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Pure Appl. Chem., 2005, Vol. 77, No. 6, pp. 995-1000

Photosensitization by chiral drugs: Looking for stereodifferentiating photoprocesses in the presence of biomolecules

Virginie Lhiaubet-Vallet

Instituto de Tecnología Química UPV-CSIC, Universidad Politécnica de Valencia, Avenida de Los Naranjos s/n, 46022 Valencia, Spain

Photoreactivity of chiral carprofen (CP) and ofloxacin in the presence of two biomolecules, namely, DNA and human serum albumin (HSA), has been reported. Analysis of the photosensitization of 2'-deoxyguanosine and thymidine (Thd) by high-performance liquid chromatograpy has shown that racemic ofloxacin and levofloxacin [its (S)-stereoisomer] acts by a mixed type I/type II mechanism, while CP does not lead to significant degradation of the nucleosides. Studies on DNA relaxation have revealed formation of single-strand breaks and specific alterations of DNA bases. Ofloxacin and levofloxacin photoinduce direct single-strand breaks and formation of purine and pyrimidine oxidative photoproducts; no Thd dimer has been detected. CP produces only photosensitized single-strand breaks. Moreover, DNA photosensitization has shown a weak enantiodifferentiation in favor of levofloxacin and (S)-CP.
In the case of HSA, a remarkable stereodifferentiation has been found in the interaction between the excited triplet state of CP and protein. Time-resolved laser flash photolysis measurements revealed the presence of two components with different lifetimes that have been assigned to complexation of CP to the two binding sites of albumin. Moreover, photobinding of the drug to protein and formation of the dehalogenated photoproduct of CP proceed via stereodifferentiating photoprocesses.