Model studies of DNA C5' radicals. Selective generation and reactivity of 2'-deoxyadenosin-5'yl radical (Articolo in rivista)

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  • Model studies of DNA C5' radicals. Selective generation and reactivity of 2'-deoxyadenosin-5'yl radical (Articolo in rivista) (literal)
Anno
  • 2003-01-01T00:00:00+01:00 (literal)
Alternative label
  • 29207 CHATGILIALOGLU CHRYSSOSTOMOS ; 7896 MAURIZIO GUERRA; 13368 MULAZZANI QUINTO (2003)
    Model studies of DNA C5' radicals. Selective generation and reactivity of 2'-deoxyadenosin-5'yl radical
    in Journal of the American Chemical Society (Print)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • 29207 CHATGILIALOGLU CHRYSSOSTOMOS ; 7896 MAURIZIO GUERRA; 13368 MULAZZANI QUINTO (literal)
Pagina inizio
  • 3839 (literal)
Pagina fine
  • 3848 (literal)
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  • 125 (literal)
Rivista
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  • E' stato condotto uno studio sul comportamento di radicali generati su molecole di nucleosidi come modello del danneggiamento radicalico del DNA. In particolare la formazione di radicali nella posizione 5' della molecola di deoxy adenosina è noto essere un evento che avviene nell'ambiente biologico, ed in questo lavoro viene studiata la ciclizzazione di questo radicale sulla base. Si forma cosi' un derivato ciclonucleosidico di importanza sia farmacologica che biologica. La reattività del radicale in 5' viene anche studiata con l'ausilio della radiolisi pulsata e viene anche esaminato il percorso favorito energeticamente delle specie transienti mediante modellistica molecolare. (literal)
Note
  • ISI Web of Science (WOS) (literal)
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  • ISOF, Consiglio Nazionale delle Ricerche, Via P. Gobetti 101, 40129 Bologna, Italy (literal)
Titolo
  • Model studies of DNA C5' radicals. Selective generation and reactivity of 2'-deoxyadenosin-5'yl radical (literal)
Abstract
  • The reaction of hydrated electrons (eaq-) with 8-bromo-2¢-deoxyadenosine has been investigated by radiolytic methods coupled with product studies and addressed computationally by means of DFTB3LYP calculations. Pulse radiolysis revealed that this reaction was complete in ca. 0.3 ns, and, at this time,no significant absorption was detected. The spectrum of a transient developed in 20 ns has an absorbance in the range 300-500 nm (lmax = 9600 M-1 cm-1 at 360 nm), and it was assigned to aromatic aminyl radical 3. Computed vertical transitions (TD-UB3LYP/6-311+G*) are in good agreement with the experimental observations. Radical 3 is obtained by the following reaction sequence: one-electron reductive cleavage of the C-Br bond that gives the C8 radical, a fast radical translocation from the C8 to C5¢ position, and an intramolecular attack of the C5¢ radical at the C8,N7 double bond of the adenine moiety. The rateconstant for the cyclization is 1.6 x 105 s-1. On the basis of the theoretical findings, the cyclization step is highly stereospecific. The rate constants for the reactions of C5' and aminyl 3 radicals with different oxidants were determined by pulse radiolysis methods. The respective rate constants for the reaction of 2'-deoxyadenosin-5'-yl radical with dioxygen, Fe(CN)6 3-, and MV2+ in water at ambient temperature are 1.9 x 10(9), 4.2 x 10(9), and 2.2 x 10(8) M(-1) s(-1). The value for the reaction of aminyl radical 3 with Fe(CN)6(3-)is 8.3 x 10(8) M(-1) s(-1), whereas the reaction with dioxygen is reversible. Tailored experiments allowed the reaction mechanism to be defined in some detail. A synthetically useful radical cascade process has alsobeen developed that allows in a one-pot procedure the conversion of 8-bromo-2¢-deoxyadenosine to 5',8- cyclo-2'-deoxyadenosine in a diastereoisomeric ratio (5' R):(5' S) ) 6:1 and in high yield, by reaction withhydrated electrons in the presence of K4Fe(CN)6. (literal)
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