INFLUENCE OF SOLVENT POLARITY AND PROTICITY ON THE PHOTOCHEMICAL PROPERTIES OF NORFLOXACIN

The fluoroquinolone antibacterial norfloxacin (NF) is a moderate photo sensitizer of singlet molecular oxygen (O-1(2)), We have studied photo sensitization by NF as a function of medium polarity and proticity in solvent mixtures, We have used 1,4-dioxane and propylene carbonate mix tures to keep proticity constant while modulating polarity, and water/ D2O and ethylene carbonate mixtures to alter proticity without large c hanges in polarity. The absorption spectrum of NF was little affected by solvent changes, as compared to the fluorescence spectrum that exhi bited 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 highe r value (similar to 0.14) when proticity was increased by added water, up to 0.2 mol fraction, to ethylene carbonate. Less pronounced, the i ncreasing polarity in 1,4-dioxane/propylene carbonate mixtures affecte d the fluorescence yield much less. Norfloxacin produces O-1(2) and is able to quench O-1(2). The rate constant for O-1(2) quenching is 4.5 x 10(7) M-1 s(-1) in propylene carbonate but decreases ca four times i n D2O. The quantum yield of O-1(2) photogeneration was also up to five times higher in solvents that were both protic and polar than vice ve rsa, Our data show that NF is more photochemically active in an enviro nment that is both protic and polar, This suggests the involvement of polar excited state(s) and possible proton/hydrogen transfer during ph otoexcitation. 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/tissu e regions.