Search Results (176)

Organic redox-active molecules are promising catholyte materials for aqueous organic redox flow batteries (AORFBs), yet they often suffer from low solubility and poor cycling stability. Herein, we report a series of water-soluble phenothiazine derivatives functionalized with quaternary ammonium groups. The optimized compound, N,N,N-trimethyl-1-(10H-phenothiazin-10-yl) propan-2-aminium chloride (TMiPrPTCl), exhibits exceptional solubility (2.69 M in water) and a high redox potential (0.902 V vs. SHE). A comparative study of four derivatives reveals that side-chain length and branching critically modulate both solubility and degradation pathways: while three-carbon-linked analogs N,N,N-trimethyl-3-(10H-phenothiazin-10-yl)propan-1-aminium chloride (TMPrPTCl) degrade primarily via irreversible oxidation to sulfoxide, two-carbon-linked species (TMiPrPTCl) undergo additional side-chain cleavage, leading to rapid capacity fade. Although the quaternization strategy successfully achieves record solubility, the electrochemical stability remains a key challenge. Post-cycling analysis confirms the loss of redox activity and the formation of inert products. This work highlights the delicate balance between solubility enhancement and molecular stability, providing clear design guidelines for future phenothiazine-based catholytes. Full article

Single-molecule white-light emitters have attracted much attention due to their potential applications in white organic light-emitting diodes (WOLEDs). Their key advantage lies in the ability to use a simple device structure, akin to that of monochromatic OLEDs, to produce WOLEDs. This approach not only simplifies the fabrication process but also reduces costs, improves device stability, and provides a shortcut for the rapid commercialization of WOLEDs. In this study, two novel single-molecule white-light emitters, SRFR-1PTZ (10-(4′-(9H-9,9′-spirobi[fluoren]-2-yl)-4a,10a-dihydro-10H-phenothiazine) and SRFR-2PTZ (2,7-bis(4a,10a-dihydro-10H-phenothiazin-10-yl)-9,9′-spirobi[fluorene]), were designed and synthesized, and successfully implemented in WOLED devices. Comprehensive photophysical characterization revealed that both compounds exhibited dual-emission characteristics in dichloromethane solution, displaying simultaneous fluorescence and phosphorescence. Notably, thermally activated delayed fluorescence (TADF) was clearly observed for SRFR-1PTZ, whereas SRFR-2PTZ did not exhibit TADF behavior. Electroluminescence studies demonstrated that both SRFR-1PTZ and SRFR-2PTZ served as good color-stable cool-white-light emitters under driving voltages of 7–10 V. Full article

In conventional low-viscosity solvents, magnetic field effects (MFEs) in photoredox catalysis are often negligible because photogenerated radical ion pairs (RIPs) diffuse apart before significant spin evolution occurs. This study reports using ionic liquids (ILs) as a tunable homogeneous “solvent cage” to observe distinct low-field MFEs in the phenothiazine-mediated photoinduced reductive dechlorination of aryl chlorides. Experimental results demonstrate that MFEs increase significantly with bulk viscosity, reaching saturation at approximately 1000 Gs with a maximum enhancement of about 15%, consistent with the hyperfine coupling mechanism (HFCM). Femtosecond transient absorption spectroscopy (fs-TA) reveals that the ionic liquid environment effectively reduces the radical cage escape rate, matching it with the spin evolution rate. This allows the external magnetic field to intervene in the back electron transfer (BET) process. However, unlike strongly confined micellar systems, the contribution of the triplet charge recombination (TCR) pathway here is moderate, intrinsically limiting the magnetic enhancement amplitude. These findings establish that MFE magnitude is determined by both viscosity-controlled cage dynamics and the efficiency of the TCR channel, providing a mechanistic basis for designing spin-modulated homogeneous photoredox systems. Full article

Phenothiazine is a heteroaromatic molecule capable of various noncovalent interactions, including halogen bonding and π-stacked association. Despite its broad use in functional materials and pharmaceutical ingredients, a systematic comparison of these interaction modes has been lacking. Here, we report a combined experimental and computational study of intermolecular interactions of phenothiazine with a prototypical halogen-bond (HaB) donor (tetrabromomethane), planar π-electron acceptors (tetracyanopyrazine and tetrafluoro-p-benzoquinone), and multifunctional species capable of both interaction types (iodo- and bromo-3,5-dinitrobenzenes). X-ray structural analysis revealed that CBr₄ forms exclusively C–Br···π halogen bonds with the aromatic rings of phenothiazine, whereas all π-acceptors yield alternating donor–acceptor stacks characterized by multiple short contacts indicative of multicenter interactions. Notably, co-crystals of iodo- and bromodinitrobenzenes with phenothiazine display only π-stacked architectures. Density-functional calculations showed that isolated HaB complexes involving N, S, or π sites of phenothiazine possess comparable binding energies (≈−3 kcal mol⁻¹), whereas π-stacked complexes are substantially stronger (≈−9–12 kcal mol⁻¹). QTAIM, NCI, NBO, and energy-decomposition analyses indicated that while amounts of charge transfer in halogen-bonded and π-stacked complexes are comparable, the enhanced stability of the latter originates primarily from a large dispersion contribution. These results rationalize the solid-state preference for π-stacking over halogen bonding in systems where both motifs are accessible and clarify the hierarchy and physical origin of noncovalent interactions involving phenothiazine, providing guidance for the design of supramolecular assemblies and functional materials based on this versatile electron donor. Full article

Background: Phenothiazine derivatives bearing trifluoromethyl substituents have attracted increasing interest as multifunctional scaffolds in drug repositioning strategies, particularly in cancer and infectious diseases. Structural modification of classical phenothiazines by incorporation of a quinoline moiety has previously been shown to enhance biological activity. Objectives: The present study aimed to develop an efficient synthesis of 8-trifluoromethylquinobenzothiazines and to evaluate the anticancer and antibacterial potential of their N-substituted analogues inspired by triflupromazine, trifluoperazine, and fluphenazine. Methods: 6H-8-Trifluoromethylquinobenzothiazine was synthesized by cyclization of 2-amino-4-trifluoromethylbenzenethiol and 3-bromo-2-chloroquinoline. The resulting quinobenzothiazine, unsubstituted at the nitrogen atom, was subjected to N-alkylation reactions to afford eleven new 6-dialkylaminoalkyl derivatives. Structural elucidation was performed using NMR and HRMS techniques. Anticancer activity was evaluated by MTT assay against human breast (MDA-MB-231), pancreatic (Mia-PaCa-2), and lung (A-549) carcinoma cell lines, as well as normal HaCaT keratinocytes. Antibacterial activity was assessed by MIC/MBC determination against selected Gram-positive and Gram-negative reference strains and clinical isolates. Results: Among the synthesized compounds, derivatives 8 and 12 exhibited the most favorable anticancer profiles, showing micromolar cytotoxicity (IC₅₀ ≈ 4–10 µM) against lung and pancreatic cancer cells combined with moderate selectivity toward cancer cells over normal keratinocytes. Compound 6 displayed lower cytotoxic potency but a notably high selectivity index due to minimal toxicity toward normal cells. In antibacterial assays, compound 3 exhibited activity against Gram-positive bacteria, including a methicillin-resistant Staphylococcus aureus isolate, with MIC values ranging from 7.8 to 15.6 µg/mL. The corresponding MBC values were equal to or twofold higher than the MICs (MBC/MIC = 1–2), fulfilling commonly accepted criteria for bactericidal activity (MBC/MIC ≤ 4). OD-based growth kinetics confirmed concentration-dependent inhibition of S. aureus growth. Conclusions: The obtained results identify 8-trifluoromethylquinobenzothiazines as a promising class of multifunctional compounds. Selected derivatives combine anticancer activity with acceptable selectivity or display potent antibacterial effects against clinically relevant Gram-positive pathogens. Full article

Heterocyclic compounds have enormous pharmacological potential and therefore play a key role in the design of new drugs. Dipyridothiazines, both heterocyclic compounds and phenothiazine derivatives, exhibit promising anticancer, immunostimulatory, and antioxidant activities. The aim of this study was to design, synthesize, and evaluate the cytotoxicity of new 10-heteroaryl dipyridothiazines based on 2,7- and 3,6-diazaphenothiazine cores. The structural characterization of the new compounds was confirmed by spectroscopic methods. Cytotoxicity analysis was performed using the MTT assay against human keratinocytes (HaCaT) and two types of cancer cell lines: breast cancer (MDA-MB-231), lung carcer (A-549). The reference drugs used in the study were doxorubicin and cisplatin. The group of derivatives studied included active compounds as well as inactive derivatives. In order to explain differences in an activity level, molecular modelling supported by molecular dynamics was performed on histone deacetylase 6 (HDAC6), a known therapeutic target associated with oncogenic transformation and cancer metastasis. Molecular docking indicated that the derivative formed on the 2,7-diazaphenothiazine core is a more potent HDAC6 inhibitor, characterized by more stable binding and more favourable complex energy, despite minimal structural differences compared to the compound formed on the 3,6-diazaphenothiazine core. A preliminary SAR analysis was performed. Full article

The development of new photoinitiators for photocurable systems has gained increasing interest in response to regulatory and environmental requirements, including efficient absorption in the UV/Vis range and reduced toxicity. Among emerging light-sensitive compounds, oxime esters have attracted growing attention as efficient radical photoinitiators. In this paper, five series of oxime esters based on carbazole, coumarin, carbazole–coumarin, phenothiazine, and triphenylamine scaffolds were described. Their high performance in photopolymerization processes was presented, demonstrating their ability to act as both type I and type II photoinitiators, as confirmed by high monomer conversion degrees. These data highlight oxime esters as versatile photoinitiating systems and provide a basis for further structural optimization aimed at improving water solubility and enabling comprehensive cytotoxicity assessment. Full article

This review offers a focused overview of the strategies used to build and modify phenothiazine (PTZ) derivatives. It covers both classical synthetic approaches and advances reported since 2014, including transition metal-catalyzed transformations and greener techniques, such as electrosynthesis, microwave-assisted reactions, and ultrasound-promoted methods. Each strategy is evaluated with respect to efficiency, scalability, and sustainability. In parallel, the review surveys the diverse bioactivity profiles of PTZ derivatives, ranging from antipsychotic, anticancer, and antimicrobial activities to emerging applications in photodynamic therapy and neuroprotection. By correlating synthetic accessibility with biological potential, this review provides an integrated perspective that highlights advances achieved since 2014 and outlines future opportunities for rational PTZ design and applications. Full article

The aim of this work was to prepare new heterodimeric molecules containing pharmacophoric fragments of 3-cyanoquinoline/3-aminothieno[2,3-b]pyridine/3-aminothieno[2,3-b]quinoline on one side and phenothiazine on the other. The products were synthesized via selective S-alkylation of readily available 2-thioxo-3-cyanopyridines or -quinolines with N-(chloroacetyl)phenothiazines, followed by base-promoted Thorpe–Ziegler isomerization of the resulting N-[(3-cyanopyridin-2-ylthio)acetyl]phenothiazines. We found that both the S-alkylation and the Thorpe–Ziegler cyclization reactions, when conducted with KOH under heating, were accompanied to a significant extent by a side reaction involving the elimination of phenothiazine. Optimization of the conditions (0–5 °C, anhydrous N,N-dimethylacetamide and NaH or t-BuONa as non-nucleophilic bases) minimized the side reaction and increased the yields of the target heterodimers. The structures of the products were confirmed by IR spectroscopy, ¹H, and ¹³C DEPTQ NMR studies. It was demonstrated that the synthesized 3-aminothieno[2,3-b]pyridines can be acylated with chloroacetyl chloride in hot chloroform. The resulting chloroacetamide derivative reacts with potassium thiocyanate in DMF to form the corresponding 2-iminothiazolidin-4-one; in this process, phenothiazine elimination does not occur, and the Gruner–Gewald rearrangement product was not observed. The structural features and spectral characteristics of the synthesized 2-iminothiazolidin-4-one derivative were investigated by quantum chemical methods at the B3LYP-D4/def2-TZVP level. A range of drug-relevant properties was also evaluated using in silico methods, and ADMET parameters were calculated. A molecular docking study identified a number of potential protein targets for the new heterodimers, indicating the promise of these compounds for the development of novel antitumor agents. Full article

Background/Objectives: Malaria remains the most critical parasitic disease globally, responsible for over 600.000 deaths annually. In sub-Saharan Africa, co-infections of Plasmodium falciparum with other pathogens, particularly Staphylococcus aureus, are common in children with severe malaria. Therefore, the design of new compounds targeting both pathogens appears to be an urgent priority. Methods: A small series of hybrid compounds was designed and synthesized by linking the pharmacophore of the antimalarial drug chloroquine with the phenothiazine core. These compounds were tested in vitro against a panel of microbial strains and further analyzed through in silico simulations to predict their physical-chemical properties. Results: Compounds 4b and 5b emerged the most potent candidates of the series, showing a sub-micromolar inhibitory activity on P. falciparum, and a promising micromolar potency on S. aureus alongside with a low toxicity on mammalian cells. Molecular docking followed by molecular dynamics (MD) simulations identified the respiratory membrane NDH-2 enzyme as common target in both pathogens. Conclusions: Both experimental and computational findings provide compelling evidence for the use of the designed compounds in a STOP strategy, i.e., Same-Target-Other-Pathogen, to treat malaria and bacterial infections concurrently. Full article

Macrocyclic arenes are rich-electron macrocycles bridged by methylene or methyl groups from aromatic rings substituted by hydroxyl or alkoxy groups. It has attracted great interest in host–guest chemistry and supramolecular self-assembly due to its clear cavity, adjustable structure and multifunctional binding ability. In particular, nitrogen-containing macrocyclic arenes including (hetero) aromatic moieties—constructed from building blocks such as pyrrole, carbazole, phenothiazine, and imidazole—have undergone rapid development, yielding a new generation of functional macrocycles, including calix[4]carbazoles, Tröger’s base-derived macrocycles, and phenothiazine-based architectures. These nitrogen-functionalized macrocycles feature rich chemical derivatization potential, unique structural and host–guest characteristics, and exceptional photophysical properties. They show great promise in molecular recognition, selective adsorption and separation, and the development of advanced functional materials. This review summarizes recent advances in the design, synthesis, and application of nitrogen-containing macrocyclic arenes, with a particular focus on structure–property relationships and emerging functions. Full article

This study explores the visible-light-driven photolysis of Ferrioxalate complexes for the degradation of Toluidine Blue (TB), a persistent phenothiazine dye, using a 1 L recirculating batch-loop photoreactor. The reactor system incorporated two tubular photochemical units (35 cm × 3 cm each) in series: the first equipped with an immersed blue fluorescent lamp (12 W, 30 cm-tube), and the second with dual external blue LED lamps (18 W total, 30 cm) encasing a double-walled glass cell. Continuous flow between the units was maintained via a peristaltic pump. Experimental investigations were used to evaluate the effects of key parameters such as Fe(III) and oxalate concentrations, initial TB load, pH, light source, flow rate, ligand type, dissolved gas type, external H₂O₂ addition, and the presence of various inorganic ions. The results demonstrate efficient dye degradation, with ~75% TB removal within 1 h under combined fluorescent and LED irradiation, where each reactor contributing comparably. The optimal performance was achieved at pH 4, with a 10 oxalate-to-Fe(III) molar ratio (1 mM:0.1 mM) and a flow rate of 25 mL s⁻¹. Among various ligands tested (oxalate, acetate, citrate, EDTA), oxalate proved to be the most effective. The presence and type of anions significantly influenced degradation efficiency due to their potential scavenging effects. Although the process achieved high dye removal, TOC analysis indicated only moderate mineralization, suggesting the accumulation of non-colored intermediates. External H₂O₂ addition moderately improved TOC removal, likely due to enhanced hydroxyl radical generation via the Fenton mechanism. These findings highlight the promise of Ferrioxalate-based photochemical systems under visible light for dye removal, while also emphasizing the need for further research into by-product identification, mineralization enhancement, and toxicity reduction to ensure safe effluent discharge. Full article

Background and Objectives: Feces-induced peritonitis (FIP), a clinically relevant model of polymicrobial sepsis, induces systemic inflammation and acute lung injury (ALI). Methylene blue (MB), a phenothiazine-based compound, exhibits vasoregulatory, antioxidant, and anti-inflammatory properties in the context of sepsis. This study aimed to evaluate the protective effects of MB on pulmonary injury in a rat model of FIP-induced sepsis. Materials and Methods: Forty male Wistar rats were randomly assigned to four groups: control, FIP, FIP + Saline, and FIP + MB. MB was administered intraperitoneally at a dose of 20 mg/kg, 1 h after FIP induction. At 24 h post-induction, plasma levels of inflammatory markers [interleukin-6 (IL-6), interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP)], oxidative stress marker [malondialdehyde (MDA)], metabolic indicator [lactic acid], and vascular signaling marker [cyclic guanosine monophosphate (cGMP)] were measured. Lung injury was evaluated through histopathological analysis and thoracic computed tomography (CT)-based Hounsfield unit (HU) quantification, while pulmonary function was assessed via arterial blood gas analysis, including arterial oxygen pressure (PaO₂) and carbon dioxide pressure (PaCO₂). Results: FIP induction led to significant increases in plasma levels of IL-6, IL-1β, TNF-α, CRP, MDA, cGMP, and lactic acid, accompanied by elevated CT attenuation (HU) values and a marked reduction in arterial PaO₂ and PaCO₂. MB treatment significantly decreased the levels of IL-6, IL-1β, TNF-α, CRP, MDA, lactic acid, and cGMP, improved PaO₂, and attenuated both histopathological lung injury and CT-assessed parenchymal density. No significant differences were observed in PaCO₂ among the groups. Conclusions: MB mitigates inflammation, oxidative damage, and pulmonary dysfunction in FIP-induced sepsis. Further studies are warranted to optimize dosing and timing and to evaluate long-term outcomes. Full article

Doxorubicin (Dox) is a potent anthracycline antitumor drug whose clinical utility is significantly restricted by its dose-dependent, cumulative cardiotoxicity, driven by increased oxidative stress, impaired antioxidant defenses, and apoptosis-mediated cardiomyocyte loss. Methylene blue (MB), a phenothiazine derivative with well-documented redox-modulating properties, is being explored as a viable cardioprotective agent due to its antioxidant and anti-apoptotic effects. This study evaluated the protective role of MB against Dox-induced cardiotoxicity in rats by examining its impact on oxidative stress markers (Kelch-like ECH-associated protein 1; KEAP1, nuclear factor erythroid 2-related factor 2; NRF2, Glutathione peroxidase 4; GPX-4, 8-hydroxy-2′-deoxyguanosine; 8-OHdG), neurohormonal indicators (noradrenaline), cardiac injury biomarkers (troponin I), and apoptotic mediators (p53, Caspase-3). Forty male albino rats were divided equally into four groups: control, Dox (15 mg/kg, i.p.), MB alone (4 mg/kg/day, p.o. for 7 days), and Dox plus MB. Dox administration significantly increased serum troponin I and noradrenaline levels, elevated cardiac KEAP1 and 8-OHdG, and reduced NFE2L2, NRF2, and GPX-4 expression. It also upregulated p53 and Caspase-3 and caused marked myocardial degeneration, necrosis, and inflammatory infiltration. MB co-treatment significantly reduced troponin I and noradrenaline levels, restored KEAP1/NFE2L2 (NRF2)/GPX-4 pathway balance, decreased oxidative DNA damage, and attenuated p53 and Caspase-3 activation, preserving myocardial architecture with minimal inflammatory changes. These findings demonstrate that MB confers potent cardioprotection against Dox-induced cardiac injury by enhancing antioxidant defenses, limiting oxidative DNA damage, suppressing apoptosis, and normalizing neurohormonal imbalance, suggesting its promise as an adjunctive strategy to mitigate anthracycline-associated cardiotoxicity. Full article