Environmental impact of PFAS: Filling data gaps using theoretical quantum chemistry and QSPR modeling.

Per- and polyfluorinated alkyl substances (PFAS), known for their widespread environmental presence and slow degradation, pose significant concerns. Of the approximately 10,000 known PFAS, only a few have undergone comprehensive testing, resulting in limited experimental data. In this study, we employed a combination of physics-based methods and data-driven models to address gaps in PFAS bioaccumulation potential. Using the COnductor-like Screening MOdel for Realistic Solvents (COSMO-RS) method, we predicted n-octanol/water partition coefficients (logKOW), crucial for PFAS bioaccumulation. Our developed Quantitative Structure-Property Relationship (QSPR) model exhibited high accuracy (R2 = 0.95, RMSEC = 0.75) and strong predictive ability (Q2LOO = 0.93, RMSECV = 0.83). Leveraging the extensive NORMAN, we predicted logKOW for over 4,000 compounds, identifying 244 outliers out of 4519. Further categorizing the database into eight Organisation for Economic Co-operation and Development (OECD) categories, we confirmed fluorine atoms role in enhanced bioaccumulation. Utilizing predicted logKOW, water solubility logSW, and vapor pressure logVP values, we calculated additional physicochemical properties that are responsible for the transport and dispersion of PFAS in the environment. Parameters such as Henry's Law (kH), air-water partition coefficient (KAW), octanol-air coefficient (KOA), and soil adsorption coefficient (KOC) exhibited favorable correlations with literature data (R2 > 0.66). Our study successfully filled data gaps, contributing to the understanding of ubiquitous PFAS in the environment and estimating missing physicochemical data for these compounds.

Covalent organic framework reinforced hollow fiber bar for extraction and detection of bisphenols from beverages.

Bisphenols (BPs) can migrate from packaging materials into foods, resulting in potentially harmful residues. For example, accumulation of BPs is associated with endocrine disorders. Owing to matrix effects, development of an effective and eco-friendly sample pretreatment would be helpful for BPs detection in beverages packed in plastic containers. In this work, an extraction bar, composed of hollow fiber (HF) functionalized with covalent organic frameworks (COF@Tp-NDA) and 1-ocanol, was prepared for extraction of five BPs simultaneously. The synergistic effect of COF@Tp-NDA and 1-octanol improved the extraction efficiency of BPs from milk-based beverage, juice, and tea beverage. Under optimal conditions, limits of detection ranged from 0.10 to 2.00 ng mL-1 (R2 ≥ 0.9974) and recoveries ranged from 70.1 % to 106.8 %. This method has the potential to enrich BPs, supporting their accurate determination in complex beverages.

Measurement of Henry's law constants of ethyl nitrate in deionized water, synthetic sea salt solutions, and n-octanol.

Ethyl nitrate (EN; C2H5ONO2) is an important component of atmospheric "odd nitrogen" (NOy) whose main source is marine emissions. To correctly describe its air-water transfer and model its global distribution, accurate values for its temperature- and salinity-dependent Henry's law solubility constants are needed. Here, we report Henry's law (HScp) constants for EN in deionized (DI) water, synthetic sea salt solutions (SSS), and n-octanol at temperatures between 278.2 K and 303.2 K. For DI water, HScp constants of (2.03 ± 0.06) M atm-1 at 293.2 K and (4.88 ± 0.13) M atm-1 at 278.2 K were observed (all stated uncertainties are at the 1σ level). The data are best described by ln(HScp(aq)/[Matm-1]) = -(16.2 ± 0.4)+(4.94 ± 0.11) × 103/T and ln(HScp(octanol)/[Matm-1]) = -(11.1 ± 1.9)+(4.15 ± 0.33) × 103/T, from which the octanol-water partition coefficient (KOW) was calculated. A temperature-independent salting-out factor of 1.25 ± 0.03 and Setschenow constant of KS = (0.33 ± 0.04) mol kg-1 were determined for SSS. Liquid-phase losses of EN were negligible in all solvents (kl < 1 × 10-4 s-1). The HScp(aq) values agree with results by Kames (1993) but are between 2% (at 303.2 K) and 19% (at 278.2 K) lower than the widely used parameterization by Kames and Schurath (1992), indicating a systemic bias in the EN literature and modelling of the Earth's nitrogen cycle.

Multiomics reveals the formation pathway of volatile compounds in preserved egg yolk (PEY) induced by NaCl: Based on the model of PEY and salted egg yolk (SEY) treated with/without NaCl.

The models of preserved egg yolk (PEY) and salted egg yolk both treated with or without NaCl were performed to explore the effect of NaCl on the characteristic volatile compounds (VOCs) in PEY. 1-hexanol, 2-heptanone, isoamyl acetate, etc., compounds were confirmed as the characteristic VOCs in PEY mainly induced by NaCl and the formation of 1-octanol, 2-pentylfuran, ammonia, etc., characteristic VOCs induced by NaCl may depend on the combined effect of Cu2+ and OH-. Among them, 1-hexanol and 2-heptanone were formed from linoleic acid in PS(18:0_18:2) and oleic acid in PG(22:6_18:1), respectively, through multi-omics and correlation analysis. Meanwhile, 1-octanol may originated from ß-oxidation of oleic acid in PS(18:1); 2-pentylfuran and ammonia maybe derived from the derivative of aspartate and the degradation of l-methionine, respectively. Moreover, this study provides a new insight to parse the influence of NaCl with/without other exogenous factors on the formation of VOCs in food products.

Application of micellar liquid chromatography to model ecotoxicity of pesticides. Comparison with immobilized artificial membrane chromatography and n-octanol-water partitioning.

The potential of Micellar Liquid Chromatography (MLC) to model ecotoxicological endpoints for a series of pesticides was investigated. To exploit the flexibility in MLC conditions, different surfactants were employed and retention mechanism was tracked and compared to Immobilized Artificial Membrane (IAM) chromatographic retention and n-octanol- water partitioning, logP. Neutral polyoxyethylene (23) lauryl ether (Brij-35), anionic sodium dodecyl sulfate (SDS) and cationic cetyltrimethylammonium bromide (CTAB) were used in presence of PBS at pH=7.40 and acetonitrile as organic modifier when necessary. Similarities/ dissimilarities between MLC retention and IAM or logP were investigated by Principal Component Analysis (PCA) and Liner Solvation Energy Relationships (LSER). LSER revealed that hydrogen bonding acidity is the most important factor for differentiation between MLC and IAM or logP. The impact of hydrogen bonding is exemplified in the relationships of MLC retention factors with IAM or logP, which necessitate the inclusion of a relevant descriptor. PCA further revealed that MLC retention factors are clustered together with IAM indices and logP within a broader ellipse formed by ecotoxicological endpoints, involving LC50/ EC50 values of six aquatic organisms namely Rainbow Trout, Fathead Minnow, Bluegill Sunfish, Sheepshead Minnow, Eastern Oyster and Water Flea as well as LD50 values of Honey Bee, thus justifying their use to construct relevant models. Satisfactory specific models for individual organisms, as well as general fish models, were obtained, in most cases, upon combination of MLC retention factors with Molecular Weight (MW) or/ and hydrogen bond parameters. All models were evaluated and compared to previously reported IAM and logP based models using an external validation data set. Predictions with Brij-35 and SDS based models were comparable, although slightly inferior than those obtained with IAM, while they were in all cases better than those obtained with logP. CTAB led to a satisfactory prediction model for Honey Bee, but it was found less suitable for aquatic organisms.

Improved GNNs for Log D7.4 Prediction by Transferring Knowledge from Low-Fidelity Data.

The n-octanol/buffer solution distribution coefficient at pH = 7.4 (log D7.4) is an indicator of lipophilicity, and it influences a wide variety of absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties and druggability of compounds. In log D7.4 prediction, graph neural networks (GNNs) can uncover subtle structure-property relationships (SPRs) by automatically extracting features from molecular graphs that facilitate the learning of SPRs, but their performances are often limited by the small size of available datasets. Herein, we present a transfer learning strategy called pretraining on computational data and then fine-tuning on experimental data (PCFE) to fully exploit the predictive potential of GNNs. PCFE works by pretraining a GNN model on 1.71 million computational log D data (low-fidelity data) and then fine-tuning it on 19,155 experimental log D7.4 data (high-fidelity data). The experiments for three GNN architectures (graph convolutional network (GCN), graph attention network (GAT), and Attentive FP) demonstrated the effectiveness of PCFE in improving GNNs for log D7.4 predictions. Moreover, the optimal PCFE-trained GNN model (cx-Attentive FP, Rtest2 = 0.909) outperformed four excellent descriptor-based models (random forest (RF), gradient boosting (GB), support vector machine (SVM), and extreme gradient boosting (XGBoost)). The robustness of the cx-Attentive FP model was also confirmed by evaluating the models with different training data sizes and dataset splitting strategies. Therefore, we developed a webserver and defined the applicability domain for this model. The webserver (http://tools.scbdd.com/chemlogd/) provides free log D7.4 prediction services. In addition, the important descriptors for log D7.4 were detected by the Shapley additive explanations (SHAP) method, and the most relevant substructures of log D7.4 were identified by the attention mechanism. Finally, the matched molecular pair analysis (MMPA) was performed to summarize the contributions of common chemical substituents to log D7.4, including a variety of hydrocarbon groups, halogen groups, heteroatoms, and polar groups. In conclusion, we believe that the cx-Attentive FP model can serve as a reliable tool to predict log D7.4 and hope that pretraining on low-fidelity data can help GNNs make accurate predictions of other endpoints in drug discovery.

Hydrophobic Ion Pairing of Small Molecules: How to Minimize Premature Drug Release from SEDDS and Reach the Absorption Membrane in Intact Form.

The present work aimed to form hydrophobic ion pairs (HIPs) of a small molecule remaining inside the oily droplets of SEDDS to a high extent. HIPs of ethacridine and various surfactants classified by functional groups of phosphates, sulfates, and sulfonates were formed and precipitation efficiency, log Dn-octanol/water, and solubility in different excipients were investigated. Most lipophilic HIPs were incorporated into SEDDS and evaluated regarding drug release. Docusate HIPs showed the highest increase in lipophilicity with a precipitation efficiency of 100%, a log Dn-octanol/water of 2.66 and a solubility of 132 mg/mL in n-octanol, 123 mg/mL in oleyl alcohol, and 40 mg/mL in medium chain triglycerides. Docusate HIPs were incorporated into three SEDDS of increasing lipophilicity (F1 < F2 < F3) based on medium chain triglycerides, oleyl alcohol, Kolliphor EL, and Tween 80 (F1: 1 + 5 + 2 + 2; F2: 3 + 3 + 2 + 2; F3: 5 + 1 + 4 + 0). Highest achievable payloads ranged from 74.49 mg/mL (F3) to 97.13 mg/mL (F1) and log DSEDDS/RM increased by at least 7.5 units (4.99, F1). Drug release studies via the diffusion membrane method confirmed minor release of docusate HIPs from all SEDDS (<2.7% within 4 h). In conclusion, highly lipophilic HIPs remain inside the oily phase of SEDDS and likely reach the absorption membrane in intact form.

In silico package models for deriving values of solute parameters in linear solvation energy relationships.

Environmental partitioning influences fate, exposure and ecological risks of chemicals. Linear solvation energy relationship (LSER) models may serve as efficient tools for estimating environmental partitioning parameter values that are commonly deficient for many chemicals. Nonetheless, scarcities of empirical solute parameter values of LSER models restricted the application. This study developed and evaluated in silico methods and models to derive the values, in which excess molar refraction, molar volume and logarithm of hexadecane/air partition coefficient were computed from density functional theory; dipolarity/polarizability parameter, solute H-bond acidity and basicity parameters were predicted by quantitative structure-activity relationship models developed with theoretical molecular descriptors. New LSER models on four physicochemical properties relevant with environmental partitioning (n-octanol/water partition coefficients, n-octanol/air partition coefficients, water solubilities, sub-cooled liquid vapour pressures) were constructed using the in silico solute parameter values, which exhibited comparable performance with conventional LSER models using the empirical solute parameter values. The package models for deriving the LSER solute parameter values, with advantages that they are free of instrumental determinations, may lay the foundation for high-throughput estimating environmental partition parameter values of diverse organic chemicals.

On-chip electromembrane extraction of some polar acidic drugs from plasma samples by the development of an active and efficient polymeric support for liquid membrane based on electrospinning process.

Electromembrane extraction (EME), despite its high performance in the extraction of highly polar basic analytes, has challenges in extracting polar acidic compounds. This is the result of a lack of access to the suitable supported liquid membrane (SLM) for this group of analytes. Therefore, it would be valuable to provide a suitable solution for this problem. Accordingly, in the present study, a new method based on on-chip EME followed by HPLC with UV detection was developed for the extraction and determination of some polar acidic drugs in order to provide high extraction efficiency. Here, a new polymeric sheet was introduced as a support for SLM immobilization, which is not only used to impregnate 1-octanol as SLM but also enhances extraction recovery by exerting effective interactions with target acidic analytes. The polymeric sheet was composed of nanofibers prepared by electrospinning polycaprolactone blended with a composite of graphene oxide and aluminum polycations. Encapsulation of the composite in polycaprolactone nanofibers improved the extraction efficiency of polar acidic compounds by creating additional interactions with the target analytes, including hydrogen bonding, dipole-dipole, π-π stacking, and anion exchange process. The electrospun nanofiber-based sheet was characterized by FE-SEM, EDX, elemental mapping, TEM, and AFM. The extraction parameters were further optimized with an orthogonal-rotatable central composite design (CCD). Applying CCD determined optimal conditions by minimum experiments, and interactions between the parameters were clarified. Under optimized conditions, the proposed method provided extraction recoveries from 36.5 to 64.1%, relative standard deviations less than 5.7% (n = 4), and detection limits of 0.3-0.5 µg L-1. Furthermore, the proposed method was successfully used for the determination of target analytes in plasma samples, providing good accuracy (87-110%) and precision (3.2-8.8%).

Analysis of volatile metabolite variations in strip green tea during processing and effect of rubbing degree using untargeted and targeted metabolomics.

Strip green tea (SGT) is widely distributed in China owing to its unique appearance and aroma but the evolution and formation mechanisms of volatile metabolites (VMs) during SGT processing, and especially in the unique process of rubbing, remain unclear. In this study, based on untargeted metabolomics, 217 VMs (8 categories) were identified, and fixation and rubbing processes were found to be key for SGT aroma formation. Moreover, targeted metabolomics was applied to obtain 38 differential VMs and their related substances, of which fatty acid-derived volatiles (14 VMs) and glycoside-derived volatiles (8 VMs) showed significant contributions to SGT aroma, and their derivation laws during SGT manufacturing were clarified. Furthermore, the effect of rubbing degree on volatile metabolite formation was explored, and 11 key differential VMs were screened by variable importance in projection, and odor activity value analyses. Appropriate rubbing promoted the loss of grassy VMs (such as 1-octanol and 2-pentyl-furan) and enrichment of floral/fruity VMs (such as trans-ß-ionone, nonanal, geraniol, citral, (Z)-3,7-dimethyl-2,6-octadien-1-ol, and (Z)-hexanoic acid, 3-hexenyl ester). Our study not only enriches the chemical theory of green tea processing but also provides technical support for the precision directional processing of high-quality SGT.

Predictive Models of Gas/Particulate Partition Coefficients (KP) for Polycyclic Aromatic Hydrocarbons and Their Oxygen/Nitrogen Derivatives.

Polycyclic aromatic hydrocarbons (PAHs) and their oxygen/nitrogen derivatives released into the atmosphere can alternate between a gas phase and a particulate phase, further affecting their environmental behavior and fate. The gas/particulate partition coefficient (KP) is generally used to characterize such partitioning equilibrium. In this study, the correlation between log KP of fifty PAH derivatives and their n-octanol/air partition coefficient (log KOA) was first analyzed, yielding a strong linear correlation (R2 = 0.801). Then, Gaussian 09 software was used to calculate quantum chemical descriptors of all chemicals at M062X/6-311+G (d,p) level. Both stepwise multiple linear regression (MLR) and support vector machine (SVM) methods were used to develop the quantitative structure-property relationship (QSPR) prediction models of log KP. They yield better statistical performance (R2 > 0.847, RMSE < 0.584) than the log KOA model. Simulation external validation and cross validation were further used to characterize the fitting performance, predictive ability, and robustness of the models. The mechanism analysis shows intermolecular dispersion interaction and hydrogen bonding as the main factors to dominate the distribution of PAH derivatives between the gas phase and particulate phase. The developed models can be used to predict log KP values of other PAH derivatives in the application domain, providing basic data for their ecological risk assessment.

Experimental Examination of Solubility and Lipophilicity as Pharmaceutically Relevant Points of Novel Bioactive Hybrid Compounds.

The important physicochemical properties of three novel bioactive hybrid compounds with different groups (-CH3, -F and -Cl) were studied, including kinetic and thermodynamic solubility in pharmaceutically relevant solvents (buffer solutions and 1-octanol) as well as partition coefficient in system 1-octanol/buffer pH 7.4. The aqueous solubility of these chemicals is poor and ranged from 0.67 × 10-4 to 1.98 × 10-3 mol·L-1. The compounds studied are more soluble in the buffer pH 2.0, simulating the gastrointestinal tract environment (by an order of magnitude) than in the buffer pH 7.4 modelling plasma of blood. The solubility in 1-octanol is significantly higher; that is because of the specific interactions of the compounds with the solvent. The prediction solubility behaviour of the hybrid compounds using Hansen's three-parameter approach showed acceptable results. The experimental solubility of potential drugs was successfully correlated by means of two commonly known equations: modified Apelblat and van't Hoff. The temperature dependencies of partition coefficients of new hybrids in the model system 1-octanol/buffer pH 7.4 as a surrogate lipophilicity were measured by the shake flask method. It was found that compounds demonstrated a lipophilic nature and have optimal values of partition coefficients for oral absorption. Bioactive assay manifested that prepared compounds showed antifungal activities equal to or greater than fluconazole. In addition, the thermodynamic aspects of dissolution and partition processes have been examined. Bioactive assay manifested that prepared compounds showed antifungal activities equal to or greater than the reference drug.

Fast Prediction of Lipophilicity of Organofluorine Molecules: Deep Learning-Derived Polarity Characters and Experimental Tests.

Fast and accurate estimation of lipophilicity for organofluorine molecules is in great demand for accelerating drug and materials discovery. A lipophilicity data set of organofluorine molecules (OFL data set), containing 1907 samples, is constructed through density functional theory (DFT) calculations and experimental measurements. An efficient and interpretable model, called PoLogP, is developed to predict the n-octanol/water partition coefficient, log Po/w, of organofluorine molecules on the basis of the descriptors of polarization, which is a combination of polarity descriptors, including the molecular polarity index and molecular polarizability (α), and hydrogen bond (HBs) index, consisting of the number of donors (NHBD) and acceptors (NHBA and NHB-FA). The present PoLogP with a combination of polarity descriptors is demonstrated to perform better than the dipole moment (µ) alone for the F-contained molecules. With the aid of a multilevel attention graph convolutional neural network model, the fast generation of polarity descriptors of organofluorine molecules could be achieved with the DFT accuracy based only on a topological molecular graph structure. The performance of PoLogP is further validated on synthesized organofluorine molecules and 2626 non-fluorinated molecules with satisfactory accuracy, highlighting the potential usage of PoLogP in high-throughput screening of the functional molecules with the desired solubility in various solvent media.

Effects of Physicochemical Properties of Constituent Ions of Ionic Liquid on Its Permeation through a Silicone Membrane.

Ionic liquids (ILs), defined as liquid salts composed of anions and cations, have the advantage of allowing constituent ions to be stably absorbed through biological membranes, such as skin. However, limited information is currently available on the effects of the physicochemical properties of constituent ions on the membrane permeation of ILs. Therefore, we herein investigated the effects of the polarity of constituent cations on the membrane permeation of each constituent ion from IL. Various ILs were prepared by selecting lidocaine (LID) as a cation and a series of p-alkylbenzoic acids with different n-octanol/water partition coefficients (Ko/w) as anions. These ILs were applied to a skin model, a silicone membrane, and membrane permeability was investigated. The membrane permeabilities of p-alkylbenzoic acids from their single aqueous suspensions were also measured for comparison. The membrane permeability of p-alkylbenzoic acid from the aqueous suspension increased at higher Ko/w. However, the membrane permeability of ILs was similar regardless of the Ko/w of the constituent p-alkylbenzoic acid. Furthermore, the membrane permeability of the counterion LID remained unchanged regardless of the constituent p-alkylbenzoic acid. These results suggest that even when the Ko/w of IL constituents markedly differs, the resulting IL does not affect membrane permeability.

A case study on the influence of hydrophilicity on the signal enhancement by dynamic nuclear polarization.

In this work, the behavior of four different commercially available polarizing agents is investigated employing the non-ionic model surfactant 1-octanol as analyte. A relative method for the comparison of the proportion of the direct and indirect polarization transfer pathways is established, allowing a direct comparison of the polarization efficacy for different radicals and different parts of the 1-octanol molecule despite differences in radical concentration or sample amount. With this approach, it could be demonstrated that the hydrophilicity is a key factor in the way polarization is transferred from the polarizing agent to the analyte. These findings are confirmed by the determination of buildup times Tb, illustrating that the choice of polarizing agent plays an essential role in ensuring an optimal polarization transfer and therefore the maximum amount of enhancement possible for DNP enhanced NMR measurements.

1-Octanol emitted by Oecophylla smaragdina weaver ants repels and deters oviposition in Queensland fruit fly.

Humans have used weaver ants, Oecophylla smaragdina, as biological control agents to control insect pests in orchards for many centuries. Over recent decades, the effectiveness of weaver ants as biological control agents has been attributed in part to deterrent and oviposition inhibiting effects of kairomones produced by the ants, but the chemical identity of these kairomones has remained unknown. We have identified the kairomone responsible for deterrence and oviposition inhibition by O. smaragdina, providing a significant advance in understanding the chemical basis of their predator/prey interactions. Olfactometer assays with extracts from weaver ants demonstrated headspace volatiles to be highly repellent to Queensland fruit fly, Bactrocera tryoni. Using electrophysiology and bioassays, we demonstrate that this repellence is induced by a single compound, 1-octanol. Of 16 compounds identified in O. smaragdina headspace, only 1-octanol evoked an electrophysiological response from B. tryoni antennae. Flies had greatly reduced oviposition and spent significantly less time in an olfactometer arm in the presence of 1-octanol or a synthetic blend of headspace volatiles containing 1-octanol than in the presence of a synthetic blend of headspace volatiles without 1-octanol, or clean air. Taken together, our results demonstrate that 1-octanol is the functional kairomone component of O. smaragdina headspace that explains repellence and oviposition deterrence, and is hence an important contributor to the effectiveness of these ants as biological control agents.

Self-Assembly and Micellar Transition in CTAB Solutions Triggered by 1-Octanol.

This study exploits higher-order micellar transition ranging from ellipsoidal to rodlike to wormlike induced by 1-octanol (C8OH) in an aqueous solution of cetyltrimethylammonium bromide (CTAB), characterizing phase behavior, rheology, and small-angle neutron scattering (SANS). The phase diagram for the ternary system CTAB-C8OH-water was constructed, which depicted the varied solution behavior. Such performance was further inferred from the rheology study (oscillatory-shear frequency sweep (ω) and viscosity (η)) that displayed an interesting solution behavior of CTAB solutions as a function of C8OH. It was observed that at low C8OH concentrations, the solutions appeared viscous/viscoelastic fluids that changed to an elastic gel with an infinite relaxation time at higher concentrations of C8OH, thereby confirming the existence of distinct micelle morphologies. Small-angle neutron scattering (SANS) provided various micellar parameters such as aggregation numbers (Nagg) and micellar size/shape. The experimental results were further validated with a computational simulation approach. The molecular dynamic (MD) study offered an insight into the molecular interactions and aggregation behavior through different analyses, including radial distribution function (RDF), radius of gyration (Rg), and solvent-accessible surface area (SASA).

Preparation of an isorhamnetin phospholipid complex for improving solubility and anti-hyperuricemia activity.

To improve the solubility and anti-hyperuricemia activity of the insoluble natural flavonoid isorhamnetin (ISO), an isorhamnetin phospholipid complex (ISO-PC) was prepared. ISO-PC was prepared through solvent evaporation and its prescription process was optimized. The formation of ISO-PC was verified via multiple characterization methods. Parameters such as drug loading, solubility, octanol-water partition coefficient, stability, and in vivo anti-hyperuricemia activity of ISO-PC were investigated. The complexation efficiency of ISO-PC was 95.1% ± 0.56%. The characterization results confirmed that ISO-PC was bound by intermolecular interactions between ISO and phospholipids. Compared with ISO, the solubility of ISO-PC in water and 1-octanol increased by 122 and 16.5 times, respectively. In addition, the octanol-water partition coefficient decreased to 1.08. Pharmacodynamic studies have reported that ISO-PC has a more significant effect on reducing serum uric acid levels and renal protection. In conclusion, the findings of this study suggested that ISO-PC could be used as a promising formulation to improve the solubility and the anti-hyperuricemia activity of ISO.

Effects of Lipophilicity and Structural Features on the Antiherpes Activity of Digitalis Cardenolides and Derivatives.

There is growing interest in exploring Digitalis cardenolides as potential antiviral agents. Hence, we herein investigated the influence of structural features and lipophilicity on the antiherpes activity of 65 natural and semisynthetic cardenolides assayed in vitro against HSV-1. The presence of an α,ß-unsaturated lactone ring at C-17, a ß-hydroxy group at C-14 and C-3ß-OR substituents were considered essential requirements for this biological activity. Glycosides were more active than their genins, especially monoglycosides containing a rhamnose residue. The activity enhanced in derivatives bearing an aldehyde group at C-19 instead of a methyl group, whereas inserting a C-5ß-OH improved the antiherpes effect significantly. The cardenolides lipophilicity was accessed by measuring experimentally their log P values (n-octanol-water partition coefficient) and disclosed a range of lipophilicity (log P 0.75±0.25) associated with the optimal antiherpes activity. In silico studies were carried out and resulted in the establishment of two predictive models potentially useful to identify and/or optimize novel antiherpes cardenolides. The effectiveness of the models was confirmed by retrospective analysis of the studied compounds. This is the first SAR study addressing the antiherpes activity of cardenolides. The developed computational models were able to predict the active cardenolides and their log P values.

Effect of n-octanol on impurity removal by reverse flotation of magnesite ore.

Dodecylamine is one of the most commonly used amine collectors for the reverse flotation of magnesite ore. Through a combination of experimental research and computational simulation, the effect of n-octanol on the removal of impurities by the reverse flotation of magnesite ore was studied. The test results show that when the dosage of dodecylamine was 60 mg/L, the flotation rates of magnesite and dolomite were 59.53% and 58.02%, respectively, and the flotation rate of quartz was 97.60%. In the presence of n-octanol, the flotation rate of magnesite decreased to 56.41%, and the flotation rates of dolomite and quartz increased to 61.30% and 99.59%, respectively. The test results show that the addition of n-octanol can improve the selectivity of minerals under the same amount of collector. The adsorption of dodecylamine (dodecylamine and n-octanol) on the surface of magnesite, dolomite and quartz was simulated using quantum chemical calculations based on density functional theory (DFT) and implemented in the CASTEP module of Materials Studio. The results show that dodecylamine can adsorb to magnesite, dolomite and quartz, and the adsorption effect was strongest on quartz. After adding n-octanol, the population value of the bond between the agent and magnesite decreased from 0.19 to 0.17, indicating that the adsorption effect of the agent on magnesite was weakened. The population value of the bond between the drug and dolomite increased from 0.19 to 0.23, indicating that the adsorption effect of the drug on dolomite was enhanced. H28, H29, and H2 in the drug form bonds with O12, O20, and O20 on the surface of quartz (101), respectively, and the population values were 0.43, 0.25, and 0.09, respectively. The adsorption sites of the drug and the quartz were increased, and the adsorption effect of the quartz was markedly improved. The test and simulation results show that the dosage of the agent can be reduced in the presence of n-octanol. N-octanol is not only beneficial to the removal of silicon by amine reverse flotation but also has a certain beneficial effect on the removal of calcium by reverse flotation.