Members Of Series Research Articles

Cr silicate as a prototype for engineering magnetic phases in air-stable two-dimensional transition-metal silicates

Identifying environmentally inert, ferromagnetic two-dimensional (2D) materials with high Curie temperatures (T c) down to the single layer limit has been an obstacle to fundamental studies of 2D magnetism and application of 2D heterostructures to spin-polarized devices. To address this challenge, the growth, structure and magnetic properties of a 2D Cr-silicate single layer on Pt(111) was investigated experimentally and theoretically. The layer was grown by sequentially depositing SiO and Cr followed by annealing in O2. Scanning tunneling microscopy (STM), low-energy electron diffraction (LEED), and low energy electron microscopy all indicated a well-ordered layer that uniformly covered the surface, with STM and LEED indicating that the silicate relaxed to its favored lattice constant. Further experimental characterizations demonstrated that the Cr was nominally 3+ but with a lower electron density than typical trivalent Cr compounds. Comparison with theory identified a Cr2Si2O9 structure that resembles a single layer of a dehydrogenated dioctahedral silicate. Magnetic circular dichroism in x-ray absorption spectroscopy revealed a ferromagnetically ordered state up to at least 80 K. Theoretical analysis revealed that the Cr in a dehydrogenated Cr-silicate/Pt(111) is more oxidized than Cr in freestanding Cr2Si2O9H4 layers. This greater oxidation was found to enhance ferromagnetic coupling and suggests that the magnetism may be tuned by doping. The 2D Cr-silicate is the first member of a broad series of possible layered first-row transition metal silicates with magnetic order; thus, this paper introduces a new platform for investigating 2D ferromagnetism and the development of magnetoelectronic and spintronic devices by stacking 2D atomic layers.

A Pyridyl-Furan Series Developed from the Open Global Health Library Block Red Blood Cell Invasion and Protein Trafficking in Plasmodium falciparum through Potential Inhibition of the Parasite's PI4KIIIB Enzyme.

With the resistance increasing to current antimalarial medicines, there is an urgent need to discover new drug targets and to develop new medicines against these targets. We therefore screened the Open Global Health Library of Merck KGaA, Darmstadt, Germany, of 250 compounds against the asexual blood stage of the deadliest malarial parasite Plasmodium falciparum, from which eight inhibitors with low micromolar potency were found. Due to its combined potencies against parasite growth and inhibition of red blood cell invasion, the pyridyl-furan compound OGHL250 was prioritized for further optimization. The potency of the series lead compound (WEHI-518) was improved 250-fold to low nanomolar levels against parasite blood-stage growth. Parasites selected for resistance to a related compound, MMV396797, were also resistant to WEHI-518 as well as KDU731, an inhibitor of the phosphatidylinositol kinase PfPI4KIIIB, suggesting that this kinase is the target of the pyridyl-furan series. Inhibition of PfPI4KIIIB blocks multiple stages of the parasite's life cycle and other potent inhibitors are currently under preclinical development. MMV396797-resistant parasites possess an E1316D mutation in PfPKI4IIIB that clusters with known resistance mutations of other inhibitors of the kinase. Building upon earlier studies that showed that PfPI4KIIIB inhibitors block the development of the invasive merozoite parasite stage, we show that members of the pyridyl-furan series also block invasion and/or the conversion of merozoites into ring-stage intracellular parasites through inhibition of protein secretion and export into red blood cells.

Petrological Traverse of the Olivine Cumulate Séítah Formation at Jezero Crater, Mars: A Perspective From SuperCam Onboard Perseverance

AbstractSéítah is the stratigraphically lowest formation visited by Perseverance in the Jezero crater floor. We present the data obtained by SuperCam: texture by imagery, chemistry by Laser‐Induced Breakdown Spectroscopy, and mineralogy by Supercam Visible and Infrared reflectance and Raman spectroscopy. The Séítah formation consists of igneous, weakly altered rocks dominated by millimeter‐sized grains of olivine with the presence of low‐Ca and high‐Ca pyroxenes, and other primary minerals (e.g., plagioclase, Cr‐Fe‐Ti oxides, phosphates). Along a ∼140 m long section in Séítah, SuperCam analyses showed evidence of geochemical and mineralogical variations, from the contact with the overlying Máaz formation, going deeper in the formation. Bulk rock and olivine Mg#, grain size, olivine content increase gradually further from the contact. Along the section, olivine Mg# is not in equilibrium with the bulk rock Mg#, indicating local olivine accumulation. These observations are consistent with Séítah being the deep ultramafic member of a cumulate series derived from the fractional crystallization and slow cooling of the parent magma at depth. Possible magmatic processes and exhumation mechanisms of Séítah are discussed. Séítah rocks show some affinity with some rocks at Gusev crater, and with some Martian meteorites suggesting that such rocks are not rare on the surface of Mars. Séítah is part of the Nili Fossae regional olivine‐carbonate unit observed from orbit. Future exploration of Perseverance on the rim and outside of the crater will help determine if the observations from the crater floor can be extrapolated to the whole unit or if this unit is composed of distinct sub‐units with various origins.

Aromaticity of Osmaacenes in Their Lowest-Lying Singlet and Triplet States.

The aromatic character of a series of osmaacenes in their lowest-lying singlet and triplet states was thoroughly examined by means of the magnetically induced current densities and multicentre delocalization indices (MCIs). Both employed approaches agree that the osmabenzene molecule (OsB) in the S0 state exhibits dominant π-Hückel-type aromatic character, with a small but nonnegligible amount of π-Craig-Möbius aromaticity. Contrary to benzene, which is antiaromatic in the T1 state, OsB preserves some of its aromaticity in the T1 state. In higher members of the osmaacene series in the S0 and T1 states, the central Os-containing ring becomes nonaromatic, acting as a barrier between the two side polyacenic units which, on the other hand, exhibit a significant extent of π-electron delocalization.

АВТОРСЬКА ІНТУЇЦІЯ ТА ІНТРОСПЕКЦІЯ В ПРОЦЕСІ ФОРМУВАННЯ ТА РЕАЛІЗАЦІЇ СИНОНІМІЧНИХ СТРУКТУР (на матеріалі сучасної французької художньої прози)

The article studies intuitive mechanisms of sublinguistic schemes, primary structures and synonymic transforms formation in modern French fiction and mechanisms of synonymic preferential options actualization in correlation with the (auto)observation. This led to the use of the introspection method, the procedure of inverse reconstruction (discourse → language) of virtual (linguistic) transformational processes and the “alternative” linguistic experiment consisting in the artificial substitution of some utterance by a synonymic one. The goal of the article is to study intuitive mechanisms of synonymic constructions creation and realization in correlation with the observation of the facts and events of the real world and the introspection, alongside with the inverse reconstruction of the virtual transformational processes as an “alternative” linguistic experiment strategy. In the course of analysis we have found that the prearranged situation correlates with the addresser’s observation of the facts of reality, and that the mechanisms of prelinguistic, linguistic and discourse intuitions work at the level of three components of G. Guillaume’s speech act causation – mental operations → language → discourse, that is in the process of unconscious, subconscious and conscious activity of psychomechanisms (cognitive polyoperations) – and correlate with the introspection. It was proved that formation, exteriorization and interiorization of synonymic discourse innovations is the bidirectional process. The addressee reveals the author’s communicative intention to simplify or to complicate the information and the peculiarities of his/her idiostyle through two stages of the “alternative” linguistic experiment. First stage is an inverse reconstruction of the primary structure and extended, reduced and equal by quantity ludic and non-ludic synonymic transformants (microfields) of the functional-semantic macrofield virtual synonymic series by means of exteriorized synonymic discourse innovations observation and interiorization as a result of the author’s observation of facts of objective reality – introspection which cover the prelinguistic, linguistic and discursive intuitions. Second stage is to determine the degree of co(n)textual (linguistic and / or situational) pertinence of each member in synonymic series and to justify preferential option co(n)textual adequation. It was revealed that the inverse reconstruction is possible to realize only up to the primary structure which is formed in the process of the conscious activity of psychomechanisms because the pre-linguistic cognitive polyoperations and subconscious sublinguistic schemes aren’t available for the analysis of information recipient.

Discovery and Validation of the Binding Poses of Allosteric Fragment Hits to Protein Tyrosine Phosphatase 1b: From Molecular Dynamics Simulations to X-ray Crystallography.

Fragment-based drug discovery has led to six approved drugs, but the small sizes of the chemical fragments used in such methods typically result in only weak interactions between the fragment and its target molecule, which makes it challenging to experimentally determine the three-dimensional poses fragments assume in the bound state. One computational approach that could help address this difficulty is long-timescale molecular dynamics (MD) simulations, which have been used in retrospective studies to recover experimentally known binding poses of fragments. Here, we present the results of long-timescale MD simulations that we used to prospectively discover binding poses for two series of fragments in allosteric pockets on a difficult and important pharmaceutical target, protein tyrosine phosphatase 1b (PTP1b). Our simulations reversibly sampled the fragment association and dissociation process. One of the binding pockets found in the simulations has not to our knowledge been previously observed with a bound fragment, and the other pocket adopted a very rare conformation. We subsequently obtained high-resolution crystal structures of members of each fragment series bound to PTP1b, and the experimentally observed poses confirmed the simulation results. To the best of our knowledge, our findings provide the first demonstration that MD simulations can be used prospectively to determine fragment binding poses to previously unidentified pockets.

Synthesis and Structure of P-Halogenated Benzazaphospholes and Their Reactivity toward Pt(0) Sources

Dearomatization of the five-membered ring of N-Dipp (Dipp = 2,6-diisopropylphenyl)-substituted benzazaphosphole 2 with HCl generated 1–Cl, which undergoes substitution with halide sources to provide the remaining members of the P-halogenated series (1–F, 1–Br, and 1–I). These P-heterocycles (1) were characterized by multinuclear [31P{1H}, 1H, 13C{1H}, and 19F (if applicable)] NMR spectroscopy, elemental analysis, and X-ray crystallography. 1H and 13C{1H} NMR spectroscopy revealed that derivatives 1–F, 1–Cl, and 1–Br have C1 symmetry in solution. In contrast, 1–I has effective Cs symmetry in solution due to a rapid, concentration-dependent, inversion at phosphorus, shown by density functional theory (DFT) calculations (B3LYP-D3/6-311G**++) to involve a dimeric iodine-bridged transition structure. In the solid state, 1–F through 1–I all exhibited C1 symmetry with varying degrees of elongation of their P–X bonds. Elongation of the P–X bonds is shown by DFT/natural bond orbital studies to involve NLP → σ*(P–X) negative hyperconjugation, which increases down the halogen series but is less pronounced than that for the closely related NHP–X counterparts (3–F through 3–I). Treatment of 1–Br/I with [Pt(P(t-Bu)3)2] afforded Pt(I)–Pt(I) dimers 4–Br/I, which were characterized by 31P{1H}, 1H, and 13C{1H} NMR spectroscopy, elemental analysis, and X-ray crystallography. Addition of 1–F to Pt(PPh3)4 gave Pt(1–F)(PPh3)2 (6), a coordination compound in which the P-heterocyclic ligand is bound through its lone pair without P–F bond cleavage. Recrystallization attempts resulted in ligand exchange, furnishing Pt(0) complex 7, which features 1–F and PPh3 donors in a 2:1 ratio. Reactions of 1–Cl with all tested starting materials produced unidentifiable product mixtures by 31P{1H} NMR spectroscopy, but the combination of Pt(PPh3)4 or Pt(PPh3)2(C2H4) and 1–Cl in acetone generated an unisolable Pt complex containing tentatively assigned PtP2 metallacyclopropane structural unit 8.

Modelling Manoeuvrability in the Context of Ship Collision Analysis Using Non-Linear FEM

Ship collisions are rare events that may have a significant impact on the safety of people, ships, and other marine structures, as well as on the environment. Because of this, they are extensively studied but events that just precede collision are often overlooked. To rationally assess collision risks and consequences, a ship’s trajectory, and consequently the velocity and collision angle, should be known. One way to achieve this is through accurate modelling of ship manoeuvrability in collision analysis using non-linear FEM (NFEM). The Abkowitz manoeuvring model is implemented in the LS-Dyna software code and is therefore coupled with FEM calculations. Hydrodynamic forces are calculated in each time step of the LS-Dyna calculation and added to the FE model continuously through calculation. The accuracy of the calculations depends on the choice of and values of hydrodynamic derivatives from the Abkowitz model. Abkowitz’s model derives hydrodynamic forces in the Taylor expansion series to provide hydrodynamic derivatives. The application of the procedure is sensitive on higher-order Taylor series members. This article reviews different sets of hydrodynamic derivatives available for the KVLCC2 ship. Each of them is incorporated into the LS-Dyna NFEM solver by a user-made Fortran subroutine, with standard Zigzag and turning manoeuvres simulated and results compared with the experimental tests. As a result, the optimal selection of hydrodynamic derivatives is determined, laying a foundation for assessing the risk of ship collision due to different ship manoeuvres prior to the collision itself.

Composites of Montmorillonite and Titania Nanoparticles Prepared by Inverse Microemulsion Method: Physico-Chemical Characterization.

TiO2/montmorillonite composites were synthesized using inverse micellar route for the preparation of titania nanoparticles (4-6 nm diameter) in 1-hexanol and for the dispersion of one of the clay components. Two series of composites were obtained: one derived from cetyltrimethylammonium organomontmorillonite (CTA-Mt), exfoliated in 1-hexanol, and the other from sodium form of montmorillonite (Na-Mt) dispersed by formation of an inverse microemulsion in 1-hexanol. The TiO2 content ranged from 16 to 64 wt.%. The composites were characterized with X-ray diffraction, scanning/transmission electron microscopy/energy dispersive X-ray spectroscopy, thermal analysis, and N2 adsorption-desorption isotherms. The Na-Mt-derived component was shown to undergo transformation to CTA-Mt, as indicated by basal spacing of 17.5 nm, due to the interaction with the CTABr surfactant in inverse microemulsion. It was also better dispersed and intermixed with TiO2 nanoparticles. As a result, the TiO2/Na-Mt series displayed superior textural properties, with specific surface area up to 256 m2g-1 and pore volume up to 0.247 cm3g-1 compared with 208 m2g-1 and 0.231 cm3g-1, respectively, for the TiO2/CTA-Mt counterpart. Members of both series were uniformly mesoporous, with the dominant pore size around 5 nm, i.e., comparable with the dimensions of titania nanoparticles. The advantage of the adopted synthesis method is discussed in the context of other preparative procedures used for manufacturing of titania-clay composites.

Stratigraphy, volcanic processes and evolution of the Martin Vaz archipelago

The volcanic Martin Vaz Archipelago consists of four Plio-Pleistocene small islands (total area of 0.37 km2) in the South Atlantic Ocean in front of Brazil's coast. Together with Trindade Island, the archipelago corresponds to the easternmost portion of the Vitória-Trindade Seamount Chain (VTC).We performed geological mapping, coupled with X-ray diffraction, petrography, scanning electron microscopy, and lithogeochemistry analyses at Martin Vaz samples. Four lithostratigraphic units were identified (i) Martin Vaz Formation records older explosive phonolitic activity. It is interpreted as resulting from hydromagmatic volcanism; (ii) Subvolcanic phonolites consist of a dome (cryptodome) and plug morphologies, which represent the most voluminous rocks at Martin Vaz Archipelago; (iii) Mirante Formation records hyper-concentrated density currents of ultrabasic rocks; and (iv) Atobá Formation is composed of ultrabasic to intermediate lavas of basanitic to phonolitic composition, interpreted as a result of Strombolian (Fountain Fed)/Hawaiian volcanism.The volcanic rocks described at Martin Vaz Archipelago and Trindade Island represent the final members of the nephelinite-phonolite series, with a significant absence of intermediate phases. Basanites of the Martin Vaz, Mirante, and Atobá formations are geochemically similar to the nephelinites of Trindade Island. In the same way, the geochemical characteristics of phonolites from subvolcanic bodies and the Bandeira Member are similar to those observed on the phonolites of Trindade Island. Geochemical and thermodynamic modeling suggest cogeneticity between ultrabasic and phonolitic magmas. Fractional crystallization about 0.5 GPa and at low water pressures explain the chemical evolution trends observed. Geochemical characteristic points to melts of a metasomatized source composed of garnet wehrlite and/or hornblendite.The new data allowed for the elaboration of a novel conceptual model for the geological evolution of the Martin Vaz Archipelago, one of the last volcanic manifestations in the Brazilian territory.

Calamities causing loss of museum collections: a historical and global perspective on museum disasters.

With alarming frequency, significant collections in natural history museums have been destroyed or damaged through insurrections, cyclones, wars, fires, floods, or earthquakes particularly in the nineteenth century but continuing into the twentieth century with World War II bombings, fires, and earthquakes being the primary causes of loss in fifty-seven institutions across thirty countries. We review the loss or damage of museum collections globally, and their varied causes. We emphasize the benefits of dispersal of a sample of paratypes across institutions as an essential feature of taxonomic practice. We argue that museums do not own type material but are acting as perpetual custodians of type material on behalf of science and society in general, and that museums, therefore, have an obligation to minimize the risk to their collections. The significance of the loss of type material would be ameliorated if, when there are numerous paratypes or syntypes, members of a type series were distributed among several institutions. This is currently common practice but historically this was not always the case and might not be possible if only a single holotype is available. We also reaffirm the need for scientists around the globe to develop specific protocols to protect collections of biological and cultural materials from loss or damage from natural and human-created disasters now and into the future. We comment on recent moves to modify the Zoological Code of Nomenclature to allow the use of images as "type" material when describing new species with the image serving as a substitute for "physical" specimens deposited in museum collections. Although our focus is on herpetological collections, our particular interest and area of expertise, our observations apply broadly to all collections, including those of animals, plants, and anthropological or ethnographic material.

The Effect of Hydrogenation on the Contest between Aromaticity and Antiaromaticity in Norcorrole.

Magnetic shielding studies demonstrate that successive hydrogenation of NiII norcorrole (NiNc), a stable molecule combining aromatic and antiaromatic features, first weakens and then eliminates the central antiaromatic region, even though the NiNc antiaromatic "core", a 14-membered conjugated cycle with 16 π electrons, is formally preserved throughout the H2 NiNc-H8 NiNc series. The differences between aromatic and non-aromatic isotropic shielding distributions and nucleus-independent chemical shift (NICS) values in these hydrogenated porphyrin analogues are highlighted by comparing the results for the members of the H2 NiNc-H8 NiNc series to those for the aromatic NiII porphyrin complex. The results strongly support the unexpected and counterintuitive conclusion that H8 NiNc will be nonaromatic, without even a trace of antiaromaticity. Based on these findings, H8 NiNc is predicted to be the most stable member of the H2 NiNc-H8 NiNc series.

Fern Macroflora Identified in the Basal Danian of the Raton Formation Supports Palynological Signal of a Widespread “Postdisaster” Fern Flora

Premise of research. From a purely palynological perspective, lowest Danian fern-dominated assemblages of the Williston Basin (North Dakota and southwestern Saskatchewan) and the Raton Basin (northeastern New Mexico and southeastern Colorado) appear indistinguishable, although this perspective has yet to be corroborated by macrofloral studies across this same region. No ferns have been collected from the lowest Danian barren series of the Raton Formation in more than a century, and this section remains sparsely sampled.Methodology. New collections of fossil ferns from the basal portion of the barren series or informal middle member of the Raton Formation, which directly overlies the K/Pg boundary, are compared with contemporaneous assemblages in other North American depositional basins.Pivotal results. Dennastra sorimarginata McIver and Basinger (Dennstaedtiaceae Lotsy) and Woodwardia arctica (Heer) Brown (Blechnaceae Newman) that produce Cyathidites diaphana (Wilson and Webster) Nichols and JL Brown and Laevigatosporites haardtii (Potonié and Venitz) Thomson and Pflug, respectively, are recognized as characteristic ferns in the basal portion of the barren series, in addition to Osmunda macrophylla Penhallow.Conclusions. In accordance with palynological perspectives, lowest Danian fern macrofossil assemblages from the Raton Basin support the concept of a geographically widespread “postdisaster” pteridophyte flora represented predominantly by Dennstaedtiaceae and Blechnaceae, with other minor components of more northern assemblages. The enigmatic hypothesis of a landscape dominated by anemiaceous or schizaeaceous ferns is rejected on the basis of this new evidence, which suggests that Cyathidites diaphana–producing dennstaedtiaceous ferns were the K/Pg boundary “disaster taxon” and among those that flourished in the Raton Basin.

Infrared spectra study of the Moslavacka Gora (Croatia) tourmalines O-H stretching region: Inference of fluid involvement in the Late Cretaceous igneous evolution of a complex Adria-Europe convergence zone

Infrared spectra (IR) in the O-H stretching region were recorded for natural tourmalines from the magmatic and magmatic-hydrothermal systems of Moslavacka Gora (Croatia). Samples of disseminated tourmaline (schorl) representing magmatic products were collected from leucogranite. Nodular tourmaline (intermediate members of the schorl-dravite series) from twomica granite represents a magmatic-hydrothermal mineral related to the final stage of granite crystallization. IR spectra of the typically disseminated tourmaline show four sharp O-H stretching bands: 3643, 3633, 3550, and 3484 cm?1, while typical nodular tourmaline shows spectra with asymmetric and relatively broad O-H stretching bands on 3635 and 3554 cm?1 with shoulders at the higher and lower wavenumber side. The broadening in the lower wavenumber region of nodular tourmaline compared to disseminated tourmaline indicates a higher water content in the nodular type. At the same time, the observed shifts between the corresponding bands can be explained by the shortening of the O-H1 and O-H3 distances, which can be attributed to different genetic and/or evolutionary processes. According to the models applicable to the Moslavacka Gora, disseminated tourmaline from the leucogranite can be considered a typical magmatic (pegmatitic) product and a standard accessory phase of the leucogranite. The origin of nodular tourmaline, which was the last mineral to crystallize in the evolved Late Cretaceous granitic system of Moslavacka Gora, is attributed to the interaction of a fluid phase from the residual granitic melt with the fluid originating from the wall-rock in the low-pressure crustal setting, which was accompanied by relatively rapid cooling. This interaction resulted in an increased dravite content of the nodular tourmaline and is reflected in the observed IR spectral features.

Argentotetrahedrite-(Cd), Ag6(Cu4Cd2)Sb4S13, a new member of the tetrahedrite group from Rudno nad Hronom, Slovakia.

AbstractArgentotetrahedrite-(Cd), Ag6(Cu4Cd2)Sb4S13, has been approved as a new mineral species by the Commission on New Minerals, Nomenclature and Classification of the International Mineralogical Association using samples from Rudno nad Hronom, Slovak Republic. It occurs as anhedral grains up to 30 μm in size, steel-grey to black in colour, with a metallic lustre, in association with greenockite and other tetrahedrite-group minerals [argentotetrahedrite-(Zn) and tetrahedrite-(Zn)], earlier base-metal minerals, Ag sulfides and sulfosalts (acanthite, pyrargyrite and polybasite) and later galena. Argentotetrahedrite-(Cd) is isotropic, grey in colour, with a creamy tint and rapidly (tens of minutes) tarnishes to orange–brown. Reflectance data for Commission on Ore Mineralogy (COM) wavelengths in air are [λ (nm), R (%)]: 470, 30.4; 546, 30.3; 589, 30.3; and 650, 28.7. The chemical formula of the samples studied, recalculated on the basis of ΣMe = 16 atoms per formula unit, is: (Ag3.28Cu2.72)Ʃ6.00[Cu4(Cd1.68Fe0.27Zn0.16)]Ʃ6.11(Sb3.71As0.15)Ʃ3.86S12.79. Argentotetrahedrite-(Cd) is cubic, I$\bar{4}$3m, with a = 10.65(2) Å, V = 1208(4) Å3 and Z = 2. Argentotetrahedrite-(Cd) is isotypic with other members of the tetrahedrite group. The structural relationship between argentotetrahedrite-(Cd) and other members of the freibergite series are discussed and previous findings of this species are briefly reviewed.

Anti-leishmanial physalins-Phytochemical investigation, in vitro evaluation against clinical and MIL-resistant L. tropica strains and in silico studies.

Cutaneous leishmaniasis (CL) is a major health problem in over 98 countries of the world, including Pakistan. The current treatments are associated with a number of adverse effects and availability problem of drugs. Therefore, there is an urgent need of easily available and cost effective treatments of CL- in Pakistan. The bioassay-guided fractionation and purification of crude extract of Physalis minima has led to the isolation of a new aminophysalin B (1), and eight known physalins, physalin B (2), 5ß,6ß-epoxyphysalin B (3), 5α-ethoxy-6ß-hydroxy-5,6-dihydrophysalin B (4), physalin H (5), 5ß,6ß-epoxyphysalin C (6), and physalin G (7), K (8), and D (9). It is worth noting that compound 1 is the second member of aminophysalin series, whereas compound 6 was fully characterized for the first time. The structures of compounds 1-9 were elucidated by spectroscopic techniques Whereas, the structural assignments of compounds 1 and 8 were also supported by single-crystal X-ray diffraction studies. The anti-leishmanial activity of isolated physlains 1-9 was evaluated against Leishmania major and Leishmania tropica promastigotes. Compounds 2, 3, and 5-7 (IC50 = 9.59 ± 0.27-23.76 ± 1.10 μM) showed several-fold more potent activity against L. tropca than tested drug miltefosine (IC50 = 42.75 ± 1.03 μm) and pentamidine (IC50 = 27.20 ± 0.01 μM). Whereas compounds 2, 3 and 5 (IC50 = 3.04 ± 1.12-3.76 ± 0.85 μM) were found to be potent anti-leishmanial agents against L. major, several fold more active than tested standard miltefosine (IC50 = 25.55 ± 1.03 μM) and pentamidine (IC50 = 27.20 ± 0.015 μM). Compounds 4 (IC50 = 74.65 ± 0.81 μM) and 7 (IC50 = 39.44 ± 0.65 μM) also showed potent anti-leishmanial ativity against the miltefosine-unresponsive L. tropica strain (MIL resistant) (miltefosine IC50 = 169.55 ± 0.78 μM). Molecular docking and predictive binding studies indicated that these inhibitors may act via targeting important enzymes of various metabolic pathways of the parasites.

Cage hydrocarbons as linkers in dimeric drug design: Case studies with trimethoprim and tedizolid

The looming threat of a “post-antibiotic era” has been caused by a rapid rise in antibacterial resistance and subsequent depletion of effective antibiotic agents in the clinic. An efficient strategy to address this shortfall lies in the reengineering of pre-existing and commercially available antibiotic drugs. This is exemplified by dimerization, a design concept in which two pharmacophores are covalently linked to form a new chemical entity. The cage hydrocarbons cubane (1), bicyclo[2.2.2]octane (BCO) (2), adamantane (3), and bicyclo[1.1.1]pentane (BCP) (4) present themselves as an attractive family of linkers in this regard. In this report, all four hydrocarbon cages were employed as linkers in a series of dimers based on the commercially available antibiotics trimethoprim and tedizolid. A detailed synthetic roadmap for the protection and deprotection of each pharmacophore is outlined. Several members of the trimethoprim series showed activity on par with that of their trimethoprim progenitor, although this was not the case for the tedizolid series. The design strategy outlined herein highlights the utility of the group as a platform for the rapid and modular construction of future novel antibiotics.

СONSTRUCTIONS MONOPRÉDICATIVES POLYSYNONYMIQUES MONO- ET POLYTRANSFORMATIONNELLES AU NIVEAU D’UN SYNTAGME ET DE L’ÉNONCÉ DANS LA PROSE FRANÇAISE DU XXe SIÈCLE

This paper is dedicated to the studies of monopredicative polysynonymic utterances at the level of syntagm or proposition in semantic-syntactical, pragmatic and stylistic aspects in the continuum language – discourse. They define these constructions as virtual (linguistic) mono- and polytransformational unities phenomenologically reconstructed from a primary structure which are actualized in the form of compressed, extended or quantitatively equicomponential preferential options. By the way of inverse reconstruction and linguistic experiment they determine the degree of co(n)textual pertinence of each member of synonymic series and they reveal strategies of the author’s linguistic gamе.

High-pressure stabilisation of R = Y member of R2CuTiO6 double perovskite series

Double perovskite oxides of the A2B’B″O6 type with Jahn-Teller active Cu2+ as the B′ constituent have gained considerable research interest in recent years. For fundamental studies, the rare earth element (R) based systems such as R2CuTiO6 form an intriguing research platform as they allow systematic chemical-pressure studies by simply controlling the size of the R constituent. However, for the R2CuTiO6 compounds conventional ambient-pressure high-temperature synthesis yields an orthorhombic (Pnma) double perovskite structure for the largest R constituents (La–Gd) only, while the compounds with the smaller R:s adopt a hexagonal structure. Here we demonstrate a hexagonal-to-perovskite structure conversion for the R ​= ​Y compound achieved through a high-pressure (HP) high-temperature treatment at 4 ​GPa and 1000 ​°C. Structural details of the thus stabilized new double perovskite phase of Y2CuTiO6 are addressed through a combined DFT simulation and Rietveld refinement study, revealing signs towards the rare layered-type ordering of the B-site (Cu and Ti) cations. Similar to the previously reported R2CuTiO6 perovskite phases with R ​= ​La, Pr, and Nd, the R ​= ​Y member is found paramagnetic throughout the measured temperature range of 5–300 ​K. From UV–vis absorption measurements the optical bandgap is estimated to be ca 3.4 ​eV.

Exponential type orbitals with hyperbolic cosine function basis sets for isoelectronic series of the atoms Be to Ne

Abstract Exponential type orbital with hyperbolic cosine basis functions, proposed recently for Hartree–Fock–Roothaan calculations of neutral atoms, are studied in detail for the calculations of isoelectronic series of atoms from Be to Ne. Calculations are performed for the neutral and the first 20 cationic members of the isoelectronic series of each atom in its ground state. Three of the most popular exponential type orbitals (Slater type functions, B functions and ψ (α) functions with α = 2) are combined with modified hyperbolic cosine function cosh(βr + γ) to improve the basis function quality within the minimal basis sets framework. Performances of the basis functions are compared with each other by using the same number of variational parameters in them. The obtained results are also compared with numerical Hartree–Fock and extended Slater type basis set results. The presented accuracy of the minimal basis descriptions of atomic systems supports the usage of these unconventional basis functions in electronic structure and property calculations.