C5′- and C3′-sugar radicals produced via photo-excitation of one-electron oxidized adenine in 2′-deoxyadenosine and its derivatives

We report that photo-excitation of one-electron-oxidized adenine [A(-H)•] in dAdo and its 2′-deoxyribonucleotides leads to formation of deoxyribose sugar radicals in remarkably high yields. Illumination of A(-H)• in dAdo, 3′-dAMP and 5′-dAMP in aqueous glasses at 143 K leads to 80-100% conversion to sugar radicals at C5′ and C3′. The position of the phosphate in 5′- and 3′-dAMP is observed to deactivate radical formation at the site of substitution. In addition, the pH has a crucial influence on the site of sugar radical formation; e.g. at pH ∼5, photo-excitation of A(-H)• in dAdo at 143 K produces mainly C5′• whereas only C3′• is observed at high pH ∼12. (13)C substitution at C5′ in dAdo yields (13)C anisotropic couplings of (28, 28, 84) G whose isotropic component 46.7 G identifies formation of the near planar C5′•. A β-(13)C 16 G isotropic coupling from C3′• is also found. These results are found to be in accord with theoretically calculated (13)C couplings at C5′ [DFT, B3LYP, 6-31(G) level] for C5′• and C3′•. Calculations using time-dependent density functional theory [TD-DFT B3LYP, 6-31G(d)] confirm that transitions in the near UV and visible induce hole transfer from the base radical to the sugar group leading to sugar radical formation

One-ElectronOxidation of Gemcitabine and Analogs:Mechanism of Formation of C3? and C2? Sugar Radicals

Gemcitabine is a modified cytidine analog having two fluorine atoms at the 2?-position of the ribose ring. It has been proposed that gemcitabine inhibits RNR activity by producing a C3?? intermediate via direct H3?-atom abstraction followed by loss of HF to yield a C2?? with 3?-keto moiety. Direct detection of C3?? and C2?? during RNR inactivation by gemcitabine still remains elusive. To test the influence of 2?- substitution on radical site formation, electron spin resonance (ESR) studies are carried out on one-electron oxidized gemcitabine and other 2?-modified analogs, i.e., 2?-deoxy-2?-fluoro-2?-C-methylcytidine (MeFdC) and 2?-fluoro-2?-deoxycytidine (2?-FdC). ESR line components from two anisotropic ?-2?-F-atom hyperfine couplings identify the C3?? formation in one-electron oxidized gemcitabine, but no further reaction to C2?? is found. One-electron oxidized 2?-FdC is unreactive toward C3?? or C2?? formation. In one-electron oxidized MeFdC, ESR studies show C2?? production presumably from a very unstable C3?? precursor. The experimentally observed hyperfine couplings for C2?? and C3?? match well with the theoretically predicted ones. C3?? to C2?? conversion in one-electron oxidized gemcitabine and MeFdC has theoretically been modeled by first considering the C3?? and H3O+ formation via H3?-proton deprotonation and the subsequent C2?? formation via HF loss induced by this proximate H3O+. Theoretical calculations show that in gemcitabine, C3?? to C2?? conversion in the presence of a proximate H3O+ has a barrier in agreement with the experimentally observed lack of C3?? to C2?? conversion. In contrast, in MeFdC, the loss of HF from C3?? in the presence of a proximate H3O+ is barrierless resulting in C2?? formation which agrees with the experimentally observed rapid C2?? formation

Magnetically Frustrated Quaternary Chalcogenides with Interpenetrating Diamond Lattices

A series of quaternary sulfides of the composition Na3MGaS4 (M = Mn (1), Fe (2), and Co (3)) have been synthesized in sealed quartz ampules. In these compounds, divalent transition metal and Ga occupy the same crystallographic site in the Ga-S network, forming a supertetrahedral, T2 (adamantane) unit, through the corner-sharing of four M/GaS4 tetrahedra. The corner sulfur atoms of the T2 clusters are further connected to similar T2 units to form an open continuous three-dimensional (3D) anionic framework of composition {[Ga2M2S8]n}6-. The framework resembles a zinc blende structure type if each T2 cluster is considered as a single tetrahedron and two such frameworks are intertwined to generate channels wherein reside the extra-framework Na+ ions. Placement of transition metals (Mn or Fe or Co) in the corner of a perfect supertetrahedron, adamantane building unit, generates an ideal lattice for geometrical magnetic frustration, which, on dilution with nonmagnetic metal (Ga), creates an ideal case for random frustration. Preliminary magnetic measurements indicate high negative values of the Weiss constant (-200 to -400 K) and the absence of any magnetic ordering, reinforcing the presence of magnetic frustration in all of these compounds

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

Radiation-produced electrons initiate various reaction processes that are important to radiation damage to biomolecules. In this work, the site of attachment of the prehydrated electrons with methyl acetoacetate (MAA, CH3-CO-CH2-COOCH3) at 77 K and subsequent reactions of the anion radical (CH3-CO•−-CH2-COOCH3) in the 77 to ca. 170 K temperature range have been investigated in homogeneous H2O and D2O aqueous glasses by electron spin resonance (ESR) spectroscopy. At 77 K, the prehydrated electron attaches to MAA forming the anion radical in which the electron is delocalized over the two carbonyl groups. This species readily protonates to produce the protonated electron adduct radical CH3-C(•)OH-CH2-COOCH3. The ESR spectrum of CH3-C(•)OH-CH2-COOCH3 in H2O shows line components due to proton hyperfine couplings of the methyl and methylene groups. Whereas, the ESR spectrum of CH3-C(•)OH-CH2-COOCH3 in D2O glass shows only the line components due to proton hyperfine couplings of CH3 group. This is expected since the methylene protons in MAA are readily exchangeable in D2O. On stepwise annealing to higher temperatures (ca. 150 to 170 K), CH3-C(•)OH-CH2-COOCH3 undergoes bimolecular H-atom abstraction from MAA to form the more stable radical, CH3-CO-CH•-COOCH3. Theoretical calculations using density functional theory (DFT) support the radical assignments

Ultrafast Processes Occurring in Radiolysis of Highly Concentrated Solutions of Nucleosides/Tides

Among the radicals (hydroxyl radical (•OH), hydrogen atom (H•), and solvated electron (esol−)) that are generated via water radiolysis, •OH has been shown to be the main transient species responsible for radiation damage to DNA via the indirect effect. Reactions of these radicals with DNA-model systems (bases, nucleosides, nucleotides, polynucleotides of defined sequences, single stranded (ss) and double stranded (ds) highly polymeric DNA, nucleohistones) were extensively investigated. The timescale of the reactions of these radicals with DNA-models range from nanoseconds (ns) to microseconds (µs) at ambient temperature and are controlled by diffusion or activation. However, those studies carried out in dilute solutions that model radiation damage to DNA via indirect action do not turn out to be valid in dense biological medium, where solute and water molecules are in close contact (e.g., in cellular environment). In that case, the initial species formed from water radiolysis are two radicals that are ultrashort-lived and charged: the water cation radical (H2O•+) and prethermalized electron. These species are captured by target biomolecules (e.g., DNA, proteins, etc.) in competition with their inherent pathways of proton transfer and relaxation occurring in less than 1 picosecond. In addition, the direct-type effects of radiation, i.e., ionization of macromolecule plus excitations proximate to ionizations, become important. The holes (i.e., unpaired spin or cation radical sites) created by ionization undergo fast spin transfer across DNA subunits. The exploration of the above-mentioned ultrafast processes is crucial to elucidate our understanding of the mechanisms that are involved in causing DNA damage via direct-type effects of radiation. Only recently, investigations of these ultrafast processes have been attempted by studying concentrated solutions of nucleosides/tides under ambient conditions. Recent advancements of laser-driven picosecond electron accelerators have provided an opportunity to address some long-term puzzling questions in the context of direct-type and indirect effects of DNA damage. In this review, we have presented key findings that are important to elucidate mechanisms of complex processes including excess electron-mediated bond breakage and hole transfer, occurring at the single nucleoside/tide level