Paper 76

Abstract Title:

INTERACTION OF PHOSPHATE IONS WITH EXCITED STATES IN THE PHOTODEFLUORINATION OF NORFLOXACIN, ENOXACIN AND LOMEFLOXACIN.

Authors:

S. Monti, S. Sortino, E. Fasani and A. Albini

Institutions:

Istituto FRAE-CNR, Bologna, ItalyDipartimento Scienze Chimiche, Universit` di Catania, ItalyDipartimento di Chimica Organica, Universit` di Pavia, Italy

Key Words:

Abstract:

Several studies on the photodegradation of therapeutically used members of the class of fluoroquinolenes (FQ) in neutral aqueous media showed that in norfloxacin (NOR), the analogue 8-aza derivative enoxacin (ENX) and lomefloxacin (LOM), photodefluorination is practically the exclusive photochemical process. The photodecomposition quantum yields exhibit a medium dependence: in neutral phosphate buffer they are lower than in water. The difference is large in the case of NOR and ENX, where a clear correlation with the buffer concentration was observed. The medium nature also affects the structure of the defluorinated photoproducts formed. In water irradiation of NOR and ENX leads to the corresponding phenols, through a formal nucleophilic substitution of the fluorine in position 6 with an OH group. With the 6,8-difluoroderivative LOM, release of fluoride selectively occurs from position 8 and the main photoproduct arises from cyclization through attack onto the N-ethyl chain. In neutral phosphate buffer LOM, NOR and ENX undergo a different photochemistry. In this case, the products result from both reductive defluorination of the heteroaryl ring and oxidative fragmentation of the piperazine ring. In this study we examined the excited state deactivation pathways of NOR, ENX and LOM in aqueous media at neutral pH by nanosecond and picosecond time resolved spectroscopic techniques. Steady state and time resolved experiments support that both the excited singlet and the triplet states of these heterocycles are quenched by the phosphate anions. Electron transfer quenching of the triplet state appears to be the key process leading to the photoproducts typical of phosphate buffer.