Modeling the photochemistry of lomefloxacin, a reference phototoxic drug, by steady state and time-resolved experiments and DFT and post-HF calculations (Articolo in rivista)

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  • Modeling the photochemistry of lomefloxacin, a reference phototoxic drug, by steady state and time-resolved experiments and DFT and post-HF calculations (Articolo in rivista) (literal)
Anno
  • 2008-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1002/chem.200701099 (literal)
Alternative label
  • M. Freccero, E. Fasani, M. Mella, I. Manet, S. Monti, A. Albini (2008)
    Modeling the photochemistry of lomefloxacin, a reference phototoxic drug, by steady state and time-resolved experiments and DFT and post-HF calculations
    in Chemistry (Weinh., Print)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • M. Freccero, E. Fasani, M. Mella, I. Manet, S. Monti, A. Albini (literal)
Pagina inizio
  • 653 (literal)
Pagina fine
  • 663 (literal)
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  • 14 (literal)
Rivista
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • I. Manet, S. Monti: ISOF-CNR In collaborazione con il Dipartimento di Chimica Organica dell’università di Pavia (literal)
Titolo
  • Modeling the photochemistry of lomefloxacin, a reference phototoxic drug, by steady state and time-resolved experiments and DFT and post-HF calculations (literal)
Abstract
  • The irradiation in water of 1-ethyl-6,8-difluoro-7(3-methylpiperazino)3-quinolone-2-carboxylic acid (lomefloxacin), a bactericidal agent whose use is limited by its serious phototoxicity (and photomutagenicity in the mouse), leads to formation of the aryl cation in position eight that inserts into the 1-ethyl chain. Trapping of the cation was examined and it was found that chloride and bromide straightforwardly add in position eight, but with iodide and with pyrrole the 1-(2-iodoethyl) and the 1-[2-(2-pyrrolyl)ethyl] derivatives are formed. Flash photolysis reveals the triplet of lomefloxacin, a short-lived species (lambda(max)=370nm, tau= 40 ns) that generates the triplet cation (lambda(max)= 480 nm, tau approximate to 120 ns). The last intermediate is quenched both by halides and by pyrrole. DFT and post-HF methods have shown that the triplet is the lowest state of the cation (Delta G(ST)= 13.3 kcal mol(-1)) and intersystem crossing (ISC) to the singlet has no role because a less endothermic process occurs, that is, intramolecular hydrogen abstraction from the N-ethyl chain (9.2 kcal mol(-1)) that finally leads to cyclization. The halides form weak complexes with the triplet cation (k(q) from 4.9 x 10(8) for Cl- to 7.0 x 10(9) M-1S-1 for I-). With Cl- and Br- ISC occurs in the complex along with C-8-X bond formation. However, this latter process is slow with bulky iodide and with neutral pyrrole, and in these cases moderately endothermic electron transfer (ca. 7 kcal mol(-1)) yielding the 8-quinolinyl radical occurs. Hydrogen exchange leads to a new radical on the I-ethyl chain and to the observed products. These findings suggest that the mutagenic activity of the DNA-intercalated drug involves attack of the photogenerated cation to the heterocyclic bases. (literal)
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