Free radical induced one-electron oxidation of the phenothiazines chlorpromazine and promethazine

Abstract

Absolute rate constants have been measured for the reactions of the protonated forms of chlorpromazine and promethazine, CZH⁺ and PZH⁺, with the electrophilic radicals ˙OH, Br₂^–˙, (SCN)₂^–˙, I₂^–˙, N₃˙, TI²⁺, TI(OH)⁺, (t-C₄H₉S t-C₄H₉)⁺˙, (CH₃SSCH₃)⁺˙, and lipoate⁺˙ in the pH range 2–8. Values for these one-electron oxidations vary from k= 3.1 × 10⁸ mol^–1 dm³ s^–1 for [(t-C₄H₉S t-C₄H₉)⁺˙+ PZH⁺] to 5.5 × 10⁹ mol^–1 dm³ s^–1 for (Br₂^–˙+ CZH⁺). The yields of the oxidation products, PTZH²⁺˙, vary from 28% for (˙OH + CZH⁺) to 97% for [(SCN)₂˙^–+ CZH⁺]. The PTZH²⁺˙ radical cations exhibit characteristic absorption spectra with two maxima around 270 and 510 nm, and extinction coefficients of ε(CZH²⁺˙)= 56 000 mol^–1 dm³ cm^–1 at 270 nm and 12 000 mol^–1 dm³ cm^–1 at 510 nm, and ε(PZH²⁺˙)= 62 500 mol^–1 dm³ cm^–1 at 265 nm and 9 500 mol^–1 dm³ cm^–1 at 505 nm. A transient absorption around 350 nm observed in the reaction of the phenothiazines with hydroxyl radicals is most probably the ˙OH–adduct, PTZH(OH)⁺˙. The mechanism of the ˙OH-radical-induced oxidation of phenothiazines suggested in an earlier publication has been confirmed and enlarged.