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Hydrazoic acid (HN3) and its deprotonated form azide ion (N3−) (AHA) are toxic because they inhibit the cytochrome c oxidase complex IV (CoX IV) embedded in the inner mitochondrial membrane that forms part of the enzyme complexes involved in cellular respiration. Critical to its toxicity is the inhibition of CoX IV in the central nervous system and cardiovascular system. Hydrazoic acid is an ionizable species and its affinity for membranes, and the associated permeabilities, depend on the pH values of aqueous media on both sides of the membranes. In this article, we address the permeability of AHA through the biological membrane. In order to understand the affinity of the membrane for the neutral and ionized form of azide, we measured the octanol/water partition coefficients at pH values of 2.0 and 8.0, which are 2.01 and 0.00034, respectively. Using a Parallel Artificial Membrane Permeability Assay (PAMPA) experiment, we measured the effective permeability through the membrane, which is logPe − 4.97 and − 5.26 for pH values of 7.4 and pH 8.0, respectively. Experimental permeability was used to validate theoretical permeability, which was estimated by numerically solving a Smoluchowski equation for AHA diffusion through the membrane. We demonstrated that the rate of permeation through the cell membrane of 8.46·104 s−1 is much higher than the rate of the chemical step of CoX IV inhibition by azide of 200 s−1. The results of this study show that transport through the membrane does not represent the rate-limiting step and therefore does not control the rate of CoX IV inhibition in the mitochondria. However, the observed dynamics of azide poisoning is controlled by circulatory transport that takes place on a time scale of minutes. [ABSTRACT FROM AUTHOR]

This study aimed at predicting the n-octanol/water partition coefficient (Kow) of 43 organophosphorous insecticides. Quantitative structure–property relationship analysis was performed on the series of 43 insecticides using two different methods, linear (multiple linear regression, MLR) and non-linear (artificial neural network, ANN), which Kow values of these chemicals to their structural descriptors. First, the data set was separated with a duplex algorithm into a training set (28 chemicals) and a test set (15 chemicals) for statistical external validation. A model with four descriptors was developed using as independent variables theoretical descriptors derived from Dragon software when applying genetic algorithm (GA)–variable subset selection (VSS) procedure. The values of statistical parameters, R2, Q2 ext, SDEPext and SDEC for the MLR (94.09 %, 92.43 %, 0.533 and 0.471, respectively) and ANN model (97.24 %, 92.17 %, 0.466 and 0.332, respectively) obtained for the three approaches are very similar, which confirmed that the employed four parameters model is stable, robust and significant.

The octanol/water partition coefficient for nanoparticles is an important criterion to estimate the ecological fate of these new fast disseminate in everyday life substances. The validation of the predictive potential of models is a key component of quantitative structure–property relationships (QSPRs). The so-called system of self-consistent of the models is, maybe, a new approach for the validation of the predictive potential. The measure of self-consistency is the average of the correlation coefficient on different validation sets observed for different models. The aim of the present study was the checking up the suitability of the self-consistency of models obtained by two approaches to select a better modelling approach of octanol/water partition coefficients for gold nanoparticles (GNPs). The above models are based on a representation of GNPs by so-called quasi-SMILES which are special sequences of symbols which translate data on architecture and conditions of acting of GNPs. The first approach is the Monte Carlo optimization of the correlation coefficient between the observed and predicted endpoint. The second is the modification of the first approach via an additional criterion, so-called the index of the ideality of correlation. The self-consistency and predictive potential of the second approach are better. The system of self-consistency of models is studied for modeling of octanol/water partition coefficient of GNPs, for the first time. Article Highlights: The quasi-SMILES applied as the representation of gold nanoparticles (GNPs). Quasi-SMILES are symbols that code the molecular structure and experimental conditions. The symbols of quasi-SMILES were used to the definition of optimal descriptors (OD). One-variables correlation of the OD is a predictive model for logP of GNPs. The system of self-consistent of models is a new way to validate a model. The average determination coefficient (validation set) of five random splits is 0.901. [ABSTRACT FROM AUTHOR]

Spotted-wing drosophila (Drosophila suzukii Matsumura) is a major pest of soft-skinned fruit and due to the low infestation tolerance for marketable fruit, growers take preventive actions to hinder spotted-wing drosophila damages. Insecticides application is one of the measures taken by growers. Although intensive spraying programs have been used to manage spotted-wing drosophila, its early infestation, rapid reproduction, and vast range of host have caused damage to still occur in fruit, including tart cherries, Prunus ceraus (Linnaeus). Therefore, there is a merit for information on insecticide's curative activity to understand whether sprays manage spotted-wing drosophila individuals within infested fruit. Tart cherry fruit were exposed to spotted-wing drosophila adults for 3 d. After this infestation period, insecticides were applied 1 and 3 d later. Small larvae, large larvae, and pupae were counted 9 d after initial infestation. A parallel set of insecticide-treated tart cherries were subjected to residue analysis. Phosmet and spinetoram were able to reduced live spotted-wing drosophila counts compared with the control at all life stages and insecticide application times, whereas zeta-cypermethrin, acetamiprid, and cyantraniliprole were less consistent in reducing spotted-wing drosophila numbers. Chromobacterium subtsugae demonstrated no curative action. Residue analysis demonstrated that zeta-cypermethrin residues mostly remained on fruit surface. Small portions of phosmet, spinetoram, and cyantraniliprole were able to penetrate fruit surfaces and move into subsurface tissues. Acetamiprid was the only compound which >47% penetrated into the fruit subsurface consistently across both years. Curative activity demonstrated in this study can provide additional tactics for spotted-wing drosophila management in tart cherry Integrated Pest Management (IPM) programs. [ABSTRACT FROM AUTHOR]

In this study quantum mechanical methods were used to predict the solvation energies of a series of drug-like molecules both in water and in octanol, in the context of the SAMPL6 n-octanol/water partition coefficient challenge. In pharmaceutical design, n-octanol/water partition coefficient, LogP, describes the drug's hydrophobicity and membrane permeability, thus, a well-established theoretical method that rapidly determines the hydrophobicity of a drug, enables the progress of the drug design. In this study, the solvation free energies were obtained via six different methodologies (B3LYP, M06-2X and ωB97XD functionals with 6-311+G** and 6-31G* basis sets) by taking into account the environment implicitly; the methodology chosen (B3LYP/6-311+G**) was used later to evaluate ΔGsolv by using explicit water as solvent. We optimized each conformer in different solvents separately, our calculations have shown that the stability of the conformers is highly dependent on the solvent environment. We have compared implicitly and explicitly solvated systems, the interaction of one explicit water with drug-molecules at the proper location leads to the prediction of more accurate LogP values. [ABSTRACT FROM AUTHOR]

• High temperature EtOH/H 2 O employed as a green mobile phase for log P determination. • Equal Collander fit with high temperature EtOH/H 2 O or ambient MeOH/H 2 O mobile phases. • High temperature ethanol/water shown to be a better mobile phase via LSER comparison. • Significant differences between LSERs of EtOH and MeOH pure H 2 O extrapolated systems. High temperature ethanol/water was explored as a green eluent in the reversed-phase liquid chromatographic approximation of pure water retention (log k w) and subsequent estimation of the octanol/water partition coefficient (log P) via the Collander equation and the Leave-One-Out method. As part of this work, linear solvation energy relationships were employed to compare the log k w extrapolated systems based on high temperature ethanol/water, ambient acetonitrile/water, and ambient methanol/water mobile phases. Based on the comparisons of the three organic modifiers, high temperature ethanol/water mobile phases were observed to provide the best estimation of log P. This conclusion is based on a high log P correlation of 0.968 R2 and a near unity cos θ value of 0.997 between LSER coefficient vectors of ethanol/water estimated log P and octanol/water log P systems. The method employed in this work, further, provided high correlation for the hydrogen-bonding basicity term between the two systems. [ABSTRACT FROM AUTHOR]

Predictive model of logP for Pt(II) and Pt(IV) complexes built up with the Monte Carlo method using the CORAL software has been validated with six different splits into the training and validation sets. The improving of the predictive potential of models for six different splits has been obtained using so-called index of ideality of correlation. The suggested models give possibility to extract molecular features, which cause the increase or vice versa decrease of the logP. [ABSTRACT FROM AUTHOR]

Partition coefficients between human stratum corneum lipids and water ( K sclip/w ) are collected or deduced from a variety of sources in a manner that approximately doubles the available data compared to the current state-of-the-art model (Hansen et al., Adv Drug Deliv Rev . 2013;65(2):251-264). An additional datum for water itself in porcine SC that considerably extends the molecular size and lipophilicity range of the data set is considered. The data are analyzed in terms of an extended linear free energy relationship involving octanol/water partition coefficients, Abraham solvation parameters, and a secondary, power law molecular weight dependence. The optimum fit to log K sclip/w for the full data set reduces the standard error of prediction from 0.50 for a Hansen-like model to 0.39; corresponding multiplicative errors in K sclip/w are reduced from a factor of 3.1 to one of 2.5. The difference in performance is driven by the water datum, which requires a more complex dependence on molecular size than that afforded by Abraham parameters. In the absence of the water value, the Hansen-like model, which does not include a dependence on molecular size, is essentially optimum. A comparison is presented to fluid-phase phospholipid–water systems, which have a demonstrably different structure–property relationship. [ABSTRACT FROM AUTHOR]

In this paper, we present group-contribution (GC) based property models for the estimation of physical properties of amino acids using their molecular structural information. The physical properties modelled in this work are normal melting point ( T m ), aqueous solubility ( W s ), and octanol/water partition coefficient ( K ow ) of amino acids. The developed GC-models are based on the published GC-method by Marrero and Gani (2001) with inclusion of new structural parameters (groups and molecular weight of compounds). The main objective of introducing these new structural parameters in the GC-model is to provide additional structural information for amino acids having large and complex structures and thereby improve the predictions of physical properties of amino acids. The group-contribution values were calculated by regression analysis using a data-set of 239 values for T m , 211 values for W s , and 335 values for K ow . Compared to other currently used GC-models, the developed models make significant improvements in accuracy with average absolute error of 10.8 K for T m and logarithm-unit average absolute errors of 0.16 for K ow and 0.19 for W s . [ABSTRACT FROM AUTHOR]

Reversed-phase liquid chromatography (RPLC) based octanol-water partition coefficient (logP) or distribution coefficient (logD) determination methods were revisited and assessed comprehensively. Classic isocratic and some gradient RPLC methods were conducted and evaluated for neutral, weak acid and basic compounds. Different lipophilicity indexes in logP or logD determination were discussed in detail, including the retention factor logk w corresponding to neat water as mobile phase extrapolated via linear solvent strength (LSS) model from isocratic runs and calculated with software from gradient runs, the chromatographic hydrophobicity index (CHI), apparent gradient capacity factor (k g ’) and gradient retention time (t g ). Among the lipophilicity indexes discussed, logk w from whether isocratic or gradient elution methods best correlated with logP or logD. Therefore logk w is recommended as the preferred lipophilicity index for logP or logD determination. logk w easily calculated from methanol gradient runs might be the main candidate to replace logk w calculated from classic isocratic run as the ideal lipophilicity index. These revisited RPLC methods were not applicable for strongly ionized compounds that are hardly ion-suppressed. A previously reported imperfect ion-pair RPLC method was attempted and further explored for studying distribution coefficients (logD) of sulfonic acids that totally ionized in the mobile phase. Notably, experimental logD values of sulfonic acids were given for the first time. The IP-RPLC method provided a distinct way to explore logD values of ionized compounds. [ABSTRACT FROM AUTHOR]

Salinity has been reported to influence the water solubility of organic chemicals entering marine ecosystems. However, limited data are available on salinity impacts for chemicals potentially entering seawater. Impacts on water solubility would correspondingly impact chemical sorption as well as overall bioavailability and exposure estimates used in the regulatory assessment. The pesticides atrazine, fipronil, bifenthrin, and cypermethrin, as well as the crude oil constituent dibenzothiophene together with 3 of its alkyl derivatives, all have different polarities and were selected as model compounds to demonstrate the impact of salinity on their solubility and partitioning behavior. The n-octanol/water partition coefficient ( KOW) was measured in both distilled-deionized water and artificial seawater (3.2%). All compounds had diminished solubility and increased KOW values in artificial seawater compared with distilled-deionized water. A linear correlation curve estimated salinity may increase the log KOW value by 2.6%/1 log unit increase in distilled water ( R2 = 0.97). Salinity appears to generally decrease the water solubility and increase the partitioning potential. Environmental fate estimates based on these parameters indicate elevated chemical sorption to sediment, overall bioavailability, and toxicity in artificial seawater. These dramatic differences suggest that salinity should be taken into account when exposure estimates are made for marine organisms. Environ Toxicol Chem 2017;36:2274-2280. © 2017 SETAC [ABSTRACT FROM AUTHOR]

Octanol/water ( K OW ) and octanol/air ( K OA ) partition coefficients are two important physicochemical properties of organic substances. In current practice, K OW and K OA values of some polychlorinated biphenyls (PCBs) are measured using generator column method. Quantitative structure–property relationship (QSPR) models can serve as a valuable alternative method of replacing or reducing experimental steps in the determination of K OW and K OA . In this paper, two different methods, i.e., multiple linear regression based on dragon descriptors and hologram quantitative structure–activity relationship, were used to predict generator-column-derived log K OW and log K OA values of PCBs. The predictive ability of the developed models was validated using a test set, and the performances of all generated models were compared with those of three previously reported models. All results indicated that the proposed models were robust and satisfactory and can thus be used as alternative models for the rapid assessment of the K OW and K OA of PCBs. [ABSTRACT FROM AUTHOR]

In this study, mesoporous silica (meso-silica) MCM-41 and those with the templates retained were synthesized and characterized. Adsorption capacities of the synthesized materials towards typical quinolone antibiotic pollutants, enrofloxacin and norfloxacin as representative, were investigated, and effects of the alkyl chain length of the templates on the adsorption capacity were evaluated. The results of this study indicated that the retained templates enhanced the adsorption capacities ( Q max ) of the meso-silica MCM-41 toward hydrophobic enrofloxacin, but had an inhibitory effect on that towards hydrophilic norfloxacin, which were attributed to the hydrophobic inter-environment created by the long alkyl chains of the retained templates. Importantly, the adsorption capacity increased with the increase of the alkyl chain length of the retained templates. [ABSTRACT FROM AUTHOR]

For a chromatographic column, phase ratio Φ is defined as the ratio between the volume of the stationary phase V st and the void volume of the column V 0 , and it is an important parameter characterizing the HPLC process. Although apparently simple, the evaluation of Φ presents difficulties because there is no sharp boundary between the mobile phase and the stationary phase. In addition, the boundary depends not only on the nature of the stationary phase, but also on the composition of the mobile phase. In spite of its importance, phase ratio is seldom reported for commercially available HPLC columns and the data typically provided by the vendors about the columns do not provide key information that would allow the calculation of Φ based on V st and V 0 values. A different procedure for the evaluation of Φ is based on the following formula: log k′ j = a log K ow,j + log Φ , where k ′ j is the retention factor for a compound j that must be a hydrocarbon, K ow ,j is the octanol/water partition coefficient, and a is a proportionality constant. Present study describes the experimental evaluation of Φ based on the measurement of k ′ j for the compounds in the homologous series between benzene and butylbenzene for three C18 columns: Gemini C18, Luna C18 both with 5 μm particles, and a Chromolith Performance RP-18. The evaluation was performed for two mobile phase systems at different proportions of methanol/water and acetonitrile/water. The octanol/water partition coefficients were obtained from the literature. The results obtained in the study provide further support for the new procedure for the evaluation of phase ratio. [ABSTRACT FROM AUTHOR]

A high-throughput method for determining the octanol/water partition coefficient ( P o/w ) of a large variety of compounds exhibiting a wide range in hydrophobicity was established. The method combines a simple shake-flask method with a novel two-phase solvent system comprising an acetonitrile–phosphate buffer (0.1 M, pH 7.4)—1-octanol (25:25:4, v/v/v; AN system). The AN system partition coefficients ( K AN ) of 51 standard compounds for which log P o/w (at pH 7.4; log D ) values had been reported were determined by single two-phase partitioning in test tubes, followed by measurement of the solute concentration in both phases using an automatic flow injection-ultraviolet detection system. The log K AN values were closely related to reported log D values, and the relationship could be expressed by the following linear regression equation: log D = 2.8630 log K AN  –0.1497( n = 51). The relationship reveals that log D values (+8 to –8) for a large variety of highly hydrophobic and/or hydrophilic compounds can be estimated indirectly from the narrow range of log K AN values (+3 to –3) determined using the present method. Furthermore, log K AN values for highly polar compounds for which no log D values have been reported, such as amino acids, peptides, proteins, nucleosides, and nucleotides, can be estimated using the present method. The wide-ranging log D values (+5.9 to –7.5) of these molecules were estimated for the first time from their log K AN values and the above regression equation. [ABSTRACT FROM AUTHOR]

A new model for a large dataset on octanol/water partition coefficient (log P , n = 10005) has been built with the CORAL software ( http://www.insilico.eu/coral ). The simplified molecular input-line entry system (SMILES) is used to represent the molecular structure. Building up the model includes three phases: (i) distribution of available data into the sub-training set ( n = 2634), calibration set ( n = 2528), test set ( n = 2410), and validation set ( n = 2433). No data on compounds distributed into the validation set is involved in building up model: these compounds are used solely to check up predictive potential of the built model. The statistical characteristics of the model for external validation set are the following: r 2 = 0.89, s = 0.59. The mechanistic interpretation of the model is discussed. [ABSTRACT FROM AUTHOR]

Here we present a miniaturized assay, referred to as Carrier-Mediated Distribution System (CAMDIS) for fast and reliable measurement of octanol/water distribution coefficients, log D oct . By introducing a filter support for octanol, phase separation from water is facilitated and the tendency of emulsion formation (emulsification) at the interface is reduced. A guideline for the best practice of CAMDIS is given, describing a strategy to manage drug adsorption at the filter-supported octanol/buffer interface. We validated the assay on a set of 52 structurally diverse drugs with known shake flask log D oct values. Excellent agreement with literature data ( r 2 = 0.996, standard error of estimate, SEE = 0.111), high reproducibility (standard deviation, SD < 0.1 log D oct units), minimal sample consumption (10 μL of 100 μM DMSO stock solution) and a broad analytical range (log D oct range = −0.5 to 4.2) make CAMDIS a valuable tool for the high-throughput assessment of log D oct . [ABSTRACT FROM AUTHOR]

Phase ratio Φ for an HPLC column is a common parameter being defined as the ratio between the volume of the stationary phase V st and the void volume of the column V 0 . Although apparently simple, the evaluation of phase ratio presents difficulties because there is no sharp boundary between the mobile phase and the stationary phase, and different mobile phases lead to different “effective” phase ratios. A considerable number of studies have been dedicated to the evaluation of V st and V 0 with the goal of obtaining the value for Φ . However, the parameter is seldom reported for common commercially available columns and key information for its calculation (e.g. the weight of column packing) is not typically reported by the vendors. Present study describes a novel procedure for the evaluation of phase ratio for a chromatographic column when used with a given mobile phase. The procedure allows the calculation of Φ only from the measurements of retention factors k’ for two hydrocarbons i and j, for which the octanol/water partition coefficients log K ow are known. A theoretical support for this procedure based on solvophobic theory of interactions in solution is presented, and several experimental results reported in the literature are used to demonstrate the validity of the procedure. [ABSTRACT FROM AUTHOR]

Four microemulsion liquid chromatography (MELC) systems and one micellar liquid chromatography (MLC) system have been evaluated as potential high-throughput screening platforms capable of modeling the partitioning behaviors of drug compounds in an n-octanol/water system and predicting their lipophilicity ( i.e. , log P values). The microemulsion mobile phases is consisted of sodium dodecyl sulfate (SDS), butanol, octane, heptanes, octanol and water. A linear solvation energy relationship (LSER)-based method was used to compare the MELC and MLC systems, as well as several other biochemical systems, and to identify the optimal system by comparing their Euclidean distances with the LSER coefficients. The most effective MELC system had a mobile phase consisting of 3.0% (w/w) SDS, 6.0% (w/w) butanol, 0.8% (w/w) octanol, and 90.2% (w/w) water (pH 6.4). The results showed that it gave superior results to the other chromatographic systems in terms of its ability to predict the log P values of drug compounds. [ABSTRACT FROM AUTHOR]

Abstract: Since sorption is an essential process with regard to attenuation of organic pollutants during subsurface flow, information on the sorption properties of each pollutant are essential for assessing their environmental fate and transport behavior. In the present study, the sorption behavior of 20 wastewater originated organic micropollutants was assessed by means of sediment column experiments, since experimentally determined data for these compounds are not or sparsely represented in the literature. Compounds investigated include various psychoactive drugs, phenazone-type pharmaceuticals and β-blockers, as well as phenacetine, N-methylphenacetine, tolyltriazole and para-toluenesulfonamide. While for most of the compounds no or only a low sorption affinity was observed, an elevated tendency to sorb onto aquifer sand was obtained for the β-blockers atenolol, propranolol and metoprolol. A comparison between experimental data and data estimated based on the octanol/water partition coefficient following the QSAR approach demonstrated the limitations of the latter to predict the adsorption behavior in natural systems for the studied compounds. [Copyright &y& Elsevier]

The objective of the study was assessment of occurrence and removal of two groups of persistent organic pollutants: polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) in landfill leachate (LL) treated in three constructed wetland systems (CWs) of different construction and flow regime. Two subsurface flow systems (SSF) were analyzed: one with horizontal flow and the second one consisting of two vertical flow beds followed by a horizontal flow bed. The third CW was a surface flow (SF) system, consisting of 10 ponds connected in series. The concentrations of 12 PAHs and 7 PCBs were measured in the samples of LL after subsequent treatment stages and in the sediment samples from the SF system as well as in the substrate samples from the SSF flow systems. It was confirmed that the major mechanism of PCB and PASH removal in CW systems was adsorption to the bottom sediments (in the SF system) or substrate of the beds (in the SSF systems) as well as adsorption to suspended solids, followed by sedimentation. The compounds characterized by higher octanol/water partition coefficient were more effectively retained in the sediments. Also removal of these substances occurred in the earlier stages of treatment. [ABSTRACT FROM AUTHOR]

Abstract: To develop alkyl halides for a promising prodrug system, a 5-fluorouracil prodrug containing a bromoethyl group (5-FUBr) was synthesized and its hydrophobicity, cytotoxicity and DNA-bonding ability were investigated in detail. Compare with 5-fluorouracil, 5-FUBr exhibits a great advantage of hydrophobicity and shows significant reduction in toxic side effect. To explore the mechanism of action of 5-FUBr at the molecular level, X-ray crystallography and molecular docking were exploited to make a more detailed analysis of the bromoethyl contribution to the construction of meaningful structure–activity relationship. Details of X-ray crystal structure of 5-FUBr suggest that 5-fluorouracil may be more apt to be released from 5-FUBr. The appearance of the bromoethyl group in 5-FUBr makes a remarkable impact on inhibition of thymidylate synthase (TS), and theimpact of subtle structural variation between 5-fluorouracil and 5-FUBr should be taken into account in the process of developing this family of 5-fluorouracil prodrugs. [Copyright &y& Elsevier]

Abstract: Several physico-chemical properties relevant to determine the environmental impact of ionic liquids – aqueous solubility, octanol/water partition coefficient, chromatographically derived lipophilicity and infinite dilution diffusion coefficients in water – were measured in ionic liquids based on pyridinium, ammonium and pyrrolidinium cations with bis(trifluoromethylsulfonyl)imide anions. The influence of the presence of hydroxyl or ester groups in the physico-chemical properties of these liquids was checked. It appeared that the presence of functional oxygenated moieties reduces the lipophilicity of ionic liquids and so decreases the risk of bioaccumulation in environment. [Copyright &y& Elsevier]

Abstract: Several physico-chemical properties relevant to determine the environmental impact of ionic liquids – aqueous solubility, octanol-water partition coefficient and diffusion coefficients in water at infinite dilution – together with toxicity and biodegradability of ionic liquids based on 1-alkyl-3-methylimidazolium cations with or without different oxygenated functional groups (hydroxyl, ester and ether) are studied in this work. The presence of oxygen groups on the imidazolium cation reduces the toxicity of ionic liquids 1-alkyl-3-methylimidazolium with bis(trifluoromethylsulfonyl)imide or octylsulfate anions and simultaneously decreases the value of their octanol–water partition coefficient. The presence of ester functions renders the ionic liquids more easily biodegradable, especially for long alkyl side-chains in the cation but leads to hydrolysis with the formation of reaction products that accumulate. The imidazolium ring is resistant to biodegradability and to abiotic degradation. The oxygen functionalised ionic liquids are more soluble in water and, diffuse more slowly in this medium. [Copyright &y& Elsevier]

Predictive quantitative structure - property relationships (QSPR) have been established for normal boiling points and octanol/water partition coefficient for acyclic and cyclic hydrocarbons using optimal descriptors calculated with simplified molecular input line entry system (SMILES). The probabilistic criteria for a rational definition of the domain of applicability of these models are discussed. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Abstract: The use of subcritical water as an eluent for reversed-phase liquid chromatography is further explored. Shape selectivity as well as thermodynamic values for solute transfer were measured and compared to those seen with traditional ambient methanol/water and acetonitrile/water mobile phases. Linear solvation energy analysis was also used to analyze extrapolated values of the retention factor in pure water at ambient temperatures () for subcritical water and ambient hydroorganic mobile phases. Results indicate that it is likely that a large disruption in the hydrogen-bonding network of water at high temperatures causes unique chromatographic selectivity, as well as prohibits accurate extrapolation from high temperature to ambient conditions using pure water. Additionally, subcritical water was not found to be a suitable mobile phase for determining for use in estimating octanol/water partition coefficients. [ABSTRACT FROM AUTHOR]

Abstract: Three different splits into the subtraining set (n = 22), the set of calibration (n = 21), and the test set (n = 12) of 55 antineoplastic agents have been examined. By the correlation balance of SMILES-based optimal descriptors quite satisfactory models for the octanol/water partition coefficient have been obtained on all three splits. The correlation balance is the optimization of a one-variable model with a target function that provides both the maximal values of the correlation coefficient for the subtraining and calibration set and the minimum of the difference between the above-mentioned correlation coefficients. Thus, the calibration set is a preliminary test set. [Copyright &y& Elsevier]

Comparison of the quantitative structure—property relationships (QSPR) based on optimal descriptors calculated with the International Chemical Identifier (InChI) and QSPR based on optimal descriptors calculated with simplified molecular input line entry system has shown that the InChI-based optimal descriptors give more accurate prediction for the logarithm of octanol/water partition coefficient of platinum complexes. [ABSTRACT FROM AUTHOR]

The radiation-induced emulsion graft polymerization method is limited for applying concentrations higher than the monomer concentration that enables stable formation of monomer micelles. Furthermore, foaming may occur because of the presence of the surfactant, which is essential for the formation of micelles, resulting in likely splashing around a highly flammable monomer emulsion. In the present study, to overcome these issues, we investigate the effect of added alcohols on the grafting of glycidyl methacrylate (GMA) in emulsion graft polymerization. By adding hydrophobic alcohols to the GMA monomer emulsion of the given system, we succeeded in increasing polymerization rate at low monomer concentrations and developing a highly safe method of emulsion graft polymerization. By adding 0.5 wt% of hydrophobic alcohol such as 1-octanol to the GMA monomer emulsion, the degree of grafting was 4 times higher than in the case without addition. In addition, we successfully reduced the foamability of the GMA monomer emulsion deriving from the surfactant. This is a novel graft polymerization method with promising wide industrial application, as it brings improvements for the existing issues of the conventional emulsion graft polymerization method — (1) emulsion stability under low concentration monomer and (2) process stability due to foaming of the monomer emulsion during polymerization. • Effect of added alcohols on the grafting of glycidyl methacrylate in emulsion graft polymerization was investigated. • The added hydrophobic alcohol such as 1-octanol contributes to the stability of the monomer micelles. • The octanol/water partition coefficient of added alcohol is strongly affected by the degree of grafting. • The hydrophobic alcohol also has a defoaming function, which completely suppressed the foaming of the surfactant-derivative monomer solution. [ABSTRACT FROM AUTHOR]

Abstract: Simplified molecular input line entry system (SMILES) has been utilized in constructing quantitative structure–property relationships (QSPR) for octanol/water partition coefficient of vitamins and organic compounds of different classes by optimal descriptors. Statistical characteristics of the best model (vitamins) are the following: n =17, R 2 =0.9841, s =0.634, F =931 (training set); n =7, R 2 =0.9928, s =0.773, F =690 (test set). Using this approach for modeling octanol/water partition coefficient for a set of organic compounds gives a model that is statistically characterized by n =69, R 2 =0.9872, s =0.156, F =5184 (training set) and n =70, R 2 =0.9841, s =0.179, F =4195 (test set). [Copyright &y& Elsevier]

Abstract: A regression method was developed for the hydrophobicity ruler approach, which is an indirect method for determining the octanol/water partition coefficients of very hydrophobic compounds. Two constants introduced into the mathematical model were obtained by regression of the absorption data sampled before the partition equilibrium. A water miscible organic solvent was used to increase the solubility of the very hydrophobic compounds in the aqueous solution so that the hydrophobicity scale was reduced and the equilibration was accelerated. Polydimethylsiloxane/methanol aqueous solution and a series of 21 polychlorinated biphenyls (PCBs) were used to demonstrate the regression method. The PCB compounds with known experimental log K o/w values served as reference compounds, while the PCB compounds without known log K o/w values were determined. The distribution coefficients (log K p/s), uptake and elimination rate constants were obtained from the two regression constants for each compound (reference or unknown). The correlation of the log K p/s values of the reference PCB compounds with their log K o/w values was linear (log K o/w =2.69log K p/s +0.76, R 2 =0.97). The log K o/w values were compared with literature values and suggested that some values from the literature far off the calibration line could be inaccurate. The critical experimental factors, the merits of the regression method were discussed. [Copyright &y& Elsevier]

Abstract: Comparison of QSPR models for vitamins and for various substances, which are not vitamins indicates that vitamins have less number of molecular features (topologic and kinds of atomic orbitals), but, most probably, more complex mechanisms of interactions with molecules of water and octanol. [Copyright &y& Elsevier]

Fifteen experimental literature data sets on the acute toxicity of substituted nitrobenzenes to algae (Scenedesmus obliquus, Chlorella pyrenoidosa, C. vulgaris), daphnids (Daphnia magna, D. carinata), fish (Cyprinus carpio, Poecilia reticulata), protozoa (Tetrahymena pyriformis), bacteria (Phosphobacterium phosphoreum), and yeast (Saccharomyces cerevisiae) were used to establish quantum chemistry based quantitative structure-activity relationships (QSARs). The logarithm of the octanol/water partition coefficient, log Kow, and the energy of the lowest unoccupied molecular orbital, Elumo, were used as descriptors. Suitable QSAR models (0.65 < r2 < 0.98) to predict acute toxicity of substituted mononitrobenzenes to protozoa, fish, daphnids, yeast, and algae have been derived. The log Kow was a sufficient descriptor for all cases, with the additional Elumo descriptor being required only for algae. The QSARs were found to be valid for neutral substituted mononitrobenzenes with no -OH, -COOH, or -CN substituents attached directly to the ring. From the 100,196 European Inventory of Existing Commercial Substances (EINECS), 497 chemicals were identified that fit the selection criteria for the established QSARs. Based on these results, an advisory tool has been developed that directs users to the appropriate QSAR model to apply for various types of organisms within specified log Kow ranges. Using this tool, it is possible to obtain a good indication of the toxicity of a large set of EINECS chemicals and newly developed substituted mononitrobenzenes to five different organisms without the need for additional experimental testing. [ABSTRACT FROM AUTHOR]

Abstract: We investigated the 13C-labeling kinetics of the emission of two major monoterpenes emitted by needles of Mediterranean conifer Pinus pinea L., monoterpene alcohol linalool and non-oxygenated monoterpene trans-β-ocimene. These data were further used to develop and parameterize a dynamics monoterpene emission model, predicting the emissions of monoterpenes with contrasting physico-chemical properties to environmental changes. All monoterpenes emitted were labeled by 13C in short pulse-labeling experiments. 13C-labeling experiments further indicated for these two monoterpenes comprising 77% of total emissions that a major part of the emissions of these two monoterpenes relied on recently synthesized carbon not on specific storage compartments within the resin ducts. However, labeling kinetics suggested existence of transient storage pools, located within the needle aqueous and lipid phases. For linalool, we found half-lives of 13min for the aqueous phase storage and 3h for the lipid phase while trans-β-ocimene exhibit an aqueous phase half-life of 2 and 15min for the lipid phase, overall indicating that the transient storage due to limited monoterpene volatility can significantly alter the emission dynamics. The key physico-chemical characteristics determining the time constants of the transient storage pools were the Henry''s law constant (liquid/gas phase partition coefficient) and the octanol/water (lipid/liquid) phase partition coefficient. As monoterpene Henry''s law constants vary over four orders of magnitude and octanol/water partition coefficients over three orders of magnitude, the capacity for non-specific storage, and damping of the effects of rapidly changing environmental conditions is expected to strongly vary among different monoterpenes. Overall, our study suggests that non-specific storage due to limited volatility is a common phenomenon of common of plant-emitted compounds. [Copyright &y& Elsevier]

Abstract: To model the emission dynamics and changes in fractional composition of monoterpenoids from plant leaves, temperature dependencies of equilibrium coefficients must be known. Henry’s law constants (H pc, Pam3 mol−1 and octanol/water partition coefficients (K OW, molmol−1) were determined for 10 important plant monoterpenes at physiological temperature ranges (25–50°C for H pc and 20–50°C for K OW). A standard EPICS procedure was established to determine H pc and a shake flask method was used for the measurements of K OW. The enthalpy of volatilization (ΔH vol) varied from 18.0 to 44.3kJmol−1 among the monoterpenes, corresponding to a range of temperature-dependent increase in H pc between 1.3- and 1.8-fold per 10°C rise in temperature. The enthalpy of water–octanol phase change varied from −11.0 to −23.8kJmol−1, corresponding to a decrease of K OW between 1.15- and 1.32-fold per 10°C increase in temperature. Correlations among physico-chemical characteristics of a wide range of monoterpenes were analyzed to seek the ways of derivation of H pc and K OW values from other monoterpene physico-chemical characteristics. H pc was strongly correlated with monoterpene saturated vapor pressure (P v), and for lipophilic monoterpenes, ΔH vol scaled positively with the enthalpy of vaporization that characterizes the temperature dependence of P v Thus, P v versus temperature relations may be employed to derive the temperature relations of H pc for these monoterpenes. These data collectively indicate that monoterpene differences in H pc and K OW temperature relations can importantly modify monoterpene emissions from and deposition on plant leaves. [Copyright &y& Elsevier]

Abstract: The octanol–air partition coefficient (K OA) is useful for predicting the partitioning behavior of organic compounds between air and environmental matrices such as soil, vegetation, and aerosol particles. At present, experimentally determined K OA values are available for only several hundred compounds. Therefore, the ability to estimate K OA is necessary for screening level evaluation of most chemicals. Although it is possible to estimate K OA from the octanol–water partition coefficient (K OW) and Henry’s law constant (HLC), various concerns have been raised in regard to the usability of this estimation methodology. This work examines the accuracy and usability of K OW and HLC in application to a comprehensive database set of K OA values for screening level environmental assessment. Results indicate that K OW and HLC can be used to accurately predict K OA even when estimated K OW and HLC values are used. For an experimental dataset of 310log K OA values for different compounds, the K OW–HLC method was statistically accurate as follows: correlation coefficient (r 2): 0.972, standard deviation: 0.526, absolute mean error: 0.358 using predominantly experimental K OW and HLC values. When K OW and HLC values were estimated (using the KOWWIN and HENRYWIN programs), the statistical accuracy was: correlation coefficient (r 2): 0.957, standard deviation: 0.668, absolute mean error: 0.479. [Copyright &y& Elsevier]

The use of a recently proposed hydrophobic similarity index for the alignment of molecules and the prediction of their differences in biological activity is described. The hydrophobic similarity index exploits atomic contributions to the octanol/water transfer free energy, which are evaluated by means of the fractional partitioning scheme developed within the framework of the Miertus-Scrocco-Tomasi continuum model. Those contributions are used to define global and local measures of hydrophobic similarity. The suitability of this computational strategy is examined for two series of compounds (ACAT inhibitors and 5-HT3 receptor agonists), which are aligned to maximize the global hydrophobic similarity using a Monte Carlo-simulated protocol. Indeed, the concept of local hydrophobic similarity is used to explore structure–activity relationships in a series of COX-2 inhibitors. Inspection of the 3D distribution of hydrophobic/hydrophilic contributions in the aligned molecules is valuable to identify regions of very similar hydrophobicity, which can define pharmacophoric recognition patterns. Moreover, low similar regions permit to identify structural elements that modulate the differences in activity between molecules. Finally, the quantitative relationships found between the pharmacological activity and the hydrophobic similarity index points out that not only the global hydrophobicity, but its 3D distribution, is important to gain insight into the activity of molecules. [ABSTRACT FROM AUTHOR]

Abstract: The experimental octanol/water partition coefficient data, of 108 compounds from the data set [Rytting, E., Lentz, K.A., Chen, X., Qian, F., Venkatesh, S., 2004. A quantitative structure–property relationship for predicting drug solubility in PEG 400/water cosolvent systems. Pharm. Res. 21, 237–244] was compared to calculated values using the computer programs ClogP®, ACD/logPdb® and KowWin®. It was found that all the three programs have a user friendly interface but ClogP® appears to be the more accurate predictor of log K ow. [Copyright &y& Elsevier]

Abstract: A co-polymer of poly(N-isopropylacrylamide) (85%) co-butyl acrylate (10%) co-methacrylic acid (5%) (NIPAM/BA/MAA) (85/10/5) microgel was synthesised and investigated as a potential pH and temperature sensitive transdermal delivery device. Three compounds having different octanol/water partition coefficients and solubilities were incorporated into the microgel, namely: salicylamide (SA), methyl paraben (MP) and propyl paraben (PP). Physico-chemical characterisation of these microgel–drug complexes showed that microgels incorporating MP and SA have smaller volumes after changing environmental pH or temperature when compared with the co-polymer NIPAM/BA/MAA (85/10/5) alone. This reduction in volume could be attributed to the incorporation of the compounds into the microgel particles, having a shielding effect on the charged groups present within the network. Diffusion studies, across human skin, were performed at 305K in the range of pH 3–7 for saturated solutions of SA, MP and PP, and for microgel particles incorporating the three compounds. The transport rate for these microgels incorporating MP was reduced by 2/3-fold compared to the saturated solution, by one order of magnitude for PP, meanwhile the transport rate for these microgels incorporating SA is the same order of magnitude as that for the corresponding saturated solutions. Transdermal release studies of the saturated colloidal dispersions indicated that pH control of the drug release was marginal. The incorporation of compounds into the pH/temperature sensitive co-polymer NIPAM/BA/MAA (85/10/5) and the subsequent release depends on the octanol/water partition coefficient and solubility of the respective compound. [Copyright &y& Elsevier]

Active ingredients have been around in cosmetics for a long time but have they really resulted in active cosmetic products? In order to achieve this, the right active needs to be delivered to the right location at the right concentration for the correct period of time. And the extent (and therefore the concentration) of this delivery depends on the formulation. From a rather theoretical approach based on the polarity of the active ingredient, the stratum corneum and the oil phase, the Relative Polarity Index was established that enables the selection of a suitable emollient for ensuring skin penetration of the active ingredient. Practical examples subsequently show the validity of this approach that demonstrates that one can regulate the delivery of an active molecule (and therefore the efficacy of a cosmetic formulation) by selection and control of the emollient system. Cosmetic formulations are generally quite complex mixtures and subsequent experiments using different emulsifier systems indicated that this component of a cosmetic formulation could also have an impact on steering the active ingredient to the right layer of the skin, although it is too early to be able to derive general rules from this. [ABSTRACT FROM AUTHOR]

Quantitative structure-activity relationships (QSARs) based on the octanol/water partition coefficient were employed to predict acute toxicities of 36 substituted aromatic compounds and their mixtures. In this study, the model developed by Verhaar et al. was modified and used to calculate octanol/water partition coefficients of chemical mixtures. To validate the model, acute toxicities of these chemicals were measured to Vibrio fischeri in terms of EC 50 . The results indicated that the obtained QSAR models could be used to predict toxicities of samples consisting of these substituted aromatic compounds, individually or in combinations. The obtained equations were proved to be robust enough by using the leave-one-out test method. By classifying these chemicals into two groups, polar and non-polar, the toxicities of chemical mixtures within each group can be predicted accurately from their calculated partition coefficients. [ABSTRACT FROM AUTHOR]

For estimating log P values of a group of organic compounds, a back-propagation neural network with a 9–6–1 architecture was developed with optimal learning rate (ε) and momentum (μ) of 0.24 and 0.82, respectively. A collection of 131 organic compounds was chosen as data set that consists of normal hydrocarbons, alcohols, ethers, amines, ketones, acids, benzene derivatives, phenols, and aldehydes. The data set was divided into a training set consisting of 118 molecules and a prediction set consisting of 18 molecules. The most important properties that affect the partition coefficients of organic compounds (surface/volume, dipole moment, and those which are related to electrostatic potentials such as the sum of charges on the carbon atoms) were used as descriptors. These descriptors were obtained using AM1 semiempirical MO method for the gas phase geometries. The descriptors were selected via developing a multiple linear regression analysis. The ANN calculated values of partition coefficients (log Ps) for molecules of the training and prediction sets are in good agreement with the experimental values. [ABSTRACT FROM AUTHOR]

Liquid aqueous solubility (Sw,L), octanol/water partition coefficients (Kow), liquid vapor pressure (Pv,L), and Henry’s law constants (Hc) were estimated for 20 methylated naphthalenes ranging from monomethyl to tetramethylnaphthalenes. Chromatographic methods were used for the estimation. Chromatographic retention measurements were conducted for 11 reference compounds and regressions were fit between the retention indices and the physicochemical properties. HPLC octadecylsilyl column with acetonitrile/water eluent was used for the estimation of Sw,L and Kow. Two GC columns, HP5-MS and a more hydrophobic HP-1, were tested for the estimation of Pv,L. Measured retention indices for the methylated naphthalenes were entered to the regression equations to calculate the physicochemical properties for these compounds. Literature values, where available, were used to validate the calculated values. The method accurately estimated the physicochemical properties. Estimated Sw,L and Pv,L decreased with the number of methyl groups. Kow increased with the number of methyl groups. There was no obvious relation between Hc and the number of methyl groups. Log Sw,L ranged from 0.885 for 1,2,5,6-tetramethylnaphthalene to 2.269 for 1-methylnaphthalene (mmol/m3). Log Kow varied from 3.89 for 1-methylnaphthalene to 4.95 for 1,2,5,6-tetramethylnaphthalene. Log Pv,L ranged from −0.983 for 1,2,5,6-tetramethylnaphthalene to 0.789 for 2-methylnaphthalene (Pa). Log Hc varied from 1.03 for 1,4,5-trimethylnaphthalene to 1.73 for 2,6-dimethylnaphthalene (Pa m3/mol). There were no apparent effects of GC column hydrophobicity on the accuracy of the results. Estimation of Sw,L and Kow based on GC retention indices was not as accurate as with HPLC. Comparison of the estimated values with values predicted by EPIWIN indicated that EPIWIN is useful in giving order-of-magnitude prediction of physicochemical properties. [Copyright &y& Elsevier]

The n-octanol/water partition coefficients (Kow) and water solubilities (Sw) of 11 phenylacrylates were determined by the shake-flask method. Their capacity factors (k′) were determined by reversed-phase high performance liquid chromatography (RP-HPLC) with C18 column and methanol water eluent. It was found that both log Kow and log Sw had good correlations with log k′, respectively. Linear solvation energy parameters, describing the interaction of molecules accurately, were calculated for these compounds and used to predict their partition properties. Results demonstrated that three partition properties could be predicted precisely with similar models based on linear solvation energy relationships, which indicated the similarity of their partition mechanisms. [ABSTRACT FROM AUTHOR]

Purpose. Canalicular multispecific organic anion transporter (cMOAT/MRP2) is known to exhibit a broad substrate specificity toward amphiphatic organic anions, including methotrexate (MTX). The present study aims to identify the physicochemical properties of MTX derivatives that correlate with recognition specificity by cMOAT/MRP2. Methods. We examined the inhibitory effect of MTX and 24 analogs on the transport of [3H]–S–(2,4–dinitrophenyl)glutathione by cMOAT/MRP2. The affinity constants of these compounds were compared with their physicochemical parameters. The primary active transport of several compounds was also confirmed. Results. The affinity constants closely correlated with the octanol/water partition coefficient (clogP), and a linear combination of polar and nonpolar surface areas. The affinity for cMOAT/MRP2 also closely correlated with the molecular weight, which also showed a significant correlation with nonpolar surface area and clogP. Conclusions. Recognition by cMOAT/MRP2 depends on a balance of dynamic surface properties between the polar and nonpolar regions of MTX analogs. The so–called “molecular weight threshold” for the cMOAT/MRP2 affinity of these compounds can be explained by their physicochemical parameters, especially their nonpolar surface areas. [ABSTRACT FROM AUTHOR]