Visible-light-induced degradation of medicaments. Kinetics and mechanism of the Vitamin B2-sensitised-photooxidation of Isoproterenol

WALTER A. MASSAD; SONIA BERTOLOTTI; NORMAN A. GARCÍA

PHOTOCHEMISTRY AND PHOTOBIOLOGY

Año: 2004 vol. 79 p. 428 - 433

0031-8655

The sensitized photooxidation promoted by daylight absorbing compounds appears as a plausible course to produce the photodegradation of catecholamines. We report the kinetics and mechanism of Vitamin B2 (Riboflavin (Rf)) sensitized photooxidation of Isoproterenol (Iso), a synthetic sympathomimetic drug structurally related to epinephrine, employing water as a solvent.  A weak dark complex Rf-Iso is formed, only detectable at relatively high Iso concentrations (> 10 mM), with a mean value of 13 ± 3 M-1 for the apparent association constant. Under aerobic sensitizing conditions (Rf ~ 0.02 mM and Iso ~ 0.5 mM) two oxidative mechanisms operate, mediated by singlet molecular oxygen (O2(1Dg)) and superoxide radical anion (O2·–). Our analysis shows that  the main reaction pathway is an electron-transfer-mediated quenching of triplet excited Rf (3Rf*) by Iso. It produces the species Iso·+ and the species Rf·–. The last one, in a subsequent reaction path, generates O2·–, which is mainly responsible for Iso-photooxygenation. In a lesser important process, energy transfer of the 3Rf* to dissolved oxygen generates O2(1Dg). The kinetic balance between chemical and physical quenching of O2(1Dg) by Iso indicates that the process is highly dominated by the physical, not chemical, interaction. The results, which can be extrapolated to a in vivo condition, show the susceptibility of Iso to undergoes visible-light-induced photodegradation in the presence of dye-sensitizers present in the environment.