Retarded photooxidation of cyamemazine in biomimetic microenvironments

Abstract

Cyamemazine (CMZ) is a neuroleptic drug that mediates cutaneous phototoxicity in humans. Here, the photobehavior of CMZ has been examined within (1)-acid glycoproteins, - and -cyclodextrins and SDS micelles. In all these microenvironments, CMZ emission was enhanced and blue-shifted, and its lifetime was longer. Irradiation of the entrapped drug at 355nm, under air; led to the N,S-dioxide. Within glycoproteins or SDS micelles the reaction was clearly slower than in phosphate buffered solution (PBS); protection by cyclodextrins was less marked. Transient absorption spectroscopy in PBS revealed formation of the triplet state ((3)CMZ*) and the radical cation (CMZ(+center dot)). Upon addition of glycoprotein, the contribution of CMZ(+center dot) became negligible, whereas (3)CMZ* dominated the spectra; in addition, the triplet lifetime became considerably longer. In cyclodextrins, this occurred to a lower extent. In all microheterogeneous systems, quenching by oxygen was slower than in solution; this was most remarkable inside glycoproteins. The highest protection from photooxidation was achieved inside SDS micelles. The results are consistent with photooxidation of CMZ through photoionization and subsequent trapping of the resulting radical cation by oxygen. This reaction is extremely sensitive to the medium and constitutes an appropriate probe for localization of the drug within a variety of biological compartments.