Lidia Chomicz

Electron-induced elimination of the bromide anion from brominated nucleobases : a computational study

The enhancement of radiodamage to DNA labeled with halonucleobases is attributed to the reactive radical produced from a halonucleobase by the attachment of an electron. We examined at the B3LYP/6-31++G** level electron capture by four brominated nucleobases (BrNBs): 8-bromo-9-methyladenine, 8-bromo-9-methylguanine, 5-bromo-1-methylcytosine, and 5-bromo-1-methyluracil followed by the release of the bromide anion and a nucleobase radical. We demonstrate that neutral BrNBs in both gas and aqueous phases are better electron acceptors than unsubstituted NBs and that resulting anion radicals, BrNBs(•-), can easily transform into the product complex of the bromide anion and the nucleobase radical ([Br(-)···NB(•)]). The overall thermodynamic stimulus for the process starting with the neutral BrNB and ending with the isolated bromide anion and the NB(•) radical is similar in the case of all four BrNBs studied, which suggests their comparable radiosensitizing capabilities.

Valence anions of N-acetylproline in the gas phase: Computational and anion photoelectron spectroscopic studies

We report the photoelectron spectrum of anionic N-acetylproline, (N-AcPro)(-), measured with 3.49 eV photons. This spectrum, which consists of a band centered at an electron binding energy of 1.4 eV and a higher energy spectral tail, confirms that N-acetylproline forms a valence anion in the gas phase. The neutrals and anions of N-AcPro were also studied computationally at the B3LYP∕6-31++G(d,p) level. Based on the calculations, we conclude that the photoelectron spectrum is due to anions which originated from proton transfer induced by electron attachment to the π* orbital localized at the acetyl group of N-AcPro. We also characterized the energetics of reaction paths leading to pyrrolidine ring opening in the anionic N-AcPro. These data suggest that electron induced decomposition of peptides/proteins comprising proline strongly depends on the presence of proton donors in the close vicinity to the proline residue.

Presolvated low energy electron attachment to peptide methyl esters in aqueous solution: C-O bond cleavage at 77 K.

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 γ-irradiation in neutral 7.5 M LiCl-D2O aqueous glasses at low temperatures. For glycine methyl ester, electron addition at 77 K 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 77 K and cleave the carboxyl ester groups to produce methyl radicals. On annealing to 160 K, electron adducts at the peptide links undergo chain scission to produce alanyl radicals and on further annealing to 170 K 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.

Radicals Formed in N-Acetylproline by Electron Attachment: Electron Spin Resonance Spectroscopy and Computational Studies

In this study, the reactions of electrons with N-acetylproline are investigated by electron spin resonance (ESR) spectroscopy and density functional theory. Electrons are produced by γ irradiation or by photoionization of K(4)Fe(CN)(6) in neutral 7.5 M LiCl-D(2)O aqueous glasses at low temperatures with identical results. Electrons are found to add to both the peptide bond and the carboxyl group of the acetyl-proline moiety at 77 K. On annealing, both the electron adducts undergo fragmentation of the peptide bond between the nitrogen and the α carbon of the peptide structure. However, the peptide bond electron adduct radical reacts much more rapidly than the carboxyl group electron adduct radical. The DFT calculations predict that the carboxyl adduct is substantially more stable than the peptide bond adduct, with the activation barrier to N-Cα cleavage 3.7 kcal/mol for the amide electron adducts and 23 kcal/mol for the carboxyl electron adducts in inagreement with the relative reactivity found by experiment.