Partition Coefficient Research Articles

Effect of phase exchange kinetics on Taylor dispersion of chemically reactive solutes in an oscillatory magnetohydrodynamics flow between two parallel plates

The study of kinetic sorptive effects on the transport phenomena of reactive solute has numerous real-world applications, including in the industrial and environmental sectors. These kinds of investigations become more realistic when an oscillatory pressure gradient with both the reversible and irreversible reactions at the channel walls is considered in a magnetohydrodynamics flow. In the past, Ng and Yip [J. Fluid Mech. 446, 321–345 (2001)] studied the effect of sorptive phase exchange at boundaries on the solute transport phenomena in an open-channel flow using Mei's multiple-scale homogenization technique. They considered fluid flows without magnetic field and boundary absorption. This work uses the above-mentioned method to investigate the phase exchange kinetics of Taylor dispersion phenomena in a two-dimensional magnetohydrodynamics fluid flowing through a parallel channel. The paper discusses how various parameters and dimensionless numbers, such as the Hartmann, oscillatory Reynolds, and Damkohler, affect the flow velocity, transport coefficient, multi-dimensional concentration distributions, and transverse variation rate. Due to the strong magnetic field, the flow velocity and Taylor dispersivity are adversely affected and conspicuously reduced. Additionally, for large Damkohler numbers, the total dispersion coefficient and the Taylor dispersion coefficient both decrease. However, the longitudinal concentration distribution rises with the Hartmann number and partition coefficient. It is worth noting that in the presence of unequal boundary absorption, there is no occurrence of transverse symmetry in solute concentration at any given time. Controlling various processes of tracer dispersion in environmental systems, especially water purification and the chemical industry, may benefit from these intriguing findings.

Predicting lung exposure of intramuscular niclosamide as an antiviral agent: Power-law based pharmacokinetic modeling.

Niclosamide, a potent anthelmintic agent, has emerged as a candidate against COVID-19 in recent studies. Its formulation has been investigated extensively to address challenges related to systemic exposure. In this study, niclosamide was formulated as a long-acting intramuscular injection to achieve systemic exposure in the lungs for combating the virus. To establish the dose-exposure relationship, a hamster model was selected, given its utility in previous COVID-19 infection studies. Pharmacokinetic (PK) analysis was performed using NONMEM and PsN. Hamsters were administered doses of 55, 96, 128, and 240 mg/kg with each group comprising five animals. Two types of PK models were developed, linear models incorporating partition coefficients and power-law distributed models, to characterize the relationship between drug concentrations in the plasma and lungs of the hamsters. Numerical and visual diagnostics, including basic goodness-of-fit and visual predictive checks, were employed to assess the models. The power-law-based PK model not only demonstrated superior numerical performance compared with the linear model but also exhibited better agreement in visual diagnostic evaluations. This phenomenon was attributed to the nonlinear relationship between drug concentrations in the plasma and lungs, reflecting kinetic heterogeneity. Dose optimization, based on predicting lung exposure, was conducted iteratively across different drug doses, with the minimum effective dose estimated to be ~1115 mg/kg. The development of a power-law-based PK model proved successful and effectively captured the nonlinearities observed in this study. This method is expected to be applicable for investigating the drug disposition of specific formulations in the lungs.

Machine learning screening tools for the prediction of extraction yields of pharmaceutical compounds from wastewaters

Pharmaceutical compounds have become an increasingly important source of pollutants in wastewaters being conventional treatments ineffective in removing them, so they are commonly discharged into the environment. Pharmaceuticals can be successfully removed using liquid-liquid extraction, and COSMO-RS can be used to predict interactions and identify the most promising solvents. However, COSMOtherm models cannot account for key process parameters, which reduces the accuracy of these computational models. Therefore, there is a need for alternative computational approaches to accurately predict the extraction yields of pharmaceuticals which can incorporate both processing and interaction variables. This work used machine learning to predict the extraction yield of eleven pharmaceuticals using eight solvents. Six regression models and two classification models were explored. The best performance was obtained with ANN regressor (test MAE: 4.510, test R2: 0.884) and RF classifier (test accuracy: 0.938, test recall: 0.974). The RF regression analysis and classification also showed key extraction yield features: solvent-to-feed ratio, n–octanol–water partition coefficient, hydrogen bond and Van der Waals contributions to excess enthalpy, and pH distance to nearest pKa. Machine learning showed as an excellent tool for screening and selecting the most promising solvents and process conditions to remove pharmaceuticals from wastewater.

Greenhouse gases capture applying impregnated silica with ionic liquids, deep eutectic solvents, and natural deep eutectic solvents.

The development of technologies to capture greenhouse gases (GHGs) like carbon dioxide (CO2) and nitrous oxide (N2O) is vital for climate change mitigation. Ionic liquids (ILs), deep eutectic solvents (DES), and natural deep eutectic solvents (NADES) are promising absorbents to abate GHGs emissions. However, their high viscosity limits the gas-liquid contact, as consequence of the mass transfer. To overcome this, their impregnation onto porous silica gel has been carried out, increasing the gas-liquid contact area. The present study analyzes the effect of size particle of silica gel impregnated with ILs, DES, and NADES over the CO2 and N2O capture at atmospheric conditions. The degree of impregnation of silica particles was determined by thermogravimetric analysis (TGA). The identification of functional groups present on the surface of silica, ILs, DES, and NADES was performed using Fourier-transform infrared spectroscopy (FTIR), and their crystalline structure was determined by X-ray diffraction (XRD). The partition coefficient of CO2 and N2O between gas and ILs, DES, and NADES was determined by a static headspace method. Results show that the degree of solvent impregnation on silica gel ranged from 36.8 to 43.0% w/w, the partition coefficient of CO2 in the impregnated silica varied from 0.005 to 0.067, and for N2O, from 0.005 to 0.032. This suggests that impregnated particles have a greater affinity for N2O compared to CO2. Using impregnated particles requires only 40% of the bulk solvent to achieve a similar GHG capture capacity compared to using bulk solvents.

Passive biomonitoring for per- and polyfluoroalkyl substances using invasive clams, C. fluminea

Per- and polyfluoroalkyl substances (PFAS) are a class of toxic manufactured chemicals in commercial and consumer products. They are resistant to environmental degradation and mobile in soil, air, and water. This study used the introduced bivalve Corbicula fluminea as a passive biomonitor at sampling locations in a primary drinking water source in Virginia, USA. Many potential PFAS sources were identified in the region. Perfluorohexane sulfonate (PFHxS) and 6:2 fluorotelomer sulfonic acid (6:2 FTS) levels were highest downstream of an airport. The highest levels of short-chain carboxylic acids were in locations downstream of a wastewater treatment plant. Measured PFAS concentrations varied by location in C. fluminea, sediment, and surface water samples. Two compounds were detected across all three mediums. Calculated partitioning coefficients confirm bioaccumulation of PFAS in C. fluminea and sorption to sediment. C. fluminea bioaccumulated two PFAS not found in the other mediums. Perfluoroalkyl carboxylic acids and short-chain compounds dominated in clam tissue, which contrasts with findings of accumulation of longer-chain and perfluorosulfonic acids in fish. These findings suggest the potential for using bivalves to complement other organisms to better understand the bioaccumulation of PFAS and their fate and transport in a freshwater ecosystem.

Decoding degassing modes of magma chamber of arc volcanoes: Insights from CO2/Cl and Cl/H2O ratios of magmatic fluids in groundwater

The H2O-CO2-Cl composition of the fluids released from the magma chambers for arc volcanoes was calculated based on the solubilities of H2O and CO2 in the silicate melt and the partition coefficient of Cl between the aqueous fluid and melt for the stages defined by a simple evolution model of the magma chamber. The degassing modes consisted of mafic bubbling (MB: first boiling) and felsic bubbling (FB: second boiling) releasing fluids as separate bubbles due to the mafic magma supply and felsic magma formation by differentiation, respectively, and felsic solidification (FS) releasing fluid due to felsic pluton formation. The variations in the CO2/Cl and Cl/H2O ratios of the fluids were examined for each degassing mode at pressures ranging from 150 to 400 MPa and were found to have very large variations at 0.00024–845 for CO2/Cl and 0.00043–0.041 for Cl/H2O. The CO2/Cl is concluded to be a good indicator of magma chamber conditions because each mode has a specific ratio distinguished from that of the other modes; i.e., CO2/Cl > 43 for MB, 0.027–23 for FB, and < 0.62 for FS.The alteration of magmatic composition of fluid during ascent was discussed considering the phase separation of fluid, CO2 bubbling in groundwater, dissolution, and deposition of minerals; furthermore, the limitation of the method when applied to natural groundwater systems were outlined. This method was tested for a natural volcanic system, the Kuju volcano in central Kyusyu, Japan, which is an active volcano complex composed of various magma types from rhyolitic to basaltic, replacing the eruption centers from west to east. Groundwater samples from springs and boreholes were collected and analyzed for chemical and isotopic compositions to determine the magmatic H2O, dissolved inorganic carbon (DIC), and Cl concentrations. The new approach to determine the magmatic CO2 concentration in groundwater using 3He concentration proposed herein cancelled the effect of carbonate deposition/dissolution, addition of DIC from organic matter, and bubbling of CO2. The estimated magmatic CO2/Cl ratios were 0.0009–14, which overlapped consistently with the modeled variation in the CO2/Cl ratio. The spatial variation of magmatic CO2/Cl in groundwater showed that higher-CO2/Cl are found near the central part of the volcanic complex which composed of felsic to mafic volcanoes, and low-CO2/Cl are only found around old felsic volcanoes. The CO2 bubbling springs were found to be associated with younger mafic volcanoes. The condition of the magma chambers, as shown by the spatial variation in CO2/Cl, were consistent with the record of the eruptive activities of the Kuju volcano. The CO2/Cl method proposed in this study using groundwater is useful for estimating magmatic conditions in chambers.

Partitioning recombinant chitinase from Nicotiana benthamiana by an aqueous two-phase system based on polyethylene glycol and phosphate salts

The objectives of this study were to purify 42 kDa chitinase derived from Trichoderma asperellum SH16 produced in Nicotiana benthamiana by a polyethylene glycol (PEG)/salt aqueous two-phase system (ATPS). The specific activities of the crude chitinase and the partially purified chitinase from N. benthamiana were about 251 unit/mg and 386 unit/mg, respectively. The study found the 300 g/L PEG 6000 + 200 g/L potassium phosphate (PP) and 300 g/L PEG 6000 + 150 g/L sodium phosphate (SP) systems had the highest partitioning efficiency for each salt in primary extraction. However, among the two types of salt, PP displayed higher efficiency than SP, with a partitioning coefficient K of 4.85 vs. 3.89, a volume ratio V of 2.94 vs. 2.68, and a partitioning yield Y of approximately 95 % vs. 83 %. After back extraction, the enzymatic activity of purified chitinase was up to 834 unit/mg (PP) and 492 unit/mg (SP). The purification factors reached 3.32 (PP) and 1.96 (SP), with recovery yields of about 59 % and 61 %, respectively. SDS-PAGE and zymogram analysis showed that the recombinant chitinase was significantly purified by using ATPS. The purified enzyme exhibited high chitinolytic activity, with the hydrolysis zone's diameter being around 2.5 cm–3 cm. It also dramatically reduced the growth of Sclerotium rolfsii; the colony diameter after treatment with 60 unit of enzyme for 104 spores was only about 1 cm, compared to 3.5 cm in the control. The antifungal effect of chitinase suggests that this enzyme has great potential for applications in agricultural production as well as postharvest fruit and vegetable preservation.

Topically applied GHK as an anti-wrinkle peptide: Advantages, problems and prospective

Introduction: Peptides are promising and attractive anti-wrinkle active ingredients, amongst which glycyl-histidyl-lysine peptide (GHK) is one of the most broadly promoted peptide for topical application. This simple sequence of amino acid residues not only has the capability of tissue regeneration and the enhancement of collagen and glycosaminoglycans synthesis but also is able to increase nerve outgrowth and angiogenesis. Consequently, GHK has several properties, from wound healing to prevention/reduction wrinkles. GHK-Cu and Pal-GHK are metal complex and palmitoylated derivatives of GHK, respectively. Although GHK-Cu and Pal-GHK are widely used in anti-wrinkle products available on the cosmetic market, the published information on their skin permeability, effectiveness, physicochemical properties and so on is insufficient. Methods: This review aims to highlight whether GHK is sufficiently effective on wrinkle prevention/reduction. Apart from the effectiveness, another question that is tried to be answered is whether skin permeability of GHK allows it to act as an anti-wrinkle peptide at its site of action? Skin permeation enhancement methods employed so far are also reviewed. Results: Based on cellular studies, undoubtedly, GHK can be considered as an anti-wrinkle ingredient. Although GHK-Cu and Pal-GHK have been of interest as effective peptides to be incorporated in the anti-wrinkle products, there is a surprising absence of clinical studies using them. Metal complexation and chemical modification with a hydrophobic moiety increase permeability of this peptide. Besides, cell penetrating peptides seem promising to increase skin permeation of GHK and its derivatives. Skin pretreatment with microneedles also has the potential to be further studied for permeation enhancement of such peptides. As peptide ingredients, their formulation may encounter some challenges, mainly due to their hydrophilic (high aqueous solubility and low partition coefficient) and unstable nature. Conclusion: Although GHK-Cu and Pal-GHK are effective and relatively skin permeable, their permeability could be successfully increased using permeation enhancement methodologies.

Solubilization study of antihypertensive drug Irbesartan in EO-PO based polymeric nanomicelle and optimization of its release behavior

Irbesartan (IRB) has low bioavailability due to its poor aqueous solubility and dissolution rate, thereby making it imperative to understand their absorption behavior. The present research work is aimed for improvement of solubilization of IRB, by investigating the effect of molecular characteristics/hydrophobicity of Pluronic® copolymers; P84 and F108 micelles with and without added salt (NaCl). The solubility of IRB was increased with copolymer concentration. Effect of added salt (NaCl) showed completely opposite behavior for both the copolymers; where F108 with NaCl has adverse effect on IRB solubilization and considerable decrease was observed. The micelle/water partition coefficient and the standard free energy change (∆G◦) were also evaluated from thermodynamic view point. The in vitro release kinetics of IRB drug was carried out for 1% P84 with and without 1 M NaCl and compared with its release in water. It was found that P84/NaCl reduces the release rate more efficiently for IRB compared to other systems. There are few reports about the solubilization improvement of IRB; but this is the first time where the study of Pluronic® micelle carried out for IRB solubilization with varying solvent condition as per best of our knowledge. This information can be useful to understand the solubilization behaviour of Pluronic® copolymers available in varieties of molecular weights and can be used to identify possible solvent condition for newer applications of Pluronic® copolymers in pharmaceutical field.

Surface-active ionic liquids as drug carriers: A physico-chemical study

This work evaluates the potential of two surface active ionic liquids (SAILs) 1-dodecyl-3-methylimidazolium bromide and 1-tetradecyl-3-methylimidazolium bromide as drug carrier for ciprofloxacin (CPF) and compares them with their conventional counterparts dodecyltrimethylammonium bromide and tetradecyltrimethylammonium bromide using spectroscopic and electrochemical techniques. Different physico-chemical parameters including critical micelle concentration (CMC), binding constants, partition coefficients and their corresponding free energy changes, thermodynamic parameters of micellization and redox behavior of micelle-drug systems were investigated. Both the SAILs demonstrated higher solubilization powers and binding constants owing to the less polar nature of imidazolium ring. Lower CMCs indicated relatively stronger hydrophobic forces existing in all SAILs-CPF systems tested. The cyclic voltammetry displayed shifting of oxidation peaks towards higher positive potential in the micellar region indicating the protection of CPF against oxidation. This work demonstrates the benefits of using SAILs as drug carriers due to their lower CMCs, improved binding and partition coefficients, and favorable electrochemical results.

Central Nervous System Distributional Kinetics of Selected Histone Deacetylase Inhibitors.

Histone deacetylase expression and activity are often dysregulated in central nervous system (CNS) tumors, providing a rationale for investigating histone deacetylase inhibitors (HDACIs) in selected brain tumor patients. Although many HDACIs have shown potential in in vitro studies, they have had modest efficacy in vivo This lack of activity could be due to insufficient CNS exposure to the unbound drug. In this study, we investigated the systemic pharmacokinetics and subsequent CNS distribution of two potent HDACIs, vorinostat and quisinostat, in the murine model. Both compounds undergo in vitro degradation in mouse plasma, requiring precautions during sample processing. They also have short half-lives in vivo, in both plasma and CNS, which may lead to diminished efficacy. Transgenic transporter-deficient mouse models show that the CNS delivery of vorinostat was not limited by the two major blood-brain barrier efflux transporters, p-glycoprotein and breast-cancer-resistance protein. Vorinostat had an unbound CNS tissue-to-plasma partition coefficient of 0.06 {plus minus} 0.02. Conversely, the exposure of unbound quisinostat in the brain was only 0.02 {plus minus} 0.001 of that in the plasma, and the CNS distribution of quisinostat was limited by the activity of p-glycoprotein. To gain further context for these findings, the CNS distributional kinetics for vorinostat and quisinostat were compared to another hydroxamic acid HDACI, panobinostat. A comprehensive understanding of the CNS target exposure to unbound HDACI, along with known potencies from in vitro testing, can inform the prediction of a therapeutic window for HDACIs that have limited CNS exposure to unbound drug and guide targeted dosing strategies. Significance Statement This study indicates that quisinostat and vorinostat are susceptible to enzymatic degradation in the plasma, and to a lesser degree, in the target CNS tissues. Employing techniques that minimize the post-sampling degradation in plasma, brain and spinal cord, accurate CNS distributional kinetic parameters for these potentially useful compounds were determined. A knowledge of CNS exposure (Kp,uu), time to peak, and duration can inform dosing strategies in preclinical and clinical trials in selected CNS tumors.

Migration of l-Selenomethionine in the Water-Soil Interface Dominated by Iron Oxides.

Organic selenium (Se) accounts for up to 10-80% of total Se in soils, and l-selenomethionine (SeMet) is a typical organic Se species. However, the migration of SeMet in soils remains elusive. This study investigated the solid-liquid distribution, adsorption, desorption by phosphate, and self-oxidization of SeMet in solution under the influence of ferrihydrite, goethite, and hematite through batch experiments. Iron oxides could adsorb a much larger amount of SeMet than inorganic Se. At the initial Se element concentrations of 0-200 mg/L, the solid/liquid partition coefficient of SeMet was constant, which was 0.41, 0.43, and 0.50 on ferrihydrite, goethite, and hematite, respectively. In addition, the adsorption process of SeMet on the three iron oxides could be well described by the linear driving force model. Accordingly, the intraparticle diffusion coefficient of SeMet in ferrihydrite, goethite, and hematite was 1.4 × 103, 7.9 × 104, and 1.2 × 105 nm2/min, respectively. The adsorption of SeMet on the three iron oxides was slightly influenced by the pH and the coexisting ions, such as Cl-, NO3-, SO42-, and H2PO4-. The desorption ratio of SeMet on the three iron oxides by phosphate was lower than 2.5%. SeMet would aggregate the nanoparticles of iron oxides, resulting in a synergistic effect on the adsorption of phosphate. The oxidization ratio of SeMet was 23.9% in the solution, while it decreased to 17.1-17.5% in iron oxide suspensions. For this oxidization process, the three iron oxides exhibited varying effects to decelerate SeMet oxidation, as represented by the equivalent reaction. The findings of this study reveal the migration of SeMet in the water-soil interface under the influence of iron oxides, which can improve the understanding of Se cycling in the environment as well as provide some guidance for the better utilization of Se in soils and environmental remediation of Se pollution.

Clarifications on the intersectional MAIHDA approach: A conceptual guide and response to Wilkes and Karimi (2024)

Intersectional Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy (MAIHDA) has been welcomed as a new gold standard for quantitative evaluation of intersectional inequalities, and it is being rapidly adopted across the health and social sciences. In their commentary “What does the MAIHDA method explain?”, Wilkes and Karimi (2024) raise methodological concerns with this approach, leading them to advocate for the continued use of conventional single-level linear regression models with fixed-effects interaction parameters for quantitative intersectional analysis.In this response, we systematically address these concerns, and ultimately find them to be unfounded, arising from a series of subtle but important misunderstandings of the MAIHDA approach and literature. Since readers new to MAIHDA may share confusion on these points, we take this opportunity to provide clarifications. Our response is organized around four important clarifications: (1) At what level are the additive main effect variables defined in intersectional MAIHDA models? (2) Do MAIHDA models have problems with collinearity? (3) Why does the Variance Partitioning Coefficient (VPC) tend to be small, and the Proportional Change in Variance (PCV) tend to be large in MAIHDA? and (4) What are the goals of MAIHDA analysis?

The incorporation of strontium and barium into the otoliths of the flounder Paralichthys olivaceus at early life stages demonstrates resilience to ocean acidification.

Ocean acidification could modify the bioavailability and chemical properties of trace elements in seawater, which could affect their incorporation into the calcareous structures of marine organisms. Fish otoliths, biomineralized ear stones made by aragonite, are suspended within the endolymph fluid of teleosts, indicating that the elemental incorporation of otoliths might also be susceptible to ocean acidification. In this study, we evaluated the combined effects of CO2-induced ocean acidification (pH 8.10, 7.70, and 7.30, corresponding to ocean acidification scenarios under the representative concentration pathway 8.5 model as projected by the Intergovernmental Panel on Climate Change) and water elemental concentrations of strontium (Sr) and barium (Ba; low, medium, and high) on elemental incorporation into otoliths of the flounder Paralichthys olivaceus at early life stages. Our results revealed that the elemental incorporation of Sr and Ba into otoliths was principally dependent on the corresponding water elemental concentrations rather than on ocean acidification. Moreover, the partition coefficients (DMe) of Sr and Ba may stabilize after dynamic equilibrium is reached as the water elemental concentration increases, but are not affected by ocean acidification. Therefore, the incorporation of Sr and Ba into otoliths of the flounder at early life stages may not serve as an effective indicator of ocean acidification. In other words, the findings suggest that ocean acidification does not impact the incorporation of Sr and Ba incorporation into otoliths when tracing the temperature or salinity experiences of the flounder. Our findings will provide new knowledge for understanding the potential ecological effects of ocean acidification on the recruitment dynamics of fish species.

Evaluation of Drug Blood-Brain-Barrier Permeability Using a Microfluidic Chip.

The blood-brain-barrier (BBB) is made up of blood vessels whose permeability enables the passage of some compounds. A predictive model of BBB permeability is important in the early stages of drug development. The predicted BBB permeabilities of drugs have been confirmed using a variety of in vitro methods to reduce the quantities of drug candidates needed in preclinical and clinical trials. Most prior studies have relied on animal or cell-culture models, which do not fully recapitulate the human BBB. The development of microfluidic models of human-derived BBB cells could address this issue. We analyzed a model for predicting BBB permeability using the Emulate BBB-on-a-chip machine. Ten compounds were evaluated, and their permeabilities were estimated. Our study demonstrated that the permeability trends of ten compounds in our microfluidic-based system resembled those observed in previous animal and cell-based experiments. Furthermore, we established a general correlation between the partition coefficient (Kp) and the apparent permeability (Papp). In conclusion, we introduced a new paradigm for predicting BBB permeability using microfluidic-based systems.

Physiologically Based Pharmacokinetic Modeling: The Reversible Metabolism and Tissue-Specific Partitioning of Methylprednisolone and Methylprednisone in Rats.

The pharmacokinetics (PK) of methylprednisolone (MPL) exhibited tissue-specific saturable binding and reversible conversion with its metabolite, methylprednisone (MPN). Blood and 11 tissues were collected in male rats after intravenous (i.v.) bolus doses of 50 mg/kg MPL and 20 mg/kg MPN and upon i.v. infusion of MPL and MPN at 0.3, 3, and 10 mg/h per kg. The concentrations of MPL and MPN were simultaneously measured. A comprehensive physiologically based pharmacokinetic (PBPK) model was applied to describe the plasma and tissue profiles and estimate PK parameters of the MPL/MPN interconversion system. Both dosed and formed MPL and MPN were in rapid equilibrium or achieved steady-state rapidly in plasma and tissues. MPL tissue partitioning was nonlinear, with highest capacity in liver (322.9 ng/ml) followed by kidney, heart, intestine, skin, spleen, bone, brain, muscle, and lowest in adipose (2.74 ng/ml) and displaying high penetration in lung. The tissue partition coefficient of MPN was linear but widely variable (0.15∼5.38) across most tissues, with nonlinear binding in liver and kidney. The conversion of MPL to MPN occurred in kidney, lung, and intestine with total clearance of 429 ml/h, and the back conversion occurred in liver and kidney at 1342 ml/h. The irreversible elimination clearance of MPL was 789 ml/h from liver and that of MPN was 2758 ml/h with liver accounting for 44%, lung 35%, and kidney 21%. The reversible metabolism elevated MPL exposure in rats by 13%. This highly complex PBPK model provided unique and comprehensive insights into the disposition of a major corticosteroid. SIGNIFICANCE STATEMENT: Our dual physiologically based pharmacokinetic (PBPK) study and model of methylprednisolone/methylprednisone (MPL/MPN) with multiple complexities reasonably characterized and parameterized their disposition, and provided greater insights into the interpretation of their pharmacodynamics in rats. Drug knowledge gained in this study may be translatable to higher-order species to appreciate the clinical utility of MPL. The complex model itself is instructive for advanced PBPK analysis of drugs with reversible metabolism and/or nonlinear tissue partitioning features.

Combined effects of pH and dissolved organic matter on the availability of pharmaceuticals and personal care products in aqueous environment

The interaction between pharmaceuticals and personal care products (PPCPs) with dissolved organic matter (DOM) can alter their bioavailability and toxicity. Nevertheless, little is known about how pH and DOM work together to affect the availability of PPCPs. This study investigated the impact of pH and DOM on the availability of seven PPCPs, namely Carbamazepine, Estrone, Bisphenol A, Testosterone Propionate, Triclocarban, 4-tert-Octylphenol and 4-n-Nonylphenol, using negligible depletion solid-phase microextraction (nd-SPME). The uptake kinetics of PPCPs by the nd-SPME fibers increased proportionally with DOM concentrations, likely due to enhanced diffusive conductivity in the unstirred water layer. At neutral pH, the partitioning coefficients of PPCPs for Humic Acid (log KDOC 3.87–5.25) were marginally higher than those for Fulvic Acid (log KDOC 3.64–5.11). Also, the log KDOC values correlated linearly with the log DOW (pH 7.0) values of PPCPs, indicating a predominant role for hydrophobic interactions in the binding of DOM and PPCPs. Additionally, specific interactions like hydrogen bonding, π-π, and electrostatic interactions occur for certain compounds, influenced by the polarity and spatial conformation of the compounds. For these ionizable PPCPs, the log DDOC values exhibit a strong dependence on pH due to the dual influence of pH on both DOM and PPCPs. The log DDOC values rose from pH 1.0 to 3.0, peaked at pH 5.0 to 9.0, and then (sharply) declined from 11.0 to 13.0. The reasons are that in strong acidic circumstances, the coiled and compressed shape of DOM inhibits the hydrophobic interaction, whereas in strong alkaline conditions, significant electrostatic repulsion reduces the sorption. This study reveals that the effects of DOM on the bioavailability of PPCPs are dependent on both pH and the specific compound involved.

Hydrophobic Sorption Properties of an Extended Series of Anionic Per- and Polyfluoroalkyl Substances Characterized by C18 Chromatographic Retention Measurement.

Partitioning from water to nonaqueous phases is an important process that controls the behavior of contaminants in the environment and biota. However, for ionic chemicals including many perfluoroalkyl and polyfluoroalkyl substances (PFAS), environmentally relevant partition coefficients cannot be predicted using the octanol/water partition coefficient, which is commonly used as a hydrophobicity indicator for neutral compounds. As an alternative, this study measured C18 liquid chromatography retention times of 39 anionic PFAS and 20 nonfluorinated surfactants using isocratic methanol/water eluent systems. By measuring a series of PFAS with different perfluoroalkyl chain lengths, retention factors at 100% water (k0) were successfully extrapolated even for long-chain PFAS. Molecular size was the most important factor determining the k0 of PFAS and non-PFAS, suggesting that the cavity formation process is the key driver for retention. Log k0 showed a high correlation with the log of partition coefficients from water to the phospholipid membrane, air/water interface, and soil organic carbon. The results indicate the potential of C18 retention factors as predictive descriptors for anionic PFAS partition coefficients and the possibility of developing a more comprehensive multiparameter model for the partitioning of anionic substances in general.

Evidences for the influence from key chemical structures of per- and polyfluoroalkyl substances on their environmental behaviors

This study carried out the atmospheric and precipitation observation in Beijing for nearly one year, and firstly simultaneously observed the pollution characteristics of PFASs and their main isomers, focusing on their gas-particle partitioning mechanism and dry and wet deposition characteristics. After deducting PFASs in the aqueous phase of particulate matter, the gas-particle partitioning coefficients (−7.04 to −5.49) were about 3–4 units smaller than before (−2.77 to −1.51), and all were smaller than 0, which indicated that each PFAS and isomer were more distributed in the gas phase. Dry deposition was dominant in the atmospheric deposition of each PFAS and isomer with relative contribution of 66 ± 17%, but the relative contribution of dry deposition was significantly different. It was found that the gas-particle partitioning coefficient can be influenced by key chemical structures such as carbon chain length, functional group type, and isomer structure. Furthermore, the gas-particle partitioning can influence the dry and wet deposition of PFASs. Specifically, PFASs with longer carbon chains, carboxylic acid functional group (compared to sulfonic acid functional group) or PFOA branched chain structures had larger gas-particle partitioning coefficients and can be more distributed in the hydrophobic phase of particulate matter, and their relative contributions of dry deposition were smaller.

Molecular and electrostatic origins of mixed salt partitioning phenomena in uncharged poly(ethylene oxide)-based membranes

Despite the increasing interest in membranes for water purification and resource recovery from aqueous electrolyte mixtures, few studies rigorously investigate the influence of salt solution composition (e.g., mole fraction and total salt concentration) on membrane material properties such as partition coefficients. Here, we systematically investigate the influence of solution composition on the partitioning of ionic species from binary aqueous salt solutions into crosslinked poly(ethylene glycol) diacrylate membranes at fixed ionic strength. These results are compared to partition coefficients observed for pure salt solutions. We observe large systematic deviations between the pure salt and mixed salt ion partition coefficients, indicating that the single salt partition coefficients that are often reported do not describe the more complex and realistic mixed salt scenario. Free energy calculations from molecular dynamics simulations, coupled with equilibrium thermodynamic modeling, indicate that mixed salt partitioning trends result from (i) different ions exhibiting different affinities for the membrane and (ii) the constraint of global electrical neutrality within the membrane. With this physical insight, we develop a simple approach to predicting the concentration of various ions in a membrane equilibrated with a mixed salt solution which requires no adjustable parameters.