It has long been assumed that the population of radicals trapped in irradiated DNA (that is, the radicals escaping recombination) would quantitatively account for the lesions observed in DNA. Recent results indicate that this is not the case. The yield of DNA lesions exceed the yield of trappable radicals. To account for a portion of this shortfall, it is thought that some of the initially formed 2′-deoxyribose radicals undergo a second oxidation by nearby base cation radicals to form 2′-carbocations. The carbocations react to give strand breaks and free base release. Schemes are presented to account for the major oxidation products observed including 8-oxoGua, 8-oxoAde, 5-OHMeUra, and free base release. Theoretical calculations were performed to ascertain the likelihood of the second oxidation step in these reaction pathways actually occurring, and to account for base sequence dependence and various levels of hydration.

We present an application of the linear scaling frozen density embedding (FDE) formulation of subsystem DFT to the calculation of isotropic hyperfine coupling constants (hfcc's) of atoms belonging to a guanine radical cation embedded in a guanine hydrochloride monohydrate crystal. The model systems range from an isolated guanine to a 15 000 atom QM/MM cluster where the QM region is comprised of 36 protonated guanine cations, 36 chlorine anions, and 42 water molecules. Our calculations show that the embedding effects of the surrounding crystal cannot be reproduced by small model systems nor by a pure QM/MM procedure. Instead, a large QM region is needed to fully capture the complicated nature of the embedding effects in this system. The unprecedented system size for a relativistic all-electron isotropic hfcc calculation can be approached in this work because the local nature of the electronic structure of the organic crystals considered is fully captured by the FDE approach.

For the DNA bases the pKa's of the neutral molecules have been measured, and a review article by Steenken provides a convenient summary of the experimental pKa's of the DNA radical ions. The purpose of the present work is to attempt to calculate the pKa's of the DNA radical ions and to compare these results with the experimental values. The agreement between the calculated and experimental pKa's for the guanine, cytosine, and thymine cations is very good but the pKa calculation on the adenine cation is not close to the experimental value. It is tempting to suggest that the pKa of the adenine cation is not actually ≤1 but is more likely somewhere near the calculated value of 3.9. Problems were encountered in calculating the pKa's of the one-electron reduced nucleobases because optimizations tend to produce nonplanar structures. The calculations presented show close agreement between the calculated and experimental pKa's for the thymine, cytosine, and adenine anions. Although there are no experimental data for the pKa of the guanine reduction product, the calculated value of 17.6 seems to be too high, given that for thymine the protonation is also at oxygen and results in a rather low pKa.

The nearby red supergiant (RSG) Betelgeuse has a complex circumstellar medium out to at least 0.5 parsecs from its surface, shaped by its mass-loss history within the past ≈ 0.1 Myr, its environment, and its motion through the interstellar medium (ISM). In principle its mass-loss history can be constrained by comparing hydrodynamic models with observations. Observations and numerical simulations indicate that Betelgeuse has a very young bow shock, hence the star may have only recently become a RSG. To test this possibility we calculated a stellar evolution model for a single star with properties consistent with Betelgeuse. We incorporated the resulting evolving stellar wind into 2D hydrodynamic simulations to model a runaway blue supergiant (BSG) undergoing the transition to a RSG near the end of its life. The collapsing BSG wind bubble induces a bow shock-shaped inner shell which at least superficially resembles Betelgeuse's bow shock, and has a similar mass. Surrounding this is the larger-scale retreating bow shock generated by the now defunct BSG wind's interaction with the ISM. We investigate whether this outer shell could explain the bar feature located (at least in projection) just in front of Betelgeuse's bow shock.

The process of stabilizing radiation damage in the base pair of 1-methylcytosine (1-MeC):5-fluorouracil (5FU) has been investigated. The formation of free radicals in purines and pyrimidines is influenced by the matrix in which they are irradiated. Of particular interest are the systems in which two different nucleic acid bases are complexed, providing situations that approximate the close proximity of bases in nucleic acid polymers. Detailed EPR/electron-nuclear double resonance experiments show that only the N3 protonated cytosine anion and the N1 deprotonated uracil cation are observed in single crystals of 1-MeC:5-FU, X-irradiated, and observed at 10 K. Upon warming one observes a radical formed by net hydrogen addition to C6 on uracil, and an allylic radical on the C4-C5-C6 region of the uracil. No cytosine C5 or C6 H-addition radicals are observed. The implications that free radical damage is transferred from the cytosine moiety to the uracil moiety in 1-MeC:5-FU is discussed. Single point calculations were performed on the optimized geometries at the B3LYP/6-311G(2df,p) level to obtain accurate energies and spin populations. To obtain electron affinities of the neutral'parent molecules, the larger 6-311+G(2df,p) basis set was used. Results show that the cytosine base will be the preferred site of electron addition, and the uracil base will be the site of electron loss. Additional studies were performed to investigate the influence of the hydrogen-bonded crystal matrix on the stabilities of the initial radical ions. On the basis of these studies, a proton shuttle mechanism is proposed that provides an efficient transfer of charge away from the initial sites of electron addition or electron loss, leaving behind neutral radical sites that are less susceptible to recombination.

We carried out a detailed quantum mechanical study of the unimolecular decomposition mechanism of pyridine. The critical structures of all reasonable reaction pathways were optimized by density functional theory using the B3LYP functional and 6-3IG** basis set. Relative energies were evaluated based on single-point QCISD(T)/cc-pVDZ energies. In agreement with general belief and pervious theoretical studies, the calculated results indicate that C-H bond scission in pyridine preferentially produces the o-pyridyl radical. Also in agreement with the accepted mechanism, the calculations indicate that ring-opening via C-N bond cleavage in o-pyridyl radical is more favorable than C-C bond cleavage, as the former has a significantly lower activation barrier and the resulting open-chain cyano radical is more stable than other linear CsNFL; radicals. The calculated activation energy for the formation of cyanovinylacetylene + H from the open-chain cyano radical is the lowest, compared to the other channels considered. However, activation entropy favors C-C bond cleavage producing acetylene and cyanovinyl radical instead of cyanovinylacetylene and atomic hydrogen. On the basis of the calculated activation energies and activation entropies, transition state theory predicts that, in the temperature range of 1300-1800 K, the formation of acetylene + cyanovinyl radical from o-pyridyl radical is two to three times the rate of formation of cyanovinylacetylene + H. The calculations indicate that direct C-H bond scission from all three pyridyl radicals producing 2,3- and 3,4-pyridynes is also a favorable channel from energy consideration.

Single crystals of deoxycytidine hydrochloride (CdR·HCl) have been X- irradiated at 10 K with doses up to about 150 kGy and studied using 24 GHz (K-band) EPR, ENDOR and FSE spectroscopy. In this system, the cytosine base is protonated at the N3 position. Nine different radicals were characterized and identified. Three of these are ascribed to three versions of the one- electron reduced species, probably differing in their protonation state. Radicals formed by net hydrogen addition to the cytosine C5 and C6 positions were observed at 10 K. The hydrogen-abstraction radical at the deoxyribose C1' position most probably results from initial oxidation of the base. The remaining radical species are all localized to the sugar moiety, representing products formed by net hydrogen abstraction from three of the five available carbons of the deoxyribose sugar. The lack of base-centered oxidation products as well as the structures of the one-electron reduced species is rationalized by considering the specific proton donor-acceptor properties of this crystalline lattice in comparison with similar systems.

It has long been assumed that the population of radicals trapped in irradiated DNA (that is, the radicals escaping recombination) would quantitatively account for the lesions observed in DNA. Recent results indicate that this is not the case. The yield of DNA lesions exceed the yield of trappable radicals. To account for a portion of this shortfall, it is thought that some of the initially formed 2′-deoxyribose radicals undergo a second oxidation by nearby base cation radicals to form 2′-carbocations. The carbocations react to give strand breaks and free base release. Schemes are presented to account for the major oxidation products observed including 8-oxoGua, 8-oxoAde, 5-OHMeUra, and free base release. Theoretical calculations were performed to ascertain the likelihood of the second oxidation step in these reaction pathways actually occurring, and to account for base sequence dependence and various levels of hydration.

We present an application of the linear scaling frozen density embedding (FDE) formulation of subsystem DFT to the calculation of isotropic hyperfine coupling constants (hfcc's) of atoms belonging to a guanine radical cation embedded in a guanine hydrochloride monohydrate crystal. The model systems range from an isolated guanine to a 15 000 atom QM/MM cluster where the QM region is comprised of 36 protonated guanine cations, 36 chlorine anions, and 42 water molecules. Our calculations show that the embedding effects of the surrounding crystal cannot be reproduced by small model systems nor by a pure QM/MM procedure. Instead, a large QM region is needed to fully capture the complicated nature of the embedding effects in this system. The unprecedented system size for a relativistic all-electron isotropic hfcc calculation can be approached in this work because the local nature of the electronic structure of the organic crystals considered is fully captured by the FDE approach.

For the DNA bases the pKa's of the neutral molecules have been measured, and a review article by Steenken provides a convenient summary of the experimental pKa's of the DNA radical ions. The purpose of the present work is to attempt to calculate the pKa's of the DNA radical ions and to compare these results with the experimental values. The agreement between the calculated and experimental pKa's for the guanine, cytosine, and thymine cations is very good but the pKa calculation on the adenine cation is not close to the experimental value. It is tempting to suggest that the pKa of the adenine cation is not actually ≤1 but is more likely somewhere near the calculated value of 3.9. Problems were encountered in calculating the pKa's of the one-electron reduced nucleobases because optimizations tend to produce nonplanar structures. The calculations presented show close agreement between the calculated and experimental pKa's for the thymine, cytosine, and adenine anions. Although there are no experimental data for the pKa of the guanine reduction product, the calculated value of 17.6 seems to be too high, given that for thymine the protonation is also at oxygen and results in a rather low pKa.