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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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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


Uses and needs of k ow values
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)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)


Laboratory Fish BCF Experiments

Chiou (ES&T,

1985) with Ktw

and literature

BCF data


Current k ow prediction methods
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
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 x octanol water and x heptane water of functional groups attached to benzene
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


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 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


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
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


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
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*).


Water solubilities ( Solvent-Water MixturesSw), 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


Partition coefficients in octanol water mixtures
Partition Coefficients in Octanol-Water Mixtures Solvent-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 s w and log k sw of reference solutes and their log f dv in octanol water mixtures
Log Solvent-Water MixturesSw 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


1.4 Solvent-Water Mixtures

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


Correlation of log k ow with log s w and log v chiou et al es t 2005
Correlation of Log Solvent-Water MixturesKow 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


Log k ow predictions by volume fraction based a and mole fraction based b dilute solution models
Log Solvent-Water MixturesKow 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


Predicted log k ow of nocs from log s w and log v
Predicted Log Solvent-Water MixturesKow 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


Predicted log k ow of nocs from log s w and log v1
Predicted Log Solvent-Water MixturesKow 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


Predicted log k ow of nocs from log s w and log v2
Predicted Log Solvent-Water MixturesKow 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


Predicted log k ow of nocs from log s w and log v3
Predicted Log Solvent-Water MixturesKow 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


Predicted log k ow of pesticides from log s w and log v
Predicted Log Solvent-Water MixturesKow 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


Log k ow for classes of nocs and pesticides
Solvent-Water MixturesLog 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


Predicted log k ow from log s w and log v for phenols and alcohols
Predicted Log Solvent-Water MixturesKow 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


Prediction of octanol water partition coefficients k ow by pp lsers abraham et al j pharm sci 1994
Prediction of Octanol-Water Partition Coefficients ( Solvent-Water MixturesKow) 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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