- Design and synthesis of new theranostic agents for near-infrared imaging of β-amyloid plaques and inhibition of β-amyloid aggregation in Alzheimer's disease
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The presence of amyloid plaques predisposes clinical symptoms of cognitive impairment, which occurs much earlier than other clinical symptoms and plays a crucial role in the neuropathology of AD. Thus, developing probes for Aβ species imaging could be used for early diagnosis of AD, and blocking the initial steps of Aβ aggregation with small molecules has emerged as a valid disease-modifying therapy for Aβ. Herein, we report the design, synthesis and evaluation of a series of new theranostic agents, which can simultaneously perform near infra-red imaging of Aβ plaques, prevent self-aggregation of Aβ monomer, disaggregate preformed Aβ fibrils and play a protective effect on the toxicity of human neuroblastoma cells (SHSY5Y) induced by Aβ1–42. Most of these probes displayed maximum emission in PBS (>650 nm), which falls in the good range for NIRF probes. Importantly, these probes are found to have a high binding affinity toward Aβ aggregates, to exhibit a large fluorescence enhancement upon interaction with Aβ aggregates accompanied by a blueshift in the emission spectra of 20–40 nm and to show an excellent targeting ability for Aβ plaques in slices of brain and eye containing retina tissue from double transgenic mice. These molecules show a promising potential as theranostic agents for the diagnosis and therapy of AD.
- Dao, Pascal,Ye, Feifei,Du, Zhi Yun,Chen, Qian,Zhang, Kun,Dong, Chang Zhi,Meunier, Bernard,Chen, Huixiong
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- Alkyl length dependent reversible mechanofluorochromism of phenothiazine derivatives functionalized with formyl group
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A series of D-A typed phenothiazine derivatives functionalized by formyl group (PCAn, n = 1, 2, 4 and 6) with different lengths of N-alkyl chains have been designed and synthesized to systematically investigate the effect of chain length on their solid-state fluorescence properties. The results showed that these compounds emitted strong fluorescence in solutions and solid states with 52%, 42%, 49% and 45% solid-state absolute fluorescence quantum yield (ΦF), respectively. Their emission wavelengths were strongly affected by solvent polarity, indicating intramolecular charge transfer (ICT) transitions. Interestingly, PCAn solids exhibit not only naked-eye visible and reversible mechanochromic behavior, but chain length-dependent emission properties. PCA1 shows smaller fluorescence spectrum shifts (22 nm) under mechanical force stimuli. Homologs with longer alkyl chains exhibit similar mechanochromic behaviors but larger fluorescence contrasts after grinding except for PCA6. Moreover, the fluorescence emission of ground solid PCA1 and PCA4 can recover at room temperature, PCA2 need high temperatures for fluorescence to be restored, and XRD and DSC revealed that the transformation between crystalline and amorphous states upon various external stimuli was responsible for the MFC behavior. This work demonstrates the feasibility of tuning the solid-state optical properties of fluorescent organic compounds by combining the simple alteration of chemical structure and the physical change of aggregate morphology under external stimuli.
- Jia, Junhui,Wu, Yuying
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- Selective oxidaton methods for preparation of N-alkylphenothiazine sulfoxides and sulfones
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Efficient and selective oxidation methods for preparation of N-alkylphenothiazine sulfoxides 2a-h and sulfones 3a-h starting from N-alkylphenothiazines 1a-h are described.
- Tosa, Monica,Paizs, Csaba,Majdik, Cornelia,Poppe, Laszlo,Kolonits, Pal,Silberg, Ioan A.,Novak, Lajos,Irimie, Florin-Dan
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- Molecular hybridization approach for phenothiazine incorporated 1,2,3-triazole hybrids as promising antimicrobial agents: Design, synthesis, molecular docking and in silico ADME studies
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The objective of the current study is to synthesize a library consisting of four sets of phenothiazine incorporated 1,2,3-triazole compounds using molecular hybridization approach. In total, 36 new hybrid molecules were synthesized and screened for in vitro growth inhibition activity against Mycobacterium tuberculosis H37Rv strain (ATCC-27294). Among the tested compounds, nineteen compounds exhibited significant activity with MIC value 1.6 μg/mL, which is twofold higher than the MIC value of standard first-line TB drug Pyrazinamide. In addition, all these compounds are proved to be non-toxic (with selective index > 40) against VERO cell lines. However, these compounds did not inhibit significantly the growth of Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa strains: the activity profile is similar to that observed for standard anti-TB drugs (isoniazid and pyrazinamide), indicating the specificity of these compounds towards the Mycobacterium tuberculosis strain. Also, we report the molecular docking studies against two target enzymes (Inh A and CYP121) to further validate the antitubercular potency of these molecules. Furthermore, prediction of in silico-ADME and pharmacokinetic parameters indicated that these compounds have good oral bioavailability. The results suggest that these phenothiazine incorporated 1,2,3-triazole compounds are a promising class of molecular entities for the development of new antitubercular leads.
- Reddyrajula, Rajkumar,Dalimba, Udayakumar,Madan Kumar
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- Trans -A2B-corrole bearing 2,3-di(2-pyridyl)quinoxaline (DPQ)/phenothiazine moieties: Synthesis, characterization, electrochemistry and photophysics
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Two novel donor-acceptor systems (F10C-PTZ and F10C-DPQ) were designed and synthesized, in which corrole is an acceptor and either phenothiazine (PTZ) or 2,3-di(2-pyridyl)quinoxaline (DPQ) is an energy/electron donor. These dyads represent some of the few examples of photostable corrole dyads reported in the literature, but the first example of 2,3-di(2-pyridyl)quinoxaline (DPQ) containing meso substituted corrole (F10C-DPQ) also directly connected PTZ to the meso position of corrole (F10C-PTZ). Both the dyads were characterized by high-resolution mass spectrometry (HR-MS), NMR (1H, 13C, 19F) spectroscopy, UV-Vis spectroscopy, steady state fluorescence, time-resolved fluorescence (TCSPC, MCP-PMT), electrochemical methods (CV, DPV) as well as theoretical calculations (DFT, TD-DFT). From absorption and electrochemical studies it is evident that there exist minimum π-π interactions between two hetero chromophoric units in the dyads. The steady state fluorescence studies indicate that an efficient quenching of emission corresponding to the PTZ unit in the F10C-PTZ dyad is attributed to the singlet-singlet energy transfer from PTZ to corrole. In addition to the spectral overlap, excitation spectra provided additional evidence for intramolecular energy transfer. Whereas in the F10C-DPQ dyad, a reductive electron transfer, from the ground state of DPQ to the excited state of corrole, was observed. The negative free energy (ΔG) for charge separation, anodic shift of reduction potential of corrole and the frontier molecular orbital (LUMO) location provide addition support for charge transfer. The solvent dependent rate of an energy and electron transfer was discussed.
- Kandhadi, Jaipal,Yan, Wei-Cong,Cheng, Fan,Wang, Hui,Liu, Hai-Yang
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- Development of Phenothiazine-Based Theranostic Compounds That Act Both as Inhibitors of β-Amyloid Aggregation and as Imaging Probes for Amyloid Plaques in Alzheimer's Disease
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Early detection of Alzheimer's disease (AD) is imperative in enabling the understanding and clinical treatment of this disorder, as well as in preventing its progression. Imaging agents specifically targeting Aβ plaques in the brain and the retina may lead to the early diagnosis of AD. Among them, near-infrared fluorescent (NIRF) imaging has emerged as an attractive tool to noninvasively identify and monitor diseases during the preclinical and early stages. In the present study, we report the design, synthesis, and evaluation of a series of new near-infrared fluorescent probes. Most of these probes displayed maximum emission in PBS (>650 nm), which falls in the good range for NIRF probes. Among them, 4a1 showed the highest affinity toward Aβ aggregates (Kd = 7.5 nM) and an excellent targeting ability for Aβ plaques in slices of brain and retina tissue from double transgenic mice. These compounds are also found to effectively prevent Aβ fibril formation and disaggregate preformed Aβ fibrils, showing a promising potential as theranostic agents for the diagnosis and therapy of AD.
- Dao, Pascal,Ye, Feifei,Liu, Yan,Du, Zhi Yun,Zhang, Kun,Dong, Chang Zhi,Meunier, Bernard,Chen, Huixiong
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- A turn-on fluorescent BOPHY probe for Cu2+ ion detection
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A new fluorine-boron compound BOPHY-PTZ was designed and synthesized. The fluorescent dye was used as a highly sensitive probe for Cu2+ ion detection. The mechanism of detection involved Cu2+ ion oxidation of the phenothiazine (PTZ) moiety and blocked the intramolecular charge transfer (ICT) process from the electron-donating PTZ moiety to the electron-accepting BOPHY moiety. BOPHY-PTZ showed a weak fluorescence in solution. However, it displayed a strong fluorescence signal enhancement upon the addition of Cu2+ ions, and 1.0 nM concentration of Cu2+ can be clearly detected. The assay is simple, sensitive and convenient, and it exhibits excellent selectivity for Cu2+ ions over the other metal ions. The BOPHY-PTZ probe could be used for Cu2+ ion detection in practical samples and for environmental monitoring related applications.
- He, Chunhua,Zhou, Huipeng,Yang, Na,Niu, Niu,Hussain, Ejaz,Li, Yongxin,Yu, Cong
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- Tuning the coordination properties of phenothiazine by regioselective introduction of diphenylphosphanyl groups
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The palladium and platinum complexes of the newly synthesized 1-(diphenylphosphino)-10-methyl-10H-phenothiazine (1) and the previously reported 3-(diphenylphosphino)-10-alkyl-10H-phenothiazine [alkyl = Me (2), Et (3)] and 4-(diphenylphosphino)-10-ethyl-10H-phenothiazine (4) were prepared. Density functional calculations were carried out to explain the electronic properties of compounds 1, 3 and 4. Compounds 1, 3 and 4 can interact with DNA, as was observed in agarose gel electrophoresis experiments. In addition, the cytotoxicity of the platinum complexes of ligands 2 and 4 towards breast, colorectal and hepatocarcinoma cell lines was studied. This journal is
- Filip,Gl,Lupan,Perde-Schrepler,L?nnecke,Surducan,Gin,Hey-Hawkins,Silaghi-Dumitrescu
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- Photoinduced Electron Transfer from N-Alkylphenothiazines to Interface Water of Sodium Dodecyl Sulfate Micelles as a Function of Poly(ethylene oxide) Interaction with the Interface
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Photoinduced electron transfer from N-alkylphenothiazines (PCn, n = 1, 3, 6, 12, and 16) solubilized in sodium dodecyl sulfate (SDS) micelle interacting with poly(ethylene oxide) (PEO) to interface D2O as an electron acceptor is studied with electron spin resonance (ESR) and electron spin echo modulation.The photoproduced radicals are identified as the N-alkylphenothiazine cation radical and the surfactant alkyl chain radical of SDS.The total photoyield decreased from PC1 to PC3 and then increased to PC16.The photoyields increased monotonically with increasing PEO concentration.The photoyields are correlated with the deuterium modulation depth of PCn+ with D2O at the micelle interface as a function of the alkyl chain length of PCn and the concentration of PEO since the modulation depth measures relative changes in the interaction distance between the phenothiazine moiety and interface D2O.The photoyield and deuterium modulation depth trends show a good correlation which indicates that the electron transfer from phenothiazine moiety to interface water is mainly controlled by the distance between them, which is controllably varied by the alkyl chain length of phenothiazine and the intercalation of PEO into the interface region of the SDS micellar headgroup.
- Kang, Young Soo,Kevan, Larry
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- Benzothiazole-Phenothiazine Conjugate Based Molecular Probe for the Differential Detection of Glycated Albumin
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Glycation of albumin proteins is considered the pathophysiological hallmark of several chronic fatal disorders, including diabetes mellitus (DM) and Alzheimer's disease (AD). The optical detection of glycated albumin is a simple and cost-effective tool with diagnostic implications for DM and AD. Herein, we developed a cyano derivative of the benzothiazole-phenothiazine conjugate (TCNP) -based far-red fluorescence probe for the differential detection of glycated bovine serum albumin (BSAG) over native BSA and oxidized BSA (BSAO). The selective fluorescence enhancement of TCNP in the presence of native BSA and BSAO and significant quenching in the presence of BSAG account for the distinct interaction between the probe and different structural variants of BSA. The high photostability and differential response towards native BSA and BSAG infer that TCNP is a potential molecular tool to assess the glycation induced structural changes of albumins.
- Kumar, Ashish,Datta, Lakshmi Priya,Samanta, Sourav,Arora, Harshit,Govindaraju, Thimmaiah
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- Phenothiazine-oxadiazole push-pull fluorophores: Combining high quantum efficiency, excellent electrochemical stability and facile functionalization
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A series of five novel sky-blue to green emitting push-pull fluorophores based on phenothiazine donor and 1,3,4-oxadiazole acceptor were synthesized and characterized. Their doped thin films (5 wt% in PMMA) showed high quantum efficiencies (ФPL) from 0.63 to 0.77. These fluorophores also underwent remarkably reversible oxidations and reductions suggesting their excellent electrochemical stability. Facile tuning of photophysical, thermal and electrochemical properties of the fluorophores could be achieved by optimizing the functional group attached to the 1,3,4-oxadiazole moiety. Finally, we propose that further functionalization of these fluorophores can be easily achieved and as a proof of concept the synthesis of a vinyl polymer derivative Poly(PO-Tol) was demonstrated.
- Wong, Michael Y.,Leung, Louis M.
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- Structure-reactivity relationship of probes based on the H2S-mediated reductive cleavage of the CC bond
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Recently, we discovered the H2S-mediated reductive cleavage of the CC bond, and applied this reaction to design probes for the detection of H2S. To extensively elucidate the structure-reactivity relationship, our current work further investigated the effect of substitutes that connected to the CC bond on the H2S-mediated reductive cleavage, wherein different kinds of electron-withdrawing groups (such as pyridine, bipyridine, terpyridine) and electron donating groups (such as carbazole, N,N-dimethylaniline and phenothiazine) were conjugated to the CC bond of interest. Experimental results and DFT calculations showed that the strength of the electron-donating and withdrawing substitutes could significantly affect the reductive cleavage of the CC bond. Unexpectedly, the reductive cleavage was not influenced by the change of the C(2) and C(3) positions in phenothiazine. On this basis, two probes (NPTZ-P1 and NPTZ-P2) with a C(3)-substituted phenothiazine were thus developed and successfully applied for sensing exogenous H2S in living HeLa cells, which implied their potential in bioimaging. This study provides further understanding on the structure-reactivity relationship of the H2S-mediated reductive cleavage of the CC bond, and is also valuable for exploring new reactions of the CC bond in organic synthesis. This journal is
- Tan, Jingyun,Wang, Chunfei,Zhang, Xuanjun
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- Charge Separation in Donor-Chromophore-Acceptor Assemblies: Linkage and Driving Force Dependence of Photoinduced Electron Transfers
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A series of covalently linked Ru(bipyridine)3-donor-acceptor complexes was prepared where the donor-to-chromophore and acceptor-to-chromophore methylene chain lengths were varied.Time-resolved absorption studies were performed to elucidate intramolecular electron transfer rates.The electron donor in the above series is a phenothiazine moiety linked to a bipyridine by a (-CH2-)p, p=3-8 chain, and the electron acceptor is an N,N'-diquaternary-2.2'-bipyridinium moiety linked to a bipyridine by a (-CH2-)m, m=2,3,4 chain.Oxidative quenching of the Ru(bipyridine)3 metal-to-ligand charge transfer (MLCT) state followed by phenothiazine- to-ruthenium electron transfer resulted in a long-lived charge-separated state.A wavelength-dependent excitation resulted in a slowly decaying absorption which is assigned to the excited-state phenothiazine.The magnitude of this component in the transient absorption serves as an internal standard for determining relative quantum yield for formation of the charge-separated state.Marcus inverted region behavior was observed in back electron transfer.Rate constants for electron transfer from phenothiazine to Ru(III) decreased as the length of the bridging chain increased from p=4 to 8.Chain length independence of the back electron transfer rate in the series of complexes with varied chromophore-acceptor distances (m=2,3, and 4) suggests the formation of an association complex during oxidative quenching of MLCT state and argues against a ?-bond superexchange pathway for back electron transfer.
- Larson, S.L.,Elliott, C.Michael,Kelley, D.F.
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- Corrole-phenothiazine and porphyrin-phenothiazine dyads connected at β-position: Synthesis and photophysical properties
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Two novel donor-acceptor dyads, in which phenothiazine (PTZ) connected at β-pyrrolic position of either freebase corrole (TPC) or freebase porphyrin (TPP) via vinylic spacer have been synthesized. Both the dyads were characterized by ESI-MS, IR, 1H NMR (1D and 2D 1H-1H COSY and J-Resolved), UV–Vis, Study state Fluorescence, Time-resolved fluorescence (Time-correlated single photon counting (TCSPC), Streak Camera) as well as electrochemical methods. In the absorption spectra of the dyads, both Soret and Q-bands were red shifted by 8–20?nm indicating weak electronic communication between the two chromophores. However, the fluorescence emission from the PTZ of the dyad was efficiently quenched (96–99%) as compared to pristine PTZ where the dyad was excited at 310?nm, which is attributed to singlet-singlet excited energy transfer. Fluorescence emission from porphyrin part of the TPP-PTZ dyad also quenched when excite the dyad at 420?nm, which is ascribed to photoinduced electron transfer from ground state of PTZ to excited state of porphyrin. In contrast, when excite the corrole at 420?nm in TPC-PTZ dyad, we found there are no significant changes in photophysical properties. In both the cases the solvent dependence of the rate of energy and electron transfer was observed.
- Kandhadi, Jaipal,Cheng, Fan,Wang, Hua-Hua,Ali, Atif,Wang, Li-Li,Wang, Hui,Liu, Hai-Yang
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- ELECTRON TRANSFER REACTIONS AT n-GaP (100) and (111) IN ACETONITRILE SOLUTIONS FACILITATED BY CATION ADSORPTION.
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Electron transfer reactions occurring at n-GaP (111) and (100) electrodes have been investigated in acetonitrile solutions. In the presence of strongly oxidizing cations, such as 10-methylphenothiazine (10-MP** plus ** multiplied by (times) ), Ferrocene (Cp//2Fe** plus ) and tetrathiafulvalen (TTF** plus ** multiplied by (times) ), it is shown that electron transfer proceeds directly from the conduction band to cations adsorbed at the semiconductor surface. Differential capacitance and photo/dark-current measurements have been used to identify a considerable positive shift of the flatband potential (U//F//B) in the presence of the oxidizing cation. This phenomenon is absent in the presence of a similarly oxidizing neutral species. No evidence was obtained to support the model which proposes mediated electron transfer via surface states deep in the band gap.
- McIntyre,Gerischer
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- Cation radicals of N-substituted phenothiazines
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The reaction of N-substituted phenothiazines with certain acceptors (halogenated solvents CHCl3, CH2Br2, CCl4, o-chloranil, AlCl3, SnCl4, concentrated H2SO4, concentrated HNO3 in HClO4) has been studied by EPR spectroscopy. The hyperfine structure in the EPR spectra of the cation radicals is analyzed. To interpret the EPR spectra obtained in terms of the MNDO-PM3 method we carried out a calculation of the electronic structure of phenothiazine cation radicals containing N-CH3 and N-CH2R substituents. In these radical systems, there are significant steric hindrances to conformational rotation of the CH2 substituent around the N-C bond leading to a conformation with magnetically non-equivalent protons in the methylene group. 1996 Plenum Publishing Corporation.
- Tomilin,Konovalova,Yuzhalkin,Ryabkina,Sanaeva
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- MECHANISMS OF LIGHT-INITIATED REDOX REACTIONS OF COPPER(II)-CYCLIC POLYAMINE SURFACTANT ASSEMBLIES.
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Photo-induced reduction of Cu**2** plus ion by organic electron donors was studied, main attention being paid to the decay kinetics of the cathionized donor using two kinds of Cu**2** plus ions; one is free to move around the micellar surface of copper(II) dodecyl sulfate(Cu(DS)//2), the other being fixed in a cyclic polyamine, Cu**2** plus complex of 2-tetradecyl-1,4,7,10-tetraazacyclododecane (CPA). Sodium 12-(10-phenothiazinyl)dodecanesulfonate (PTHDS) functions quite similarly to N-methylphenothiazine (MPTH) in an electron transfer reaction in Cu(DS)//2 micelles, and the reduced Cu** plus is ejected from the micelles. In the MPTH-CPA system, MPTH** plus is completely ejected from the host micelle in the CPA micellar system. In consequence, the decay of the cationized donor obeys a second-order rate law, while the rate constant becomes much less.
- Moroi
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- Elucidating the Excited State of Mechanoluminescence in Organic Luminogens with Room-Temperature Phosphorescence
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Two stable, purely organic luminogens exhibit both mechano- (ML) and photoluminescence (PL) with dual fluorescence–phosphorescence emissions at room temperature. Careful analysis of the crystal structures, coupled with theoretical calculations, demonstrate that room-temperature phosphorescence and ML properties are strongly related to molecular packing. In particular, the formation and fracture of molecular dimers with intermolecular charge-transfer properties has a significant effect on intersystem crossing, as well as excited triplet state emissions, in both PL and ML processes.
- Yang, Jie,Gao, Xuming,Xie, Zongliang,Gong, Yanbin,Fang, Manman,Peng, Qian,Chi, Zhenguo,Li, Zhen
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- Bis(pentafluorophenyl)phenothiazylborane-an intramolecular frustrated Lewis pair catalyst for stannane dehydrocoupling
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We synthesized a novel Lewis acidic aminoborane containing a phenothiazyl substituent and demonstrated its potential to catalytically promote the dehydrocoupling of tin hydrides. The observed reactivity would imply a homolytic frustrated Lewis pair type mechanism, however computational analysis suggests a heterolytic mechanism for this reaction. This result represents one of the first frustrated Lewis pair systems to dehydrocouple stannanes in a heterolytic fashion.
- Bentley, Jordan N.,Caputo, Christopher B.,Pradhan, Ekadashi,Zeng, Tao
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supporting information
p. 16054 - 16058
(2020/12/03)
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- Synthesis, spectral characterization and antitumor activity of phenothiazine derivatives
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Different types of phenothiazine derivatives were synthesized by reactions of 10-alkyl-10H-phenothiazine-3-carbaldehydes. Structures of the prepared compounds were confirmed through spectroscopic techniques such as IR, 1H NMR, 13C NMR and mass spectroscopy. All the compounds were studied for their antitumor activities.
- Venkatesan, Kasi,Satyanarayana, Vardhineedi Sri Venkata,Sivakumar, Amaravadi,Ramamurthy, Chitteti,Thirunavukkarusu, Chinnasamy
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p. 2722 - 2728
(2020/04/16)
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- Phenothiazine derivative as well as preparation method and application thereof
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The invention provides a phenothiazine derivative. The phenothiazine derivative has a structure shown as a formula (I) or a formula (II), wherein in the formula (I), R[1] is selected from one or moreof H, CH3, C2H5, the formula shown in the description and the formula shown in the description; n is an integer and is 1 or 2; in the formula (II), R[1] is selected from one or more of the formula shown in the description and the formula shown in the description. The phenothiazine derivative with the specific structure, provided by the invention, has relatively good water solubility, high sensitivity, good selectivity, good light stability and high bioavailability, and has very good affinity with Abeta1-42 aggregates. Therefore, the phenothiazine derivative provided by the invention not only can be used as a fluorescent molecular probe applied to imaging of Abeta protein plaques, but also can be used for early diagnosis of Alzheimer's disease.
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Paragraph 0054; 0087; 0088
(2018/07/28)
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- Full-color ultralong organic phosphorescent material as well as preparation method and application thereof
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The invention belongs to the field of preparation of pure organic phosphorescent materials and discloses a full-color ultralong organic phosphorescent material as well as a preparation method and application thereof, The full-color ultralong organic phosphorescent material is characterized in that phenothiazine chromophore is introduced into an electron-withdrawing group to realize an excitation light source-dependent pure organic ultralong phosphorescent material. The material has the following characteristics that the raw materials are low in price, and a synthetic method is simple and convenient; secondly, a synthesized material has long phosphorescence life and high quantum efficiency; thirdly, by changing the wavelength of an excitation light source, full-color ultralong organic phosphorescent emission from blue light to red light is realized. With special optical properties, the material has a potential application value in the fields of data encryption and full-color display.
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Paragraph 0062; 0063
(2018/03/25)
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- Nitrosonium ion catalysis: aerobic, metal-free cross-dehydrogenative carbon-heteroatom bond formation
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Catalytic cross-dehydrogenative coupling of heteroarenes with thiophenols and phenothiazines has been developed under mild and environmentally benign reaction conditions. For the first time, NOx+ was applied for catalytic C-S and C-N bond formation. A comprehensive scope for the C-H/S-H and C-H/N-H cross-dehydrogenative coupling was demonstrated with >60 examples. The sustainable cross-coupling conditions utilize ambient oxygen as the terminal oxidant, while water is the sole by-product.
- Bering, Luis,D'Ottavio, Laura,Sirvinskaite, Giedre,Antonchick, Andrey P.
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supporting information
p. 13022 - 13025
(2018/11/23)
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- Efficient synthesis of phenothiazine-based heterocyclic derivatives and their biological studies
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Phenothiazine incorporated xanthene and 1,4-dihydropyridine derivatives were prepared by using N-alkyl-phenothiazine-3-carbaldehydes using one-pot reaction under reflux/ultrasonic irradiation. The synthesized compounds were characterized by using Fourier-transform infrared, 1H NMR, 13C NMR, and mass spectral data. Antibacterial activities of the synthesized compounds were screened against four different bacterial strains. The compound 5a and 5b showed good activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Bacillus cereus, and Klebsiella pneumoniae whereas compounds 4a and 4b show good activity against S. aureus and E. coli. The free radical-scavenging activities of synthesized compounds were screened, and the results were reported.
- Venkatesan,Satyanarayana,Sivakumar
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p. 367 - 372
(2018/09/29)
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- Novel phenothiazine derivative and preparation method and application thereof
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The invention discloses a novel phenothiazine derivative and a preparation method and application thereof, and belongs to the technical field of biological medicines. The invention particularly discloses a compound of a structural general formula I and salts, applicable in pharmacy, of the compound, and the compound and the salts can be used as near-infrared fluorescent molecular probes. The invention further provides a preparation method of the molecular probes and application of the molecular probes. Fluorescent molecules are novel in structure, good in sensitivity and selectivity and good in light stability. The molecules and Abeta(1-42) aggregates have good affinity, and meanwhile auto-polymerization of beta-amyloid protein can be well inhibited. Therefore, the probes can be applied to imaging of Abeta amyloid plaque and can be used for treating the Alzheimer's disease.
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Paragraph 0039; 0040; 0041
(2017/01/02)
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- Multifunctional near infrared fluorescence magnetic nanoparticles as well as preparation method and application thereof
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The invention discloses multifunctional near infrared fluorescence magnetic nanoparticles as well as a preparation method and application thereof. The magnetic nanoparticles have a magnetic resonance imaging function and an optical imaging effect, is not only used for Alzheimer disease amyloid protein A beta plaque image, but also achieving an inhibiting effect on A beta-sample amyloid protein polymerization.
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Paragraph 0039; 0040; 0041
(2017/01/23)
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- N-substituted phenothiazine derivatives: How the stability of the neutral and radical cation forms affects overcharge performance in lithium-ion batteries
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Phenothiazine and five N-substituted derivatives were evaluated as electrolyte additives for overcharge protection in LiFePO4/synthetic graphite lithium-ion batteries. We report on the stability and reactivity of both the neutral and radical-cation forms of these six compounds. While three of the compounds show extensive overcharge protection, the remaining three last for only one to a few cycles. UV/Vis studies of redox shuttle stability in the radical cation form are consistent with the overcharge performance: redox shuttles with spectra that show little change over time exhibit extensive overcharge performance, whereas those with changing spectra have limited overcharge protection. In one case, we determined that a C-N bond cleaves upon oxidation, forming the phenothiazine radical cation and leading to premature overcharge protection failure; in another case, poor solubility appears to limit protection.
- Narayana, Kishore Anand,Casselman, Matthew D.,Elliott, Corrine F.,Ergun, Selin,Parkin, Sean R.,Risko, Chad,Odom, Susan A.
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p. 1179 - 1189
(2015/04/27)
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- N-methylation of aromatic amines and N-heterocycles under acidic conditions with the TTT (1,3,5-trioxane-triethylsilane-trifluoroacetic acid) system
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A novel reductive N-methylation protocol under acidic conditions with the TTT (1,3,5-trioxane-triethylsilane-trifluoroacetic acid) system is disclosed. This method is highly specific for aromatic amines and several N-heterocycles (indoles and annulated analogues, phenoxazine, phenothiazine), insensitive to steric hindrance, and compatible with a wide range of functional groups. Further the N-methylation step can be combined with an in situ N-Boc deprotection. Compounds in which the nucleophilicity of the NH group is eliminated by protonation under the reaction conditions (aliphatic amines, azaarenes of noteworthy basicity) are inert. In several examples, it was demonstrated that the TTT system is complementary to other N-methylation protocols.
- Popp, Tobias A.,Bracher, Franz
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p. 3333 - 3338
(2016/11/29)
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- Hydrogenation of sulfoxides to sulfides under mild conditions using ruthenium nanoparticle catalysts
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The first demonstration of the hydrogenation of sulfoxides under atmospheric H2 pressure is reported. The highly efficient reaction is facilitated by a heterogeneous Ru nanoparticle catalyst. The mild reaction conditions enable the selective hydrogenation of a wide range of functionalized sulfoxides to the corresponding sulfides. The high redox ability of RuO x nanoparticles plays a key role in the hydrogenation.
- Mitsudome, Takato,Takahashi, Yusuke,Mizugaki, Tomoo,Jitsukawa, Koichiro,Kaneda, Kiyotomi
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supporting information
p. 8348 - 8351
(2014/08/18)
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- Fluorescent rhodanine-3-acetic acids visualize neurofibrillary tangles in Alzheimer's disease brains
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There is a high demand for the development of an imaging agent for neurofibrillary tangles (NFTs) detection in Alzheimer's diagnosis. In the present study, a series of rhodanine-3-acetic acids was synthesized and evaluated for fluorescence imaging of NFTs in brain tissues of AD patients. Five out of seven probes have shown excellent binding affinity to NFTs over amyloid plaques in the Thiazine red R displacement assay. However, the selectivity in this in vitro assay is not confirmed by the histopathological evaluation, which indicates significant differences in the binding sites in the assays. Probe 6 showed binding affinity (IC50 = 19 nM) to tau aggregates which is the highest among this series. Probes 2, 3, 4 and 5 display IC50 values of lower than 100 nM to tau aggregates to displace Thiazine red R. Evaluation of the cytotoxicity of these five probes with human liver carcinoma cells revealed that these compounds excert negligible cytotoxicity. The in vivo studies with zebrafish embryos confirmed negligible cytotoxicity at 24 and 72 h post fertilization.
- Anumala, Upendra Rao,Gu, Jiamin,Lo Monte, Fabio,Kramer, Thomas,Heyny-Von Hau?en, Roland,H?lzer, Jana,Goetschy-Meyer, Valerie,Sch?n, Christian,Mall, Gerhard,Hilger, Ingrid,Czech, Christian,Herms, Jochen,Schmidt, Boris
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p. 5139 - 5144
(2013/09/02)
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- Phenothiazine derivatives as organic sensitizers for highly efficient dye-sensitized solar cells
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A series of organic dyes containing a phenothiazine central unit were synthesized and were used effectively in the fabrication of dye-sensitized solar cells (DSSCs). A cyanoacrylate moiety was added at the C(3) position of the phenothiazine as an electron acceptor, and a triarylamine moiety was attached at the C(7) position as an electron donor. The DSSCs made with these dyes displayed remarkable quantum efficiency, ranging from 4.2-6.2% under an AM 1.5 solar condition (100 mW cm-2). A variety of substituents, i.e., methyl, hexyl and triphenylamino groups, were added at the N(10) of phenothiazine in order to optimize the incident photon-to-current conversion efficiency. Along the main chromophore a thiophenylene group was inserted at different positions to examine its influence on the properties of devices. The best performance was found in compound NSPt-C6, in which a hexyl group was attached at the N(10) of phenothiazine and a thiophenylene at the C(7) position. It displayed a short-circuit current (Jsc) of 14.42 mA cm -2, an open-circuit voltage (Voc) of 0.69 V, and a fill factor (ff) of 0.63, corresponding to an overall conversion efficiency of 6.22%. Their photophysical properties were analyzed with the aid of a time-dependent density functional theory (TDDFT) model with the B3LYP functional. Their photovoltaic behavior was further elucidated by the electrochemical impedance spectroscopy.
- Yang, Chih-Jen,Chang, Yuan Jay,Watanabe, Motonori,Hon, Yung-Son,Chow, Tahsin J.
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supporting information; experimental part
p. 4040 - 4049
(2012/05/31)
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- N-methylation of NH-containing heterocycles with dimethyl carbonate catalyzed by TMEDA
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A practical method for N-methylation of NH-containing heterocycles using an environmentally safe and less toxic methylating reagent, dimethyl carbonate, has been developed. N,N,N',N'-tetramethylethylenediamine (TMEDA), an extremely active organocatalyst for the methylation of imides, indoles, benzimidazoles, and piperazines in conjunction with dimethyl carbonate, can lead to N-methylation products with high conversion. The reaction sequence consists of competing alkylation and acylation pathways and involves TMEDA as a nucleophilic catalyst. A possible reaction mechanism is discussed based on the reaction results.
- Zhao, Sheng-Yin,Zhang, Hai-Quan,Zhang, Deng-Qing,Shao, Zhi-Yu
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experimental part
p. 128 - 135
(2011/11/01)
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- Electroluminescence characteristics of a new green-emitting phenothiazine derivative with biphenyl benzimidazole substituent
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We report on the synthesis and electroluminescence characteristics of a new green-emitting material, 3,7-bis(1-(biphenyl-4-yl)benzimidazol-2-yl)10- methylphenothiazine (PhBBMP) containing the electron-donating phenothiazine core and the electron-accepting biphenyl benzimidazole substituent. An optimized OLED device with the structure of [ITO/NPB (40nm)/PhBBMP (30nm)/BCP (10nm)/TPBI (30nm)/LiF (1nm)/Al (100nm)] exhibited a luminous efficiency of 4.5cd/A and an external quantum efficiency of 0.9% at 100mA/cm2, and the maximum luminance of 12,000cd/m2 with the CIE 1931 chromaticity coordinates of (0.21, 0.54). A more balanced charge carrier injection and the charge confinement in the emitting layer cooperatively contributed to improve the performance of the device prepared with the PhBBMP emitting layer.
- Kim, Young Chul,Lee, Sun-Hee,Kim, Man Su,Cha, Yong-Bum,Ahn, Kwang-Hyun
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scheme or table
p. 36 - 43
(2011/07/09)
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- Synthesis of 3,7-disubstituted 10-methylphenothiazines
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Lithiation at the C-3 and C-7 positions of N-methylphenothiazine (1) can be achieved by halogen metal exchange reaction starting from 3,7-dibromo-10-methylphenothiazine (2). Reaction of the lithiated species with carbon, sulfur and silicon electrophiles results in new 3,7-disubstituted 10-methylphenothiazines 4a-g. The described procedure gives high yield and an easy excess to important enzyme mediators.
- Ebdrup, S?ren
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p. 1107 - 1109
(2007/10/03)
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- Preparation of 3-substituted 10-methylphenothiazines
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Lithiation at the C-3 position of 10-methylphenothiazine can be achieved by a BuILi-Br exchange reaction starting from 3-bromo-10-methylphenothiazine. Reaction of the lithiated species with different electrophiles gives rise to different new and well known compounds which due to their radical properties are important enzyme enhancers. The described procedure gives moderate to high yield and easy access to C-3 substituted derivatives.
- Ebdrup, Soren
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p. 1147 - 1150
(2007/10/03)
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- Electron Transfer to Excited Doublet States. Photoirradiation of 10-Methylphenothiazine Cation Radical Perchlorate in Solutions of Phenylacetylene and p-Tolylacetylene in Acetonitrile
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10-Methylphenothiazine cation radical perchlorate (MP.+ClO4-) underwent slow reaction with p-tolylacetylene (PTA) and phenylacetylene (PA) in solution in acetonitrile in the dark.Perchlorate salts (3a and 3b) assumed to be bis-adducts of MP.+ClO4- to the alkyne were formed.In contrast, irradiation of such solutions with visible light (λ > 400 nm) caused oxidation of the alkyne. 2-Methyl-3,6-di-p-tolylpyridine (1a) and 1,4-di-p-tolyl-5,6-dioxa-1,3-cyclohexadiene (2a) were formed from PTA, whereas 2-methyl-3,6-diphenylpyridine (1b) and 1-phenylnaphthalene (4b) were formed from PA.Irradiation of a solution of MP.+ClO4- and 1-pentyne gave only a trace of 2-methyl-3,6-dibutylpyridine (1c).
- Shine, Henry J.,Zhao, Da-Chuan
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p. 4086 - 4089
(2007/10/02)
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- THE EFFECT OF THE STRUCTURE OF THE SUBSTITUENT IN POSITION TEN ON THE VOLTAMMETRIC BEHAVIOUR OF PHENOTHIAZINE DERIVATIVES
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The electrochemical oxidation of seven derivatives of phenothiazine substituted in position 10 on the phenothiazine skeleton has been studied in acetonitrile, using a platinum disc electrode.The electron donor properties of the derivatives that depend on the substituent structure and the presence of nucleophiles in acetonitrile were followed.The diffusion coefficients for the formation of the radical cations were from 10-5 to 10-6 cm2 s-1 and depended on the concentration of the acid in acetonitrile medium.A determination of these substances has beenproposed, using differential pulse voltammetry, with a detection limit of 1*10-7 mol l-1.
- Zimova, Nad'a,Nemec, Ivan,Ehlova, Miroslava,Waisser, Karel
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- Coulombic Effect on Photoinduced Electron-Transfer Reactions between Phenothiazines and Viologens
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Photoinduced electron-transfer reactions between excited phenothiazine derivatives (PTH) and viologens (V) were investigated in aqueous acetonitrile at room temperature.Ionic substituents on PTH or V strongly affected the reaction kinetics, and the Coulombic effects on the reactions were interpreted by the work terms wr and wp, where r and p represent reactants and products, respectively.Fluorescence quenching reactions proceeded with the diffusion-controlled rate constants which were dependent on wr and were explained by the Debye-Smoluchowski equation.Charge separation efficiency (F) corresponding to the cage escape yield of geminate ion radical pair strongly depended on (wp - wr), which indicated that (i) the back-electron-transfer rate determined F and (ii) the Coulombic work terms decided the back-electron-transfer rate.Quantitative teatments of the present results demonstrated that Coulombic effects can be used effectively to generate highly efficient photoredox systems.
- Kawanishi, Yuji,Kitamura, Noboru,Tazuke, Shigeo
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p. 2469 - 2475
(2007/10/02)
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- Endor Studies of Cation Radicals from Pharmacologically Active Phenothiazines
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A variety of substituted phenothiazine cation radicals, including those from pharmacologically active derivatives, e.g. chloropromazine, alimemazine and laevomepromazine, have been studied by means of ENDOR and TRIPLE resonace spectroscopy.These techniques allowed accurate determinations of hyperfine coupling constants, including their signs.Conclusions concerning molecular structure (e.g. twist angles) could be drawn, supporting previous investigations of the interrelationship of molecular conformations with the pharmacological potential, i.e. neuroleptic, antihistaminic or anti-Parkinsonian.
- Helle, N.,Kurreck, H.,Bock, M.,Kieslich, W.
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p. 964 - 970
(2007/10/02)
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- Free Radical Studies by Resonance Raman Spectroscopy: Phenothiazine, 10-Methylphenothiazine, and Phenoxazine Radical Cations
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The free radical cations of phenothiazine, 10-methylphenothiazine, and phenoxazine have been formed by chemical oxidation of their parent compounds.The radicals all possess complex, intense visible absorption bands which allow excitation of their resonance Raman spectra throughout the visible region.The point-group symmetries of the parent compounds in solution have been determined as Cs for both phenothiazine and 10-methylphenothiazine, and C2v for phenoxazine.A partial assignment of the Raman bands has been made for each radical cation studied.The relative intensities of Raman bands and the parent-to-radical frequency shifts observed have been interpreted in terms of the structural changes which occur on radical formation.An analysis of the phenothiazine radical cation visible absorption bands, supplemented by resonance Raman data and excitation profiles, has yielded information on the excited-state geometry.
- Hester, Ronald E.,Williams, Kenneth P. J.
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p. 852 - 859
(2007/10/02)
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- An Isolation and Liquid Phase EPR Spectra of the Cation Radical Salts of N-Methyl and N-Ethylphenothiazinium Perchlorate
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N-Methyl and N-ethylphenothiazines were oxidized with bromine and sodium perchlorate to give stable cation radical salts.Their well-resolved epr spectra were obtained in nitromethane solution.In order to assign the hfs constants, the cation radicals of N-deuteriomethyl and N-deuterioethylphenothiazines were prepared with lead tetraacetate and trifluoroacetic acid in solutions.
- Fujita, Hideo,Yamauchi, Jun
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p. 1053 - 1056
(2007/10/02)
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- Phenothiazinyl sulfides
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A new group of compounds, generically classed as phenothiazinyl sulfides, are described having the formula: STR1 wherein n is 1 or 2, x and/or y and/or z represent 0, 1 or 2; R1 may be H, alkyl, aryl, alkaryl, acyl, haloacyl and biologically activating aminoalkyl groups known in the medicinal arts, such as --(CH2)3 --N(CH3)2, STR2 and -[2-(1-methyl-2-piperidyl)ethyl]; and R2 and/or R3 and/or R4 and/or R5 and/or R6 and/or R7 represent H, OH, Cl, Br, F, CF3, SH, NO2, CN, COOH, alkyl, alkoxy, sulfamoyl, dimethylsulfamoyl, dimethyl amino, aryl, alkaryl, acyl, aryloxy, methyl sulfonyl, methyl thio, and -S-phenothiazinyl substitutents; and as charge-transfer complexes of iodine therewith in which the number of moles of iodine associated with the molecule equals 1.5 (range 0.75 to 3.0) times the number of phenothiazinyl groups in the molecule. Methods for the preparation of the compounds are described. The phenothiazinyl sulfides appear to be active in the same industrial and biological applications as phenothiazine and its corresponding derivatives, and show distinctive activity in various uses and as charge-transfer complexes of novel electrochemical properties as illustrated, in-vitro, in combination with iodine as a cathode material.
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