Self sensitized photooxidation of N-methyl phenothiazine: acidity control of the competition between electron and energy transfer mechanisms

Abstract

The reaction pathways following electronic excitation of 10-methyl phenothiazine (MPS) in the presence of oxygen have been investigated as a contribution to establish the mechanisms involved in the phototoxic reactions related to phenothiazine drugs. In the context of previously published results, the pathways of oxidation via the radical cation and/or by reactive oxygen species, such as singlet oxygen and superoxide anion, are of particular interest. The effects of polarity of the medium as well as of proton donors on the different reaction pathways, in particular on the formation of reactive oxygen species and the intermediates of the oxidation of 10-methyl phenothiazine, have been investigated. No reaction was observed in non-polar solvents. In polar solvents, both self-sensitized and sensitized singlet oxygen generation lead to the oxidation of MPS and the production of 10-methyl phenothiazine sulfoxide (MPSO) most probably via a zwitterionic persulfoxide. During self-sensitized photooxidation of MPS in the presence of proton donors, such as carboxylic acids, the zwitterionic intermediate is protonated to the corresponding cation that in turn facilitates the reaction with a second molecule of MPS. In the presence of strong acids however, the formation of the radical cation of MPS and of the superoxide anion, by electron transfer from the triplet excited state of MPS to molecular oxygen, competes efficiently with singlet oxygen formation. In this case, the scavenging of the superoxide anion by protons to yield its conjugated acid (hydroperoxyl radical) and the subsequent disproportionation of the latter prevents back electron transfer.

Environmental fate and effect assessment of thioridazine and its transformation products formed by photodegradation

“…The increase in absorbance in some wavelengths can interfere in the propagation of the irradiation in the whole reactor. Such behavior was also found in the photodegradation of N-methyl phenothiazine as an indicative of self-sensitized photooxidation (Manju et al, 2012). Thus, the suggested two steps of the first-order exponential decay can be attributed to a fast initial degradation of the parent compound, followed by a reduced degradation rate due to the concurrence with newly formed TPs.…”

“…When a compound is excited to a triplet state, it might further react forming TPs, or may return to the normal state because of the quenching action of the dissolved oxygen (Ryan et al, 2010). On the other hand, Manju et al (2012) have proposed the generation of ROS through self-sensitization for a phenothiazine derivative through the formation of superoxide anion-like intermediary such as [THI ,þ /O 2 ,À ], which in acidic medium can further generate H 2 O 2 .…”

“…The TP 339 and TP 355 are carbazole ring derivatives and were formed through sulfoxide elimination. Manju et al (2012) have proposed sulfoxide elimination during the exposition of N-methyl phenothiazine for long irradiation times during photolysis. The TP 245 (2-methylthiophenothiazine) is proposed to be formed through N-dealkylation step from THI and elimination of the substituent group R1 on the position N-10.…”

“…(A) Initial conditions of photolysis: 800 mL, [THI$HCl] 0 50 mg L À1 , pH 6.5 and temperature 20 ± 2 C. A is the peak area of the respective TP and A 0 is the initial peak area of THI at time 0 min. Due to the photo-instability of THI (Nałecz-Jawecki et al, 2008) and autocatalytic characteristics of phenothiazine derivatives (Manju et al, 2012), TP 387 II (THI-2-SO) was already present in the sample of THI before photolysis. Fig.…”

“…It is worth to note that self-sensitization is concentration dependent and is likely to occur during photodegradation processes in higher concentrations of the target compound. Manju et al (2012) have investigated the self-sensitization on the monochromatic photolysis of N-methyl phenothiazine and have proposed a reaction with reactive oxygen species (ROS) leading to the formation of sulfoxidation products. Therefore, the degradation mechanism observed might be through direct and indirect photolysis caused by ROS such as 1 O 2 , HO 2 and H 2 O 2 (Latch et al, 2003).…”