Metal Propionate Solutions for High-Throughput Liquid-Assisted Manufacturing of Superconducting REBa2Cu3O7-δ (RE = Y, Gd, Sm, and Yb) Films.

The cost-effective synthesis of a series of metal propionate powders (copper, yttrium, barium, samarium, gadolinium, and ytterbium) is developed through single chemical reactions resulting in five novel crystalline forms. These complexes are valuable precursors for the preparation of epitaxial REBa2Cu3O7-δ (REBCO) superconducting films (here, RE = Y, Sm, Gd, and Yb) through the innovative transient liquid-assisted growth (TLAG) process based on chemical solution deposition (CSD). TLAG-CSD shows impressive results with YBa2Cu3O7-δ (YBCO), obtaining critical current densities of 2.6 MA/cm2 (77 K) on 500 nm films at unprecedented growth rates (50-2000 nm/s), boosting unprecedented high-throughput industrial production. With a cardinal concern on designing the pyrolysis toward optimal nanocrystalline films for TLAG, an analysis of the thermal behavior of the synthesized precursors is essential. Decomposition pathways for each metal propionate are established, and compatibility with TLAG-CSD is corroborated. Metal-organic solutions for these REBCO systems are successfully prepared, and their rheological properties and thermal behavior are analyzed. This work demonstrates homogeneous nanocrystalline films through propionate-based REBCO precursor solutions, including several rare-earth ions, which display exemplary chemical and microstructural characteristics crucial for TLAG, and provides a base for a wide variety of CSD-based functional oxides.

Exploring ortho-dianthrylbenzenes for molecular solar thermal energy storage.

Molecular solar thermal systems, which absorb light, store it, and release it as heat, have been extensively researched, yet many potential candidates remain unexplored. To expand this range, five specifically designed ortho-dianthrylbenzenes were investigated. Anthracene dimers have been underexplored due to issues like photooxidation and varying photodimerization efficiency. The presented systems address these challenges by aryl-linking two anthracene moieties, achieving photodimerization quantum yields ranging from 11.5% to 16% in mesitylene. The impact of donor or acceptor groups on energy storage time (9-37 years), energy storage density (0.14-0.2 MJ kg-1), and solar energy storage efficiency (0.38-0.66%) was evaluated. The experimental results, supported by density functional theory-based modeling, highlight the potential of anthracene-based photoswitches for molecular solar thermal applications and encourage further exploration of similar systems.

Direct Synthesis of 2-Hydroxytrifluoroethylacetophenones via Organophotoredox-Mediated Net-Neutral Radical/Polar Crossover.

Alkene difunctionalization is a very attractive tool in synthetic organic chemistry. Herein, we disclose an operationally and practically simple method to access 2-hydroxytrifluoroethylacetophenones from styrene derivatives via photoredox catalysis. This light-mediated transformation promotes the generation of the 1-hydroxy-2,2,2-trifluoroethyl carbon-centered radical as key synthon, which undergoes Giese addition with styrenes followed by a Kornblum oxidation process. The presented method is not only mild and cost-effective, but also utilizes an organic photocatalyst and DMSO as oxidant. Experimental investigations support the operative mechanism via net-neutral radical/polar crossover.

Using electric fields to control insects: current applications and future directions.

Chemical-based interventions are mostly used to control insects that are harmful to human health and agriculture or that simply cause a nuisance. An overreliance on these insecticides however raises concerns for the environment, human health, and the development of resistance, not only in the target species. As such, there is a critical need for the development of novel nonchemical technologies to control insects. Electrocution traps using UV light as an attractant are one classical nonchemical approach to insect control but lack the specificity necessary to target only pest insects and to avoid harmless or beneficial species. Here we review the fundamental physics behind electric fields (EFs) and place them in context with electromagnetic fields more broadly. We then focus on how novel uses of strong EFs, some of which are being piloted in the field and laboratory, have the potential to repel, capture, or kill (electrocute) insects without the negative side effects of other classical approaches. As EF-insect science remains in its infancy, we provide recommendations for future areas of research in EF-insect science.

Cocrystallization of Antifungal Compounds Mediated by Halogen Bonding.

The application of halogen bonding in pharmaceutical chemistry remains a challenge. In this work, novel halogen-bonded cocrystals based on azole antifungal active pharmaceutical ingredients (APIs) and the ditopic molecule 1,4-diiodotetrafluorobenzene are reported. Their crystal structural features, spectroscopic properties, and thermal stability were studied. The components are bound through I···N from the triazole moieties present in all of the compounds. The molecular electrostatic potential (MEP) surfaces and quantum theory of atoms in molecules (QTAIM) calculations are used to rationalize the presence of hydrogen and halogen bonds in the resulting structures and their energetic analysis. The relative halogen bond ability of the different groups of voriconazole, fluconazole, and itraconazole was analyzed using MEP surfaces, demonstrating this approach to be an interesting tool to predict halogen-bonding preferences.

Air- and Water-Stable Heteroleptic Copper (I) Complexes Bearing Bis(indazol-1-yl)methane Ligands: Synthesis, Characterisation, and Computational Studies.

A series of four novel heteroleptic Cu(I) complexes, bearing bis(1H-indazol-1-yl)methane analogues as N,N ligands and DPEPhos as the P,P ligand, were synthesised in high yields under mild conditions and characterised by spectroscopic and spectrometric techniques. In addition, the position of the carboxymethyl substituent in the complexes and its effect on the electrochemical and photophysical behaviour was evaluated. As expected, the homoleptic copper (I) complexes with the N,N ligands showed air instability. In contrast, the obtained heteroleptic complexes were air- and water-stable in solid and solution. All complexes displayed green-yellow luminescence in CH2Cl2 at room temperature due to ligand-centred (LC) phosphorescence in the case of the Cu(I) complex with an unsubstituted N,N ligand and metal-to-ligand charge transfer (MLCT) phosphorescence for the carboxymethyl-substituted complexes. Interestingly, proper substitution of the bis(1H-indazol-1-yl)methane ligand enabled the achievement of a remarkable luminescent yield (2.5%) in solution, showcasing the great potential of this novel class of copper(I) complexes for potential applications in luminescent devices and/or photocatalysis.

A novel series of pyrazole derivatives toward biological applications: experimental and conceptual DFT characterization.

A new series of 13 pyrazole-derivative compounds with potential antifungal activity were synthetized with good yields. The series have the (E)-2-((1-(R)-3,5-dimethyl-1H-pyrazol-4-yl)diazenyl)phenol general structure and were characterized by means of X-ray diffraction, UV-Vis, FTIR, 1H-NMR, 13C-NMR, and two-dimensional NMR experiments. This experimental characterization was complemented by DFT simulations. A deep insight regarding molecular reactivity was accomplished employing a conceptual DFT approach. In this sense, dual descriptors were calculated at HF and DFT level of theory and GGV spin-density Fukui functions. The main reactive region within the molecules was mapped through isosurface and condensed representations. Finally, chemical descriptors that have previously shown to be close related to biological activity were compared within the series. Thus, higher values of chemical potential ω and electrophilicity χ obtained for compounds 10, 9, 8, 6 and 7, in this order, suggest that these molecules are the better candidates as biological agents.

Uracil Derivatives for Halogen-Bonded Cocrystals.

Among non-covalent interactions, halogen bonding is emerging as a new powerful tool for supramolecular self-assembly. Here, along with a green and effective method, we report three new halogen-bonded cocrystals containing uracil derivatives and 1,2,4,5-tetrafluoro-3,6-diiodobenzene as X-bond donor coformer. These multicomponent solids were prepared both by solvent-drop grinding and solution methods and further characterized by powder and single-crystal X-ray diffraction, Fourier-transformed infrared spectroscopy, and thermal methods (TGA-DSC). In order to study the relative importance of hydrogen versus halogen bonds in the crystal packing, computational methods were applied.

Benzofuranyl-2-imidazoles as imidazoline I2 receptor ligands for Alzheimer's disease.

Recent findings unveil the pharmacological modulation of imidazoline I2 receptors (I2-IR) as a novel strategy to face unmet medical neurodegenerative diseases. In this work, we report the chemical characterization, three-dimensional quantitative structure-activity relationship (3D-QSAR) and ADMET in silico of a family of benzofuranyl-2-imidazoles that exhibit affinity against human brain I2-IR and most of them have been predicted to be brain permeable. Acute treatment in mice with 2-(2-benzofuranyl)-2-imidazole, known as LSL60101 (garsevil), showed non-warning properties in the ADMET studies and an optimal pharmacokinetic profile. Moreover, LSL60101 induced hypothermia in mice while decreased pro-apoptotic FADD protein in the hippocampus. In vivo studies in the familial Alzheimer's disease 5xFAD murine model with the representative compound, revealed significant decreases in the protein expression levels of antioxidant enzymes superoxide dismutase and glutathione peroxidase in hippocampus. Overall, LSL60101 plays a neuroprotective role by reducing apoptosis and modulating oxidative stress.

Tryptophanol-Derived Oxazolopyrrolidone Lactams as Potential Anticancer Agents against Gastric Adenocarcinoma.

Gastric cancer is one of the deadliest cancers in modern societies, so there is a high level of interest in discovering new drugs for this malignancy. Previously, we demonstrated the ability of tryptophanol-derived polycyclic compounds to activate the tumor suppressor protein p53, a relevant therapeutic target in cancer. In this work, we developed a novel series of enantiomerically pure tryptophanol-derived small molecules to target human gastric adenocarcinoma (AGS) cells. From an initial screening of fourteen compounds in AGS cell line, a hit compound was selected for optimization, leading to two derivatives selective for AGS gastric cells over other types of cancer cells (MDA-MB-231, A-549, DU-145, and MG-63). More importantly, the compounds were non-toxic in normal cells (HEK 293T). Additionally, we show that the growth inhibition of AGS cells induced by these compounds is mediated by apoptosis. Stability studies in human plasma and human liver microsomes indicate that the compounds are stable, and that the major metabolic transformations of these molecules are mono- and di-hydroxylation of the indole ring.

Studies on the Enantioselective Synthesis of E-Ethylidene-bearing Spiro[indolizidine-1,3'-oxindole] Alkaloids.

A synthetic route for the enantioselective construction of the tetracyclic spiro[indolizidine-1,3'-oxindole] framework present in a large number of oxindole alkaloids, with a cis H-3/H-15 stereochemistry, a functionalized two-carbon substituent at C-15, and an E-ethylidene substituent at C-20, is reported. The key steps of the synthesis are the generation of the tetracyclic spirooxindole ring system by stereoselective spirocyclization from a tryptophanol-derived oxazolopiperidone lactam, the removal of the hydroxymethyl group, and the stereoselective introduction of the E-ethylidene substituent by acetylation at the α-position of the lactam carbonyl, followed by hydride reduction and elimination. Following this route, the 21-oxo derivative of the enantiomer of the alkaloid 7(S)-geissoschizol oxindole has been prepared.

Characterization of crystalline forms of gaxilose, a diagnostic drug.

Lactose intolerance is a pathology caused by lactase enzyme deficiency, usually produced in the intestinal cells provoking symptoms as abdominal pain, bloating, diarrhea, gas and nausea. Gaxilose, 4-O-ß-D galactopyranosyl-d-xylose, is used as a diagnostic drug for a non-invasive method for hypolactasia diagnosis. To date, no definitive guide for identifying gaxilose and distinguishing between crystalline forms is available. Data have been collected from a number of different analytical techniques in order to provide a full characterization of the compound and a simple method to discriminate between two solid forms.

Lead(ii) coordination polymers driven by pyridine-hydrazine donors: from anion-guided self-assembly to structural features.

In this work, we report extensive experimental and theoretical investigations on a new series of PbII coordination polymers exhibiting extended supramolecular architectures, namely [Pb2(LI)(NCS)4]n (1), [Pb(HLII)I2]n (2), [Pb(LIII)I]n (3) and [Pb(HLIV)(NO3)2]n·nMeOH (4), which were self-assembled from different PbII salts and various pyridine-hydrazine based linkers, namely 1,2-bis(pyridin-3-ylmethylene)hydrazine (LI), (pyridin-4-ylmethylene)isonicotinohydrazide (HLII), 1-(pyridin-2-yl)ethylidenenicotinohydrazide (HLIII) and phenyl(pyridin-2-yl)methylenenicotinohydrazide (HLIV), respectively. It is recognized that the origin of self-assembling is fundamentally rooted in a dual donor (6s2/6p0 hybridized lone electron pair) and electrophilic behaviour of PbII. This allows production of extended topologies from a 1D polymeric chain in 4 through a 2D layer in 2 to the 3D frameworks in 1 and 3, predominantly due to the cooperative action of both covalent and non-covalent tetrel interactions of the overall type Pb-X (X = O, N, S, I). Counterintuitively, the latter, seemingly weak interactions, have appeared to be even stronger than the typical covalent bonds due to the presence of a bunch of supportive London dispersion dominated contacts: ππ, Lpπ, C-HO, C-HI, C-HH-C as well as more typical mainly electrostatically driven N-HO or N/O-HO hydrogen bonds. It is revealed that the constituting generally strong tetrel type Pb-X (X = O, N, S, I) bonds, though dominated by a classic Coulomb term, are therefore characterized by a very important London dispersion constituent, extremely strong relativistic effects and the two way dative-covalent Pb ↔ X electron charge delocalization contribution as revealed by the Extended Transition State Natural Orbital for Chemical Valence (ETS-NOCV) charge and energy decomposition scheme. It unravels that the pyridine-hydrazine linkers are also excellent London dispersion donors, and that together with the donor-acceptor properties of the heavy (relativistic) PbII atoms and nucleophilic counterions lead to extended self-assembling of 1-4.

New Sensitive and Selective Chemical Sensors for Ni2+ and Cu2+ Ions: Insights into the Sensing Mechanism through DFT Methods.

We report the synthesis and theoretical study of two new colorimetric chemosensors with special selectivity and sensitivity to Ni2+ and Cu2+ ions over other metal cations in the CH3CN/H2O solution. Compounds (E)-4-((2-nitrophenyl)diazenyl)-N,N-bis(pyridin-2-ylmethyl)aniline (A) and (E)-4-((3-nitrophenyl)diazenyl)-N,N-bis(pyridin-2-ylmethyl)aniline (B) exhibited a drastic color change from yellow to colorless, which allows the detection of the mentioned metal cations through different techniques. The interaction of sensors with these metal ions induced a new absorption band with a hypsochromic shift to the characteristic signal of the free sensors. A theoretical study via time-dependent density functional theory (TD-DFT) was performed. This method has enabled us to reproduce the hypsochromic shift in the maximum UV-vis absorption band and explain the selective sensing of the ions. For all of the systems studied, the absorption band is characterized by a π → π* transition centered in the ligand. Instead of Ni2+ and Cu2+ ions, the transition is set toward the σ* molecular orbital with a strong contribution of the 3dx2-y2 transition (π → 3dx2-y2). These absorptions imply a ligand-to-metal charge transfer (LMCT) mechanism that results in the hypsochromic shift in the absorption band of these systems.

Identification of tetracyclic lactams as NMDA receptor antagonists with potential application in neurological disorders.

N-Methyl-d-aspartate receptors (NMDARs) are crucial for the normal function of the central nervous system (CNS), and fundamental in memory and learning-related processes. The overactivation of these receptors is associated with numerous neurodegenerative and psychiatric disorders. Therefore, NMDAR is considered a relevant therapeutic target for many CNS disorders. Herein, we report the synthesis and pharmacological evaluation of a new scaffold with antagonistic activity for NMDAR. Specifically, a chemical library of eighteen 1-aminoindan-2-ol tetracyclic lactams was synthesized and screened as NMDAR antagonists. The compounds were obtained by chiral pool synthesis using enantiomerically pure 1-aminoindan-2-ols as chiral inductors, and their stereochemistry was proven by X-ray crystallographic analysis of two target compounds. Most compounds reveal NMDAR antagonism, and eleven compounds display IC50 values in a Ca2+ entry-sensitive fluo-4 assay in the same order of magnitude of memantine, a clinically approved NMDAR antagonist. Docking studies suggest that the novel compounds can act as NMDAR channel blockers since there is a compatible conformation with MK-801 co-crystallized with NMDAR channel. In addition, we show that the tetracyclic 1-aminoindan-2-ol derivatives are brain permeable and non-toxic, and we identify promising hits for further optimization as modulators of the NMDAR function.

Bicyclic α-Iminophosphonates as High Affinity Imidazoline I2 Receptor Ligands for Alzheimer's Disease.

Imidazoline I2 receptors (I2-IR), widely distributed in the CNS and altered in patients that suffer from neurodegenerative disorders, are orphans from a structural point of view, and new I2-IR ligands are urgently required for improving their pharmacological characterization. We report the synthesis and three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of a new family of bicyclic α-iminophosphonates endowed with relevant affinities for human brain I2-IR. Acute treatment in mice with a selected compound significantly decreased Fas-associated protein with death domain (FADD) in the hippocampus, a key signaling mediator of neuroprotective actions. Additionally, in vivo studies in the familial Alzheimer's disease 5xFAD murine model revealed beneficial effects in behavior and cognition. These results are supported by changes in molecular pathways related to cognitive decline and Alzheimer's disease. Therefore, bicyclic α-iminophosphonates are tools that may open new therapeutic avenues for I2-IR, particularly for unmet neurodegenerative conditions.

Synthesis, reactivity, X-ray characterization and docking studies of N7/N9-(2-pyrimidyl)-adenine derivatives.

The reaction of adenine with 2-chloropyrimidine yields as a major product the unexpected N7-(2-pyrimidyl)-adenine (1) and as a minor one N9-(2-pyrimidyl)-adenine (2). Both compounds have been characterized by X-ray diffraction analysis. Moreover, we report the formation of a 1:1 co-crystal (3) composed by compound (1) and adenine that was formed serendipitously during the synthesis of (1). Unexpectedly, the treatment of (1) with Brönsted acids like HCl or HNO3 causes the opening of the imidazole ring of the N7-substituted adenine, yielding N5-(pyrimidin-2-yl)pyrimidine-4,5,6-triamine (4-7) which we have X-ray characterized in its neutral, (4), monoprotonated [nitrate salt (6)] and diprotonated forms [hydrochloride salt (5) and, also, a tetrachlorozincate salt (7)]. Finally, we have used compound (5) as ligand to synthesize and X-ray characterize its complexes with Ir(III) and Ag(I) (compounds (8) and (9), respectively), where the latter is a 2D coordination polymer and the former is a discrete mononuclear complex. We have studied the supramolecular assemblies formed in the solid state by using density functional theory (DFT) calculations. Finally, DNA-docking studies of several compounds have been carried out in order to analyze their ability to interact with the DNA.

Topochemical nitridation of Sr2FeMoO6.

The topotactic nitridation of cation ordered, tetragonal Sr2FeMoO6 in NH3 at moderate temperatures leads to cubic, Fm3[combining macron]m double perovskite oxynitride Sr2FeMoO4.9N1.1 where double-exchange interactions determine ferromagnetic order with TC ≈ 100 K. Substitution of oxide by nitride induces bond asymmetries and local electronically driven structural distortions, which combined with Fermi level lowering restricts charge itinerancy to confined regions and preclude spontaneous long-range magnetic order. Under a magnetic field, ferromagnetic correlations expand, favoring charge delocalization and a negative magnetoresistance is observed.

A Straightforward Synthesis of Functionalized cis-Perhydroisoquinolin-1-ones.

Base-catalyzed annulation reactions of 5,6-dihydro-2(1H)-pyridones with Nazarov-type reagents are reported. The effect of the solvent polarity and the concentration of the reagents is studied. The process involves two successive Michael additions and stereoselectively provides functionalized cis-perhydroisoquinolin-1-ones.