Michael D. Sevilla

The Role of Charge and Spin Migration in DNA Radiation Damage

High energy radiation damage to DNA results in direct ionization of DNA and its immediate surroundings. Holes are generated throughout the DNA and its first hydration layer in accord with the electron density and the electrons produced add randomly to the DNA bases. Within a short time frame the holes move to the most stable site, the guanine base, or react by deprotonation thus localizing the damage. Electrons rapidly transfer to the DNA bases of highest electron affinity, thymine and cytosine. From these initial events the major products of radiation damage to DNA result. In Chap. 7, Becker, Adhikary and Sevilla have reviewed the recent efforts that have elucidated hole and electron transfer processes within DNA and from its hydration layer. In addition recent results are presented and discussed in this chapter. demonstrating that visible light induces hole transfer to other bases, as well as, most significantly, to the sugar phosphate backbone resulting in sugar radicals and ultimately strand breaks, i.e. a significant DNA damage.

Radiation Effects On DNA: Theoretical Investigations Of Electron, Hole And Excitation Pathways To DNA Damage

Radiation induced DNA damage is the most significant biological effect of radiation. Initially, radiation interacts with each component of DNA randomly resulting in DNA holes, electrons and excited states. Holes and electrons undergo rapid transfer to the most stable sites followed by proton transfer processes. These initial effects depend on the fundamental properties of DNA such as ionization potentials and electron affinities which are amenable to high level ab initio theories such as density functional theory. In this review, the recent theoretical treatments of these likely radiation intermediates are discussed. Topics include DNA base and base pair electron affinities, ionization potentials, proton transfer processes, solvation effects on the electron affinity of bases and base pairs, the role of low energy electrons (LEEs) in DNA damage, and sugar radical formation from hole excited states. These results clearly show a role for molecular orbital theories in developing a full explanation of the radiation damage processes

Electron Spin Resonance of Radicals in Irradiated DNA

Ionizing radiation produces DNA-cation radical (hole) and DNA-anion radical formation by random direct ionization of DNA and its microenvironments (e.g., layer of hydration) as well as excitation events. The best overall estimate of the probability of direct ionization at a given site in DNA (e.g., the sugar-phosphate backbone or the DNA bases) is provided by the number of valence electrons at that site. ESR spectroscopic studies at low temperature (e.g., 4 K, 77 K) have provided the direct evidence that via rapid charge (hole and excess electron transfer) processes, the hole is localized on the base of lowest ionization energy, guanine, and the excess electron is localized on the most electron affinic bases—thymine and cytosine. The guanine cation radical may deprotonate, undergo nucleophilic addition reactions such as water addition, or may even cause one-electron oxidation of a proximate sugar radical (double oxidation). The anion radical can undergo reversible as well as irreversible protonations. Also, prior to its thermalization, the prehydrated excess electron leads to frank strand break formation in DNA via dissociative electron attachment. In addition, recent ESR efforts have established that in the excited base cation radical, charge and spin transfer occur to the sugar-phosphate backbone and its subsequent kinetically controlled deprotonation within the lifetime of the excited state leads to the formation of strand break precursor sugar radical. These and other mechanisms of direct-type effect-induced DNA-radical formation that lead to production of stable damage, such as, strand breaks, are discussed in this chapter.

Thermally Induced Oxidation of [FeII(tacn)2](OTf)2 (tacn = 1,4,7-triazacyclononane)

We previously reported the spin-crossover (SC) properties of [FeII(tacn)2](OTf)2 (1) (tacn = 1,4,7-triazacyclononane) [Eur. J. Inorg. Chem. 2013, 2115]. Upon heating under dynamic vacuum, 1 undergoes oxidation to generate a low spin iron(III) complex. The oxidation of the iron center was found to be facilitated by initial oxidation of the ligand via loss of an H atom. The resulting complex was hypothesized to have the formulation [FeIII(tacn)(tacn-H)](OTf)2 (2) where tacn-H is N-deprotonated tacn. The formulation was confirmed by ESI-MS. The powder EPR spectrum of the oxidized product at 77 K reveals the formation of a low-spin iron(III) species with rhombic spectrum (g = 1.98, 2.10, 2.19). We have indirectly detected H2 formation during the heating of 1 by reacting the headspace with HgO. Formation of water (1HNMR in anhydrous d6-DMSO) and elemental mercury were observed. To further support this claim, we independently synthesized [FeIII(tacn)2](OTf)3 (3) and treated it with one equiv base yielding 2. The structures of 3 was characterized by X-ray crystallography. Compound 2 also exhibits a low spin iron(III) rhombic signal (g = 1.97, 2.11, 2.23) in DMF at 77 K. Variable temperature magnetic susceptibility measurements indicate that 3 undergoes gradual spin increase from 2 to 400 K. DFT studies indicate that the deprotonated nitrogen in 2 forms a bond to iron(III) exhibiting double bond character (Fe-N, 1.807 Å).