Biomimetic Chromatographic Studies Combined with the Computational Approach to Investigate the Ability of Triterpenoid Saponins of Plant Origin to Cross the Blood–Brain Barrier

Biomimetic (non-cell based in vitro) and computational (in silico) studies are commonly used as screening tests in laboratory practice in the first stages of an experiment on biologically active compounds (potential drugs) and constitute an important step in the research on the drug design process. The main aim of this study was to evaluate the ability of triterpenoid saponins of plant origin to cross the blood–brain barrier (BBB) using both computational methods, including QSAR methodology, and biomimetic chromatographic methods, i.e., High Performance Liquid Chromatography (HPLC) with Immobilized Artificial Membrane (IAM) and cholesterol (CHOL) stationary phases, as well as Bio-partitioning Micellar Chromatography (BMC). The tested compounds were as follows: arjunic acid (Terminalia arjuna), akebia saponin D (Akebia quinata), bacoside A (Bacopa monnieri) and platycodin D (Platycodon grandiflorum). The pharmacokinetic BBB parameters calculated in silico show that three of the four substances, i.e., arjunic acid, akebia saponin D, and bacoside A exhibit similar values of brain/plasma equilibration rate expressed as logPS_Fubrain (the average logPS_Fubrain: −5.03), whereas the logPS_Fubrain value for platycodin D is –9.0. Platycodin D also shows the highest value of the unbound fraction in the brain obtained using the examined compounds (0.98). In these studies, it was found out for the first time that the logarithm of the analyte–micelle association constant (logK_MA) calculated based on Foley’s equation can describe the passage of substances through the BBB. The most similar logBB values were obtained for hydrophilic platycodin D, applying both biomimetic and computational methods. All of the obtained logBB values and physicochemical parameters of the molecule indicate that platycodin D does not cross the BBB (the average logBB: −1.681), even though the in silico estimated value of the fraction unbound in plasma is relatively high (0.52). As far as it is known, this is the first paper that shows the applicability of biomimetic chromatographic methods in predicting the penetration of triterpenoid saponins through the BBB.     

Chromatographic Evaluation of Octadecyl-Bonded SiO2/SiO2-Based Stationary Phase for Reversed-Phase High Performance Liquid Chromatography

A new type of octadecyl-bonded SiO₂/SiO₂ (ODSS) core–shell monodisperse silica spheres was prepared as a high performance liquid chromatography stationary phase. The chromatographic performance was evaluated and compared with totally porous octadecyl-bonded SiO₂. Various methods were used for characterization of the two column packings for reversed-phase chromatography in terms of permeability, hydrophobic selectivity, sensitivity, stability and hydrophobicity. The results showed that the ODSS-based stationary phase has enhanced permeability, good hydrophobic selectivity, high chemical stability and sensitivity. Acidic, basic and neutral aromatic compounds were separated on the two types of stationary phases. The ODSS-based stationary phase has good selectivity and gives symmetrical narrow peaks under reversed-phase conditions.     

Hydrophobicity Parameter (log Kow) Estimation for Some Phenolic Compounds of Pharmaceutical Interest from Retention Studies with Mobile Phase Composition in Reversed‐Phase Liquid Chromatography

Abstract:

Chromatographic retention of some phenolic compounds (impurities of related pharmaceutical active substances) was studied for different organic modifier contents in mobile phase. Their capacity factors k′ versus organic modifier content (acetonitrile, or methanol) in mobile phase were measured and the corresponding dependences were studied by linear and polynomial regressions and then they were extrapolated to a mobile phase with no content in organic modifier in order to estimate their octanol/water partition coefficient (log K_ow). The values of log K_ow from retention data were compared to known shake‐flask experimental values and theoretical values predicted by fragment methodology. Linear dependences for methanol and second‐degree polynomial dependences for acetonitrile between organic modifier volume percentage and log k′ provided good estimation of log K_ow. The chromatographic method can be considered as a method of choice for estimating hydrophobicity parameter for different solutes. The linear dependence between extrapolated values of log k′ for 0% organic modifier and log K_ow estimated by means of fragment methodology for the model compounds can be used to predict chromatographic retention of other similar compounds.     

Supramolecular Chromatographic Separation of C60 and C70 Fullerenes: Flash Column Chromatography vs. High Pressure Liquid Chromatography

A silica-bound C-butylpyrogallol[4]arene chromatographic stationary phase was prepared and characterised by thermogravimetric analysis, scanning electron microscopy, NMR and mass spectrometry. The chromatographic performance was investigated by using C₆₀ and C₇₀ fullerenes in reverse phase mode via flash column and high-pressure liquid chromatography (HPLC). The resulting new stationary phase was observed to demonstrate size-selective molecular recognition as postulated from our in-silico studies. The silica-bound C-butylpyrogallol[4]arene flash and HPLC stationary phases were able to separate a C₆₀- and C₇₀-fullerene mixture more effectively than an RP-C₁₈ stationary phase. The presence of toluene in the mobile phase plays a significant role in achieving symmetrical peaks in flash column chromatography.     

Compositional dependence of phase structure and electrical properties in (K0.50Na0.50)0.97Bi0.01(Nb1−xZrx)O3 lead-free ceramics

(K_0.50Na_0.50)_0.97Bi_0.01(Nb_1-xZr_x)O₃ (KNBNZ) lead-free ceramics were prepared by the conventional solid-state sintering process. Their phase structure is dependent on the Zr content in the investigated range, and the ceramics endure a phase transition from pseudocubic to orthorhombic with increasing Zr content. Improved piezoelectric properties have been observed when the poling temperature is located at ~100 °C because of the coexistence of orthorhombic and tetragonal phases. Their dielectric and piezoelectric properties were enhanced by doping Zr, the ceramic with x=0.02 showing optimal electrical properties, i.e., d₃₃~161 pC/N, k_p~0.41, Q_m~81, T_c~370 °C, and T_o−t~130 °C. These results show that the KNBNZ ceramic is a promising lead-free piezoelectric material.     

Pyrolysis of pine wood in a slowly heating fixed-bed reactor: Potassium carbonate versus calcium hydroxide as a catalyst

Catalytic pyrolysis of pine wood was carried out in a fixed-bed reactor heated slowly from room temperature to 700 °C under a stream of purging argon to examine the effects of the physically mixed K₂CO₃ or Ca(OH)₂ on the pyrolysis behaviors. K₂CO₃ demonstrated a stronger catalysis for decomposition of hemicellulose, cellulose and lignin constituents, leading to the reduced yield of liquid product in conjunction with the increased yields of gaseous and char products because of the promoted secondary reactions of liquid product. With the addition of 17.7 wt.% of K₂CO₃, none of saccharides, aldehydes and alcohols was formed and the formation of acids, furans and guaiacols was substantially reduced, whereas the yields of alkanes and phenols were increased. Potassium led to an increase in the cumulative yields of H₂, CO₂ and CO at 700 °C. Ca(OH)₂ somewhat promoted the decomposition of cellulose and lignin constituents, and the effect of Ca(OH)₂ on the yields of liquid and char was opposite to that of K₂CO₃. With the addition of 22.2 wt.% Ca(OH)₂, some groups of liquid product such as acids and aldehydes disappeared completely and the yields of saccharides, furans and guaiacols were somewhat reduced, while the yield of alcohols was remarkably increased in contrast to the result of K₂CO₃. The addition of Ca(OH)₂ did not significantly change the total yield of gaseous product at 700 °C but enhanced the yield of H₂.     

Ozone Treatment of Tannery Wastewater Monitored by Conventional and Substance Specific Wastewater Analyses

Ozone is an unstable and highly reactive gas applied in drinking water or wastewater treatment to oxidize and/or mineralize pollutants. Its application in wastewater treatment leads to a destruction of persistent pollutants combined with an improvement of biodegradability. The oxidation of organic and inorganic compounds in tannery wastewater at different pHs applying O₃ was studied. Results after O₃-treatment were determined by conventional wastewater parameters, e.g., total organic carbon (TOC), biochemical oxygen demand after 5 days (BOD₅), and chemical oxygen demand (COD), as well as by substance-specific mass spectrometric analytical techniques, i.e., gas chromatography—mass spectrometry (GC/MS) and liquid chromatography—mass and tandem mass spectrometry (LC/MS and—MSⁿ). In parallel, variations in the toxicity of the tannery wastewater against water organisms before and after O₃-treatment were determined by means of biotoxicity testing, i.e., Daphnia magna Straus and Vibrio fischeri bioassays.     

Microstructure and electrical properties of (Na0.5K0.5)1−2xMgxNbO3–Bi0.5Na0.5TiO3 lead-free piezoelectric ceramics

0.975[(Na_0.5K_0.5)_1−2xMg_xNbO₃]–0.025(Bi_0.5Na_0.5TiO₃) (KNMN–BNT, x=0, 0.01, 0.02, 0.03, 0.04 and 0.05) lead-free piezoelectric ceramics were fabricated by the conventional solid-state sintering method. The dependence of Mg content on the microstructure and electrical properties of the ceramics is investigated. The X-ray diffraction (XRD) analysis revealed that an appropriate amount of Mg diffused into the KNN–BNT lattice to form a stable solid solution, the ceramics possessed a pure perovskite structure, and a morphotropic phase boundary (MPB) between the orthorhombic and tetragonal phases was observed with the composition of 0.02≤x≤0.05. The orthorhombic–tetragonal transition temperature (T_O–T) is less than 95 °C and the Curie temperature (T_c) is almost unchanged (~360 °C) with the increase of MgO content. The ceramics with x=0.02 showed enhanced piezoelectric and ferroelectric properties because of close proximity to the MPB, i.e., d₃₃~210 pC/N, k_p~0.41, 2E_c~22.4 kV/cm and 2P_r~39.2 μC/cm². Moreover, the dielectric properties exhibited optimal effects with x=0.02, that is ε_r~637 and tan δ~0.09. These results indicate that the introduction of MgO is an effective method to improve the density as well as the electrical properties and the temperature stability of the KNN–BNT ceramics. As a result, the KNMN–BNT ceramic is a promising candidate for lead-free piezoelectric materials.     

The Synthesis of New N2S2‐Macrocyclic Schiff Base Ligands and Investigation of Their Ion Extraction Capability from Aqueous Media

Abstract

Two new macrocyclic Schiff bases, (5) and (7), containing nitrogen‐sulfur donor atoms were designed and synthesized by reaction of α,α′ bis(o‐aminophenylthio)‐1,2‐xylene with glyoxal and phthaldialdehyde, respectively. The liquid‐liquid extraction of metal picrates such as Ag⁺, Hg²⁺, Cd²⁺, Zn²⁺, Cu²⁺, Ni²⁺, Mn²⁺, K⁺, and Na⁺ from aqueous phase to the organic phase was carried out using the novel ligands. The effect of chloroform and dichloromethane as organic solvents over the metal picrate extractions was investigated at 25±0.1°C by using UV‐visible spectrometry. The extractability and selectivity of the tested metal picrates were evaluated. The values of the extraction constants (log K_ex) were determined for the extracted complexes.     

Acid/base and hydrogen bonding effects on the proton-coupled electron transfer of quinones and hydroquinones in acetonitrile: Mechanistic investigation by voltammetry, H NMR and computation

This report seeks to address the role of hydrogen bonding with Brønsted acids and bases in proton-coupled electron transfer (PCET) as it pertains to concerted or stepwise pathways of quinone (Q) and hydroquinone (QH₂) electrochemistry. This study was performed using a series of techniques that included cyclic voltammetry (CV), digital simulations, computational chemistry and ¹H NMR. Hydrogen bonding was inferred by a decrease in diffusion coefficient (D) values measured using a pulsed gradient echo- (PGE-) ¹H NMR technique. Changes of 40.8% and 37.9% in D values were only noted after the addition of two equivalents of acetate to 1,4-hydroquinone (1,4-QH₂) and catechol (1,2-QH₂), respectively. In contrast, the D values for the addition of selected amines (pyridine, N,N-diisopropylethylamine and triethylamine) changed only 3.2% on average. Quantum mechanical calculations were conducted to determine the pK_a of all quinoid species to serve as a starting point for the determination of equilibrium constants in voltammetric simulations. Simulations indicate that 1,4-benzoquinone undergoes stepwise electron-proton transfer upon addition of acetic acid, N-ethyldiisopropylammonium perchlorate and pyridinium nitrate and were simulated without the presence of hydrogen bonds. The QH₂ compounds show stepwise proton-electron transfers after addition of the both the conjugate amines and acetate.     

A rod-spacer mixed ligands MOF [Mn3(HCOO)2(D-cam)2(DMF)2]n as coating material for gas chromatography capillary column

The interest in metal-organic frameworks (MOFs) is rapidly expanding because of their fascinating architectures and intriguing topologies which allowed for potential applications in gas storage, separation, heterogeneous catalysis, and several other areas. As suitable chromatographic separation media, several MOFs have been employed as stationary phase for gas chromatography and high-performance liquid chromatography. In this work we report the use of a mixed ligands rod-spacer MOF [Mn₃(HCOO)₂(D-cam)₂(DMF)₂]_n as coating material for capillary column of gas chromatographic separation of a series of biochemical important compounds having linear alkyl hydrocarbon (aldehyde, alcohol and ester), aromatic hydrocarbon with two phenyls (ether, ester and ester with alcohol) and aromatic hydrocarbon (ester, ester with amino and two esters). The mixture of functional ligands, good thermal and chemical stabilities and host-guest interaction sites of the MOF are attributes to the good efficiency in gas chromatographic separation.     

Relationship between fracture toughness determined by surface crack in flexure and fracture resistance measured by indentation fracture for silicon nitride ceramics with various microstructures

The reliability of the Vickers indentation fracture (IF) method for various types of silicon nitride (Si₃N₄) ceramics was assessed by comparing the fracture resistance, K_R obtained from the IF test with the fracture toughness, K_Ic from the surface crack in flexure (SCF) technique in the same crack depth region. The K_R of a fine-grained and equiaxed Si₃N₄ matched with the K_Ic from the SCF test when Miyoshi's equation was used, while the K_Ic of a bearing-grade Si₃N₄ was found to lie between K_R values calculated with Niihara's equation (higher side) and Miyoshi's equations (lower side). In the case of coarse Si₃N₄ with elongated grains, the K_R determined using Niihara's equation gave the best fit with K_Ic. The inconsistent outcomes were explained by the probable mechanisms, indicating that the K_R from the IF test cannot be correlated directly with the K_Ic unless the effective crack length for the IF test was clarified.     

Separation of Triacylglycerol Species from Interesterified Oils by High-Performance Liquid Chromatography

Using a 1,3-regioselective lipase as a catalyst, soybean oil and olive oil were interesterified with the short-chain triacylglycerol tributyrin (1,2,3-tributyrylglycerol) to produce mixtures of structured triacylglycerols (SL-TAG). The SL-TAG were purified by column chromatography and analyzed by both normal-phase (silica column; NP_SIL) and reversed-phase [octadecyl silane (ODS) column] high-performance liquid chromatography (HPLC). Individual SL-TAG molecular species were detected by evaporative light-scattering detection, and characterized by mass spectrometry. NP_SIL HPLC successfully separated the newly synthesized SL-TAG into two groups of TAG: one composed of one butyryl group and two long-chain fatty acyl groups (from soybean or olive oil); the second was composed of two butyryl groups and one long-chain fatty acyl group. The SL-TAG species were further analyzed by reversed-phase HPLC which gave a more detailed separation of the TAG species present in the two SL-TAG.     

Production of Monoacylglycerols from Fully Hydrogenated Palm Oil Catalyzed by Hydrotalcite Loaded with K2CO3

This study reports a new method of producing high-purity monoacylglycerols (MAGs) by glycerolysis of fully hydrogenated palm oil (FHPO) catalyzed by hydrotalcite loaded with K₂CO₃ (K₂CO₃/HT). The effects of reaction temperature, reaction time, catalyst (K₂CO₃/HT) loading, and mass ratio of FHPO to glycerol on glycerolysis were investigated. The selected conditions included a reaction temperature of 200°C, K₂CO₃/HT loading at 0.8 wt.% (FHPO mass), a 5:2 mass ratio of FHPO to glycerol, and a reaction time of 2 h. Under these selected conditions, the yield of MAGs in the acylglycerol phase reached 46.8 wt.%. A two-stage molecular distillation was introduced to purify MAGs, and the final MAG product was obtained with a purity of 96.6 wt.% and a recovery of 96.8%. Furthermore, the recycled K₂CO₃/HT was reactivated with restored catalytic efficiency through impregnation, carbonation, and recalcination.     

The performances of higher alcohol synthesis over nickel modified K2CO3/MoS2 catalyst

Ni modified K₂CO₃/MoS₂ catalyst was prepared and the performance of higher alcohol synthesis catalyst was investigated under the conditions: T = 280–340 °C, H₂/CO (molar radio) = 2.0, GHSV = 3000 h^− 1, and P = 10.0 MPa. Compared with conventional K₂CO₃/MoS₂ catalyst, Ni/K₂CO₃/MoS₂ catalyst showed higher activity and higher selectivity to C₂⁺OH. The optimum temperature range was 320–340 °C and the maximum space-time yield (STY) of alcohol 0.30 g/ml h was obtained at 320 °C. The selectivity to hydrocarbons over Ni/K₂CO₃/MoS₂ was higher, however, it was close to that of K₂CO₃/MoS₂ catalyst as the temperature increased. The results indicated that nickel was an efficient promoter to improve the activity and selectivity of K₂CO₃/MoS₂ catalyst.     

Column Selection for Biomedical Analysis Supported by Column Classification Based on Four Test Parameters

This article focuses on correlating the column classification obtained from the method created at the Katholieke Universiteit Leuven (KUL), with the chromatographic resolution attained in biomedical separation. In the KUL system, each column is described with four parameters, which enables estimation of the F_KUL value characterising similarity of those parameters to the selected reference stationary phase. Thus, a ranking list based on the F_KUL value can be calculated for the chosen reference column, then correlated with the results of the column performance test. In this study, the column performance test was based on analysis of moclobemide and its two metabolites in human plasma by liquid chromatography (LC), using 18 columns. The comparative study was performed using traditional correlation of the F_KUL values with the retention parameters of the analytes describing the column performance test. In order to deepen the comparative assessment of both data sets, factor analysis (FA) was also used. The obtained results indicated that the stationary phase classes, closely related according to the KUL method, yielded comparable separation for the target substances. Therefore, the column ranking system based on the F_KUL-values could be considered supportive in the choice of the appropriate column for biomedical analysis.     

Wax analysis of vegetable oils using liquid chromatography on a double-adsorbent layer of silica gel and silver nitrate-impregnated silica gel

A chromatographic method is described to measure the crystallizable wax content of crude and refined sunflower oil. It can also be applied to any other vegetable oil. The preparative liquid chromatography step on a glass column containing a silica gel adsorbent superimposed upon a silver nitrate-impregnated silica gel support is used to isolate a wax fraction which is then analyzed by gas chromatography. The recovered wax fraction contains, in addition to the crystallizable waxes, hydrocarbons and other compounds with gas chromatographic retention times corresponding to waxes with chain lengths C₃₄−C₄₂. These compounds are short-chain saturated waxes in fruit oils, such as grapeseed and pomace. In seed oils such as sunflower, soybean or peanut, the compounds initially referred to as “soluble esters” are identified as monounsaturated waxes, esters of long-chain saturated fatty acids, and a monounsaturated alcohol, mainly eicosenoic alcohol. Such waxes are absent from corn or rice bran oils.     

An efficient approach for direct synthesis of K0.5Na0.5NbO3 powders

Pure K_0.5Na_0.5NbO₃ powders were prepared at low temperatures by an efficient method using Na₂CO₃, K₂CO₃ and Nb₂O₅ as raw materials and urea as fuel. The phase evolution of the powders was investigated by X-ray diffractometer (XRD) and thermo gravimetric analysis-differential scanning calorimeter (TG-DSC). The phase composition and morphology of the powders were characterized by electron probe microanalysis (EPMA) and scanning electron microscope (SEM), respectively. The results reveal that single-phase K_0.5Na_0.5NbO₃ powder can be obtained at 550 °C by the method. The as-prepared powder is stoichimetric, fine and well-developed.     

Preparation, GIAO NMR Calculations and Acidic Properties of Some Novel 4,5-dihydro-1H-1,2,4-triazol-5-one Derivatives with Their Antioxidant Activities

Six novel 3-alkyl(aryl)-4-(p-nitrobenzoylamino)-4,5-dihydro-1H-1,2,4-triazol-5- ones (2a-f) were synthesized by the reactions of 3-alkyl(aryl)-4-amino-4,5-dihydro-1H- 1,2,4-triazol-5-ones (1a-f) with p-nitrobenzoyl chloride and characterized by elemental analyses and IR, ¹H-NMR, ¹³C-NMR and UV spectral data. The newly synthesized compounds 2 were titrated potentiometrically with tetrabutylammonium hydroxide in four non-aqueous solvents such as acetone, isopropyl alcohol, tert-butyl alcohol and N,N-dimethylformamide, and the half-neutralization potential values and the corresponding pK_a values were determined for all cases. Thus, the effects of solvents and molecular structure upon acidity were investigated. In addition, isotropic ¹H and ¹³C nuclear magnetic shielding constants of compounds 2 were obtained by the gauge-including-atomic-orbital (GIAO) method at the B3LYP density functional level. The geometry of each compound has been optimized using the 6-311G basis set. Theoretical values were compared to the experimental data. Furthermore, these new compounds and five recently reported 3-alkyl-4-(2-furoylamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (3a–c,e,f) were screened for their antioxidant activities.