Asynchronous parametric excitation: validation of theoretical results by electronic circuit simulation

Nonlinear Dynamics - A validation of recent theoretical results on the stability effects of asynchronous parametric excitation is presented. In particular, the coexistence of both resonance and...     

Protein–ligand docking using FFT based sampling: D3R case study

Fast Fourier transform (FFT) based approaches have been successful in application to modeling of relatively rigid protein–protein complexes. Recently, we have been able to adapt the FFT methodology to treatment of flexible protein–peptide interactions. Here, we report our latest attempt to expand the capabilities of the FFT approach to treatment of flexible protein–ligand interactions in application to the D3R PL-2016-1 challenge. Based on the D3R assessment, our FFT approach in conjunction with Monte Carlo minimization off-grid refinement was among the top performing methods in the challenge. The potential advantage of our method is its ability to globally sample the protein–ligand interaction landscape, which will be explored in further applications.     

The dependence of the conduction band edge of the alkali earth metal bismuthates on their composition

We present a comparative analysis of the conduction band edge of the alkali earth metal bismuthates containing Mg, Ca, Sr, and Ba. The conduction band edges were computed using the method suggested by Butler and Ginley. The calculations reveal that they depend on the bismuthate’s composition and vary over a wide range. We demonstrate that the energy of the conduction band increases in the series Ca?→?Sr?→?Ba. It also increases with an increase of the alkali earth metal content. The performed calculations help to determine the potential alkali earth metal bismuthate photocatalysts. The most promising compositions found in this study include strontium and barium bismuthates in which the number of the alkali earth metal atoms in the cationic sublattice exceeds the number of the bismuth atoms.     

Image of the Spectral Measure of a Jacobi Field and the Corresponding Operators

By definition, a Jacobi field is a family of commuting selfadjoint three-diagonal operators in the Fock space The operators J(ϕ) are indexed by the vectors of a real Hilbert space H₊. The spectral measure ρ of the field J is defined on the space H₋ of functionals over H₊. The image of the measure ρ under a mapping is a probability measure ρ_K on T₋. We obtain a family J_K of operators whose spectral measure is equal to ρ_K. We also obtain the chaotic decomposition for the space L²(T₋, d_{ρ K}).     

Parametric analysis of the oscillatory solutions to stochastic differential equations with the Wiener and Poisson components by the Monte Carlo method

Using the Monte Carlo method, we address the influence of the Wiener and Poisson random noises on the behavior of oscillatory solutions to systems of stochastic differential equations (SDEs). For the linear and Van der Pol oscillators, we study the accuracy of estimates of the functionals of numerical solutions to SDEs obtained by the generalized explicit Euler method. For a linear oscillator, we obtain the exact analytical expressions for the mathematical expectation and the variance of the SDE solution. These expressions allow us to investigate the dependence of the accuracy of estimates of the solution moments on the values of SDE parameters, the size of meshsize, and the ensemble of simulated trajectories of the solution. For the Van der Pol oscillator, we study the dependence of the frequency and the damping rate of the oscillations of the mathematical expectation of SDE solution on the values of parameters of the Poisson component. The results of the numerical experiments are presented.     

Identification of extracellular nanoparticle subsets by nuclear magnetic resonance

Exosomes are a subset of secreted lipid envelope-encapsulated extracellular vesicles (EVs) of 50–150 nm diameter that can transfer cargo from donor to acceptor cells. In the current purification protocols of exosomes, many smaller and larger nanoparticles such as lipoproteins, exomers and microvesicles are typically co-isolated as well. Particle size distribution is one important characteristics of EV samples, as it reflects the cellular origin of EVs and the purity of the isolation. However, most of the physicochemical analytical methods today cannot illustrate the smallest exosomes and other small particles like the exomers. Here, we demonstrate that diffusion ordered spectroscopy (DOSY) nuclear magnetic resonance (NMR) method enables the determination of a very broad distribution of extracellular nanoparticles, ranging from 1 to 500 nm. The range covers sizes of all particles included in EV samples after isolation. The method is non-invasive, as it does not require any labelling or other chemical modification. We investigated EVs secreted from milk as well as embryonic kidney and renal carcinoma cells. Western blot analysis and immuno-electron microscopy confirmed expression of exosomal markers such as ALIX, TSG101, CD81, CD9, and CD63 in the EV samples. In addition to the larger particles observed by nanoparticle tracking analysis (NTA) in the range of 70–500 nm, the DOSY distributions include a significant number of smaller particles in the range of 10–70 nm, which are visible also in transmission electron microscopy images but invisible in NTA. Furthermore, we demonstrate that hyperpolarized chemical exchange saturation transfer (Hyper-CEST) with ¹²⁹Xe NMR indicates also the existence of smaller and larger nanoparticles in the EV samples, providing also additional support for DOSY results. The method implies also that the Xe exchange is significantly faster in the EV pool than in the lipoprotein/exomer pool.

Diffusion and xenon NMR based methods to determine a very broad range of sizes and sub-sets of extracellular vesicles.     

One-Pot Solvent-Involved Synthesis of 5-O-Substituted 5H-Chromeno[2,3-b]pyridines

Chromeno[2,3-b]pyridines are substances demanded in medicinal and material chemistry. PASE (pot, atom, and step economy) and in particular one-pot approaches are key green chemistry techniques that are applied for the synthesis of heterocyclic compounds. In this case, the PASE approach was extended with ‘component economy’, as solvent was used also as reactant (solvent-involved reaction). This approach was adopted for the one-pot synthesis of previously unknown O-substituted 5-alkoxy-5H-chromeno[2,3-b]pyridines via two-step transformation, namely the reaction of salicylaldehydes and malononitrile dimer, with the subsequent addition of alcohol. The mechanistic studies revealed the possibility of concurrent reaction. The studies aided in optimizing the reaction conditions for the best yields (77–93%). Thus, the one-pot reaction proceeds efficient and quickly, and the work-up procedure (only simple filtering) is very convenient. The structure of synthesized chromeno[2,3-b]pyridines was confirmed by 2D NMR spectroscopy.     

Phase transitions in K3AlF6

Phase transitions in the elpasolite-type K₃AlF₆ complex fluoride were investigated using differential scanning calorimetry, electron diffraction and X-ray powder diffraction. Three phase transitions were identified with critical temperatures , and . The α-K₃AlF₆ phase is stable below T₁ and crystallizes in a monoclinic unit cell with a=18.8588(2)Å, b=34.0278(2)Å, c=18.9231(1)Å, β=90.453(1)° (a=2a_c−c_c, b=4b_c, c=a_c+2c_c; a_c, b_c, c_c—the basic lattice vectors of the face-centered cubic elpasolite structure) and space group I2/a or Ia. The intermediate β phase exists only in very narrow temperature interval between T₁ and T₂. The γ polymorph is stable in the T₂<T<T₃ temperature range and has an orthorhombic unit cell with a=36.1229(6)Å, b=17.1114(3)Å, c=12.0502(3)Å (a=3a_c−3c_c, b=2b_c, c=a_c+c_c) at 250 °C and space group Fddd. Above T₃ the cubic δ polymorph forms with a_c=8.5786(4)Å at 400 °C and space group . The similarity between the K₃AlF₆ and K₃MoO₃F₃ compounds is discussed.     

One-step synthesis of heterocyclic privileged medicinal scaffolds by a multicomponent reaction of malononitrile with aldehydes and thiols

Heterocyclic privileged medicinal scaffolds involving pyridine, 1,4-dihydropyridine, chromeno[2,3-b]pyridine, and dihydro-1,4-dithiepine frameworks are prepared via a single-step multicomponent reaction of structurally diverse aldehydes with various thiols and malononitrile. Mechanistic studies of the synthetic pathway leading to pyridines reveal that 1,4-dihydropyridines undergo oxidation by the intermediate Knoevenagel adducts rather than by air oxygen. The use of o,o'-disubstituted aromatic aldehydes leads to the corresponding 1,4-dihydropyridines, whereas salicylic aldehydes result in chromeno[2,3-b]pyridines. Reactions of ethanedithiol as a thiol component produce dimeric pyridines with sterically unencumbered aldehydes, while o,o'-disubstituted aromatic aldehydes give dihydro-1,4-dithiepines. Thus, depending on the aldehyde and thiol types, diverse libraries of medicinally relevant compounds can be prepared by a simple one-step process involving no chromatography.     

Femtosecond midinfrared study of aggregation behavior in aqueous solutions of amphiphilic molecules

We study the spectral and orientational dynamics of HDO molecules in aqueous solutions of different concentrations of tertiary butyl alcohol (TBA) and trimethylamine-N-oxide (TMAO). The spectral dynamics is investigated with femtosecond two-dimensional infrared spectroscopy of the O-H stretch vibration of HDO:D(2)O, and the orientational dynamics is studied with femtosecond polarization-resolved pump-probe spectroscopy of the O-D stretch vibration of HDO:H(2)O. Both the spectral and orientational dynamics are observed to show bimodal behavior: part of the water molecules shows spectral and orientational dynamics similar to bulk liquid water and part of the water molecules displays a much slower dynamics. For low solute concentrations, the latter fraction of slow water increases linearly as a function of solute molality, indicating that the slow water is contained in the solvation shells of TBA and TMAO. At higher concentrations, the fraction of slow water saturates. The saturation behavior is much stronger for TBA solutions than for TMAO solutions, indicating the aggregation of the TBA molecules.