Presolvated Low Energy Electron Attachment to Peptide Methyl Esters in Aqueous Solution: C–O Bond Cleavage at 77 K

Abstract

In this study, the reactions of presolvated electrons with glycine methyl ester and N-acetylalanylalanine methyl ester (N-aAAMe) are investigated by electron spin resonance (ESR) spectroscopy and DFT calculations. Electrons were produced by gamma irradiation in neutral 7.5 M LiCl-D2O aqueous glasses at low temperatures. For glycine methyl ester electron addition at 77K results in both N-terminal deamination to form a glycyl radical and C-O ester bond cleavage to form methyl radicals. For samples of N-acetylalanylalanine methyl ester electrons are found to add to the peptide bonds at 77K and cleave the carboxyl ester groups to produce methyl radicals. On annealing to 160K electron adducts at the peptide links undergo chain scission to produce alanyl radicals and further annealing to 170K α-carbon peptide backbone radicals are produced by hydrogen abstraction. DFT calculations for electron addition to the methyl ester portion of N-aAAMe show the cleavage reaction is highly favorable (free energy equals to −30.7 kcal/mol) with the kinetic barrier of only 9.9 kcal/mol. A substantial electron affinity of the ester link (38.0 kcal/mol) provides more than sufficient energy to overcome this small barrier. Protonated peptide bond electron adducts, also show favorable N-C chain cleavage reactions of −12.7 to −15.5 kcal/mol with a barrier from 7.4 to 10.0 kcal/mol. The substantial adiabatic electron affinity (AEA) of the peptide bond and ester groups provides sufficient energy for the bond dissociation.

Gamma and ion-beam irradiation of DNA: Free radical mechanisms, electron effects, and radiation chemical track structure

“…Though this work is very interesting, since the solutes did not have high enough solute concentrations to scavenge extremely short lived (0.3 ps) e pre − , the role of e pre − is an open question. Very recently, the reactions of e pre − with glycine methyl ester and N-acetylalanylalanine methyl ester have been investigated using ESR at 77 K and density functional theory (DFT) (Kheir et al, 2013). In this study, it was found that e pre − adds to the peptide bonds initially at 77 K and subsequently cleaves the carboxylic ester group to produce methyl radical.…”

Presolvated Electron Reactions with Methyl Acetoacetate: Electron Localization, Proton-Deuteron Exchange, and H-Atom Abstraction

“…After the solute is fully dissolved, the solution has been bubbled with nitrogen gas for 5 min to remove oxygen from the samples. Subsequently, the solution is drawn into a 4 mm quartz tube and rapidly cooled to 77 K in liquid nitrogen to form a clear transparent glass as in our earlier works [ 8 , 9 , 10 , 11 , 13 , 14 , 15 , 16 , 18 , 19 , 20 ].…”

“…For many molecular systems with functional groups that can capture electrons such as ketones, esters, carboxylic acids, and peptides, it is well known that the anion radicals formed on e pre − addition undergo subsequent reactions [ 8 , 9 , 10 , 11 ]. For peptides, the most common reaction of the anion radical is either deamination or deamidation.…”

“…170 K temperature range employing electron spin resonance (ESR) spectroscopy and density functional theory (DFT). We note that irradiation of 7.5 M LiCl aqueous glasses at 77 K produces only two intermediates: prehydrated electrons and Cl 2 • − [ 10 , 13 , 14 ]. In our system Cl 2 • − is unable to one-electron oxidize simple aliphatic ketones or esters and thus does not interfere with the study of the reactions of prehydrated electron [ 10 ].…”

“…We note that irradiation of 7.5 M LiCl aqueous glasses at 77 K produces only two intermediates: prehydrated electrons and Cl 2 • − [ 10 , 13 , 14 ]. In our system Cl 2 • − is unable to one-electron oxidize simple aliphatic ketones or esters and thus does not interfere with the study of the reactions of prehydrated electron [ 10 ]. The combination of experimental and theoretical results clearly shows that in MAA the initial localization of the electron is chiefly at the carbonyl site and that protonation of the carbonyl group further localizes the electron to this site.…”