Generation of Detectable Singlet Aryl Cations by Photodehalogenation of Fluoroquinolones

Abstract

Nanosecond laser flash photolysis (lambdaexc = 355 nm) of neutral aqueous solutions of lomefloxacin (LFX, a 8-fluorinated 7-amino-4-quinolone-3-carboxylic acid derivative) produces a detectable transient species, which shows an absorption maximum at 490 nm and can be assigned to an aryl cation. This intermediate has a lifetime of ca. 200 ns in net water, reacts with Br- and Cl- with rate constants of 3.6 x 10(9) M(-1) s(-1) and 4.1 x 10(8) M(-1) s(-1), respectively, and shows a lack of reactivity toward molecular oxygen. From the photolysis of BAY y3118 (BAY, a 8-chlorinated analogue), an aryl cation is also generated, showing absorption maximum at 480 nm (lifetime of ca. 1 micros in net water) and a reaction rate constant of 9 x 10(9) M(-1) s(-1) with Br(-). The existence of these highly reactive species arising from direct photolysis of LFX and BAY can justify the photogenotoxic properties associated with these antibacterial drugs likely due to direct reaction of their cations with DNA.