Detection of Aromatic Hydrocarbons in Aqueous Solutions Using Quartz Tuning Fork Sensors Modified with Calix[4]arene Methoxy Ester Self-Assembled Monolayers: Experimental and Density Functional Theory Study.

Quartz tuning forks (QTFs), which were coated with gold and with self-assembled monolayers (SAM) of a lower-rim functionalized calix[4]arene methoxy ester (CME), were used for the detection of benzene, toluene, and ethylbenzene in water samples. The QTF device was tested by measuring the respective frequency shifts obtained using small (100 µL) samples of aqueous benzene, toluene, and ethylbenzene at four different concentrations (10-12, 10-10, 10-8, and 10-6 M). The QTFs had lower limits of detection for all three aromatic hydrocarbons in the 10-14 M range, with the highest resonance frequency shifts (±5%) being shown for the corresponding 10-6 M solutions in the following order: benzene (199 Hz) > toluene (191 Hz) > ethylbenzene (149 Hz). The frequency shifts measured with the QTFs relative to that in deionized water were inversely proportional to the concentration/mass of the analytes. Insights into the effects of the alkyl groups of the aromatic hydrocarbons on the electronic interaction energies for their hypothetical 1:1 supramolecular host-guest binding with the CME sensing layer were obtained through density functional theory (DFT) calculations of the electronic interaction energies (ΔIEs) using B3LYP-D3/GenECP with a mixed basis set: LANL2DZ and 6-311++g(d,p), CAM-B3LYP/LANL2DZ, and PBE/LANL2DZ. The magnitudes of the ΔIEs were in the following order: [Au4-CME⊃[benzene] > [Au4-CME]⊃[toluene] > [Au4-CME]⊃[ethylbenzene]. The gas-phase BSSE-uncorrected ΔIE values for these complexes were higher, with values of -96.86, -87.80, and -79.33 kJ mol-1, respectively, and -86.39, -77.23, and -67.63 kJ mol-1, respectively, for the corresponding BSSE-corrected values using B3LYP-D3/GenECP with LANL2dZ and 6-311++g(d,p). The computational findings strongly support the experimental results, revealing the same trend in the ΔIEs for the proposed hypothetical binding modes between the tested analytes with the CME SAMs on the Au-QTF sensing surfaces.

Publisher Correction: Electronic structure of the parent compound of superconducting infinite-layer nickelates.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Electronic structure of the parent compound of superconducting infinite-layer nickelates.

The search continues for nickel oxide-based materials with electronic properties similar to cuprate high-temperature superconductors1-10. The recent discovery of superconductivity in the doped infinite-layer nickelate NdNiO2 (refs. 11,12) has strengthened these efforts. Here, we use X-ray spectroscopy and density functional theory to show that the electronic structure of LaNiO2 and NdNiO2, while similar to the cuprates, includes significant distinctions. Unlike cuprates, the rare-earth spacer layer in the infinite-layer nickelate supports a weakly interacting three-dimensional 5d metallic state, which hybridizes with a quasi-two-dimensional, strongly correlated state with [Formula: see text] symmetry in the NiO2 layers. Thus, the infinite-layer nickelate can be regarded as a sibling of the rare-earth intermetallics13-15, which are well known for heavy fermion behaviour, where the NiO2 correlated layers play an analogous role to the 4f states in rare-earth heavy fermion compounds. This Kondo- or Anderson-lattice-like 'oxide-intermetallic' replaces the Mott insulator as the reference state from which superconductivity emerges upon doping.

Plasma membrane damage repair is mediated by an acid sphingomyelinase in Entamoeba histolytica.

Entamoeba histolytica is a pathogen that during its infective process confronts the host defenses, which damages the amoebic plasma membrane (PM), resulting in the loss of viability. However, it is unknown whether amoebic trophozoites are able to repair their PM when it is damaged. Acid sphingomyelinases (aSMases) have been reported in mammalian cells to promote endocytosis and removal of PM lesions. In this work, six predicted amoebic genes encoding for aSMases were found to be transcribed in the HM1:IMSS strain, finding that the EhaSM6 gene is the most transcribed in basal growth conditions and rendered a functional protein. The secreted aSMase activity detected was stimulated by Mg+2 and inhibited by Co+2. Trophozoites that overexpress the EhaSM6 gene (HM1-SM6HA) exhibit an increase of 2-fold in the secreted aSMase activity. This transfectant trophozoites exposed to pore-forming molecules (SLO, Magainin, ß-Defensin 2 and human complement) exhibited an increase from 6 to 25-fold in the secreted aSMase activity which correlated with higher amoebic viability in a Ca+2 dependent process. However, other agents that affect the PM such as hydrogen peroxide also induced an increase of secreted aSMase, but to a lesser extent. The aSMase6 enzyme is N- and C-terminal processed. Confocal and transmission electron microscopy showed that trophozoites treated with SLO presented a migration of lysosomes containing the aSMase towards the PM, inducing the formation of membrane patches and endosomes in the control strain. These cellular structures were increased in the overexpressing strain, indicating the involvement of the aSMase6 in the PM injury repair. The pore-forming molecules induced an increase in the expression of EhaSM1, 2, 5 and 6 genes, meanwhile, hydrogen peroxide induced an increase in all of them. In all the conditions evaluated, the EhaSM6 gene exhibited the highest levels of induction. Overall, these novel findings show that the aSMase6 enzyme from E. histolytica promotes the repair of the PM damaged with pore-forming molecules to prevent losing cell integrity. This novel system could act when encountered with the lytic defense systems of the host.

Design and synthesis of 2-Substituted-4-benzyl-5-methylimidazoles as new potential Anti-breast cancer agents to inhibit oncogenic STAT3 functions.

STAT3 signaling is known to be associated with tumorigenesis and further cancer cell-intrinsic activation of STAT3 leads to altered regulation of several oncogenic processes. Given the importance of STAT3 in cancer development and progression particularly breast cancer, it is crucial to discover new chemical entities of STAT3 inhibitor to develop anti-breast cancer drug candidates. Herein, 4-benzyl-2-benzylthio-5-methyl-1H-imidazole (2a) and 4-benzyl-5-methyl-2-[(2,6-difluorobenzyl)thio]-1H-imidazole (2d) from a group of thirty imidazole-bearing compounds showed greater STAT3 inhibition than their lead compounds VS1 and the oxadiazole derivative MD77. Within all tested compounds, ten derivatives effectively inhibited the growth of the two tested breast cancer cells with IC50 values ranging from 6.66 to 26.02 µM. In addition, the most potent derivatives 2a and 2d inhibited the oncogenic function of STAT3 as seen in the inhibition of colony formation and IL-6 production of breast cancer cell lines. Modeling studies provided evidence for the possible interactions of the synthesized compounds with the key residues of the STAT3-SH2 domain. Collectively, our present study suggests 2-substituted-4-benzyl-5-methylimidazoles are a new class of anti-cancer drug candidates to inhibit oncogenic STAT3 function.

Demystifying and unravelling the molecular structure of the biopolymer sporopollenin.

RATIONALE: We report the unsolved molecular structure of the complex biopolymer sporopollenin exine extracted from Lycopodium clavatum pollen grains. METHODS: TOF-SIMS and CID-MS/MS, MALDI-TOF-MS and CID-TOF/TOF-MS/MS were used for the analysis of this complex biopolymer sporopollenin exine extracted from Lycopodium clavatum pollen grains. Solid-state 1 H- and 13 C-NMR, 2D 1 H-1 H NOESY, Rotor-synchronized 13 C{1 H} HSQC, and 13 C{1 H} multi CP-MAS NMR experiments were used to confirm the structural assigments revealed by MS and MS/MS studies. Finally, high-resolution XPS was used to check for the presence of aromatic components in sporopollenin. RESULTS: The combined MS and NMR analyses showed that sporopollenin contained poly(hydroxy acid) dendrimer-like networks with glycerol as a core unit, which accounted for the sporopollenin empirical formula. In addition, these analyses showed that the hydroxy acid monomers forming this network contained a ß-diketone moiety. Moreover, MALDI-TOF-MS and MS/MS allowed us to identify a unique macrocyclic oligomeric unit composed of polyhydroxylated tetraketide-like monomers. Lastly, high-resolution X-ray photoelectron spectroscopy (HR-XPS) showed the absence of aromaticity in sporopollenin. CONCLUSIONS: We report for the first time the two main building units that form the Lycopodium clavatum sporopollenin exine. The first building unit is a macrocyclic oligomer and/or polymer composed of polyhydroxylated tetraketide-like monomeric units, which represents the main rigid backbone of the sporopollenin biopolymer. The second building unit is the poly(hydroxy acid) network in which the hydroxyl end groups can be covalently attached by ether links to the hydroxylated macrocyclic backbone to form the sporopollenin biopolymer, a spherical dendrimer. Such spherical dendrimers are a typical type of microcapsule that have been used for drug delivery applications. Finally, HR-XPS indicated the total absence of aromaticity in the sporopollenin exine.

The local structure of self-doped BiS2-based layered systems as a function of temperature.

We have studied the local structure of layered Eu(La,Ce)FBiS2 compounds by Bi L3-edge extended X-ray absorption fine structure (EXAFS) measurements as a function of temperature. We find that the BiS2 sub-lattice is largely distorted in EuFBiS2, characterized by two different in-plane Bi-S1 distances. The distortion is marginally affected by partial substitutions of Ce (Eu0.5Ce0.5FBiS2) and La (Eu0.5La0.5FBiS2). The temperature dependence of the local structure distortion reveals an indication of possible charge density wave like instability in the pristine self-doped EuFBiS2 and Ce substituted Eu0.5Ce0.5FBiS2 while it is suppressed in La substituted Eu0.5La0.5FBiS2. In compounds with higher superconducting transition temperature, the axial Bi-S2 bond distance is elongated and the related bond stiffness decreased, suggesting some important role of this in the charge transfer mechanism for self-doping in the active BiS2-layer. In-plane Bi-S1 distances are generally softer than the axial Bi-S2 distance and they suffer further softening by the substitutions. The results are discussed in relation to an important role of the Bi defect chemistry driven asymmetric local environment in the physical properties of these materials.

Calix[3]arene-Analogous Metacyclophanes: Synthesis, Structures and Properties with Infinite Potential.

Calixarene-analogous metacyclophanes (CAMs) are a special class of cyclophanes that are cyclic polyaromatic hydrocarbons containing three or more aromatic rings linked by one or more methylene bridging groups. They can be considered to be analogues of calixarenes, since, in both types of molecules, the component aromatic rings are linked by methylene groups, which are meta to each other. Since the prototype or classical calix[4]arene consists of four benzene rings each linked by methylene bridges, which are also meta to each other, it can be considered to be an example of a functionalized [1.1.1.1]metacyclophane. A metacyclophane (MCP) that consists of three individual hydroxyl-group functionalized aromatic rings linked by methylene groups, e.g., a trihydroxy[1.1.1]MCP may therefore, by analogy, be termed in the broadest sense as a "calix[3]arene" or a "calix[3]arene-analogous metacyclophane". Most of the CAMs reported have been synthesized by fragment coupling approaches. The design, synthesis and development of functionalized CAMs, MCPs, calixarenes and calixarene analogues has been an area of great activity in the past few decades, due their potential applications as molecular receptors, sensors and ligands for metal binding, and for theoretical studies, etc. In this review article, we focus mainly on the synthesis, structure and conformational properties of [1.1.1]CAMs, i.e., "calix[3]arenes" and their analogues, which contain three functionalized aromatic rings and which provide new scaffolds for further explorations in supramolecular and sensor chemistry.

The reaction of arylmethyl isocyanides and arylmethylamines with xanthate esters: a facile and unexpected synthesis of carbamothioates.

An unexpected formation of carbamothioates by a sodium hydride-mediated reaction of arylmethyl isocyanides with xanthate esters in DMF is reported. The products thus obtained were compared with the carbamothioates obtained by the sodium hydride-mediated condensation of the corresponding benzylamines and xanthate esters in DMF. To account for these unexpected reactions, a mechanism is proposed in which the key steps are supported by quantum chemical calculations.

Decoupling Carrier Concentration and Electron-Phonon Coupling in Oxide Heterostructures Observed with Resonant Inelastic X-Ray Scattering.

We report the observation of multiple phonon satellite features in ultrathin superlattices of the form nSrIrO_{3}/mSrTiO_{3} using resonant inelastic x-ray scattering (RIXS). As the values of n and m vary, the energy loss spectra show a systematic evolution in the relative intensity of the phonon satellites. Using a closed-form solution for the RIXS cross section, we extract the variation in the electron-phonon coupling strength as a function of n and m. Combined with the negligible carrier doping into the SrTiO_{3} layers, these results indicate that the tuning of the electron-phonon coupling can be effectively decoupled from doping. This work both showcases a feasible method to extract the electron-phonon coupling in superlattices and unveils a potential route for tuning this coupling, which is often associated with superconductivity in SrTiO_{3}-based systems.

A Hexahomotrioxacalix[3]arene-Based Ditopic Receptor for Alkylammonium Ions Controlled by Ag⁺ Ions.

A receptor cone-1 based on a hexahomotrioxacalix[3]arene bearing three pyridyl groups was successfully synthesized, which has a C3-symmetric conformation and is capable of binding alkylammonium and metal ions simultaneously in a cooperative fashion. It can bind alkylammonium ions through the -cavity formed by three aryl rings. This behaviour is consistent with the cone-in/cone-out conformational rearrangement needed to reorganize the cavity for endo-complexation. As a C3-symmetrical pyridyl-substituted calixarene, receptor cone-1 can also bind an Ag⁺ ion, and the nitrogen atoms are turned towards the inside of the cavity and interact with Ag⁺. After complexation of tris(2-pyridylamide) derivative receptor cone-1 with Ag⁺, the original C3-symmetry was retained and higher complexation selectivity for n-BuNH3⁺ versus t-BuNH3⁺ was observed. Thus, it is believed that this receptor will have a role to play in the sensing, detection, and recognition of Ag⁺ and n-BuNH3+ ions.

Calixazulenes: azulene-based calixarene analogues - an overview and recent supramolecular complexation studies.

Some of the least studied calixarenes are those that consist of azulene rings bridged by -CH2- groups. Since Lash and Colby's discovery of a simple and convenient method for producing the parent all-hydrocarbon calix[4]azulene, there have been two other all-hydrocarbon calix[4]azulenes which have been synthesized in good yields by their method. This allowed studying their supramolecular properties. This report is of our latest work on the solution-state supramolecular complexation of one of these calix[4]azulenes, namely tetrakis(5,7-diphenyl)calix[4]azulene or "OPC4A", with several electron-deficient tetraalkyammonium salts. As a result of more recent methods developed by us and others employing Suzuki-Miyaura cross-coupling reactions to produce additional functionalized azulenes, the promise of further greater functionalized calixazulenes lies in store to be investigated.

Synthesis and conformations of [2.n]metacyclophan-1-ene epoxides and their conversion to [n.1]metacyclophanes.

A series of syn- and anti-[2.n]metacyclophan-1-enes have been prepared in good yields by McMurry cyclizations of 1,n-bis(5-tert-butyl-3-formyl-2-methoxyphenyl)alkanes. Significantly, acid catalyzed rearrangements of [2.n]metacyclophan-1-enes afforded [n.1]metacyclophanes in good yield. The ratios of the products are strongly regulated by the number of methylene bridges present. The percentages of the rearrangement products increase with increasing length of the carbon bridges. Characterization and the conformational studies of these products are described. Single crystal X-ray analysis revealed the adoption of syn- and anti-conformations. DFT calculations were carried out to estimate the energy-minimized structures of the synthesized metacyclophanes.

The thyroxine-containing thyroglobulin peptide (aa 2549-2560) is a target epitope in iodide-accelerated spontaneous autoimmune thyroiditis.

Enhanced iodide ingestion is known to accelerate the incidence and severity of spontaneous autoimmune thyroiditis [iodide-accelerated spontaneous autoimmune thyroiditis (ISAT)] in NOD.H2(h4) mice. CD4+ cells are required for the development and maintenance of ISAT, but their target epitopes remain unknown. In this study, we show that the previously identified thyroglobulin (Tg) T cell epitope p2549-2560 containing thyroxine at position 2553 (T4p2553) induces thyroiditis as well as strong specific T and B cell responses in NOD.H2(h4) mice. In ISAT, activated CD4+ T cells specific for T4p2553 are detected before the disease onset in thyroid-draining cervical lymph nodes only in mice placed on an iodide-rich diet and not in age-matched controls. In addition, selective enrichment of CD4+ IFN-γ+ T4p2553-specific cells is observed among cervical lymph node cells and intrathyroidal lymphocytes. T4p2553 was equally detectable on dendritic cells obtained ex vivo from cervical lymph node cells of NaI-fed or control mice, suggesting that the iodide-rich diet contributes to the activation of autoreactive cells rather than the generation of the autoantigenic epitope. Furthermore, spontaneous T4p2553-specific IgG are not detectable within the strong Tg-specific autoantibody response. To our knowledge, these data identify for the first time a Tg T cell epitope as a spontaneous target in ISAT.

A study of temperature dependent local atomic displacements in a Ba(Fe(1-x)Co(x))2As2 superconductor.

We have studied the local structure of a Ba(Fe(1-x)Co(x))2As2 superconductor using temperature dependent extended X-ray absorption fine structure (EXAFS) measurements. Polarized EXAFS at the Fe K-edge on an optimally doped (x = 0.06) single crystal has permitted us to determine atomic displacements across the superconducting transition temperature (T(c)). The Fe-As bondlength hardly shows any change with temperature; however, the Fe-Fe sublattice reveals a sharp anomaly across T(c), indicated by a significant drop in mean square relative displacements, similar to the one known for cuprates and A15-type superconductors. We have also found a large atomic disorder around the substituted Co, revealed by polarized Co K-edge EXAFS measurements. The Co-Fe/Co bonds are more flexible than the Fe-Fe bonds with the As-height in Co-containing tetrahedra being larger than the one in FeAs4. The results suggest that the local Fe-Fe bondlength fluctuations and the atomic disorder in this sub-lattice should have some important role in the superconductivity of Ba(Fe(1-x)Co(x))2As2 pnictides.

Synthesis and conformational studies of chiral macrocyclic [1.1.1]metacyclophanes containing benzofuran rings.

Macrocyclic [1.1.1]metacyclophanes (MCPs) containing benzene and benzofuran rings linked by methylene bridges and which can be viewed as calixarene analogues, have been synthesized by demethylation of [3.3.1]MCP-diones with trimethylsilyl iodide (TMSI) in MeCN. The [3.3.1]MCP-diones are synthesized by using (p-tolylsulfonyl)methyl isocyanide (TosMIC) as the cyclization reagent in N,N-dimethylformamide (DMF) with an excess of sodium hydride. (1)H NMR spectroscopy revealed that the remaining hydroxyl group on the phenyl ring is involved in intramolecular hydrogen bonding with the oxygen of one of the benzofuran rings. O-Methylation at the lower rim of monohydroxy[1.1.1]MCP in the presence of K2CO3 in acetone afforded a novel and inherently chiral calixarene analogue, namely the macrocyclic [1.1.1]MCP, possessing C1 symmetry. The inherent chirality of the two conformers was characterized by (1)H NMR spectroscopy by addition of an excess of Pirkle's chiral shift reagent, which caused a splitting of the corresponding methylene protons to AB patterns. Single crystal X-ray analysis revealed the adoptation of a hemisphere-shaped cone isomer. DFT calculations were carried out to investigate the energy-minimized structures and the hydrogen bonds of the synthesized MCPs.

The first study about the relationship between the extractability of thiacalix[4]arene derivatives and the position of the coordination binding sites.

Three organic ionophores (2-4) based on the p-tert-butylthiacalix[4]arene backbone, blocked in the 1,3-alternate conformation, bearing two pyridyl coordinating moieties (ortho for 2, meta for 3 and para for 4), have been synthesized and characterized in the solid state. The solvent extraction experiments with the metal ions showed that the ability of these derivatives to complex with Ag(+) appeared to be largely dependent on the position of the nitrogen atoms of the pyridyl ring. Two different complexation modes have been confirmed by 1H NMR titration. Ionophore 2 armed with two pyridyl moieties, complexed with Ag(+) cation through N···Ag(+)···S interactions; however, ionophore 3 and ionophore 4 complexed with Ag(+) through metal-nitrogen (N···Ag(+)) interactions. The DFT computational studies were consistent with the experimental findings. These findings will provide us with an important rule to design an appropriate thiacalix[4]arene ionophore in the future. Another study on the possibility for application of ionophores 2-4 for the treatment of waste water containing Cr(VI) and Cr(III), showed that ionophore 3 was useful in the application of the solvent extraction method in selective treatment of waste water containing Cr(VI) and Cr(III) prior to discharge.

The nanoscale structure and unoccupied valence electronic states in FeSe1-xTex chalcogenides probed by X-ray absorption measurements.

We have studied the nanoscale structure and unoccupied electronic states in FeSe1-xTex by a combined analysis of Se K, Te L1 and Fe K-edges X-ray absorption measurements. Extended X-ray absorption fine structure (EXAFS) results show that iron-chalcogen (Fe-Se and Fe-Te) distances in ternary FeSe1-xTex are similar to those measured for binary FeSe and FeTe. The local Fe-Se/Te distances determined by different absorption edges fit well in the characteristic Z-plot of random alloys, providing unambiguous support to the inhomogeneous nanoscale structure of the ternary FeSe1-xTex system. X-ray absorption near-edge structure (XANES) spectra reveal a gradual evolution of the unoccupied valence electronic states as a function of Te-substitution in FeSe1-xTex. The Fe 3d-Se 4p/Te 5p hybridization is found to decrease with Te-substitution, accompanied by an increase in unoccupied Se 4p states and a decrease in unoccupied Te 5p states. The results are discussed in the frame of local inhomogeneity in the FeSe1-xTex system driven by random alloying of Se/Te atoms.

The effect of RE substitution in layered REO(0.5)F(0.5)BiS2: chemical pressure, local disorder and superconductivity.

We have studied the effect of RE substitution on the structure and the local atomic disorder in REO0.5F0.5BiS2 (RE = rare-earth) to understand their correlation with the bulk superconductivity in these materials. The mean RE size, affecting the chemical pressure, has been varied in two series namely Ce1-xNdxO0.5F0.5BiS2 and Nd1-ySmyO0.5F0.5BiS2. The lattice parameters evolve anomalously, showing an anisotropic shrinkage (elongation) of the c-axis (a-axis) to an isotropic expansion of the lattice with increasing mean RE size. The Bi L3-edge extended X-ray absorption fine structure (EXAFS) measurements are performed to investigate local displacements in the BiS2 lattice, revealing a large disorder and a sharp boundary between the Ce-containing and Sm-containing series with a distinct local structure. The results suggest that the bulk superconductivity in REO0.5F0.5BiS2 is correlated with anomalous atomic displacements in the Bi-S1 network, likely to be a combined effect of active Bi 6s electronic states and a possible Jahn-Teller-like instability of the Bi 6px/6py electrons.

Identification of the Thermal Activation Network in Human 15-Lipoxygenase-2: Divergence from Plant Orthologs and Its Relationship to Hydrogen Tunneling Activation Barriers.

The oxidation of polyunsaturated fatty acids by lipoxygenases (LOXs) is initiated by a C-H cleavage step in which the hydrogen atom is transferred quantum mechanically (i.e., via tunneling). In these reactions, protein thermal motions facilitate the conversion of ground-state enzyme-substrate complexes to tunneling-ready configurations and are thus important for transferring energy from the solvent to the active site for the activation of catalysis. In this report, we employed temperature-dependent hydrogen-deuterium exchange mass spectrometry (TDHDX-MS) to identify catalytically linked, thermally activated peptides in a representative animal LOX, human epithelial 15-LOX-2. TDHDX-MS of wild-type 15-LOX-2 was compared to two active site mutations that retain structural stability but have increased activation energies (Ea) of catalysis. The Ea value of one variant, V427L, is implicated to arise from suboptimal substrate positioning by increased active-site side chain rotamer dynamics, as determined by X-ray crystallography and ensemble refinement. The resolved thermal network from the comparative Eas of TDHDX-MS between wild-type and V426A is localized along the front face of the 15-LOX-2 catalytic domain. The network contains a clustering of isoleucine, leucine, and valine side chains within the helical peptides. This thermal network of 15-LOX-2 is different in location, area, and backbone structure compared to a model plant lipoxygenase from soybean that exhibits a low Ea value of catalysis compared to the human ortholog. The presented data provide insights into the divergence of thermally activated protein motions in plant and animal LOXs and their relationships to the enthalpic barriers for facilitating hydrogen tunneling.