Spectroscopic Properties of Fluoroquinolone Antibiotics and Nanosecond Solvation Dynamics in Aerosol-OT Reverse Micelles

Abstract

Among fluoroquinolone antibiotics, ofloxacin (OFL) and norfloxacin (NOR) have piperazinyl groups but flumequine (FLU) does not have this substitutent. The emission spectra of OFL and NOR are strong, broad structureless bands with large Stokes' shifts in water but the emission intensities are very weak in organic solvents. Thus we find that these compounds exist as different chemical species in various solvents. A continuous red shift in the emission bands for OFL and NOR is observed as the water concentration within the aerosol-OT (AOT; sodium 1,4-bis[2-ethylhexyl]sulfosuccinate) micelle increases or temperature of this solution rises. From the fluorescence anisotropy measurements of OFL and NOR, we assume the intramolecular charge transfer after excitation from the nitrogen of the piperazinyl group to the keto oxygen. Theoretical calculations further support this observation. Multifrequency phase and modulation experiments and time-resolved emission spectra clearly show the occurrence of intramolecular charge transfer and the subsequent nanosecond water reorganization around OFL or NOR in the AOT micelle. Upon increasing the water concentration within the AOT micelle, the relaxation rate increases because of the large amount of free water. The emission spectra of FLU do not exhibit any significant response to the physical properties of their environment.

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

“…It was soon realized that these compounds such as OFL and NOR, which have the piperazinyl group, were much more active in vitro and that they showed a broader range of antibacterial activity compared with the drugs without a piperazinyl group, such as FLU. The two groups of drugs, with or without the piperazine substituent, exhibit completely different antibacterial responses and chemical properties in various environments, as described previously (2,6). These differences are governed by the presence of the piperazinyl group at 7‐carbon atom.…”

“…OFL and NOR were found to be present as neutral zwitterionic forms in aqueous solution, but they were present as molecular forms in organic solvents such as methanol and acetonitrile. Also, we found the excited‐state intramolecular charge transfer (CT) from nitrogen atom of piperazinyl group to keto oxygen in aqueous solution (2,7). Because OFL and NOR have a strong sensitivity to the environments and proper solubility in various solvent systems, these antibiotics will function as excellent fluorescence probes.…”

“…For OFL and NOR, fluorescence emission was observed from an intramolecular CT state (2). In many cases, the formation of the CT state is accompanied by an isomerization reaction in which the donor moiety twists with respect to the acceptor (8–10).…”

“…Because these two groups of drugs, OFL and NOR, and FLU have quite different photochemical properties, we can suggest that there is a major difference between these two kinds of drugs, with respect either to their mode of action, or to their mechanism of penetration into bacteria (6). Furthermore, it is reported that all these drugs are able to induce photosensitivity reaction in human skin by sunlight (2,11,12). This phototoxicity will occur in any subject with sufficient cutaneous photosensitizer exposed to enough irradiation of appropriate wavelength, but the mechanism still remains unknown.…”

Pulse radiolysis study on several fluoroquinolones

“…Apart from this reaction, other photochemical properties of FQs, such as decarboxylation, side-chain degradation, the effect of medium, and pH dependence of FQ excited states were also investigated by photochemists, and have also been reported in detail (Albini and Monti, 2003;Bilski et al, 1996;Bilski et al, 1998;Fasani et al, 1998;Sortino et al, 1998;Fasani et al, 1999a,b;Sortino et al, 1999;Bazin et al, 2000;Park et al, 2000;Sortino et al, 2000;Fasani et al, 2001;Monti and Sortino 2002;Park et al, 2002a,b;Viola et al, 2004;Lorenzo et al, 2008a,b;Lorenzo et al, 2009;Ge et al, 2010).…”