1. 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

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

3. Water solubilities (S w ), octanol-water partition coefficients(K ow ), and lipid triolein-water partition coefficients (K tw ) of organic compounds Compoundlog S w (mol/L)log K ow log K tw Benzene-1.642.132.25 Toluene-2.252.692.77 Ethylbenzene-2.843.153.27 1,3,5-Trimethylbenzene-3.093.423.56 1,2-Dichlorobenzene-2.983.383.51 1,2,4-Trichlorobenzene-3.724.024.12 1,2,3,5-Tetrachlorobenzene(-4.53)4.594.69 Hexachlorobutadiene-5.014.905.04 Pentachlorobenzene(-5.18)5.205.27 Hexachlorobenzene(-5.57)5.505.50 2-PCB(-4.57)4.514.77 2,4’-PCB(-5.28)5.105.30 2,5,2’,5’-PCB - -6.115.81

5. Lipid triolein-water partition coefficients (K tw ) and fish bioconcentration factors (BCF) lipid (Laboratory Experiments) Compoundlog K tw log (BCF) lipid log (BCF) lipid (guppies) a (rainbow trout) b 1,2-Dichlorobenzene 3.513.51-3.80 1,3-Dichlorobenzene 3.633.70-4.02 1,4-Dichlorobenzene 3.553.263.64-3.96 Hexachloroethane4.213.79-4.13 1,2,3-Trimethylbenzene4.194.114.15-4.47 1,2,4-Trimethylbenzene 4.124.19-4.56 1,3,5-Trichlorobenzene4.364.154.34-4.67 1,2,3,4-Tetrachlorobenzene4.684.80-5.13 1,2,3,5-Tetrachlorobenzene 4.694.86 1,2,4,5-Tetrachlorobenzene 4.704.80-5.17 Hexachlorobutadiene5.044.84-5.29 Pentachlorobenzene5.275.425.19-5.36 Hexachlorobenzene5.505.465.16-5.37 a Könemann and van Leeuwen (Chemosphere, 1980) ; b Oliver and Nimii (ES&T, 1983)

6. Laboratory Fish BCF Experiments Chiou (ES&T, 1985) with K tw and literature BCF data

7. Current K ow 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 (S w ) - Polyparameter Linear Solvation Energy Relationships (pp-LSERs)

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

9.  X, π X (octanol-water), and π X (heptane-water) of Functional Groups Attached to Benzene CompoundGroup  X π X (oct-w) π X (hep-w) Benzene - -0 00 TolueneCH 3 0.60 0.56 0.59 EthylbenzeneC 2 H 5 1.20 1.021.17 o-Xylene1-CH 3 -2-CH 3 1.08 0.991.13 FlurorbenzeneF0.16 0.140.19 ChlorobenzeneCl0.72 0.710.69 BromobenzeneBr0.91 0.860.84 m-Dichlorobenzene1-Cl-3-Cl1.40 1.251.28 1,2,4-Trichlorobenzene1,2,4-(Cl) 3 1.93 1.891.89 AnilineNH 2 - 1.24 - 1.23 - 2.22 m-Chloroaniline1-NH 2 -3-Cl - 0.27 - 0.25 - 1.55 BenzaldehydeCHO - 0.23 - 0.65 - 1.21 PhenolOH - 1.70 - 0.67 - 3.18 Benzoic acidCOOH - 0.73 - 0.28 - 2.98 Phenylacetic acidCH 2 COOH - 1.15 - 0.83 - 3.33

10. 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 K ow = – log S w – log V o * – log F dv log F dv = log  o * + log (  w /  w * ) S w = Solute water solubility (mol/L) V o * = 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

11. Solute Water Solubility For solid compounds, the S w is that for the supercooled liquid: S w (supercooled liquid) = S w * (solid) (F sl ) where log (F sl ) = (  H f /2.303R) [(T m  T)/T.T m ]

12. Typical log K ow - log S w Correlations Chiou et al. (ES&T, 1982) for mostly substituted benzenes: log K ow = - 0.862 log S w - 0.710 Mackay et al. (Chemosphere, 1980) for substituted benzenes, PAHs, and others: log K ow = - log S w + 0.254

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

14. Polyparameter LSERs for Partition Coefficients (Tafts, Abraham, Kamlet, Taylor) For Any Partition Coefficient (K): log K = c + rR 2 + sπ 2 + a  2 + b  2 + vV x R 2 = Solute excess molar refraction π 2 = Solute dipolarity  2 = Solute H-bond acidity  2 = Solute H-bond basicity V x = Solute characteristic volume

15. Solvent-Water Partition Coefficients for Dilute Solutes: Using the volume fraction as the basis to express the Solute activity, one obtains instead log K ow = – log S w – log V – log F dv log F dv = log  o * + log (  w /  w * ) S w = 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

16. Perfect Partition Coefficients for Dilute Solutes in Any Solvent-Water Mixtures log K º sw = - log S w - log V Note: K º sw is numerically equal to the ratio of the molar concentration of a pure liquid solute (i.e., 1/V) to its molar solubility in water (S w ). K º sw or K ow shows a dependence on solute molar volume (V) rather than on solvent molar volume (V o * ).

17. Water solubilities (S w ), octanol-water partition coefficients(K ow ), and triolein-water partition coefficients (K tw ) of organic compounds (K ow  K tw, no dependence on the solvent size) Compoundlog S w (mol/L)log K ow log K tw Benzene-1.642.132.25 Toluene-2.252.692.77 Ethylbenzene-2.843.153.27 1,3,5-Trimethylbenzene-3.093.423.56 1,2-Dichlorobenzene-2.983.383.51 1,2,4-Trichlorobenzene-3.724.024.12 1,2,3,5-Tetrachlorobenzene(-4.53)4.594.69 Hexachlorobutadiene-5.014.905.04 Pentachlorobenzene(-5.18)5.205.27 Hexachlorobenzene(-5.57)5.505.50 2-PCB(-4.57)4.514.77 2,4’-PCB(-5.28)5.105.30 2,5,2’,5’-PCB - -6.115.81

18. Partition Coefficients in Octanol-Water Mixtures log K ow = log K º sw - log F dv or log K ow = - log S w - log V - log F dv where log F dv = log  o * + log (  w /  w * )

19. Log S w and Log Kº sw of Reference Solutes and Their Log F dv in Octanol-Water Mixtures Compound (n = 33)- log S w log K º sw log K ow log F dv Diethyl ether 0.0899 1.070.830.24 Aniline0.4101.451.090.36 Dichloromethane0.6411.831.510.32 Carbon tetrachloride2.283.302.730.57 Benzene1.642.692.130.56 Ethyl benzene2.823.743.150.59 1,3-Dichlorobenzene3.074.013.440.57 1,2,3,4-Tetrachlorobenz4.595.434.600.83 1-Hexene3.083.983.390.59 n-Octane5.246.025.180.84 Naphthalene (3.09)3.993.36 0.63 Phenanthrene (4.48)5.254.460.79 2,2’,5-PCB (5.83)6.485.600.88 2,2’,3,3’,4,4’-PCB (7.59)8.126.981.14 Chlorpyrifos (5.68)6.295.271.02 Lindane (3.62)4.393.720.67 p,p’-DDT (6.79)7.406.361.04

20. - log S w 012345678 log F dv 0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 log F dv = - 0.116 log S w + 0.268

21. Correlation of Log K ow with Log S w and Log V Chiou et al. (ES&T, 2005) Substituting log F dv = - 0.116 log S w + 0.268 into log K ow = - log S w - log V - log F dv gives log K ow = - 0.884 log S w - log V - 0.268

22. Log K ow 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) Dichloromethane1.51 1.49 1.26 1,2-dichloroethane 1.761.771.62 Chloroform 1.901.901.76 Trichloroethylene2.532.532.42 Substituted Benzenes (V = 0.10 - 0.14 L/mol) Toluene2.692.692.65 1,4-Xylene3.183.143.15 1,2,3-Trichlorobenzene4.043.983.98 Large-Sized Solutes (V = 0.27 - 0.39 L/mol) 2,2’,3,3’,5,5’,6,6’-PCB7.117.117.42 Dieldrin4.554.534.79 Ethion5.075.135.49 Leptophos6.316.346.60 Nonylphenol-4EOs4.244.314.77 (A): log K ow = - 0.884 log S w - log V - 0.268; (B): log K ow = - 0.862 log S w + 0.710

23. Predicted Log K ow of NOCs from Log S w and Log V S w - log S w - log V Pred Expt  Compound (ppm) (mol/L) (L/mol) log K ow log K ow log K ow ALHCs Cyclohexane 55.83.180.9633.513.44-0.07 n-Heptane 2.934.530.8324.574.66 0.09 1-Octene 2.704.620.8024.624.57-0.05 1-Hexyne 3602.360.9372.752.73-0.02 HALHCs 1,2-Dichloromethane 8.7E31.061.1041.771.76-0.01 TCE 1.37E31.981.0452.532.53 0 1-Bromoheptane 6.654.430.8044.454.36-0.09 Hexachlorobutadiene 2.555.010.8104.974.90-0.07 ALBZs Styrene 3002.540.9362.912.95 0.04 1,3,5-Trichlorobenzene 69.23.240.8653.463.42-0.04 1,2,4,5-Tetrachlorobenz 3.48 (4.02) (0.795)4.084.100.02 Hexamethylbenzene 0.235 (4.68) (0.704)4.574.61 0.04

24. Predicted Log K ow of NOCs from Log S w and Log V S w - log S w - log V Pred Expt  Compound (ppm) (mol/L) (L/mol) log K ow log K ow log K ow Anilines 3-Toluidine 1.50E40.850.9651.451.42-0.03 N,N-Dimethylaniline 1.11E32.040.8952.432.31-0.12 Ethers MTBE5.16E40.230.9250.860.940.08 Anisole 20301.730.9642.222.11-0.11 Diphenyl ether 18 (3.95) (0.800)4.024.080.06 Esters Ethyl acetate8.04E40.0401.0100.780.73-0.05 Ethyl benzoate 7202.320.8452.632.64 0.01 Di-butyl phthalate 13.04.330.5754.144.08-0.06 Di-octyl phthalate4.6E-48.930.3998.028.100.08

25. Predicted Log K ow of NOCs from Log S w and Log V S w - log S w - log V Pred Expt  Compound (ppm) (mol/L) (L/mol) log K ow log K ow log K ow HABZs Fluorobenzene 15501.791.0272.342.27-0.07 Iodobenzene 2292.950.9513.293.28-0.01 1,4-Dichlorobenzene 73 (3.03) (0.828)3.343.370.03 1,2,3-Trichlorobenzene 16.3 (3.79) (0.903)3.984.04 0.06 1,2,4,5-Tetrachlorobenzene 0.29 (4.70) (0.848)4.734.70-0.03 Hexachlorobenzene 5.0E-3 (5.71) (0.741)5.525.50-0.02 PAHs Acenaphthene 3.93 (3.89) (0.830)4.003.92-0.08 Fluorene 1.90 (4.14) (0.814)4.214.18-0.03 Phenanthrene 1.29 (4.48) (0.773)4.464.46 0 1,4,5-Trimethylnaphthalene 2.1 4.91 0.7604.834.87 0.04 Pyrene 0.135 (4.92) (0.753)4.834.880.05 Benzo(a)anthracene 0.014 (5.89) (0.694)5.635.61-0.02

26. Predicted Log K ow of NOCs from Log S w and Log V S w - log S w - log V Pred Expt  Compound (ppm) (mol/L) (L/mol) log K ow log K ow log K ow PCBs 2,4’-PCB 0.637 (5.34) (0.674)5.135.10-0.03 2,2’,5,5’-PCB 0.046 (6.19) (0.615)5.825.81-0.01 2,2’,4,4’,6,6’-PCB 4.1E-4 (8.24) (0.526)7.547.55 0.01 2,2’,3,3’,5,5’,6,6’-PCB 3.93E-4 (7.78) (0.499)7.117.11 0 2,2’,3,3’,4,5,5’,6,6’-PCB 1.8E-5 (9.04) (0.467)8.198.16-0.03 DXDBFs 2,8-Dichlorodibenzofuran0.0145 (5.67) (0.739)5.485.44-0.04 1,2,3,4-Tetrachlorodioxin6.3E-4 (6.75) (0.668)6.376.20-0.17 Heterocyclics Carbazole 1.03 (3.00) (0.830)3.213.29 0.08 Benzo(b)thiophene 130 (2.94) (0.933)3.263.26 0

27. Predicted Log K ow of Pesticides from Log S w and Log V S w - log S w - log V Pred Expt  Compound (ppm) (mol/L) (L/mol) log K ow log K ow log K ow OGCLs Dieldrin 0.465 (4.73) (0.616)4.534.55 0.02 Heptachlor 0.056 (6.05) (0.645)5.735.730 p,p’-DDE 0.040 (6.15) (0.627)5.805.77-0.03 OGPPs Chlorfenvinphos 145 3.39 (0.578)3.313.23-0.08 Ethion 1.15.54 0.5015.135.07-0.06 Leptophos 0.021 (6.83) (0.570)6.346.31-0.03 Carbamates Oxamyl 2.83E5 (-0.87) (0.646) - 0.39 - 0.43-0.04 Aldicarb 6.02E3 (0.59) (0.798)1.051.130.08 Carbaryl 104 (2.09) (0.742)2.322.31-0.01 AUTZs Alachlor 240 (2.89) (0.623)2.912.92 0.01 Linuron 75 (2.57) (0.701)2.702.76-0.06 Atrazine 30 (2.37) (0.741)2.572.64 0.07

28.  Log K ow for Classes of NOCs and Pesticides Class No.  log K ow ALHCs 140.07 HALHCs220.07 ALBZs150.06 HABZs140.04 Anilines 60.06 Ethers 70.09 Esters110.06 PAHs230.07 PCBs260.07 DXDBFs 50.13 Heterocyclics 60.11 OGCLs 70.03 OGPPs140.11 Carbamates100.07 AUTZs140.07 Total 194 Ave. 0.074

29. Predicted Log K ow from Log S w and Log V for Phenols and Alcohols S w Pred Expt  Compound (ppm) - log S w - log V log K ow log K ow log K ow Phenols Phenol7.65E4 (-0.01) (1.051)0.781.450.67 2,4,6-Trimethylphenol1.01E3 (1.67) (0.907)2.112.730.72 2-Chlorophenol1.15E4 (1.05) (0.990)1.652.15 0.50 2,4,5-Tichlorophenol 649 (2.09) (0.881)2.463.721.26 4-Octylphenol12.6(4.05) (0.685)3.994.12 0.13 Nonylphenol-4EOs7.65(4.71) (0.411)4.314.24-0.07 Alcohols n-Hexanol5.84E4 (1.24) (0.903)1.732.030.30 n-Heptanol1.68E3(1.84) (0.849)2.212.57 0.36 n-Octanol495(2.42) (0.801)2.673.15 0.48 Benzyl alcohol3.8E4(0.45) (0.983)1.121.10-0.02

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