The applicability of the kinetic method for measuring relative affinities of macromolecules for polyatomic substrates

This paper is a review of the kinetic method for the determination of thermochemical values for gas-phase molecules. In addition, we have explored the utility of the kinetic method to obtain meaningful relative binding energies of macromolecules for polyatomic substrates using a system comprising poly(methylmethacrylate) (PMMA) oligomers and doubly protonated diaminoalkanes. The major factors which determined the suitability of the kinetic method for this system were identified as (i) the structural arrangement of the parent ion complex, (ii) possible reverse activation barriers, and (iii) the evaluations of Δ(ΔS‡). Molecular mechanics/molecular dynamics (MM/MD) simulations, together with ion mobility spectrometry, suggests the parent ion complexes represent a relatively equal sharing of the substrate between two the PMMA oligomers within the complex and that the two PMMA oligomers interact almost exclusively with the substrate, and not with each other. MS/MS of the trimeric parent complexes resulted in one PMMA unit leaving as a neutral which suggests very limited coulombic repulsion (that would contribute to a reverse activation barrier). The drift times of PMMA-diaminoalkane complexes that were generated directly by ESI-MS or by dissociation of a trimeric PMMA-diaminoalkane-PMMA complex were found to be identical, and when combined with MM/MD simulations suggested that the product PMMA-diaminoalkane dication has the same conformation as it does when part of a trimeric complex. This is evidence for Δ(ΔS‡) ≃ Δ(ΔS) and using a statistical mechanics approach, Δ(ΔS) ≃ 0. The effective temperature variable in the kinetic method expression was found to decrease as a function of the size of the trimeric complex, suggesting that the population distribution of the dissociating ensemble of complexes narrows as size increases.