Nanosecond time-resolved resonance Raman and absorption studies of the photochemistry of chlorpromazine and related phenothiazine derivatives

Abstract

Nanosecond time-resolved resonance Raman and absorption spectra of chlorpromazine and related phenothiazine derivatives were measured with the purpose of obtaining information on the photo-produced chemical species responsible for phototoxicity and photoallergy of chlorpromazine, a major tranquilizing drug. It was observed that the photoreaction of chlorpromazine in the nanosecond time domain involved four transients: T1 (absorption peak at 480 nm), cation radical CR (at 525 nm), and two unknown transients X (at 560 nm) and Y (at 380 nm). T1 was characterized as an n–π* state on the basis of resonance Raman results. The production of CR was a biphotonic process via S1 with 308 nm excitation. X was generated from CR and was converted into Y. Neither process was affected by oxygen. A species corresponding to X was also observed for 2-chlorophenothiazine but not for phenothiazine and promazine which have no C—Cl bond, suggesting that the generation of X may be related to a photoinduced cleavage of the C—Cl bond. It was not clarified, however, whether X is a direct product of the photo-induced dechlorination or a compound derived from it. Since the generation of Y from X was not affected by the presence of oxygen, Y is not a complex compound with O2. Chlorpromazine is known to be an order of magnitude more phototoxic and photoallergic than promazine and it therefore seems probable that either X or Y or both play important roles in the adverse side effects of the drug. Copyright © 2000 John Wiley & Sons, Ltd.