Octanol-water Coefficient Research Articles

Elucidating impacts of partitioning and transmembrane permeability on absorption of chemicals in human gastrointestinal tract

Estimating the fraction absorbed (Fabs) of orally ingested chemicals in the human gastrointestinal tract is pivotal for assessing chemical concentrations in the systemic circulation and informing potential toxicological impacts, especially in the era of “new approach methods” targeting chemical screening and prioritization. Here, we present an input-parsimonious and computationally efficient approach to support the screening-level estimation of Fabs from partitioning (characterized using the octanol–water partition coefficient at pH 7.4, KOW) and transmembrane permeability (characterized using the Caco-2 apparent permeability, Papp,Caco-2), based on a mechanistic description of processes involved in chemical absorption:Fabs=1-e-164571-2.40×10-9+2.40×10-9∙KOW∙10.0075∙1Papp,Caco-2-10.001530.346+10.00115Our approach demonstrates satisfactory performance in predicting Fabs for 176 hydrophobic and hydrophilic organic chemicals, with a Pearson correlation coefficient greater than 0.75 and a root mean square error of approximately 15 % in absolute Fabs values between experimental measurements and predictions. Our results show that the Fabs of highly hydrophobic chemicals (KOW > 108) are closely dependent on partitioning, whereas the Fabs of relatively hydrophilic chemicals (KOW < 106) are sensitive to transmembrane permeability. We also demonstrate that transmembrane permeability and partitioning are not interdependent, and both should be treated as fundamental chemical properties in predicting Fabs.

Evaluating microplastic particles as vectors of exposure for plastic additive chemicals using a food web model

Microplastic particles (MPs) represent potential hazards for humans and wildlife, including as vectors for chemical exposure (e.g. plastic additives and pollutants sorbed from the surrounding environment). The leaching of chemicals from MPs has been identified as a potential exposure pathway but the relative magnitude of this pathway under environmentally relevant conditions remains unclear. Here, we describe a modification of the ACC-HUMANSTEADY bioaccumulation model to include dietary exposure to MPs containing either accumulated chemicals from the surrounding environment or embedded plastic additive chemicals (PACs). Chemical transfer to humans and wildlife is described using two-film resistance concepts assuming spheroidal particles of different sizes. The relative contribution of MPs and environmental media to the estimated daily chemical intake in humans was assessed in various exposure scenarios, for a range of hypothetical chemicals with varying octanol-water and air-water partition coefficients (KOW and KAW, respectively; i.e. 0 < log KOW <8 and − 5 < log KAW < 3). Results imply that MPs could act as sources of exposure to chemical additives when the ingestion rate of 1 μm MPs is ≥ 10 mg d− 1, and the concentration of hydrophobic plastic additive is ≥ 5% wt wt− 1. The contribution made by MPs as vectors of exposure decreased with increasing particle size and decreasing ingestion rates of MPs. Human health risks were evaluated for four specific PACs to illustrate the application of the model for risk assessment. Risks were negligible when the ingestion rate of MPs was < 100 μg d− 1. Uncertainties are high regarding the characterization and quantification of ingestion of MPs by humans and wildlife, including particle sizes and polymer composition, as well as on the presence of PACs in MPs. These data gaps need to be addressed if the issue of MPs as vectors of chemical exposure is to be fully understood. The work illustrates that mechanistic models, which account for all major exposure pathways, can be used to identify the importance of different exposure pathways, help prioritize research needs and support decision making.

A comparative study for organophosphate triesters and diesters in mice via oral gavage exposure: Tissue distribution, excreta elimination, metabolites and toxicity

Organophosphate triesters (tri-OPEs) and diesters (di-OPEs) may threaten human health through dietary intake, whereas little information is available about their fate in mammals. Herein, mice exposure experiments were carried out through gavage with six tri-OPEs and six di-OPEs, respectively. The residual levels of di-OPEs in mice were generally higher than those of tri-OPEs. The residual di-OPEs mainly distributed in the liver and blood while the most tri-OPEs remained in stomach, indicating easier transfer and lower metabolism levels of di-OPEs. The accumulation of tri- and di-OPEs with large octanol–water partition coefficients and long carbon chain were observed in tissues and feces, implying that the elimination of these OPEs through fecal excretion is an important elimination pathway. A total of 86 OPE metabolites were found in murine urine and feces, 57 of which were identified for the first time. For tri-OPEs, carboxylated OPEs had higher peak intensities and fewer interference factors among the metabolites, which could serve as ideal biomarkers. The predicted oral median lethal doses of OPEs and corresponding metabolites showed an increased toxicity of some hydroxylated OPEs and di-OPEs, needing further attention. These results provided new insights and evidence on the fates and biomarkers of OPEs exposure for mammals.

Fouling of Reverse Osmosis (RO) and Nanofiltration (NF) Membranes by Low Molecular Weight Organic Compounds (LMWOCs), Part 1: Fundamentals and Mechanism.

Reverse osmosis (RO) and nanofiltration (NF) are ubiquitous technologies in modern water treatment, finding applications across various sectors. However, the availability of high-quality water suitable for RO/NF feed is diminishing due to droughts caused by global warming, increasing demand, and water pollution. As concerns grow over the depletion of precious freshwater resources, a global movement is gaining momentum to utilize previously overlooked or challenging water sources, collectively known as "marginal water". Fouling is a serious concern when treating marginal water. In RO/NF, biofouling, organic and colloidal fouling, and scaling are particularly problematic. Of these, organic fouling, along with biofouling, has been considered difficult to manage. The major organic foulants studied are natural organic matter (NOM) for surface water and groundwater and effluent organic matter (EfOM) for municipal wastewater reuse. Polymeric substances such as sodium alginate, humic acid, and proteins have been used as model substances of EfOM. Fouling by low molecular weight organic compounds (LMWOCs) such as surfactants, phenolics, and plasticizers is known, but there have been few comprehensive reports. This review aims to shed light on fouling behavior by LMWOCs and its mechanism. LMWOC foulants reported so far are summarized, and the role of LMWOCs is also outlined for other polymeric membranes, e.g., UF, gas separation membranes, etc. Regarding the mechanism of fouling, it is explained that the fouling is caused by the strong interaction between LMWOC and the membrane, which causes the water permeation to be hindered by LMWOCs adsorbed on the membrane surface (surface fouling) and sorbed inside the membrane pores (internal fouling). Adsorption amounts and flow loss caused by the LMWOC fouling were well correlated with the octanol-water partition coefficient (log P). In part 2, countermeasures to solve this problem and applications using the LMWOCs will be outlined.

Using physicochemical properties to predict the impact of natural dissolved organic carbon on transepithelial potential in the freshwater rainbow trout (Oncorhynchus mykiss) at neutral and acidic pH.

Dissolved organic carbon (DOC) is a complex mixture of molecules that varies in composition based on origin as well as spatial and temporal factors. DOC is an important water quality parameter as it regulates many biological processes in freshwater systems, including the physiological function of the gills in fish. These effects are often beneficial, especially at low pH where DOCs mitigate ion loss and protect active ion uptake. DOCs of different compositions and quality have varied ionoregulatory effects. The molecular variability of DOCs can be characterized using optical and chemical indices, but how these indices relate to the physiological effects exerted by DOCs is not well understood. We tested the effects of five naturally sourced DOCs, at both pH 7 and pH 4, on transepithelial potential (TEP) (a diffusion potential between the blood plasma and the external water) in rainbow trout. The five chosen DOCs have been well characterized and span large differences in physicochemical characteristics. Each of the DOCs significantly influenced TEP, although in a unique manner or magnitude which was likely due to their physicochemical characteristics. These TEP responses were also a function of pH. With the goal of determining which physicochemical indices are predictive of changes in TEP, we evaluated correlations between various indices and TEP at pH 7 and pH 4. The indices included: specific absorbance coefficient at 340nm, molecular weight index, fluorescence index, octanol-water partition coefficient, molecular charge, proton binding index, % humic acid-like, % fulvic acid-like, and % protein-like components by parallel factor analysis on fluorescence data (PARAFAC). Our results demonstrate the novel finding that there are three particularly important indices that are predictors of changes in TEP across pHs in rainbow trout: specific absorbance coefficient at 340nm, octanol-water partition coefficient; and proton binding index.

Occurrence and fate of atmospheric short/medium chain chlorinated paraffins: Size distribution and inhalation exposure

Chlorinated paraffins (CPs) are intricate industrial compounds synthesized through alkane chlorination. Researches on the size distribution of short-chain (SCCPs) and medium-chain chlorinated paraffins (MCCPs) in atmospheric particulate matter (PM) are limited. Here, we conducted a thorough investigation on the size-dependent distribution characteristics, deposition behavior in respiratory tract, and health risks associated with CPs in atmospheric PM. The concentration of SCCPs in atmospheric particulate matter (PM10) was much higher than MCCPs, with concentration ranges of 2.53–31.8 and 1.07–4.62 ng m−3, respectively. Concentrations of CPs increase with decreasing PM size, peaking at aerodynamic diameters (Dp) < 0.49 μm. Physicochemical properties influence the distribution of CP homologs in PM. Those with lower vapor pressure, higher octanol-air and octanol-water partition coefficients tended to accumulate in PM with larger geometric mean diameters. Most of the inhaled CPs in PM deposited in the upper airways, with a small amount in the trachea and alveolar regions. The estimated daily intakes values were highest when Dp < 0.49 μm. Particle size is an essential determinant for the deposition of inhaled CPs in PM and should be considered in health risk assessments.

Unpuzzling spatio-vertical and multi-media patterns of aniline accelerators/antioxidants in an urban estuary

Aniline accelerators and antioxidants (AAs) are high-production-volume industrial additives that have recently attracted emerging concern given their ubiquity in environmental compartments and the associated (eco)toxic effects. Nonetheless, available information on the multi-media behavior of AAs and their transformation products (TPs) remains scarce. Therefore, we determined the residues of twenty-four AA(TP)s in paired dissolved phases (i.e., filtered water), suspended particulate matter (SPM), and sediment samples collected from the Yangtze River Estuary (YRE), a highly urbanized estuary in the East China. The median total concentrations of targeted compounds were 0.73 ng/g dw, 34.4 ng/L, and 39.6 ng/L in sediments, surface and bottom water, respectively. Diphenylamine (DPA) was the most abundant congener in SPM, while 1,3-diphenylguanidine (DPG) and dicyclohexylamine (DChA) dominated in the dissolved phases and sediments. Various anthropogenic emissions and (a)biotic degradation may collectively shape the matrix-specific accumulation patterns and spatial trends of these compounds across the YRE. However, the vertical patterns of AA(TP)s were obscure, probably due to the estuarine hydrodynamics and/or the modest sample size. The SPM fractions of AA(TP)s in water (Ф: 7.9–100%) and the sediment sorption coefficients (KOC: 0.01–6.56) both positively correlated with their hydrophobicity as indicated by the octanol-water partition coefficient (KOW). Moreover, risk quotients implied moderate to high aquatic toxicity posed by several AA(TP)s at certain YRE sites. The estimated total annual fluxes of our analytes transported via water and sediments towards the East China Sea were 5.90–365.5 tons and 4.23–1,100 kg, respectively. This work provides a systematic investigation of multi-media processes and ecological risks of AA(TP)s in a highly-urbanized estuary, contributing to holistic comprehension of these emerging contaminants in estuarine environments.

Occurrence, distribution, and dietary risk assessment of pesticides in apples at the provincial scale

Apples are widely favored by consumers, but the presence of pesticide residues can pose risks to their quality and safety. This study investigated the residual levels of pesticides in commercial apples from 11 cities in Shanxi Province, using analytical methods to detect 102 pesticides. A total of 34 pesticides were detected, with the highest detection rate observed for carbendazim (78.95%), tebuconazole (57.14%), and acetamiprid (53.38%). Pesticide concentrations ranged from below 2 μg/kg to 522.96 μg/kg, with all levels remaining within the maximum residue limits (MRLs) in China. The retention factors, which characterize the distribution pattern, exhibited a significantly positive correlation with the base-10 logarithms of the octanol-water partition coefficient (pKow). All detected pesticides showed acceptable acute dietary risks, with values below 21.33% for different consumer groups, as assessed by deterministic and probabilistic models. This study enhances the understanding of residual pesticide levels and dietary risks of pesticides in apples at the provincial scale and promotes the rational application of pesticides.

Concentrations, Partitioning and Ecological Risk of Pharmaceuticals and Personal Care Products in UK Freshwater Sediment

Pharmaceuticals and personal care products (PPCPs) have received increasing attention in recent years as emerging contaminants that could adversely affect human health and the environment. While previous studies focused mainly on water, little is known about the occurrence and risk of PPCPs in sediment. The present study investigated 30 widely used PPCPs in sediment samples from two rivers and two canals in the UK. Average Σ30PPCPs concentrations in sediments were 129, 79, 62 and 110ng/g dry weight in the River Tame, Coventry Canal, River Severn, and Birmingham & Worcester canal, respectively. Amoxicillin, gabapentin, caffeine, propranolol, DEET, naproxen, diclofenac Na, meclofenamic acid and β-estradiol were detected in all studied locations. The highest concentration measured was 43.6ng/g of diclofenac (Coventry Canal). The octanol-water partition coefficient (Log KOW) of target PPCPs, and their experimentally measured sediment–water distribution coefficient (Log KP), showed a significant positive correlation, indicating the partitioning of PPCPs between water and sediment may be attributed, at least partially, to their lipophilicity. The ecological risk of target PPCPs in sediment to aquatic biota was assessed using a risk quotient (RQ) approach. The estimated RQ values for amoxicillin on Cyanobacteria were > 1 in all studied locations, indicating high risk to freshwater Cyanobacteria, while 17-α-ethinyl estradiol and caffeine posed high ecological risk (RQ > 1) to fish. These results highlight the need for better removal efficiency of PPCPs by wastewater treatment plants to prevent their accumulation in sediment and call for further development of effect-based sediment quality standards.

Kinetics of uptake, translocation, and metabolism of organophosphate esters in japonica rice (Oryza sativa L.): Hydroponic experiment combined with model

Hydroponics combined with fugacity model was employed to investigate the kinetics of uptake, accumulation, and metabolism of organophosphate esters (OPEs) by japonica rice. The time-dependent process for uptake and accumulation of 5 OPEs and their diester-metabolites in both rice root and shoot fitted well with the pseudo-first-order kinetic model. The peak OPE accumulations in rice root and shoot were significantly positively or negatively correlated with their octanol-water partition coefficient (logKow) respectively, but not for their apparent accumulation rates. Root concentration factors (RCFs) and root-to-shoot translocation factors (TFs) of OPEs were found to be positively and negatively correlated with their logKow, respectively. Triphenyl phosphate with benzene ring substituents showed the highest RCF, but the lowest TF, because of its high potential for root adsorption due to the π electron-rich structures. Sterilized root exudates can hinder the root adsorption and absorption of OPEs from solution probably through competitive adsorption of OPEs with root surface. The first-hand transport and metabolism rates were also obtained by generating these rates to fit the dynamic fugacity model with the measurement values. The simulation indicated that the kinetics of OPE accumulation in rice plants may be controlled by multiple processes and physicochemical properties besides Kow.

Machine learning model to predict rate constants for sonochemical degradation of organic pollutants

In this study, machine learning (ML) algorithms were employed to predict the pseudo-1st-order reaction rate constants for the sonochemical degradation of aqueous organic pollutants under various conditions. A total of 618 sets of data, including ultrasonic, solution, and pollutant characteristics, were collected from 89 previous studies. Considering the difference between the electrical power (Pele) and calorimetric power (Pcal), the collected data were divided into two groups: data with Pele and data with Pcal. Eight input variables, including frequency, power density, pH, temperature, initial concentration, solubility, vapor pressure, and octanol–water partition coefficient (Kow), and one target variable of the degradation rate constant, were selected for ML. Statistical analysis was conducted, and outliers were determined separately for the two groups. ML models, including random forest (RF), extreme gradient boosting (XGB), and light gradient boosting machine (LGB), were used to predict the pseudo-1st-order reaction rate constants for the removal of aqueous pollutants. The prediction performance of the ML models was evaluated using different metrics, including the root mean squared error (RMSE), mean absolute error (MAE), and R squared (R2). A significantly higher prediction performance was obtained using data without outliers and augmented data. Consequently, all the applied ML models could be used to predict the sonochemical degradation of aqueous pollutants, and the XGB model showed the highest accuracy in predicting the rate constants. In addition, the power density and frequency were the most influential factors among the eight input variables in prediction with the Shapley additive explanation (SHAP) values method. The degradation rate constants of the two pollutants over a wide frequency range (20–1,000 kHz) were predicted using the trained ML model (XGB) and the prediction results were analyzed.

Co-exposure to Organophosphate esters (OPEs) and Cadmium alleviated their accumulation in rice (Oryza sativa L.) by inhibiting transports' transcription

Combined contamination of Organophosphate esters (OPEs) and heavy metal has been concerning on their potential threaten to human health through food chain. In order to estimate effects of OPEs and heavy metal's combined contamination on crop, the growth of rice seedlings, pollutant accumulations and their involved in transcript regulation pathway under OPEs and Cd contamination were investigated. In results, only single OPEs pollution improved the biomass of rice, while single Cd pollution inhibited the growth of plants. Although the combined contaminations of OPEs and Cd also showed negative effect for plant growth, OPEs could alleviate the negative effect of Cd on rice. The Octanol-water partition coefficients (log Kow) of OPEs were positively correlated with root concentration factor (RCF) values in the trend line and negatively correlated with shoot concentration factor (SCRF) and translocation factor (TF). OPEs and Cd inferred with each other's accumulations in plants through reducing RCF, SCRF and TF. After addition of Cd, the expressions of OsTIL, OsLTP4, OsLTPL1, and OsMLP423 genes involved in OPEs accumulation were downregulated. Moreover, the presence of Cd also affected the binding sites and binding energy of the four proteins with OPEs. Meanwhile, the expression of OsNramp1, OsNramp5, OsHMA2, OsGS1, and OsPCS1 genes involved in Cd accumulation and toleration were also downregulated after addition of OPEs. These results suggested that OPEs and Cd directly repressed each other gene transcript involved in accumulation and toleration process.

Quantum-Mechanics Calculations Elucidate Skin-Sensitizing Pharmaceutical Compounds.

Skin sensitization is a critical end point in occupational toxicology that necessitates the use of fast, accurate, and affordable models to aid in establishing handling guidance for worker protection. While many in silico models have been developed, the scarcity of reliable data for active pharmaceutical ingredients (APIs) and their intermediates (together regarded as pharmaceutical compounds) brings into question the reliability of these tools, which are largely constructed using publicly available nonspecialty chemicals. Here, we present the quantum-mechanical (QM) Computer-Aided Discovery and REdesign (CADRE) model, which was developed with the bioactive and structurally complex chemical space in mind by relying on the fundamentals of chemical interactions in key events (versus structural attributes of training-set data). Validated in this study on 345 APIs and intermediates, CADRE achieved 95% accuracy, sensitivity, and specificity and a combined 79% accuracy in assigning potency categories compared to the mouse local lymph node assay data. We show how historical outcomes from CADRE testing in the pharmaceutical space, generated over the past 10 years on ca. 2500 chemicals, can be used to probe the relationships between sensitization mechanisms (or the underlying chemical classes) and the probability of eliciting a sensitization response in mice of a given potency. We believe this information to be of value to both practitioners, who can use it to quickly screen and triage their data sets, as well as to model developers to fine-tune their structure-based tools. Lastly, we leverage our experimentally validated subset of APIs and intermediates to show the importance of dermal permeability on the sensitization potential and potency. We demonstrate that common physicochemical properties used to assess permeation, such as the octanol-water partition coefficient and molecular weight, are poor proxies for the more accurate energy-pair distributions that can be computed from mixed QM and classical simulations using model representations of the stratum corneum.

Organophosphate esters in terrestrial environments of Fildes Peninsula, Antarctica: Occurrence, potential sources, and bioaccumulation

Despite growing concerns regarding the long-range transport (LRT) and ecological risks of organophosphate esters (OPEs), information on the environmental behaviors of OPEs in polar terrestrial ecosystems remains inadequate. In the present study, 10 OPEs were analyzed in soil and vegetation samples collected from Fildes Peninsula, Antarctica. The OPE concentrations in Antarctic soils, mosses, and lichens ranged from 0.87 to 15.7 ng/g dry weight (dw), 9.8 to 113 ng/g dw, and 3.6 to 75.2 ng/g dw, respectively. Non-chlorinated OPEs predominated in terrestrial matrices, accounting for approximately 76 % of the OPE composition. Source identification indicated that OPE contamination in Antarctica likely resulted from local anthropogenic sources and LRT. Moreover, the bioaccumulation behavior of OPEs from soil to vegetation was assessed using bioconcentration factors (BCFs), revealing a significant non-linear trend of initial increase and subsequent decrease in BCFs relative to the lipophilicities of the octanol-air partition coefficient (log KOA) and octanol-water partition coefficient (log KOW). While low levels of OPEs in Antarctic terrestrial environments were reported in this study, their sustained inputs and potential ecological risks in polar regions warrant further attention.

ExpoNano: A Strategy Based on Hyper-Cross-Linked Polymers Achieves Urinary Exposome Assessment for Biomonitoring.

Urinary analysis of exogenous and endogenous molecules constitutes an efficient, noninvasive approach to evaluate human health status. However, the exposome characterization of urinary molecules remains extremely challenging with current techniques. Herein, we develop an ExpoNano strategy based on hyper-cross-linked polymers (HCPs) to achieve ultrahigh-throughput measurement of exo/endogenous molecules in urine. The strategy includes a simple trapping-detrapping procedure (15 min) with HCPs in enzymatically treated urine, followed by mass spectrometer determination. Molecules that can be determined by ExpoNano have a wide range of molecular weight (75-837 Da) and Log Kow (octanol-water partition coefficient; -9.86 to 10.56). The HCPs can be repeatedly used five times without decreasing the trapping efficiency. Application of ExpoNano in a biomonitoring study revealed a total of 63 environmental chemicals detected in >50% of the urine pools collected from Chinese adults living in 13 cities, with a median concentration of 0.026-47 ng/mL, while nontargeted analysis detected an additional 243 exogenous molecules. Targeted and nontargeted analysis also detected 926 endogenous molecules in pooled urine. Collectively, the ExpoNano strategy demonstrates unique advantages over traditional urine analysis approaches, including a wide range of analytes, satisfactory trapping efficiency, high simplicity and reusability, and extremely reduced time demand and financial cost.

PICKAPEP: An application for parameter calculation and visualization of cyclized and modified peptidomimetics.

The interest in peptides and especially in peptidomimetic structures has risen enormously in the past few years. Novel modification strategies including nonnatural amino acids, sophisticated cyclization strategies, and side chain modifications to improve the pharmacokinetic properties of peptides are continuously arising. However, a calculator tool accompanying the current development in peptide sciences towards modified peptides is missing. Herein, we present the application PICKAPEP, enabling the virtual construction and visualization of peptidomimetics ranging from well-known cyclized and modified peptides such as ciclosporin A up to fully self-designed peptide-based structures with custom amino acids. Calculated parameters include the molecular weight, the water-octanol partition coefficient, the topological polar surface area, the number of rotatable bonds, and the peptide SMILES code. To our knowledge, PICKAPEP is the first tool allowing users to add custom amino acids as building blocks and also the only tool giving the possibility to process large peptide libraries and calculate parameters for multiple peptides at once. We believe that PICKAPEP will support peptide researchers in their work and will find wide application in current as well as future peptide drug development processes. PICKAPEP is available open source for Windows and Mac operating systems (https://urldefense.com/v3/__https://www.research-collection.ethz.ch/handle/20.500.11850/681174__;!!N11eV2iwtfs!qt5f_2lNd6IZUDH1HVSVwg0zYzS8-nFazQ8c61jS5GaD5vkVS5C3igyfh3haJRnaX8ugW7o9VWUiCihPqcptmaWoqwYf9LvZTQ$).

Martini 3 coarse-grained models of the niosomes based on Span60 and Tween60

Sorbitan stearate (span60) and polysorbate 60 (tween60) are surfactants widely used in many industries due to their emulsifying properties. In the present study, we used molecular dynamics (MD) simulations to analyze the stability of niosome bilayers formed by the non-ionic surfactants span60 and tween60 in terms of cholesterol density and temperature. To overcome the length scale limitations of MD simulations, we developed and validated two approximate coarse-grained (CG) models to describe the span60 and tween60 structures using the improved Martini 3 CG model. To verify the accuracy of the theoretical CG model representing the hydrophobic properties of span60 and tween60, we measured the octanol–water partition coefficient and compared the theoretical predictions with experimental outcomes. The consistency between the theoretical and experimental outcomes indicates the accuracy of our theoretical models. The results of this study can be used in research for drug delivery systems based on the niosomes formed by span60 and Tween60.

Characterization of The Permeation Properties of Membrane Filters and Sorption Properties of Sorbents Used for Polar Organic Chemical Integrative Samplers.

Polar organic chemical integrative samplers (POCIS) are promising devices for measuring the time-weighted average concentrations of hydrophilic compounds in aquatic environments. However, the mechanisms underlying compound uptake by POCIS remain unclear. We investigated the permeation kinetics of polyethersulfone and polytetrafluoroethylene membrane filters, and the sorption kinetics of Oasis HLB (Waters), Envi-Carb (Supelco), and Oasis WAX (Waters) sorbents. The log octanol-water partition coefficient (KOW) values of the 19 targeted compounds ranged from -0.55 to 6.0. The overall mass-transfer coefficients were negatively correlated with KOW, indicating that interactions between hydrophobic compounds and the membrane inhibit permeation. The sorption rate coefficient showed no correlation with KOW and depended on the type of sorbent used. These results imply that the uptake of highly hydrophilic compounds by POCIS is determined by both the membrane and the sorbent kinetics; however, membrane kinetics dominate the uptake of hydrophobic compounds. Environ Toxicol Chem 2024;43:2115-2121. © 2024 SETAC.

Estimating Octanol-Water Partition Coefficients of Novel Brominated Flame Retardants by Reversed-Phase High-Performance Liquid Chromatography and Computational Models.

Legacy brominated flame retardants, including polybrominated diphenyl ethers (PBDEs), have been classified as persistent organic pollutants and replaced with novel brominated flame retardants (NBFRs). The octanol-water partition coefficients (log KOW) of NBFRs have been computationally estimated, but the log KOW values provided by these methods can differ by 1 to 3 orders of magnitude. Given the importance of this parameter in fate and toxicity models, we indirectly measured the log KOW values of eight NBFRs by their capacity factor (k') on a reversed-phase high-performance liquid chromatography (HPLC) C18 column by isocratic elution and compared these measured values with those estimated by nine computational models. Log KOW values were obtained for the NBFRs 1,2-bis(2,4,6-tribromophenoxy) ethane, pentabromobenzene, pentabromoethylbenzene, pentabromotoluene, 2-ethylhexyl 2,3,4,5-tetrabromobenzoate, allyl 2,4,6-tribromophenylether, 2,3-dibromopropyl-2,4,6-tribromophenyl ether, and bis(2-ethylhexyl) tetrabromophthalate. A training set of phthalates, polychlorinated biphenyls, PBDEs, and halogenated benzenes were chosen to obtain the log k'-log KOW calibration for the NBFRs. The computational models KowWIN, XLogP3, EAS-E Suite, COSMOtherm, DirectML, and Abraham polyparameter linear free energy relationships all predicted the log KOW values of the calibration compounds to within 1 order of magnitude without significant bias. The median of these models predicted log KOW values for the calibration compounds that were close to those known in the literature with root mean square error (RMSE) = 0.224 and for the NBFRs that were close to those measured by HPLC (RMSE = 0.334). Environ Toxicol Chem 2024;43:2105-2114. © 2024 SETAC.

Synthesis, characterization, and mechanistic insights into the enhanced anti-inflammatory activity of baicalin butyl ester via the PI3K-AKT pathway.

To investigate the anti-inflammatory activity and mechanism of Baicalin derivative (Baicalin butyl ester, BE). BE was synthesized and identified using UV-Vis spectroscopy, FT-IR spectroscopy, mass spectrometry (MS) and high-performance liquid chromatography (HPLC) methods. Its anti-inflammatory potential was explored by an in vitro inflammation model. Network pharmacology was employed to predict the anti-inflammatory targets of BE, construct protein-protein interaction (PPI) networks, and analysis topological features and KEGG pathway enrichment. Additionally, molecular docking was conducted to evaluate the binding affinity between BE and its core targets. qRT-PCR analysis was conducted to validate the network pharmacology results. The organizational efficiency was further evaluated through octanol-water partition coefficient and transmembrane activity analysis. UV-Vis, FT-IR, MS, and HPLC analyses confirmed the successfully synthesis of BE with a high purity of 93.75%. In vitro anti-inflammatory research showed that BE could more effectively suppress the expression of NO, COX-2, IL-6, IL-1β, and iNOS. Network pharmacology and in vitro experiments validated that BE's anti-inflammatory effects was mediated through the suppression of SRC, HSP90AA1, PIK3CA, JAK2, AKT1, and NF-κB via PI3K-AKT pathway. Molecular docking results revealed that the binding affinities of BA to the core targets were lower than those of BE. The Log p-value of BE (1.7) was markedly higher than that of BA (-0.5). Furthermore, BE accumulated in cells at a level approximately 200 times greater than BA. BE exhibits stronger anti-inflammatory activity relative to BA, possibly attributed to its better lipid solubility and cellular penetration capabilities. The anti-inflammatory mechanism of BE may be mediated through the PI3K-AKT pathway.