7640-51-9Relevant articles and documents
A mechanistic study on the disproportionation and oxidative degradation of phenothiazine derivatives by manganese(III) complexes in phosphate acidic media
Wisniewska, Joanna,Rzesnicki, Pawel,Topolski, Adrian
scheme or table, p. 767 - 774 (2012/07/01)
The oxidative degradation of phenothiazine derivatives (PTZ) by manganese(III) was studied in the presence of a large excess of manganese(III)-pyrophosphate (P2O7 2-), phosphate (PO4 3-), and H+ ions using UV-vis. spectroscopy. The first irreversible step is a fast reaction between phenothiazine and manganese pyrophosphate leading to the complete conversion to a stable phenothiazine radical. In the second step, the cation radical is oxidized by manganese to a dication, which subsequently hydrolyzes to phenothiazine 5-oxide. The reaction rate is controlled by the coordination and stability of manganese(III) ion influenced by the reduction potential of these ions and their strong ability to oxidize many reducing agents. The cation radical might also be transformed to the final product in another competing reaction. The final product, phenothiazine 5-oxide, is also formed via a disproportionation reaction. The kinetics of the second step of the oxidative degradation could be studied in acidic phosphate media due to the large difference in the rates of the first and further processes. Linear dependences of the pseudo-first-order rate constants (k obs) on [Mn III] with a significant non-zero intercept were established for the degradation of phenothiazine radicals. The rate is dependent on [H+] and independent of [PTZ] within the excess concentration range of the manganese(III) complexes used in the isolation method. The kinetics of the disproportionation of the phenothiazine radical have been studied independently from the further oxidative degradation process in acidic sulphate media. The rate is inversely dependent on [PTZ+.], dependent on [H+], and increases slightly with decreasing H+ concentration. Mechanistic consequences of all these results are discussed.
Side-Chain Effects on Phenothiazine Cation Radical Reactions
Sackett, Patricia Holt,Mayausky, J. S.,Smith, Theresa,Kalus, Susan,McCreery, Richard L.
, p. 1342 - 1347 (2007/10/02)
The cation radical of each of the phenothiazine tranquilizers is a likely intermediate in the metabolism of the drugs to at least two of the three major metabolic classes, the sulfoxides and the hydroxylated derivatives.Previous work has shown that the reactions of the radical are highly dependent on the environment, patricularly the presence of nucleophiles.The present report discusses the effect of cation radical structure on the formation of sulfoxide and hydroxylated metabolites in vitro.Cyclic voltammetry, spectrophotometry, and liquid chromatography were used to examine reactions of various phenothiazine radicals in aqueous buffers.A radical with a three-carbon aliphatic side chain (e.g., chlorpromazine) forms solely sulfoxide and parent unless amine nucleophiles are present, in which case hydroxylation occurs.A shorter side chain (e.g., promethazine) causes radical dimerization and pronounced hydroxylation, regardless of external nucleophiles.A piperazine side chain (e.g., fluphenazine) promotes hydroxylation, with some sulfoxide observed.The results indicate that a deprotonated amine is necessary for hydroxylation and that the amine may be present in the original drug rather than an external nucleophile.In addition to information about cation radical reactions, the redox properties of several different phenothiazines are presented.
