Z. Phys. Chem. 218 (2004) 17–49  by Oldenbourg Wissenschaftsverlag, München Kinetic Hydrogen/Deuterium Isotope Effects in Multiple Proton Transfer Reactions By Hans-Heinrich Limbach 1 , ∗ , Oliver Klein 1 , Juan Miguel Lopez Del Amo 2 , and Jose Elguero 2 1 Institut für Chemie der Freien Universität Berlin, Takustrasse 3, D-14195 Berlin, Germany 2 Instituto de Qu´ ımica M´ edica, CSIC, Juan de la Cierva 3, E-28006 Madrid, Spain Dedicated to Prof. Dr. Herbert Zimmermann on the occasion of his 75 th birthday (Received May 20, 2003; accepted July 8, 2003) Multiple Proton Transfer / Kinetic Isotope Effects In this paper, a description of multiple kinetic isotope effects (MKIE) of degenerate double, triple and quadruple proton transfer reactions in terms of formal kinetics is developped. Both single and multiple barrier processes are considered, corresponding to so-called “concerted” and “stepwise” reaction pathways. Each step is characterized by a rate constant and the transfer of a given H isotopes or ensemble of H isotopes. The MKIE are expanded in terms of kinetic H/D isotope effects P contributed by single sites in which a proton is transferred in the rate limiting steps. By combination with a modified Bell tunneling model the formalism developed can be used in order to take into account tunneling effects of both concerted and stepwise multiple proton transfers at low temperatures. 1. Introduction Proton transfer constitutes a very complex process, consisting not only of the transfer of a proton but also of diffusion, transport of electrical charges, reori- entation and reorganisation of the solvent molecules, hydrogen bond breaking and forming processes. One way to obtain information about these elementary steps is the measurement and interpretation of kinetic H/D isotope effects. The first theories of these effects were developed by Bigeleisen [1] by a combi- nation of transition state theory and the theory of isotopic fractionation, and by Bell [2], who included tunneling phenomena at low temperatures. Later * Corresponding author. E-mail: limbach@chemie.fu-berlin.de