Entropy Is the Major Driving Force for Fragmentation of Proteins and Protein−Ligand Complexes in the Gas Phase

This paper presents a critical analysis of Arrhenius parameters for gas-phase fragmentation of proteins and protein−ligand complexes reported in the literature. We demonstrate that there is a surprisingly strong correlation between the Arrhenius activation energy ( E a ) and the preexponential factor ( A ). This correlation becomes extremely important for reactions characterized by very high or very low values of A . This correlation is a direct consequence of the relative change in the spacing between vibrational levels of the reactant and the transition state for reaction. Converting the Arrhenius activation energy into the threshold energy for the reaction using Tolman's theorem reveals the true magnitude of the correlation between molecular complexity and stability. Tolman's correction factor (Δ E corr ) increases linearly with log( A ) from 3 kcal/mol for log( A ) = 16.2 to 36.4 kcal/mol for log( A ) = 39.2. Threshold energies extracted from the Arrhenius activation parameters for 56 different reactions are the same within the experimental error bars, while the preexponential factors differ by many orders of magnitude. This indicates that activation entropy is the major driving force for dissociation of proteins and protein−ligand complexes in the gas phase.