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Photochemistry of the Phototoxic Drug Lomefloxacin: Paths Observed in the Presence of Amines or NaOH and from the Methyl Ester
Author(s) -
Fasani Elisa,
Mella Mariella,
Albini Angelo
Publication year - 2004
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200400466
Subject(s) - chemistry , lomefloxacin , photochemistry , aqueous solution , phototoxicity , medicinal chemistry , heterolysis , carbene , stereochemistry , organic chemistry , catalysis , biochemistry , norfloxacin , ciprofloxacin , in vitro , antibiotics
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 C 8 −F bond in triplet lomefloxacin to give the corresponding triplet aryl cation. Due to the multiplicity, the C 8 site has a carbene rather than a localized cation character. Under these conditions — the amino group in the 4′‐position is free — the main process is formal hydride transfer from the 3′‐position and the minor one attack of the 4′‐amino group at the C 6 −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. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)