Photochemistry of the Phototoxic Drug Lomefloxacin: Paths Observed in the Presence of Amines or NaOH and from the Methyl Ester

The photochemistry of the fluoroquinolone drug lomefloxacin has been examined in aqueous solution in the presence of aliphatic amines (0.01 and 0.2 M) as well as 0.01 M NaOH; a fairly efficient decomposition (Φ = 0.2 to 0.4) takes place. Under the above conditions the product distribution is the same and differs from that previously observed in neutral and acidic aqueous solution. Five products have been characterized, all of them resulting from reductive elimination of the fluorine in the 8-position and some alteration of the piperazine side-chain. All of the products are rationalized as resulting from the heterolytic cleavage of the C8−F bond in triplet lomefloxacin to give the corresponding triplet aryl cation. Due to the multiplicity, the C8 site has a carbene rather than a localized cation character. Under these conditions the main process is formal hydride transfer from the 3'-position and the minor one attack of the 4'-amino group at the C6−F bond. In accordance with this rationalization, the methyl ester of lomefloxacin exhibits a closely analogous photochemistry under neutral conditions. The cationic intermediate may be involved in the observed phototoxicity of the drug, via an oxygen-independent path.