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.

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).…”

Spectroscopic Properties of the Quercetin–Divalent Metal Complexes in Hydro‐Organic Mixed Solvent

“…19,20 As it is very difficult to study flavonoid-metal chelation directly in vivo, the comprehensive spectroscopic investigations are performed in biological simulations, such as a CH 3 OH-H 2 O mixed solvent. The CH 3 OH-H 2 O mixtures are regarded as biologically mimetic systems because they simultaneously show low polarity and a partially aqueous content, always present in the biological systems.…”

Photoinduced decarboxylation of 9‐oxo‐6,9‐dihydro[1,2,5]selenadiazolo[3,4‐f]quinoline‐8‐carboxylic acid

“…The structure, the substituent's character and its position play a dominant role in the photophysical and photochemical behavior of quinolone derivatives . However, the photoinduced reaction pathways are significantly influenced by the presence of oxygen, the properties of the solvent used, and in aqueous media, by the ions present in the solutions, along with the pH value . The irradiation of 6‐monofluoroquinolones in water leads to a defluorination coupled with a photosubstitution of the fluorine atom by a hydroxyl group generating 6‐hydroxyquinolones, but the presence of a second halogen atom (X) at position 8 of the quinolone skeleton results in the fragmentation of this C–X bond via aryl cation formation .…”

“…However, the photoinduced reaction pathways are significantly influenced by the presence of oxygen, the properties of the solvent used, and in aqueous media, by the ions present in the solutions, along with the pH value . The irradiation of 6‐monofluoroquinolones in water leads to a defluorination coupled with a photosubstitution of the fluorine atom by a hydroxyl group generating 6‐hydroxyquinolones, but the presence of a second halogen atom (X) at position 8 of the quinolone skeleton results in the fragmentation of this C–X bond via aryl cation formation . On the other hand, decarboxylation constitutes the dominant photoinduced process for nonfluorinated quinolones, where the photoreactions of nalidixic acid (Scheme ) were intensively investigated .…”