Phenoxazine Derivatives Research Articles

Complexes of microsomal cytochrome P-450 with imidazole, benzotriazole, phenoxazine, and diphenylamine derivatives studied by electronic absorption spectroscopy

Complexes of microsomal cytochrome P-450 with imidazole, benzotriazole, phenoxazine, and diphenylamine derivatives studied by electronic absorption spectroscopy

Interaction of substituted phenoxazine chemosensitizers with bovine serum albumin

The binding of 10-[3′-[ N-bis(hydroxyethyl)amino]propyl]phenoxazine [BPP], 10-[3′-[ N-bis(hydroxyethyl)amino]propyl]-2-chlorophenoxazine [BPCP], 10-[3′-[ N-bis-(hydroxyethyl)amino]propyl]-2-trifluoromethylphenoxazine [BPFP], 10-(3′- N-pyrrolidino propyl)-2-chlorophenoxazine [PPCP] or 10-(3′- N-pyrrolidinopropyl)-2-trifluoromethyl-phenoxazine [PPFP] to bovine serum albumin (BSA) has been measured by gel filtration and equilibrium dialysis methods. The binding of these modulators to bovine serum albumin based on dialysis experiments has been characterized by the following parameters: percentage ( β) of bound drug, the association constant ‘ K 1’, the apparent binding constant ‘ k’ and the free energy Δ F°. The binding of phenoxazine derivatives to bovine serum albumin is correlated with their octanol–water partition coefficient, log 10 P. In addition, the displacing activity of hydroxyzine and acetylsalicylic acid on the binding of phenoxazines to albumin has been studied. The results of the displacing experiments showed that the phenoxazine benzene rings and the tertiary amines attached to the side chain of the phenoxazine moiety are bound to a hydrophobic area on the albumin molecule.

Radiative and nonradiative electron transfer in donor–acceptor phenoxazine and phenothiazine derivatives

Radiative and nonradiative electron transfer (exemplified by the CT fluorescence and nonradiative charge recombination process in the singlet manifold, respectively) in a series of donor–acceptor phenoxazine and phenothiazine derivatives is reported. An analysis of the CT fluorescence leads to the quantities relevant for the radiative electron transfer in the Marcus inverted region. Using a nonadiabatic theory of electron transfer and the latter parameters, the rate constants for nonradiative electron transfer can be predicted. Electronic coupling elements V 0 between the 1 CT state and the ground state obtained from the radiative rates are in agreement with those calculated from the simple LCAO MO model which assumes that V 0 are mainly determined by the interactions between the atoms forming the A–D bond.

Covalent modification of sheep liver cytosolic aldehyde dehydrogenase by the oxidative addition of coloured phenoxazine, phenothiazine and phenazine derivatives.

Aldehyde dehydrogenase acts as an esterase towards reactive esters such as p-nitrophenyl acetate, and although the subject of prolonged debate, it is now generally believed that the dehydrogenase and esterase actions of the enzyme involve the same active site and catalytic groups (see Kitson and Kitson, 1996, and references therein). With p -nitrophenyl dimethylcarbamate, the reactivity (compared to the acetate) is so drastically reduced that it takes several hours for this ‘substrate’ to acylate cytosolic aldehyde dehydrogenase (ALDH-l), and the rate of subsequent deacylation is essentially zero (Kitson et al., 1991). Thus the carbamate acts as an active-site-directed irreversible inactivator of the enzyme. It was thought that resorufin dimethylcarbamate (see Figure 1) would react likewise, but since the molar absorptivity of the resorufin anion (69,700) is so much greater than that of p-nitrophenoxide (18,320) (Kitson, 1996), the resorufin carbamate would be a much more sensitive active site titrant than the p-nitrophenyl compound. The results reported and discussed below show that this expectation was not borne out. Resorufin dimethylcarbamate does inactivate ALDH-I, but the chemistry of the reaction is more complicated and interesting than the simple acylation process expected from the previous work with the p-nitrophenyl equivalent; it may be termed ‘oxidative addition’.KeywordsMethylene BlueEthyl EtherCovalent ModificationOxidative AdditionSubstitution MechanismThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Structural Studies of Some Phenoxazine Derivatives

The compound 10-3′-chlorobutyl phenoxazine (A), crystallizes in the triclinic space group P 1 with a = 11.664(2) Å, b = 12.6292(2) Å, c = 10.5832(14) Å, α = 113.041(9)°, β = 99.543 (11)°, γ = 83.340 (10)°, V = 1412.5(3) Å3 and Z = 2. The structure is refined to R = 0.102. There are two molecules in the asymmetric unit. The packing of the molecules shows stacking along all the three axes. When viewed down, b, the two molecules of the asymmetric unit appear almost perpendicular to each other. The compound, 10-(3′-N-Pyrrolidinopropyl)-2-trifluoro methyl phenoxazine hydrochloride (B), crystallizes in the monoclinic space group C2/c with a = 25.046(13) Å, b = 11.638(6) Å, c = 14.384(28 Å), β = 107.25(8)°, V = 4003(2) Å3 and Z = 8. The structure is refined to R = 0.065. the packing of the molecules shows stacking when viewed down b axis. The compound, 10-(N-morpholinoacetyl)-2-trifluoromethyl phenoxazine (C), crystallizes in the monoclinic space group P21/n with a = 12.710(4) Å, b = 8.5163(14) Å, c = 17.157(4) Å, β = 108.62(2)°, V = 1759.9(7) Å3 and Z = 4. The structure is refined to R = 0.041. The packing of the molecules shows layered arrangement when viewed along b. The compound, 10-(N-chloroacetyl)-2-trifluoromethyl phenoxazine (D), crystallizes in the monoclinic space group P21/a with a = 8.888(2) Å, b = 10.870(1) Å, c = 14.544(2) Å, β = 102.48(2)°, V = 1372(4) Å3 and Z = 2. The structure is refined to R = 0.089. Intra and intermolecular hydrogen bonds are observed in the structure. The compound, 10-N-piperidino acetyl phenoxazine (E), crystallizes in the monoclinic space group P21/a with a = 12.314(4) Å, b = 9.108(3) Å c = 14.586(4) Å, β = 106.26(2)°, V = 1621.4(8) Å3 and Z = 4. The structure is refined to R = 0.08. Packing of molecules shows stacking in two layers when viewed along b. One layer has the three fused rings and other layer has the cyclohexane ring.

Persistent Spectral Hole Burning of Phenoxazine and Phenothiazine Derivatives in Poly(vinyl alcohol) and the Effect of the Addition of N,N,N′,N′-Tetramethyl-p-phenylenediamine

Abstract The photochemical behavior at cryogenic temperatures of phenoxazine and phenothiazine dyes in poly(vinyl alcohol) was investigated by using persistent spectral hole burning. The importance of hydrogen-bondings has been confirmed by measuring the effects of the addition of N,N,N′,N′-tetramethyl-p-phenylenediamine on the holewidth and the hole area of various cationic dyes at 20 K. The hydrogen bonds around the ring-N atom affect the total dephasing time, while the hydrogen bonds around the amino groups as the substituents and around the ring-N atom control the efficiency of hole formation.

Electron‐Transfer Chemistry and Redox‐Switching of Stilbene‐Like Heteroaromatic Compounds — Syntheses, Optoelectrochemical and ESR/ENDOR Studies

AbstractRedox‐active compounds, in which the electron donor and the acceptor subunits are covalently linked by a vinylene spacer group were synthesised and their properties were investigated by cyclovoltammetry, spectroelectrochemistry, and ESR/ENDOR spectroscopy. — 10‐Methylphenothiazinyl, 10‐methylphenoxazinyl, and phenoxathiinyl were used as electron‐donating groups whereas 9,10‐anthraquinon‐2‐yl and phenyl groups were employed as acceptors. The synthesis of the push‐pull‐substituted stilbenes 1a, 1b, 1c, 2a, 2b and 2c was achieved by Wittig coupling of the heterocyclic aldehydes with the anthraquinoyl or phenyl phosphonium salts. The diastereoisomers were separated either by chromatography or by crystallization. — The redox potentials of the (Z) and (E) isomers differ only slightly. Spectroelectrochemical measurements indicate that the radical cations of the phenothiazine and phenoxazine derivatives undergo rearrangement from the (Z) to the (E) isomers. On the other hand, electron attachment leads to configurationally stable radical anions. This behaviour is rationalised in terms of the electron distribution reflected by the hyperfine data established by ESR/ENDOR spectroscopy.

Synthetic applications of functionalized phosphoranylideneamino-1,4-benzoquinones: Preparation of oxazolo[5,4- b]phenoxazine, 4 H-[3,1]benzoxazino-5,8-quinone and benzoxazole derivatives

The aza-Wittig reaction of the triphenylphosphoranylideneamino-1,4-benzoquinone 1 with aryl isocyanates and aroyl chlorides allows the preparation of oxazolo[5,4- b]phenoxazine and benzoxazole derivatives. The same reaction using 7 as iminophosphoranoquinone provides substituted benzoxazoles and the previously unreported 4 H-[3,1]benzoxazino-5,8-quinones.

Electropolymerization of phenothiazine, phenoxazine and phenazine derivatives: Characterization of the polymers by UV-visible difference spectroelectrochemistry and Fourier transform IR spectroscopy

The discrepancies observed between the redox potential values of poly(phenothiazines or phenoxazines) obtained from cyclic voltammetry and from spectroelectrochemical measurements (curves of Δ A vs. E ) suggests that the polymer films are not homogeneous, but include some amount of monomeric species which tend to detach from the electrode surface after electrochemical scanning. The polymerization of the phenazine neutral red, however, gave rise to a homogeneous film. On the contrary, the stability of the polymer film was found to be strongly dependent on the nature of the parent monomer. A model for the structure of poly(phenothiazines or phenoxazines) is proposed on the basis of their optical and vibrational spectra. In every case, the mechanism of electropolymerization seems to involve the formation of a cation-radical species after release of one hydrogen atom from the monomer at high positive potentials. When the monomer has a primary or secondary amino group as ring substituent, the polymer may be composed of phenothiazine units linked through one secondary or tertiary amine moiety. However, when the monomer has only tertiary amino groups as ring substituents (as methylene blue), the cation-radical species are only formed at extremely positive potentials, close to the potential of oxygen evolution, and it would be possible that at least one of the tertiary amino groups could be oxidized before the formation of the cation-radical yielding an oxime derivative of the monomer and formaldehyde as subproduct. However, the great similarity of the spectra of poly(thionine), poly(azur A) and poly(methylene blue) suggests that the kind of linkage between monomer units is the same in all these polymers.

ChemInform Abstract: Synthesis and Spectral Properties of Benzo(b)phenoxazine Derivatives

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Surface‐modified gold electrodes for electrocatalytic oxidation of NADH based on the immobilization of phenoxazine and phenothiazine derivatives on self‐assembled monolayers

AbstractSelf‐assembled monolayers of cystamine and cysteine chemisorbed on gold electrode surfaces have been used as a support for covalent immobilization of some phenoxazine and phenothiazine derivatives. The covalent attachment was achieved after previous functionalization of the free amino groups on the electrode surface with bifunctional reagents (terephthaloyl chloride and 1,6‐hexamethylene diisocyanate) able to react with the imino form of the amino group in position 3 of the phenoxazine and phenothiazine derivatives.In every case, a shift of the redox potentials between 130 and 180 mV towards more positive potentials, as well as an increase in the peak‐topeak separation between anodic and cathodic peaks was observed after covalent attachment. The surface coverages (10−11 < Γ < 10−10 mol/cm2) obtained from the cyclic voltammograms were those for a not densely packed monolayer and varied depending on the redox compound immobilized. The surface‐modified electrodes obtained were afterwards used for the electrocatalytic oxidation of NADH.UV‐vis spectroscopy was used to monitor the successive steps of surface modification using gold semitransparent electrodes. The total surface coverage of redox mediator on the electrode surface could also be calculated from the optical difference spectra between the oxidized and the reduced state obtained ‘in situ’ in a spectroelectrochemical cell.

Spectroelectrochemical detection of phenothiazine and phenoxazine derivatives covalently bound to self-assembled cystamine monolayers

Abstract The phenothiazine derivatives, Toluidine Blue O and Azur A, and the phenoxazine derivative Nile Blue were bound covalently to self-assembled cystamine monolayers chemisorbed on gold electrodes by derivatization of the surface amino groups with two different bifunctional spacers: terephthaloyl chloride and 1,6-hexamethylene-diisocyanate. The formation of the amido- and urea-derivatives of the parent compounds after covalent immobilization induces a shift of their redox potentials towards more positive values which can easily be detected by cyclic voltammetry. UV-Vis difference spectroelectrochemistry has been used to characterize the electroactive species immobilized onto transparent gold electrode surfaces in both oxidation states. In every case, the oxidized-minus-reduced (and reduced-minus-oxidized) difference spectra of the immobilized redox species show a shift of the UV maxima towards longer wavelengths and a shift of the Vis maximum towards shorter wavelengths when compared with their parent compounds. Each redox species showed different optical characteristics depending on the spacer used for immobilization. For phenothiazine derivatives immobilized with 1,6-hexamethylene di-isocyanate the total surface coverages obtained by optical methods were close to those obtained by cyclic voltammetry. However, for the same derivatives immobilized with terephthaloyl chloride, and for Nile Blue, independently of the spacer used, higher surface coverages were found by optical methods than by cyclic voltammetry.

Responses of H + selective solvent polymeric membrane electrodes fabricated from modified PVC membranes

Potentiometric responses of a novel class of pH sensitive ionophores, namely several phenoxazine derivatives, were tested in different modified PVC matrices. The ionophores were compounded into liquid membranes as usual or were covalently coupled to the polymeric matrix. The general analytical performance of the membranes and other membrane characteristics ( i.e., resistance and response time, as measures of membrane decomposition or structural changes) were followed in time. The transient responses of membranes with mobile ionophores in high molecular weight (HMW) and carboxylated PVC (PVC-COOH) were compared to those with immobilized ionophores. The response time of membranes with immobilized ionophores was found to be between those with mobile ionophores in HMW (fast response) and PVC-COOH (sluggish response). Accordingly, the rate of response was correlated primarily to the -COOH content of the membranes.

The potentiometric pH response of chromoionophores used in optical sensors

Recently, we reported the advantageous properties of some H+-selective electrodes based on a novel class in ionophores [1] which were mainly used as chromoionophores in optical sensors. The performances of solvent polymeric membranes containing three similar phenoxazine derivatives (ETH 2439, ETH 5294 and ETH 5350, commercial products from Fluka AG, Buchs, Switzerland) were studied and compared with H+-selective glass electrodes and membranes with tridodecylamine (TDDA) as the ionophore. These electrodes showed the expected properties (linear range, selectivity and response time) except for the one with the membrane containing ETH 5350. A considerable loss of this ionophore from the membrane phase cast with polar (2-nitrophenyl-octylether, o-NPOE) or nonpolar (bis(1-butylpentyl)adipate, BBPA) plasticizer into the sample solution was observed. Consequently, we reported that electrodes constructed with the ETH 5350 carrier were not satisfactory for pH measurement [1]. It can be estimated from the constitution of the three phenoxazine derivatives that their partition coefficients between the organic membrane and water are rather similar. Judging from a theoretical estimation according to the Hansch parameters [2], ETH 5350 tends to be even more lipophilic than the other two phenoxazines shown in Fig. 1. Therefore the observed differences in the dissolu-

Hydrogen peroxide and .beta.-nicotinamide adenine dinucleotide sensing amperometric electrodes based on electrical connection of horseradish peroxidase redox centers to electrodes through a three-dimensional electron relaying polymer network

Abstract : Hydrogen peroxide is efficiently electroreduced at an electrode modified with a hydrophilic, permeable film of horseradish peroxidase (HRP) covalently bound to a 3-dimensional epoxy network having polyvinyl pyridine (PVP)-complexed Os(bpy)2Cl+3/+2 redox centers. The sensitivity of the resulting H202 cathode at O.OV(SCE) is 1Acm(-2)M(-1). Its current increases linearly with H2O2 concentration in the 1x10(-7)M(-)2x10(-4)M range. Related NAD(P)H cathodes are based on stoichiometric homogeneous reduction of 02 to H202 by NADH or NAD(P)H. The reduction involves two known steps. In the first step, NAD(P)H transfers two electrons and a proton to a dissolved quinoid. The quinoids are typically derived of phenazines, however phenothiazine and phenoxazine derivatives are also useful. In the second step, two electrons and a proton are transferred from the reduced quinoid to O2. This reaction produces H202 and the original quinoid. Because the two reactions are quantitative, the sensitivity and the linear range of the resulting NADH and NADPH electrodes are identical with those of the H202 electrode, 1Acm(-2)M(-1) and 1x10(-7)M (-2)2x10(-4)M respectively.

ChemInform Abstract: Synthesis of Crowned Phenoxazine Derivatives.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Carbon-Paste Electrodes with Incorporated Lactate Oxidase and Mediators

Abstract Amperometric bipelectrodes based on carbon paste modified with L-lactate oxidase and mediators are described which are sensitive to L-lactaie. Several ferrocenes and phenoxazine derivatives as mediators are evaluated, with Meldola blue exhibiting the best results. With ferrocene derivatives the bioelectrodes were operated at potential of 0.2-0.4 V (vs SCE). The apparent Michaelis constants for the calibration curves of the bioelectrodes are different depending on the chosen mediator and varied in the range from 0.9 to 3.6 mM L-lactate. The pH optimum in the case of the 1,1′-dimethylferrocene bioelectrode was 9.3 and the limiting sensitivity was determined to be 31 μA/mM cm−2. Covered by a Nation membrane, the electrode sensitivity was in the range of 3.2-4.4 μA/mM cm−2 at pH 7.0 and the calibration range was linear up to 2-2.5 mM L-lactate. The bioelectrode based on Meldola blue mediated electron transfer at potentials between 0.05-0.25 V. The Km(app) was 17.0 and 18.2 mM at 0.1 and 0.05 V, respe...

New neutral carrier-based H + selective membrane electrodes

H +-selective membrane electrodes based on two neutral ion carriers of the class of phenoxazine derivatives which contain different lipophilic imino chains (9-(diethylamino)-5-octadecanoylimino-5 H- benzo[ a]phenoxazine and 9-(dimethylamino)-5-[4-(16-butyl-2,14-dioxo-3,15-dioxaeicosyl)phenylimino]- 5 H-benzo[ a]phenoxazine respectively) are described. Both ionophores, previously used as chromo-ionophores in optode construction, with added potassium tetrakis( p-chlorophenyl) borate (KTpClPB) as cation exchanger sites were embedded into a high molecular weight poly(vinyl chloride) matrix containing o-nitrophenyl octyl ether ( o-NPOE) as plasticizer. Both polymeric pH electrodes exhibited near -Nernstian responses over the ranges depending on the pK of the ionophore within the membrane used as electroactive material. The selectivities and other main characteristics of the electrodes are presented.

Synthesis of crowned phenoxazine derivatives

Synthesis of crowned phenoxazine derivatives

Phenothiazine and phenoxazine derivatives of nafazatrom. In vitro evaluation as 5-lipoxygenase and iron-dependent lipid peroxidation inhibitors.

A series of phenothiazine and phenoxazine analogs of nafazatrom were prepared and evaluated as 5-lipoxygenase and iron-dependent lipid peroxidation inhibitors (rabbit brain homogenate) in vitro. Nafazatrom and two representatives from the described series were also evaluated as peroxyl radical and superoxide anion scavengers.