Studies on the oxidation of phenothiazine derivatives

The sulfoxides of pharmacologically active phenothiazine derivatives have been widely studied as biological transformation products in body fluids and tissue (1,2). The majority of the work has been devoted to the development of analytical techniques for detection of these products (2,3,4).     

Synthesis of the piperidinone metabolites of piperidine type phenothiazine antipsychotic drugs via ruthenium tetroxide oxidation

The lactam metabolites of the piperidine type phenothiazine antipsychotic drugs thioridazine, mesoridazine and sulforidazine were synthesized in six steps from commercially available 2-(2-hydroxyethyl)piperidine. The key step involved ruthenium tetroxide oxidation of N-protected 2-(2-chloroethyl)piperidine. The products were then oxidized to obtain the phenothiazine ring 5-sulfoxide analogues.     

氮氧自由基研究 XVIII: 水溶液中哌啶氮氧自由基单电子氧化电极反应动力学参数的测定

本文报道于酸性水溶液中, 以单电流阶跃法, 单电位阶跃法, 计时电量法和循环伏安法测定了2,2,6,6-四甲基-4-羟基哌啶-1-氧自由基的扩散系数及其在碳糊和铂工作电极上的单电子氧化反应的传递系数. 以及该电极反应的标准速率常数.     

Some one-electron oxidation reactions of biheteroorganic derivatives with Ge-Hg and Ge-Li groupings

Conclusions 4-Bromo-2,4,6-tri-tert-butylcyclohexadien-2,5-one and the 2,4,6-tri-tert-butylphenoxyl radical function as a one-electron oxidizing agent in reactions with biheteroorganic compounds that contain the Ge-Hg and Ge-Li bonds.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 3, pp. 685–688, March, 1978.     

Dynamic study of photosensitized one-electron oxidation of polyG by menadione

Quinones including menadione are ubiquitous in nature. They play important roles in aerobic respira- tion and photosynthesis[1,2]. In addition, exogenous quinones are used as antibiotics and anticancer drugs. Their function is closely related to their red…     

Pulse radiolysis study of one-electron oxidation of thionine in aqueous solutions

One-electron oxidation of thionine has been studied using specific oxidizing radicals such as Cl⁻Tl(II) and N₃ generated by pulse radiolysis of aqueous solutions. The semioxidized thionine exhibited threepK’s indicating four conjugate acid-base forms. N₃ radicals were found to be less efficient in oxidizing thionine as compared to Cl ₂ ⁻ , Tl²⁺ and Tl(OH)⁺. The rate constants for electron abstraction from thionine by Cl ₂ ⁻ , Tl²⁺, Tl(OH)⁺, Tl(OH)₂ and N₃ were evaluated. The spectra of different protonated forms of semioxidized thionine and the extinction coefficients at λ_max are presented. Reaction of OH radicals with thionine gave transient products whose spectra and acid-base properties were different from those of semioxidized thionine. The rate constant for formation of the product transient agrees well with competition kinetic value for reaction of OH with thionine reported earlier.     

Regulation of one-electron oxidation rate of guanine by base pairing with cytosine derivatives

Effects of base pairing on the one-electron oxidation rate of guanine derivatives, guanine, 8-bromoguanine, and 8-oxo-7,8-dihydroguanine have been studied. The one-electron oxidation rate of guanine derivatives was determined by triplet-quenching experiments, using N,N'-dibutylnaphthaldiimide (NDI) in the triplet excited state (3NDI*) and fullerene (C(60)) in the triplet excited state ((3)C(60*)) as oxidants. In all three guanine derivatives studied here, acceleration of the one-electron oxidation was observed upon hydrogen bonding with cytosine, which demonstrates lowering of the oxidation potential of guanine derivatives by base pairing with cytosine. When a methyl or bromo group was introduced to the C5 position of cytosine, acceleration or suppression of the one-electron oxidation relative to the guanine:cytosine base pair was observed, respectively. The results demonstrate that the one-electron oxidation rate of guanine in DNA can be regulated by introducing a substituent on base pairing cytosine.     

Photocatalytic one-electron oxidation of biphenyl derivatives strongly coupled with the TiO2 surface

One-electron oxidation of various biphenyl derivatives such as biphenyl (BP), 4-hydroxybiphenyl (HBP), 4,4'-biphenol (DHBP), 4-methoxy-4'-hydroxybiphenyl (MHBP), 4-cyano-4'-hydroxybiphenyl (CNHBP), 4-biphenylmethanol (BPM), and 4-biphenylethanol (BPE) adsorbed on the surface of TiO2 powder slurried in acetonitrile has been investigated by time-resolved diffuse reflectance spectroscopy. From the Langmuir adsorption isotherms for BP and HBP, it is suggested that the OH group plays an important role in adsorbing on the surface ofTiO2. The spectroscopic characteristics of charge transfer complexes of substrates and the TiO2 surface have been studied by steady-state diffuse reflectance spectroscopy. The high efficiency of a one-electron oxidation reaction was observed for hydroxyl-substituted BPs (HBP, DHBP, MHBP, CNHBP), compared with BPM and BPE, indicating that the strength of the electronic coupling element (H(DA)) between the electron acceptor and donor is a key factor in the one-electron oxidation of a substrate adsorbed on the TiO2 powder. The effects of the distance between the electron donor and the acceptor on the electronic coupling element are also discussed.     

ESR study of polypropylene photostabilisation by sterically hindered piperidine derivatives

ESR spectra of sterically hindered piperidine derivatives embedded in polypropylene are superpositions of signals arising from radicals of different mobility. Analysis of the spectra at different temperatures gives information on the mobility and distribution of radicals in solution and in polymer media. At the temperature of irradiation, radicals are homogeneously distributed also in a polymer matrix.During irradiation the concentration of radicals first increases then, after reaching a maximum, decreases. This intermediate character is the result of simultaneous formation and reaction of nitroxyl radicals with radicals arising from polypropylene photo-oxidation.Maximum radical concentration is reached at higher dosage, and subsequent decrease in concentration is slower when hydroxy-benzophenone is applied together with the piperidine derivative. In case of joint application of the latter with a nickel complex, on the other hand, no radical formation can be detected in the polymer before, or in the course of irradiation.     

A theoretical study on the structure and properties of phenothiazine derivatives and their radical cations

Semiempirical CNDO, AM1, PM3 and ab initio HF/STO-3G, HF/3-21G(d), and HF/6-31(d) methods were employed in the geometry optimization of the phenothiazine and the corresponding radical cation. The results obtained from the PM3 performances were as good as those from the ab initio calculations in the structure optimization of both phenothiazine and phenothiazine radical cation. The PM3 method was used to optimize the structures of a series of N-substituted phenothiazine derivatives and their radical cations. The PM3-optimized results were then analyzed with the ab initio calculation at the 6-311G(d,p) level, which yielded the total energy, frontier molecular orbitals, dipole moments, and charge and spin density distributions of the phenothiazine derivatives and their radical cations.     

哌啶氧铵盐对醇氧化反应的活性和选择性

系统地研究了12种具有不同4-位取代基(R=H、CH~3O、Cl)及反离子(X=Cl、BF~4、ClO~4、Br或Br~3)的2, 2, 6, 6-四甲基哌啶氧铵盐对醇的氧化反应, 发现这些氧铵盐都能以很高的由率将一级醇氧化为醛, 二级醇氧化为酮。氧化反应的活性与4-位取代基及反离子有关。当反离子相同时, 反应活性的顺序为Cl>CH~3O>H;当4-位取代基相同时, 反应活性的顺序为Cl^-》BF~4^->ClO~4^->Br^-。氧化反应的选择性主要与反离子有关, 当反离子为Cl^-时, 主要氧化一级醇; 当反离子为BF~4^-、ClO~4^-、Br^-或Br~3^-时, 主要氧化二级醇。     

Pulse radiolysis study on one-electron oxidation of 1-naphthylamine-4-sulphonic acid in aqueous solutions

Reactions of 1-naphthylamine-1-sulphonic acid (NASA) with hydroxyl radicals and oneelectron oxidants such as N₃, Br₂ ^- and Cl₂ ^- radicals have been studied at various pHs using pulse radiolysis technique. Rate constants for the reaction of N₃ and Br₂ ^-. radicals with NASA at neutral pH were found to be 5 × 10⁹ and 4 × 10⁸ dm³ mol^-1 s^-1 respectively. These reactions led to the formation of a cation radical (semi-oxidized species). OH radical reaction with NASA (k = 7.2 × 10⁹ dm³ mol^-1 s^-1) at neutral pH gave a mixture of species, namely, a semi-oxidized species as well as an adduct species. Cl₂ ^-. radicals reacted with NASA rather slowly (k = 7 × 10⁷ dm³ mol^-1 s^-1) at pH 1 to give the semioxidised species. However, even at pH 1, OH radical reaction with NASA gave a mixture containing semi-oxidized as well as an adduct species. The OH-adduct species having _max at 340 nm decays at acidic pHs to give semi-oxidized species having _max at 370 nm. Electron adduct of NASA was found to be a strong reducing radical.     

Effect of netropsin on one-electron oxidation of duplex DNA

The effect of netropsin on the oxidative reactions of duplex DNA was examined. One-electron oxidation of DNA creates a radical cation that migrates through duplex DNA and reacts primarily at GG steps. Netropsin is a dication that specifically binds primarily by hydrogen bonding in the minor groove at sites that have four or more contiguous A.T base pairs. We showed that the oxidation potential of netropsin is less than that of any of the four nucleobases. We find that netropsin quenches the oxidative reactions of DNA independent of whether it is specifically bound. Within the Perrin model of static quenching, a netropsin within a rather large fixed volume around the DNA is an effective quencher.     

A pulse radiolysis study of free radicals formed by one-electron oxidation of the antimalarial drug pyronaridine

Free radicals from one-electron oxidation of the antimalarial drug pyronaridine have been studied by pulse radiolysis. The results show that pyronaridine is readily oxidised to an intermediate semi-iminoquine radical by inorganic and organic free radicals, including those derived from tryptophan and acetaminophen. The pyronaridine radical is rapidly reduced by both ascorbate and caffeic acid. The results indicate that the one-electron reduction potential of the pyronaridine radical at neutral pH lies between those of acetaminophen (707 mV) and caffeic acid (534 mV). The pyronaridine radical decays to produce the iminoquinone, detected by electrospray mass spectrometry, in a second-order process that density functional theory (DFT) calculations (UB3LYP/6-31+G*) suggest is a disproportionation reaction. Important calculated dimensions of pyronaridine, its phenoxyl and aminyl radical, as well as the iminoquinone, are presented. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Potentiometric study of reaction between tetrabutylammonium periodate and phenothiazine in chloroform; application to the analysis of phenothiazine derivatives

The reaction between tetrabutylammonium periodate and phenothiazine in the presence of the strong acids in chloroform was studied by potentiometry and the reaction pathways were determined. The oxidimetric titration conditions of phenothiazine derivatives using a standardized chloroform solution of tetrabutylammonium periodate were optimized and a potentiometric detection of end points was utilized. The relative standard deviation for the determination of 5 mg phenothiazines was obtained about 1-1.5%. The method was applied for the determination of phenothiazines in various pharmaceutical preparations after extraction into chloroform.     

The singlet oxygen oxidation of chlorpromazine and some phenothiazine derivatives. Products and reaction mechanisms

A kinetic and product study of the reactions of chlorpromazine 1, N-methylphenothiazine 2, and N-ethylphenothiazine 3 with singlet oxygen was carried out in MeOH and MeCN. 1 undergoes exclusive side-chain cleavage, whereas the reactions of 2 and 3, in MeOH, afforded only the corresponding sulfoxides. A mechanism for the reaction of 1 is proposed where the first step involves an interaction between singlet oxygen and the side-chain dimethylamino nitrogen. This explains why no side-chain cleavage is observed for 2 and 3.     

Substituent effects in the one-electron reduction of anthraquinone derivatives

Polarographic reduction against (C₂H₅)₄NBr as background in dimenthyformamide has been applied to 17 anthraquinones with - and -substituents. There are two pronounced half-waves, which correspond to two one-electron degrees of reduction, a semiquinone anion being formed as intermediate. An ESR signal is produced when this radical is formed by electrolysis with a cathode potential equal to E_1/2. The observed E_1/2 fit Hammett's equation closely. The relation E_1/2 to donor-acceptor aspects of the substituents is discussed.     

Effect of SDS micelles on the reactivity of 4′-methoxyflavylium ion: A stopped-flow and photochemical study

The network of chemical reactions of the compound 4′-methoxyflavylium was studied in the presence of SDS micelles, using stopped-flow, UV–vis absorption and flash photolysis techniques. The results were compared with analogous experiments carried out in water. The large stabilization of the flavylium cation onto the micelles was proven to be due to an increase in the rate of the dehydration reaction, rather than a decrease of the hydration reaction; the cis–trans isomerisation of the chalcone was not affected by the micelles. It is shown that SDS micelles can be considered as an external stimulus capable of changing the system from one state to another.