The defluorination reaction of lomefloxacin (LF) was investigated using femtosecond transient absorption (fs-TA), nanosecond transient absorption (ns-TA) and nanosecond transient resonance Raman (ns-TR2) spectroscopic techniques in neutral water solution at pH 7.2. Density functional theory (DFT) calculations were employed to help interpret the experimental results. Comparison of the resonance Raman and DFT results revealed that the tautomeric form of LF was the predominant species in neutral water (pH=7.2) solution and also the predominant form that undergoes photoexcitation in neutral aqueous systems. The fs-TA results indicated that the first excited singlet state species (S1) did not undergo efficient intersystem crossing (ISC) to transform into the excited triplet state, instead, partially decayed to the ground state via fluorescence emission and partially underwent the cleavage of the carbon-fluorine bond at position 8 to produce a singlet aryl cation. The ns-TR2 result provided direct evidence for the formation of the singlet aryl cation species. Subsequently, the transformation from the singlet cation to a triplet carbene via an ISC process was observed in the ns-TA spectra. Finally, the triplet carbene experienced a cyclization reaction with the N-ethyl chain to form the tricyclic product.  The implications of the observed reaction mechanism for fluoroquinlone compounds and their phototoxicity is discussed.

Excited singlet state modulated defluorination and carbene intermediate induced cyclization for lomefloxacin in neutral water solution

245th National Meeting (2013)

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