Influence of Solvent Polarity and Proticity on the Photochemical Properties of Norfloxacin

Abstract

The fluoroquinolone antibacterial norfloxacin (NF) is a moderate photosensitizer of singlet molecular oxygen (1O2). We have studied photosensitization by NF as a function of medium polarity and proticity in solvent mixtures. We have used 1,4-dioxane and propylene carbonate mixtures to keep proticity constant while modulating polarity, and water/D2O and ethylene carbonate mixtures to alter proticity without large changes in polarity. The absorption spectrum of NF was little affected by solvent changes, as compared to the fluorescence spectrum that exhibited as much as a 50 nm blue-shift, e.g. 1,4-dioxane versus D2O. The quantum yield of NF fluorescence saturated at an almost 10 times higher value (approximately 0.14) when proticity was increased by added water, up to 0.2 mol fraction, to ethylene carbonate. Less pronounced, the increasing polarity in 1,4-dioxane/propylene carbonate mixtures affected the fluorescence yield much less. Norfloxacin produces 1O2 and is able to quench 1O2. The rate constant for 1O2 quenching is 4.5 x 10(7) M-1 s-1 in propylene carbonate but decreases ca four times in D2O. The quantum yield of 1O2 photogeneration was also up to five times higher in solvents that were both protic and polar than vice versa. Our data show that NF is more photochemically active in an environment that is both protic and polar. This suggests the involvement of polar excited state(s) and possible proton/hydrogen transfer during photoexcitation. Similar processes may initiate the phototoxic response reported in some patients treated with the fluoroquinolone drugs. The phototoxicity of NF and other fluoroquinolone antibiotics may strongly depend on their localization in hydrophilic or hydrophobic cell/tissue regions.

Photosensitization Reactions of Fluoroquinolones and Their Biological Consequences

“…The C8 site has a carbene rather than a localized cation character (73). Again, influence of solvent polarity and proticity on the photochemical properties of NOR suggests that the phototoxicity of this drug and other FQs may strongly depend on its localization in hydrophilic or hydrophobic cell ⁄ tissue regions (74).…”

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

“…During the recent past years, many studies concerning the fluorate derivatives have shown that its spectral properties are highly dependent on the pH and polarity of medium. For example, for norfloxacin, the quantum yield of fluorescence increases almost 10 times when the proticity of medium is increased (4). For enoxacin, the fluorescence and photodegradation quantum yields are also highly dependent on pH (5).…”

Photoinduced N-Demethylation of Rufloxacin and its Methyl Ester Under Aerobic Conditions¶

“…The mechanistic insight gained in the present work allows for the explanation of previous observations on the photochemistry of a number of fluoroquinolones. Norfloxacin and ciprofloxacin are not only able to produce 1 O 2 but also are able to quench it (13,30). On the other hand, one of the observed processes in these fluoroquinolones, as well as in lomefloxacin, levofloxacin, enoxacin, etc., is the ring cleavage of the amino substituent attached to position 7 of the basic system.…”