Photonucleophilic aromatic substitution of 6-fluoroquinolones in basic media:: Triplet quenching by hydroxide anion

Photoreaction of 1-ethyl-6-fluoro-7-(I-piperazinyl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (norfloxacin, NFX) and other 6-fluoroquinolones in aqueous solution gives rise to the corresponding 6-hydroxy derivatives. Although two mechanisms have been proposed for this photonucleophilic aromatic substitution, direct evidence for any of them is still missing. Obtaining such evidence requires work in basic media, where intramolecular electron transfer from the piperazine ring to the quinolone system is the almost exclusive singlet deactivation pathway. To overcome this problem, the 4'-N-acetyl derivative of norfloxacin (ANFX) has been employed in the present paper due to the lower availability of the N lone pair. The photochemical and photophysical properties of ANFX have been studied in aqueous solutions at pH between 7.4 and 13. As expected, fluorescence of ANFX is not significantly quenched in basic media. Furthermore, the excited triplet state (lambda(max) = 620 nm) reacts with hydroxide anions with a rate constant of (0.3 +/- 0.1) x 10(6) M-1 s(-1). This supports a direct attack by hydroxide anions to the excited triplet state with subsequent release of fluoride as the operating mechanism. The fact that the reaction is inhibited by the presence of naproxen (a water-soluble naphthalene derivative) as triplet quencher clearly confirms the mechanistic assignment.