Spectroscopic Properties of Various Quinolone Antibiotics in Aqueous–organic Solvent Mixtures¶

Abstract

The spectroscopic properties of enoxacin (ENO), oxolinic acid (OXO) and nalidixic acid (NAL) were studied in various H2O-CH3OH and H2O-CH3CN mixed solvents because these solvents were thought to behave as a biological mimetic system. ENO has piperazinyl group, but OXO and NAL do not have this substituent. The fluorescence emission spectra of ENO were very sensitive to the composition of the solvents. In the Lippert-Mataga analysis of the steady-state fluorescence data, clear reverse solvatochromism was exhibited for ENO in both mixed solvents. This observation can be explained using the excited state twisted intramolecular charge transfer (TICT) from the nitrogen of the piperazinyl group to the keto oxygen. Theoretical calculations further support this observation. The nonradiative and radiative rate constants of these molecules were analyzed as a function of dipolarity-polarizability (pi*) and hydrogen bond donor acidity (alpha) of the mixed solvents. These results for ENO were consistent with the suggested mechanism of the TICT very well. The influence of bulk dielectric effect was more significant relative to the specific hydrogen bonding interactions. The emission spectra of OXO and NAL do not exhibit any characteristic responses to the properties of the solvent.

Structure and Medium Effects on the Photochemical Behavior of Nonfluorinated Quinolone Antibiotics†

“…The fluorescence quenching also has been found in some fluorate quinolones bearing the piperazinyl group when the solvent was changed from water to organic solvents (28,29). This has been attributed to a rapid nonradiative deactivation via intramolecular electron transfer from the piperazinyl to the fluoroquinolone ring in organic solvents (22,28). As proposed for several quinolones (6,7,29), the main species of PM existing in nonprotic solvents can be considered to be the intramolecularly hydrogen-bonded species, Ia in Scheme 2.…”

“…These values show that U F for OX is almost invariant with the solvents. Park et al (28) also reported that U F for this compound is constant in wateracetonitrile and water-methanol mixtures.…”

“…Because ethylene glycol, dimethylformamide and acetonitrile have almost the same polarity ( $ 37), the marked increase in the fluorescence in the protic solvents could be attributed to specific solutesolvent interactions. The fluorescence quenching also has been found in some fluorate quinolones bearing the piperazinyl group when the solvent was changed from water to organic solvents (28,29). This has been attributed to a rapid nonradiative deactivation via intramolecular electron transfer from the piperazinyl to the fluoroquinolone ring in organic solvents (22,28).…”

Photophysics and Photochemistry of Nalidixic Acid†

“…In TFE the spectrum was blueshifted by 10 nm with respect to THF, suggesting that specific solute-solvent interactions in the singlet excited state occurs. The shift in the emission spectrum could be also interpreted in terms of a small difference between the dipole moments of the So and S1 states (12). On the other hand, the fluorescence quantum yields slightly decrease in protic solvents.…”

“…In spite of the photosensitizing reaction associated to this drug, the photophysical behavior has received less attention. Fluorescence spectra and fluorescence quantum yields have been reported for NA and related compounds at some pH (3), and recently in some mixed solvents (12). Photophysical studies in different environments are of relevant importance because the regions where the drug can be localized differ drastically in polarity, and the polarity can influence the reactions responsible for NA phototoxicity.…”