Regression method of the hydrophobicity ruler approach for determining octanol/water partition coefficients of very hydrophobic compounds

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 logK(o/w) values served as reference compounds, while the PCB compounds without known logK(o/w) values were determined. The distribution coefficients (logK(p/s)), uptake and elimination rate constants were obtained from the two regression constants for each compound (reference or unknown). The correlation of the logK(p/s) values of the reference PCB compounds with their logK(o/w) values was linear (logK(o/w)=2.69logK(p/s)+0.76, R(2)=0.97). The logK(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.     

Quantitative structure-activity relationships of nitroaromatics toxicity to the algae (Scenedesmus obliguus)

The DFT-B3LYP method, with the basis set 6-311G( * *), was employed to calculate the molecular geometries and electronic structures of 25 nitroaromatics. The acute toxicity (-lgEC(50)) of these compounds to the algae (Scenedesmus obliguus) along with hydrophobicity described by logK(OW), and two quantum chemical parameters-energy of the lowest unoccupied molecular orbital, E(LUMO), and the charge of the nitro group, [ForQ(NO2), were used to establish the quantitative structure-activity relationships (QSARs). For 18 mononitro derivatives, the hydrophobicity parameter logK(OW) could interpret the toxic mechanism successfully. Dinitro aromatic compounds were susceptible to be reduced to aniline for their electrophilic nature. Their toxicity was controlled mainly by electronic factors instead of hydrophobicity. The electronic parameters, E(LUMO) and Q(NO2), were used to yield the following model: -lg EC(50) = 3.746 - 25.053 E(LUMO) + 6.481 Q(NO2) (n=22, R=0.926, SE=0.206, F=56.854, P<0.001). The predicted toxic values using the above equation are in good agreement with the experimental values.     

Physicochemical properties of selected polybrominated diphenyl ethers and extension of the UNIFAC model to brominated aromatic compounds

The aqueous solubilities (S(w)) at various temperatures from 283 K to 308 K and 1-octanol/water partition coefficients (K(ow)) for four polybrominated diphenyl ethers (PBDEs: 4,4'-dibromodiphenyl ether (BDE-15), 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), 2,2',4,4',5-pentabromodiphenyl ether (BDE-99), and 2,2',4,4',5,5'-hexabromodiphenyl ether (BDE-153)) were measured by the generator column method. The S(w) and K(ow) data revealed the effect of bromine substitution and basic structure on S(w) and K(ow). To estimate the infinite dilution activity coefficients (gamma(i)(w,infinity)) of the PBDEs in water from the S(w) data, enthalpies of fusion and melting points for those compounds were measured with a differential scanning calorimeter. Henry's Law constants (H(w)) of the PBDEs were derived from the determined gamma(i)(w,infinity) and literature vapor pressure data. Some physicochemical characteristics of PBDEs were also suggested by comparing the present property data with that of polychlorinated dibenzo-p-dioxins, brominated phenols and brominated benzenes in past studies. Furthermore, in order to represent different phase equilibria including solubility and partition equilibrium for other brominated aromatic compounds using the UNIFAC model, a pair of UNIFAC group interaction parameters between the bromine and water group were determined from the S(w) and K(ow) data of PBDEs and brominated benzenes. The ability of the determined parameters to represent both properties of brominated aromatics was evaluated.     

Acute toxicity of substituted phenols to Rana japonica tadpoles and mechanism-based quantitative structure-activity relationship (QSAR) study.

Acute 12 h and 24 h lethal toxicity (12 h-LC50 and 24 h-LC50) of 31 substituted phenols to Rana japonica tadpoles was determined. Results indicate that toxicity of phenols to tadpoles varied only slightly with length of exposure and the 12-h test could serve as surrogate of the 24-h test. A mechanism-based quantitative structure-activity relationship (QSAR) method was employed and 1-octanol/water partition coefficient (log K(ow))-dependent models were developed to study different modes of toxic action. Most phenols elicited their response via a polar narcotic mechanism and an excellent logK(ow)-dependent model was obtained. Soft electrophilicity and pro-electrophilicity were observed for some phenols and a good log K(ow)-dependent model was also achieved. Additionally, the significant dissociation of carboxyl on benzoic acid derivatives sharply reduced their toxicity. A statistically robust QSAR model was developed for all studied compounds with the combined application of log K(ow), energy of lowest unoccupied orbital (E(lumo)), heat of formation (HOF) and the first-order path molecular connectivity dices (1chi(p)).     

Estimation of selected physicochemical properties for methylated naphthalene compounds

Liquid aqueous solubility (S(w,L)), octanol/water partition coefficients (K(ow)), liquid vapor pressure (P(v,L)), and Henry's law constants (H(c)) 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 S(w,L) and K(ow). Two GC columns, HP5-MS and a more hydrophobic HP-1, were tested for the estimation of P(v,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 S(w,L) and P(v,L) decreased with the number of methyl groups. K(ow) increased with the number of methyl groups. There was no obvious relation between H(c) and the number of methyl groups. Log S(w,L) ranged from 0.885 for 1,2,5,6-tetramethylnaphthalene to 2.269 for 1-methylnaphthalene (mmol/m(3)). Log K(ow) varied from 3.89 for 1-methylnaphthalene to 4.95 for 1,2,5,6-tetramethylnaphthalene. Log P(v,L) ranged from -0.983 for 1,2,5,6-tetramethylnaphthalene to 0.789 for 2-methylnaphthalene (Pa). Log H(c) varied from 1.03 for 1,4,5-trimethylnaphthalene to 1.73 for 2,6-dimethylnaphthalene (Pa m(3)/mol). There were no apparent effects of GC column hydrophobicity on the accuracy of the results. Estimation of S(w,L) and K(ow) 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.     

Soot sorption of non-ortho and ortho substituted PCBs

Field-observations of distribution coefficients well above expectations from bulk organic-matter partitioning for several chlorinated aromatic compound classes have lead to the hypothesis that enhanced affinity to soot may not be limited to polycyclic aromatic hydrocarbons but may extend as a significant process for a wider range of hydrophobic organic compounds. This suggestion was here tested in soot-column sorption experiments with a series of ortho- and non-ortho substituted polychlorinated biphenyls (PCBs), using diesel particulate matter (NIST standard reference material SRM-1650) as model soot sorbent. For congeners of similar hydrophobicity, considerably higher affinities toward the soot sorbent were observed for the non-ortho substituted PCBs. Mono- to tetra-ortho substituted PCBs exhibited log-based soot-water distribution coefficients (K(sc)) from 5.25 to 5.51 l/kg(sc) at solute concentrations corresponding to 1-13 microg/l. In contrast, biphenyl, mono- and dichloro- non-ortho substituted PCBs yielded logK(sc) values between 5.09 and 6.35 l/kg(sc). These results are 20-50, and 75-110 times higher, respectively, than the corresponding K(ow)-predicted K(oc) numbers. This strong interaction with soot, particularly of non-ortho substituted PCBs, may fundamentally affect their environmental distribution and bioavailable exposure.     

Partitioning of selected environmental pollutants into organic matter as determined by solid-phase microextraction

Partitioning/sorption of selected environmental pollutants (PCBs, organochlorine insecticides, triazine and amide herbicides) into dissolved humic acids (HA), soil and mineral substances was evaluated by measuring their free concentrations by solid-phase microextraction (SPME). Compounds were chosen to cover a wide range of logK(ow) (2.2-7.6). Two different types of partitioning behaviour for dissolved HA were observed. Compounds with logK(ow)>5 partitioned almost instantly into HA fraction and the remaining free fraction remained rather constant. LogK(HA) and logK(DOC) were calculated and found to be similar for commercial HA, HA standard and isolated HA. The behaviour of these compounds in soil suspension was similar, but strong sorption on CaCO3 and Florisil was also noticed. For compounds with logK(ow)<5, we have not noticed significant changes in free concentrations in HA solutions over time. In soil suspension, however, some sorption/partitioning was observed over time for some compounds, but it was matching the sorption on CaCO3 and Florisil.     

QSAR study on the toxicity of substituted benzenes to the algae (Scenedesmus obliquus).

50% effective inhibition concentration 48h-EC50 of 40 substituted benzenes to the algae (Scenedesmus obliquus) was determined. The energy of the lowest unoccupied molecular orbital (E(LUMO)) was calculated by the quantum chemical method MOPAC6.0-AM1. By using E(LUMO) and the hydrophobicity parameter log K(OW) the quantitative structure-activity relationship model (QSAR) was developed: log1/EC50=0.272 logK(OW) - 0.659E(LUMO) + 2.54, R2 = 0.793, S.E. = 0.316, F = 71.07, n = 40. A series of equations were obtained about the measured EC50 values of different subclasses of compounds. For those compounds containing double -NO2, their toxicity may be related chiefly to the intracellular reduction of -NO2 obtaining electron, while for anilines and phenols, K(OW) contributes most to the QSAR and E(LUMO) very little.     

Uptake rates of alkylphenols, PAHs and carbazoles in semipermeable membrane devices (SPMDs) and polar organic chemical integrative samplers (POCIS)

Passive sampling devices provide a useful contribution to the monitoring of contaminants in the aquatic environment. However, calibration data needed for the calculation of water concentrations from sampler accumulations are restricted to a limited number of compound classes. Thus uptake of a range of alkylated phenols (AP), polycyclic aromatic hydrocarbons (PAH) and carbazoles was determined for semipermeable membrane devices (SPMDs) and polar organic chemical integrative samplers (POCIS) using a flow through exposure system. Sampling rates ranged from 0.02 to 0.26 l d(-1) for POCIS and 0.02 to 13.83 l d(-1) for SPMDs. Observed SPMD uptake was also compared to that predicted by an empirical model including the use of performance reference compounds (PRCs). Predicted sampling rates did not differ by more than a factor of 1.3 from experimental values for PAH, providing further evidence that the PRC approach can be successfully used to determine in situ sampling rates for these compounds. Experimental sampling rates for AP in SPMDs were, however, much lower than predicted. This discrepancy was too large to be explained by small uncertainties in the calibration system or in the calculations. Based on these data we conclude that while hydrophobic AP are accumulated by SPMDs their partitioning cannot be predicted from their logK(ow) using current methods. Due to this lower than expected uptake, sampling rates were only higher in SPMDs than POCIS in the range of logK(ow)>5.0. Simultaneous deployment of both sampler types allows the study of compounds with a broad range of physicochemical properties.     

Predicting organic contaminant concentrations in sediment porewater using solid-phase microextraction

Because of its cost and time saving features, solid-phase microextraction (SPME) is a leading candidate as a biomimic technique in assessing the bioavailable fraction of hydrophobic organic contaminants (HOCs) in sediment porewater. However, no predictive modeling framework in which to systematically address the effect of key parameters on SPME performance for this application exists. In this study, we derived two governing equations to predict (1) the minimum sediment volume (V(s)min) required to achieve non-depletive conditions, and (2) dissolved phase HOC porewater concentrations (C(pw)) as functions of HOC- and sediment specific characteristics in a conceptual three compartment system. The resulting model predicted that V(s)min was independent of HOC concentrations both in sediment and porewater, but did vary with hydrophobicity (characterized by logK(ow)), the fraction of sediment porewater (f(pw)), and the volume (V(f)) of the SPME sorbent phase. Moreover, the effects of these parameters were minimized (i.e., V(s)min reached plateaus) as logK(ow) approached 4-5. Model predictions of C(pw), a surrogate for SPME-based detection limits in porewater, decreased with increasing sediment volume (V(s)) at low V(s) values, but rapidly leveled off as V(s) increased. A third result suggested that the sediment HOC concentration required for SPME is completely independent of K(ow). These results suggest that relatively small sediment volumes participate in exchange equilibria among sediment, porewater and the SPME fiber, and that large sediment HOC reservoirs are not needed to improve the detection sensitivity of SPME-based porewater samplers. The ultimate utility of this modeling framework will be to assist future experimental designs and help predict in situ bioavailability of sediment-associated HOCs.     

Quantitative structure-toxicity relationship study of lethal concentration to tadpole (Bufo vulgaris formosus) for organophosphorous pesticides

In the present study more than 1,000 structural parameters of 41 organophosphorus pesticides (OPs) were calculated using the software ChemOffice 8.03 and Dragon 2.1. Then, with multivariate linear regression and best subset regression analyses, different equations were derived to calculate the lethal toxicity, LC(50), for these 41 organophosphorous pesticides found in tadpoles (Bufo vulgaris formosus). An equation was developed for all selected OPs, especially those with relatively low toxicity levels (LC(50)>4.5mM) that accounted for 89.09% of the variability in the toxic effect. The equation indicated that the main contributions to OPs toxicity with tadpoles were the electrostatic contribution qH(+) (maximum net positive H atomic charge), spatial autocorrelation (MATS7 m) and hydrophobicity (lgK(ow)), with the two former being the most important parameters. For OPs with high toxicity, however, different structural parameters were introduced. The following equation was developed with LC(50)<4.5mM. These equations implied that with different levels of toxicity there could have different mechanisms in the tadpole. Furthermore, the results showed that molecular structural parameters had a particular value in modeling chemical reactivity within a homologous series of compounds.     

Estimating K(oc) for persistent organic pollutants: limitations of correlations with K(ow)

The n-octanol/water partition coefficient (K(ow)) is commonly used to predict the soil or aquatic particle water partition coefficient normalized to organic carbon (K(oc)). Many correlations are available covering several chemical classes and ranges of hydrophobicity. This work indicates the K(ow) may not be a strong predictor for persistent organic pollutants (POPs) which are defined here as chemicals with logK(ow) > 5.0. In addition, the correlation developed in this work for POPs will still result in a predicted value which is of by a factor of 15. Accordingly, care must be taken when applying K(oc) estimations using K(ow) for POPs until more suitable correlations are developed.     

Molecular hologram derived quantitative structure-property relationships to predict physico-chemical properties of polychlorinated biphenyls

Polychlorinated biphenyls (PCBs) congeners with various degrees of chlorination and substitution patterns are among the most widespread and persistent man-made organic pollutants. They are toxic, lipophilic and tend to be bioaccumulated. The knowledge of the physico-chemical properties is very useful to explain the environmental behavior of PCBs and to perform an exposure assessment. In this paper, we have used a new molecular representation, the molecular hologram, to generate quantitative structure-property relationship models to predict the physico-chemical properties of biphenyl and all of its chlorinated congeners. The investigated properties include 1-octanol/water partition coefficient (logK(ow)), aqueous solubility (-logS(w)), aqueous activity coefficient (-logY(w)), Total molecular surface area, Henry's law constant (logH). The results show that this new quantitative structure-activity relationship approach presents highly predictive models for important physico-chemical properties of PCBs.     

Uptake of PAHs into polyoxymethylene and application to oil-soot (lampblack)-impacted soil samples

Polyoxymethylene (POM) is a polymeric material used increasingly in passive sampling of hydrophobic organic contaminants such as PAHs and PCBs in soils and sediments. In this study, we examined the sorption behavior of 12 PAH compounds to POM and observed linear isotherms spanning two orders of magnitude of aqueous concentrations. Uptake kinetic studies performed in batch systems for up to 54 d with two different volume ratios of POM-to-aqueous phase were evaluated with coupled diffusion and mass transfer models to simulate the movement of PAHs during the uptake process and to assess the physicochemical properties and experimental conditions that control uptake rates. Diffusion coefficients of PAHs in POM were estimated to be well correlated with diffusants' molecular weights as D(POM) proportional, variant(MW)(-3), descending from 2.3 x 10(-10) cm(2) s(-1) for naphthalene to 7.0 x 10(-11) cm(2) s(-1) for pyrene. The uptake rates for PAHs with log K(ow)<5.8 were controlled by the POM phase and the hydrophobicity of PAH compounds. For more hydrophobic PAH compounds, the aqueous boundary layer played an increasingly important role in determining the overall mass transfer rate. The POM partitioning technique was demonstrated to agree well with two other procedures for measuring PAH soil-water distribution coefficients in oil-soot (lampblack) containing soil samples.     

The partitioning of alkylphenolic surfactants and polybrominated diphenyl ether flame retardants in activated sludge batch tests

Polybrominated diphenyl ethers and nonylphenol polyethoxylates have been reported to be estrogenic and may enter the aquatic environment through the discharge of treated sewage effluent. Therefore, their fate during wastewater treatment processes is an important factor in determining their environmental impact. Batch tests with activated sludge from a Husmann apparatus were used to determine the effects of physico-chemical properties and sludge characteristics on the partitioning of polybrominated diphenyl ether flame retardants and nonylphenol polyethoxylate surfactants during biological wastewater treatment. Hydrophobic compounds, those with high logK(ow) values, were sorbed more rapidly and to a greater extent to the solid phase than more soluble compounds. For these hydrophobic compounds sorption may become an increasingly important removal mechanism as sludge age and therefore solids content increase. The initial rate of partitioning was greatest for the most hydrophobic compounds but all rates diminished with time as a result of progressive saturation of sorbent binding sites, a reduction of sorbate availability and as a consequence of the system reaching equilibrium. The sorption of polybrominated diphenyl ethers fit Freundlich adsorption isotherms demonstrating generally increasing adsorption capacity and efficiency with increasing hydrophobic nature. A correlation between increasing logK(ow) and increasing organic matter content was also observed for both polybrominated diphenyl ethers and nonylphenol polyethoxylates indicating the organic content of mixed liquor will also be influential in removing compounds during wastewater treatment.     

Structure-activity relationships and response-surface analysis of nitroaromatics toxicity to the yeast (Saccharomyces cerevisiae)

Inhibition of growth of the yeast Saccharomyces cerevisiae (Cmiz, the minimum concentration that produced a clear inhibition zone within 12 h) for 24 nitroaromatic compounds was investigated and a quantitative structure-activity relationship (QSAR) developed based on hydrophobicity expressed as the l-octanol/water partition coefficient in logarithm form, log K(ow), electrophilicity based on the energy of the lowest unoccupied orbital (E(lumo)). All nitrobenzene derivatives exhibited enhanced reactive toxicity than baseline. The toxicities of mono-nitrobenzenes and di-nitrobenzenes were elicited by different mechanisms of toxic action. For mono-nitro-derivatives, both significant log K(ow) based and strong E(lumo)-dependent relationships were observed indicating that their toxicities were affected both by the penetration process and the interaction with target sites of interaction. The toxicities of di-nitrobenzenes were greater than mono-nitrobenzenes and no log K(ow)-dependent but highly significant E(lumo)-based relationship was obtained. This suggests that toxicity of di-nitrobenzenes was highly electrophilic and involved mainly their in vivo electrophilic interaction with biomacromolecules. In an effort to model the elevated toxicity of all nitrobenzenes, a response-surface analysis was performed and this resulted in a highly predictive two-variable QSAR without reference to their exact mechanisms (Cmiz = 0.41 log K(ow) - 0.89 E(lumo) - 0.46, r2 = 0.87, Q2 = 0.86, n = 24).