Bilski P, Martinez L J, Koker E B, Chignell C F
Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Photochem Photobiol. 1998 Jul;68(1):20-4.
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.
氟喹诺酮类抗菌药诺氟沙星（NF）是单线态分子氧（1O2）的中度光敏剂。我们研究了NF在溶剂混合物中作为介质极性和质子性的函数的光敏作用。我们使用1,4 - 二氧六环和碳酸丙烯酯混合物来保持质子性恒定，同时调节极性，以及水/D2O和碳酸亚乙酯混合物来改变质子性，而极性变化不大。与荧光光谱相比，NF的吸收光谱受溶剂变化的影响较小，荧光光谱例如在1,4 - 二氧六环与D2O之间表现出高达50 nm的蓝移。当向碳酸亚乙酯中加入水使质子性增加至0.2摩尔分数时，NF荧光的量子产率饱和在几乎高近10倍的值（约0.14）。不太明显的是，1,4 - 二氧六环/碳酸丙烯酯混合物中极性的增加对荧光产率的影响要小得多。诺氟沙星产生1O2并能够淬灭1O2。在碳酸丙烯酯中1O2淬灭的速率常数为4.5×10(7) M-1 s-1，但在D2O中降低约四倍。在质子性和极性兼具的溶剂中，1O2光生成的量子产率也比反之的情况高出多达五倍。我们的数据表明，NF在质子性和极性兼具的环境中光化学活性更高。这表明在光激发过程中涉及极性激发态以及可能的质子/氢转移。类似的过程可能引发一些接受氟喹诺酮类药物治疗的患者中报道的光毒性反应。NF和其他氟喹诺酮类抗生素的光毒性可能强烈取决于它们在亲水性或疏水性细胞/组织区域中的定位。
