Singlet molecular oxygen-mediated photo-oxidation of tetracyclines: kinetics, mechanism and microbiological implications.

Members of the biologically active series tetracyclines (TCs) suffer visible light-promoted photodynamic degradation to different extents, depending on their respective chemical structures and reaction conditions (solvent polarity and pH). The photo-oxidation is accompanied by a partial loss of the antimicrobial power. The photodamage is very fast in the alkaline pH range and less aggressive. although not negligible in kinetic terms, in the physiological pH region. Photo-oxidation quantum efficiencies, evaluated for eight TC derivatives, through singlet molecular oxygen [O2(1Delta(g))] phosphorescence detection, spectrophotometric and polarographic methods, range from 0.12 to 0.65 as upper limits in alkaline medium. The photo-oxidation essentially proceeds via a O2(1Delta(g)) mediated process, with rose bengal or eosine as dye-sensitizers, Nevertheless, as a minor reactive pathway,the excited triplet state of the dye sensitizers interacts with TCS in a competitive process with O2(1Delta(g) generation. The O2(1Delta(g)-mediated photo-oxidation of TCs appears to be a plausible mechanism to account for their phototransformations in biological media, in the presence of visible-absorbing pigments. In both highly and moderately polar media, the quenching of the excited oxygen species is mainly represented by a reactive interaction. It is exerted by the TC molecule through a cooperative effect from the different contributions of several nuclear and extranuclear O2(1Delta(g)-sensitive substituents, as discussed in detail in this paper. The TC lower than 0.03 in the most favourable cases. Nevertheless, the TC photoproduct, formed through direct irradiation, efficiently generates O2(1Delta(g) with Phi(Delta)=0.24. This important finding constitutes the first direct evidence of Type II sensitization by TC photoproducts, and could contribute to the elucidation of the mechanism of TC phototoxicity.

Influence of the peptide bond on the singlet molecular oxygen-mediated (O2[1 delta g]) photooxidation of histidine and methionine dipeptides. A kinetic study.

The dye-sensitized photooxidation of L-histidine (His) and L-methionine (Met) and their simplest dipeptides with glycine (Gly) (His-Gly, Gly-His Gly-Met) and Met-methyl ester (Met-ME) mediated by singlet molecular oxygen (O2[1 delta g]) was studied. The overall rate constants in acetonitrile-H2O (kt) for O2(1 delta g) quenching were measured by time-resolved phosphorescence detection. In H2O a competitive kinetic method was employed. In both solvents the reactive rate constants (kr) were determined to discriminate between the overall and physical contributions to the quenching. The kinetic and mechanistic aspects of the interaction are discussed. For His-Gly, the peptide bond has practically no effect on the kinetics of photooxidation. For Gly-His the overall rate constant is much higher than that for His and His-Gly, in both H2O and acetonitrile-H2O. The main contribution to kt (for Gly-His) is the physical quenching of O2(1 delta g). In water the kt/kr ratio for free His and His-Gly is 1.0, reaching a value of 2.0 in the organic solvent-H2O mixture. The rates of -NH2 loss upon sensitized photooxidation in all cases parallel the trend of kr values. The main results for the His series indicate that: (1) a polar environment favors autoprotection (i.e. an increase in the contribution of physical quenching) against photodynamic effects; (2) only the rate constant for reactive interaction with O2(1 delta g) does not depend on the location of the peptide bond involving His. For Met derivatives the kt values are higher in both solvents than that for free Met.(ABSTRACT TRUNCATED AT 250 WORDS)