selected hydrogen transfer reactions in organic molecules and enzymes are reviewed with the focus on systems exhibiting temperature-independent kinetic isotope effects. The latter can be rationalized in terms of a 'pre-tunneling state' which is formed from the reactants by heavy atom motions and which represents a suitable molecular configuration for tunneling to occur. Within the Bell-Limbach tunneling model, formation of the pre-tunneling state dominates the Arrhenius curves of the H and the D transfer even at higher temperatures if a large energy E(m) is required to reach the pre-tunneling state. Tunneling from higher vibrational levels and the over-barrier reaction via the transition state which lead to temperature-dependent kinetic isotope effects dominate the Arrhenius curves only if E(m) is small compared to the energy of the transition state. Using published data on several hydrogen transfer systems, the type of motions leading to the pre-tunneling state is explored. Among the phenomena which lead to large energies of the pre-tunneling state are (i) cleavage of hydrogen bonds or coordination bonds of the donor or acceptor atoms to molecules or molecular groups in order to allow the formation of the pre-tunneling state, (ii) the occurrence of an energetic intermediate on the reaction pathway within which tunneling takes place, and (iii) major reorganization of a molecular skeleton, requiring the excitation of specific vibrations in order to reach the pre-tunneling state. This model suggests a solution to the puzzle of Kwart's findings of temperature-independent kinetic isotope effects for hydrogen transfer in small organic molecules. Copyright (C) 2010 John Wiley & Sons, Ltd.