Search Results (124)

The persilylated Si₃–Si₇ analogues of the C₃–C₇ aromatic molecules and ions with all hydrogen or all fluorine atoms at silicon have been calculated at high levels of theory, up to MP2/aug-cc-pVTZ for all species and CCSD/6-311++G** for Si₃ and Si₄ species, both in the gas phase and in a polar solvent (water). The aromaticity of the calculated species was estimated using structural, energetic, and NMR criteria. (SiF)₃⁺ cations are more aromatic than (SiH)₃⁺ by the NICS (nuclear-independent chemoical shift) but less aromatic by the ASE (aromatic stabilization energy) criterion. Dications (SiX)₄²⁺ are planar (X = H) or slightly puckered (X = F); the ASE decreases by 4–5 kcal/mol upon going from gas to solution, or from X = H to X = F. Dianions (SiX)₄²⁻are nonplanar and antiaromatic. The ASE for the slightly distorted-from-planarity anion Si₅H₅⁻ is ~53 kcal/mol, vs. 85 kcal/mol for its carbon analogue. The structure of Si₆X₆ molecules strongly depends on the level of calculations. The NICS and ASE values have been calculated for planar Si₆H₆ and (SiH)₇⁺ but not for strongly distorted Si₆F₆ and (SiF)₇⁺ species. Full article

The trade-off between the ionic conductivity and the stability of the proton exchange membrane (PEM) is a major concern in the development of PEM water electrolysis (PEMWE). This review focuses on the design and fabrication of homogeneous and composite PEMs for water electrolysis and establishes the structure–performance relationships between the membrane chemical/physical structures and their efficiency metrics—specifically, proton conductivity, hydrogen permeability, and chemical and mechanical stability. A special focus is placed on the fundamental connection between the microstructure and performance of membrane materials. At the molecular level, we systematically illustrate the design principles for main chains, side chains, and sulfonate groups, covering both fluorinated PEMs (encompassing perfluorinated and partially fluorinated membranes) and non-fluorinated PEMs (including aromatic polymers with heteroatom backbones and all-carbon backbones). At the macroscopic level, the review provides an in-depth exploration of two primary modification strategies: creating composites with organic polymers and with inorganic nanofillers. In summary, this review elucidates how these composite approaches leverage material synergies to improve the membrane’s mechanical integrity, proton conduction efficiency, and chemical resistance and offers a theoretical framework for the rational design of next-generation, high-performance PEMs to advance the commercialization of PEMWE technology. Full article

In 2025, the U.S. Food and Drug Administration (FDA) approved 44 new drugs, reflecting a slight decrease compared to previous years but maintaining the overall trends in pharmaceutical innovation. Biologics accounted for 25% of approvals, including nine monoclonal antibodies (mAbs), two antibody–drug conjugates (ADCs), and one fusion protein, with cancer remaining the primary therapeutic focus. TIDES, comprising three oligonucleotides and one peptide, continued to consolidate their presence in the market, with the three oligonucleotides featuring N-acetylgalactosamine (GalNAc) for liver-targeted delivery. Small molecules dominate the remainder, with a high prevalence of N-aromatic moieties and fluorine atoms present in most of the molecules. Peptide manufacturing and sustainability concerns, including PFAS usage, remain key challenges. Despite these advances, the high cost of innovative therapies limits access, particularly in low- and middle-income countries. This report provides a structural and chemical analysis of the newly approved drugs, highlighting trends in molecular design, therapeutic areas, and technological innovations shaping modern drug discovery. Full article

Steroidal compounds lie at the crossroads of inflammation and cancer, where modulation of common signaling pathways creates opportunities for dual-action therapeutic intervention. Accumulating evidence indicates that their anti-inflammatory and antitumor activities are frequently interconnected, reflecting shared molecular mechanisms that regulate immune signaling, oxidative stress, cell proliferation, and apoptosis. This review provides a critical and comparative analysis of major classes of bioactive steroids—including furanosteroids, neo-steroids, aromatic steroids, α,β-epoxy steroids, peroxy steroids, cyanosteroids, nitro- and epithio steroids, halogenated steroids (fluorinated, chlorinated, brominated, iodinated), and steroid phosphate esters—with emphasis on their dual anti-inflammatory and anticancer potential. More than one thousand steroidal metabolites derived from plants, fungi, marine organisms, bacteria, and synthetic sources are surveyed. While the majority exhibit either anti-inflammatory or antineoplastic activity alone, only a limited subset displays potent activity in both domains. Comparative evaluation highlights the structural features that favor dual functionality, including epoxide, peroxide, nitrile, nitro, halogen, and phosphate ester moieties, as well as rearranged or heteroatom-enriched steroidal frameworks. Where available, biological data from in vitro and in vivo assays (IC₅₀ values, enzyme inhibition, cytokine modulation, and antiproliferative effects) are summarized and critically compared. Special attention is given to rare natural metabolites—such as polyhalogenated marine steroids, phosphorylated sterols, and heteroatom-containing derivatives—as well as synthetic analogues designed to enhance cytotoxic or immunomodulatory efficacy. Mechanistically, steroids exhibiting dual activity commonly modulate convergent signaling pathways, including NF-κB, JAK/STAT, MAPK, PI3K/AKT, redox homeostasis, and apoptosis regulation. Collectively, these findings underscore the potential of structurally optimized steroids as multifunctional therapeutic agents and provide a framework for the rational design of next-generation anti-inflammatory and anticancer drugs. Full article

Ultra-high voltage (UHV) power transmission has become a prerequisite for the development of clean energy. However, arcs generated by UHV circuit breakers can easily lead to safety incidents, and developing arc-extinguishing gases with low global warming potential (GWP) presents certain challenges. It is a fact that fluorolefins, as a class of fluorinated compounds with low GWP, show high application potential in replacing traditional arc-extinguishing agents. In this study, all six conjugated perfluorinated compounds, including C₆F₆ and C₆F_8, were calculated within the density functional theory (DFT) framework at the B3LYP/6-311+G(d,p) level. The dipole moments, HOMO/LUMO energy gaps, and the inherent aromaticity of annular molecules under external electric fields of these fluorinated molecules are investigated accordingly. By analyzing these results, it is found that the influence of the conjugated structure on the stability of arc-extinguishing gases under high-voltage conditions was partially elucidated, providing useful insights for the subsequent development of environmentally friendly and high-performance arc-extinguishing gases. Full article

Thermal [2+2] cycloaddition (22CA) reactions of perfluorobicyclo[2.2.0]hex-1(4)-ene (PFBHE) and bicyclo[2.2.0]hex-1(4)-ene (BHE) with ethylene, benzene and styrene were investigated through the Molecular Electron Density Theory (MEDT) at the UM06-2X/6-311G(d,p) level in benzene. Scrutiny of the DFT-based reactivity indices indicates that the presence of the eight fluorines in PFBHE notably expands the electrophilic nature of this species, participating in polar reactions. These 22CAs proceed through a stepwise mechanism, while the non-polar 22CA reaction of BHE with ethylene requires high energy around 26.6 kcal·mol⁻¹, the polar 22CA reaction of PFBHE with styrene requires a low activation energy of 13.2 kcal·mol⁻¹. The polar 22CA reaction of PFBHE with benzene presents the highest activation energy, 28.3 kcal·mol⁻¹, because of the loss of its aromatic character. Scrutiny of the electron localization function (ELF) at the TSs associated with the first step points that the creation of the C1–C3 bond set about, while that at the TSs associated with the ring-closure means that the creation of the C2–C4 bond has not started yet. At the end, a Relative Interacting Atomic Energy (RIAE) study of these thermal 22CA processes shows that while at the non-polar TS1a-I both interacting frameworks are electronically destabilized, at the polar TS1a-IV, the hefty global electron density transfer (GEDT) goes ahead towards PFBHE, causing a strong electronic stabilization of this framework, markedly reducing the RIAE activation energy. Full article

The aim of this study was to investigate the nucleation, growth, and surface deposition of poly(2,2,2-trifluoroethyl methacrylate) [poly(TFEMA)] from the one-phase, cloud point, and two-phase regions of a supercritical CO₂–toluene solvent. A ternary mixture of 20 wt% toluene + 79 wt% scCO₂ + 1 wt% poly(TFEMA) at 40.0 °C was exposed to a fluorine-doped tin oxide (FTO) surface for 30 min at pressures placing the solution in (i) a one-phase region (15.86 MPa), (ii) the cloud point (12.37 MPa), and (iii) a two-phase region (8.96 MPa). Using the Altunin–Gadetskii–Haar–Gallagher–Kell (AG–HGK) equation of state (EOS), the corresponding CO₂ densities are 793.9, 729.2, and 477.8 kg m⁻³. Scanning electron microscopy (SEM) and particle-size analysis (sample sizes N = 852–1177) show particle-size distributions (PSDs) that are well described by the following lognormal form: the mean diameter increases monotonically with a decrease in pressure (1.767 μm → 2.605 μm → 2.863 μm), while dispersion tightens slightly near the cloud point (coefficient of variation, CV: ≈0.47 → 0.44) and then broadens strongly in the two-phase region (CV ≈ 1.02). Morphologies transition from sparse, compact islands (one-phase) to agglomerated, necked spheres (cloud point) and finally hierarchical populations containing hollow/pitted large particles (two-phase). These outcomes are consistent with a phase-state-controlled shift in nucleation pathways, as follows: from heterogeneous surface nucleation in the one-phase regime to homogeneous nucleation with agglomeration at the cloud point, and to homogeneous nucleation with coalescence and solvent capture in the two-phase regime. The results provide a mechanistic basis and practical design rules for pressure-programmable control of fluoropolymer coatings prepared from scCO₂/aromatic-cosolvent systems. Full article

Near-ultraviolet photoluminescence liquid-crystalline molecules (PLLCs) have attracted attention for temperature-responsive photoluminescence (PL) modulation and ON/OFF sensing under external stimuli. We recently developed mesogenic dimers composed of two hexyloxy-substituted, fluorinated tolane-type cores linked by alkylene-1,n-dioxy chains that exhibited near-UV PL in the solid state. However, the formation of LC phases and the temperature range of the LC state were limited. To improve LC phase stability, in this study, we extended the flexible terminal chains and repositioned the fluorinated aromatic rings from the outer to the inner core positions. Accordingly, we synthesized mesogenic dimers with even-numbered alkylene-1,n-dioxy linkers (hexylene, octylene, and decylene) and outer- or inner-ring fluorination. Outer-ring fluorination led to high melting temperatures and stable crystalline phases with limited mesophase formation. In contrast, inner-ring fluorination induced nematic phases upon heating and cooling owing to zig-zag molecular structures that disrupted crystallinity. Photophysical studies confirmed near-UV PL in solution and solid states; however, the quantum yield of the solution PL was low (<0.01). In the solid state, the PL efficiencies and wavelengths were influenced by the fluorinated aromatic ring position and linker length. This study provides important molecular design criteria for developing stable LC materials with tunable near-UV luminescence for temperature-responsive optical devices. Full article

Acyl chloride alcoholysis is a fundamental and typically high-yielding method for ester synthesis. However, competitive side reactions can occur when the acyl chloride possesses multiple electrophilic sites and the alcohol is a strong nucleophile. We report an example of this phenomenon: the reaction of pentafluorobenzoyl chloride with 1,1,1,3,3,3-hexafluoropropan-2-ol yields not only the expected ester but also a significant quantity of the 1,1,1,3,3,3-hexafluoropropan-2-yl 2,3,5,6-tetrafluoro-4-((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)benzoate. The formation of the latter results from an effective nucleophilic aromatic substitution (S_NAr) at the para-fluorine position of the pentafluorophenyl ring by the hexafluoroisopropoxide anion. Full article

Background/Objectives: Pancreatic cancer is the seventh most lethal type of cancer in the world, and its treatment, which is largely inefficient, is based on surgery and/or non-specific chemotherapy. Its malignant features are characterized by complex cell signaling pathways, which can be used as targets for new drugs. Methods: In this study, glucal-based compounds were synthetized, with substitution based on fluorine, nitrogen and aromatic ring addition. The compounds were tested in the pancreatic cell culture Mia-PaCa-2 and cell viability was assessed, with further IC50 calculation, stability and selectivity. Molecular docking was performed to evaluate the probable molecular target for 5b and in silico physicochemical properties were determined. Results: One molecule, named 5b, with two fluorine atoms inserted in the aromatic ring, exerted potent inhibitory activity on cell growth (IC50 = 1.39 µM), which was selective for pancreatic cells. Through molecular docking studies, the compound was found to be positioned in the active site of JAK3, indicating inhibition of such protein, which has a role in tumoral cell growth. Moreover, 5b was stable for 24 months and had physicochemical properties to permeate cell membranes, good oral absorption, and low potential to cause toxicity. Conclusions: These data suggest that 5b can be druggable and can be considered as a prototype for a new course of treatment in pancreatic cancer. Full article

In this paper, we present our investigations into the detonation performance and stability variations caused by replacing the -CF₃ or -OCF₃ group with -SF₅. The widely applied DFT B3LYP/cc-pVTZ approach was employed to evaluate the HOMO–LUMO gap, cohesive energy, chemical hardness, and electronegativity. Based on these parameters, we predict the changes in chemical and thermal stability resulting from the inclusion of -SF₅ instead of -CF₃ or -OCF₃. Our results indicate that, in some cases, the density of fluorine-containing nitro compounds decreases due to the presence of the pentafluorosulfanyl group. Additionally, machine learning techniques were used to determine the detonation pressure and velocity of fluorine–sulfur-containing compounds. Our findings suggest that fluorine-containing nitro compounds exhibit better detonation performance and stability than fluorine–sulfur-containing ones. Overall, the pentafluorosulfanyl groups inclusion of aromatic polynitro compounds improved neither the stability nor the detonation properties such as -CF₃ or -OCF₃ groups. Full article

The crystal structures, interactions, and contacts analyses of four N-(ferrocenylalkyl)benzene-carboxamide derivatives are described as the N-(ferrocenylmethyl)benzenecarboxamide 4a, N-(ferrocenylmethyl)-2,6-difluorobenzenecarboxamide 4e, N-(ferrocenylmethyl)pentafluorobenzenecarboxamide 4f and N-(ferrocenylethyl)-4-fluorobenzenecarboxamide 5. Intermolecular amide⋯amide hydrogen-bonding interactions as 1D intermolecular chains are present in all four crystal structures, with N⋯O distances ranging from 2.819 (2) to 2.924 (3) Å. Three of the crystal structures have one molecule per asymmetric unit, except the phenyl 4a, which has Z’=2. In the structure of 4a, Fc(C-H)⋯(phenyl) and _phenylC-H⋯π(C₅H₄) ring interactions dominate the interaction landscape, together with (1:1) face-to-face (phenyl)⋯(phenyl) and (C₅H₅)⋯(C₅H₅) ring stacked pairs (Fc = ferrocenyl moiety). In 4e, interlocking ferrocenyls, short C-H⋯(C-F) and C-H⋯O hydrogen bonds are the only additional notable intermolecular interactions. In the pentafluorophenyl derivative 4f, a remarkable selection of interactions is present with interwoven 1D ferrocenyl⋯(C₆F₅) stacking and C-H⋯F interactions; molecules aggregate forming impressive 1D columns comprising intertwined (Fc⋯C₆F₅⋯)_n ring stacking. In the ethyl bridged system 5, C-H⋯F and C-H⋯π (arene) contacts with (4-fluorobenzene) ring⋯ring pairs combine and stack about inversion centres. The reported para-F substituted structure REYWOU (4d) is used for comparisons with the 4a, 4e, 4f, and 5 crystal structures. In view of the rich interaction chemistry, contacts enrichment analyses of the Hirshfeld surface highlights several interesting features in all five ferrocenylalkylcarboxamide structures. Full article

The complex of hypofluorous acid with acetonitrile—HOF•CH₃CN—is the only substance possessing a truly electrophilic oxygen. This fact makes it the only tool suitable for transferring oxygen atoms to sites that are not accessible to this vital element. We will review here most of the known organic reactions with this complex, which is easily made by bubbling dilute fluorine through aqueous acetonitrile. The reactions of HOF•CH₃CN with double bonds produce epoxides in a matter of minutes at room temperature, even when the olefin is electron-depleted and cannot be epoxidized by any other means. The electrophilic oxygen can also substitute deactivated tertiary C-H bonds via electrophilic substitution, proceeding with full retention of configuration. Using this complex enables transferring oxygen atoms to a carbonyl and oxidizing alcohols and ethers to ketones. The latter could be oxidized to esters via the Baeyer–Villiger reaction, proving once again the validity of the original Baeyer mechanism. Azines are usually avoided as protecting groups for carbonyl since their removal is problematic. HOF•CH₃CN solves this problem, as it is very effective in recreating carbonyls from the respective azines. A bonus of the last reaction is the ability to replace the common ¹⁶O isotope of the carbonyl with the heavier ¹⁷O or ¹⁸O in the simplest and cheapest possible way. The reagent can transfer oxygen to most nitrogen-containing molecules. Thus, it turns practically any azide or amine into nitro compounds, including amino acids. This helps to produce novel α-alkylamino acids. It also attaches oxygen atoms to most tertiary nitrogen atoms, including certain aromatic ones, which could not be obtained before. HOF•CH₃CN was also used to make five-member cyclic poly-NO derivatives, many of them intended to be highly energetic materials. The nucleophilic sulfur atom also reacts very smoothly with the reagent in a wide range of compounds to form sulfone derivatives. While common sulfides are easily converted to sulfones by many orthodox reagents, electron-depleted ones, such as R_f-S-Ar, can be oxidized to R_f-SO₂-Ar only with this reagent. The mild reaction conditions also make it possible to synthesize a whole range of novel episulfones and offer, as a bonus, a very easy way to make S^xO₂, x being any isotope variation of oxygen. These mild conditions also helped to oxidize thiophene to thiophen-S,S-dioxide without the Diels–Alder dimerizations, which usually follow such dioxide formation. The latter reaction was a prelude to a series of preparations of [all]-S,S-dioxo-oligothiophenes, which are important for the efficient preparation of active layers in field-effect transistors (FETs), as such oligomers are considered to be important for organic semiconductors for light-emitting diodes (LEDs). Several types of these oligothiophenes were prepared, including partly or fully oxygenated ones, star-oligothiophenes, and fused ones. Several [all]-S,S-dioxo-oligo-thienylenevinylenes were also successfully prepared despite the fact that they also possess carbon–carbon p centers in their molecules. All oxygenated derivatives have been prepared for the first time and have lower HOMO-LUMO gaps compared to their parent compounds. HOF•CH₃CN was also used to oxidize the surface of the nanoparticles of oligothiophenes, leaving the core of the nanoparticle unchanged. Several highly interesting features have been detected, including their ability to photostimulate the retinal neurons, especially the inner retinal ones. HOF•CH₃CN was also used on elements other than carbon, such as selenium and phosphor. Various selenides were oxidized to the respective selenodioxide derivatives (not a trivial task), while various phosphines were converted efficiently to the corresponding phosphine oxides. Full article

ATP analogues are essential tools in enzymology and structural biology, but the structural and functional implications of their chemical modifications on nucleotide-binding proteins are often underappreciated. To address this, we evaluated a panel of ATP analogues, focusing on thiosubstituted and fluorinated molecules, using the AAA+ ATPase p97 as a benchmark system. Hydrolysis stability and impact on protein conformation, binding modes, and kinetics of enzymatic catalysis were assessed by protein-detected methyl NMR and ligand-detected ¹⁹F NMR in solution, as well as ³¹P solid-state NMR of nucleotides within protein sediments. ATPγS and AMP-PNP emerged as the most suitable analogues for preserving pre-hydrolysis states over extended periods, despite undergoing gradual hydrolysis. In contrast, both AMP-PCP and α/β-thiosubstituted analogues failed to induce native protein conformations in p97. Notably, we demonstrate a novel real-time NMR setup to explore the effect of nucleotide mixtures on cooperativity and the regulation of enzymes. Additionally, aromatic fluorine TROSY-based ¹⁹F NMR shows promise for direct ligand detection in solution, even in the context of large macromolecular complexes. These findings provide critical guidance for selecting ATP analogues in functional and structural studies of nucleotide-binding proteins. Full article

The U.S. Food and Drug Administration (FDA) has authorized 50 new drugs in 2024, which matches the average figure for recent years (2018–2023). The approval of 13 monoclonal antibodies (mAbs) sets a new record, with these molecules accounting for more than 25% of all drugs authorized this year. Three proteins have been added to the list of biologics, and with the inclusion of four TIDES (two oligonucleotides and two peptides), only one in three approved drugs this year is a small molecule. As of 2023, no antibody-drug conjugates (ADCs) have reached the market this year. Two deuterated drugs have been approved, bringing the total approvals for this class of compounds to four. This year saw the authorization of two more PEGylated drugs—both peptides—highlighting a renewed interest in this strategy for extending drug half-life, despite the setback caused by the withdrawal of peginesatide from the market in 2014 due to adverse side effects. N-aromatic heterocycles and fluorine atoms are present in two-thirds of all the small molecules approved this year. Herein, the 50 new drugs authorized by the FDA in 2024 are analyzed exclusively on the basis of their chemical structure. They are classified as the following: biologics (antibodies, proteins), TIDES (oligonucleotides and peptides), combined drugs, natural products, F-containing molecules, nitrogen aromatic heterocycles, aromatic compounds, and other small molecules. Full article