SINGLET MOLECULAR OXYGEN-MEDIATED PHOTOOXIDATION OF TETRACYCLINES - KINETICS, MECHANISM AND MICROBIOLOGICAL IMPLICATIONS

Members of the biologically active series tetracyclines (TCs) suffer v isible-light-promoted photodynamic degradation to different extents, d epending on their respective chemical structures and reaction conditio ns ( solvent polarity and pH). The photo-oxidation is accompanied by a partial loss of the antimicrobial power. The photodamage is very East in the alkaline pH range and less aggressive, although not negligible in kinetic terms, in the physiological pH region. Photo-oxidation qua ntum efficiencies, evaluated for eight TC derivatives, through singlet molecular oxygen [O-3((1)Delta(g))] phosphorescence detection, spectr ophotometric and polarographic methods, range from 0.12 to 0.65 as upp er limits in alkaline medium. The photo-oxidation essentially proceeds via a O-2((1)Delta(g))-mediated process, with rose bengal or eosine a s dye-sensitizers. Nevertheless. as a minor reactive pathway, the exci ted triplet state of the dye sensitizers interacts with TCs in a compe titive process with O-2((1)Delta(g)) generation. The O-2((1)Delta(g))- mediated photo-oxidation of TCs appears to be a plausible mechanism to account for their phototransformations in biological media, in the pr esence of visible absorbing pigments, In both highly and moderately po lar media, the quenching of the excited oxygen species is mainly repre sented by a reactive interaction. It is exerted by the TC molecule thr ough a cooperative effect from the different contributions of several nuclear and extranuclear O-2((1)Delta(g))-sensitive substituents, as d iscussed in detail in this paper. The TC phenolic function plays the d riving role as a O-2((1)Delta(g))-quencher only at pH values higher th an 9. The quantum yields for O-2((1)Delta(g)) generation (Phi(Delta)) by TCs, upon direct photo-irradiation. have also been investigated. Th is family of compounds possesses extremely poor Phi(Delta) values, low er than 0.03 in the most favourable cases. Nevertheless, the TC photop roduct, formed through direct irradiation, efficiently generates O-2(( 1)Delta(g)) with Phi(Delta) = 0.24. This important finding constitutes the first direct evidence of Type II sensitization by TC photoproduct s, and could contribute to the elucidation of the mechanism of TC phot otoxicity. (C) 1998 Elsevier Science S.A. All rights reserved.