Spectroscopic Properties of Fluoroquinolone Antibiotics in Water–methanol and Water–acetonitrile Mixed Solvents¶

Abstract

The fluorescence properties of ofloxacin (OFL), norfloxacin (NOR) and flumequine (FLU) were studied in H2O-CH3OH and H2O-CH3CN mixed solvents because these solvents were thought to behave as a biological mimetic system. The emission spectra of OFL and NOR were very sensitive to the composition of the solvents. In the Lippert-Mataga analysis of the steady-state fluorescence data of OFL and NOR, clear reverse solvatochromism was exhibited in both mixed solvents. This observation can be explained by the twisted excited-state intramolecular charge transfer, which is accelerated by water. Theoretical treatments further support these results. The radiative and nonradiative rate constants were analyzed as a function of solvent dipolarity-polarizability (pi*) and hydrogen-bond donor acidity (alpha). These results were well consistent with the suggested mechanism of the excited-state chemical process of OFL and NOR, which depended upon the solvent-solute interactions such as bulk dielectric effects and specific hydrogen-bonding interactions. However, the influence of dielectric effects was more significant. The solvent structures of H2O-CH3CN and the preferential solvation by water were also examined. The emission spectra of FLU do not exhibit any characteristic responses to the properties of the environment.

Femtosecond Transient Absorption Spectroscopy Study of the Early Events of Norfloxacin in Aqueous Solutions with Varying pH Values

“…11,14 Among FQs, norfloxacin [1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, NF], first synthesized in 1980 by introducing a piperazine ring at the carbon-7 of quinolone, 21 is a hydrophobic broadspectrum antibacterial drug with a half-life of 3.0−4.5 h. 22 It shows higher antibacterial activity and a broader substrate scope due to the presence of the piperazinyl ring, compared with other members in the same drug family devoid of this ring. 23 However, it has been reported that NF is able to induce phototoxicity in animals and humans, 24 which was initially speculated to be mediated by photosensitization mediated by singlet oxygen but was recently revised to be the result of a defluorination reaction. Although the latter is an uncommon reaction for fluoroaromatics due to the fairly high dissociation energy of the carbon−fluorine bond (up to ∼120 kcal/ mol), 25,26 it has been established that heterolytic C−F bond cleavage is more efficient for the tautomeric form than for the cationic or anionic form in some molecules.…”

Spectroscopic Properties of Morin in Various CH3OH–H2O and CH3CN–H2O Mixed Solvents

“…Contrary to the k nr , the k r value seldom exhibits any clear trend as a function of solvatochromic parameter of mixed solvents because the change in k r in various solvent compositions is irregular. This phenomenon may be caused by the fact that the quantum yield of morin is very sensitive to the solvatochromic parameter of solvents, and CH 3 CN–H 2 O mixtures exhibit preferential solvation and microheterogeneity . Therefore, the ln(k r ) vs π * and ln(k r ) vs α plots measured at different excitation and emission wavelength do not exhibit any great differences.…”

“…Solubility of morin in CH 3 CN is much greater than that in H 2 O. Because CH 3 CN and H 2 O have quite different solvatochromic properties, contrary to the CH 3 OH–H 2 O mixtures, CH 3 CN–H 2 O mixed solvents show a wide diversity of features and behavior according to the composition . In CH 3 CN–H 2 O mixtures, three different kinds of mixtures can be distinguished, although boundaries of these mixtures are not sharp.…”

“…(II) In intermediate mixtures (0.16–0.71 mole fraction of CH 3 CN), H 2 O–CH 3 CN mixtures show microheterogeneity, i.e . there are clusters of molecules of the same kind surrounded by regions where molecules of both kinds are near each other . Also, the free water molecules begin to appear in the mixture and then begin to interact with the solute.…”

“…The π * and α values of the CH 3 OH–H 2 O mixed solvents will be proportion to the solvent composition within experimental errors. The π * and α of CH 3 CN–H 2 O mixed solvents was obtained from the literatures as described previously . All experiments were performed with low concentration solutions (below 2×10 −5 m ) to prevent any primary and secondary interfilter effects.…”