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Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Mesenchymal-epithelial transition (MET) signaling pathway plays a role in the pathogenesis of selected patients with papillary renal cell carcinoma (PRCC). In the phase II PAPMET trial (ClinicalTrials.gov identifier: NCT02761057), cabozantinib significantly prolonged progression-free survival and improved objective response rate compared with sunitinib in patients with advanced PRCC. Here, we present the final overall survival (OS) analysis. In this multicenter, randomized phase II, open-label trial, 147 patients with advanced PRCC who have received up to one previous therapy (excluding vascular endothelial growth factor-directed agents) were assigned to sunitinib, cabozantinib, crizotinib, or savolitinib. Ultimately, savolitinib and crizotinib arms were closed because of futility. With a median follow-up of 17.5 months, the median OS was 21.5 months (95% CI, 12.0 to 28.1) with cabozantinib and 17.3 months (95% CI, 12.8 to 21.8) with sunitinib (hazard ratio, 0.83; 95% CI, 0.51 to 1.36; P = .46). The OS landmark estimates for cabozantinib and sunitinib were 50% versus 39% at 24 months and 32% versus 28% at 36 months. In conclusion, we observed no significant difference in OS across treatment arms. Although cabozantinib represents a well-supported option for advanced PRCC, the lack of survival benefit underscores the need to develop novel therapies for this disease.

Covalent organic frameworks (COFs) are new class of organic porous materials with tunable pore size and low weight density, demonstrating remarkable potential applications in gas storage, gas separation, and catalysis. The inherent periodic porosity of COF monolayers (MLs) establishes anchoring sites for single atoms. Using first-principles calculations, we study the structural and electronic properties of atom-embedded C 6 N 6 and B 6 O 6 MLs. Subsequently, the intercalation of atoms between C 6 N 6 and B 6 O 6 bilayers (BLs) and their heterostructure (HTS) are investigated. Our findings show the significant effects of embedded atoms on the structural parameters of the host material. Notably, the Li atom anchors within the pore region of C 6 N 6 ML without forming bonds, while it establishes two σ bonds with O atoms in B 6 O 6 ML. The Cs atom forms six bonds in both MLs and resides between layers in BLs. In the HTS, the Cs atom forms six bonds with N atoms of the C 6 N 6 layer, positioning in the middle of the layers. Calculations reveal that Li and Cs atoms induce a red shift in energy, leading to a semiconductor–metal transition. Conversely, the insertion of an F atom induces a blue shift in energy, creating a midgap state at the Fermi energy. [ABSTRACT FROM AUTHOR]

We designed a trigonal symmetric imine-linked covalent organic framework (COF), TFPC-DAB, with control over the angularity of the building units, where a bent C2-symmetric diamine, such as 1,3-diaminobenzene (1,3-DAB or DAB), with an exo-angle of 120° was used instead of those with an exo-angle of 180°, in combination with a C3-symmetric trialdehyde, such as tri(4-formylphenoxy)cyanurate (TFPC). Its synthesis was accomplished by reacting the building units in a mixture of mesitylene/dioxane/6 M acetic acid under solvothermal conditions. The phase purity, thermal stability, and porosity of TFPC-DAB were established by various analytical techniques. Utilizing the Density Functional Tight Binding (DFTB+) simulation and Pawley refinement, the best fit of the small angle x-ray pattern was found to have an AA stacking of TFPC-DAB in the trigonal space group P3 with low refinement parameters. Such smart materials are in huge demand to detect hazardous corrosive chemicals, such as HCl and NH3. The dual features of electron deficient π-acidic triazine moiety and heteroatoms (N/O) from TFPC and electron rich phenyl units from DAB embodied in the framework enhance its luminescent property and thereby make it suitable for solvent-based HCl and NH3 sensing. The detection limits for HCl and NH3 in methanol were found to be 14 and 82 ppb, respectively. The effect of solvent polarity on the sensing studies was observed with much lower detection limits in dioxane: 2.5 and 11 ppb for HCl and NH3, respectively. A detailed theoretical calculation using density functional theory and configurational bias Monte Carlo modules was conducted for understanding interactions between the COF and HCl or NH3 analytes. [ABSTRACT FROM AUTHOR]

Vital to the treatment of influenza is the use of antivirals such as Oseltamivir (Tamiflu) and Zanamivir (Relenza); however, antiviral resistance is becoming an increasing problem for these therapeutics. The RNA-dependent RNA polymerase acidic N-terminal (PAN) endonuclease, a critical component of influenza viral replication machinery, is an antiviral target that was recently validated with the approval of Baloxavir Marboxil (BXM). Despite its clinical success, BXM has demonstrated susceptibility to resistance mutations, specifically the I38T, E23K, and A36 V mutants of PAN. To better understand the effects of these mutations on BXM resistance and improve the design of more robust therapeutics, this study examines key differences in protein-inhibitor interactions with two inhibitors and the I38T, E23K, and A36 V mutants. Differences in inhibitor binding were evaluated by measuring changes in binding to PAN using two biophysical methods. The binding mode of two distinct inhibitors was determined crystallographically with both wild-type and mutant forms of PAN. Collectively, these studies give some insight into the mechanism of antiviral resistance of these mutants.

Enasidenib (ENA) is an inhibitor of isocitrate dehydrogenase 2 (IDH2) approved for the treatment of patients with IDH2-mutant relapsed/refractory acute myeloid leukemia (AML). In this phase 2/1b Beat AML substudy, we applied a risk-adapted approach to assess the efficacy of ENA monotherapy for patients aged ≥60 years with newly diagnosed IDH2-mutant AML in whom genomic profiling demonstrated that mutant IDH2 was in the dominant leukemic clone. Patients for whom ENA monotherapy did not induce a complete remission (CR) or CR with incomplete blood count recovery (CRi) enrolled in a phase 1b cohort with the addition of azacitidine. The phase 2 portion assessing the overall response to ENA alone demonstrated efficacy, with a composite complete response (cCR) rate (CR/CRi) of 46% in 60 evaluable patients. Seventeen patients subsequently transitioned to phase 1b combination therapy, with a cCR rate of 41% and 1 dose-limiting toxicity. Correlative studies highlight mechanisms of clonal elimination with differentiation therapy as well as therapeutic resistance. This study demonstrates both efficacy of ENA monotherapy in the upfront setting and feasibility and applicability of a risk-adapted approach to the upfront treatment of IDH2-mutant AML. This trial is registered at www.clinicaltrials.gov as #NCT03013998.

Oxylipins are a group of bioactive fatty acid metabolites generated via enzymatic oxygenation. They are notably involved in inflammation, pain, vascular tone, hemostasis, thrombosis, immunity, and coagulation. Oxylipins have become the focus of therapeutic intervention since they are implicated in many conditions, such as nonalcoholic fatty liver disease, cardiovascular disease, and aging. The liver plays a crucial role in lipid metabolism and distribution throughout the organism. Long-term exposure to pesticides is suspected to contribute to hepatic carcinogenesis via notable disruption of lipid metabolism. Prometryn is a methylthio-s-triazine herbicide used to control the growth of annual broadleaf and grass weeds in many cultivated plants. The amounts of prometryn documented in the environment, mainly waters, soil and plants used for human and domestic consumption are significantly high. Previous research revealed that prometryn decreased liver development during zebrafish embryogenesis. To understand the mechanisms by which prometryn could induce hepatotoxicity, the effect of prometryn (185 mg/kg every 48 h for seven days) was investigated on hepatic and plasma oxylipin levels in mice. Using an unbiased LC-MS/MS-based lipidomics approach, prometryn was found to alter oxylipins metabolites that are mainly derived from cytochrome P450 (CYP) and lipoxygenase (LOX) in both mice liver and plasma. Lipidomic analysis revealed that the hepatotoxic effects of prometryn are associated with increased epoxide hydrolase (EH) products, increased sEH and mEH enzymatic activities, and induction of oxidative stress. Furthermore, 9-HODE and 13-HODE levels were significantly increased in prometryn treated mice liver, suggesting increased levels of oxidation products. Together, these results support that sEH may be an important component of pesticide-induced liver toxicity.

Graphene oxide (GO) was used as sorbent in dispersive solid phase extraction (DSPE) to enrich and extract some triazine herbicides from environmental water samples. It can form dispersed colloids in aqueous phase and provides rich functional groups for the formation of hydrogen bonding or π–π electrostatic interaction with benzene ring organic compounds containing oxygen and nitrogen functional groups. GO was synthesised by modified Hummers method and characterised with Fourier transform infrared (FT-IR) spectroscopy. As complete collection of GO after adsorption process is difficult task, in this established salt-assisted (SA)-GO-DSPE method, it was found to be aggregated and centrifuged in the presence of NaCl. The optimum value for main parameters that influenced extraction efficiency were investigated. Under the optimised conditions, low limits of detection (LODs) (0.12–0.80 ng mL −1), limits of quantification (LOQ) (0.4–2.68 ng mL −1), and good extraction recoveries (69.06–95.53%) were obtained for simultaneous extraction of simazine (SIZ), atrazine (ATZ), propazine (PRZ)) and prometryn (PRN). The relative standard deviations (RSD) of intraday (n = 6) and interday (n = 9) precisions were 2.54 to 5.84% and 4.38 to 8.56%, respectively. At the end, the applicability of the method was evaluated and target analytes were not detected in real samples. The proposed method is environment friendly and promising for trace analysis of pesticides including the target herbicides in environmental water samples. [ABSTRACT FROM AUTHOR]

Persistent, mobile, and toxic compounds released to the environment are likely to pollute drinking water sources due to their slow environmental degradation (persistency) and high water solubility (mobility). The aim of the present study was to create in vitro hazard profiles for 16 triazoles, 9 triazines, and 11 poly- and perfluoroalkyl substances (PFAS) based on their agonistic and antagonistic effects in estrogen receptor (ER), androgen receptor (AR), and thyroid hormone receptor (TR) reporter gene assays, their ability to bind human transthyretin (TTR), and their effects on steroidogenesis. The triazole fungicides tetraconazole, bitertanol, fenbuconazole, tebuconazole, cyproconazole, difenoconazole, propiconazole, paclobutrazol, and triadimenol had agonistic or antagonistic effects on the ER and AR. Difenoconazole, propiconazole, and triadimenol were also found to be TR antagonists. The triazine herbicide ametryn was an ER, AR, and TR antagonist. The same 9 triazole fungicides and the triazines atrazine, deethyl-atrazine, and ametryn affected the secretion of steroid hormones. Furthermore, PFAS compounds PFBS, PFHxS, PFHxA, PFOS, PFOA, and GenX and the triazoles bitertanol, difenoconazole, and 4-methyl benzotriazole were found to displace T4 from TTR. These results are in line with earlier in vitro and in vivo studies on the endocrine-disrupting properties of triazines, triazoles, and PFAS. The present study demonstrates that this battery of in vitro bioassays can be used to profile compounds from different classes based on their endocrine-disrupting properties as a first step to prioritize them for further research, emission reduction, environmental remediation, and regulatory purposes. [ABSTRACT FROM AUTHOR]

The reaction between 2‐hydroxy‐1‐naphthaldehyde and 3‐hydrazino‐5,6‐diphenyl‐1,2,4‐triazine produced a novel hydrazone ligand (DTHMN), which reacted with Cu(II) and Zn(II) metal ion in molar ratio 1:1, giving octahedral Cu(II)‐DTHMN and tetrahedral Zn(II)‐DTHMN nanosized complexes. The structural geometries have been elucidated on the basis of elemental analysis, nuclear magnetic resonance, infrared, electronic, and electron spin resonance spectra, and magnetic and molar conductance measurements as well as x‐ray diffraction and thermal analysis. TEM analysis showed that Zn(II)‐DTHMN complex has nano‐rode morphology shape. On the other hand, Cu(II)‐DTHMN has sphere shape within nanodomain. The DTHMN ligand exhibits ONN chelating sites through N‐triazine ring, azomethine nitrogen, and deprotonated OH group, forming the mononuclear metal complexes. The synthesized compounds showed a distinct solvatochromic behavior in different polar solvents. A bathochromic alteration is observed when moving from less to high polar solvents, indicating strong solute–solvent interactions accompanied by intramolecular charge transfer (ICT). The ground and excited state dipole moments of these compounds were determined experimentally by solvatochromic shift method using Bilot–Kawski, Lippert–Mataga, Bakhshiev, and Kawski–Chamma–Viallet functions and a microscopic Reichardt's solvent polarity parameter (ETN). The dipole moment is increased significantly upon excitation referring to stabilizing the excited species includes n–π* transition by polarity of solvent. The experimental results are generally consistent with those values obtained by B3LYP/GENECP method at 6‐311G(d,p) basis set for C, H, N, and O atoms and SDD (Stuttgart/Dresden) basis set for the metal atoms. The compounds were tested for antimicrobial efficiency against Gram‐positive bacteria, Gram‐negative bacteria, and fungus strain. Finally, molecular docking was used to study the interactions between donors (the current compounds) and receptors FabH–CoA complex (PDB code: 1HNJ). [ABSTRACT FROM AUTHOR]

A facile synthetic routes to access some new heterocyclic systems containing potent pharmacophoric groups such as pyrazole, pyrazolo[5,1-c]-1,2,4-triazine, 1,2,4-triazino[4,3-a]benzimidazole, and pyridine moieties linked to pyridine-carboxamide moiety are reported. Construction of the target compounds was achieved via reaction of 3-oxo-butanamides 1a,b with hydrazonoyl halides, heterocyclic diazonium salts, and malononitrile derivatives, respectively. The structures of the new products were confirmed by all possible spectral and elemental analyses. The antibacterial assessment showed that one product was moderately active against both K. pneumonia and S. aureus. [ABSTRACT FROM AUTHOR]

A novel analogue of hybrid spirooxindoles was synthesized employing a systematic multistep synthetic approach. The synthetic protocol was designed to obtain a series of spirooxindole derivatives incorporating triazolyl- s -triazine framework via [3 + 2] cycloaddition (32CA) reaction of azomethine ylide (AY) with the corresponding chalcones (6a-d). Unexpectedly, the reaction underwent an alternate route, leading to the cleavage of the s-triazine moiety and yielding a series of spirooxindole derivatives incorporating a triazole motif. A comprehensive investigation of the 32CA reaction mechanism was conducted using Molecular Electron Density Theory (MEDT). The viability of all compounds was evaluated through an MTT assay, and the IC50 values were determined using Prism Software. The antiproliferative efficacy of the synthesized chalcones and the corresponding spirooxindole derivatives was assessed against two cancer cell lines: MDA-MB-231 (triple-negative breast cancer) and HepG2 (human hepatoma). These findings were compared with Sorafenib, which was used as a positive control. The results revealed that chalcones (6c and 6d) were the most active among the tested chalcones, with IC50 values of 7.2 ± 0.56 and 7.5 ± 0.281 µM for (6c) and of 11.1 ± 0.37 and 11.0 ± 0.282 µM for (6d) , against MDA-MB-231 and HepG2, respectively. Spirooxindoles (9b, 9c, 9h, and 9i) exhibited the highest activity with IC50 values ranging from 16.8 ± 0.37 µM to 31.3 ± 0.86 µM against MDA-MB-231 and 13.5 ± 0.92 µM to 24.2 ± 0.21 µM against HepG2. In particular, spirooxindole derivatives incorporating 2,4-dichlorophenyl moiety were the most active, with an IC50 of 16.8 ± 0.37 µM for (9h) against MDA-MB-23 and 13.5 ± 0.92 µM for (9i) against HepG2. Interestingly, the IC50 of compound (6c) (7.2 µM) exhibited better activity than that of Sorafenib (positive control) (9.98 µM) against MDA-MB-231. Molecular docking, ADMET, and molecular dynamic simulations were conducted for the promising candidates (6b, 6c, and 9h) to explore their binding affinity in the EGFR active site. [ABSTRACT FROM AUTHOR]

ABSTRACT The study focuses on the synthesis and characterization of a new mesoporous polysulfonamide stabilizer using condensation polymerization and the nanocasting technique. The resulting material, PGTSA, was modified with copper ions and used as a nanocatalyst in the reaction of benzaldehydes, 1H‐tetrazole‐5‐amine, and malononitrile. The performance of the mesoporous PGTSA/Cu (II) was compared with non‐porous PGTSA/Cu (II), highlighting the significance of support porosity in catalytic activity and loading of copper species. Based on the analysis of the ICP and catalytic performance, it was observed that mesoporous PGTSA/Cu (II) exhibited a higher level of catalytic activity compared to PGTSA/Fe3O4/Cu (II) and non‐porous PGTSA/Cu (II). Also, the catalytic activity of the aryl aldehyde was significantly influenced by its electrical characteristics. The recovery and reusability of the PGTSA/Cu (II) catalyst are noteworthy aspects, highlighting the practicality and sustainability of the catalytic system. The amount of copper in fresh catalyst and the recycled catalyst after six times recycling is 1.57% and 1.52%, respectively. Therefore, ICP‐OEIS analysis indicated that copper leaching of this catalyst is very low. The procedure offered high product yields, easy recovery of the nanocatalyst, remarkable reusability, short reaction times, and compatibility with various substrates. [ABSTRACT FROM AUTHOR]

ABSTRACT A series of new 4a,7a‐diarylperhydroimidazo[4,5‐e][1,2,4]triazine‐3‐thiones were synthesized from 4,5‐diaryl‐4,5‐dihydroxyimidazolidin‐2‐ones and thiosemicarbazide in high yields, and their interaction with ethyl phenylpropiolate was studied. An effective method for the regioselective synthesis of imidazo[4,5‐e][1,3]thiazino[3,2‐b][1,2,4]triazines as new heterocycic system derivatives was proposed based on the reaction of aforementioned imidazotriazinethiones with ethyl phenylpropiolate in the presence of MeONa in methanol. The reaction is initiated by a Michael‐type addition of the imidazotriazinethiones to the triple bond of ethyl phenylpropiolate followed by intramolecular cyclization. [ABSTRACT FROM AUTHOR]

A microwave‐assisted synthesis of 7‐amino‐1,2,4‐triazolo[1,5‐a][1,3,5]triazine‐2‐propanamides was developed using a three‐component, catalyst‐free reaction of cyanamide and trimethyl orthoformate with 3‐(5‐amino‐1H‐1,2,4‐triazol‐3‐yl)propanamides (3). The reaction tolerated structurally diverse substrates and proceeded chemo‐ and regio‐selectively, affording the target compounds in high purity in 5–10 minutes. The convenient chromatography‐free isolation and purification of the products add practicality to this method. The structural features of the prepared compounds were investigated using dynamic NMR spectroscopy, X‐ray crystallography and computational chemistry calculations. X‐ray crystallography performed on a representative compound, 3‐(7‐amino‐1,2,4‐triazolo[1,5‐a][1,3,5]triazin‐2‐yl)‐N‐(4‐benzyl)propanamide (4 l), showed the overall molecular conformation to adopt the shape of the letter C. Notable localisation of π‐electron density is found within the 1,2,4‐triazolo[1,5‐a][1,3,5]triazine system; a relatively short C−NH2 bond is consistent with restricted rotation about this bond. This study also presents a detailed analysis of the molecular interactions in 4 l using DFT and QTAIM methods with a focus on the hydrogen‐bonding and π‐stacking interactions that influence the molecular packing of 4 l. The findings reveal the significant roles of N−H⋅O, N−H⋅N and C−H⋅N interactions, along with electrostatically enhanced π⋅π contacts. A broad screening for insecticidal, fungicidal and herbicidal properties identified several compounds with potent herbicidal activity against Matricaria inodora. [ABSTRACT FROM AUTHOR]

Covalent organic frameworks (COFs) have attracted growing interests as new material platform for a range of applications. In this study, a triazine‐carbazole‐based covalent organic framework (COF‐TCZ) was designed as highly porous material with conjugated donor‐acceptor networks, and feasibly synthesized by the Schiff condensation of 4,4′,4′′‐(1,3,5‐triazine‐2,4,6‐triyl)tr ianiline (TAPB) and 9‐(4‐formylphenyl)‐9H‐carbazole‐3,6‐dicarbaldehyde (CZTA) under the solvothermal condition. Considering the effect of linkage, the imine‐linked COF‐TCZ was further oxidized to obtain an amide‐linked covalent organic framework (COF‐TCZ‐O). The as‐synthesized COFs show high crystallinity, good thermal and chemical stability, and excellent photoactive properties. Two π‐conjugated triazine‐carbazole‐based COFs with tunable linkages are beneficial for light‐harvesting capacity and charge separation efficiency, which are empolyed as photocatalysts for the oxidation reaction of N‐aryltetrahydroisoquinoline. The COFs catalyst systems exhibit the outstanding photocatalytic performance with high conversion, photostability and recyclability. Photoelectrochemical tests were employed to examine the behavior of photogenerated charge carriers in photo‐illumination system. The control experiments provide further insights into the nature of photocatalysis. In addition, the current research also provided a valuable approach for developing photofunctional COFs to meet challenge in achieving the great potential of COFs materials in organic conversion. [ABSTRACT FROM AUTHOR]

The development of adsorbent materials for highly efficient iodine capture is in high demand from the perspective of ecological environment and human health. Herein, two covalent organic frameworks (COFs), JLNU-312 and JLNU-313, were successfully synthesized for iodine adsorption. The obtained JLNU-COFs possess high crystallinity and one-dimensional mesoporous channels. Iodine adsorption experiments demonstrated that both COF materials exhibit effective performance for iodine adsorption, with a maximum amount of up to 4.67 g g−1 for JLNU-312 and 2.47 g g−1 for JLNU-313. Moreover, both JLNU-COFs have good stability, reusability and iodine retention capacity. Theoretical calculations clearly show that the higher adsorption performance of JLNU-312 is also due to the strong interaction between the adsorbed iodine and the abundant triazine nitrogen-rich adsorption sites uniformly distributed in the pore. This work shows that effective iodine adsorbents can be achieved by introducing nitrogen-rich sites into the framework of COF materials. [ABSTRACT FROM AUTHOR]

Glioblastoma, the most aggressive form of brain tumor, poses significant challenges in terms of treatment success and patient survival. Current treatment modalities for glioblastoma include radiation therapy, surgical intervention, and chemotherapy. Unfortunately, the median survival rate remains dishearteningly low at 12-15 months. One of the major obstacles in treating glioblastoma is the recurrence of tumors, making chemotherapy the primary approach for secondary glioma patients. However, the efficacy of drugs is hampered by the presence of the blood-brain barrier and multidrug resistance mechanisms. Consequently, considerable research efforts have been directed toward understanding the underlying signaling pathways involved in glioma and developing targeted drugs. To tackle glioma, numerous studies have examined kinase-downstream signaling pathways such as RAS-RAF-MEKERK-MPAK. By targeting specific signaling pathways, heterocyclic compounds have demonstrated efficacy in glioma therapeutics. Additionally, key kinases including phosphatidylinositol 3-kinase (PI3K), serine/threonine kinase, cytoplasmic tyrosine kinase (CTK), receptor tyrosine kinase (RTK) and lipid kinase (LK) have been considered for investigation. These pathways play crucial roles in drug effectiveness in glioma treatment. Heterocyclic compounds, encompassing pyrimidine, thiazole, quinazoline, imidazole, indole, acridone, triazine, and other derivatives, have shown promising results in targeting these pathways. As part of this review, we propose exploring novel structures with low toxicity and high potency for glioma treatment. The development of these compounds should strive to overcome multidrug resistance mechanisms and efficiently penetrate the blood-brain barrier. By optimizing the chemical properties and designing compounds with enhanced drug-like characteristics, we can maximize their therapeutic value and minimize adverse effects. Considering the complex nature of glioblastoma, these novel structures should be rigorously tested and evaluated for their efficacy and safety profiles. [ABSTRACT FROM AUTHOR]

Iron(III)- and iodide-promoted efficient synthesis of pyrimidines from biomass-based alkyl lactates, inorganic ammonium, and aldehydes was carried out. This multicomponent reaction efficiently proceeded through a series of condensation, dehydrogenation coupling, and condensation steps to form C–N and C–C bonds, respectively. This protocol strikingly features sustainable catalysis using Earth-abundant metals and NH4I as a substrate and catalyst. When using biomass-based alkyl lactate as a raw material, the alkyl lactate can be reused, and clean byproducts can be obtained. More than 30 pyrimidines and 7 triazines were synthesized in isolated yields of up to 92%. In addition, the analysis of several dimensions of green indicators proves the greenness of this work. Promising applications of biobased alcohols and inorganic salts in sustainable organic synthesis are represented by this work. [ABSTRACT FROM AUTHOR]

We present a novel approach for the room temperature synthesis and integration of Ru nanoparticles into a Z-scheme heterojunction comprising graphitic carbon nitride (CN) and zeolitic imidazolate framework-8 (ZIF-8). This heterojunction demonstrates outstanding efficiency in sunlight-driven hydrogen (H 2) generation via water splitting. Various structural and spectroscopic analyses elucidate Ru nanoparticles' successful incorporation and synergistic effects within the CN/ZIF-8 heterojunction because the decrease in interplanar spacing due to π-π stacking interactions between aromatic rings of tri- s -triazine in CN and imidazole rings in ZIF-8. The Z-scheme configuration facilitates efficient charge separation and promotes H 2 production. Additionally, Ru nanoparticles offer alternative electron transfer pathways, enhancing carrier separation and prolonging the lifespan of photoinduced charges compared to CN and ZIF-8 alone. Notably, RZCN-2 heterojunction exhibited significantly enhanced hydrogen production, reaching 5245 μmol g−1 h−1. By analyzing work functions and energy band structures, we demonstrate that the strong interfacial electric fields across the Z-scheme heterojunction effectively mitigate the recombination of photogenerated charges while maintaining the necessary redox capacity for efficient H 2 production. The room temperature synthesis and integration of Ru nanoparticles provide a practical and effective strategy for optimizing photocatalytic activity and promoting sustainable energy conversion, thereby advancing photocatalytic technologies. • Room temperature preparation and incorporation of Ru NP into CN, and ZIF-8 to construct Z-scheme heterojunction. • Loading Ru NP enhanced NIR light absorbance for better HER. • Narrow VB energy of CN, and ZIF-8 synergistically built electric field among RZCN-2 heterojunction. • RZCN-2 photocatalyst exhibits large surface area and long decay time for photoexcited charged carriers. • The optimal RZCN-2 demonstrated outstanding H 2 generation up to 5245 μmolg−1h−1. [ABSTRACT FROM AUTHOR]

Flexible poly-Lewis acids (PLA) based on the tribenzotriquinacene (TBTQ) scaffold have been synthesised. Hydrosilylation of 4b,8b,12b-triallyltribenzotriquinacene and subsequent exchange of the chlorine substituents with weaker coordinating triflate groups afforded a novel triple silyl-functionalised PLA. By regioselective hydroboration of triallyl–TBTQ with various organoboranes, PLAs with different Lewis acidities were obtained. The synthesised PLAs were combined with neutral bases in host–guest experiments. DOSY NMR spectroscopy was performed to elucidate the complexation process in solution. These experiments revealed a highly dynamic interaction between the boron-functionalised PLA and triazine. However, the addition of one equivalent of tris(dimethylphosphino(methyl))phenylsilane led to the formation of a 1 : 1 adduct, which was confirmed by diffusion experiments. [ABSTRACT FROM AUTHOR]

The photocatalytic reduction of CO2 represents an environmentally friendly and sustainable approach for generating valuable chemicals. In this study, a thiophene‐modified highly conjugated asymmetric covalent triazine framework (As‐CTF‐S) is developed for this purpose. Significantly, single‐component intramolecular energy transfer can enhance the photogenerated charge separation, leading to the efficient conversion of CO2 to CO during photocatalysis. As a result, without the need for additional photosensitizers or organic sacrificial agents, As‐CTF‐S demonstrates the highest photocatalytic ability of 353.2 µmol g−1 and achieves a selectivity of ≈99.95% within a 4 h period under visible light irradiation. This study provides molecular insights into the rational control of charge transfer pathways for high‐efficiency CO2 photoreduction using single‐component organic semiconductor catalysts. [ABSTRACT FROM AUTHOR]

In this contribution, a new Schiff‐base hybrid cross‐linked polymer (TFPT‐SHCP) derived from triazine derivatives and silsesquioxanes was developed, and its photocatalytic performance was systematically investigated. Compared with traditional organic Schiff base catalysts, in TFPT‐SHCP, organic inorganic hybrid silsesquioxanes monomers at the molecular level can serve as a sturdy host backbone, bringing structural ultrastability to the final material. And their excellent strength and durability make them have good application prospects in water treatment. Furthermore, the introduction of triazine derivatives with excellent photoelectric performance and the construction of −C=N‐ result in excellent photocatalytic performance of TFPT‐SHCP. The as‐prepared TFPT‐SHCP exhibits excellent degradation capacity of various organic pollutants under visible light catalysis, with degradation rate constants for Congo Red (CR), rhodamine B (RB) and tetracycline hydrochloride (TH) reaching 0.302 min−1, 0.121 min−1, 0.161 min−1, respectively. Under simulated outdoor conditions, dye solutions with concentrations up to 500 ppm can be degraded to complete decolorization within 5 weeks. This work demonstrates the enormous potential of POSS‐based Schiff base materials as a platform for visible light catalysts, paving the way for the pre design and functionalization of related materials in the future. [ABSTRACT FROM AUTHOR]

Porous organic polymers have an outstanding performance in the field of photocatalysis with the advantage of diverse structure composition and purposeful molecular design. However, the inherent high impedance and poor electrical conductivity of organic semiconductors still restrict the charge transfer efficiency and thus discount the photocatalytic performance. Herein, the study reports a highly conductive covalent triazine framework (CTF) loading carbon quantum dots (CQDs) into porous as electron transport medium. The addition of CQDs (0.5 wt%) can enhance the electronic conductivity of CTF by tenfold. In addition, the as‐prepared CQD‐CTFs express much‐promoted charge separation and transfer efficiency. Furthermore, the embedded CQDs can improve the oxidization capacity and increase the affinity of H+ due to the more negative zeta potential. The enhanced oxidizing ability and increased H+ affinity are positive for water oxidation reaction (WOR) and oxygen reduction reaction (ORR) process in hydrogen peroxide (H2O2) generation, respectively. The optimized CQD‐CTF exhibits a high H2O2 generation rate of up to 1036 µmol g−1 h−1 in pure water without any sacrificial agent under visible light, which is 4.6 times than pristine CTF. This work provides a new idea for efficient H2O2 production of organic semiconductors. [ABSTRACT FROM AUTHOR]

In recent years, the global perspective of small molecule activation has directed the focus towards biomimetic oxidations. Phenoxazinone synthase and catechol oxidase, two vital metalloenzymes, have drawn the attention of the scientific community towards their catalytic performances. Different transition metal-based complexes have been investigated to mimic their activities, yet many factors related to their mechanistic aspects and structure–activity relationship still lack detailed investigation. To get better insights into these factors, two penta-coordinated cis-dichloro and dibromo Cu(II) complexes [Cu(L)Cl2] 1 and [Cu(L)Br2] 2 (where L = N,N-dimethyl-4,6-di(pyridin-2-yl)-1,3,5-triazin-2-amine) were synthesized and comprehensively characterized through various spectroscopic and analytical tools such as UV-vis, FT-IR, NMR, EPR and ESI-MS. The redox behaviour of ligands as well as both the copper complexes were analysed. The molecular structure of 1 and 2 was elucidated via single-crystal X-ray diffraction analysis and a distorted square pyramidal geometry was determined. The halogen atoms (Cl for 1 and Br for 2) are found to be coordinated in a cis fashion for better substrate attachment. Catalytic performances towards the oxidation of o-aminophenol (OAPH) and 3,5-di-tert-butylcatechol (3,5-DTBC) were investigated using UV-vis spectrophotometry. Significant kinetic parameters towards the catalytic activities for 1 and 2 were determined. In terms of OAPH oxidation ability, both complexes were found to be quite comparable, with 2 having greater catalytic performance (Kcat = 156.7 h−1) than 1 (Kcat = 124.5 h−1). However, 2 shows remarkably superior activity for 3,5-DTBC oxidation (Kcat = 367.8 h−1, ∼4.5 times) than 1 (Kcat = 82.2 h−1). The mass spectrometric investigation provides information about the probable mechanistic path towards the oxidation of both the substrates. Iodometric titration experiments were performed to identify H2O2 formation, which proves the involvement of molecular O2 during the catalytic oxidation. Overall, this study offers a detailed investigation on the significance of structural lability and their profound catalytic activities for biomimetic applications, which may open a new direction toward future advancements. [ABSTRACT FROM AUTHOR]

Photocatalytic hydrogen evolution reaction (HER) is a very promising and sustainable technology, yet precisely exploring effective HER photocatalysts remains a critical challenge due to the rapid charge recombination. In this work, a brand‐new S‐scheme heterojunction is successfully designed and constructed by in situ growth of twinned Zn0.5Cd0.5S Solid Solution (CZS) on a novel fluorenone‐based covalent triazine framework (FOCTF). The S‐scheme heterojunctions is identified via in situ irradiation XPS, and electron spin resonance, which can greatly improve the photocatalytic HER rate and stability. Under illumination, the highest photocatalytic HER rate of well‐designed CZS‐FOCTF is 247.62 mmolg−1h−1, 3.83 times as high as that of pure CZS. Experimental and theoretical investigations corroborate that the new FOCTF has a well‐matched staggered band alignment and work function difference with CZS. The as‐fabricated CZS‐FOCTF S‐scheme heterojunction can establish a favorable internal electric field, which accelerates the directional S‐scheme charge migration, thereby enhancing the separation and utilization efficiency of carriers. This finding precisely achieves the spatially oriented powerful electron transport and separation at the interfaces of inorganic–organic hybrid heterojunctions. It is thus desirable that this work can furnish an alternative strategy to rationally design new CZS‐based S‐scheme heterojunction photocatalysts based on novel organic oxidation semiconductors for diversified photocatalytic reactions. [ABSTRACT FROM AUTHOR]

A general and convenient selective direct arylation of the 3‐position of triimidazo[1,2‐a:1',2'‐c:1",2"‐e][1,3,5]triazine (1) with (hetero)aryl halides in DMA was successfully achieved in the presence of K2CO3 as the base and a catalyst precursor consisting of Pd(OAc)2 and P(2‐furyl)3. Electron‐poor and ‐rich (hetero)aryl moieties, including the strongly deactivated and sterically encumbered 2,4,6‐trimethoxyphenyl unit, are well tolerated in the electrophilic partner. The data obtained in this synthetic study support a reaction mechanism involving an electrophilic attack of an arylpalladium‐(II) halide species onto the triazine ring. [ABSTRACT FROM AUTHOR]

Nucleoside analogs GS-441524 and remdesivir (GS-5734) are effective in treating cats with feline infectious peritonitis (FIP). However, no studies have compared the efficacy between antiviral medications. The objective of this study was to evaluate the efficacy of orally administered GS-442514 (12.5-15 mg/kg) compared to orally administered remdesivir (25-30 mg/kg) in a double-blinded non-inferiority trial. Eighteen cats with effusive FIP were prospectively enrolled and randomly assigned to receive either GS-442514 or remdesivir. Cats were treated daily for 12 weeks and evaluated at week 0, 12, and 16. Survival and disease remission at week 16 were compared between groups. Five of 9 (55%) cats treated GS-441524 and 7/9 (77%) cats treated with remdesivir survived, with no difference in survival rate (p = 0.2). Remdesivir fulfilled the criteria for non-inferiority with a difference in survival of 22% (90% CI; -13.5-57.5%). Three of the 18 cats died within 48 h of enrollment. Excluding these cats, 5/6 (83%) of the cats treated with GS-441524 and 7/9 (77%) of the cats treated with remdesivir survived. These findings suggest that both orally administered GS-441524 and remdesivir are safe and effective anti-viral medications for the treatment of effusive FIP. Further optimization of the first 48 h of treatment is needed.

To study the contribution of three-body dispersion to crystal lattice energies, we compute the three-body contributions to the lattice energies for crystalline benzene, carbon dioxide, and triazine using various computational methods. We show that these contributions converge quickly as the intermolecular distances between the monomers grow. In particular, the smallest value among the three pairwise intermonomer closest-contact distances, Rmin, shows a strong correlation with the three-body contribution to the lattice energy, and, here, the largest of the closest-contact distances, Rmax, serves as a cutoff criterion to limit the number of trimers to be considered. We considered all trimers up to R max = 15 A ̊ . The trimers with R min < 4 A ̊ contribute 90.4%, 90.6%, and 93.9% of the total three-body contributions for crystalline benzene, carbon dioxide, and triazine, respectively, for the coupled-cluster singles, doubles, and perturbative triples [CCSD(T)] method. For trimers with R min > 4 A ̊ , the second-order Møller–Plesset perturbation theory (MP2) supplemented with the Axilrod–Teller–Muto (ATM) three-body dispersion correction reproduces the CCSD(T) values for the cumulative three-body contributions with errors of less than 0.1 kJ mol−1. Moreover, three-body contributions are converged within 0.15 kJ mol−1 by R max = 10 A ̊ . From these results, it appears that in molecular crystals where dispersion dominates the three-body contribution to the lattice energy, the trimers with R min > 4 A ̊ can be computed with the MP2+ATM method to reduce the computational cost, and those with R max > 10 A ̊ appear to be basically negligible. [ABSTRACT FROM AUTHOR]

Hexahydro-1,3,5-trinitro-1,3,5-triazine, or Royal Demolition Explosive (RDX), is a major component of plastic explosives such as C-4. Acute exposures from intentional or accidental ingestion are a documented clinical concern, especially among young male U.S. service members in the armed forces. When ingested in large enough quantity, RDX causes tonic-clonic seizures. Previous in silico and in vitro experiments predict that RDX causes seizures by inhibiting α1β2γ2 γ-aminobutyric acid type A (GABAA) receptor-mediated chloride currents. To determine whether this mechanism translates in vivo, we established a larval zebrafish model of RDX-induced seizures. After a 3 h of exposure to 300 µM RDX, larval zebrafish exhibited a significant increase in motility in comparison to vehicle controls. Researchers blinded to experimental group manually scored a 20-min segment of video starting at 3.5 h post-exposure and found significant seizure behavior that correlated with automated seizure scores. Midazolam (MDZ), an nonselective GABAAR positive allosteric modulator (PAM), and a combination of Zolpidem (α1 selective PAM) and compound 2-261 (β2/3-selective PAM) were effective in mitigating RDX-triggered behavioral and electrographic seizures. These findings confirm that RDX induces seizure activity via inhibition of the α1β2γ2 GABAAR and support the use of GABAAR-targeted anti-seizure drugs for the treatment of RDX-induced seizures.

Influenza is one of the leading causes of disease-related mortalities worldwide. Several strategies have been implemented during the past decades to hinder the replication cycle of influenza viruses, all of which have resulted in the emergence of resistant virus strains. The most recent example is baloxavir marboxil, where a single mutation in the active site of the target endonuclease domain of the RNA-dependent-RNA polymerase renders the recent FDA approved compound ∼1000-fold less effective. Raltegravir is a first-in-class HIV inhibitor that shows modest activity to the endonuclease. Here, we have used structure-guided approaches to create rationally designed derivative molecules that efficiently engage the endonuclease active site. The design strategy was driven by our previously published structures of endonuclease-substrate complexes, which allowed us to target functionally conserved residues and reduce the likelihood of resistance mutations. We succeeded in developing low nanomolar equipotent inhibitors of both wild-type and baloxavir-resistant endonuclease. We also developed macrocyclic versions of these inhibitors that engage the active site in the same manner as their 'open' counterparts but with reduced affinity. Structural analyses provide clear avenues for how to increase the affinity of these cyclic compounds.

BACKGROUND: This Phase 1b study (B2151002) evaluated the PI3K/mTOR inhibitor gedatolisib (PF-05212384) in combination with other anti-tumour agents in advanced solid tumours. METHODS: Patients with various malignancies were administered gedatolisib (90‒310 mg intravenously every week [QW]) plus docetaxel (arm A) or cisplatin (arm B) (each 75 mg/m2 intravenously Q3W) or dacomitinib (30 or 45 mg/day orally). The safety and tolerability of combination therapies were assessed during dose escalation; objective response (OR) and safety were assessed during dose expansion. RESULTS: Of 110 patients enrolled, 107 received gedatolisib combination treatment. Seven of 70 (10.0%) evaluable patients had dose-limiting toxicities; the most common was grade 3 oral mucositis (n = 3). Based upon reprioritisation of the sponsors portfolio, dose expansion focused on arm B, gedatolisib (180 mg QW) plus cisplatin in patients (N = 22) with triple-negative breast cancer (TNBC). OR (95% CI) was achieved in four of ten patients in first-line (overall response rate 40.0% [12.2-73.8%]) and four of 12 in second/third-line (33.3% [9.9-65.1%]) settings. One patient in each TNBC arm (10%, first-line; 8.3%, second/third-line) achieved a complete response. CONCLUSIONS: Gedatolisib combination therapy showed an acceptable tolerability profile, with clinical activity at the recommended Phase 2 dose in patients with TNBC. CLINICAL TRIAL: ClinicalTrial.gov: NCT01920061.

In this study, a previously unreported 3-((4-(isopropylamino)-6-(methylthio)-1,3,5-triazin-2-yl) amino) butyric acid hapten was designed and synthesized. This maximized the exposure of the antigen-determinant isopropyl of prometryn to the immune system in animals to induce the production of anticipated highly specific anti-prometryn antibodies. The hapten has a molecular weight of 285.37 Da. The compound was confirmed by nuclear magnetic resonance hydrogen spectroscopy (1H NMR), nuclear magnetic resonance carbon spectroscopy (13C NMR), and high-resolution mass spectrometry (HRMS). By using the active ester approach, immunogens and coated antigens were created. Bovine serum albumin (BSA) was used as an immunogen, along with the successfully produced hapten, to immunize mice. The IC50 value of mouse monoclonal anti-prometryn antibody (mAb) 7D4 (the quantity of analyte that generated 50% prometryn inhibition) was 3.9 ng/mL. The anti-prometryn mAb was of the IgG1 subclass. The IC20 (80% binding level (B/B0) of prometryn)-IC80 (20% binding level (B/B0) of prometryn) range of the anti-prometryn monoclonal antibody standard curve working range was 0.9-18.1 ng/mL. The prepared mAb has good characteristics because it can specifically recognize prometryn, and the cross-reaction rates for ametryn, desmetryn, and terbumeton were 34.77%, 18.09%, and 7.64%, respectively. The cross-reaction rate with the other seven triazines was less than 1%. The hapten structure proposed can serve as an additional tool for modulating selectivity in detecting triazines.

Crystal engineering is emerging as an important approach to design functional materials. In this work, we explore the scope of a sulfonate–pyridinium supramolecular synthon to design the organic salt [(TPT-H)2+(NDSA-H)2−·4H2O] (1), based on 1,5-naphthalenedisulfonic acid (NDSA-2H) and 2,4,6-tris(2-pyridyl)-s-triazine (TPT). Structural studies of 1 establish proton transfer between crystal formers and their aggregation through the water-masked sulfonate–pyridinium synthon to form one-dimensional hydrogen bonded tapes, which further aggregate through weak π–π and C–H⋯O interactions to form a three-dimensional layered solid. The greenish solid 1 exhibits mild charge transfer interactions in the solid-state, as indicated by the red-shift of the absorption beyond 400 cm−1 in the diffuse reflectance spectrum. Interestingly, 1 exhibit mild brownish emission (λmax = 550 nm), which undergoes remarkable blue-shifting on exposure to ammonia fumes (λmax = 450 nm), heat (λmax = 494.8 nm), and grinding (λmax = 542.9 nm). This multi-stimuli responsive behavior of 1 has been investigated in detail, with the help of diffuse reflectance, fluorescence, thermal, spectroscopic, and diffraction studies, and a plausible commentary of the behavior in light of its structure is provided. The intriguing multi-stimuli response behavior of 1 indicates the potential scope of sulfonate–pyridinium based organic salts in applications as sensors and intelligent materials. [ABSTRACT FROM AUTHOR]

The present personalized account summarizes various cyclization reactions, including multicomponent and domino processes, which are directed towards the synthesis of complex heterocyclic products. Domino Knoevenagel/hetero‐Diels‐Alder reactions provide a synthesis of annulated quinol‐2‐ones. The combination of Knoevenagel reactions with [3+2] cycloadditions of nitrogen ylides afford complex spiroheteriocyclic products. Domino Knoevenagel/enamine cyclization reactions result in the formation of condensed purine analogues. Formal [3+3] cyclizations of pyridinium salts allow for a rapid assembly of bridged heterocyclic systems and include the employment of thioxindoles and cyclohexane‐1,3‐diones as dinucleophilic building blocks. The formal [3+3] cyclization of thioxindoles with fluoroaroyl chlorides, such as 2‐fluorobenzoyl chlorides and 2‐chloropyridine‐3‐carboxylic chloride, give rise to the synthesis of condensed benzothiophenes. The cyclization of heterocyclic enamines with diimines and triazines afford various purine analogues by domino [4+2]/retro [4+2] reactions. The formal [3+3] cyclization of 2,4,6‐tris(trifluoromethyl)‐1,3,5‐triazine with 1,3‐bis(silyloxy)‐1,3‐butadienes afford, depending on the conditions, 2,6‐bis(trifluoromethy)pyrid‐4‐ones or triazaadamantanone derivatives. Heating of 2‐ethynylpyridines with electron‐rich dienes afforded 2‐(2‐methoxyphenyl)pyridines by a domino [4+2]/retro [4+2] process. The reaction of 2‐ethynylpyridines with enones afforded indolizines by a formal [3+3] cyclization. The reaction of trifluoromethyl‐substituted 1,3‐diketones with lithiated alkynes afforded 3‐hydroxy‐pent‐4‐yn‐1‐ones. Formal [5+1] cyclization of the latter with urea afforded trifluoromethyl‐substituted pyridines. The Pd catalyzed formal [3+2] cyclizations of 2,3‐dihalopyridines with imines afforded a series of regioisomeric 4‐ and 7‐azaindoles. [ABSTRACT FROM AUTHOR]

Separation of the mixture of ethylene (C2H4) and ethane (C2H6) to produce polymer-grade C2H4 is of prime importance in the petrochemical industry. In this context, metal–organic frameworks (MOFs) featuring tunable pore metrics and surface chemistry, especially those with inverse C2H6/C2H4 adsorption selectivity, hold great promise in energy-effective purification of C2H4 by adsorptive separation, but often encounter the well-known trade-off between adsorption selectivity and capacity. In this work, we report two new MOFs by deploying the pore-space-partition (PSP) strategy for the purpose of reducing the pore aperture size while retaining the gas-accessible pore volume. As a result, Ni-bodc-tpt (bodc = bicyclo[2.2.2]octane-1,4-dicarboxylic acid, tpt = 2,4,6-tri(4-pyridyl)-1,3,5-triazine) by combining optimal pore size, large cage pore volume, and rich C–H binding sites exhibits concurrently high C2H6 adsorption capacity (131.65 cm3 g−1) and C2H6/C2H4 selectivity (1.8) at 298 K and 1 bar, which is superior or comparable to many benchmark C2H6-selective MOFs. A dynamic breakthrough experiment demonstrates that high-purity C2H4 (>99.9%) can be harvested in one step from a binary mixture of C2H6/C2H4 (50/50, v/v), attesting to the feasibility of this new MOF as a prospective C2H4 purification agent. [ABSTRACT FROM AUTHOR]

Achieving precise control over regioselectivity and stereoselectivity in the hydroelementation of terminal allenes presents a formidable challenge. Despite the existence of various catalytic methods for their functionalization, this entire class of reactions remains significantly underdeveloped and demands extensive research. Here, we report a method for the hydroelementation of allenes using inexpensive PN5P pincer cobalt complexes built on a triazine backbone. Depending on the substituent at the ring, the method enables the selective synthesis of E‐alkenylsilane or Z‐allylborane derivatives. In the presented approach, silanes and pinacoloboranes play a dualistic role of simultaneous activator and substrate excluding the need for the addition of external bases. Finally, the application potential of the obtained compounds was demonstrated by performing further functionalizations of the obtained compounds. [ABSTRACT FROM AUTHOR]

Small‐molecule reactions at the 2′‐OH groups of RNA enable useful applications for transcriptome technology and biology. To date, all reactions have involved carbonyl acylation and mechanistically related sulfonylation, limiting the types of modifications and properties that can be achieved. Here we report that electron‐deficient heteroaryl species selectively react with 2′‐OH groups of RNA in water via SNAr chemistry. In particular, trialkyl‐ammonium (TAA)‐activated aromatic heterocycles, prepared in one step from aryl chloride precursors, give high conversions to aryl ether adducts with RNAs in aqueous buffer in ~2–3 h. Remarkably, a TAA triazine previously used only for reaction with carboxylic acids, shows unprecedented selectivity for RNA over water, reacting rapidly with 2′‐OH groups while exhibiting a half‐life in water of >10 days. We further show that a triazine aryl species can be used as a probe at trace‐level yields to map RNA structure in vitro. Finally, we prepare a number of functionalized trialkylammonium triazine reagents and show that they can be used to covalently label RNA efficiently for use in vitro and in living cells. This direct arylation chemistry offers a simple and distinct structural scaffold for post‐synthetic RNA modification, with potential utility in multiple applications in transcriptome research. [ABSTRACT FROM AUTHOR]

Peptide and protein postmodification have gained significant attention due to their extensive impact on biomolecule engineering and drug discovery, of which cysteine‐specific modification strategies are prominent due to their inherent nucleophilicity and low abundance. Herein, the study introduces a novel approach utilizing multifunctional 5‐substituted 1,2,3‐triazine derivatives to achieve multifaceted bioconjugation targeting cysteine‐containing peptides and proteins. On the one hand, this represents an inaugural instance of employing 1,2,3‐triazine in biomolecular‐specific modification within a physiological solution. On the other hand, as a powerful combination of precision modification and biorthogonality, this strategy allows for the one‐pot dual‐orthogonal functionalization of biomolecules utilizing the aldehyde group generated simultaneously. 1,2,3‐Triazine derivatives with diverse functional groups allow conjugation to peptides or proteins, while bi‐triazines enable peptide cyclization and dimerization. The examination of the stability of bi‐triazines revealed their potential for reversible peptide modification. This work establishes a comprehensive platform for identifying cysteine‐selective modifications, providing new avenues for peptide‐based drug development, protein bioconjugation, and chemical biology research. [ABSTRACT FROM AUTHOR]

The method for the preparation of 3,6-disubstituted 1,2,4-triazines based on condensation reaction between easily available α-imino esters and isonitrosoacetophenone hydrazones was reported. The significant differences in reaction conditions, ratio of products, and yields between the developed method and the earlier reported approach were demonstrated. The corresponding 2,5-disubstituted pyridines were synthesized from the prepared 1,2,4-triazines, and their photophysical properties were studied. Studies of the photo-physical properties revealed low and moderate luminescence quantum yields, and negligible solvatochromic behavior in case of 4-methoxyphenylpyridine derivative due to the role of donating methoxy group, however, with a low linearity of a Lippert–Mataga plot. Nevertheless, 2,5-disubstituted pyridines are of interest due to simple protocols of synthesis, moderate photophysical properties, and potential applicability in different scientific and industrial areas. [ABSTRACT FROM AUTHOR]

2,4,6-Triaryl 1,3,5-triazine and 2-arylbenzothiazole derivatives have high biological activity potentials that are present in many natural and medicinal products. For these reasons, the synthesis of 2,4,6-triaryl 1,3,5-triazine and 2-arylbenzothiazole derivatives is of great interest among synthetic chemists. In this synthetic approach, we found that the utilization of Fe3O4@DH/Ph-ImH-Phen-CuCl2 nanocomposite in the presence of KOAc in ChCl/urea as solvent is an ecofriendly and efficient catalytic system for the synthesis of triazine and 2-arylbenzothiazole derivatives. Under this catalytic system, a broad range of 2,4,6-triaryl 1,3,5-triazine and 2-arylbenzothiazole derivatives were successfully synthesized with high to excellent yields. Compared to previously reported methods, this method has advantages such as synthesis of 2,4,6-triaryl 1,3,5-triazine and 2-arylbenzothiazole products with high to excellent yields, performance of reactions in ChCl/urea as green solvent, simple separation of the Fe3O4@DH/Ph-ImH-Phen-CuCl2 nanocatalyst only with an external magnet, high reusability of Fe3O4@DH/Ph-ImH-Phen-CuCl2 nanocatalyst, good characterization of the structure of copper nanomagnetic catalyst, and good characterization of the 2,4,6-triaryl 1,3,5-triazine and 2-arylbenzothiazole products by 1HNMR and 13CNMR spectroscopic techniques. [ABSTRACT FROM AUTHOR]

H2S and CO2 are considered two main impurities of natural gas and biogas. These impurities must be removed in order to achieve economic and environmental restrictions. Adsorption is a promising technology studied to achieve this goal. Among alternative adsorbents studied to capture H2S and CO2, porous aromatic frameworks (PAFs) had shown potential application because of suitable selectivity and remarkable adsorption capacity. However, H2S and CO2 adsorption/desorption data on PAF-30 are still scarce in literature. Thus, in this work, H2S (up to 2.5 bar) and CO2 and CH4 (up to 50 bar) adsorption/desorption isotherms on PAF-30 were determined at 293, 303 and 313 K for the first time in literature. PAF-30 was synthesized and characterized by XRD, FTIR, 13C-NMR, Ar and CO2 physisorption, SEM, TEM, TGA and DSC analyzes. Then, adsorption isotherms were determined gravimetrically. Experimental data were modelled with Jensen-Seaton equation. The results indicated that PAF-30 presents adsorption capacities in the order H2S > CO2 > CH4. Adsorption/desorption branches do not match for systems studied, due to a hysteresis effect. Adsorption capacity decreases with temperature, indicating that physisorption is the main phenomenon observed. Experimental data were represented by Jensen-Seaton model. Thermodynamic analysis showed that all systems are exothermic and spontaneous. Working capacities obtained indicate that temperature reduces the performance for gas purification and that H2S systems are affected by hysteresis loop. Moreover, cyclic adsorption results show that PAF-30 has potential to be applied and further studied in PSA simulations for H2S and CO2 capture under high-pressure conditions. [ABSTRACT FROM AUTHOR]

In this work, ultraviolet (UV)-/ultrasound (US)-based advanced oxidation processes were used to removal of Reactive Red 120 (RR120). The optimum conditions were determined as initial dye concentration = 100mg L−1, hydrogen peroxide concentration (H2O2) = 100 mg L−1, pH = 3 for the UV/H2O2 process, iron dosage (Fe2+) = 50 mg L−1, [H2O2] = 250mg L−1, pH = 3, ultrasound frequency = 53 kHz, and ultrasound power = 90 W for the sono-Fenton (Fe/H2O2/US) process. Besides, in the mineralization study, total organic carbon (TOC) reductions were 37.5%, 43.7%, 50.5%, and 58.9% for Fe/H2O2/US, UV/H2O2, foto-Fenton (Fe/H2O2/UV), and sono-photo-Fenton (Fe/H2O2/UV/US) processes, respectively. The sole and other processes removal percentages were below 27%. These results help us to understand how these different advanced oxidation processes removal performances by means of decolorization efficiencies are similar like as TOC reduction. A significant reduction in removal performance (27.8% because tert-butyl alcohol) of was found compared with no addition of radical scavenger (89.2%) in UV/H2O2. For sono-Fenton, the same situation was occurred, and the removal efficiency was decreased from 70.2 to 42.5% because of sodium azide radical scavenger. In the water matrix study, regardless of this process in the area of removal performance, the major issue of some ions persistence. (The performance declined 89.2–40.7% due to the carbonate ions for UV/H2O2; increased 70.2–82.1% due to the carbonate ions for sono-Fenton.) These findings may shed light on these processes' behavior of azo dyes in some specific scenarios such as laboratory or pilot scale utilization. [ABSTRACT FROM AUTHOR]

C-H borylation is a powerful strategy for the construction of C-B bonds due to the synthetic versatility of C-B bonds. Various transition metals affect the powerful functionalization of C-H bonds, of which Ir is the most common. Substrate-directed methods have enabled directed Ir-catalyzed C-H borylation at the ortho position. Amongst the powerful directing groups in Ir-catalyzed C-H borylation are N-containing carbocyclic systems. This review covers substrate-directed Ir-catalyzed ortho-C-H borylation of aromatic C(sp2)-H bonds in N-containing carbocyclic compounds, such as anilines, amides, benzyl amines, hydrazones, and triazines. [ABSTRACT FROM AUTHOR]

The electronic excitations of conformationally constrained bithiophene cage systems as previously investigated by Lewis et al. (J. Am. Chem. Soc. 143, 18548 (2021)) are revisited, employing the correlated ab initio Scaled Opposite‐Spin Algebraic Diagrammatic Construction Second Order electronic structure method. Quantitative descriptors are determined to assess the extent of charge transfer between the bithiophene moieties and the capping domains, represented by either phenyl or triazine groups. The investigation substantiates intrinsic differences in the photophysical behavior of these two structural variants and reveals the presence of lower‐energy excited states characterized by noteworthy charge transfer contributions in the triazine cage system. The manifestation of this charge transfer character is discernible even at the Franck–Condon geometry, persisting throughout the relaxation of the excited state. By examining isolated monomer building blocks, we confirm the existence of analogous charge transfer contributions in their excitations. Employing this methodological approach facilitates the prospective identification of potential wall/cap chromophore pairs, wherein charge transfer pathways can be accessed within the energetically favorable regime. [ABSTRACT FROM AUTHOR]

The evaluation of bis-1,2,4-triazine complexants containing eight-carbon, alkoxy-functionalized phenyl substituents at the 3,3′-positions for selective minor actinide extraction in simulated high level waste is reported. The complexant retained chemoselective extraction efficiency of actinides over lanthanides while breaking through the nonpolar diluent solubility and hydrolytic stability barriers that limit many BTP complexants. Thus, we report a BTP complexant that is readily soluble in both kerosene and isooctanol without forming precipitates, emulsions, or third phase after contact with nitric acid and extracts 241Am3+ from 154Eu3+. Separations and spectroscopic data are reported herein. [ABSTRACT FROM AUTHOR]

Herein we report the first microwave‐assisted one‐pot three‐step metal‐free [4+2] procedure for the synthesis of 5,6‐substituted‐3‐hydrazinyl‐1,2,4‐triazines directly from commercially available aromatic and heteroaromatic ketones. The 3‐hydrazinyl‐1,2,4‐triazine can be isolated or further elaborated, after a simple work‐up, by direct condensation with different aldehydes or ketones to provide highly functionalized hydrazone‐derivatives. This protocol represents a rapid, efficient, and sustainable approach for the development of new highly functionalized 1,2,4‐triazine derivatives with potential biological interest. [ABSTRACT FROM AUTHOR]

Exploring innovative strategies for molecular structuring of dynamic materials that combine self‐correcting intrinsic reversibility with the robustness of covalent bonds, has been a long‐standing objective from applications perspective in fields ranging from molecular engineering to nanotechnology and interfacial science. To establish dynamic covalent chemistry approaches combined with interfacial polymerization, herein, a distinct synthetic approach is reported to develop disulfide‐bridged 2D polymeric C3N3S3 triazine thin‐films by interfacial thiol‐disulfide dynamic exchange process crosslinking tritopic planar 1,3,5‐triazine‐2,4,6‐trithiol molecular tectons via intermolecular disulfide formation in the presence of I2 vapors at the air/water interface under redox condition. The resulting centimeter‐scale polymeric thin‐films are covalently cross‐linked, dynamic in nature, featuring tunable thickness (6–200 nm) and significant morphological variations are realized under the influence of varying reaction time, concentration and types of reducing agents. Notably, C3N3S3 polymer thin films exhibit a transflectance of around 99.5% in the range from 430 to 1800 nm, show high refractive indices (1.730–1.488) and optical anisotropy with uniaxial negative birefringence. The C3N3S3 free‐standing polymer thin‐films can be easily transferred to different substrates or possibly into application‐relevant forms for device fabrications, making this useful from materials application perspective. [ABSTRACT FROM AUTHOR]

Ethanamizuril (EZL) is a new anticoccidial drug developed by our Shanghai Veterinary Research Institute. Since EZL is almost insoluble in water, we conducted a study to improve the solubility of EZL by forming inclusion complexes with β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD). In this study, we performed molecular docking and then systematically compared the interactions of EZL with β-CD and HP-β-CD in both aqueous solution and the solid state, aiming to elucidate the solubilization effect and mechanism of cyclodextrins (CDs). The interactions were also examined in the solid state using DSC, PXRD, and FT-IR. The interactions of EZL with CDs in an aqueous solution were investigated using PSA, UV-vis spectroscopy, MS, 1H NMR, and 2D ROESY. The results of phase solubility experiments revealed that both β-CD and HP-β-CD formed inclusion complexes with EZL in a 1:1 molar ratio. Among them, HP-β-CD exhibited higher Kf (stability constant) and CE (complexation efficiency) values as well as a stronger solubilization effect. Furthermore, the two cyclodextrins were found to interact with EZL in a similar manner. The results of our FT-IR and 2D ROESY experiments are in agreement with the theoretical results derived from molecular simulations. These results indicated that intermolecular hydrogen bonds existing between the C=O group on the triazine ring of EZL and the O-H group of CDs, as well as the hydrophobic interactions between the hydrogen on the benzene ring of EZL and the hydrogen of CDs, played crucial roles in the formation of EZL/CD inclusion complexes. The results of this study can lay the foundation for the future development of high-concentration drinking water delivery formulations for EZL. [ABSTRACT FROM AUTHOR]

New approaches based on multicomponent condensation reactions were proposed to the synthesis of new heterocyclic derivatives of malononitrile dimer of the series of 7-oxa-1,3,6-triazabenzo[no]tetraphene, 1,2,3,4-tetrahydropyrazolo[1,5-a][1,3,5]triazine, 1,3,5,5-tetracyanocyclohex-3-ene, 3,9-diazaspiro[5.5]undeca-1,4-diene and 1Н,5Н-spiro[3,7-diazabicyclo[3.3.1]non-2-ene-9,4'-piperidine]. Structure of the products was studied using mass spectrometry, IR and NMR spectroscopy, as well as X-ray diffraction analysis. [ABSTRACT FROM AUTHOR]