Coulomb-Assisted Dissociative Electron Attachment: Application to a Model Peptide Monika Sobczyk, ‡,§ Iwona Anusiewicz, ²,‡,§ Joanna Berdys-Kochanska, ‡,§ Agnieszka Sawicka, ‡,§ Piotr Skurski, ‡,§ and Jack Simons* ,‡ Chemistry Department and Henry Eyring Center for Theoretical Chemistry, UniVersity of Utah, Salt Lake City, Utah 84112, U.S.A., and Department of Chemistry, UniVersity of Gdansk, 80-952 Gdansk, Poland ReceiVed: August 16, 2004; In Final Form: October 12, 2004 The fragmentation of positively charged gas-phase samples of peptides is used to infer the primary structure of such molecules. In electron capture dissociation (ECD) experiments, very low-energy electrons attach to the sample and rupture bonds to effect the fragmentation. It turns out that ECD fragmentation tends to produce cleavage of very specific types of bonds. In earlier works by this group, it has been suggested that the presence of positive charges produces stabilizing Coulomb potentials that allow low-energy electrons to exothermically attach to σ* orbitals of certain bonds and thus to cleave those bonds. In the present effort, the stabilizing effects of Coulomb potentials due to proximal positive charges are examined for a small model peptide molecule that contains a wide range of bond types. Direct attachment of an electron to the σ* orbitals of eight different bonds as well as indirect σ bond cleavage, in which an electron first binds to a carbonyl CdO π* orbital, are examined using ab initio methods. It is found that direct attachment to and subsequent cleavage of any of the eight σ bonds is not likely except for highly positively charged samples. It is also found that attachment to aCdO π* orbital followed by cleavage of the nitrogen-to-R-carbon bond is the most likely outcome. Interestingly, this bond cleavage is the one that is seen most commonly in ECD experiments. So, the results presented here seem to offer good insight into one aspect of the ECD process, and they provide a means by which one can estimate (on the basis of a simple Coulomb energy formula) which bonds may be susceptible to cleavage by low-energy electron attachment. I. Introduction We recently showed 1 that low-energy electrons (i.e., with kinetic energies near zero) could directly and even vertically (i.e., at the equilibrium geometry of the neutral) attach to and subsequently fragment S-S σ bonds in disulfide-linked dimers of Ac-Cys-Ala n -Lys (with n ) 10, 15, and 20) that are protonated at their two Lys sites. An example of such a species is shown in Figure 1 where the alanine helices are shown in red, the cystine linkage containing the S-S bond appears in the center, and the two Lys sites are at the termini. In the mechanism treated in ref 1, an electron enters the S-S antibonding σ* orbital to form a metastable anion that can either undergo electron autodetachment at a rate of ca. 10 15 -10 14 s -1 or fragment (promptly because of the repulsive nature of the σ* anion’s energy surface) to form an R-S radical and an -S- R′ anion. The yield of bond cleavage is governed by competition between fragmentation on the σ* surface and autodetachment. The ab initio calculations of ref 1 were carried out on a very simple model of the disulfide shown in Figure 1, the H 3 C-S- S-CH 3 molecule. The R-S-S-R′ neutral and corresponding anion potential energy curves for dimethyl disulfide as functions of the S-S distance are depicted below in Figure 2. Although there had been previously very good theoretical studies 3 of reductive S-S bond cleavage, they have not focused on the regions of the anion’s energy surface, at which this species is electronically metastable to autodetachment. For example, they did not consider direct near-vertical electron attachment to the σ* orbital of the S-S bond to produce an unstable σ* anion. Rather, these studies were limited to treating * Corresponding author. E-mail: simons@chemistry.utah.edu. ² A holder of a Foundation for Polish Science (FNP) Award. ‡ University of Utah. § University of Gdansk. Figure 1. Structure of an (AcCA15K + H)2 2+ disulfide-linked dimer from ref 2. The disulfide linkage is at the center, and the two protonated sites are at the left and right ends. Figure 2. Energies of the dimethyl disulfide neutral (circles) and σ* anion (triangles) as functions of the S-S bond length (Å) with all other geometrical degrees of freedom relaxed to minimize the energy. 250 J. Phys. Chem. A 2005, 109, 250-258 10.1021/jp0463114 CCC: $30.25 © 2005 American Chemical Society Published on Web 12/13/2004