Transcript Document

Predicting Octanol-Water Partition Coefficients
(Kow) 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 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
Benzene
Toluene
Ethylbenzene
1,3,5-Trimethylbenzene
1,2-Dichlorobenzene
1,2,4-Trichlorobenzene
1,2,3,5-Tetrachlorobenzene
Hexachlorobutadiene
Pentachlorobenzene
Hexachlorobenzene
2-PCB
2,4’-PCB
2,5,2’,5’-PCB
log Sw (mol/L)
-1.64
-2.25
-2.84
-3.09
-2.98
-3.72
(-4.53)
-5.01
(-5.18)
(-5.57)
(-4.57)
(-5.28)
--
log Kow
log Ktw
2.13
2.69
3.15
3.42
3.38
4.02
4.59
4.90
5.20
5.50
4.51
5.10
6.11
2.25
2.77
3.27
3.56
3.51
4.12
4.69
5.04
5.27
5.50
4.77
5.30
5.81
Lipid triolein-water partition coefficients (Ktw) and fish
bioconcentration factors (BCF)lipid (Laboratory Experiments)
Compound
log Ktw
1,2-Dichlorobenzene
1,3-Dichlorobenzene
1,4-Dichlorobenzene
Hexachloroethane
1,2,3-Trimethylbenzene
1,2,4-Trimethylbenzene
1,3,5-Trichlorobenzene
1,2,3,4-Tetrachlorobenzene
1,2,3,5-Tetrachlorobenzene
1,2,4,5-Tetrachlorobenzene
Hexachlorobutadiene
Pentachlorobenzene
Hexachlorobenzene
3.51
3.63
3.55
4.21
4.19
4.12
4.36
4.68
4.69
4.70
5.04
5.27
5.50
a
log (BCF)lipid
log (BCF)lipid
(guppies)a
(rainbow trout)b
3.51-3.80
3.70-4.02
3.26
3.64-3.96
3.79-4.13
4.11
4.15-4.47
4.19-4.56
4.15
4.34-4.67
4.80-5.13
4.86
4.80-5.17
4.84-5.29
5.42
5.19-5.36
5.46
5.16-5.37
Könemann and van Leeuwen (Chemosphere, 1980) ; b Oliver and Nimii (ES&T,
1983)
Laboratory Fish BCF Experiments
Chiou (ES&T, 6
1985) with Ktw
and literature
BCF data
Rainbow trout
Guppies
4
Log (BCF)lipid
2
0
0
2
4
Log K tw
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)
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
Benzene
Group
--
X
Toluene
CH3
Ethylbenzene
πX (oct-w)
0
πX (hep-w)
0
0.60
0.56
0.59
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
0
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 + 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
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
Benzene
Toluene
Ethylbenzene
1,3,5-Trimethylbenzene
1,2-Dichlorobenzene
1,2,4-Trichlorobenzene
1,2,3,5-Tetrachlorobenzene
Hexachlorobutadiene
Pentachlorobenzene
Hexachlorobenzene
2-PCB
2,4’-PCB
2,5,2’,5’-PCB
log Sw (mol/L)
-1.64
-2.25
-2.84
-3.09
-2.98
-3.72
(-4.53)
-5.01
(-5.18)
(-5.57)
(-4.57)
(-5.28)
--
log Kow
log Ktw
2.13
2.69
3.15
3.42
3.38
4.02
4.59
4.90
5.20
5.50
4.51
5.10
6.11
2.25
2.77
3.27
3.56
3.51
4.12
4.69
5.04
5.27
5.50
4.77
5.30
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)
Diethyl ether
Aniline
Dichloromethane
Carbon tetrachloride
Benzene
Ethyl benzene
1,3-Dichlorobenzene
1,2,3,4-Tetrachlorobenz
1-Hexene
n-Octane
Naphthalene
Phenanthrene
2,2’,5-PCB
2,2’,3,3’,4,4’-PCB
Chlorpyrifos
Lindane
p,p’-DDT
- log Sw
0.0899
0.410
0.641
2.28
1.64
2.82
3.07
4.59
3.08
5.24
(3.09)
(4.48)
(5.83)
(7.59)
(5.68)
(3.62)
(6.79)
log Kºsw
1.07
1.45
1.83
3.30
2.69
3.74
4.01
5.43
3.98
6.02
3.99
5.25
6.48
8.12
6.29
4.39
7.40
log Kow
0.83
1.09
1.51
2.73
2.13
3.15
3.44
4.60
3.39
5.18
3.36
4.46
5.60
6.98
5.27
3.72
6.36
log Fdv
0.24
0.36
0.32
0.57
0.56
0.59
0.57
0.83
0.59
0.84
0.63
0.79
0.88
1.14
1.02
0.67
1.04
1.4
1.2
log Fdv = - 0.116 log Sw + 0.268
log Fdv
1.0
0.8
0.6
0.4
0.2
0.0
0
1
2
3
4
- log Sw
5
6
7
8
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
1,4-Xylene
1,2,3-Trichlorobenzene
2.69
3.18
4.04
2.69
3.14
3.98
2.65
3.15
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
Dieldrin
4.55
4.53
Ethion
5.07
5.13
Leptophos
6.31
6.34
Nonylphenol-4EOs
4.24
4.31
7.42
4.79
5.49
6.60
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
Compound
Sw
(ppm)
- log Sw - log V
(mol/L) (L/mol)
Pred
Expt
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
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
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
HALHCs
ALBZs
Predicted Log Kow of NOCs from Log Sw and Log V
Compound
Sw
(ppm)
- log Sw - log V
(mol/L) (L/mol)
Pred
log Kow
Expt

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
MTBE
5.16E4
0.23
0.925
0.86
0.94
0.08
Anisole
Diphenyl ether
2030
18
1.73
(3.95)
0.964
(0.800)
2.22
4.02
2.11
4.08
-0.11
0.06
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
Ethers
Esters
Ethyl acetate
Predicted Log Kow of NOCs from Log Sw and Log V
Compound
Sw
- log Sw
(ppm) (mol/L)
- log V
(L/mol)
Pred
log Kow
Expt

log Kow log 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
16.3
0.29
5.0E-3
(3.79)
(4.70)
(5.71)
(0.903)
(0.848)
(0.741)
3.98
4.73
5.52
4.04
4.70
5.50
0.06
-0.03
-0.02
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
1,2,3-Trichlorobenzene
1,2,4,5-Tetrachlorobenzene
Hexachlorobenzene
PAHs
Predicted Log Kow of NOCs from Log Sw and Log V
Sw
(ppm)
- log Sw
(mol/L)
- log V
(L/mol)
Pred
Expt
log Kow
log Kow

log Kow
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
3.93E-4
(7.78)
(0.499)
7.11
7.11
0
1.8E-5
(9.04)
(0.467)
8.19
8.16
-0.03
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
Compound
PCBs
2,2’,3,3’,5,5’,6,6’-PCB
2,2’,3,3’,4,5,5’,6,6’-PCB
DXDBFs
Predicted Log Kow of Pesticides from Log Sw and Log V
Compound
OGCLs
Sw
(ppm)
- log Sw
(mol/L)
- log V
(L/mol)
Pred
Expt
log Kow
log Kow

log Kow
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
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
Oxamyl
2.83E5
(-0.87)
(0.646)
- 0.39
- 0.43
-0.04
Aldicarb
Carbaryl
6.02E3
104
(0.59)
(2.09)
(0.798)
(0.742)
1.05
2.32
1.13
2.31
0.08
-0.01
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
OGPPs
Carbamates
AUTZs
 Log Kow for Classes of NOCs and Pesticides
Class
No.
ALHCs
HALHCs
ALBZs
HABZs
Anilines
Ethers
Esters
PAHs
PCBs
DXDBFs
Heterocyclics
OGCLs
OGPPs
Carbamates
AUTZs
Total
14
22
15
14
6
7
11
23
26
5
6
7
14
10
14
194
 log Kow
0.07
0.07
0.06
0.04
0.06
0.09
0.06
0.07
0.07
0.13
0.11
0.03
0.11
0.07
0.07
Ave. 0.074
Predicted Log Kow from Log Sw and Log V
for Phenols and Alcohols
Compound
Sw
(ppm)
Pred
- log Sw - log V
log Kow
Expt

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
Nonylphenol-4EOs
12.6
7.65
(4.05)
(4.71)
(0.685)
(0.411)
3.99
4.31
4.12
4.24
0.13
-0.07
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
Alcohols
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