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Uses and Needs of K ow Values

Predicting Octanol-Water Partition Coefficients ( K ow ) from Water Solubility and Molar Volumes Cary T. Chiou National Cheng Kung Univ., Tainan,Taiwan U.S. Geological Survey, Denver, CO, USA. Uses and Needs of K ow Values.

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Uses and Needs of K ow Values

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  1. Predicting Octanol-Water Partition Coefficients (Kow) from Water Solubility and Molar VolumesCary T. ChiouNational Cheng Kung Univ., Tainan,TaiwanU.S. Geological Survey, Denver, CO, USA

  2. Uses and Needs of Kow Values • Kow is a general partition indicator for organic compounds in environmental studies • Kow approximates Klipid-w for assessing the bioconcentration factors of compounds • Kow’s are unavailable for many compounds • Inconsistent Kow’s for given compounds (differing often by 1-2 orders of magnitude)

  3. Water solubilities (Sw), octanol-water partition coefficients(Kow), and lipid triolein-water partition coefficients (Ktw) of organic compounds Compound log Sw (mol/L) log Kow log Ktw Benzene -1.64 2.13 2.25 Toluene -2.25 2.69 2.77 Ethylbenzene -2.84 3.15 3.27 1,3,5-Trimethylbenzene -3.09 3.42 3.56 1,2-Dichlorobenzene -2.98 3.38 3.51 1,2,4-Trichlorobenzene -3.72 4.02 4.12 1,2,3,5-Tetrachlorobenzene (-4.53) 4.59 4.69 Hexachlorobutadiene -5.01 4.90 5.04 Pentachlorobenzene (-5.18) 5.20 5.27 Hexachlorobenzene (-5.57) 5.50 5.50 2-PCB (-4.57) 4.51 4.77 2,4’-PCB (-5.28) 5.10 5.30 2,5,2’,5’-PCB - - 6.11 5.81

  4. Lipid triolein-water partition coefficients (Ktw) and fish bioconcentration factors (BCF)lipid(Laboratory Experiments) Compound log Ktw log (BCF)lipidlog (BCF)lipid (guppies)a(rainbow trout)b 1,2-Dichlorobenzene 3.51 3.51-3.80 1,3-Dichlorobenzene 3.63 3.70-4.02 1,4-Dichlorobenzene 3.55 3.26 3.64-3.96 Hexachloroethane 4.21 3.79-4.13 1,2,3-Trimethylbenzene 4.19 4.11 4.15-4.47 1,2,4-Trimethylbenzene 4.12 4.19-4.56 1,3,5-Trichlorobenzene 4.36 4.15 4.34-4.67 1,2,3,4-Tetrachlorobenzene 4.68 4.80-5.13 1,2,3,5-Tetrachlorobenzene 4.69 4.86 1,2,4,5-Tetrachlorobenzene 4.70 4.80-5.17 Hexachlorobutadiene 5.04 4.84-5.29 Pentachlorobenzene 5.27 5.42 5.19-5.36 Hexachlorobenzene 5.50 5.46 5.16-5.37 aKönemann and van Leeuwen (Chemosphere, 1980) ;bOliver and Nimii (ES&T, 1983)

  5. Laboratory Fish BCF Experiments Chiou (ES&T, 1985) with Ktw and literature BCF data

  6. Current Kow Prediction Methods Indirect Experimental Methods: -HPLC Retention Time or Volume using a chosen stationary phase Molecular Computation Models: - Fragment or Group Constants (f and ) - Molecular Volumes or Areas - Correlations with Water Solubility (Sw) - Polyparameter Linear Solvation Energy Relationships (pp-LSERs)

  7. Substituent Contribution to Partition Coefficient Fujita et al. (J. Am. Chem. Soc., 1964): πX = log KX - log KR KX = partition coefficient of solute with substituent X KR = partition coefficient of the reference solute R Chiou et al. (J. Pharm. Sci., 1982) show: πX = X - log [(o*)X/(o*)R] where X=log [(Sw)R/(Sw)X]

  8. X, πX (octanol-water) , and πX (heptane-water) of Functional Groups Attached to Benzene Compound Group XπX (oct-w) πX (hep-w) Benzene - - 0 0 0 Toluene CH3 0.60 0.56 0.59 Ethylbenzene C2H5 1.20 1.02 1.17 o-Xylene 1-CH3-2-CH3 1.08 0.99 1.13 Flurorbenzene F 0.16 0.14 0.19 Chlorobenzene Cl 0.72 0.71 0.69 Bromobenzene Br 0.91 0.86 0.84 m-Dichlorobenzene 1-Cl-3-Cl 1.40 1.25 1.28 1,2,4-Trichlorobenzene 1,2,4-(Cl)3 1.93 1.89 1.89 Aniline NH2 - 1.24 - 1.23 - 2.22 m-Chloroaniline 1-NH2-3-Cl - 0.27 - 0.25 - 1.55 Benzaldehyde CHO - 0.23 - 0.65 - 1.21 PhenolOH - 1.70 - 0.67- 3.18 Benzoic acidCOOH - 0.73 - 0.28- 2.98 Phenylacetic acidCH2COOH - 1.15 - 0.83- 3.33

  9. Solvent-Water Partition Coefficients for Dilute Solutes: Using the mole fraction as the basis to express the solute activity (i.e., by Raoult’s Law), one obtains log Kow = – log Sw –log Vo* – log Fdv log Fdv = log o* + log (w/ w*) Sw = Solute water solubility (mol/L) Vo* = Molar volume of the water-saturated solvent (e.g., octanol) (L/mol) o*, w, w* are the solute activity coefficients in water-saturated solvent (octanol), pure water, and solvent-saturated water

  10. Solute Water Solubility For solid compounds, the Sw is that for the supercooled liquid: Sw(supercooled liquid) = Sw* (solid) (Fsl) where log (Fsl) = (Hf/2.303R) [(Tm  T)/T.Tm]

  11. Typical log Kow - log Sw CorrelationsChiou et al. (ES&T, 1982) for mostly substituted benzenes:log Kow = - 0.862 log Sw -0.710Mackay et al. (Chemosphere, 1980) for substituted benzenes, PAHs, and others:log Kow = - log Sw + 0.254

  12. Remarks:-Accurately predicts the log Kow for solutes similar in size to substituted benzenes - Underpredicts the log Kow for small-sized solutes (e.g., dichloromethane & TCE)- Overpredicts the log Kow for large-sized solutes (many PCBs, PAHs, & Pesticides)- Raout’s law is not generally accurate for the partition of all dilute solutes

  13. Polyparameter LSERs for Partition Coefficients(Tafts, Abraham, Kamlet, Taylor) For Any Partition Coefficient (K): log K = c + rR2 + sπ2 + a2 + b2 + vVx R2 = Solute excess molar refraction π2 = Solute dipolarity 2 =Solute H-bond acidity 2 = Solute H-bond basicity Vx = Solute characteristic volume

  14. Solvent-Water Partition Coefficients for Dilute Solutes: Using the volume fraction as the basis to express the Solute activity, one obtains instead log Kow = – log Sw –log V – log Fdv log Fdv = log o* + log (w/ w*) Sw = Solute water solubility (mol/L) V = Solute Molar volume (L/mol) o*, w, w* are the equivalent solute activity coefficients on a volume-fraction basis

  15. Perfect Partition Coefficients for Dilute Solutes in Any Solvent-Water Mixtures log Kºsw = - log Sw - log V Note: Kºswis numerically equal to the ratio of the molar concentration of a pure liquid solute (i.e., 1/V) to its molar solubility in water (Sw). Kºswor Kow shows a dependence on solute molar volume (V) rather than on solvent molar volume (Vo*).

  16. Water solubilities (Sw), octanol-water partition coefficients(Kow), and triolein-water partition coefficients (Ktw) of organic compounds(Kow Ktw, no dependence on the solvent size) Compound log Sw (mol/L) log Kow log Ktw Benzene -1.64 2.13 2.25 Toluene -2.25 2.69 2.77 Ethylbenzene -2.84 3.15 3.27 1,3,5-Trimethylbenzene -3.09 3.42 3.56 1,2-Dichlorobenzene -2.98 3.38 3.51 1,2,4-Trichlorobenzene -3.72 4.02 4.12 1,2,3,5-Tetrachlorobenzene (-4.53) 4.59 4.69 Hexachlorobutadiene -5.01 4.90 5.04 Pentachlorobenzene (-5.18) 5.20 5.27 Hexachlorobenzene (-5.57) 5.50 5.50 2-PCB (-4.57) 4.51 4.77 2,4’-PCB (-5.28) 5.10 5.30 2,5,2’,5’-PCB - - 6.11 5.81

  17. Partition Coefficients in Octanol-Water Mixtures log Kow = log Kºsw - log Fdv or log Kow = - log Sw - log V - log Fdv where log Fdv = log o* + log (w/w*)

  18. Log Sw and Log Kºsw of Reference Solutes and Their Log Fdv in Octanol-Water Mixtures Compound(n = 33)- log Sw log Kºsw log Kow log Fdv Diethyl ether 0.0899 1.07 0.83 0.24 Aniline 0.410 1.45 1.09 0.36 Dichloromethane 0.641 1.83 1.51 0.32 Carbon tetrachloride 2.28 3.30 2.73 0.57 Benzene 1.64 2.69 2.13 0.56 Ethyl benzene 2.82 3.74 3.15 0.59 1,3-Dichlorobenzene 3.07 4.01 3.44 0.57 1,2,3,4-Tetrachlorobenz 4.59 5.43 4.60 0.83 1-Hexene 3.08 3.98 3.39 0.59 n-Octane 5.24 6.02 5.18 0.84 Naphthalene (3.09) 3.99 3.36 0.63 Phenanthrene (4.48) 5.25 4.46 0.79 2,2’,5-PCB (5.83) 6.48 5.60 0.88 2,2’,3,3’,4,4’-PCB (7.59) 8.12 6.98 1.14 Chlorpyrifos (5.68) 6.29 5.27 1.02 Lindane (3.62) 4.39 3.72 0.67 p,p’-DDT (6.79) 7.40 6.36 1.04

  19. 1.4 1.2 1.0 log Fdv 0.8 0.6 0.4 0.2 0.0 0 1 2 3 4 5 6 7 8 - log Sw log Fdv = - 0.116 log Sw + 0.268

  20. Correlation of Log Kow with Log Sw and Log VChiou et al. (ES&T, 2005) Substituting log Fdv = - 0.116 log Sw + 0.268 into log Kow = - log Sw - log V - log Fdv gives log Kow = - 0.884 log Sw - log V - 0.268

  21. Log Kow Predictions by Volume-Fraction-Based (A) and Mole-Fraction-Based (B) Dilute-Solution Models Compound Experimental Pred. (A) Pred. (B) Small-Sized Solutes (V = 0.064 - 0.090 L/mol) Dichloromethane 1.51 1.49 1.26 1,2-dichloroethane 1.76 1.77 1.62 Chloroform 1.90 1.90 1.76 Trichloroethylene2.53 2.53 2.42 Substituted Benzenes (V = 0.10 - 0.14 L/mol) Toluene 2.69 2.69 2.65 1,4-Xylene 3.18 3.14 3.15 1,2,3-Trichlorobenzene4.04 3.98 3.98 Large-Sized Solutes (V = 0.27 - 0.39 L/mol) 2,2’,3,3’,5,5’,6,6’-PCB 7.11 7.11 7.42 Dieldrin 4.55 4.53 4.79 Ethion 5.07 5.13 5.49 Leptophos6.31 6.34 6.60 Nonylphenol-4EOs 4.24 4.31 4.77 (A): log Kow = - 0.884 log Sw - log V - 0.268; (B): log Kow = - 0.862 log Sw + 0.710

  22. Predicted Log Kow of NOCs from Log Sw and Log V Sw- log Sw- log VPred Expt Compound (ppm) (mol/L) (L/mol) log Kow log Kow log Kow ALHCs Cyclohexane 55.8 3.18 0.963 3.51 3.44 -0.07 n-Heptane 2.93 4.53 0.832 4.57 4.66 0.09 1-Octene 2.70 4.62 0.802 4.62 4.57 -0.05 1-Hexyne 360 2.36 0.937 2.75 2.73 -0.02 HALHCs 1,2-Dichloromethane 8.7E3 1.06 1.104 1.77 1.76 -0.01 TCE 1.37E3 1.98 1.045 2.53 2.53 0 1-Bromoheptane 6.65 4.43 0.804 4.45 4.36 -0.09 Hexachlorobutadiene 2.55 5.01 0.810 4.97 4.90 -0.07 ALBZs Styrene 300 2.54 0.936 2.91 2.95 0.04 1,3,5-Trichlorobenzene 69.2 3.24 0.865 3.46 3.42 -0.04 1,2,4,5-Tetrachlorobenz 3.48 (4.02) (0.795) 4.08 4.10 0.02 Hexamethylbenzene 0.235 (4.68) (0.704) 4.57 4.61 0.04

  23. Predicted Log Kow of NOCs from Log Sw and Log V Sw- log Sw- log V Pred Expt  Compound (ppm) (mol/L) (L/mol) log Kow log Kow log Kow Anilines 3-Toluidine 1.50E4 0.85 0.965 1.45 1.42 -0.03 N,N-Dimethylaniline 1.11E3 2.04 0.895 2.43 2.31 -0.12 Ethers MTBE 5.16E4 0.23 0.925 0.86 0.94 0.08 Anisole 2030 1.73 0.964 2.22 2.11 -0.11 Diphenyl ether 18 (3.95) (0.800) 4.02 4.08 0.06 Esters Ethyl acetate 8.04E4 0.040 1.010 0.78 0.73 -0.05 Ethyl benzoate 720 2.32 0.845 2.63 2.64 0.01 Di-butyl phthalate 13.0 4.33 0.575 4.14 4.08 -0.06 Di-octyl phthalate 4.6E-4 8.93 0.399 8.02 8.10 0.08

  24. Predicted Log Kow of NOCs from Log Sw and Log V Sw- log Sw- log V Pred Expt  Compound (ppm) (mol/L) (L/mol) log Kow log Kowlog Kow HABZs Fluorobenzene 1550 1.79 1.027 2.34 2.27 -0.07 Iodobenzene 229 2.95 0.951 3.29 3.28 -0.01 1,4-Dichlorobenzene 73 (3.03) (0.828) 3.34 3.37 0.03 1,2,3-Trichlorobenzene 16.3 (3.79) (0.903) 3.98 4.04 0.06 1,2,4,5-Tetrachlorobenzene 0.29 (4.70) (0.848) 4.73 4.70 -0.03 Hexachlorobenzene 5.0E-3 (5.71) (0.741) 5.52 5.50 -0.02 PAHs Acenaphthene 3.93 (3.89) (0.830) 4.00 3.92 -0.08 Fluorene 1.90 (4.14) (0.814) 4.21 4.18 -0.03 Phenanthrene 1.29 (4.48) (0.773) 4.46 4.46 0 1,4,5-Trimethylnaphthalene 2.1 4.91 0.760 4.83 4.87 0.04 Pyrene 0.135 (4.92) (0.753) 4.83 4.88 0.05 Benzo(a)anthracene 0.014 (5.89) (0.694) 5.63 5.61 -0.02

  25. Predicted Log Kow of NOCs from Log Sw and Log V Sw- log Sw- log VPred Expt Compound (ppm) (mol/L) (L/mol) log Kow log Kow log Kow PCBs 2,4’-PCB 0.637 (5.34) (0.674) 5.13 5.10 -0.03 2,2’,5,5’-PCB 0.046 (6.19) (0.615) 5.82 5.81 -0.01 2,2’,4,4’,6,6’-PCB 4.1E-4 (8.24) (0.526) 7.54 7.55 0.01 2,2’,3,3’,5,5’,6,6’-PCB 3.93E-4 (7.78) (0.499) 7.11 7.11 0 2,2’,3,3’,4,5,5’,6,6’-PCB 1.8E-5 (9.04) (0.467) 8.19 8.16 -0.03 DXDBFs 2,8-Dichlorodibenzofuran 0.0145 (5.67) (0.739) 5.48 5.44 -0.04 1,2,3,4-Tetrachlorodioxin 6.3E-4 (6.75) (0.668) 6.37 6.20 -0.17 Heterocyclics Carbazole 1.03 (3.00) (0.830) 3.21 3.29 0.08 Benzo(b)thiophene 130 (2.94) (0.933) 3.26 3.26 0

  26. Predicted Log Kow of Pesticides from Log Sw and Log V Sw- log Sw- log VPred Expt Compound (ppm) (mol/L) (L/mol) log Kow log Kow log Kow OGCLs Dieldrin 0.465 (4.73) (0.616) 4.53 4.55 0.02 Heptachlor 0.056 (6.05) (0.645) 5.73 5.73 0 p,p’-DDE 0.040 (6.15) (0.627) 5.80 5.77 -0.03 OGPPs Chlorfenvinphos 145 3.39 (0.578) 3.31 3.23 -0.08 Ethion 1.1 5.54 0.501 5.13 5.07 -0.06 Leptophos 0.021 (6.83) (0.570) 6.34 6.31 -0.03 Carbamates Oxamyl 2.83E5 (-0.87) (0.646) - 0.39 - 0.43 -0.04 Aldicarb 6.02E3 (0.59) (0.798) 1.05 1.13 0.08 Carbaryl 104 (2.09) (0.742) 2.32 2.31 -0.01 AUTZs Alachlor 240 (2.89) (0.623) 2.91 2.92 0.01 Linuron 75 (2.57) (0.701) 2.70 2.76 -0.06 Atrazine 30 (2.37) (0.741) 2.57 2.64 0.07

  27.  Log Kow for Classes of NOCs and Pesticides Class No.  log Kow ALHCs14 0.07 HALHCs 22 0.07 ALBZs 15 0.06 HABZs 14 0.04 Anilines 6 0.06 Ethers 7 0.09 Esters 11 0.06 PAHs 23 0.07 PCBs 26 0.07 DXDBFs 5 0.13 Heterocyclics 6 0.11 OGCLs7 0.03 OGPPs 14 0.11 Carbamates 10 0.07 AUTZs 14 0.07 Total 194 Ave. 0.074

  28. Predicted Log Kow from Log Sw and Log V for Phenols and Alcohols SwPred Expt Compound (ppm) - log Sw - log V log Kow log Kow log Kow Phenols Phenol 7.65E4 (-0.01) (1.051) 0.78 1.45 0.67 2,4,6-Trimethylphenol 1.01E3 (1.67) (0.907) 2.11 2.73 0.72 2-Chlorophenol 1.15E4 (1.05) (0.990) 1.65 2.15 0.50 2,4,5-Tichlorophenol 649 (2.09) (0.881) 2.46 3.72 1.26 4-Octylphenol 12.6 (4.05) (0.685) 3.99 4.12 0.13 Nonylphenol-4EOs 7.65 (4.71) (0.411) 4.31 4.24 -0.07 Alcohols n-Hexanol 5.84E4 (1.24) (0.903) 1.73 2.03 0.30 n-Heptanol 1.68E3 (1.84) (0.849) 2.21 2.57 0.36 n-Octanol 495 (2.42) (0.801) 2.67 3.15 0.48 Benzyl alcohol 3.8E4 (0.45) (0.983) 1.12 1.10 -0.02

  29. Prediction of Octanol-Water Partition Coefficients (Kow) by pp-LSERs(Abraham et al., J. Pharm. Sci., 1994) log Kow = 0.088 + 0.562 R2 - 1.054 2H + 0.034 2H - 3.460 2H + 3.814Vx with n = 613 and SD = 0.116 Note:No pesticides and complex molecules

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