883554-61-8Relevant academic research and scientific papers
Photoreactivity of fluoroquinolones: Nature of aryl cations generated in water
Soldevila, Sonia,Bosca, Francisco
scheme or table, p. 3940 - 3943 (2012/10/18)
The nature of stabilized aryl cations generated from photodehalogenations of fluoroquinolones in aqueous media has been studied by comparing the photophysical and photochemical behavior of lomefloxacin (LFX) and its N(4′)-acetylated form (ALFX). Photoproduct studies, laser flash photolysis, and emission measurements have shown that this small peripheral modification produces important changes in the properties of the singlet aryl cations generated. Also, in basic medium, a new photodehalogenation pathway for 6,8-dihalogenated fluoroquinolones has been observed.
Modeling the hotochemistry of the reference phototoxic drug lomefloxacin by steady-state and time-resolved experiments, and DFT and post-HF calculations
Freccero, Mauro,Fasani, Elisa,Mella, Mariella,Manet, Ilse,Monti, Sandra,Albini, Angelo
, p. 653 - 663 (2008/12/21)
The irradiation in water of 1ethyl-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 l-(2-iodoethyl) and the l-[2-(2-pyrrolyl)ethyl] derivatives are formed. Flash photolysis reveals the triplet of lomefloxacin. a short-lived species (λmax = 370 nm. τ = 40 ns) that generates the triplet cation (λmax = 480 nm, τ ≈ 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 (ΔG 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 (kq from 4.9×108 for CF to 7.0× 109M-1 S-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 mor-1) yielding the 8-quinolinyl radical occurs. Hydrogen exchange leads to a new radical on the 1-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.
