Apparent Partition Coefficient Research Articles

Skin deposition and permeation kinetics of cannabidiol and delta-9-tetrahydrocannabinol from cannabis extract containing gels

The study aimed to investigate the deposition and permeation characteristics of phytocannabinoids, namely delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), from cannabis extract containing gels. Cannabis extract with 26.3 % CBD and 28.4 % THC was used. The impact of permeation enhancers, namely propylene glycol, diethylene glycol monoethyl ether (DEGEE), ethanol (EtOH), and terpenes (eucalyptol and menthol), was examined. All cannabis extract gels had a pH range of 6.71–6.81 and a viscosity range of 456.6–4068.7 mPa⋅s. The phytocannabinoid release from the gels followed Zero-order kinetics with a rate of 14.5–25.7 μg⋅h−1 for CBD and 10.0−22.6 μg⋅h−1 for THC. A gel containing 12.5 % DEGEE and 12.5 % EtOH exhibited the highest release rate. The initial skin deposition followed Zero-order kinetics and reached a maximum level after 4 h. Permeation of phytocannabinoids closely followed Higuchi kinetics, with a rate of 0.14–54.21 μg⋅h−1/2 for CBD and 0.23−67.02 μg⋅h−1/2 for THC. A gel containing 25 % DEGEE and 25 % EtOH exhibited the highest apparent skin partition coefficient (K) value, resulting in the greatest phytocannabinoid deposition and permeation. Terpene introduction (5 %) significantly reduced the release rate, K value, and total skin absorption of phytocannabinoids. These findings offer useful insights into selecting the appropriate vehicle for cannabis extract topical products.

Uranium partitioning between apatite and hydrothermal fluids at 150–250 °C

This experimental study is focused on the immobilization of dissolved uranium (U) via its entrapment by apatite at hydrothermal conditions. Experiments on apatite crystallization were conducted in 0.5 M sodium chloride (NaCl) solutions at temperatures of 150, 200, and 250 °C. Uranium was introduced into the system as a solid compound (UO3), which controlled the concentration of dissolved U in the hydrothermal fluids. The results showed that U contents in apatite exceed U concentrations in co-existing fluid by 2–3 orders of magnitude. Apparent Nernst partition coefficients (DU) and exchange coefficient (KU/Ca) were evaluated. Experimentally determined DU values were consistent with DU predicted by the Lattice Strain Model at 200 and 250 °C. The obtained KU/Ca values shows dependence on temperature. The results lay the foundation for further assessment of uranium immobilization in apatite and other minerals at repository conditions.

Adenosine Triphosphate Mediates Phase Separation of Disordered Basic Proteins by Bridging Intermolecular Interaction Networks.

Adenosine triphosphate (ATP) is an abundant molecule with crucial cellular roles as the energy currency and a building block of nucleic acids and for protein phosphorylation. Here we show that ATP mediates the phase separation of basic intrinsically disordered proteins (bIDPs). In the resulting condensates, ATP is highly concentrated (apparent partition coefficients up to 7700) and serves as bridges between bIDP chains. These liquid-like droplets have some of the lowest interfacial tension (∼25 pN/μm) but high zero-shear viscosities (1-15 Pa s) due to the bridged protein networks, and yet their fusion has some of the highest speeds (∼1 μm/ms). The rapid fusion manifests extreme shear thinning, where the apparent viscosity is lower than zero-shear viscosity by over 100-fold, made possible by fast reformation of the ATP bridges. At still higher concentrations, ATP does not dissolve bIDP droplets but results in aggregates and fibrils.

Zinc complexes of chloroquine and hydroxychloroquine versus the mixtures of their components: Structures, solution equilibria/speciation and cellular zinc uptake

The zinc complexes of chloroquine (CQ; [Zn(CQH+)Cl3]) and hydroxychloroquine (HO-CQ; [Zn(HO-CQH+)Cl3]) were synthesized and characterized by X-Ray structure analysis, FT-IR, NMR, UV–Vis spectroscopy, and cryo-spray mass spectrometry in solid state as well as in aqueous and organic solvent solutions, respectively. In acetonitrile, up to two Zn2+ ions bind to CQ and HO-CQ through the tertiary amine and aromatic nitrogen atoms (KN-aminCQ = (3.8 ± 0.5) x 104 M−1 and KN-aromCQ = (9.0 ± 0.7) x 103 M−1 for CQ, and KN-aminHO-CQ = (3.3 ± 0.4) x 104 M−1 and KN-aromHO-CQ = (1.6 ± 0.2) x 103 M−1 for HO-CQ). In MOPS buffer (pH 7.4) the coordination proceeds through the partially deprotonated aromatic nitrogen, with the corresponding equilibrium constants of KN-arom(aq)CQ = (3.9 ± 1.9) x 103 M−1and KN-arom(aq)HO-CQ = (0.7 + 0.4) x 103 M−1 for CQ and HO-CQ, respectively. An apparent partition coefficient of 0.22 was found for [Zn(CQH+)Cl3]. Mouse embryonic fibroblast (MEF) cells were treated with pre-synthesized [Zn((HO-)CQH+)Cl3] complexes and corresponding ZnCl2/(HO-)CQ mixtures and zinc uptake was determined by application of the fluorescence probe and ICP-OES measurements. Administration of pre-synthesized complexes led to higher total zinc levels than those obtained upon administration of the related zinc/(hydroxy)chloroquine mixtures. The differences in the zinc uptake between these two types of formulations were discussed in terms of different speciation and character of the complexes. The obtained results suggest that intact zinc complexes may exhibit biological effects distinct from that of the related zinc/ligand mixtures.

Kinetic partitioning of trace cations between zoned clinopyroxene and a variably cooled-decompressed alkali basalt: Thermodynamic considerations on lattice strain and electrostatic energies of substitution

We present kinetic partitioning data for trace cations measured in zoned clinopyroxene crystals obtained from a variably cooled and decompressed olivine basalt erupted at Mt. Etna volcano in Italy. Supersaturation effects and compositional heterogeneities at the interface melt lead to the development of sector zoning, concentric zoning, and patchy zoning in clinopyroxene crystals. Apparent partition coefficients between compositionally different growth layers and adjacent melts (Di) for isovalent groups of trace elements are tested for internal consistency on the thermodynamic basis of lattice strain (ΔGstrain) and electrostatic (ΔGelec) energies of substitutions. The excess energy of partitioning (ΔGpartitioning) for trace cations in zoned crystals accounts for a kinetic incorporation control leading to large enthalpic effects through distortion of the lattice and changes in the electrostatic forces. ΔGpartitioning depends upon the complementary relationship between ΔGstrain and ΔGelec, which is the most appropriate thermodynamic description for the accommodation of rare earth elements and high field strength elements in the lattice site of zoned crystals. Polyhedral sectors, skeletal forms, and overgrowth zones have Di values settled by the number of charge-balanced and -imbalanced configurations taking place in the lattice site as a function of aluminium in tetrahedral coordination, and crystal structural changes produced by heterovalent cation substitutions. In an energetically unstable macroscopic system ruled by cooling and decompression, thermodynamic requirements for the crystallochemical control of Di encompass the attainment of local equilibrium at the crystal-melt interface via the establishment of small-volume reaction kinetics. The requisite of local interface equilibrium is however susceptible to the anisotropic growth velocity of each specific clinopyroxene surface, thereby giving reason to different energetic properties of the crystallographic site. This axiomatic control requires that transition metal cations partition also in consideration of electronic effects related to the crystal field stabilization energy. The overriding implication is that Di values for trace cations having different size, charge, and electronic configuration serve as sensitive probes of the different crystal growth mechanisms, surface incorporation sites, and arrangements of atoms at the lattice-scale. In this perspective, fractional crystallization modeling of 2011–2013 bulk rock data from lava fountains indicates that the compositional evolution of magmas erupted at Mt. Etna cannot be described by a unique equilibrium value of Di for a given clinopyroxene-melt interface. The leverage of interface kinetics is distinctively dominant along the subvolcanic plumbing system, thereby requiring that values of Di differ for structurally and compositionally distinct zones in clinopyroxene phenocrysts. To successfully interpret the trace element signature of Etnean magmas, the archetypal constancy of partition coefficient at bulk thermodynamic equilibrium must be in some measure reappraised in favor of the establishment of a local interface equilibrium upon highly dynamic crystallization and growth conditions.

Partitioning and isotopic fractionation of Li between mineral phases and alkaline to calc-alkaline melts of explosive and effusive eruptions

Evaluating the lithium (Li) budget of alkaline to calc-alkaline melts and their co-existing mineral phases is crucial to understanding which magmatic or post-eruptive processes can influence the Li contents and isotopic compositions of volcanic deposits. This is also important to be able to better constrain how economically relevant Li deposits form. The lithium contents of many different eruptions from different tectonic settings (intraplate, subduction zone, extensional environment) and cooling environments (quenched, quickly cooled and slowly cooled) were studied by combining new and literature data that were obtained using LA-ICP-MS. We found that the Li concentrations in melt inclusions and re-entrants are independent of tectonic setting (hotspot, subduction zone and rifting) and rarely exceed 100 ppm. When melt inclusions are re-homogenised the Li concentration increases which can lead to the overestimation of the Li budget of a magma.The highest Li concentrations in the alkaline suite of samples were found in groundmass glass (reaching up to 318 ppm). The Li contents in the co-existing mineral phases decrease in the following order: biotite (0.8–99.3 ppm), plagioclase (0.9–25.1 ppm), clinopyroxene (0.6–31.0 ppm) and sanidine (0.5–38.7 ppm). The highest Li concentrations in the calc-alkaline suite of samples were found in the biotite crystals (10.2–2314 ppm) followed by the groundmass glass (2.1–176 ppm). The Li contents are lower in the other mineral phases, from plagioclase (1.4–35.0 ppm), quartz (3.2–21.1 ppm), olivine (1.0–16.3 ppm), sanidine (0.3–8.1 ppm) to clinopyroxene (0.7–21.8 ppm). The Li concentrations in groundmass glass and co-existing crystal phases are independent of the tectonic setting but appear to be more closely related to their cooling environment. To evaluate the influence of the different cooling environments the Li isotopic compositions (per mil deviation of 7Li/6Li ratio relative to L-SVEC reference material) of different eruptions were also determined. The Li isotopic compositions of groundmass glass and mineral phases reveal a range in δ7Li composition spanning up to 6 ‰ for alkaline samples and >10‰ between bulk sample and mineral phases for calc-alkaline samples. The cooling environment of the samples has a large impact on the Li isotopic compositions of the mineral phases with only quartz seemingly unaffected. Rapidly quenched samples may retain their magmatic δ7Li compositions or will only experience small amounts of diffusional overprinting (e.g., by degassing) whereas slowly cooled samples will experience a prolonged diffusional exchange between minerals and matrix overprinting their magmatic δ7Li compositions.The Li inventory in quartz crystals may be influenced by the tectonic setting and water concentration in the crystals. To further assess the influence of tectonic settings on Li behaviour we used a large data set which is based on the 13 alkaline to calc-alkaline eruptions from different tectonic settings and calculated the apparent partition coefficients (Kds) between groundmass glass and co-existing mineral phases. Biotite crystals (alkaline systems) return the highest Kds (subduction-extensional setting: 0.01–0.57, oceanic hotspot: 0.17–2.65) whereas sanidine crystals yield the lowest Kds. Sanidines from the subduction-extensional setting (alkaline trend) have the lowest Kds (0.01–0.07; one outlier ranging from 0.02 to 0.24), followed by the oceanic hotspot setting (alkaline trend, 0.02–0.09) and the extensional setting (calc-alkaline trend; 0.01–0.15). Plagioclase crystals from the subduction-extensional setting (alkaline trend) yield Kds between 0.01 and 0.29, crystals from subduction zone settings (0.06–0.81) and extensional settings (0.09–0.50) have larger ranges in their Kds. The clinopyroxene crystals from the subduction zone settings (calc-alkaline trend) have the largest range in Kds (0.03–0.99), followed by the oceanic hotspot setting (alkaline trend, 0.06–0.48) and subduction-extensional setting (alkaline trend, 0.01–0.22). Quartz crystals (only from the calc-alkaline trend) from subduction zone settings have lower Kds (0.09–0.13) compared to the extensional settings (Bishop Tuff: 0.14–0.28; Caetano Tuff: 0.73–0.94). The wide variety of processes that can affect final Li abundances in melt and crystals (degassing, scavenging into fluids, intra-crystal diffusion, hydration of glasses) makes estimating the partition coefficients particularly difficult and results in the wide ranges observed here. Targeted experimental work would thus help to better constrain the behaviour of Li in alkaline compositions.

Uranium uptake by phosphate minerals at hydrothermal conditions

The goal of this work was to evaluate the immobilization of uranium (U) through crystallization of calcium phosphate minerals (phosphates), which have a strong ability to absorb and retain dissolved uranyl, and therefore, are useful in various geological and environmental applications. To date, most of the experimental studies have been conducted at room temperature and high temperature assessments on uranium immobilization rely on the extrapolation procedure, which is not always accurate. To evaluate uranium partition coefficients between phosphates and hydrothermal fluid, we performed a series of crystallization experiments at 25–350 °C and various aqueous uranium concentrations.Crystallization occurred through the transformation of brushite to monetite or/and apatite in aqueous solutions doped with uranium aliquots. Solid products were extracted and characterized with X-ray diffraction (XRD) and scanning electron microscopy (SEM). The local bonding environment and valence state of uranium in apatite were determined via X-ray absorption spectroscopy (XAS). Uranium concentration in crystals and coexisting solutions were measured with inductively coupled plasma mass spectrometry (ICP-MS). Apparent partition coefficients were calculated as Nernst partition coefficients (DU) and Doener-Hoskins partition coefficients (KD−HU/Ca) (to account for closed reservoir effect). Experimental DU values were compared with those calculated using the lattice strain model. Results showed that >92% of U added to solutions was extracted via this crystallization method and KD−HU/Ca decreases with increasing phosphate crystallization temperature. Thus, phosphates, especially apatite, has a strong potential to immobilize uranium under hydrothermal conditions and can be used in the development of engineering barriers to further improve the efficiency of existing backfill materials in the disposal of nuclear waste.

Bilayer-modifying potency of antipsychotics as a function of pH.

Antipsychotic drugs (APDs) have complex pharmacological profiles with a range of putative membrane protein targets and off-target effects. We have previously shown that APDs, including chlorpromazine (CPZ) and trifluoperazine (TFP), alter lipid bilayer properties as detected by bilayer-spanning gramicidin channels, which raises the possibility that at least part of their non-specific effects may be mediated by the bilayer. Following Malheiros et al. (1998) and Ahyayaych et al. (2003), who showed that the bilayer affinity of a titratable drug depends on its charge, being higher for neutral molecules, we explored the role of charge on the bilayer-modifying potencies of CPZ and TFP at pHs between 4 and 10. (Short-term exposure to pH 10 does not cause measurable changes in bilayer properties.) Using dynamic and electrophoretic light scattering to monitor partitioning of the charged species, we found that increasing pH produced a decrease in the magnitude of the zeta potential for both CPZ and TFP with little effect on the particle size distribution. Using gramicidin channels as probes, we found that the bilayer-modifying potencies of the drugs varied with changes in pH: the potency of CPZ increased modestly with increasing pH, while the potency of TFP varied little at low concentrations (3 and 10 µM) but decreased as pH increased at 30 µM. From experiments changing the total lipid concentration in the system, we found that the apparent partition coefficient of CPZ increased from pH 4 to pH 10, whereas that for TFP decreased. We conclude that the bilayer-modifying potency of a titratable drug is different for the neutral and charged species, with the charged species being more bilayer-modifying per molecule in the membrane.

Preparation, Characterization and Transdermal Permeation of Losartan-Amlodipine Molecular Salt

Drug molecular salt composed of the antihypertensive compound losartan (LOS) as the anion and the antihypertensive drug amlodipine (AMLO) was prepared. The prepared salt (LOS-AMLO) was characterized by measurement of purity, water content, solubility, partition coefficient, and melting behavior in addition to common spectroscopic techniques (UV, FTIR and NMR). NMR spectral shifts of particular protons of LOS in particular were quite useful in explaining the points of interaction and association between the two ionic species so that a 3D structure could be proposed. LOS-AMLO exhibited a significantly lower melting point than its parent compounds (65 oC) which places the salt within the ionic liquids category, in a broad sense of the definition. LOS-AMLO was found to have much lower solubility than LOS with a substantially higher apparent partition coefficient. The high partition coefficient together with lower melting temperature is favorable properties for the transdermal permeation of pharmaceuticals. However, diffusion studies through the human stratum corneum, from an aqueous solution based on propylene glycol revealed a vast decrease in the permeation of both drugs from the molecular (ionic liquid) salt form. Interestingly the experiment demonstrated that the salt structure might be maintained during permeation but with indications of strong chemical interaction between the salt and the constituents of the barrier.

A study on the enrichment mechanism of three nitrophenol isomers in environmental water samples by charge transfer supramolecular-mediated hollow fiber liquid-phase microextraction.

To explore the mechanism of extraction and enrichment of three nitrophenol isomers by charge-transfer supramolecular synergistic three-phase microextraction system, a charge transfer supramolecular-mediated hollow fiber liquid-phase microextraction (CTSM-HF-LPME) combined with high-performance liquid chromatography-ultraviolet detector (HPLC-UV) method was established for the determination of real environmental water samples. In this study, the three nitrophenols (NPs) formed charge-transfer supramolecules with electron-rich hollow fibers, which promoted the transport of NPs in the three-phase extraction system and greatly increased the EFs of NPs. The relationships between the EFs of NPs and their solubility, pKa, apparent partition coefficient, equilibrium constant, and structural property parameters were investigated and discussed. At the same time, most of factors affecting the EFs of NPs were investigated and optimized, such as the type of extraction solvent, pH value of sample phase and acceptor phase, extraction time, and stirring speed. Under optimal conditions, the EFs of o-nitrophenol, m-nitrophenol, and p-nitrophenol were 163, 145, and 87, respectively. With good linearity in the range of 5 × 10-7 ~ 1µg/mL, and the limit of detection of 0.1pg/mL, the relative standard deviations of the method precision were lower than 7.4%, and the average recoveries were between 98.6 and 106.4%. This method had good selectivity and sensitivity, satisfactory precision, and accuracy and had been successfully applied to the trace detection of real water samples.

Mucosal Delivery of Cannabidiol: Influence of Vehicles and Enhancers.

In this study, the mucosal permeation and deposition of cannabidiol (CBD) with neat and binary vehicles were investigated. Permeation experiments were performed using static diffusion cells coupled with fresh porcine esophageal mucosa. The CBD–vehicle solutions were applied at a fixed dose (~5 mg/cm2), and the corresponding permeation parameters were calculated. In neat vehicles, the permeation flux (Jss) ranged from 0.89 ± 0.15 to 179.81 ± 23.46 µg·cm−2·h−1, while the CBD deposition ranged from 11.5 ± 1.8 to 538.3 ± 105.3 μg·cm−2. Propylene glycol (PG) and diethylene glycol monoethyl ether (DEGEE) yielded the highest permeability (Ps) and CBD deposition, while medium-chain triglycerides (MCT) yielded the lowest Ps and deposition. This was due to the difference in apparent partition coefficient (K), which is related to the solubility of CBD in the vehicle. The PG:DEGEE binary vehicle boosted Jss (1.5–1.6 fold) and deposition (2.0–2.7 folds) significantly, compared to neat DEGEE. The combination of DEGEE with MCT dramatically enhanced Jss (11–44 fold) and deposition (1.6–4.7 fold). The addition of lipophilic enhancers, laurocapram, and oleic acid, to PG:DEGEE and DEGEE:MCT vehicles significantly reduced Jss (0.3–0.7 fold) and deposition (0.4–0.8 fold) while nerolidol had no effect. These permeation reductions were found to be related to modification of the K and/or diffusivity values. This study provides useful basic information for the development of CBD formulations intended for transmucosal delivery.

The spectrophotometric determination of lipophilicity and dissociation constants of ciprofloxacin and levofloxacin

Lipophilicity plays a significant role in the permeability of the drugs through cell membranes and impacts the drug activity in the human body. In this paper, the spectrophotometric method was used to determine the apparent partition coefficients of two amphoteric drugs: ciprofloxacin and levofloxacin. The apparent partition coefficient was determined with the classic shake-flask method with n-octanol according to OECD guidelines. The lipophilicity profiles in a wide range of pH were determined and described quantitatively with the quadratic function. Basing on the macro- and microdissociation constants, the true partition coefficient for both drugs was calculated. Both levofloxacin and ciprofloxacin were lipophilic. The neutral forms, i.e., zwitterionic and uncharged, dominate in the pH relevant to the one in the intestines, the place from which they are absorbed.

Solubility and partition behavior of moxifloxacin: Experimental results and thermodynamics properties

The pharmaceutically relevant physico-chemical properties as solubility and lipophilicity of antimicrobial moxifloxacin (MFX) in modelling solvents and biphasic systems were determined using the shake flask method from 293.15 to 313.15 K. The equilibrium MFX solubility (x, mol. frac.) was changed in next order: ethanol (1.08 · 10−2) > 1-octanol (1.18 · 10−3) > buffer pH 2.0 (1.37 · 10−3) > buffer pH 7.4 (6.45 · 10−4) > hexane (1.13 · 10−5). The obtained result good correlated with relative polarity of selected solvents. MFX solubility in buffer solutions is higher in an acid medium, and tends to decrease at increasing pH values, that explained by protolytic properties of compound studied. The experimental solubility values of MFX in selected solvents were mathematically described by two classical models (modified Apelblat and van’t Hoff equations) with good fitting accuracy. A graphical representation of the Hansen solubility parameters for the studied solute/solvent systems is provided in the form of a Bagley diagram. MFX was described as slightly lipophilic drug. Thermodynamic functions of solubility and transfer processes were calculated on base temperature dependencies of solubility and apparent partition coefficients, respectively. The solubility process was characterized as endothermic in the all studied solvents.

Partition of a mixture of chlorinated organic compounds in real contaminated soils between soil and aqueous phase using surfactants: Influence of pH and surfactant type

The equilibrium between surfactant adsorption and contaminants desorption was studied. Two soil samples from a polluted site with residues from lindane production, compounded of a complex mixture of 28 chlorinated organic compounds (COCs) and different concentration of COCs in soil (2.27 and 34.69 mmolCOCs·kgsoil−1), were used. Soil was in contact with aqueous surfactant solutions (1–15 g·L−1) of nonionic (E-Mulse® 3, and Tween® 80) and anionic (sodium dodecylsulfate) surfactants. Due to alkaline pH promoting the dehydrochlorination of COCs, neutral pH and strongly alkaline pH (pH > 12) were studied. It was found that the higher the COCs concentration adsorbed in soil, the higher the adsorption of the surfactants, finding an irreversible adsorption in the case of nonionic surfactants. The desorption of COCs increased with the surfactant concentration in the aqueous phase and was not selective towards any contaminant. Although at neutral pH, higher COC desorption was found with nonionic surfactants, at alkaline pH surfactant the anionic surfactant improved its COCs desorption capacity significantly. Finally, the adsorption of the surfactants was well adjusted to Langmuir, and the apparent partition coefficient predicted the partitioning of COCs between the soil and aqueous phases, which changes with the surfactant concentration in the aqueous solution.

The effect of microorganisms on the biomodification of montan resin from lignite

Montan resin (MR) is an industrial by-product or solid waste generated during the production of refined montan wax and is not typically reused. In this paper, a bio-modification method using three strains of microorganisms, Acinetobacter venetianus (AV), Pseudomonas aeruginosa (PA), and Phanerochaete chrysosporium (PC), was studied to promote the performance and bio-function of MR so that MR could be recycled. MR can be degraded by these three microorganisms, and their weight loss rates were similar over the treatment period of 15 days. Compared with the original MR, the hydrophilicity of modified MRs was improved, which was related to the increase in apparent oil-water partition coefficients (Kows) and oxygen-containing and hydrophilic groups in modified MRs based on IR and GC-MS analysis. The bio-function of modified MRs by the three strains in terms of promoting maize seed germination and seedling growth was greater compared with untreated MR. Overall, these findings indicate that biomodified MRs might have useful agriculture applications.

Synthesis, Antitumor Activity, Oil-Water Partition Coefficient, and Theoretical Calculation of 2 New Rutaecarpine Derivatives With Methoxy Groups

Two rutaecarpine (RUT) derivatives, substituted with methoxy groups, namely, 2-methoxyl rutaecarpine (RUT-OCH3, 3a), and 2,10-dimethoxy rutaecarpine (RUT-(OCH3)2, 3b), were synthesized and characterized using 1H nuclear magnetic resonance (NMR), 13C NMR and mass spectra. The in vitro antitumor activities of compounds RUT, 3a, and 3b against A549, H1299, and HepG2 cells were studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. The results showed that the activity of compounds 3a and 3b was stronger than that of compound RUT, and the activity of compound 3a was stronger than that of 3b, indicating that the activity of the compounds was improved after structural modification. The apparent oil-water partition coefficients of compound RUT, 3a, and 3b were explored using ultraviolet spectrometry. The results indicated that hydrophobicity affects the physicochemical properties of the molecules and influences antitumor activities. In addition, the Natural Electron Configuration, frontier molecular orbital (highest occupied molecular orbital, lowest unoccupied molecular orbital) bandgaps of compounds have been studied based on density functional theory (DFT) by means of DFT-B3LYP/6‐31G (d) in Gaussian 16. The calculation results showed that bandgap of 3a is highest, indicating that the stability of 3a is weakest, so 3a has higher activity than RUT and 3b, which agrees with the results of antitumor activities experiment.

Variant Offset-Type Platinum Group Element Reef Mineralization in Basal Olivine Cumulates of the Kapalagulu Intrusion, Western Tanzania

Abstract The Kapalagulu intrusion in eastern Tanzania hosts a major, 420-m-thick, stratiform/stratabound platinum group element (PGE)-bearing sulfide zone—the Lubalisi reef—within a prominent, chromititiferous, harzburgite unit close to its stratigraphic base. Several features of the vertical base and precious metal distributions (in a composite stratigraphic section based upon two deep exploration drill holes) display similarities to those of offset-type PGE reefs that formed under the overall control of Rayleigh fractionation: (1) composite layering (at several scales) defined by systematic vertical variations of sulfide and precious metal contents and intermetallic ratios, indicating repeated cycles of PGE enrichment and depletion in the order Pd-Pt-Au-Cu, and (2) in the lower part of the reef, stratigraphic offsets of the precious metal peaks below peak sulfide (Cu) content. The form and geochemistry of the reef are consistent with overturns of basal liquid layers within a liquid layering system (i.e., stable density-driven stratification of a magma chamber), plus at least two minor inputs of parental magma during which the resident magma was recharged with sulfur and metals, and the effective depletion of precious metals in the magma midway through reef development. The Lubalisi reef differs from classic offset-type PGE reefs, however, principally because individual Pd, Pt, and Au enrichment peaks are coincident, not offset. The reef is set apart from other offset-type PGE reefs in three additional ways: (1) its association with olivine cumulates that crystallized soon after initial magma emplacement and well below the first appearance of cumulus pyroxene or plagioclase (implying attainment of sulfide saturation and precious metal enrichment without prolonged concentration of sulfur and chalcophile metals by normal magma cooling and differentiation), (2) the probable role of chromite crystallization in not only triggering sulfide segregation during reef formation but also facilitating precious metal enrichment in the early stages of reef development, and (3) its great width. The early stage of fractionation may also help explain the coincident precious metal peaks through its effect on apparent precious metal partition coefficients.

Partitioning of elements between high-temperature, low-density aqueous fluid and silicate melt as derived from volcanic gas geochemistry

By comparing high-quality volcanic gas and whole rock compositions, we calculated the apparent (observed) mass partition coefficients Kd* for 58 elements on six basaltic volcanoes located in arc and rift/hotspot settings. The inferred Kd* vary from ∼1100 for sulfur to 0.0001 for zirconium, i.e., within seven orders of magnitude. Only 14 elements have Kd* > 1, including highly volatile S, Se, Te and halogens, as well as Tl, Re, Os, Bi, Cd, Au, In and As. Alkali metals have Kd* in the range from 0.1 for Cs to 0.01 for Na. Partition coefficients of other rock-forming elements are <0.001. The partition coefficients for elements depend on element speciation and concentrations of ligand-forming elements in the gas such as sulfur and chlorine. Elements transported in the gas predominantly as halides have higher partition coefficients in HCl-rich arc gases, whereas elements preferably forming sulfides, hydrides and free atoms, have higher Kd* in sulfur-rich, HCl-poor and reduced rift/hotspot gases. Degassing directly from the free melt surface is negligible; deep gas passing through the erupting vent is quickly overwhelmed by the signal of low-pressure degassing. Equilibration of rising bubbles with the surrounding melt almost eliminates the difference between Kd* calculated for degassing lava flows (no connection with deep magma) and for lava lakes and open-vent volcanoes (convective mass exchange with deep magma takes place). Diffusion does not strongly affect the apparent partitioning of magmas degassing at surface. Gas bubbles growing in near-surface silicate melts at atmospheric pressure have a large density difference compared to the surrounding melt of 12–15 thousand times. This leads to the rapid expansion of such bubbles and a decrease in the thickness of the diffusion boundary layer in the melt due to its stretching around the growing bubble, which sharply decreases diffusion fractionation. As a result, the apparent partition coefficients (Kd*) for degassing basaltic volcanoes are close to the equilibrium ones (Kd) for most of the elements. The partition coefficients of volatile elements (S and Cl) calculated from the comparison of volcanic gas and rock compositions are in agreement with the values determined previously via experiments or theoretical modeling.

In Situ Measuring Partition Coefficient at Intact Nanoemulsions: A New Application of Single-Entity Electrochemistry.

We report a new application of the single-entity electrochemistry (SEE) to in situ measure a partition coefficient at intact nanoemulsions (NEs). The partition coefficient at intact NEs is the most crucial physicochemical property to determine the uptake of delivery molecules inside NEs. It, however, has not been unequivocally elucidated by currently existing techniques based on ex situ measurements. Herein, we apply the single-entity electrochemistry (SEE) to directly and quantitatively measure the partition coefficient at NEs in situ. In this work, we use NEs featured with amphiphilic triblock copolymer (Pluronic F-127) as a model system to extract/preconcentrate 2-aminobiphenyl (2-ABP) dissolved in the water and demonstrate a new application of SEE to in situ quantitatively estimate the amounts of 2-ABP distributed into each intact NE. Our SEE measurements reveal that the partitioning is governed by extraction of 2-ABP inside NEs rather than its adsorption on the NE surface, and this extraction is remarkably efficient with up to ∼8 orders of magnitude of the preconcentration factor, thus leading to the unprecedentedly large partition coefficient of 1.9 (±1.4) × 1010. This result implies that not only the thermodynamic distribution but also the intermolecular interaction of extracted compounds inside NEs could play a significant role in the apparent partition coefficient (P = 1.9 (±1.4) × 1010). The experimentally determined partition coefficient was validated by molecular dynamics (MD) simulations with showing a stabilizing role of intermolecular interaction in the partitioned system. We further verified our methodology with other compounds exhibiting aromatic properties, e.g., ferrocenemethanol. Significantly, our new approach can be readily applicable to investigate practical NEs commercially marketed for drug, food, and cosmetics.

Characterization of oil/water partition coefficient of chishao terpene glucoside components based on contribution rate of representative components for myocardial ischemia

The components of traditional Chinese medicine(TCMCs) are the basic unit of raw materials for Chinese medicines, and their physical and chemical properties directly affect the choice of dosage forms and the optimization of prescriptions. However, most of TCMCs are multi-component complex systems, and the characterization of their overall properties is still in the exploration stage. On the basis of biological activity, the representative components are determined, and then the individual characteristics are fitted with the weight coefficient of efficacy contribution rate, which may provide reference for characterizing the overall properties of TCMCs. In this study, with the pharmacological effects of isoproterenol(ISO)-induced myocardial ischemia in rats as the indicators, the pharmacodynamic contribution rates of three representative components of chishao terpene glucoside components(CSTGCs) were evaluated by the normalization weighting method. The contribution rates of paeoniflorin, paeoniflorin and benzoylpaeoniflorin were 54.87%, 32.46% and 12.67%, respectively. The oil-water partition coefficients of paeoniflorin, albiflorin, benzoylpaeoniflorin in water and buffer solutions with different pH values were measured, and the oil-water partition coefficients of CSTGCs were characterized by the weight of their pharmacodynamics contribution rate. The results showed that the apparent oil-water partition coefficient(log P) of CSTGCs in the phosphate buffer system such as n-octanol-water(pH 2.0, 2.5, 5.0, 5.8, 6.8) were 0.18-0.22, indicating that CSTGCs have common absorption and low permeability, providing basis for the preparation of CSTGCs.