Electron capture and electron transfer dissociations are bioanalytical methods for fragmenting cations after reduction by an electron. Previous computational studies based on conventional DFT schemes have concluded that the first step of these processes, the attachment of the electron, leads to extensive delocalization of the spin density in the intermediate radical cation. Here we show that most DFT methods produce unphysical results when studying single electron reduction of a dicationic peptide. This is not the case for post-HF methods and long-range corrected functionals that show satisfying electron affinities, intermolecular interaction energies, and spin density trends. Our results suggest that the charged group with the highest electron affinity on the precursor cation is also the site of spin density in the electronic ground state after electron attachment. These findings have important implications for the interpretation of experimental data from electron-based processes in biomolecules and may guide the development of new functionals.SECTION: Molecular Structure, Quantum Chemistry, General Theory E lectron capture dissociation (ECD) 1,2 and electron transfer dissociation (ETD) 3 are efficient fragmentation techniques, available on Fourier transform ion cyclotron resonance and ion trap or Q-TOF mass spectrometers, respectively. These methods have an important potential for the structural analysis of peptides or proteins. 4À6 Electron capture by, or transfer to, cationic peptides or proteins in the gas phase characteristically results in cleavage of NÀC R bonds, which makes these techniques complementary to collision-induced dissociation (CID) where peptidic bonds are cleaved. ECD and ETD also have some advantages compared with CID: they preserve labile post-translational modifications, and they allow fragmentation of larger peptides and even entire proteins without prior digestion, making these approaches particularly suitable for top-down proteomics.In ECD and ETD, a multiply charged cation is partially reduced by receiving one electron, thereby converting it from a closed-shell specie to an intermediate cation-radical that undergoes fragmentation. The exact mechanism(s) implicated in such a process are still a matter of active discussion from both computational and experimental points of view. 7À12 Although there is consensus that the spin must become localized on a backbone carbonyl carbon to precipitate cleavage of an adjacent NÀC R bond, the pathway the electron takes to reach the carbonyl remains unresolved. Does the electron attach itself directly to an amide π* orbital, which may be an excited state (the UtahÀWashington mechanism), 13,14 or are preliminary structural rearrangement(s) needed (the Cornell mechanism)? 1 Recent theoretical studies indicate that the vertical reduction of protonated peptides lead to a highly delocalized spin density in the ground state. Delocalization could extend to spatially remote charged groups (ammonium, 15,16 guanidinium, 17 histidinium, 18 amide and/or carbonyl...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.