Polar Solutes Research Articles

The small-molecule kinase inhibitor ceritinib, unlike imatinib, causes a significant disturbance of lipid membrane integrity: A combined experimental and MD study

Ceritinib and imatinib are small-molecule protein kinase inhibitors which are applied as therapeutic agents against various diseases. The fundamentals of their clinical use, i.e. their pharmacokinetics as well as the mechanisms of the inhibition of the respective kinases, are relatively well studied. However, the interaction of the drugs with membranes, which can be a possible cause of side effects, has hardly been investigated so far. Therefore, we have characterized the interaction of both drugs with lipid membranes consisting of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) in the absence and in the presence of cholesterol. For determining the membrane impact of both drugs on a molecular level, different experimental (NMR, ESR, fluorescence) and theoretical (MD simulations) approaches were applied. The data show that ceritinib, in contrast to imatinib, interacts more effectively with membranes significantly affecting various physico-chemical membrane parameters like membrane order and transmembrane permeation of polar solutes. The pronounced membrane impact of ceritinib can be explained by a strong affinity of the drug towards POPC which competes with the POPC-cholesterol interaction by that attenuating the ordering effect of cholesterol. The data are relevant for understanding putative toxic and cytotoxic side effects of these drugs such as the triggering of cell lysis or apoptosis.

Silica-Based Stationary Phase with Surface Bound N-Acetyl-glucosamine for Hydrophilic Interaction Liquid Chromatography.

A hydrophilic silica-based stationary phase with surface bound N-acetylglucosamine (GlcNAc-silica) was prepared in house and characterized physically via Fourier transform infrared (FTIR) analysis and thermogravimetric analysis (TGA) and chromatographically over a wide range of mobile phase compositions. While both FTIR and TGA confirmed the attachment of the GlcNAc ligands to the silica surface, the chromatographic evaluation of GlcNAc-silica with polar and slightly polar standard solutes (e.g., sugars, nucleic acid fragments, phenolic, and benzoic acid derivatives) yielded the typical hydrophilic interaction liquid chromatography (HILIC) behaviors in the sense that retention increased with increases in solute polarity and the organic content (i.e., acetonitrile) of the hydro-organic mobile phase (i.e., ACN-rich mobile phase). Sugars derivatized with 1-naphthylamine (1-NA) and 2-aminoanthrcene (2-AA) such as xylose, glucose, and short chains maltooligosaccharides constituted the most polar species for HILIC retention evaluation, and in addition, the maltooligosaccharides offered a polar homologous series for gauging the hydrophilicity of GlcNAc-silica in analogy with alkylbenzene homologous series and other nonpolar homologues for evaluating the hydrophobicity of non-polar stationary phases. On the other hand, the benzoic acid and phenolic acid derivatives were the probe solutes for evaluating the HILIC retention dependence of ionizable solutes on the pH of the mobile phase. Similarly, the nucleobase and nucleoside weak basic solutes as well as some typical cyclic nucleotide acidic solutes allowed for the examination of the dependence of solute retention on the pH of the mobile as well as the polarity of the species.

Cis-trans isomerization in cyclosporin C dissolved in acetonitrile

Cyclosporin is an 11-amino acid cyclic peptide with pharmacologically valuable properties which has a variety of actual and potential applications. Its activity relies on the cell membrane permeability which, in turn, depends on the structure of cyclosporin and its ability to change the conformation. In this work, conformational exchange processes occurring in cyclosporin C were studied using one- and two-dimensional nuclear magnetic resonance spectroscopy. The free energy barrier separating two major conformers observed in polar solution (acetonitrile) was found to be 77 ± 2 kJ/mol. Less populated conformation states are also present in the solution, which agrees with the ease of formation of multiple forms revealed by MD simulations of cyclosporin C.

Dielectric behaviour and dipole moment of binary mixtures containing certain amides in benzene

Certain polar amides(v) are dissolved in benzene, a nonpolar solvent(u) to prepare binary mixtures with different composition of the amides like acetanilide, N-N-dimethyl acetamide, N-methyl acetamide, acetamide and formamide. Static relative permittivity ɛ0uv , high frequency permittivity ɛ ∞uv for different weight fraction of polar solute at 30°C are determined. The dielectric behaviour of binary mixtures are investigated under electric field of low frequency by using the Debye model for polar liquids. Static dipole moment µs , dipole moment µv from conductivity measurements and µ t from bond angle and bond moment measurements are computed. The dipole moments are consequence of attractive interaction between the adjacent molecules in binary mixture due to variation of electron densities. Hydrogen bonding, associated charge distribution among the constituent molecules, changes in bond angle values are some of the factors that give rise to dipole moment of binary mixtures. Nearly equal and close values of µs , µv and µt proves the correctness of dielectric behaviour studies of amides- benzene binary mixtures.

Polar compactons and solitons in a two dimensional optical waveguide: Theory and simulations

The propagation of optical cylindrical compactons and solitons in a two dimensional nonlocal nonlinear waveguide is deeply investigated by carrying a particular emphasis on its nonlinear response function. Considering the weakly nonlocal medium, the two dimensional nonlocal nonlinear Schrödinger equation describing the propagation of signal light is derived. This equation contains the basic nonlinear Schrödinger equation with additional nonlinear terms proportional to the second order space derivative of coordinates in the transverse directions. By seeking the solution in polar form, this equation is separated into real and imaginary parts, followed by the analysis of the equilibrium points and their stability, predicting the type of solutions. These solutions are found both with linear and nonlinear phases through direct integration. In order to seek polar solutions, the nonlocal nonlinear Schrödinger equation is expressed in cylindrical coordinate and the resulting equation, containing additional terms inversely proportional to the radius r is not easily solvable. The type of solutions of this equation is predicted by the investigation of new equilibrium points and their stability. The analytical cylindrical compactons and pulse solitons as solutions of this equation are provided by using the Rayleigh–Ritz variational method, usually used for symmetric radial solitons to approximate pulse solitons in polar coordinate, and the stability of these solutions is checked through numerical investigations.

Insight into the Structure of Victorin, the Host-Selective Toxin from the Oat Pathogen Cochliobolus victoriae. Studies of the Unique Dehydroamino Acid β-Chlorodehydroalanine.

Victorins, a family of peptide toxins, produced by the fungal pathogen Cochliobolus victoriae and responsible for disease of some oat varieties, contain a β-chlorodehydroalanine residue, ΔAla(βCl). To determine the conformational properties of this unique dehydroamino acid, a series of model compounds was studied using X-ray, NMR, and FT-IR methods, supported by theoretical calculations. The ΔAla(βCl) geometrical isomers differ in conformational profile. The isomer Z prefers the helical conformation α (φ, ψ = -61°, -24°), PPII type conformation β (φ, ψ = -47°, 136°), and semiextended conformation β2 (φ, ψ = -116°, 9°) in weakly and more polar solutions. The isomer E prefers mainly the extended conformation C5 (φ, ψ = -177°, 160°), but with an increase of the environment polarity also conformations β (φ, ψ = -44°, 132°) and α (φ, ψ = -53°, -39°). In the most stable conformations the N-H···Cl hydrogen bond (5γ) occurs, created between the chlorine atom of the side chain and the N-H donor of the flanking amide group. The method of synthesis of the β-chlorodehydroalanine residue is proposed, by chlorination of dehydroalanine and then the photoisomerization from the isomer Z to E. The presented results indicate that the assignment of the geometrical isomer of the ΔAla(βCl) residue in naturally occurring victorins still remains an open question, despite being crucial for biological activity.

Infinite Dilution Activity Coefficients and Gas–Liquid Partition Coefficients of Organic Compounds in Ionic Liquid 1-Butyl-2,3-dimethylimidazolium Thiocyanate: Measurements and LFER Calculations

Infinite dilution activity coefficients (γi∞) of 31 organic solutes (alkanes, cycloalkanes, olefins, aromatics, chlorinated alkanes, alcohols, and other polar organic solutes) in the ionic liquid (IL) 1-butyl-2,3-dimethylimidazole thiocyanate ([BMMIM][SCN]) were determined by gas–liquid chromatographic (GLC) method in the temperature range of 313.15–353.15 K. The infinite dilution partial molar excess enthalpies (H̅iE, ∞), entropies (TrefS̅iE, ∞), and Gibbs free energies (G̅iE, ∞) of the organic solutes at the reference temperature T = 298.15 K and the solubility parameters (δ3) of [BMMIM][SCN] were derived from γi∞. The gas–liquid partition coefficients (KL) of solutes at different temperatures were calculated by referring to the densities of [BMMIM][SCN]. The linear free energy relationship solvation model was used to fit the KL values, and the KL prediction model was obtained. The selectivity (Sij∞) and capacity (kj∞) of n-hexane (i)/benzene (j) and cyclohexane (i)/benzene (j) at infinite dilution at 323.15 K were calculated. The results were compared with the values of ILs with the thiocyanate anion in the literature.

Transient Terahertz Stark Effect: A Dynamic Probe of Electric Interactions in Polar Liquids

Electric forces acting on molecules in liquids at ambient temperature fluctuate at terahertz (THz) frequencies with a direct impact on their electronic and optical properties. We introduce the transient THz Stark effect to modify the electronic absorption spectra of dye molecules and, thus, elucidate and determine the underlying molecular interactions and dynamics. Picosecond electric fields of megavolts/cm induce a nonequilibrium response of the prototypical Betaine-30 in polar solution that is probed via transient absorption changes. The field-induced broadening of the absorption band follows the THz intensity in time, with a minor impact of solvent dynamics. The ground and excited state dipole energies in the THz field govern this response, allowing for a quantification of electric forces in a structurally frozen molecular environment.

Chemical composition and antifungal activity of Morinda Citrifolia fruit extract

Noni (Morinda citrifolia) fruit is a well-known plant used as a traditional medicine for preventing some diseases because of its abundance in chemical compounds. This research aimed to determine the phytochemical concentration, chemical composition, and antifungal activity of M. citrifolia fruit extract. M. citrifolia fruit was extracted with methanol and then distilled water for the partition extract. Subsequently, the extract was fractionated using various nonpolar to polar solutions, such as; chloroform, ethyl acetate, water, 2-propanol, and methanol fractions. Each fraction was evaporated until the dry extract was released. Additionally, the photochemical concentration of the M. citrifolia fruit extract was quantitatively determined using a UV-visible spectrophotometer. The chemical composition of the M. citrifolia fruit extract of each fraction was identified using gas chromatography-mass spectrometry (GC-MS). Then, the antifungal activity of M.citrifolia fruit extract against C. albicans and C. krusei was determined using the disc diffusion method. The results showed that the phytochemical concentration of the M. citrifolia fruit extract was 1970.25 ppm flavonoids, 35.61 ppm tannins, and 148.62 ppm steroids. 2-Fluorobenzoic acid, eucalyptol, 2-chloroaniline-5-sulfonic acid, hexa-decamethyl octasiloxane, and tetra-propyl stannane were found to be the major components of M. citrifolia fruit extract. According to the research, M. citrifolia fruit extract showed antifungal activity against C. albicans and C. krusei in all tested fractions. The maximum inhibition zone of C. albicans was 14.0 ± 1.00 mm in the 2-propanol fraction, while that of C. krusei was 11.7 ± 0.58 mm in the methanol fraction.

Solute-solvent interactions, electrostatic & covalent surface analysis, and pharmacokinetic studies via in-silico simulation on diethyl 3-hydroxyglutarate: Anti-hypercholesterolemia activity

In this study, theoretical investigations of the anti-hypercholesterolemia molecule diethyl 3-hydroxyglutarate (D3HG) have been carried out using DFT techniques. Vibrational spectral analyses were utilized for the structural determination after the compound's stability was identified through DFT optimization. As per the QTAIM findings, the highest electron density and electron distribution asymmetry were found at O4C9 and O510 in the molecule D3HG. Under the topological evaluation, the covalent and electrostatic interactions were assessed by Laplacian electron density (∇2ρ(r)) and reduced density gradient (RDG). Studies of solvent effects on electronic absorptions, molecular electrostatic potentials, global reactive descriptors, and Fukui functions have been analysed to understand better the mechanism causing chemical responsiveness. First-order hyperpolarizability (β) and natural bond orbital (NBO) stability calculations were also included. Solvatochromic correlations are used to approximate the referred molecule's reactions to polar and non-polar solutions as well as the solute-solvent interactions. Using Lipinski's rule, the molecule's drug-likeness study was carried out; pharmacokinetics and the D3HG molecule's interactions with iso-enzymes were also explored. A molecular docking study also demonstrates the efficacy of the title molecule to have anti-hypercholesterolemia activity.

Optimized Polarization Encoder with High Extinction Ratio for Quantum Key Distribution System

Polarization encoding is a promising approach for practical quantum key distribution (QKD) systems due to its simple encoding and decoding methodology. In this study, we propose a self-compensating polarization encoder (SCPE) based on a phase modulator, which can be composed of commercial off-the-shelf (COT) devices. We conducted a proof-of-concept experiment to test the SCPE, which demonstrated an in-system quantum bit error rate (QBER) of 0.53% and long-term running stability without any active adjustments. Additionally, we conducted experiments with transmission over commercial fiber spools of lengths up to 100 km and obtained a secure finite key rate of 3 kbps. Our polarization encoder is a promising solution for various polarization encoding protocols, including BB84, MDI, and RFI.

The temperature of maximum density of diluted aqueous solutions of non-polar solutes: A molecular simulation study using TIP4P/2005 water and LJ point solutes

The effect of non polar solutes on the temperature of maximum density of water, TMD, is analyzed in detail by means of molecular simulations over an ample pressure interval ranging from negative to very high pressures. Non polar solutes are represented by single Lennard-Jones (LJ) sites, whose non-polar character is tuned with the width and depth of the Lennard-Jones water-solute potential parameters. Our analysis is focused on the behavior of the partial molar volume of the solute at infinite solution, whose thermal dependence is correlated with changes in the TMD. We find that for pressures below −200 bar all possible LJ water-solute potential parameters decrease the TMD, i.e. the solute acts as a “structure breaker”. At higher pressures, it is always possible to find a range of LJ parameters which induce an increase of the TMD, whose magnitude rises gradually with pressure. Our results are consistent with previous simulations of non polar gases in solution and with theoretical studies in the case of small LJ centers. It will be shown that the partial molar volume of an ideal gas at infinite dilution can provide information concerning the existence and size of the LJ parameter space that induces TMD increases for a given water model. Finally, we analyze the changes in the TMD in terms of the competition between low density and high density water states. We find that the temperature dependence of the variation of the low density water mole fraction with the addition of LJ solutes seems to be at the source of the changes in the TMD.

The Role of the Anion in Imidazolium-Based Ionic Liquids for Fuel and Terpenes Processing.

The potentialities of methylimidazolium-based ionic liquids (ILs) as solvents were evaluated for some relevant separation problems-terpene fractionation and fuel processing-studying selectivities, capacities, and solvent performance indices. The activity coefficients at infinite dilution of the solute (1) in the IL (3), γ13∞, of 52 organic solutes were measured by inverse gas chromatography over a temperature range of 333.2-453.2 K. The selected ILs are 1-butyl-3-methylimidazolium hexafluorophosphate, [C4mim][PF6], and the equimolar mixture of [C4mim][PF6] and 1-butyl-3-methylimidazolium chloride, [C4mim]Cl. Generally, low polar solutes follow γ1,C4mimCl∞ > γ1,C4mimPF6+C4mimCl∞ > γ1,C4mimPF6∞ while the opposite behavior is observed for alcohols and water. For citrus essential oil deterpenation, the results suggest that cations with long alkyl chains, such as C12mim+, promote capacity, while selectivity depends on the solute polarity. Promising results were obtained for the separation of several model mixtures relevant to fuel industries using the equimolar mixture of [C4mim][PF6] and [C4mim]Cl. This work demonstrates the importance of tailoring the polarity of the solvents, suggesting the use of ILs with mixed anions as alternative solvents for the removal of aliphatic hydrocarbons and contaminants from fuels.

Effects of the protonation and the polar solvation on the molecular properties of methyl orange: A density functional theory study

AbstractMethyl orange (MO) and its protonated derivatives were investigated at the density functional theory (DFT) level using CAM‐B3LYP functional and 6‐311 + G(d,p) basis sets; their absorption spectra in aqueous solution were simulated, their relative stabilities in both the gas phase and the polar solutions were calculated, and the activation energy barrier for the cis‐to‐trans isomerization in both phases were computed. Except the protonation at the amino group, all the protonated isomers show a bathochromic shift of the most intense absorption peak. In the gas phase, the sulfonate unit turns out to be the most favorable proton acceptor. In the polar solutions, however, azo groups are more effective to accept the proton. The protonation at the azo N atom next to the phenyl‐sulfonate group significantly reduces the energy barrier for the cis‐to‐trans conversion in the aqueous solution, which suggests a swift conversion in the ground state.

Experimental study on effect of surfactant and solution property on bubble rising motion

Bubbly flows are frequently run into in industrial processes. Since liquid phases usually contain impurities, bubble interface is polluted to a certain degree. This can affect flow structures, and heat and mass transfer properties at bubble interface, leading to a significant effect on industrial efficiencies. Therefore, it is important to study the hydrodynamic characteristics of polluted bubbles. It was experimentally investigated on the effects of surfactant concentration, ionization and solvent polarity on bubble shape, rise trajectory and velocity using a high–speed camera in this paper. The present studies show that the addition of a very small amount of non–ionic surfactants (1–OA) into a polar solution (a 56% glycerol–water solution) can cause a great change in bubble rise trajectory (an inhibition of about 80% in bubble lateral migration) and a decrease in bubble rise velocity (a decrease of about 25% in bubble maximum velocity) because surfactant molecules adsorbed at bubble interface gather tightly. However, the addition of ionic surfactant (SDS) with the same concentration into a polar solution cannot cause a significant change in bubble rise trajectory and rise velocity because the distribution of surfactant molecules adsorbed at bubble interface is relatively loose due to an electrostatic effect. The addition of surfactants into a non–polar solution (Dimethyl silicone oil) cannot obviously change the above parameters due to the non–solvent effect of surfactants in non–polar solutions. Namely, surfactant molecules cannot be adsorbed at bubble interface.

Release of Volatile Cyclopentanone Derivatives from Imidazolidin-4-One Profragrances in a Fabric Softener Application

Imidazolidin-4-ones were investigated as hydrolytically cleavable profragrances to increase the long-lastingness of perfume perception in a fabric softener application. The reaction of different amino acid amides with 2-alkyl- or 2-alkenylcyclopentanones as the model fragrances to be released afforded the corresponding bi- or tricyclic imidazolidin-4-ones as mixtures of diastereoisomers, which were separated by column chromatography. In polar solution, the different stereoisomers equilibrated under thermodynamic conditions to form mixtures with constant isomeric distributions, as shown by NMR spectroscopy. Dynamic headspace analysis on dry cotton demonstrated the controlled fragrance release from the precursors in practical application. Under non-equilibrium conditions (continuous evaporation of the fragrance) and depending on the structure and stereochemistry of the profragrances, the recorded headspace concentrations of the fragrance released from the precursors increased by a factor of 2 up to 100 with respect to the unmodified reference. Prolinamide-based precursors released the highest amount of fragrance and were thus found to be particularly suitable for prolonging the evaporation of cyclopentanone-derived fragrances on a dry cotton surface.

Structural isomerism induces pH dependent AIE-coupled ESIPT: an in-depth spectroscopic exploration with application in amine vapor sensing.

A novel excited state intramolecular proton transfer probe 3-(benzo[d]thiazol-2-yl)-4-hydroxy-5-methoxybenzaldehyde (3BTHMB) was synthesized and characterized using NMR, ESIMS and single crystal diffraction studies. The steady state and time resolved studies using the time correlated single photon counting (TCSPC) technique revealed that 3BTHMB shows ESIPT reaction with a time constant of 0.10-0.15 ns and longer local emission and anion emissions of time constants 0.5-2.0 ns and 3.0-4.0 ns, respectively, that co-exist in polar solution. In a polar protic solution like methanol, the ESIPT process is damped. Interestingly, 3BTHMB shows aggregation induced emission (AIE) solely in an acidic environment, evidenced by the enhanced quantum yield of emission (∼35%) in acidic solution as well as a long lifetime component of 7.4 ns that corresponds to the lifetime in the solid state. The AIE phenomenon was explored using the DLS technique where enhancement of the hydrodynamic radius in an acidic medium was observed. The judicious positioning of the formyl group in 3BTHMB gives the mentioned probe to show AIE in an acidic medium, as opposed to its previously reported structural isomer BTHMB, which showed no AIE phenomenon as well as its parent molecule 2-(benzo[d]thiazol-2-yl)-6-methoxyphenol (TMP), which showed AIE in neutral pH. The AIE property of 3BTHMB was exploited by successful and rapid detection of amine vapor in the solid state, qualitative ratiometric detection of aqueous pH, by observing the colour change under UV light in acidic (yellow-green) and basic to neutral (blue) medium. The above results pave the way for multiutility fluorescent probes for environmental purposes along with a deep understanding of the underlying photophysical processes which bestow the probes with such outstanding utilities.

Computational study on the antioxidant activity of five plant food benzoic acid derivatives: dearomatization and stability of H abstraction radicals

In this study, we report a computational investigation of the antioxidant activity of five plant food benzoic acid derivatives, namely gallic acid (GA), para-hydroxybenzoic acid (PHBA), protocatechuic acid (PCA), syringic acid (SA), and vanillic acid (VA). Based on a series of computed thermodynamics parameters, we have developed a comparative debate regarding their free radical scavenging activity in the gas phase and polar solutions (considering water and methanol solvents). This discussion expands to the elucidation of both the most preferred mechanism and the order of antioxidant activity in each environment. Paradoxically, calculations using the harmonic oscillator model of aromaticity (HOMA) suggest that H abstraction radicals gain stability as the central benzene ring loses structural aromaticity. Finally, spin densities and Fukui function f0 appear to be good indicators of the local reactivity of the five antioxidants toward free radicals.

Synthesis and a TD-DFT study of a series of novel 3-imidazolyl-substituted coumarin molecules with large Stokes shifts

3-Imidazo[1,2-α]pyridine coumarin 3 with four different substituents were synthesised from salicylic aldehyde derivatives, ethyl acetoacetate and 2-aminopyridine, and exhibited strong blue fluorescence in non-polar solutions and large Stokes shifts (184–210 nm) in polar solutions.

Critical fluctuations in liquid-liquid extraction organic phases controlled by extractant and diluent molecular structure.

Extractant aggregation in liquid-liquid extraction organic phases impacts extraction energetics and is related to the deleterious efficiency-limiting liquid-liquid phase transition known as third phase formation. Using small angle X-ray scattering, we find that structural heterogeneities across a wide range of compositions in binary mixtures of malonamide extractants and alkane diluents are well described by Ornstein-Zernike scattering. This suggests that structure in these simplified organic phases originates from the critical point associated with the liquid-liquid phase transition. To confirm this, we measure the temperature dependence of the organic phase structure, finding critical exponents consistent with the 3D Ising model. Molecular dynamics simulations were also consistent with this mechanism for extractant aggregation. Due to the absence of water or any other polar solutes required to form reverse-micellar-like nanostructures, these fluctuations are inherent to the binary extractant/diluent mixture. We also show how the molecular structure of the extractant and diluent modulate these critical concentration fluctuations by shifting the critical temperature: critical fluctuations are suppressed by increasing extractant alkyl tail lengths or decreasing diluent alkyl chain lengths. This is consistent with how extractant and diluent molecular structure are known to impact metal and acid loading capacity in many-component LLE organic phases, suggesting phase behavior of practical systems may be effectively studied in simplified organic phases. Overall, the explicit connection between molecular structure, aggregation and phase behavior demonstrated here will enable the design of more efficient separations processes.