PCET in a Protein

In our calculations [47], we treated the net hydrogen transfer reaction catalyzed by lipoxygenase as a PCET mechanism, as illustrated in Fig. 16.9. Quantum mechanical calculations indicate that the electron transfers from the n system of the linoleic acid to an orbital localized on the Fe(III) center, and the proton transfers 

As shown in Fig. 16.10, the temperature dependence of the rates and KIEs predicted by the multistate continuum theory is in remarkable agreement with the experimental data [47]. The calculations indicate that the weak temperature dependence of the rates is due to the relatively small free energy barrier arising 

The theoretical results were generated with the multistate continuum theory including the proton donor-acceptor vibrational motion. Reproduced from Ref [47]. 

This chapter describes a general theoretical formulation for PCET and summarizes the results of applications to a wide range of different types of PCET reactions in solution and enzymes. This theoretical formulation treats the active electrons and transferring proton(s) quantum mechanically and includes the interactions among the electrons, proton(s), and solvent or protein environment. Moreover, this formulation allows the inclusion of the proton donor-acceptor motion, explicit molecular solvent and protein, and dynamical effects. The theory described here is directly applicable to nonadiabatic PCET reactions accompanied by substantial solute charge redistribution and solvent reorganization. 

Theoretical calculations on model PCET systems have assisted in the interpretation of experimental data and have provided insight into the underlying fundamental principles of PCET reactions. The theoretical framework described in this chapter enables the prediction of experimentally testable trends in rates and kinetic isotope effects. The interplay between experiment and theory will be vital to further progress in the field. 

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