Determination Of Octanol-water Partition Coefficients Research Articles

Experimental determination of octanol-water partition coefficient (KOW) of 39 liquid crystal monomers (LCMs) by use of the shake-flask method

Liquid crystal monomers (LCMs) were recently proposed as persistent, bioaccumulative, and toxic substances; however, there is a dearth of information regarding their experimental octanol-water partition coefficients (KOW). In the present study, we determined the experimental KOW values of these 39 LCMs by use of a classic shake-flask method. We observed that experimental KOW values of LCMs largely varied depending on their specific structures, and the Log transformed KOW generally fall in the range of 4.94–7.62. The experimental KOW values were further compared with those predicted by Estimation Programs Interface (EPI) Suite software. Interestingly, we observed that experimental and estimated Log KOW values were generally comparable for LCMs containing two benzene or cyclohexane rings; however, the estimated values gradually deviated from the experimental ones as the number of benzene or cyclohexane rings of LCM structures increased. Based on the experimental Log KOW values of 39 LCMs, we established a quantitative structure activity relationship (QSAR) model for predicting Log KOW values of other LCMs, for which authentic standards are not available. Adjusted square of determination coefficient (R2) of the developed model is 0.810, indicating its goodness-of-fit for estimation of Log KOW values of other substances with similar backbone structures. Overall, our present study provides the first insight on experimental Log KOW values of LCMs, and suggests that LCMs are inclined to accumulative in the fatty tissue of organisms in the aqueous environments.

Determination of octanol-water partition coefficients by an HPLC method for anticonvulsant structure-activity studies.

Octanol-water partition coefficients have been measured and calculated for eight clinically relevant anticonvulsants. For some compounds, these are the first experimentally available log P values. For the remainder of the molecules, new values have been suggested. The utility of the micro shake-flask experimental method and the ALOGP calculational method in determining anticonvulsant log P values has been demonstrated.

Separation of very hydrophobic analytes by MEKC. II. Carbon number equivalents as analyte descriptors – influence of the composition of the separation electrolyte

The use of the parameter carbon number equivalent, N(c)(*), as analyte descriptor for neutral hydrophobic solutes in EKC is investigated. The carbon number equivalent of an analyte is defined analogously to the retention index, RI, however, it is directly calculated from the regression line plotting for the members of a homologous series the logarithm of the retention factor against the number of methylene units N(c) in the alkyl chain. This plot can be obtained by using simultaneously an iteration procedure for the calculation of t(MC). For separation electrolytes containing SDS as micellar phase employing ACN, urea, and CaCl(2) as additives within a wide span of concentrations the parameter N(c)(*) is quasi-independent of the composition of the separation electrolyte, being of importance concerning identification of analytes and improving repeatability and reproducibility. With known octanol-water partition coefficients for the members of the homologous series taken as reference it is possible to transform the conventional time scale of an electropherogram into a scale of N(c)(*) or a scale of log P(OW). Due to the quasi-independence of N(c)(*) from the composition of the separation electrolyte these transformed electropherograms can be used as normalized electropherograms for identification purposes. It is also shown that the linear dependence of log P(OW) on N(c) can be the basis of the determination of octanol-water partition coefficients of solutes within a very large range (-4 < or = log P(OW) < or = 9).

Determination of octanol‐water partition coefficients for carbonate esters and other small organic molecules by microemulsion electrokinetic chromatography

Microemulsion electrokinetic chromatography (MEEKC) was assessed as a tool for determination of octanol-water partition coefficients using 34 solutes encompassing 8 carbonate esters. It was confirmed that microemulsions containing 1.44-2.88% w/w SDS, 6.49% w/w 1-butanol, and 0.82% w/w n-heptane constitute a good model of octanol-water partitioning in the pH range of 1.4-7.4. Use of the migration index concept led to improved repeatability of the MEEKC method compared to the use of retention factors. Using a dynamical coating, a high electroosmotic flow at pH 1.4 and 4.75 was achieved expanding the practical pH working range of the MEEKC system. The correlation obtained between the migration index and log P was unaffected by pH indicating that the properties of the microemulsion droplets and, thus, partitioning are independent of pH. No evidence for congeneric behavior was found for the sample set comprising solutes with different hydrogen bonding properties suggesting that simple reference compounds can be used as calibrators. Lipophilicity estimates for the series of carbonate esters were obtained. The increase in lipophilicity with chain length was smaller than expected from the Hansch substituent constant, pi.

A MICROSCALE HPLC METHOD FOR THE EVALUATION OF OCTANOL-WATER PARTITION COEFFICIENTS IN A SERIES OF NEW 2-AMINO-2-OXAZOLINES

A rapid and simple microscale method for the determination of octanol-water partition coefficients has been developed and evaluated for a series of twenty-six bioactive 2-amino-2-oxazolines. Solutes were equilibrated between n-octanol and water by using the shake-flask approach in a single partitioning. The concentration of each compound was measured in the aqueous phase before and after partitioning directly by RP-HPLC, and the peak areas ratio was used to calculate the partition coefficient log P. Log P values ranging from -0.22 to 3.69 have been determined with a precision better than ± 0.06 log unit. They were compared with the measured shake-flask octanol-water partition coefficient and with the calculated incremental Clog P values. The linear regression analyses between these lipophilic parameters show significant correlations, allowing validation of this chromatographic approach for the log P determination.

Determination of octanol-water partition coefficients of polar polycyclic aromatic compounds (N-PAC) by high performance liquid chromatography

Prediction of 1-octanol water partition coefficients for a range of polar N-PAC from HPLC capacity coefficients has been investigated. Two commercially available columns, an ODS column and a Diol column were tested with water-methanol eluents. The best prediction of log K ow for N-PAC was achieved using a Diol column with an eluent of 35% MeOH and 65% water. The results indicate that the Diol column, in reversed phase mode, is able to form hydrogen bonds with a solute. Different LFERs between retention and log K ow was found for polar and nonpolar compounds. In general log K ow increased with size and log K ow for N-PAC was 1.1-1.3 lower than log K ow for the equivalent PAH. Shielding of the nitrogen atom in the N-PAC compounds caused an increase in log K ow.

Determination of Octanol-Water Partition Coefficients, Water Solubility and Vapour Pressures of Alkyl-lead Compounds

Physico-chemical properties of alkyl-lead compounds, namely aqueous solubility, octanol–water partition coefficient (Kow), vapour pressure and Henry's Law constant, have been determined. Vapour pressures of trialkyl-lead salts at different temperatures were measured by a gas-saturation technique in which air was passed slowly through a glass column packed with pure solid alkyl-lead compounds. Kow of tetra-alkyl-lead (TAL) and trialkyl-lead (TriAL) were determined under different salinity and pH conditions, and the latter were related to the species (R3Pb+, R3PbOH0 or R3PbCl0) dominating under a particular set of conditions. Regression calculations incorporating melting point corrections relate water solubility to Kow, and provide a means of estimating either parameter for a wider range of compounds.

Indirect determination of octanol-water partition coefficients by microemulsion electrokinetic chromatography

Microemulsion electrokinetic chromatography (MEEKC) was assessed and developed as a screening tool for the indirect determination of octanol-water partition coefficients. The capacity factors from MEEKC were correlated to the octanol-water partition coefficients. The same microemulsion (50 m M SDS, 400 m M butanol and 32 m M heptane) was used at pH 1.19 and pH 12 allowing most compounds to be run in their neutral state. This procedure was evaluated using a set of 24 structurally diverse solutes and 4 homologs. It was found that MEEKC can determine a range of over 5 orders of magnitude in the log K ow covering from −1 to over 4. MEEKC provides all the advantages of an HPLC system to estimate lipophilicities including automation, small sample size, short run and analysis times and good reproducibility. However, MEEKC has neither the disadvantages of HPLC including pH limitations, column degradation and homologous series limitations nor the disadvantages of shake flask methods including large sample size, no automation and long turnaround.

Solid-Phase Microextraction as a Method for Estimating the Octanol−Water Partition Coefficient

The determination of octanol-water partition coefficients (log K(ow)) is important for the prediction of the fate of organic pollutants in the environment. Traditionally, log K(ow) values are determined by shake-flask, estimated by, e.g., HPLC retention data, or calculated, e.g., from ClogP. In this paper, an alternative approach is reported that allows log K(ow) to be estimated from solid-phase microextraction (SPME) data. Previously reported attempts to correlate SPME data with log K(ow) are discussed. The results obtained in this work for six phenols, using an 85 μm polyacrylate-coated fiber, indicate that SPME is a viable method for estimating log K(ow) values <3.5.

Determination of true octanol-water partition coefficients by means of solvent generated liquid-liquid chromatography

Compared to other methods for the determination of octanol-water partition coefficients chromatography offers a number of advantages: sample purification is unnecessary, the partition coefficients of the components of a mixture can be measured simultaneously and a minimum amount of sample is needed. In the past these determinations were almost exclusively carried out by liquid-solid chromatography (LSC) on alkyl bonded silica as stationary phase (conventionally described as ‘reversed-phase liquid chromatography; RPLC). Such systems based on liquid-solid distribution are, however, a poor simulation of liquid-liquid partition. On the other hand liquid-liquid chromatographic columns loaded with high amounts of water-saturated octanol are unstable since they suffer from “column bleeding” — a loss of the stationary liquid octanol phase caused by erosion. It is shown that the technique of solvent generated liquid-liquid chromatography (SGLLC) leads to stable columns with liquid-liquid partition as the predominant retention mechanism, if systematic errors due to specific adsorption effects are avoided by the selection of an “inert” solid support. This is demonstrated by the comparison of LSC and SGLLC data. SGLLC significantly reduces the scattering of the retention data of calibration standards around the calibration line. The use of SGLLC thus significantly improves the accuracy and precision of the resulting octanol-water partition coefficients.

Determination of Octanol-Water Partition Coefficients for a Series of Imidazolidinediones by a Novel Combination of Micro Shake-Flask and HPLC Techniques

Abstract Octanol-water partition coefficient (Log P) values for a series of 19 imidazolidinedione analogues have been determined by high performance liquid chromatography. To obtain a regression equation between log P and chromatographic log k′ values, a modified micro shake-flask method has been developed. In the shaking step, a simple syringe and test tube system was devised and has proved sufficient to ensure the proper distribution of analytes between the two phases. In addition, HPLC was used not only as a detector for the shake-flask method, but also as a technique for determining the capacity factors of the compounds. Further technique modifications include alternatives to the use of octanol and dimethyl sulfoxide (DMSO) in HPLC thereby eliminating the detrimental effect of these solvents on the stationary phase. Our micro shake-flask method is a modified version of the technique developed by Ford et al. which used a Mixxor-separator device for distribution of solute and an HPLC apparatus for the d...

Dissipation of 2,4-D glyphosate and paraquat in river water

Dissipation of herbicides in river water was determined by adding different concentrations of 2,4-D, glyphosate and paraquat to samples of river water. A small variation of dissipation of radioactivity for14C-2,4-D in higher and lower concentrations and in different samples of river water was found. But about half the radioactivity disappeared from water samples of original glyphosate concentration at 100 mg L−1 and, in the case of 100 μg L−1, only 11 to 22% remained in the samples of river water after 56 d incubation except the sample from Hsin-Tien River. More than 80% of paraquat remained in water samples. Determination of octanol-water partition coefficient (Kow) showed a large difference in amounts of 2,4-D partitioned in water phase at different pH values, 97.4% at the higher pH of ionic state and 5.2% at the lower pH of molecular state, implying that pH value of water might affect the bioaccumulation process of 2,4-D. The result showed that 95.0% of glyphosate present in water phase in ionic form (higher pH) and 82.3% in molecular form (lower pH), indicating that glyphosate might have no affect on the biomagnification, since most of glyphosate could be excreted with water by organisms.

A Rapid Microscale Method for the Determination of Partition Coefficients by HPLC

Abstract A rapid, reliable and simple microscale method for the determination of octanol-water partition coefficients has been developed and evaluated. Rapid solute partitioning and facile octanol-water phase separation is accomplished in a commercially available mixer-separator device. The relative concentration of solute in each phase is then measured directly by computer-based reverse phase HPLC. The procedure requires only 10 μg of sample, which need not be pure, and uses 1 ml or less of both n-octanol and pH 7.0 phosphate buffer. Log P values of 26 compounds, mainly nucleoside analogues with anti-HIV and antitumor activity, have been determined in the range 0.7 to -2.4 with a precision better than ±0.04 log units. For compounds with literature data available, measured log P values are in good agreement (better than ±0.2 log units) with those values obtained by traditional “shake-flask” methodology. The described method is applicable to both single compound analysis and simultaneous multiple compound determinations through use of isocratic or gradient HPLC techniques.

Extended Octanol-Water Partition Coefficient Determination by Dual-Mode Centrifugal Partition Chromatography

Abstract The range of determination of octanol-water partition coefficients by CPC has been extended by the dual-mode approach. In this mode, the analyte was pumped in the descending mode with water as the mobile phase for a predetermined time. The mode was then switched to ascending with octanol as the mobile phase. Lipophilic materials only moved partially through the system in the descending mode. They rapidly eluted in the ascending mode with good signal-to-noise. The partition coefficient was shown to equal the volume of water pumped in the descending mode divided by the retention volume in the octanol phase ascending. A systematic positive error resulted when the experimentally selected descending volume was too small.

Assessment of Centrifugal Partition Chromatography for Determination of Octanol-Water Partition Coefficients

Abstract Centrifugal partition chromatography (CPC) has been assessed as a convenient automated method for the determination of octanol-water partition coefficients (KOW) over the range of -0.5 to 2.5 log units. The stationary (Vs) and mobile phase (Vm) volumes, which are needed for the calculation of Kow, are determined in situ by injecting four compounds with known Kow. V3 and Vm were also determined by independent analytical means to demonstrate that this is a direct measurement of Kow from fundamental chromatographic principles with no unexplained fitted parameters. Propagation of error shows that a single four-component calibration with duplicate injections of each unknown is sufficient to determine log Kow with a precision of less than 0.1 log units.

An interlaboratory evaluation of the stir-flask method for the determination of octanol-water partition coefficients (log Pow)

The following note gives experimental details of the stir-flask method of log Pow determination. A summary of other more established methods of estimating or measuring octanol-water partition coefficients is also included.

Correction. Chromatographic Determination of Octanol-Water Partition Coefficients (Kow's) for 58 Polychlorinated Biphenyl Congeners

Correction. Chromatographic Determination of Octanol-Water Partition Coefficients (K_ow's) for 58 Polychlorinated Biphenyl Congeners

Chromatographic determination of octanol-water partition coefficients (Kow's) for 58 PCB polychlorinated biphenyl congeners

Octanol-water partition coefficients of 58 poly-chlorinated biphenyl (PCB) congeners have been determined by reverse-phase C/sub 18/ high-performance liquid chromatography (HPLC) of Aroclor 1242 and 1254 mixtures. High-resolution glass capillary gas-liquid chromatography was used for the detection of the eluted individual congeners. Some PCB congeners behaved atypically from other organics on reverse-phase HPLC, and empirically derived correction factors were used to adjust K/sub ow/ values. Congener log K/sub ow/ values for PCB's ranged from an average of 4.5 for N/sub Cl/ = 1 to 8.1 for N/sub Cl/ = 7. The environmental implications of PCB K/sub ow/ values and congener behavior on the C /sub 18/ reverse-phase column are discussed. 35 references.

Partition coefficients of organic chemicals derived from reversed phase thin layer chromatography: Evaluation of methods and application on phosphate esters, polychlorinated paraffins and some PCB-substitutes

The application of reversed phase high performance thin layer chromatography has been evaluated for determination of octanol-water partition coefficients (P oct) of organic chemicals. Best correlations between log P oct and R M-values were obtained on a C 18-bonded stationary phase using acetone-water or acetonitrile-water mixtures as eluting solvent. The latter mixture is preferred in work with high pressure liquid chromatography. A number of aryl and alkyl/aryl phosphate esters, polychlorinated paraffins and chemicals suggested as PCB-substitutes were chromatographed and the corresponding log P oct-values calculated. Values for the phosphate esters corresponded reasonably well with previously reported data while data for other, often more complex compound mixtures ( eg PCB-substitutes), need further evaluation. The use of the chromatographic system for screening purposes in work on environmentally significant data of possible organic pollutants is discussed.