Phenothiazines oxidation

Phenols, pAfa values of 586-589 Phenothiazine oxides, mass spectra of 130 2-Phenylsulphinyl-l-indanols, synthesis of 256... 

Fig. 6. Dependence of the logarithm of the standard rate constant of phenothiazine oxidation on a Ft electrode on the logarithm of the solvent s longitudinal relaxation time. NE, nitroethane TMS, sulfolane. For other abbreviations see 1k-blel.

Phenothiazine, oxidation inhibitor, 156, 160, 161 Phenylacetic acid, Michael addition to maleates,... 

Several stabilizers are useful in minimizing oxidative degradation during thermoplastic processing or in the bulk soHd. Phenothiazine, hindered phenohc antioxidants such as butylated hydroxytoluene, butylatedhydroxyanisole, and secondary aromatic amines in concentrations of 0.01—0.5% based on the weight of polymer, are effective. 

Oxidation of P-nicotinamide adenine dinucleotide (NADH) to NAD+ has attracted much interest from the viewpoint of its role in biosensors reactions. It has been reported that several quinone derivatives and polymerized redox dyes, such as phenoxazine and phenothiazine derivatives, possess catalytic activities for the oxidation of NADH and have been used for dehydrogenase biosensors development [1, 2]. Flavins (contain in chemical structure isoalloxazine ring) are the prosthetic groups responsible for NAD+/NADH conversion in the active sites of some dehydrogenase enzymes. Upon the electropolymerization of flavin derivatives, the effective catalysts of NAD+/NADH regeneration, which mimic the NADH-dehydrogenase activity, would be synthesized [3]. 

Phenothiazines, benzo-l,2,4-thiadiazine 1,1-oxides, fluoroquinolones, nicotinic acid, and nitrofuran derivative as potentially dangerous photosensitizers 98MI11. 

Alternately, the N-acylated derivative of the substituted phenothiazine (112) is oxidized to the corresponding sulfoxide by means of periodic acid. Saponification (113) followed by alkylation with the above side chain affords thioridazine (114)... 

Ethylene Oxide, H2COCH2 Acetylides, Fe, Sn, Organic Acids, Amines, Al oxides OH- Ions Ammonia, H, HCN > Ambient > 30 Inhibitor—Phenothiazine, Keep temp below 30° avoid active catalysts. No sparks Activation >445 =19.7 <445°=36.4 429 Use of catalysts— Fe, Sn, Organic Acids and Ammonia... 

Tompsett125 determined phenothiazine drugs in blood serum by extraction, oxidation with hydrogen peroxide to sulphoxide and evaluation spectrofluorimetrically. 

The formation of adduct is followed by fragmentation and subsequent H-atom abstraction reaction from the sulfinic acid produced. Strong acid solutions of aromatic sulfoxides like thianthrene 5-oxide (7) or phenothiazine 5-oxide (8) gives rise to ESR signals, which... 

EGC > EC = C determined using artificial water-soluble phenothiazine radical cations (Salah et al., 1995) and EGCG > EGC > ECG > C determined in a mixture of LDL and VLDL. However, in the oxidation of unilamellar liposomes of phosphatidylcholine initiated with a water-soluble azo compound at 37°C, the antioxidant activities of EGCG and EGC were lower than those of EC and ECG at pH 7.4, and their depletion of EGCG and EGC was faster than that of EC and ECG (Terao et al, 1994). 

The phenothiazines, chlorpromazine and promethazine, have been described as inhibitors of CCU-induced lipid peroxidation at relatively high concentrations in rat liver microsomes (Slater, 1968). Structural modifications of chlorpromazine were undertaken to try to increase antioxidant activity and maintain molecular lipophilicity. The 2-N-N-dimethyl ethanamine methanesulphonate-substituted phenothiazine (3) was found to be a potent inhibitor of iron-dependent lipid peroxidation. It was also found to block Cu -catalysed oxidation of LDL more effectively than probucol and to protect primary cultures of rat hippocampal neurons against hydrogen peroxide-induced toxicity in vitro (Yu et al., 1992). 

The thiazine dyes used in the preparation of this type of leuco are obtained through oxidative coupling of phenothiazine with an active methylene compound or an aniline. The reduction of the dye 23 with zinc powder in acetic acid is straightforward.9 Treatment of the leuco 24 with acetic anhydride at 40°C yields a more air stable leuco 25.9 Addition of arylsulfinic acid to thiazine dyes such as 26 produces directly leuco dyes such as 27.Sb... 

Derivatives of Methylene Violet 6 possessing long aliphatic chains are obtained by oxidative coupling of 3-acetoxyphenothiazine with a secondary amine in the presence of an oxidant such as iodine. The oxidative coupling of phenothiazine with amine is well known but in this case the reaction does not stop there but proceeds further at reflux temperatures to the phenothiazinone 74.9 Reduction of the latter dye and treatment with acetic anhydride yields the ballasted phenothiazine 6. Reaction of 75 with the dye chloroformate 70 yields the ballasted leuco dye developer 76. 

Photolysis reactions often are associated with oxidation because the latter category of reactions frequently can be initiated by light. The photooxidation of phenothiazines with the formation of N- and S-oxides is typical. But photolysis reactions are not restricted to oxidation. In the case of sodium nitroprusside, it is believed that degradation results from loss of the nitro-ligand from the molecule, followed by electronic rearrangement and hydration. Photo-induced reactions are common in steroids [36] an example is the formation of 2-benzoylcholestan-3-one following irradiation of cholest-2-en-3-ol benzoate. Photoadditions of water and of alcohols to the electronically excited state of steroids have also been observed [37],... 

Sutherland, J.B., Freeman, J.P, Heinze, T.M. et al. (2001) Oxidation of phenothiazine and phenoxazine by Cunninghamella elegans. Xenobiotica The Fate of Foreign Compounds in Biological Systems, 31, 799-809. 

Perez-Gilabert M, Sanchez-Ferrer A and Garcia-Carmona F. 1994. Enzymatic oxidation of phenothiazines by lipoxygenase/H202 system. Biochem Pharmacol 47(12) 2227-2232. 

The most commonplace substrates in energy-transfer analytical CL methods are aryl oxalates such as to(2,4,6-trichlorophenyl) oxalate (TCPO) and z s(2,4-dinitrophenyl) oxalate (DNPO), which are oxidized with hydrogen peroxide [7, 8], In this process, which is known as the peroxyoxalate-CL (PO-CL) reaction, the fluorophore analyte is a native or derivatized fluorescent organic substance such as a polynuclear aromatic hydrocarbon, dansylamino acid, carboxylic acid, phenothiazine, or catecholamines, for example. The mechanism of the reaction between aryl oxalates and hydrogen peroxide is believed to generate dioxetane-l,2-dione, which may itself decompose to yield an excited-state species. Its interaction with a suitable fluorophore results in energy transfer to the fluorophore, and the subsequent emission can be exploited to develop analytical CL-based determinations. 

Although substituted phenols (e.g., para-iodophenol, para-phenylphenol, firefly luciferin, coumaric acid) are popular enhancers, in both luminol and acridan ester oxidation, enhancers with other functional groups [24], e.g., phe-nylboronic acids [25-28], phenothiazines [29], are also useful. As an example the structure of the phenothiazine enhancer used in the Supersignal substrate family is shown in Figure 6. 

One of numerous examples of LOX-catalyzed cooxidation reactions is the oxidation and demethylation of amino derivatives of aromatic compounds. Oxidation of such compounds as 4-aminobiphenyl, a component of tobacco smoke, phenothiazine tranquillizers, and others is supposed to be the origin of their damaging effects including reproductive toxicity. Thus, LOX-catalyzed cooxidation of phenothiazine derivatives with hydrogen peroxide resulted in the formation of cation radicals [40]. Soybean LOX and human term placenta LOX catalyzed the free radical-mediated cooxidation of 4-aminobiphenyl to toxic intermediates [41]. It has been suggested that demethylation of aminopyrine by soybean LOX is mediated by the cation radicals and neutral radicals [42]. Similarly, soybean and human term placenta LOXs catalyzed N-demethylation of phenothiazines [43] and derivatives of A,A-dimethylaniline [44] and the formation of glutathione conjugate from ethacrynic acid and p-aminophenol [45,46],... 

It is interesting to compare the biphenylamine substituted compounds with the corresponding carbazoles, phenoxazines, and phenothiazines. For the triaryla-mino-based structures, the carbazole 24 has the highest oxidation potential (0.69 V vs. Ag/0.01 Ag+) [102], followed by the phenoxazine 25a (0.46 V vs. Ag/0.01 Ag+) [166]. A similar observation was made for the corresponding derivatives of 36a the phenothiazine (0.27 V vs. Fc/Fc+) and the phenoxazine (0.29 V vs. Fc/Fc+) have higher oxidation potentials than the parent compound. The carbazole 37 has an even higher oxidation potential, but in this case the oxidation is not reversible [234]. The redox properties of carbazoles are not fully understood yet. In some devices, a carbazole such as CBP (10) was used as an interface layer on the cathode side, suggesting a lower barrier for electron injection [50]. 

Phenothiazines The phenothiazines (PTZs) undergo extensive metabolism. Metabolic routes include S-oxidation, aromatic hydroxylation, N-dealkylation, N-oxidation, and a combination of these processes. Chlorpromazine, for example, possesses 168 possible metabolites, a large proportion of which are pharmacologically active compounds. The development of an HPLC assay capable of resolving a large number of these metabolites is virtually impossible and assays that permit the simultaneous determination of the parent compound and a selected number of active metabolites must suffice. The PTZ group of compounds includes chlorpromazine, thioridazine, fluphenazine, and perphenazine. 

The electron-transfer reactions between the /3-cyclodextrin (/3-CD) N-substituted phenothiazine derivatives and /3-CD.ATPO (4-acetoxy-2,2,6,6-tetramethyl-1-oxopiperidinium hexachloroantimonate) were found to be influenced by the conformations of the phenothiazine derivatives restricted by the /3-CD cavity. N-Phenylphenothiazine (PPT) and A-phenylethylphenothiazine (PEPT), included by /3-CD, can transfer an electron to the /S-CD.ATP complex. No electron transfer was observed between the /3-CD.A-benzylphenothiazine (/3-CD.BPT) complex under the same conditions. The conformation of the /3-CD.BPT complex is such that the oxidation centre was shielded by the /3-CD wall and the substituent. However, electron-transfer reactions between y-CD.BPT and /3-CD.ATP and nitric acid occurred. ... 

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