Predicting Octanol-Water Partition Coefficients (K ow ) from Water Solubility and Molar Volumes Cary...

Predicting Octanol-Water Partition Coefficients (Kow) from Water Solubility and Molar Volumes

Cary T. Chiou

National Cheng Kung Univ., Tainan,TaiwanU.S. Geological Survey, Denver, CO, USA

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)

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

Lipid triolein-water partition coefficients (Ktw) and fish bioconcentration factors (BCF)lipid (Laboratory Experiments)

Compound log Ktw log (BCF)lipid log (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

a Könemann and van Leeuwen (Chemosphere, 1980) ; b Oliver and Nimii (ES&T, 1983)

Log (BCF)lipid

Log Ktw

2

Rainbow trout

Guppies

0 4 60

2

4

6

Laboratory Fish BCF Experiments

Chiou (ES&T,

1985) with Ktw

and literature BCF data

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)

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]

X, πX (octanol-water) , and πX (heptane-water) of Functional Groups Attached to Benzene

Compound Group X πX (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

Phenol OH - 1.70 - 0.67 - 3.18

Benzoic acid COOH - 0.73 - 0.28 - 2.98

Phenylacetic acid CH2COOH - 1.15 - 0.83 - 3.33

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

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]

Typical log Kow - log Sw Correlations

Chiou et al. (ES&T, 1982) for mostly substituted benzenes:

log Kow = - 0.862 log Sw - 0.710

Mackay et al. (Chemosphere, 1980) for substituted benzenes, PAHs, and others:

log Kow = - log Sw + 0.254

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

Polyparameter LSERs for Partition Coefficients(Tafts, Abraham, Kamlet, Taylor)

For Any Partition Coefficient (K):

log K = c + rR2 + sπ2 + a2 + b2 + vVx

R2 = Solute excess molar refraction

π2 = Solute dipolarity

2 = Solute H-bond acidity

2 = Solute H-bond basicity

Vx = Solute characteristic volume

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

Perfect Partition Coefficients for Dilute Solutes in Any Solvent-Water Mixtures

log Kºsw = - log Sw - log V

Note:

Kºsw 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 (Sw).

Kºsw or Kow shows a dependence on solute molar

volume (V) rather than on solvent molar volume (Vo*).

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 2.25Toluene -2.25 2.69 2.77Ethylbenzene -2.84 3.15 3.271,3,5-Trimethylbenzene -3.09 3.42 3.561,2-Dichlorobenzene -2.98 3.38 3.511,2,4-Trichlorobenzene -3.72 4.02 4.121,2,3,5-Tetrachlorobenzene (-4.53) 4.59 4.69Hexachlorobutadiene -5.01 4.90 5.04Pentachlorobenzene (-5.18) 5.20 5.27Hexachlorobenzene (-5.57) 5.50 5.502-PCB (-4.57) 4.51 4.772,4’-PCB (-5.28) 5.10 5.302,5,2’,5’-PCB - - 6.11 5.81

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

*)

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 0.24Aniline 0.410 1.45 1.09 0.36Dichloromethane 0.641 1.83 1.51 0.32Carbon tetrachloride 2.28 3.30 2.73 0.57Benzene 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 0.831-Hexene 3.08 3.98 3.39 0.59n-Octane 5.24 6.02 5.18 0.84Naphthalene (3.09) 3.99 3.36 0.63Phenanthrene (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

- log Sw

0 1 2 3 4 5 6 7 8

log

Fd

v

0.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

log Fdv = - 0.116 log Sw + 0.268

Correlation of Log Kow with Log Sw and Log V Chiou 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

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

Trichloroethylene 2.53 2.53 2.42

Substituted Benzenes (V = 0.10 - 0.14 L/mol)

Toluene 2.69 2.69 2.651,4-Xylene 3.18 3.14 3.151,2,3-Trichlorobenzene 4.04 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 7.42Dieldrin 4.55 4.53 4.79Ethion 5.07 5.13 5.49Leptophos 6.31 6.34 6.60Nonylphenol-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

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

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



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



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 0.061,2,4,5-Tetrachlorobenzene 0.29 (4.70) (0.848) 4.73 4.70 -0.03Hexachlorobenzene 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



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

Predicted Log Kow of Pesticides from Log Sw and Log V


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

Log Kow for Classes of NOCs and Pesticides Class No. log Kow

ALHCs 14 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

OGCLs 7 0.03

OGPPs 14 0.11

Carbamates 10 0.07

AUTZs 14 0.07

Total 194 Ave. 0.074

Predicted Log Kow from Log Sw and Log V for Phenols and Alcohols

Sw Pred 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

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 2

H + 3.814Vx

with

n = 613 and SD = 0.116

Note: No pesticides and complex molecules

Predicting Octanol-Water Partition Coefficients (K ow ) from Water Solubility and Molar Volumes Cary...

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