Ultraviolet radiation thin film dosimetry: A review of properties and applications.

Spectroradiometry, radiometry, and dosimetry are employed for the measurement of ultraviolet radiation (UVR) irradiance and non-ionizing exposure. Different types of UVR dosimeter have been developed for measuring personal and environmental UVR exposures since film dosimetry was pioneered in the 1970s. An important type of dosimeter is the thin film variant, which contains materials that undergo changes in optical absorbance when exposed to UVR. These changes can be measured at a specific wavelength using a spectrophotometer. Thin film dosimeters allow UVR exposure measurements on humans at various body sites during daily activities, as well as on plants, animals, and any sites of interest when utilized in a field environment. This review examines the properties and applications of five types of thin film UVR dosimeter that have different dynamic exposure limits and spectral responses. Polysulphone, with a spectral response approximating the human erythema action spectrum, was one of the first materials employed in thin film form for the measurement of UVR exposures up to 1 day, and up to 6 days with an extended dynamic range filter. Polyphenylene oxide has been characterized and employed for personal UVR exposure measurements up to approximately four summer days and has also been used for long-term underwater UVR exposures. Phenothiazine and 8-methoxypsoralen have been reported as suitable for the measurement of longer wavelength UVA exposures. Finally, polyvinyl chloride with an extended dynamic exposure range of over 3 weeks has been shown to have predominantly a spectral response in the UVB and extending up to 340 nm.

Configurationally Stepping Confinement Achieved Tunable Chiral Near-Infrared Luminescence Supramolecular Phenothiazine Organic Framework.

Herein, thermally responsive reversible chiral supramolecules are reported, constructed by the chirality transfer from tripeptides to achiral network supramolecular organic frameworks (SOF) based on configurationally stepping confinement, which displayed not only highly selective reversible chirality transfer but also efficient enhanced near-infrared (NIR) luminescence. Taking advantage of macrocyclic confinement, CB[8] separately encapsulated two kinds of tetracationic bis(phenothiazines) derivatives (G1, G2) at 2:1 stoichiometric to form organic 2D SOFs, efficiently enhancing 12.6 fold NIR luminescence and blueshifted from 705 to 680 nm for G1, and redshifted from 695 to 710 nm for G2, respectively. Uncommonly, the tripeptide coassembled with two kinds of achiral noncovalent frameworks (G1/CB[8] or G2/CB[8]) displayed different opposite circular dichroism signals based on different binding modes and affinity, achieving chirality transfer from tripeptide to organic supramolecular assemblies with further enhanced NIR fluorescence up to 46.2 times and the quantum yield (QY) increased from 0.71% to 10.29% for G2/CB[8], showing reversible chirality transfer and tunable NIR fluorescence under thermal stimulus. Therefore, the current research has achieved controllable chirality transfer from tripeptide to the SOFs and the enhancement of tunable NIR fluorescence, which is successfully applied in thermal responsive chiral logic gates, information encryption, and cell imaging.

A Review on Recent Development of Phenothiazine-Based Chromogenic and Fluorogenic Sensors for the Detection of Cations, Anions, and Neutral Analytes.

This review provides an in-depth examination of recent progress in the development of chemosensors, with a particular emphasis on colorimetric and fluorescent probes. It systematically explores various sensing mechanisms, including metal-to-ligand charge transfer (MLCT), ligand-to-metal charge transfer (LMCT), photoinduced electron transfer (PET), intramolecular charge transfer (ICT), and fluorescence resonance energy transfer (FRET), and elucidates the mechanism of action for cation and anion chemosensors. Special attention is given to phenothiazine-based fluorescence probes, highlighting their exceptional sensitivity and rapid detection abilities for a broad spectrum of analytes, including cations, anions, and small molecules. Phenothiazine chemosensors have emerged as versatile tools widely employed in a multitude of applications, spanning environmental and biomedical fields. Furthermore, it addresses existing challenges and offers insights into future research directions, aiming to facilitate the continued advancement of phenothiazine-based fluorescent probes.

Nanomolar Hg2+ detection via phenothiazine fluorogenic chemosensor: Applications in water analysis and intracellular imaging.

A Knoevenagel condensation reaction paved the way for the development of the PTZ-BCN probe namely (z)-2-(1H-benzo[d]imidazole-2-yl)-3-(10-ethyl-10H-phenothiazin-3-yl) acrylonitrile. PTZ-BCN's spectral characteristics were verified through the application of IR, 1H NMR, 13C NMR, and HRMS techniques. The PTZ-BCN probe showed a high selectivity and sensitivity toward Hg2+ ions over other interfering competing metal ions in CH3CN: HEPES buffer (9:1, v/v) system. The addition of Hg2+ results in a notable redshift and fluorescence quenching of the PTZ-BCN probe. An examination of the interaction between the PTZ-BCN probe and Hg2+ involved recoding 1H NMR titration spectra, HRMS, DFT analysis, and Job's plot respectively. Quantification of the lowest detectable Hg2+ concentration at 2.3 nM, exhibiting a correlation coefficient of R2 = 0.9985. PTZ-BCN probe has proven effective in quantitatively determining the existence of Hg2+ in real-time water samples, test strips, solid state, and Hela living cells.

Synthesis and Structure of 5-Methyl-9-(trifluoromethyl)-12H-quino[3,4-b][1,4]benzothiazinium Chloride as Anticancer Agent.

In this work, the synthesis, structural analysis and anticancer properties of 5-methyl-9-trifluoromethyl-12H-quino[3,4-b][1,4]benzothiazinium chloride (3) are described. Compound 3 was synthesized by reacting 1-methyl-4-butylthio-3-(benzoylthio)quinolinium chloride with 4-(trifluoromethyl)aniline, respectively. The structure of the resulting product was determined using 1H-NMR and 13C-NMR spectroscopy as well as HR-MS spectrometry. The spatial geometry of agent 3 and the arrangement of molecules in the crystal (unit cell) were also confirmed using X-ray diffraction. The tetracyclic quinobenzothiazinium system is fairly planar because the dihedral angle between the planes formed by the benzene ring and the quinoline system is 173.47°. In order to obtain insight into the electronic charge distribution of the investigated molecule, electronic structure calculations employing the Density Functional Theory (DFT) were performed. Moreover, antiproliferative activity against a set of pancreatic cancer cell lines was tested, with compound 3 showing IC50 values against human primary pancreatic adenocarcinoma BxPC-3 and human epithelioid pancreatic carcinoma Panc-1 of 0.051 µM and 0.066 µM, respectively. The IC50 value of cytotoxicity/cell viability of the investigated compound assessed on normal human lung fibroblasts WI38 was 0.36 µM.

Polymers Containing Phenothiazine, Either as a Dopant or as Part of Their Structure, for Dye-Sensitized and Bulk Heterojunction Solar Cells.

Potential photovoltaic technology includes the newly developed dye-sensitized solar cells (DSSCs) and bulk heterojunction (BHJ) solar cells. Owing to their diverse qualities, polymers can be employed in third-generation photovoltaic cells to specifically alter their device elements and frameworks. Polymers containing phenothiazine, either as a part of their structure or as a dopant, are easy and economical to synthesize, are soluble in common organic solvents, and have the potential to acquire desired electrochemical and photophysical properties by mere tuning of their chemical structures. Such polymers have therefore been used either as photosensitizers in dye-sensitized solar cells, where they have produced power conversion efficiency (PCE) values as high as 5.30%, or as donor or acceptor materials in bulk heterojunction solar cells. Furthermore, they have been employed to prepare liquid-free polymer electrolytes for dye-sensitized and bulk heterojunction solar cells, producing a PCE of 8.5% in the case of DSSCs. This paper reviews and analyzes almost all research works published to date on phenothiazine-based polymers and their uses in dye-sensitized and bulk heterojunction solar cells. The impacts of their structure and molecular weight and the amount when used as a dopant in other polymers on the absorption, photoluminescence, energy levels of frontier orbitals, and, finally, photovoltaic parameters are reviewed. The advantages of phenothiazine polymers for solar cells, the difficulties in their actual implementation and potential remedies are also evaluated.

ß-Cyclodextrin mediated controlled release of phenothiazine from pH-responsive pectin and pullulan-based hydrogel optimized through experimental design.

Drugs with lower permeability and water solubility provide major challenges for producing safe and efficient formulations. The current work aims to prepare ICs of the drug phenothiazine and ß-cyclodextrin via physical, microwave, freeze-drying, and kneading methods. Many analytical methods, such as 1H NMR, ROESY, FT-IR, DSC, SEM, and XRD, were then used to confirm the formation of inclusion complexes. The natural polysaccharide-based hydrogel comprising pectin and pullulan was synthesized in air and optimized through various parameters. In order to maximize the reaction parameters, Response Surface Methodology design was employed for experimental optimization. We use FT-IR, TGA, SEM, EDX, and XRD to investigate hydrogel formation. At 37 °C, an investigation was carried out on the in vitro controlled release of PN at pH 2, 7, and 7.4. The analysis of drug release data revealed that PM and KM exhibited an initial burst release of drugs, with the MW and FD method proving to be the most suitable approach for achieving precise ICs of PN and ß-CD for sustained drug release. The kinetics of drug release were evaluated using various kinetic models, with the Riteger-Peppas and Peppas-Sahlin models demonstrating the best fit for drug release in all instances.

Synthesis of new phenothiazine derivatives: Molecular docking, assessment of cytotoxic activity and oxidant-antioxidant properties on PCS-201-012, HT-29, and SH-SY5Y cell lines.

Phenothiazine (PTZ) derivatives have been acknowledged as versatile compounds with significant implications across various areas of medicine, particularly, in cancer research. The cytotoxic effects of synthesized compounds on both normal and cancerous cells, along with their oxidant-antioxidant properties, are pivotal factors in cancer treatment strategies. In the current study, eight new PTZ derivatives were synthesized and the compounds' cytotoxic activities were assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay while the oxidant-antioxidant properties were evaluated by oxidative stress index (OSI) calculation in SH-SY5Y (a human neuroblastoma cell line), HT-29 (a human colorectal adenocarcinoma cell line), and PCS-201-012 (a human primary dermal fibroblast cell line) cells. Consequently, the half-maximal inhibitory concentration (IC50) values of compound 3a were determined to be 218.72, 202.85, and 227.86 µM while the IC50 values of compound 3b were defined to be 227.42, 199.27, and 250.11 µM in PCS-201-012, HT-29, and SH-SY5Y cells, respectively. Additionally, it was determined that the synthesized compounds demonstrated the lowest OSI in PCS-201-012 cells as compared to the other cell lines.

A New Phenothiazine-Based Fluorescent Probe for Rapid and Specific Detection of Fluoride.

Fluorescent probes with specific and rapid response to fluoride ions are important mediators for detecting fluoride ions in biological systems. In this study, a phenothiazine-based fluorescent probe, PTC, was designed and synthesized, which undergoes cleavage activation and cyclization induced by fluoride ions targeting Si-O bonds. The probe exhibits strong anti-interference properties and reaches peak fluorescence within 5 min, allowing for quantitative detection of fluoride ions content in the concentration range of 0 to 12.5µM, suitable for live cell fluorescence imaging. The research findings suggest its potential application value in biological systems.

A novel approach to investigate the combinatorial effects of TLK1 (Tousled-Like Kinase1) inhibitors with Temozolomide for glioblastoma therapy.

Glioblastoma multiforme (GBM) is an aggressive, incurable brain tumor with poor prognosis and limited treatment options. Temozolomide (TMZ) is the standard chemotherapeutic treatment for GBM, but its efficacy has drawn strong criticism from clinicians due to short survival gains and frequent relapses. One critical limitation of TMZ therapy is the hyperactivation of DNA repair pathways, which over time neutralizes the cytotoxic effects of TMZ, thus highlighting the urgent need for new treatment approaches. Addressing this, our study explores the therapeutic potential of in-house-designed phenothiazine-based Tousled-like kinase-1 (TLK1) inhibitors for GBM treatment. TLK1, overexpressed in GBM, plays a role in DNA repair. Phenothiazines are known to cross the blood-brain barrier (BBB). Among all molecules, J54 was identified as a potential lead molecule with improved cytotoxicity. In the context of O6-methylguanine-DNA methyltransferase (MGMT)-deficient GBM cells, the combined administration of phenothiazines and TMZ exhibited a collective reduction in clonogenic growth, coupled with anti-migratory and anti-invasion effects. Conversely, in MGMT-proficient cells, phenothiazine monotherapy alone showed reduced clonogenic growth, along with anti-migratory and anti-invasion effects. Notably, a synergistic increase in γH2AX levels and concurrent attenuation of DNA repair upon combinatorial exposure to TMZ and J54 were observed, implying increased cytotoxicity due to sustained DNA strand breaks. Overall, this study provides new insights into TLK1 inhibition for GBM therapy. Collectively, these findings indicate that TLK1 is one of the upregulated kinases in GBM and phenothiazine-based TLK1 inhibitors could be a promising treatment option for GBM patients.

Phenothiazine Derivatives: The Importance of Stereoisomerism in the Tolerance and Efficacy of Antimicrobials.

Stereoisomers are molecules that are identical in atomic constitution and bonding. The biological properties may, however, differ significantly between two enantiomers (individual stereoisomers). JBC 1847, a phenothiazine derivative with strong antimicrobial activity against Gram-positive bacteria, exists in two enantiomers, S and R. Under standard chemical synthesis (S)-and (R)-JBC 1847 will be present in 50/50 amount (racemic). In this study, we have investigated the antimicrobial activity, the in vivo tolerance and therapeutic efficacy of purified (S)-JBC 1847. Compared to JBC 1847 racemic, the antimicrobial activity of (S)-JBC 1847 in vitro was in the same range or slightly increased, while the maximum tolerable concentration in vivo was five times higher for (S)-JBC 1847 (5 mg/kg versus 20 mg/kg bodyweight). Furthermore, the in vivo efficacy of (S)-JBC 1847 in a mouse peritonitis MRSA model was comparable to the activity of vancomycin. In conclusion, the antimicrobial activity and tolerance of a medical stereoisomeric compound may be significantly different using purified enantiomers compared with the racemic state. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-024-01309-3.

Electrochemical Synthesis of the In Human S-oxide Metabolites of Phenothiazine-Containing Antipsychotic Medications.

The tractable preparation of Phase I drug metabolites is a critical step to understand the first-pass behaviour of novel chemical entities (NCEs) in drug discovery. In this study, we have developed a structure-electroactivity relationship (SeAR)-informed electrochemical reaction of the parent 2-chlorophenothiazine and the antipsychotic medication, chlorpromazine. With the ability to dial-in under current controlled conditions, the formation of S-oxide and novel S,S-dioxide metabolites has been achieved for the first time on a multi-milligram scale using a direct batch electrode platform. A potential rationale for the electrochemical formation of these metabolites in situ is proposed using molecular docking to a cytochrome P450 enzyme.

Rapidly responsive and highly selective NIR fluorescent probe for detecting hydrogen sulfide in food samples and living cells.

Hydrogen sulfide (H2S) is a pungent gas that is one of the key mediators of signal transduction in biological systems, and its presence is related to the freshness of some protein foods. Using phenothiazine derivatives as fluorophores and 2, 4-dinitrobenzene sulfonate (DNBS) fragments as reaction groups, a near-infrared (NIR) probe WX-HS for H2S identification was designed. With the addition of H2S, WX-HS appeared a strong fluorescence signal at 660 nm with short reaction time (90 s) and high sensitivity, and fluorescence state change from non-fluorescent to orange-red. In addition, WX-HS could effectively detect H2S produced during food oxidation. Based on its low cytotoxicity, the WX-HS probe further enabled the detection and imaging of H2S in A549 cells.

New Butterfly-Shaped Naphthalimide-Based AIE Gens: Synthesis and Photophysical Properties.

Two novel naphthalimide derivatives PTZNI-Cz and PTZNI-TPA were successfully designed and synthesized, in which phenothiazine, triphenylamine and carbazole were used as electron donors and naphthalimide was used as the electron acceptor. Their photophysical, electrochemical, and thermal properties were investigated. These derivatives showed remarkable aggregation-induced emission (AIE) effect. Furthermore, the maximum emission peaks of PTZNI-Cz and PTZNI-TPA in the thin film state are at 610 nm and 623 nm respectively, which is typical of red fluorescent materials.

Novel Dual-Emission Emitters Featuring Phenothiazine-S-Oxide and Phenothiazine-S,S-Dioxide Motifs.

In this study, we have successfully designed and synthesized two novel dual-emission emitters featuring phenothiazine-5-oxide and phenothiazine-5,5-dioxide motifs, characterized by highly lopsided and asymmetric conformational states. Through rigorous spectral examinations and DFT calculations, the compounds exhibit distinctive ICT phenomena, coupled with efficient emission in solid states and AIEE characteristics under high water fractions in DMF/H2O mixtures. These non-planar luminogens exhibit vibrant green and blue solid-state luminescence, with fluorescence quantum yields of 24.1 % and 15.21 %, respectively. Additionally, they both emit green fluorescence in THF solution, with notable emission quantum yields (QYs) 36.4 % and 30.4 %. Comprehensive theoretical investigations unveil well-defined electron cloud density separation between the energies of HOMO/LUMO levels within the two luminogens. Notably, the targeted molecule harboring the phenothiazine-S,S-dioxide motif also demonstrates remarkable reversible mechanofluorochromic properties. Moreover, we testify their potential in applications such as solid-state rewritable information storage and live-cell imaging in solution states. Through theoretical calculations and comparative studies, we have explored the intrinsic relationship between molecular structure and performance, effectively screening and identifying new fluorescent molecules exhibiting outstanding luminescent attributes. These discoveries establish a robust theoretical and technical foundation for the synthesis and application of efficient DSE-based MFC materials, opening new avenues in the realm of advanced luminescent materials.

Bis-Ortho-Donor-Modification of Boracyclic π-Electron Systems beyond Steric Protection to Produce Thermally Activated Delayed Fluorescence Materials.

Polycyclic π-conjugated compounds that contain tricoordinate boron atoms at their periphery represent an attractive class of materials with electron-accepting character. Their molecular design generally requires the introduction of a bulky aryl group onto the boron atom, where it provides predominantly kinetic stabilization. The addition of extra functionality to the aryl group on the boron atom can be expected to further expand the potential utility of this class of materials. Herein, we report the synthesis of a series of boracyclic π-conjugated molecules with firm ortho B⋅⋅⋅N nonbonding interactions by introducing N-containing electron-donors at the ortho-positions of the aryl group on the boron atom. X-ray crystallographic analysis revealed that the combination of a planar boracyclic π-skeleton with only sp2 carbons and a strong electron-donating phenothiazine moiety results in a particularly short B⋅⋅⋅N distance. Theoretical study provided insights into the inherent nature of the B⋅⋅⋅N interaction. Owing to their donor-acceptor (D-A) structures, these molecules exhibit substantially red-shifted fluorescence in solution, albeit that the fluorescence quantum yields (ΦF) are low. In contrast, when incorporated into films, these compounds exhibit thermally activated delayed fluorescence (TADF) with improved ΦF values. Organic light-emitting diodes (OLEDs) fabricated using the ortho-donor-substituted derivatives exhibit orange-red electroluminescence.

Design and synthesis of sulfonamide phenothiazine derivatives as novel ferroptosis inhibitors and their therapeutic effects in spinal cord injury.

Ferroptosis is a novel style of cell death, and studies have shown that ferroptosis is strongly associated with spinal cord injury (SCI). A large number of ferroptosis inhibitors have been reported, but so far no ferroptosis inhibitor has been used clinically. Therefore there is an urgent need to discover a better inhibitor of ferroptosis. In this study, 24 novel sulfonamide phenothiazine ferroptosis inhibitors were designed and synthesized, followed by structure-activity relationship studies on these compounds. Among them, compound 23b exhibited the best activity in Erastin-induced PC12 cells (EC50 = 0.001 µM) and demonstrated a low hERG inhibition activity (IC50 > 30 µM). Additionally, compound 23b was identified as a ROS scavenger and showed promising therapeutic effects in an SD rat model of SCI. Importantly, 23b did not display significant toxicity in both in vivo and in vitro experiments and show good pharmacokinetic properties. These findings suggest that compound 23b, a novel ferroptosis inhibitor, holds potential as a therapeutic agent for spinal cord injury and warrants further investigation.

Synthesis of New D-π-A Phenothiazine-Based Fluorescent Dyes: Aggregation Induced Emission and Antibacterial Activity.

Highly solid-state fluorescent dyes based on phenothiazine bearing sulfa-drug derivatives were successfully prepared and fully characterized by NMR, mass spectra, and elemental analysis. The prepared phenothiazine dyes bearing sulfadiazine and sulfathiazole 4-(((10-hexyl-10 H-phenothiazin-3-yl)methylene)amino)-N-(pyrimidin-2yl) benzenesulfonamide (PTZ-1) and 4-(((10-hexyl-10 H-phenothiazin-3-yl) methylene) amino)-N-(thiazol-2-yl)benzenesulfonamide (PTZ-2), showed strong emission in polycrystalline form, and significant emission in solution was observed. The quantum yield of the prepared dyes varied and decreased by increasing the solvent polarity, with the maximum recorded value being 0.63 and 0.6 in dioxane. Aggregation-induced emission (AIE) and the effect of the solvent polarity on absorption and emission spectra were investigated. The dyeing application of polyester fabrics using the prepared phenothiazine-based dyes was studied, showing very good affinity to dyed fabrics. The antibacterial affinity against gram-positive and gram-negative bacteria for the dye powder as well as the dyed PET fabric was investigated, with PTZ-2 showing better affinity against bacteria compared to PTZ-1. This multifunctional property highlights the potential uses of PTZ-1 and PTZ-2 for advanced applications in biomedicine and optoelectronics.

Chlorpromazine-Polypyrrole Drug Delivery System Tailored for Neurological Application.

Nowadays, drug delivery systems (DDSs) are gaining more and more attention. Conducting polymers (CPs) are efficiently used for DDS construction as such systems can be used in therapy. In this research, a well-known CP, polypyrrole (PPy), was synthesized in the presence of the polysaccharide heparin (HEP) and chlorpromazine (CPZ) using sodium dodecyl sulfate (SDS) as electrolyte on a steel substrate. The obtained results demonstrate the successful incorporation of CPZ and HEP into the polymer matrix, with the deposited films maintaining stable electrochemical parameters across multiple doping/dedoping cycles. Surface roughness, estimated via AFM analysis, revealed a correlation with layer thickness-decreasing for thinner layers and increasing for thicker ones. Moreover, SEM images revealed a change in the morphology of PPy films when PPy is electropolymerized in the presence of CPZ and HEP, while FTIR confirmed the presence of CPZ and HEP within PPy. Due to its lower molecular mass compared to HEP, CPZ was readily integrated into the thin polymer matrix during deposition, with diffusion being unimpeded, as opposed to films with greater thickness. Finally, the resulting system exhibited the ability to release CPZ, enabling a dosing range of 10 mg to 20 mg per day, effectively covering the therapeutic concentration range.

Design, synthesis, and molecular docking of new phenothiazine incorporated N-Mannich bases as promising antimicrobial agents.

The present work aims to synthesize four series of phenothiazine incorporation Mannich bases. Therefore, 10-methyl-10H-phenothiazine-3-sulfonamide (4) which was subjected to react with some secondary amines and formaldehyde to give the Mannich bases 5a-f, and 6-13. Compound 13 was then subjected to react with some secondary amines and formaldehyde to give the corresponding Mannich bases 14a-f. In total, twenty-two new compounds were synthesized and evaluated for in vitro growth inhibition activity against P. aeruginosa, E. coli, and S. aureus. Among the tested compounds, compounds 3, 5a, 5c, 6, 12, 13, 14d, and 14e exhibited good activity with a MIC value (12.5 µg/mL), compounds 5b, 10, 11, 14a, and 14c exhibited strong activity against the growth of S. aureus with a MIC value (6.25 µg/mL), and compound 14b superior against S. aureus with a MIC value (3.125 µg/mL) compared to drug reference ciprofloxacin with MIC value (2 µg/mL). The molecular docking investigation revealed the presence of many derivatives with high binding affinities and distinct interaction patterns with the target protein. Derivatives 14a-e emerged as the most promising possibilities, displaying the greatest binding energies and a varied variety of interaction types, including hydrogen bonding and pi interactions, over different distances, with derivative 14b exhibiting the highest binding energy at S = -8.3093 kcal/mol. These derivatives displayed superior binding affinities and various interaction mechanisms with the target protein, suggesting that they have great promise as lead compounds for future development into therapeutic medicines.