Phenothiazine Group Research Articles

Uncovering the Aggregation-Induced Emission Mechanisms of Phenoxazine and Phenothiazine Groups.

Molecules with both aggregation-induced emission (AIE) and thermally activated delayed fluorescence (TADF) properties are potential organic light-emitting diode materials; however, the AIE and TADF mechanisms are still debatable. In this work, four molecules incorporating carbazole (Cz), phenoxazine (PXZ), and phenothiazine (PTZ) as donor groups to the diphenylsulfone acceptor were investigated. The experiment results indicate that a molecule containing Cz exhibits solely TADF properties, whereas molecules containing PXZ and PTZ demonstrate both TADF and AIE characteristics. As for DPS-PTZ, the result indicates that the thin-film environment restricts molecular twisting, consequently reducing nonradiative decay, thereby attributing to the AIE property by density functional theory and molecular dynamics simulation. As for DPS-PXZ, the result suggests that the restricted access to a conical intersection in a singlet excited via an expansion in the C-S-C angle is the pivotal factor for the AIE characteristic. The C-S-C angle twist of DPS-PXZ is impeded in the aggregate state and resulted in luminescence. Understanding the mechanisms serves as a valuable guide for the development of new AIE systems, enabling their application in various practical domains.

Phenothiazine Derivatives as Small-Molecule Organic Cathodes with Adjustable Dropout Voltage and Cycle Performance.

Compared with conventional inorganic materials, organic electrodes are competitive candidates for secondary battery cathodes due to their resourcefulness, environmental friendliness, and cost-effectiveness. Much effort is devoted at the level of chemical structure, while ignoring the impact of molecular aggregation on battery behavior. Herein, this work designs a series of organic molecules with two electrochemically active phenothiazine groups linked by different lengths of alkyl chain to regulate molecular symmetry and crystallinity. The results emphasize the equally important role of molecular aggregation and chemical structure for battery performance. Among them, 2PTZ-C7H14|Li cell exhibits the most impressive cycle and rate performance. At the high rate of 50 C, it can still deliver a capacity of 63.4 mA h g-1 and 74.5% capacity retention after 10000 cycles. Besides, the dropout voltage of 2PTZ-C9H18|Li cell is only 52 mV, which is among the lowest reported for lithium-organic batteries to the best of the author's knowledge.

Polycarbazole Electropolymerization Materials with Excellent Electrochromic Performance Based on Phenothiazine/Phenoxazine Group

AbstractElectrochromic small molecules suffer from the difficult film processibility and serious dissolvability at their oxidation state, which greatly limit their applications in electrochromic areas. Here, well‐defined electrochemical polymer structures, pCZ‐FSQ and pCZ‐FEQ, are obtained by taking advantage of the unique electrochemical dimerization of carbazole, and low redox‐potential phenothiazine and phenoxazine groups are introduced as an electrochromic color‐changing unit with the interruption of conjugation between them via an alkyl chain linkage. The obtained polymer films pCZ‐FSQ and pCZ‐FEQ are composed of the independent dimeric carbazole and organic small molecule units. Finally, they exhibit outstanding electrochromic properties with optical contrast of more than 50%, switching time of less than 1 s, excellent stability (over 500 cycles of optical stability), and ultrahigh coloration efficiency (276 cm2C−1for pCZ‐FSQ,384 cm2C−1for pCZ‐FEQ). This is thought to be greatly attributed to the well‐defined electrochemical polymer structures with dual electrochromic color‐changing properties of both phenothiazine/phenoxazine and dimeric carbazole. This can also provide some implications for the future in‐depth study of small molecule electrochromism and the solution to the problem of difficult processing of small molecules.

A Series of D–A–D Structured Disilane-Bridged Triads: Structure and Stimuli-Responsive Luminescence Studies

A series of σ-π extended octamethyltetrasilanes, which have phenothiazine, 9,9-dimethyl-9,10-dihydroacridine, or phenoxazine (1, 2, and 3) groups as donor moieties and thienopyrazine or benzothiadiazole (a and b) groups as acceptor fragments, has been prepared, and their optical properties have been studied as an extension of our work. All six compounds exhibited fluorescence in the solid state with maximum wavelengths centered in the range of 400 and 650 nm upon excitation by a UV lamp. Compound 2b showed apparent dual emission behavior in solution, which depends on solvent polarity, and a reversible photoluminescent change under mechanical and thermal stimuli in the solid state. Quantum chemical calculations suggest the contribution of a quasi-axial conformer of the 9,9-dimethyl-9,10-dihydroacridine moiety in 2b to the dual emission in solution and the mechanofluoroluminescence in the solid state, similarly to 1a. These studies provide new insight into the preparation of disilane-bridged triads capable of responding to multiple stimuli.

Design, synthesis and properties of twisted D-A-D’ arylamine derivatives with solvatochromism

In this study, three molecules with distorted asymmetric D-A-D' structure were synthesized by one-step nucleophilic substitution reaction using different fluorophores (carbazole, phenoxazine, phenothiazine) as electron donors and benzophenone with distorted conformation as electron acceptor. The target compounds were all confirmed by 1H NMR, 13C NMR and EI-MS. In addition, the molecular skeleton of the target compound containing a phenothiazine donor group was further confirmed by X-ray single-crystal diffraction analysis. Combined with the results of UV–vis absorption spectra and fluorescence emission spectra, we found that the different electron donating ability of donor parts (carbazole, phenoxazine and phenothiazine) led to the blue, green and light yellow fluorescence of these compounds in the solid states. Subsequent studies showed that these three compounds all showed remarkable solvatochromism in different organic solvent due to the intramolecular charge transfer (ICT) effect, and the increase of solvent polarity induces a red-shift in the emission wavelength. The results of mechanochromic properties confirmed that only the compound containing phenothiazine fluorophore showed obvious reversible mechanochromic properties. Compounds containing carbazole and phenothiazine groups showed aggregation-induced enhanced emission (AIEE), while compound bearing phenoxazine showed typical aggregation-induced emission (AIE) behavior. Through powder X-ray diffraction (XRD) analysis experiment, crystal structure analysis and theoretical calculation, the relationship between the structure and properties of these molecules was discussed. Finally, we also preliminarily explored the application of these molecules in biological imaging, which exhibited excellent biocompatibility and cell permeability in living cells. In brief, through reasonable molecular design, the luminescent properties and solvatochromism properties of these compounds can be regulated, which provides a theoretical basis for the rational design of molecules with excellent photophysical properties.

Management of Psychiatric Disorders in Patients with Chronic Kidney Diseases.

Management of Psychiatric Disorders in Patients with Chronic Kidney Diseases.

Novel phosphorus(V) tetrabenzotriazacorroles: synthesis, characterization, optical, electrochemical, and femtosecond nonlinear optical studies.

A series of three novel tetrabenzotriazacorroles (TBCs) designed with an alkyl substituent tert-butyl group (TBC-tert), an electron donor phenothiazine group (TBC-PTZ) and an energy donor carbazole group (TBC-CBZ) on the peripheral position with phosphorus metal in the cavity have been synthesized. All three compounds were characterized using various spectroscopic techniques and we assessed their femtosecond third-order nonlinear optical (NLO) properties. TBCs exhibit the properties of both phthalocyanines and corroles as they are derived from parent phthalocyanines. The optical studies revealed a new band at ∼450 nm, which was absent in the parent phthalocyanine molecules, and all three compounds obeyed Beer-Lambert's law. Singlet-state quantum yields were measured in different solvents and were found to be in the range of 0.3 to 0.6 for TBC-tert, 0.21 to 0.25 in the case of TBC-PTZ and 0.31 to 0.41 for TBC-CBZ. Time-resolved fluorescence studies revealed lifetimes in the ns regime (typically few ns). The redox properties of the TBCs suggest that they are easier to oxidize and harder to reduce and exhibit multiple oxidation and reduction potentials. Using the Z-scan technique, the third-order NLO properties were investigated with kilohertz and megahertz repetition rate femtosecond pulses at 800 nm. We report the first observation of strong three-photon absorption in these molecules with coefficients of ∼10-22 cm3 W-2 (∼10-13 cm3 W-2) with kHz (MHz) repetition rate fs pulse excitation.

Synthesis and Photophysical Properties of Purine-Phenoxazine and Purine-Phenothiazine Conjugates

Electron donating phenoxazine and phenothiazine groups were introduced in an electron deficient purine structure through a benzene ring bridge to facilitate thermally activated delayed fluorescence. Mitsunobu and Suzuki-Miyaura reactions were used to synthesize the target compounds. Photophysical properties of target compounds were explored and quantum yields in the thin layer film reached up to 8 % and in the PMMA doped thin layer film up to 15 %.

Novel push-pull based phenothiazine-benzothiazole derivatives integrated with molecular logic gate operation for reversible volatile acid detection

• Design and synthesis of push-pull based phenothiazine benzothiazole derivatives. • Positive solvatochromism with large Stokes shifts (113-146 nm). • Naked eye colorimetric and fluorescent acid sensing behavior in solution and solid state. • Fabrication of paper strip sensors for volatile acid. • Development of INHIBIT molecular logic gate with acid and base as inputs. A series of novel push-pull based phenothiazine-benzothiazole derivatives, in which phenothiazine and benzothiazole groups act as donors and acceptors, respectively is designed and synthesized in good yields. These compounds exhibit strong fluorescence in solution and solid state. These derivatives respond to external stimuli such as solvents and acid. A positive solvatochromism with large Stokes shifts (113-146 nm) was observed. In solution state, blue shifted emission wavelengths of compounds containing electron-withdrawing aryl groups indicated reduced Intramolecular Charge Transfer (ICT). However, red shifts in solid state emission spectra of compounds with electron-withdrawing aryl groups indicated more planarity of the excited state. The naked eye detection of reversible acid/base-induced chromogenic and fluorescence switching properties were observed in both solution and the solid state upon subsequent addition of trifluoroacetic acid (TFA) and triethylamine (TEA), thereby making the synthesized derivatives efficient volatile acid-base switches. The reversible acidochromic response was further utilized for the development of inhibit (INH) molecular logic gates using TFA/ (TEA) as the chemical inputs.

A new phenothiazine derivate is active against Clostridioides difficile and shows low cytotoxicity.

The rapid evolution of antibiotic resistance in Clostridioides difficile and the consequent effects on prevention and treatment of C. difficile infections (CDIs) are matters of concern for public health. Thioridazine, a compound belonging to the phenothiazine group, has previous shown antimicrobial activity against C. difficile. The purpose of this present study was to investigate the potential of a novel phenothiazine derivative, JBC 1847, as an oral antimicrobial for treatment of intestinal pathogens and CDIs. The minimal inhibition concentration and the minimum bactericidal concentration of JBC 1847 against C. difficile ATCC 43255 were determined 4 μg/mL and high tolerance after oral administration in mice was observed (up to 100 mg/kg bodyweight). Pharmacokinetic modeling was conducted in silico using GastroPlusTM, predicting low (< 10%) systemic uptake after oral exposure and corresponding low Cmax in plasma. Impact on the intestinal bacterial composition after four days of treatment was determined by 16s rRNA MiSeq sequencing and revealed only minor impact on the microbiota in non-clinically affected mice, and there was no difference between colony-forming unit (CFU)/gram fecal material between JBC 1847 and placebo treated mice. The cytotoxicity of the compound was assessed in Caco-2 cell-line assays, in which indication of toxicity was not observed in concentrations up to seven times the minimal bactericidal concentration. In conclusion, the novel phenothiazine derivative demonstrated high antimicrobial activity against C. difficile, had low predicted gastrointestinal absorption, low intestinal (in vitro) cytotoxicity, and only induced minor changes of the healthy microbiota, altogether supporting that JBC 1847 could represent a novel antimicrobial candidate. The clinical importance hereof calls for future experimental studies in CDI models.

What Is the Most Important and Impactful Paper Related to Movement Disorder Therapy Published in the 20th Century?

What Is the Most Important and Impactful Paper Related to Movement Disorder Therapy Published in the 20th Century?

Luminescent Behavior Elucidation of a Disilane-Bridged D-A-D Triad Composed of Phenothiazine and Thienopyrazine.

A σ-π extended aryldisilane, comprising a thienopyrazine group as an acceptor fragment and phenothiazine groups as the donor moiety, has been prepared through the introduction of two Si-Si bridges (compound 1). X-ray diffraction analysis determined the crystal structure of 1, and experimental and theoretical approaches investigated its optical properties. Solvatochromic studies revealed the dual emission of 1 in all solvents tested. Compound 1 also exhibited fluorescence in the solid state upon excitation with a hand-held UV lamp, as well as mechanochromic luminescent properties. The packing mode in the crystal structure, variation of phenothiazine conformation, morphological changes between crystalline and amorphous phases are the major factors showing reversible fluorescence under external stimuli. A theoretical conformer study found that 1 exists in distinct conformational groups differing in Gibbs free energy by less than 3 kcal mol-1 . The conformer in the crystalline state of 1 can promote the complete separation of the HOMO and LUMO between the phenothiazine donor and the thienopyrazine acceptor, linked by the disilane linker. HOMO-LUMO energy transition in the crystalline state is forbidden due to the lack of frontier orbital overlap. Crystalline state emission showed LUMO → HOMO-1 transition (locally excited (LE) state). In the amorphous state, the partial presence of quasi-axial conformers allows intramolecular charge-transfer type emission via energy transfer from dominant quasi-equatorial conformers. The strategy proposed in this work provides important guidance for developing stimuli-responsive materials with controlled excited states.

Luminescent Behavior Elucidation of a Disilane‐Bridged D–A–D Triad Composed of Phenothiazine and Thienopyrazine

AbstractA σ–π extended aryldisilane, comprising a thienopyrazine group as an acceptor fragment and phenothiazine groups as the donor moiety, has been prepared through the introduction of two Si−Si bridges (compound 1). X‐ray diffraction analysis determined the crystal structure of 1, and experimental and theoretical approaches investigated its optical properties. Solvatochromic studies revealed the dual emission of 1 in all solvents tested. Compound 1 also exhibited fluorescence in the solid state upon excitation with a hand‐held UV lamp, as well as mechanochromic luminescent properties. The packing mode in the crystal structure, variation of phenothiazine conformation, morphological changes between crystalline and amorphous phases are the major factors showing reversible fluorescence under external stimuli. A theoretical conformer study found that 1 exists in distinct conformational groups differing in Gibbs free energy by less than 3 kcal mol−1. The conformer in the crystalline state of 1 can promote the complete separation of the HOMO and LUMO between the phenothiazine donor and the thienopyrazine acceptor, linked by the disilane linker. HOMO–LUMO energy transition in the crystalline state is forbidden due to the lack of frontier orbital overlap. Crystalline state emission showed LUMO → HOMO−1 transition (locally excited (LE) state). In the amorphous state, the partial presence of quasi‐axial conformers allows intramolecular charge‐transfer type emission via energy transfer from dominant quasi‐equatorial conformers. The strategy proposed in this work provides important guidance for developing stimuli‐responsive materials with controlled excited states.

Methylene blue-mediated Photodynamic Therapy in human retinoblastoma cell lines

Retinoblastoma is a malignant tumor of the retinal precursor cells and one of the rarest types of pediatric tumor, often occurring in the earliest years of life. Symptoms are conditioned by tumor size and location; one of the most recurrent symptoms is a white reflex in the pupillary area, called leukocoria or cat's eye reflex. In the present work, we studied the in vitro effectiveness of Photodynamic treatment (Pdt) in two types of human retinoblastoma, Y79 and WERI-Rb cell lines, using methylene blue (MB), a photosensitizer (PS) from the phenothiazine group. The two cell lines were incubated with varying concentrations of MB (3, 7, 10, 15, 20, 25, 30, 40, and 50μM), in the absence of light (dark cytotoxicity) and, in the presence of 664nm laser light (phototoxicity) with fluences of 1, 1.5, 3, 5, 7, 10, and 15J/cm2. The Y79 cell line showed higher cellular uptake values for MB than the WERI-Rb cell line. After three hours of incubation, the Y79 and WERI-Rb took up 48% and 34% of the total photosensitizer present in the medium, respectively. Using MTT assay, the results showed that the Y79 cell line was more affected by the photo treatment as demonstrated by the combination of MB concentration and light doses compared with WERI-Rb cell line. The results were correlated with the more pronounced singlet oxygen emission observed in Y79 cells. While MB does show efficacy for eradication of retinoblastoma in vitro, only studies in appropriate animal models will reveal whether the selectivity of photokilling at tolerable drug and light doses is sufficient to suggest clinical trials.

Color regulation for dual-states of electrochromic polymer accompanied with light induced coloration effect

With the developing demand for the smart stimuli-responsive materials, the functional conjugated polymers are appealing for the electrochromic materials, due to their adjustable structure, rapid switching time and facile processability. Series of innovative conjugated electrochromic polymers consisting of triphenylamine or phenothiazine group have been designed and synthesized. Other than the conventional electrochromic polymers, our designed polymers can control colors of both reduction and oxidation states with applied external potential. With incorporation of side anode electrochromic group, the polymers bearing triphenylamine group can achieve grey-blue color at oxidation states and those containing phenothiazine group can present dark purple color at their oxidation states. With further modification of polymer backbone, the reduction colors of electrochromic polymers can be regulated as well. Therefore, the effective combination of anode and cathode electrochromic materials in one can realize color regulation for the dual-states as expected. Additionally, the polymers bearing triphenylamine group can further achieve light induced coloration effect as the triphenylamine group can act as light-induced energy source to drive the reduction of polymer backbone. Therefore, the design and effects of these polymers can broaden application range of electrochromic polymers and provide new strategies for energy saving material design.

Force-Induced Turn-On Persistent Room-Temperature Phosphorescence in Purely Organic Luminogen.

Research of purely organic room-temperature phosphorescence (RTP) materials has been a hot topic, especially for those with stimulus response character. Herein, an abnormal stimulus-responsive RTP effect is reported, in which, purely organic luminogen of Czs-ph-3F shows turn-on persistent phosphorescence under grinding. Careful analyses of experimental results, coupled with the theoretical calculations, show that the transition of molecular conformation from quasi-axial to quasi-equatorial of the phenothiazine group should be mainly responsible for this exciting result. Furthermore, the applications of stylus printing and thermal printing are both successfully realized, based on the unique RTP effect of Czs-ph-3F.

Force‐Induced Turn‐On Persistent Room‐Temperature Phosphorescence in Purely Organic Luminogen

AbstractResearch of purely organic room‐temperature phosphorescence (RTP) materials has been a hot topic, especially for those with stimulus response character. Herein, an abnormal stimulus‐responsive RTP effect is reported, in which, purely organic luminogen of Czs‐ph‐3F shows turn‐on persistent phosphorescence under grinding. Careful analyses of experimental results, coupled with the theoretical calculations, show that the transition of molecular conformation from quasi‐axial to quasi‐equatorial of the phenothiazine group should be mainly responsible for this exciting result. Furthermore, the applications of stylus printing and thermal printing are both successfully realized, based on the unique RTP effect of Czs‐ph‐3F.

Y-shaped fluorophore: Synthesis, crystal structure and picric acid detection

Design and synthesis of a novel fluorescent probe for the detection of picric acid is a topic of an incessant research interest. In this context, we have developed a novel ‘Y’ shaped D-A-D type chromophore (TP171). Phenothiazine and methoxy phenyl groups are acting as donor whilst N-substituted imidazole as acceptor unit. As synthesized TP171 show an excellent fluorescent property with a quantum yield of 24%. Intriguingly, the TP171 fluorescent probe instantaneously responded towards the detection of picric acid with a concentration of 12 μM. The detection limit is found to be 7.95 nM.

Redox-Active Polymeric Ionic Liquids with Pendant N-Substituted Phenothiazine.

Polymers that are elastic while supporting charge transport are desirable for flexible and soft electronics. Many polymers with bulky and conjugated redox-active pendant units have high glass transition temperatures (Tg) in their neutral form that will not lead to elasticity at room temperature. Their behavior in charged form in the solid state without an electrolyte has not been extensively studied. Here, the design strategy of polymeric ionic liquid where two weakly interacting ionic groups are used to maintain a low Tg is shown to lead to flexible redox active polymers. The use of a flexible ethylene backbone and redox-active phenothiazine (PTZ)-based pendant group resulted in polymers with relatively low Tg that are electrically conductive. PTZ that was N-substituted with 2-(2-ethoxyethoxy)ethoxy)ethyl was found to promote solubility of the polymer and lower the Tg of the neutral polymer by ∼150 °C relative to that of the Tg of a variant without the N-substituent. Doping with trifluoromethanesulfonimide leads to an electrically conductive polymer without significantly increasing the Tg. Physical characterization by UV-vis-NIR spectroscopy, electron spin resonance spectroscopy, and impedance spectroscopy verified that the molecular design leads to an efficient charge hopping between the PTZ groups.

Inhibition of the replication of SARS-CoV-2 in human cells by the FDA-approved drug chlorpromazine

IntroductionUrgent action is needed to fight the ongoing coronavirus disease 2019 (COVID-19) pandemic by reducing the number of infected cases, contagiousness and severity. Chlorpromazine (CPZ), an antipsychotic from the phenothiazine group, is known to inhibit clathrin-mediated endocytosis and has antiviral activity against severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1) and Middle East respiratory syndrome coronavirus. The aim of this in-vitro study was to test CPZ against SARS-CoV-2 in monkey and human cells.Materials and methodsMonkey VeroE6 cells and human alveolar basal epithelial A549-ACE2 cells were infected with SARS-CoV-2 in the presence of various concentrations of CPZ. Supernatants were harvested at day 2 and analysed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) for the presence of SARS-CoV-2 RNA. Cell viability was assessed in non-infected cells.ResultsCPZ was found to have antiviral activity against SARS-CoV-2 in monkey VeroE6 cells, with a half maximal inhibitory concentration (IC50) of 8.2 µM, half maximal cytotoxic concentration (CC50) of 13.5 µM, and selectivity index (SI) of 1.65. In human A549-ACE2 cells, CPZ was also found to have anti-SARS-CoV-2 activity, with IC50 of 11.3 µM, CC50 of 23.1 µM and SI of 2.04.DiscussionAlthough the measured SI values are low, the IC50 values measured in vitro may translate to CPZ dosages used in routine clinical practice because of the high biodistribution of CPZ in lungs and saliva. Also, the distribution of CPZ in brain could be of interest for treating or preventing neurological and psychiatric forms of COVID-19.ConclusionsThese preclinical findings support clinical investigation of the repurposing of CPZ, a drug with mild side effects, in the treatment of patients with COVID-19.