RESUMO
Invited for the cover of this issue are the groups of Roman Dembinski, Mehran Mostafavi, and Amitava Adhikary at the Polish Academy of Sciences, Université Paris-Saclay, and Oakland University. The image depicts a doughnut as a way of illustrating the hole transfer process. Read the full text of the article at 10.1002/chem.202000247.
Assuntos
Nucleosídeos/química , Fosfatos/químicaRESUMO
The directionality of the hole-transfer processes between DNA backbone and base was investigated by using phosphorodithioate [P(S- )=S] components. ESR spectroscopy in homogeneous frozen aqueous solutions and pulse radiolysis in aqueous solution at ambient temperature confirmed initial formation of G.+ -P(S- )=S. The ionization potential of G-P(S- )=S was calculated to be slightly lower than that of guanine in 5'-dGMP. Subsequent thermally activated hole transfer from G.+ to P(S- )=S led to dithiyl radical (P-2S. ) formation on the µs timescale. In parallel, ESR spectroscopy, pulse radiolysis, and density functional theory (DFT) calculations confirmed P-2S. formation in an abasic phosphorodithioate model compound. ESR investigations at low temperatures and higher G-P(S- )=S concentrations showed a bimolecular conversion of P-2S. to the σ2 -σ*1 -bonded dimer anion radical [-P-2S - . 2S-P-]- [ΔG (150â K, DFT)=-7.2â kcal mol-1 ]. However, [-P-2S - . 2S-P-]- formation was not observed by pulse radiolysis [ΔG° (298â K, DFT)=-1.4â kcal mol-1 ]. Neither P-2S. nor [-P-2S - . 2S-P-]- oxidized guanine base; only base-to-backbone hole transfer occurs in phosphorodithioate.
Assuntos
Ânions/química , DNA/química , Guanina/química , Nucleosídeos/química , Fosfatos/química , Espectroscopia de Ressonância de Spin Eletrônica , Oxirredução , Radiólise de Impulso , Água/químicaRESUMO
This work shows that S atom substitution in phosphate controls the directionality of hole transfer processes between the base and sugar-phosphate backbone in DNA systems. The investigation combines synthesis, electron spin resonance (ESR) studies in supercooled homogeneous solution, pulse radiolysis in aqueous solution at ambient temperature, and density functional theory (DFT) calculations of in-house synthesized model compound dimethylphosphorothioate (DMTP(O-)âS) and nucleotide (5'-O-methoxyphosphorothioyl-2'-deoxyguanosine (G-P(O-)âS)). ESR investigations show that DMTP(O-)âS reacts with Cl2â¢- to form the σ2σ*1 adduct radical -P-S[Formula: see text]Cl, which subsequently reacts with DMTP(O-)âS to produce [-P-S[Formula: see text]S-P-]-. -P-S[Formula: see text]Cl in G-P(O-)âS undergoes hole transfer to Gua, forming the cation radical (Gâ¢+) via thermally activated hopping. However, pulse radiolysis measurements show that DMTP(O-)âS forms the thiyl radical (-P-Sâ¢) by one-electron oxidation, which did not produce [-P-S[Formula: see text]S-P-]-. Gua in G-P(O-)âS is oxidized unimolecularly by the -P-S⢠intermediate in the sub-picosecond range. DFT thermochemical calculations explain the differences in ESR and pulse radiolysis results obtained at different temperatures.
Assuntos
DNA , Fosfatos , DNA/química , Fosfatos/química , Radiólise de Impulso , Açúcares , EnxofreRESUMO
Two classes of azido-modified pyrimidine nucleosides were synthesized as potential radiosensitizers; one class is 5-azidomethyl-2'-deoxyuridine (AmdU) and cytidine (AmdC), while the second class is 5-(1-azidovinyl)-2'-deoxyuridine (AvdU) and cytidine (AvdC). The addition of radiation-produced electrons to C5-azido nucleosides leads to the formation of π-aminyl radicals followed by facile conversion to σ-iminyl radicals either via a bimolecular reaction involving intermediate α-azidoalkyl radicals in AmdU/AmdC or by tautomerization in AvdU/AvdC. AmdU demonstrates effective radiosensitization in EMT6 tumor cells.