Riboflavin as a sensitiser in the photodegradation of tetracyclines. Kinetics, mechanism and microbiological implications

Kinetic, mechanistic and microbiological studies focus on the visible-light-promoted photoreactions that can take place when tetracycline derivatives (TccD) are in the presence of riboflavin (Rf), and on the consequences of these phototransformations. We found that the TccD doxycycline, methacycline, chlorotetracycline, demeclocycline, oxytetracycline and the parent compound tetracycline, quenched riboflavin singlet and triplet (3Rf∗) excited states in solution. Within the sub-mM range of concentrations of TccD only the quenching of 3Rf∗ was significant. As a result the species Rf− was generated through an electron transfer event from TccD ground state. Further, experimental evidence supported the generation of superoxide radical anion (O2−). In a parallel process singlet molecular oxygen (O2(1Δg)) was produced by energy transfer from 3Rf∗ to dissolved oxygen. Kinetic evidence indicates that doxycycline, methacycline, chlorotetracycline, demeclocycline and oxytetracycline are photodegraded through both O2− and O2(1Δg) mechanisms, whereas tetracycline is comparatively less photodegradable through a dominant O2−-mediated process. It was also observed that the antibiotic activity of tetracycline decreases in a parallel fashion with the photodegradation of the drug.