The photochemistry of flutamide and its inclusion complex with beta-cyclodexarin. Dramatic effect of the microenvironment on the nature and on the efficiency of the photodegradation pathways

The photochemistry of the anticancer drug flutamide (FM), 2-methyl-N-[4-nit ro-3-(trifluoromethyl)phenyl]propanamide, in homogeneous media and in the b eta -cyclodextrin (beta -CD) cavity has been investigated. The photoreactiv ity of the free molecule has been rationalized on the basis of an intramole cular nitro to nitrite rearrangement followed by cleavage of the nitrite in termediate, The twisted geometry of the nitro group with respect to the aro matic plane plays a key role in triggering such a photoprocess. Incorporati on of FM in the beta -CD cavity leads to dramatic effects on both the effic iency and the nature of the photochemical deactivation pathways of the gues t molecule. A 20-fold increase In the FM photodecomposition quantum yield a nd the formation of photoproducts originated by both reduction of the nitro group and cleavage of the amide bond were observed in the presence of the macrocycle, Such a behavior cannot be attributed exclusively to the micropo larity of beta -CD and/or to its role as a reactant, The induced circular d ichroism spectra and the nature of the photoproducts formed in these experi mental conditions provide indications that the photoreactivity in the beta -CD microenvironment could likely be mediated by structural changes of FM u pon complexation.