Search Results (519)

A novel fluorinated diamine monomer, 4,4′-((bicyclo[2.2.1]hept- 5-ene-2,3-diylbis (methylene)) bis(oxy))bis(3- (trifluoromethyl) aniline) (NFDA), featuring a tailored alicyclic norbornane core, flexible ether linkages, and pendant trifluoromethyl groups, was successfully synthesized. This monomer was polymerized with six commercial dianhydrides to produce a series of poly(amic acid) precursors, which were subsequently converted into high-performance polyimide (PI) films via a thermal imidization process. The strategic integration of the alicyclic, ether, and fluorinated motifs within the polymer backbone resulted in materials with an exceptional combination of properties. These PI films display outstanding solubility in a wide range of organic solvents, including low-boiling options like chloroform and tetrahydrofuran, highlighting their superior solution processability. The films are amorphous and exhibit remarkable hydrophobicity, evidenced by high water contact angles (up to 109.4°) and minimal water absorption (as low as 0.26%). Furthermore, they possess excellent optical transparency, with a maximum transmittance of 86.7% in the visible region. The materials also maintain robust thermal stability, with 5% mass loss temperatures exceeding 416 °C, and offer a desirable balance of mechanical strength and flexibility. This unique set of attributes, stemming from a rational molecular design, positions these polyimides as highly promising candidates for next-generation flexible electronics and advanced photovoltaics. Full article

In the present study the stereoselective addition of malononitrile to trifluoromethyl arylketimines promoted by chiral iminophosphoranes was investigated. A panel of structurally diverse enantiopure bifunctional superbases, which include thiourea or squaramide unit and a basic site connected by a chiral scaffold, was tested in the asymmetric organocatalytic reaction, to afford an adduct featuring a quaternary stereocenter, in up to a 87/13 enantiomeric ratio. The product was then converted in a single step transformation into the corresponding enantioenriched α-CF₃ substituted quaternary aminoester, without any loss of stereochemical integrity. The absolute configuration of the final product was established by chemical correlation of the chiral compound with a known molecule. Preliminary computational studies were performed in order to elucidate the reaction mechanism and rationalize the stereochemical outcome of the reaction. Full article

The realization of desirable vertical phase separation, enabled by sequential processing that allows for the separate deposition and targeted regulation of donor and acceptor components to construct a well-defined donor–acceptor (D-A) interface, serves as a pivotal factor governing the performance of layer-by-layer organic photovoltaics (LOPVs). This study explores the utility of 4-trifluoromethyl benzoic anhydride (4-TBA), a multifunctional benzene-based solid additive, in the PM6/L8-BO LOPV system, focusing on its role in regulating the vertical phase separation of donor-PM6 and acceptor-L8-BO components to form a well-structured D-A interface. To this end, 4-TBA is doped into the donor-PM6 layer, acceptor-L8-BO layer, or both layers, and its effects on device performance are systematically characterized. The results show that simultaneous doping of 0.05 wt% 4-TBA in both PM6 and L8-BO layers yields the optimal performance, with the power conversion efficiency reaching 18.49% compared to the pristine device with a PCE of 17.05%, and this is accompanied by a significant increase in short-circuit current density from 24.71 mA/cm² to 26.65 mA/cm². Additionally, the optimal devices exhibit better stability, as unencapsulated devices retain 76% of their initial PCE after 175 h under ambient conditions compared to 73% for the devices without 4-TBA doping. Essentially, solid additive 4-TBA modulates molecular packing via its interaction between the donor and acceptor molecules and enhances molecular aggregation and hydrophobicity, thereby suppressing bimolecular and trap-assisted recombination, reducing trap density of states, and forming favorable interpenetrating networks. This work validates 4-TBA, which contains benzene rings and other functional groups, as a versatile additive suitable for the LOPV system and offers a generalizable strategy for optimizing LOPV performance by leveraging multifunctional solid additives. Full article

A strategy for constructing trifluoromethylated spiroisoxazolones has been developed. This approach relies on the 1,3-dipolar cycloaddition of CF₃-substituted nitrile imines, generated in situ from trifluoroacetyl hydrazonoyl bromides and K₂CO₃, with the exocyclic double bond of 4-benzylidene-3-methylisoxazol-5(4H)-ones. The reaction provides a series of trifluoromethylated spiro(isoxazolone-pyrazoline) derivatives in moderate to high yields (up to 93%). The protocol exhibits broad substrate compatibility with respect to aromatic substituents on both reaction partners. To the best of our knowledge, the introduction of a trifluoromethyl group at the 3-position of the pyrazoline ring via nitrile imine cycloaddition chemistry has not been previously reported. The resulting products incorporate a valuable CF₃-substituted pyrazoline pharmacophore spiro-fused to an isoxazolone core and may be of interest for medicinal chemistry programs. Full article

Background: In this study, we report a novel series of proline- and pipecolic acid-based small molecules designed as allosteric inhibitors of the NS2B/NS3 serine proteases from dengue and Zika viruses, key targets in antiviral drug discovery. Results: Enzymatic studies revealed that S-proline derivatives bearing electron-withdrawing substituents on the aromatic ring, particularly that with a trifluoromethyl group in meta position (i.e., compound 3, IC₅₀ = 5.0 µM), were the most potent against DENV NS2B/NS3, while nitro-substituted inhibitors were mostly effective only against the ZIKV protease. R-configured pipecolic acid-based derivatives were the only ones active against DENV NS2B/NS3, even if the mid-micromolar range; however, they demonstrated improved cellular efficacy since inhibitors 24 and 27 exhibiting strong activity in a DENV2 protease reporter gene assay (EC₅₀ = 5.2 and 5.1 µM, respectively). All compounds showed no cytotoxicity (CC₅₀ > 100 µM) and were selective for the viral protease over off-target serine proteases. Structure-based approaches were exploited to map the druggable allosteric site close to Asn152. Conclusions: Our findings led us to identify proline and pipecolic acid-based inhibitors as promising leads for the development of selective flaviviral NS2B/NS3 allosteric inhibitors. Full article

Tecovirimat is an antiviral agent approved for the treatment of orthopoxvirus infections including smallpox, cowpox and monkeypox. A key challenge in its synthesis lies in the generation of maleimide intermediates, which traditionally requires high-temperature thermal rearrangement and often results in low-to-moderate yields. Classical methods rely on heating in toluene above 70 °C, limiting scalability and efficiency. Herein, we present a mild and efficient organocatalytic approach to the synthesis of tecovirimat intermediates, using a room-temperature Mumm rearrangement of isomaleimide precursors. The reaction is catalyzed by 10 mol% imidazole and N-hydroxysuccinimide. As a representative example for one of the tecovirimat synthesis methods, intermediate N-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-4-(trifluoromethyl)benzamide was synthesized from p-trifluoromethylbenzohydrazide at a 71% yield over two steps. Additionally, N-(2,5-dioxopyrrol-1-yl)(tert-butoxy)formamide was obtained from Boc-hydrazide at a 37% yield. The methodology was sufficiently extended to other benzohydrazide-derived isomaleimides. To support the mechanistic rationale, preliminary PM7 semiempirical computational studies were performed, highlighting the electronic features facilitating the transformation. This work offers a practical and scalable route to tecovirimat intermediates, overcoming key synthetic bottlenecks and enhancing the efficiency of antiviral drug production. Full article

This study reports the microwave-assisted synthesis and surface modification of carbon quantum dots (CQDs) from natural precursors and their evaluation as fluorescent probes for cancer cell visualization. CQDs were obtained using amino-glucose as the carbon source and betaine, marine collagen, or dopamine as surface modifiers. Further functionalization with 7-amino-4-(trifluoromethyl)coumarin enhanced their fluorescence properties. Spectroscopic analyses confirmed successful surface modification, with coumarin-modified CQDs displaying a strong emission peak at ~500 nm and approximately 1.5-fold higher fluorescence intensity compared to unmodified CQDs. Cytotoxicity testing on MG-63 osteosarcoma cells showed cell viabilities above 80% for selected samples, fulfilling ISO 10993-5 criteria for non-toxicity. In vitro bioimaging of astrocytoma 1321N1 cells demonstrated bright and uniform intracellular staining, confirming effective cellular uptake. Compared with the literature reports of green-synthesized CQDs, our results indicate comparable or superior fluorescence performance and similar levels of biocompatibility. These findings highlight the potential of surface-engineered CQDs as biocompatible nanoprobes for cancer diagnostics and represent an initial step toward their application in the detection of circulating tumor cells (CTCs). Full article

Benign prostatic hyperplasia (BPH) is a common disease in elderly men; its occurrence is closely related to the interaction between stromal cells and epithelial cells in the prostate. This article aims to explore the potential therapeutic effect and mechanism of a new trifluoromethyl quazoline compound (kzl054) on BPH. The results showed that kzl054 had inhibitory activity that limited the growth of prostate hyperplasia cells, BPH-1, and stromal cells, WPMY-1. It could also induce apoptosis of BPH-1 cells and arrest their cell cycle. animal experiment results showed that kzl054 could effectively reduce the volume and prostate index of mouse prostate hyperplasia tissues. Through the establishment of a co-culture system of BPH-1 and WPMY-1 cells, it was found that co-culture could induce EMT in BPH-1 cells. While kzl054 could affect the secretion of TGF-β1 by competitively binding to the colchicine binding site on β-tubulin and inhibiting the expression of β-tubulin, through inhibiting the secretion of TGF-β1 by stromal cells. This study has revealed that compound kzl054 inhibits the secretion of TGF-β1 by targeting the inhibition of microtubule polymerization and regulating the epithelial cell EMT, providing potential candidate molecules and mechanisms for the development of new drugs for the treatment of BPH. Full article

Thiourea and structurally related urea derivatives are widely recognised for their ability to transport anions through hydrogen bonding interactions. The strength of these interactions correlates with the electronegativity of the ligand and the acidity of the NH hydrogens involved. Thiourea, being more acidic than urea, exhibits partial deprotonation in the presence of certain anions such as organic carboxylates, fluoride, and bromide, while remaining resistant to deprotonation by chloride. This behaviour suggests a degree of selectivity toward chloride ions. Additionally, while carbamide-containing molecules tend to aggregate—potentially reducing their ion-binding efficiency—thiourea derivatives show reduced aggregation, preserving their binding capabilities. In this study, we report the synthesis and characterisation of 21 novel thiourea derivatives obtained by reacting 2-aminobenzoylamino acid esters with various substituted phenyl isothiocyanates. Seven similar thiourea-containing molecules were made as a comparison—without the amino acids—by reacting aniline with the different phenyl isothiocyanates. The reaction kinetics were found to be influenced primarily by the electronic nature of the substituents on the phenyl ring. Electron-withdrawing groups (EWGs), such as para-nitro, 3,5-bis(trifluoromethyl), and fluorine, accelerated the reaction, while electron-donating groups (EDGs), such as para-methoxy, slowed it down. Interestingly, the nature of the amino acid precursors had no significant impact on reaction time; however, reactions with aniline proceeded the fastest. Solvent choice also played a role: reactions in N,N-dimethylformamide (DMF) proceeded faster than in acetone, although with reduced yields. Consequently, reaction conditions were optimised to balance time efficiency and product yield. To evaluate the chloride ion-binding properties of the synthesised compounds, ¹H NMR titration experiments were conducted in deuterated dimethyl sulfoxide (DMSO-d₆). The association constants (K_a) derived from these studies revealed a clear correlation with the electronic nature of the substituents. Compounds bearing EWGs exhibited enhanced chloride binding, while those with EDGs showed diminished binding affinity. Surprisingly, the presence of amino acid moieties led to a decrease in K_a values, despite the electron-withdrawing nature of the amide groups. This suggests that steric or conformational factors may play a role in modulating binding strength. Overall, the synthesised thiourea derivatives demonstrate mild, reversible chloride ion-binding behaviour, making them promising candidates for further development as selective anion receptors. The insights gained from this study contribute to a deeper understanding of structure–activity relationships in anion-binding systems and may inform the design of future supramolecular architectures with tailored ion recognition properties. Full article

Bile acids provide a versatile platform for the design of biologically active compounds due to their amphiphilic structure, biocompatibility, and capacity for diverse chemical modifications. Among them, lithocholic acid is a promising scaffold for designing and revealing new antiviral agents. A novel lithocholic acid-based 3-spiro-1,2,4-trioxolane was synthesized by Griesbaum co-ozonolysis of methyl 3-O-methyl-oximino-lithocholate and 4-(trifluoromethyl)-cyclohexanone, and its structure was confirmed by 2D NMR and X-ray crystallographic analysis. Lithocholic acid derivatives were evaluated for cytotoxicity and anti-influenza activity against A/Puerto Rico/8/34 (H1N1), showing that steroid 1,2,4-trioxolane 3 exhibited the highest potency (IC₅₀ 4.3 µM, SI 11) compared to the parent methyl-3-oxo-lithocholate 1 (IC₅₀ > 84 µM, SI 1). In silico ADME predictions revealed several favorable drug-like properties, including a highly three-dimensional structure (Fsp³ = 0.97), significant lipophilicity (LogP = 7.54), and the presence of key pharmacophores such as a peroxide moiety and a trifluoromethyl group. Taken together, a stereospecific synthesis of a lithocholic acid 3-spiro-1,2,4-trioxolane by Griesbaum co-ozonolysis was realized and the first evidence of anti-influenza activity in the steroid-1,2,4-trioxolane series was found. Full article

Type 2 diabetes mellitus remains a critical metabolic disorder requiring novel therapeutic approaches. In this work, a library of 1-deazapurine derivatives was evaluated as α-glucosidase inhibitors through molecular docking with MOE software. The three top-ranked ligands—Methyl 6-(2-hydroxybenzoyl)-3-(2-phenylethyl)imidazo[4,5-b] pyridine-5-carboxylate (–6.1247 kcal/mol), 5-(furan-2-yl)-3-(4-methoxybenzyl)-2-phenyl-7- (trifluoromethyl)imidazo[4,5-b]pyridine (–5.7030 kcal/mol), and 3-[2-phenylethyl]-5-thio phen-2-yl-7-(trifluoromethyl)imidazo[4,5-b]pyridine (–5.5403 kcal/mol)—were further validated by molecular dynamics simulations. ADMET and drug-likeness predictions confirmed favourable pharmacokinetic behaviour, gastrointestinal absorption, and oral bioavailability. These findings highlight 1-deazapurines as promising scaffolds for developing new α-glucosidase inhibitors targeting type 2 diabetes. Full article

Two diruthenium(II,II) naphthyridine complexes coordinated with 4-trifluoromethylbenzoate (O₂CPh-4-CF₃) and 3,5-bis(trifluoromethyl)benzoate (O₂CPh-3,5-diCF₃) ligands, formulated as [Ru₂(npc)₂(O₂CPh-4-CF₃)₂] (4; npc = 1,8-naphthyridine-2-carboxylate) and [Ru₂(npc)₂(O₂CPh-3,5-diCF₃)₂] (5), respectively, were synthesized and structurally characterized. Single-crystal X-ray diffraction analysis revealed that both 4 and 5 form a direct metal–metal bond between the two Ru ions (2.2893(8) and 2.2896(7) Å, respectively) and adopt a paddlewheel-type structure in which two npc and two trifluoromethyl-substituted benzoate ligands are coordinated to a Ru₂⁴⁺ core with a cis-2:2 arrangement. The temperature dependence of the magnetic susceptibility measurements of 4 and 5 exhibited very large zero-field splitting (D = 242 and 246 cm⁻¹, respectively) of the triplet ground state of the Ru₂⁴⁺ core, similar to that of [Ru₂(npc)₂(O₂CPh)₂] (3; D = 238 cm⁻¹). Owing to the effects of the trifluoromethyl substituents, compared with 3, 4 and 5 showed (i) a significant blue shift of the absorption bands in the visible region and (ii) a positive shift of the redox potentials, with both shifts becoming more pronounced as the number of trifluoromethyl substituents increased. These experimental results are in good agreement with the electronic structure results obtained from density functional theory calculations. Full article

Background/Objectives: Vector-borne diseases like malaria remain a major global health concern, worsened by insecticide resistance in mosquito populations. Quinoline-based compounds have been extensively studied for their pharmacological effects, including antimalarial and larvicidal properties. Modifying quinoline structures with hydrazone groups may enhance their biological activity and physicochemical properties. This study reports the synthesis, structural characterization, and larvicidal testing of a new series of aryl hydrazones (6a–i) derived from 8-trifluoromethyl quinoline. Methods: Compounds 6a–i were prepared via condensation reactions and characterized using ¹H NMR, ¹⁹F-NMR, ¹³C NMR, and HRMS techniques. Their larvicidal activity was tested against Anopheles arabiensis. Single-crystal X-ray diffraction (XRD) was performed on compound 6d to determine its three-dimensional structure. Hirshfeld surface analysis, fingerprint plots, and interaction energy calculations (HF/3-21G) were used to examine intermolecular interactions. Quantum chemical parameters were computed using density functional theory (DFT). Molecular docking studies were performed for the synthesized compounds 6a–i against the target acetylcholinesterase from the malaria vector (6ARY). In silico ADMET properties were also calculated to evaluate the drug-likeness of all the tested compounds. Results: Compound 6a showed the highest larvicidal activity, causing significant mortality in Anopheles arabiensis larvae. Single-crystal XRD analysis of 6d revealed a monoclinic crystal system with space group P2₁/c, stabilized by N–H···N intermolecular hydrogen bonds. Hirshfeld analysis identified H···H (22.0%) and C···H (12.1%) interactions as key contributors to molecular packing. Density functional theory results indicated a favorable HOMO–LUMO energy gap, supporting molecular stability and good electronic distribution. The most active compounds, 6a and 6d, also showed strong binding interactions with the target protein 6ARY and satisfactory ADMET properties. The BOILED-Egg model is a powerful tool for predicting both blood–brain barrier (BBB) and gastrointestinal permeation by calculating the lipophilicity and polarity of the reported compounds 6a–i. Conclusions: The synthesized arylhydrazone derivatives demonstrated promising larvicidal activity. Combined crystallographic and computational studies support their structural stability and suitability for further development as eco-friendly bioactive agents in malaria vector control. Full article

Background/Objectives: Parkinson’s disease (PD) is the second most common neurodegenerative disease (NDD), marked by the progressive loss of dopaminergic neurons in the substantia nigra that causes motor dysfunction. Growing evidence indicates that neuroinflammation plays a crucial role in the onset and progression of PD, though the exact mechanisms are still unclear. In this study, we examined the anti-inflammatory and neuroprotective effects of 4-[3-oxo-3-(2-trifluoromethyl-phenyl)-propyl]-morpholinium chloride (OTPM), a fluoxetine derivative and selective serotonin reuptake inhibitor, in both lipopolysaccharide (LPS)-stimulated BV-2 microglial cells and an MPTP-induced mouse model of PD. Methods: C57BL/6 mice were orally administered OTPM (10 mg/kg b.w.) for 7 days and intraperitoneally injected with MPTP (20 mg/kg b.w.) for one day, with four injections at 2 h intervals. Bradykinesia was assessed using the Y-maze and Pole tests. Protein and mRNA levels were examined in vitro and in vivo using Western blotting and RT-PCR. Immunofluorescence was used to assess microglial and astrocyte activation. Results: In vitro, OTPM significantly decreased nitric oxide (NO) production (p < 0.001) and suppressed the protein and mRNA expression of iNOS (p < 0.001), COX-2 (p < 0.001), and pro-inflammatory cytokines, including IL-β (p < 0.001), IL-6 (p < 0.001), and TNF-α (p < 0.01), in LPS-activated BV-2 microglia. Further mechanistic studies showed that OTPM inhibited NF-κB phosphorylation and blocked its nuclear translocation, thereby reducing inflammatory signaling. In vivo, treatment with OTPM (10 mg/kg for 7 days) significantly reduced the MPTP-induced activation of microglia (MAC-1) and astroglia (GFAP) in the brain and improved behavioral deficits associated with PD, as assessed in the Y-maze and pole tests. Conclusions: Overall, these results reveal that OTPM has strong anti-neuroinflammatory and neuroprotective properties, suggesting its potential as a new therapeutic candidate for PD and other disorders associated with neuroinflammation. Full article

Heterogeneous catalysts comprising immobilized nickel(II) complexes bearing a fluorine- or trifluoromethyl-substituted iminopyridine ligand (X_n-C₆H_5–n-N=C (CH₃)-C₅H₅N, X = F or CF₃) in fluorotetrasilicic mica interlayers were prepared by reacting Ni²⁺-exchange fluorotetrasilicic mica with the appropriate ligand. Upon activating the precatalyst with triethylaluminum or triisobutylaluminum, the generated active species showed catalytic activity for ethylene oligomerization, yielding low-molecular-weight polyethylene (PE), ethylene oligomers, and wax-like PE. The oligomer distribution almost agreed with what we expected according to the Schultz–Flory distribution. However, the amount of solid products was much higher than the theoretical value, indicating that at least two active species were formed, i.e., the oligomer and low-molecular-weight PE. The precatalyst with a 2,4-F₂C₆H₃ group on the imino nitrogen atom activated by triethylaluminum showed the highest catalytic activity for ethylene oligomerization (408 g-C₂ g-cat⁻¹ h⁻¹), with selectivities to the liquid and solid products of 51.0% and 11.5%, respectively, with the rest of the product corresponding to wax-like PE. Meanwhile, the highest selectivity to the liquid product (66.7% at 233 g-C₂ g-cat⁻¹ h⁻¹) was obtained using the precatalyst with a 2-FPh group on the imino nitrogen atom activated by triisobutylaluminum. Full article