The photophysics and photochemistry of pefloxacin(PEF),a 1-ethyl-substituted fluoroquinolone(FQ)antibiotic,were studied using transient,steady-state experimental methods and computational methods.The fundamental photo...The photophysics and photochemistry of pefloxacin(PEF),a 1-ethyl-substituted fluoroquinolone(FQ)antibiotic,were studied using transient,steady-state experimental methods and computational methods.The fundamental photoproperties of PEF and its phototoxicity toward lysozyme,a single-chain protein,were compared with those of a 1-fluorophenyl-substituted FQ antibiotic,difloxacin(DIF).The results showed that the phototoxicity was significantly decreased by the insertion of the bulky1-fluorophenyl substituent(the phototoxicity of DIF was approximately one-quarter of that observed for PEF).This trend was attributed to the lowest lying singlet state with sizeable oscillator strength(f C 0.1)being shifted from319 nm in PEF to 266 nm in DIF upon the insertion of the bulky substituent at the 1-position,as investigated by using computational methods.In addition,95%of the solar UV irradiation that reaches the earth’s surface has wavelength[315 nm.Therefore,reducing the most effective excitation wavelength by optimizing the substituent at the1-position may be a promising strategy to alleviate the phototoxicity of FQ antibiotics.These findings may be applied to other FQ antibiotics because a large number of phototoxicity studies on FQ antibiotics with different substituents at the 1-position can prove these finding’s effectiveness.Delafloxacin,an FQ antibiotic bearing a chlorine and bulky substituent at the 8-and 1-positions,respectively,exhibits no phototoxicity is the most recent example reported to date.To the best of our knowledge,this is the first transient and steady-state study of the effect of the N-1 substituent on the photochemistry and phototoxicity of FQ antibiotics.These findings will be beneficial to the development of novel FQ antibiotics without phototoxicity.展开更多
基金supported by the National Natural Science Foundation of China(No.21173252)。
文摘The photophysics and photochemistry of pefloxacin(PEF),a 1-ethyl-substituted fluoroquinolone(FQ)antibiotic,were studied using transient,steady-state experimental methods and computational methods.The fundamental photoproperties of PEF and its phototoxicity toward lysozyme,a single-chain protein,were compared with those of a 1-fluorophenyl-substituted FQ antibiotic,difloxacin(DIF).The results showed that the phototoxicity was significantly decreased by the insertion of the bulky1-fluorophenyl substituent(the phototoxicity of DIF was approximately one-quarter of that observed for PEF).This trend was attributed to the lowest lying singlet state with sizeable oscillator strength(f C 0.1)being shifted from319 nm in PEF to 266 nm in DIF upon the insertion of the bulky substituent at the 1-position,as investigated by using computational methods.In addition,95%of the solar UV irradiation that reaches the earth’s surface has wavelength[315 nm.Therefore,reducing the most effective excitation wavelength by optimizing the substituent at the1-position may be a promising strategy to alleviate the phototoxicity of FQ antibiotics.These findings may be applied to other FQ antibiotics because a large number of phototoxicity studies on FQ antibiotics with different substituents at the 1-position can prove these finding’s effectiveness.Delafloxacin,an FQ antibiotic bearing a chlorine and bulky substituent at the 8-and 1-positions,respectively,exhibits no phototoxicity is the most recent example reported to date.To the best of our knowledge,this is the first transient and steady-state study of the effect of the N-1 substituent on the photochemistry and phototoxicity of FQ antibiotics.These findings will be beneficial to the development of novel FQ antibiotics without phototoxicity.
