New Blood Coagulation Factor XIIa Inhibitors: Molecular Modeling,Synthesis, and Experimental Confirmation

In the modern world, complications caused by disorders in the blood coagulation system are found in almost all areas of medicine. Thus, the development of new, more advanced drugs that can prevent pathological conditions without disrupting normal hemostasis is an urgent task. The blood coagulation factor XIIa is one of the most promising therapeutic targets for the development of anticoagulants based on its inhibitors. The initial stage of drug development is directly related to computational methods of searching for a lead compound. In this study, docking followed by quantum chemical calculations was used to search for noncovalent low-molecular-weight factor XIIa inhibitors in a focused library of druglike compounds. As a result of the study, four low-molecular-weight compounds were experimentally confirmed as factor XIIa inhibitors. Selectivity testing revealed that two of the identified factor XIIa inhibitors were selective over the coagulation factors Xa and XIa.     

Molecular Characteristics and Antioxidant Activity of Spruce (Picea abies) Hemicelluloses Isolated by Catalytic Oxidative Delignification

Spruce (Picea abies) wood hemicelluloses have been obtained by the noncatalytic and catalytic oxidative delignification in the acetic acid-water-hydrogen peroxide medium in a processing time of 3–4 h and temperatures of 90–100 °C. In the catalytic process, the H₂SO₄, MnSO₄, TiO₂, and (NH₄)₆Mo₇O₂₄ catalysts have been used. A polysaccharide yield of up to 11.7 wt% has been found. The hemicellulose composition and structure have been studied by a complex of physicochemical methods, including gas and gel permeation chromatography, Fourier-transform infrared spectroscopy, and thermogravimetric analysis. The galactose:mannose:glucose:arabinose:xylose monomeric units in a ratio of 5:3:2:1:1 have been identified in the hemicelluloses by gas chromatography. Using gel permeation chromatography, the weight average molar mass M_w of hemicelluloses has been found to attain 47,654 g/mol in noncatalytic delignification and up to 42,793 g/mol in catalytic delignification. Based on the same technique, a method for determining the α and k parameters of the Mark–Kuhn–Houwink equation for hemicelluloses has been developed; it has been established that these parameters change between 0.33–1.01 and 1.57–472.17, respectively, depending on the catalyst concentration and process temperature and time. Moreover, the FTIR spectra of the hemicellulose samples contain all the bands characteristic of heteropolysaccharides, specifically, 1069 cm⁻¹ (C–O–C and C–O–H), 1738 cm⁻¹ (ester C=O), 1375 cm⁻¹ (–C–CH₃), 1243 cm⁻¹ (–C–O–), etc. It has been determined by the thermogravimetric analysis that the hemicelluloses isolated from spruce wood are resistant to heating to temperatures of up to ~100 °C and, upon further heating, start destructing at an increasing rate. The antioxidant activity of the hemicelluloses has been examined using the compounds simulating the 2,2-diphenyl-2-picrylhydrazyl free radicals.     

Numerical Modeling of Momentum Dispersion in Porous Media Based on the Pore Scale Prevalence Hypothesis

Transport in Porous Media - A macroscopic model that accounts for the effect of momentum dispersion on flows in porous media is proposed. The model is based on the pore scale prevalence hypothesis...     

Identification of pyrrolo-pyridine derivatives as novel class of antibacterials

Molecular Diversity - A series of 5-oxo-4H-pyrrolo[3,2-b]pyridine derivatives was identified as novel class of highly potent antibacterial agents during an extensive large-scale high-throughput...     

Charged pion condensation in anti-parallel electromagnetic fields and nonzero isospin density

The formation of charged pion condensate in anti-parallel electromagnetic fields and in the presence of the isospin chemical potential is studied in the two-flavor Nambu-Jona-Lasinio model.The method of Schwinger proper time is extended to explore the quantities in the off-diagonal flavor space,i.e.the charged pion.In this framework,π^± are treated as bound states of quarks and not as point-like charged particles.The isospin chemical potential plays the role of a trigger for charged pion condensation.We obtain the associated effective potential as a function of the strength of the electromagnetic fields and find that it contains a sextic term which possibly induces a weak first order phase transition.The dependence of pion condensation on model parameters is investigated.     

Two‐Step Oxidation Synthesis of Sulfur with a Red Aggregation‐Induced Emission

Sulfur is not normally considered a light‐emitting material, even though there have been reports of a dim luminescence of this compound in the blue‐to‐green spectral region. Now, it is shown how to make red‐emissive sulfur by a two‐step oxidation approach using elemental sulfur and Na₂S as starting materials, with a high photoluminescence quantum yield of 7.2 %. Polysulfide is formed first and is partially transformed into Na₂S₂O₃ in the first step, and then turns back to elemental S in the second step. The elevated temperature and relatively oxygen‐deficient environment during the second step transforms Na₂S₂O₃ into Na₂SO₃ incorporated with oxygen vacancies, thus resulting in the formation of a solid‐state powder consisting of elemental S embedded in Na₂SO₃. It shows aggregation‐induced emission properties, attributed to the influence of oxygen vacancies on the emission dynamics of sulfur by providing additional lower energy states that facilitate the radiative relaxation of excitons.     

Approximate Atomic Green Functions

In atomic and many-particle physics, Green functions often occur as propagators to formally represent the (integration over the) complete spectrum of the underlying Hamiltonian. However, while these functions are very crucial to describing many second- and higher-order perturbation processes, they have hardly been considered and classified for complex atoms. Here, we show how relativistic (many-electron) Green functions can be approximated and systematically improved for few- and many-electron atoms and ions. The representation of these functions is based on classes of virtual excitations, or so-called excitation schemes, with regard to given bound-state reference configurations, and by applying a multi-configuration Dirac-Hartree-Fock expansion of all atomic states involved. A first implementation of these approximate Green functions has been realized in the framework of Jac, the Jena Atomic Calculator, and will facilitate the study of various multi-photon and/or multiple electron (emission) processes.     

Revealing Phosphorus Nitrides up to the Megabar Regime: Synthesis of α′-P3N5, δ-P3N5 and PN2

Non-metal nitrides are an exciting field of chemistry, featuring a significant number of compounds that can possess outstanding material properties. These properties mainly rely on maximizing the number of strong covalent bonds, with crosslinked XN₆ octahedra frameworks being particularly attractive. In this study, the phosphorus–nitrogen system was studied up to 137 GPa in laser-heated diamond anvil cells, and three previously unobserved phases were synthesized and characterized by single-crystal X-ray diffraction, Raman spectroscopy measurements and density functional theory calculations. δ-P₃N₅ and PN₂ were found to form at 72 and 134 GPa, respectively, and both feature dense 3D networks of the so far elusive PN₆ units. The two compounds are ultra-incompressible, having a bulk modulus of K₀=322 GPa for δ-P₃N₅ and 339 GPa for PN₂. Upon decompression below 7 GPa, δ-P₃N₅ undergoes a transformation into a novel α′-P₃N₅ solid, stable at ambient conditions, that has a unique structure type based on PN₄ tetrahedra. The formation of α′-P₃N₅ underlines that a phase space otherwise inaccessible can be explored through materials formed under high pressure.     

Oxygen‐Doped Zig‐Zag Molecular Ribbons

The synthesis of a zig‐zag oxygen‐doped molecular rhombic ribbon has been achieved. This includes oxidative C?C and C?O bond formations that allowed the stepwise elongation and planarization of an oxa‐congener of 2,7‐periacenoacene. X‐ray diffraction analysis corroborated the flat structure and the zig‐zag topology of the O‐doped edges. Photophysical and electrochemical investigations showed that the extension of the peri‐xanthenoxanthene (PXX) into the molecular ribbon induces a noticeable shrinking of the molecular band gap devised by a rising of the HOMO energy level, a desirable property for p‐type organic semiconductors.