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water partition coefficients: Evaluation of six methods for highly hydrophobic aromatic hydrocarbons
Chemosphere, Vol.17, No.2, pp 345-359, 1988 Printed in Great Britain
0045-6535/88 $3.00 + .00 Pergamon Journals Ltd.
ESTIMATION OF OCTANOL/WATERPARTITION COEFFICIENTS: EVALUATION OF SIX METHODS FOR HIGHLY HYDROPHOBICAROMATIC HYDROCARBONS
W.J. Doucette 1 andA.W. Andren 2 1Division of Environmental Engineering, Utah State University, Logan, UT 84522
2Water Chemistry Program, University of Wisconsin, Madison, WI 53706
ABSTRACT Six methods for estimating log Kow were evaluated using a set of experimental values for 64 aromatic compounds. A l l log Kow values used in this evaluation were e x p e r i m e n t a l l y measured using a generater-column technique. This provided an accurate, s e l f - c o n s i s t e n t set of compounds having log Kow values ranging from 2.13 to 8.58. The estimation methods examined included two group contribution methods and four c o r r e l a t i v e methods utilizing molecular weight, HPLC retention time, molecular connectivity lndex, and total molecular surface area. INTRODUCTION Mathematical models are widely used to predict the fate and t r a n s p o r t of organic contaminants i n t h e environment. Most of these models require as input data, information about the physical and chemical properties of the compound(s) of i n t e r e s t . One of the most widely used properties in fate assessment modeling is the octanol/water partition coefficient (Kow). As a measure of the hydrophobic character of a compound, Kow , has been used for predicting adsorption and m o b i l i t y i n soils and sediments (Karickhoff, i981; Karickhoff et a t . , 1979; Schwarzenbach et a l . , t981), bioconcentration in fish (Kenaga, 1980), and aquatic t o x i c i t y (Konemann, 1980). Values for Kow are obtained by direct experimental measurement or are estimated uslng one of several techniques. While experimental values are p r e f e r r e d for use in environmental fate modeling and theoretical applications, estimated values are often used when experlmental values are unavailable or d i f f i c u l t to measure. For highly hydrophobic compounds (log Kow > 5), direct experimental measurement of Kow using traditional shake-flask methods ls e x t r e m e l y difMcult. Consequently, estimated values, calculated uslng group contributiontechnlques (Hansch and Leo, 1979;Nys andRekker, 1973) or from c o r r e l a t i o n s with reverse-phase HPLC retention times (Veith et a l . , 1979, McDuffie, 1981), have been used as a l t e r n a t i v e s to experimental data. However, because of the lack of r e l i a b l e experimental data, the accuracy of estimation techniques has been d i f f i c u l t to evaluate for compounds having log Kowgreater than 5.
345
346
A generator-column technique has been developed which permits the accurate experimental measurement of log Kow, well beyond the range of traditional shake-flask methods (DeVoe et a l . , 1981; Woodburn et a l . , 1984; ). This technique has been used to measure log Kow values for several classes of highly hydrophobic aromatic compounds including polychlorinated biphe'nyls (PCBs) ( M i l l e r et a l . , t984), polybrominated biphenyls (PBBs), polychlorinated dioxins (PCDDs), and polychlorinated furans (PCDFs) (Doucette, 1985, Doucette and Andren, 1987). Using only experimental values determined using a generator-column technique, an accurate and self-consistent set of log Kow values for 64 highly hydrophobic aromatic compounds was developed. This data set, consisting of compounds ranging in log Kow from 2.13 to 8.58 was used to develop and evaluate the six estimation methods described below. METHODS
OF EST IMA'T ION
METHOD A
This method uses e m p i r i c a l l y derived fragment constants ( f ) and s t r u c t u r a l factors (F) to d l r e c t l y calculate the log Kow of a compound from its s t r u c t u r e alone (Hansch and Leo, 1978). log Kow = sum of fragments ( f ) + sum of factors (F) Fragment constants and factors compiled (Hansch and Leo, 1978) for a large number of atoms and groups enable the calculation of log Kow for almost any compound. If an accurate measured value of log Kow is available for a s t r u c t u r a l l y s i m i l a r or "parent" compound, this measured value can be used to calculate the log Kow of the "derivative" by adding or subtracting the appropriate f or F values as shown below. log Kow ( d e r i v a t i v e ) = log
Kow (parent) + fragment ( f ) + factor (F)
Because the interaction terms in the parent molecule are already accounted f o r , this approach is p r e f e r r e d whenever a r e l i a b l e measured value is available (Leo, 1975). This approach is often used for substituted aromatic compounds and is equivalent to the widely used Tr-factor approach (Fujita et e l . , 1964;Fujita, 1966;Hansch et e l . , 1968; and Hansch and Leo, 1979). Recently, computerized versions of Hansch and Leo's method have been developed. Values used in this study, shown in Table 1, were calculated using a program developed by Leo (1985). Table I. Experimentaland predicted log Kowvalues for 65 aromatic compounds.
Compound blphenyl Z-chloroblphenyl 3-chloroblphenyl
1ogKow 1ogKow IogKow 1ogKow IogKow IogKow IogKow (e×p) (Meth A) (Meth B) (Meth C) (Meth D) (Meth E) (Meth F) 3,8g 4.03 3,79 3,69 3.88 4,35 4.52 4.38 4.74 4.56 3.g2 4.q4 4.81 4.90 4.58 4.74 4.56 4.44 4.80 4.g4
347 Table I
(cont.)
4-chloroblphenyl
4.49
4.74
4.56
-
4.44
4.80
4.94
4 , 4 ' - c l l c h l o r oblphenyl
5.53
5.46
5.32
-
5.10
5m23
5m36
3,4-dlchloroblphenyl
5,29
5.46
5.52
-
5. t0
5.24
5.31
2, Z'- dtchlor oblphenyl
4.90
5.46
5.32
-
5.10
5.24
5.28
2,4'-dlchloroblphenyl
5, 14
5.46
5.32
-
5, 10
5.24
5.32
2,5-dlchloroblphenyt
5.16
5.46
5.52
-
5.10
5.24
5.32
2,6-dlchloroblphenyl
4.93
5.46
5.23
5.10
5.24
5.28
2,2',5-trlchloroblphenyl
5.60
6.16
6.00
5.44
5,65
5.71
2,4,5-trlchloroblphenyl
5.81
6.17
5.99
5.47
5.44
5.65
5.69
2 , 4 ' , 5-t rlchloroblphenyl
5.79
6.17
6.00
-
5,44
5.64
5,74
2 , 4 , 6 - t rlchloroblphenyl
5.57
6.17
5.99
-
5.44
5.65
5.71
2,3, 4,5-tetrachloroblphenyl
5.72
6.88
6.74
-
5.89
6.04
6.02
2 , 2 ' , 4', 5, - t e t r a c hloroblphenyl
5.75
6.88
6.67
-
5.89
6.03
6.13
2 , 2 ' , 4 , 5 , 5 ' - p e n t achloroblphenyl
6.50
7.60
7.43
5.88
6.32
6.39
6.50
2,3,4,5,6-pentachloroblphenyl
6.30
7.60
7.43
-
6.32
6.40
6.36
,6,6'-hexachloroblphenyl
6,81
8.31
8,18
-
6.71
6,73
6.80
Z, 2', 4,4', 5 , 5 ' - h e x a c h l o r o b l p h e n y l
2,2,3,3
6.90
8.31
8.18
6.46
6.71
6.73
6.87
2 , 2 ' , 3, 3', 4 , 4 ' - h e x a c h l o r o b l p h e n y l
6.98
8.31
8.16
6.71
6.73
6.76 6.69
2,2", 4 , 4 ' , 6 , 6 ' - h e x a chIoroblphenyl
7.55
8.31
6.16
6.71
6.73
2 , 2 ' , 3,3', 4 , 4 ' , 6-hepta c111oroblphenyl
6.68
9.03
8.94
7.06
7.04
7.16
2 , 2 ' , 3 , 3 ' , 5, 5', 6 , 6 ' - o c t a c h l o r o b l p h e n y l
7.12
9.73
9.69
-
7.39
7.34
7.54
2 , 2 ' , 3 , 3 ' , 4 , 5 , 5 ' , 6 , 6 -nonochloroblphenyl
8.16
10.45
10.44
-
7.68
7.60
7.67 8.20
decachloroblphenyl
8.20
I 1,16
I 1.20
7.73
7,95
7.85
2-bromoblphenyl
4.59
4.89
4.83
-
5.10
5.14
5.05
3-bromoblphenyl
4.85
4.89
4.83
-
5.10
5.14
5.10
4-bromoblphenyl
4.96
4.89
4.83
-
5.10
5.14
5.10
4,4'-dlbromoblphenyl
5,72
5.75
5.85
-
6.14
5,81
5.68
2,2', 4,5,5'-pentabromoblphenyl
7.10
8.06
8.76
8.27
7,55
7.25
decabromoblphenyl
6.58
10.42
13.87
8.46
8.89
7,10
dlbenz o - p - d l o x l n
4.37
4.65
4.14
4.18
4.37
4.70
4.35
2-c h]o r odlbenz o - p - d l o x l n
4,9,1
5.47
4.89
4.98
4.89
5.1'~
4.79
I, 2 , 3 , 4 - t e t r a c h l o r o d l b e n z o - p - d l o x l n
6.20
7.70
7.12
6.86
6,26
6.08
5.91
oct a c hlo rdlbenz o - p - d t o x l n
7.59
I0.56
10.09
7.83
7.65
7.53
7.46
dlbenzofuran
4.31
4.12
4.04
3.66
4.11
4,57
4.13
2 , 8 - d t c h l o rdlbenzoi'uran
5.44
5.65
5.53
5.12
4.92
5.42
5.01
oct achlorocllbenzofuran
7.97
9.96
9.99
7.90
7.51
7.32
7.05
-
4.11
4.71
5.01
4.33
5.06
5.50
2.50
2.56
2.28
2.52
4-methylblphenyl
4.63
4.68
4.33
4 , 4 ' - d l met hv1 blphenvI
5.09
5.33
4.87
benzene
2.13
2.14
2.09
chlorobenzene
2.98
2.84
3.07
3.18
2.82
2.94
1, Z-dlchlorobenzene
3.38
3.57
3.59
-
3.77
3.35
3.31
I ,3-dlchlorobenzene
3.48
3.57
3.59
-
3.77
3.34
3.36
I , 4-dlchlorobenzene
3.36
3.57
3.59
-
3.77
3.34
3,36
I , 2 , 3 - t rlchlorobenzene
4.04
4.28
4.27
-
4.32
3.85
3.69
1 , 2 , 4 - t rlchlorobenzene
3.98
4.28
4.27
-
4.32
3.85
3.73
1,3,5-trlchlorobenzene
4.02
4.28
4.27
-
4.32
3.34
3.78
348
Table 1 (cont.) 1,2,3,4-tetrachlorobenzene
4.55
4.gg
5.02
-
4.65
4.53
4.06
1,2,3,5-tetrachlorobenzene
4.65
4.99
5.02
-
4.85
4.06
4.11 4.11
1,2,4,5-tetrachlorobenzene
4.51
4.99
5.02
-
4.85
4.49
pentachlorobenzene
5.03
5.71
5.77
5.47
5.34
4.86
4.43
he×achlorobenzene
5.47
6.q2
6.53
6.22
5.60
5.22
4.75
toluene
2.65
2.60
2.60
2.93
2.81
2.75
3.01
I ,2-dlmethylbenzene
3.13
3.14
3.14
-
3.06
3.16
3.42
I ,3-dimethylbenzene
3.18
3.14
3.14
-
3.06
3.18
3.50
I ,4-dlmethylbenzene
3.20
3.14
3.14
-
3.06
3.16
3.50
I, 2,3-t rl methylbenzene
3.55
3.58
3.58
3.81
3.51
3.57
3.62
I, 2,4-t ri methyl benzene
3.63
3.58
3.58
-
3.51
3.56
3.82
I, 2,3,4-tet ra methylbenzene
3.98
4.02
4.02
-
3.55
3.97
4.23
1.2,3. S-tetra methylbenzene
4.04
4.02
4.02
-
3.55
3.g6
4.52
he×amethylbenzene
4.61
5.16
5.16
-
4.02
4.75
4.96
bromobenzene
2.98
3.00
3.07
3.05
3.93
2.81
3.10
METHOD B This m e t h o d a l s o c a l c u l a t e s
log Kow
values directly
from
the compound's structure
using t h e a p p r o p r i a t e h y d r o p h o b i c f r a g m e n t c o n s t a n t s o r f - v a l u e s . The f - v a l u e s a r e d e r i v e d f r o m a s t a t i s t i c a l a n a l y s i s of a l a r g e data base of e x p e r i m e n t a l l o g Kow v a l u e s and a r e d e f i n e d as t h e l i p o p h i l i c c o n t r i b u t o r t o t a l l i p o p h i l i c i t y (Nys and R e k k e r , 1 9 7 5 ) .
of a s u b s t i t u e n t p a r t of a s t r u c t u r e to t h e C a l c u l a t i o n of log Kow is b a s e d on t h e
equation"
logKo~= ~ a nf i=l where
an is
a numerical
factor
indicating
the
incidence
of
a given
fragment
in
the
structure. A c o m p i l a t i o n of f - v a l u e s (Nys and R e k k e r , 1973, 1974) p e r m i t s t h e c a l c u l a t i o n of l o g Kow f o r m o s t c o m p o u n d s . The l o g Kow v a l u e s c a l c u l a t e d by t h i s m e t h o d a r e l i s t e d in T a b l e 1. METHOD C This m e t h o d is b a s e d on t h e c o r r e l a t i o n its retention time (RT) determined chromatography (RP-HPLC). In t h i s
b e t w e e n t h e log Kow v a l u e of a c o m p o u n d and
by r e v e r s e - p h a s e high technique, c o m p o u n d s of
performance liquid k n o w n l o g Kow a r e
c o r r e l a t e d to t h e i r RP-HPLC RTs and a r e g r e s s i o n e q u a t i o n is o b t a i n e d . RTs of c o m p o u n d s w i t h u n k n o w n Kow v a l u e s a r e d e t e r m i n e d and t h e i r log Kow v a l u e s a r e c a l c u l a t e d f r o m t h e regression equation. The RP-HPLCRTs used in t h i s s t u d y w e r e d e t e r m i n e d b y S a r n a et a l . ( 1 9 8 4 ) on a W a t e r s uBondpak C18 c o l u m n using a m o b i l e p h a s e of m e t h a n o l - w a t e r ( 8 5 ; 1 5 ) at a f l o w r a t e of 1.0 m L / m i n , c o r r e c t e d f o r t h e v o i d t i m e of t h e s y s t e m , and a d j u s t e d r e l a t i v e t o t h e c o r r e c t e d retention time for catechol. A
plot
of
experimental
l o g Kow vs
log
corrected
RT was
made
for
21
aromatic
349
hydrocarbons (Figure 1), including several PCBs, PCDFs, and PCDDs. Regression analysis yielded the equation: log K o w = - 1 . 8 ? O (log RT) Z+ 7.04 (log RT) + 1.289
(1)
(n = 21, R2 = 0.994) This expresslonwas used to c a l c u ] a t e t h e predicted log Kowvalues shown in Table 1.
10
8
/¢X.o
cm
s @
E
~4
0.0
0,5 HPLC
1.0
Retention
Time
1.5
2.0
( m i n ) ( M e t h o d C)
Figure I. Experimental log Kow versus log corrected HPLC retention time for 21 aromatic compounds, Retention time values determined by Sarna e t a ] . , 1984. METHOD D This method is based on the correlation between the molecular weight of a compound and its experimental log Kowva]ue. The relationship between MW and experimental log Kow for 64 aromatic compounds (shown in Figure 2) was found to be best represented by the following equation: log K o w = - l . 3 5
x 10-5 (MW) Z + 0 . 0 2 1 (MW) + 1.029
(2)
(n = 64, R2 = 0.938)
10
~8 I i
[]
"= []
o
~6 E
~=
4
200
400
Molecular
Figure 2.
600
800
1000
Weight
Experimental log Kowversus Molecular weight for 64 aromatic compounds.
350
Eliminating the two apparent high MW o u t l i e r s (penta and decabromobiphenyl) observed in Figure 2, did not s i g n i f i c a n t l y change the r e g r e s s i o n r e s u l t s as s h o w n i n equation ( 3 ) . log K o w = - I . O 8 E - 5
( M W ) 2 + O.OZO0 ( M W ) + 1.106
(3)
( n = 62 R Z = 0.943)
Equation (2) was used to c a l c u l a t e the log K o w v a l u e s in Table 1. METHOD E
This method is based on a c o r r e l a t i o n between e x p e r i m e n t a l log Kow values and m o l e c u l a r c o n n e c t i v i t y indices (MCI) calculated by the procedure of Kier and Hall (1980). To c a l c u l a t e the MCIs, the s t r u c t u r e of the molecule is drawn out in the hydrogen atom suppressed s k e l e t a l f o r m .
A simple c o n n e c t i v i t y v a l u e ( ~ u )
is then assigned to each
atom of the m o l e c u l a r skeleton. This value is expressed as 11'u - Z maximum valence and h is the number of hydrogens on the atom.
Ii, where Z is the
The f i r s t - o r d e r v a l e n c e - c o r r e c t e d m o l e c u l a r c o n n e c t i v i t y l n d e x ( 1 X V ) is computed as: IxV -- ~ ( ' ~ i
~j)
I
where
It I and'll'j
are the v a l e n c e - c o r r e c t e d connectivity values f o r the adjacent atoms i
and j and n is the number of bonds within the molecule. Additional i n f o r m a t i o n is given b y K i e r and Hall (1976, 1986). Using the e x p e r i m e n t a l log K o w v a l u e s compiled in Table 2 the r e l a t i o n s h i p between MCt and log Kow (shown in Figure 3) was best represented by the r e g r e s s i o n equation: log K o w = - O . 0 4 9 9 (MCI)E+ 1.272 ( M C I ) - 0.0853
(4)
(n= 64, R2 = 0.964) The log K o w v a l u e s calculated using this expression are listed in Table 1.
10 o
v
8
o i
e=
6
E o. ~=
[].
4
2
4
6
8
10
12
Molecular Connectivity Index (MCI)
Figure 3. E x p e r i m e n t a l tog Kow v e r s u s f i r s t o r d e r M o l e c u l a r Connectivity Indexes f o r 64 a r o m a t i c compounds.
351
Method F
This method i n v o l v e s c o r r e l a t i o n
of e x p e r i m e n t a l
log Kow v a l u e s wlth t o t a l
surface
area (TSA) v a l u e s c a l c u l a t e d using a c o m p u t e r p r o g r a m obtained f r o m the Quantum C h e m i s t r y P r o g r a m Exchange, C h e m l s t r y D e p t . , Indiana U n i v e r s i t y , B l o o m i n g t o n , Indiana, and adapted f o r use on a S p e r r y 1100 m a i n f r a m e c o m p u t e r by Loux ( 1 9 8 2 ) . In this p r o g r a m , each atom of a m o l e c u l e is r e p r e s e n t e d by a sphere c e n t e r e d at the e q u i l i b r i u m position of the n u c l e u s . The radius of the sphere is equal to that of the van der Waal r a d i u s . The p r o g r a m c a l c u l a t e s the s u r f a c e area r e p r e s e n t e d by the i n t e r s e c t i o n of all the spheres in the m o l e c u l e . A detailed d e s c r i p t i o n of the m o l e c u l a r s u r f a c e area c a l c u l a t i o n method is provided by P e a r l m a n ( 1 9 8 0 ) . Standard g e o m e t r y , s t a n d a r d i n t e r a t o m i c bond l e n g t h s , and bond angles, supplemented with X-Ray d i f f r a c t i o n data, were used in c o n s t r u c t i n g the m o l e c u l a r s t r u c t u r a l d e t a i l s . The s u b s t i t u t e d benzenes, d l b e n z o - p - d i o x i n s , and d i b e n z o f u r a n s were assumed to have a planar conformation. For the s u b s t i t u t e d b i p h e n y l s , a n o n - p l a n a r c o n f o r m a t i o n was used which gave a maximum c a l c u l a t e d TSA. The methyl groups were a p p r o x i m a t e d as a single sphere of radius Z . 0 A as suggested by Valvanl et al. ( 1 9 8 Z ) . It was also possible to c a l c u l a t e the TSA of the solute m o l e c u l e a f t e r the addition of a suitable solvent radius. C a l c u l a t i o n showed, h o w e v e r , that the addition of a s o l v e n t radius f o r w a t e r did not s i g n i f i c a n t l y i m p r o v e the c o r r e l a t i o n between TSA and log Kow (Doucette, 1985). Thus, TSA v a l u e s r e p o r t e d in this study do not i n c l u d e the s o l v e n t radius c o n t r i b u t i o n . Unlike the p r e v i o u s c o r r e l a t i v e methods presented above, r e g r e s s i o n a n a l y s i s showed that the r e l a t i o n s h i p between TSA and log Kow (shown in Figure 4) is best e x p r e s s e d as a l i n e a r f u n c t i o n where: log Kow= 0.0238 ( T S A ) - 0 . 0 9 9
(5)
(n = 64, R2= 0 . 9 4 3 ) This e x p r e s s i o n was used to c a l c u l a t e the p r e d i c t e d log K o w v a l u e s shown in Table 1.
10
~:
!
8,
O
•~
6 ¸
E 4
g oo
i
i
200
300
400
T o t a l S u r f a c e A r e a (TSA)
Figure 4. E x p e r i m e n t a l log K o w v e r s u s c a l c u l a t e d Total Surface A r e a (/~2).
352
Results and Discussion Comparison and E v a l u a t i o n of the Methods Methods
A
through
F were
used
to
predict
log
Kow v a l u e s
for
the
aromatic
h y d r o c a r b o n s tisted in Table 1. T a b l e 2 l i s ts theHPLC r e t e n t i o n t i m e s , m o l e c u l a r weights, f i r s t o r d e r m o l e c u l a r c o n n e c t i v i t y indexes, and c a l c u l a t e d t o t a l s u r f a c e areas used to develop the c o r r e l a t i v e methods C-F. A v e r a g e a b s o l u t e percent e r r o r and range of e r r o r f o r each method are given in Table 3. The p e r c ent e r r o r is defined by the f o l l o w i n g expression: % e r r o r = { ( p r e d log K o w - exp log K o w ) / e x p log Kow] x 100 (6) Thus, p o s i t i v e ~ e r r o r v a l u e s indicate the p r e d i c t e d is g r e a t e r than the e x p e r i m e n t a l v a l u e , wh i l e negative v a l u e s s h o w t h e opposite. Table 2. M o l e c u l a r weights (MW), M o l e c u l a r Connectivity Index (MCl), Total Surface A r e a , and RP-HPLC r e t e n t i o n t i m e s used to develop c o r r e l a t i o n s f o r Method C-F.
Comoound
loa Kowa Perb
MWc
MCl d
TSA e
HPLC-RTf
biphenyl
3.8g
I
154.2
4.071
19Z.34
0.38
Z-chlorobiphenyl
4.38
I
188.7
4.5g0
Z08.33
0.4Z
3-chloroblphenyl
4.58
1
188.7
4.584
z0g.87
4-chloroblphenyl
4,4g
1
188.7
4.584
zog.87
4 4'-dlchloroblphenyl
5.53
1
Z33.1
5.097
Z27.40
3 4-dlchloroblphenyl
5.zg
I
233.1
5.103
225.41
Z 2'-dlchloroblphenyl
4.90
1
Z33.1
5.103
ZZ4.3Z
Z 4'-dichloroblphenyl
5.14
1
Z33.1
5,103
Z25.86
Z 5-dlchloroblphenyl
5.16
Z
Z33.1
5.10g
ZZ5.85
Z 6-dlchloroblphenyl
4.g3
Z
233.1
5.10g
ZZ4.3Z
Z,Z',5-trlchloroblphenyl
5.60
1
Z57.5
5.6ZI
Z41.84
Z,4,5-trlchloroblphenyl
5.81
1
Z57.5
5.6ZI
Z41.3g
Z,4',5-trlchloroblphenyl
5.7g
1
Z57.5
5.615
Z43.3g
Z,4,6-trlchloroblphenyl
5.57
3
Z57.5
5.6Z1
Z41.84
Z,3,4,5-tetrachloroblphenyl
5.7Z
Z
zgz.o
6.146
Z54.g5
Z,Z',4',5,-tetrachlorobiphenyl
5.73
Z
zgz.o
6.135
z5g,41
Z,Z',4,5,5'-pentachloroblphenyl
6.50
3
3Z6.4
6.652
Z74.95
Z,3,4,5,6-pentachloroblphenyt
6.30
Z
326.4
6.670
Z68.g5
Z,Z',3,3',6,6'-hexachloroblphenyl
6.81
3
360.9
7.183
Z87.38
Z,Z',4,4',5,5'-hexachloroblphenyl
6.go
3
360.g
7.171
Z90.50
Z,Z',3,3',4,4'-hexachlorobipheny]
6.g8
Z
360.g
7.177
Z86.4g
Z,Z',4,q',6,6'-hexachloroblphenyl
7.55
Z
360.g
7.177
Zgl.36
Z,Z',3,3',4,4',6-heptachloroblphenyl
6.68
Z
3g5.3
7.6g6
30Z.48
Z,Z',3,3',5,5',6,6'-octachlorobtphenyl
7.1Z
5
4zg.8
8.ZZ0
318.47
Z,Z',3,3',4,5,5',6,6'-nonochloroblphenyl
8,16
Z
464,2
8.740
33Z.02
O. 74
0.8g
O. 84
I .00
353 (Table Z cont. ) decachlorobiphenyl
8.20
5
4g8.7
g.270
345.59
Z-bromoblphenyl
4.59
5
233.1
4.g80
214.53
3-bromobiphenyl
4.85
5
Z33.1
4.982
216.55
4-bromoblphenyl
4.g6
5
Z33.1
4.982
Z16.55
4,4'-dibromoblphenyl
5.72
5
312.0
5.833
240.83 306.13
1 .
57
I
Z,Z',4,5,5'-pentabromobiphenyl
7. IO
5
548.7
8.643
decabromoblphenyl
8.58
5
943.2
13.250 zgg. 86
dibenzo-p-dlo×In
4.37
5
184.2
4.471
185.55
0.47
Z- c hlorodibe nzo-p-dioxln
4.94
5
218.6
4.980
203.61
O. 63
1, Z, 3,4-tet rachlordlbenzo-p-dlo×In
6.Z0
5
322.0
6.Z01
250.25
1.13
oct achl or dibenzo-p-dio×in
7.59
5
459.8
8.597
314.94
1.67
dlbenzofuran
4.31
5
168.2
4.313
176.25
0.41
Z, 8-dlchlordibenzofur an
5.44
5
Z21.I
5.3Z9
21Z.76
O. 66
oct achlor odlbenzofur an
7.97
5
443.8
8.189
Z97.96
1.80
4- m ethylblphenyl
4.63
5
168.2
4.482
212.88
4,4'-dimethylblphenyl
5.09
5
182.2
4.893
Z33.36
Z.13
Z
78.2
Z.O00
lOg.Z3
2.98
2
11Z.6
Z.508
126.73
1,2-dlchlorobenzene
3.38
2
147.0
3.022
142.23
1,3-dlchlorobenzene
3.48
Z
147.0
3.017
144.24
benzene chlorobenzene
I, 4-dlchlorobenzene
3.38
2
147.0
3.015
144.24
1, Z, 3-t rlchlo robenzene
4.04
Z
181.5
3.537
157.70
1,2,4-trlchlorobenzene
3.98
2
181.5
3.530
159.72
1 ,3,5-trlchlorobenzene
4.02
Z
181.5
3.017
161.75
1,2,3,4-tetrachlorobenzene
4.55
Z
215.g
4.051
173.18
0.18
I, Z, 3,5-tet rachlorobenzene
4.65
Z
215.9
3.757
175.Z0
I ,2,4, 5-tet rachlorobenzene
4.51
2
215.9
4.2Z3
175.20
5.03
Z
250.3
4.657
188.66
0.74
5.47
2
284.8
5.086
202.12
O. 93
g2.1
Z.441
129.70
0.Z5
pentachlorobenzene
he×achlorobenzene toluene
2.65
4
1,2-dimethvlbenzene
3.13
4
106.2
2.837
146.59
1,3-dlmethvlbenzene
3.18
4
106.2
2.853
150.15
3.20
4
106.2
2.832
150.15
1,4-dl methylbenzene
1,2,3-t rlmethylbenzene
3.55
4
1Z0.2
3.Z44
163.49
1 ,2,4-trl methylbenzene
3.63
4
IZ0.2
3.Z38
163.48
1, Z,3,4-tetramethylbenzene
3.98
4
134.2
3.660
180.37
4.04
4
134.2
3.655
183.94
4.61
4
162.3
4.500
210.61
1,2,3, 5-tetramethylbenzene hexamethylbenzene
0.40
354
(Table 2 cont.) bromobenzene
z.98
4
157.0
2.492
133.40
0. Z7
a
e x p e r i m e n t a l log Kow b r e f e r e n c e s f o r e x p e r i m e n t a l log Kowvalues: (1) Woodburn et a l . , a l . , 1984; (3) Doucette a n d A n d r e n , 1987; (4) Wasik et a l . , 1981
1984; (2)
Miller et
Cmolecular weight d f i r s t o r d e r m o l e c u l a r c o n n e c t i v i t y index etotal m o l e c u l a r surface area ( ~ 2 ) f r e v e r s e - p h a s e HPLC retention t i m e from Sarna et al. 1985.
Table 3.
P r e d i c t i v e E r r o r s f o r Estimation Methods A - F .
Method
na
Average~ error
Range of% E r r o r
A (Hansch& Leo) B (Nys & Rekker)
64 64
10.34 10.03
- 4 . 7 to 36.6 - 6 . 5 to 61.6
C (HPLC-RT) D (MW)
21 64
7.01 6.17
-I0.6 to 17. I -14.8 to 31.9
E (MCI)
64
4.19
- 1 6 . 8 to 11.9
F (TSA)
64
6.11
-17.3 to 18.4
aNumber of compounds evaluated. The group contribution methods (A and B) give almost identical r e s u l t s and exhibit the l a r g e s t average % e r r o r s (10.34 and 10.03~). As i l l u s t r a t e d by Figures 6a and b, the e r r o r s seem to i n c r e a s e with increasing log Kow. For example, whlle the e r r o r in estimating the log K o w v a i u e s f o r benzene is less than 1;~, the e r r o r in estimating log Kow f o r decachlorobipheny] is about 36;~. 12 11 v
9
Z8 ~
7
E_s ~
a 2 I
I
2
•
I
3
'
I
4
I
I
5
,
I
6
I
I
7
,
I
8
I
I
I
I
,
I
I
9 10 11 12
estimated leg Kow (Method A)
Figure 5.
Experimental log K o w v e r s u s estimated log Kowusing M e t h o d A .
355
12 11 v
9
Z ~ ~ E_
s 7 6 s
~
4
~
3 2 i
I
2
I
I
3
'
I
4
I
I
5
I
I
6
"
I
'
7
I
I
8
I
9
•
I
'
I
10 11
I
2
estimated log Kow (Method B)
Figure 6.
E x p e r i m e n t a l log K o w v e r s u s estimated log Kow using Method B.
The c o r r e l a t i v e methods (C t h r o u g h F) all r e q u i r e a set of compounds with e x p e r i m e n t a l l y measured log Kow v a l u e s to develop the r e g r e s s i o n equation. These had s m a l l e r average % e r r o r v a l u e s than the two group c o n t r i b u t i o n methods, p a r t i a l l y due to the fact that the compounds used in developing the c o r r e l a t i o n equation were also used in e v a l u a t i n g the method. The r e g r e s s i o n equations developed in Methods C-F are s u m m a r i z e d in Table 4. Table 4, Regression equations used in Methods C-F to c a l c u l a t e log Kow. Method
na
Regression Equation
R2
C
21
log K o w = - l . 8 7 ( R T )
D
64
log K o w = - l . 3 5 x l O
E F
64 64
log K o w = - 0 . 0 5 0 (MCt) 2 + 1,27 (MCI) - 0.085 log K o w = 0.024 (TSA) - 0.099
2 + 7.04(RT) +1.29 - 5 (MW) 2 + 0 . 0 2 1 ( M W ) + 1 . 0 3
0.944 0,932 0.967 0.946
aNumber of compounds used to develop r e g r e s s i o n equation. Method C is p r o b a b l y the most w i d e l y used c o r r e l a t i v e technique f o r e s t i m a t i n g log Kow" It r e q u i r e s no s t r u c t u r a l i n f o r m a t i o n , but the e x p e r i m e n t a l d e t e r m i n a t i o n of RPHPLCRTs can be d i f f i c u l t f o r compounds having high log Kow ( > 6 ) . Retention t i m e - l o g Kow data was a v a i l a b l e f o r o n l y 21 compounds. While previous studies ( i . e . Ellgehausen et a1.,1981; Halky and Young, 1984) have often r e p o r t e d a l i n e a r r e l a t i o n s h i p between log Kow and log RT, Figure 1 shows that the c o r r e l a t i o n obtained here is not l i n e a r . This apparent d i s c r e p a n c y is due to the wide range of log Kow v a l u e s used in this study. For lack of e x p e r i m e n t a l data, most p r e v i o u s studies did not examine the r e l a t i o n s h i p between log Kow and log RT f o r compounds with log Kow v a l u e s g r e a t e r than 5 or 6. If the compounds having log Kow g r e a t e r than 5 are removed f r o m the data set used in this s t u d y , a more l i n e a r r e l a t i o n s h i p is observed. A l s o , in some p r e v i o u s i n s t a n c e s , log
356
Kowvalues estimated by the method ofNys andRekker, were used instead of experimental values. Since group contribution methods tend to overestimate log Kowvalues for more hydrophobic compounds, a more linear relationship would be observed for the relationship between log RT and experimental versus calculated log Kowvalues. The remaining c o r r e l a t i v e methods (D-F) utilize parameters which, to varying degrees, are related to molecular size. The size of the solute molecule is considered to be a major factor in determining its s o l u b i l i t y and partitioning behavior (Langmuir, 1925; Herman, t971, 1972;Amidon et a l . , 1974). Of the estimation techniques, method E, using f i r s t order MCIs, had the smallest average ~ e r r o r ( 4 . 1 9 ) . The f i r s t - o r d e r v a l e n c e - c o r r e c t e d MCI used in this method are easily calculated and require only knowledge of the compound's s t r u c t u r e . The main disadvantages of this method are that the physical meaning of MCIs is d i f f i c u l t to conceptualize and it does not distinguish between isomers. MethodF, using total surface area, gave the second smallest average ~ e r r o r ( 6 . 1 1 ) . This method requires a more detailed knowledge of solute s t r u c t u r a l features, including van der Waals radii, bond lengths and angles, but is more conceptually meaningful than MCI. In addition, the TSA approach has several other advantages. The effects of conformation and solvent radius can be studied. The TSA of a specific portion of a molecule can also be calculated. Thus, the effect of different functional groups can be examined (Amidon et a l . , 1974). While other c o r r e l a t i v e methods were best described by a non-linear equation, the relationship between TSA and log Kow was linear. This may have significant theoretical implications and should be f u r t h e r investigated for other classes of organic compounds. S u r p r i s i n g l y , the c o r r e l a t i o n between MW and log Kow (Method D) showed an average e r r o r ( 6 . 1 7 ) v e r y s i m i l a r to that of Method F. However, molecular weight correlations do not distinguish between isomers, and the range of e r r o r s observed with Method D is much g r e a t e r than the other c o r r e l a t i v e methods. This method can be useful for providing quick estimates of log Kow, since molecular weights are readily available. A l l c o r r e l a t i o n methods require a set of compounds with "known" log Kow values and the accuracy of the method depends on the accuracy of these "known" values. The data set used here to develop and evaluate the estimation methods consisted only of compounds with log Kowvalues measured using generator-column techniques. This data set contains compounds having log Kow values which range from approximately 2 to 8.5 and is b e l i e v e d t o be the most accurate and self-consistent set of log Kowvalues available for these aromatic compounds. Several previous studies, while developing s i m i l a r c o r r e l a t i o n methods have used data sets where estimated tog Kow values are used in place of experimental values. The inaccuracy of this approach has been discussed. When using these c o r r e l a t i o n methods it is also important to consider the range of log Kowvalues employed in developing the c o r r e l a t i o n . Correlative methods are best applied to compounds within the range of standards used to develop the c o r r e l a t i o n . SUMMARY Six methods were used to predict log Kowvalues for a set of aromatic hydrocarbons of environmental i n t e r e s t , including various PCBs, PBBs, PCDFs, and PCDDs. Predicted results were compared with log Kowvalues obtained e x p e r i m e n t a l l y . The group contribution methods of Hansch and Leo (1978) and Nys and Rekker (1973)
357
gave similar results"
both tended to overestimate log Kowvalues to compounds having log
Kow > 5. Correlative methods, using parameters such as RP-HPLC retention times, molecular connectivity indices, and total surface areas to predict log Kow , were more accurate, but required a set of compounds having accurate log Kow values. Because the experimental data used in this study contained compounds with log Kow values ranging from 2 to 8.58, the c o r r e l a t i v e methods were developed and evaluated for compounds having higher log Kow values than previously reported. The method utilizing MCIs gave the smallest average e r r o r and values were easily calculated from s t r u c t u r e alone. TSA gave similar results. While more difficult to compute, TSA values maybe more conceptually meaningful. ACKNOWLEDGEMENTS This work was funded by the University of Wisconsin Sea Grant College Program under grants from the National Sea Grant Program, National Oceanographic andAtomospheric Administration, U.S. Department of Commerce (Grant NA800-AA-D-00086, Project R/MW-21 ), and from the State of Wisconsin. REFERENCES Amidon, G. L., Yalkowsky, S. H., andValvani, S. C. 1975. Solubility of nonelectrolytes in polar solvents. V. Estimation of the solubility of aliphatic monofunctional compounds using a molecular surface area approach. J. Phys. Chem. 79: 2239Z246. DeVoe, H, M i l l e r , M . M . , andWasik, S.P. 1981. Generator columns and high pressure liquid chromatography for determining aqueous solubilities and octanol-water partition coefficients of hydrophobic substances. Nat]. Bur. Std. J. Res. 86" 361366. Doucette, W.J. andAndren, A.W. 1987. Correlation of Octanol/Water Partition Coefficients and Total Molecular Surface Area for Highly Hydrophobic Aromatic Compounds. Environ. Sci. Technol. A c c e p t e d A p r i ] 9, 1987. Doucette, W.J. 1985. Measurement and estimation of octano]/water partition coefficients and aqueous solubilities for halogenated aromatic hydrocarbons. thesis. University of Wisconsin, Madison, WI.
Ph D
Ellgehausen. H., D'Hondt, C., a n d F u e r e r , R. 1981. Reversed-phase chromatography as a general method for determining octano]/water partition coefficients. Pest Sci. /2_' 219-227. Fujita, T., Iwasa, J . , andHansch, C. 1964. A new substituent constant, ~, derived from partition coefficients. J. A m e r . Chem. Soc. 86" 5175-5180. Fujita, T. 1966. The analysis of physiological activity of substituted phenols with substituted phenols with substituent constants. J. Med. Chem. 9" ?99-800.
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McDuffie, B. 1981. Estimation of octanol/water partition coefficients for organic pollutants using reverse-phaseHPLC. Chemosphere 10" 73-83. M i l l e r , M.M., Ghodbane, S., Wasik, S.P., Tewari, Y.B. and Martire, D.E. 1984. Aqueous solubilities, octanol-water partition coefficients, and entropies of melting of chlorinated benzenes and biphenyls. J. Chem. Eng. Data. 29; 184-190. Nys, G. G., and Rekker, R. F. 1974. The Concept of hydrophobic fragmental constants ( f - v a l u e s ) . II. Extension of its applicability to the calculation of lipophilicities of aromatic and heteroaromatic s t r u c t u r e s . Eur. J. Med. Chem. 9: 561-375. Nys, G. G., andRekker, R. F. 1973. Statistical analysis of a series of partition coefficients with special reference to the predictability of folding of drug molecules. The introduction of hydrophobic fragmental constants ( f v a l u e s ) . Chem. Therm. 8: 521-555. Pearlman, R. S. 1980. Molecular Surface Areas and Volumes and Their Use in S t r u c t u r e / A c t i v i t y R e ] a t i o n s h i p s . In Physical Chemical Properties of Drugs. (Ya]kowsky, S. H., Siku]a, A. A . , andValvani, S. C., eds.) Marcel Dekker, Inc., NewYork, NY. 331 pp. Sarna, L . P . , Hodge, P.E., and Webster, G.R.B. t984. Octanol-water partition coefficients of chlorinated dioxins and dibenzofurans by reversed-phase HPLC using several C 14 columns.
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0045-6535/88 $3.00 + .00 Pergamon Journals Ltd.
ESTIMATION OF OCTANOL/WATERPARTITION COEFFICIENTS: EVALUATION OF SIX METHODS FOR HIGHLY HYDROPHOBICAROMATIC HYDROCARBONS
W.J. Doucette 1 andA.W. Andren 2 1Division of Environmental Engineering, Utah State University, Logan, UT 84522
2Water Chemistry Program, University of Wisconsin, Madison, WI 53706
ABSTRACT Six methods for estimating log Kow were evaluated using a set of experimental values for 64 aromatic compounds. A l l log Kow values used in this evaluation were e x p e r i m e n t a l l y measured using a generater-column technique. This provided an accurate, s e l f - c o n s i s t e n t set of compounds having log Kow values ranging from 2.13 to 8.58. The estimation methods examined included two group contribution methods and four c o r r e l a t i v e methods utilizing molecular weight, HPLC retention time, molecular connectivity lndex, and total molecular surface area. INTRODUCTION Mathematical models are widely used to predict the fate and t r a n s p o r t of organic contaminants i n t h e environment. Most of these models require as input data, information about the physical and chemical properties of the compound(s) of i n t e r e s t . One of the most widely used properties in fate assessment modeling is the octanol/water partition coefficient (Kow). As a measure of the hydrophobic character of a compound, Kow , has been used for predicting adsorption and m o b i l i t y i n soils and sediments (Karickhoff, i981; Karickhoff et a t . , 1979; Schwarzenbach et a l . , t981), bioconcentration in fish (Kenaga, 1980), and aquatic t o x i c i t y (Konemann, 1980). Values for Kow are obtained by direct experimental measurement or are estimated uslng one of several techniques. While experimental values are p r e f e r r e d for use in environmental fate modeling and theoretical applications, estimated values are often used when experlmental values are unavailable or d i f f i c u l t to measure. For highly hydrophobic compounds (log Kow > 5), direct experimental measurement of Kow using traditional shake-flask methods ls e x t r e m e l y difMcult. Consequently, estimated values, calculated uslng group contributiontechnlques (Hansch and Leo, 1979;Nys andRekker, 1973) or from c o r r e l a t i o n s with reverse-phase HPLC retention times (Veith et a l . , 1979, McDuffie, 1981), have been used as a l t e r n a t i v e s to experimental data. However, because of the lack of r e l i a b l e experimental data, the accuracy of estimation techniques has been d i f f i c u l t to evaluate for compounds having log Kowgreater than 5.
345
346
A generator-column technique has been developed which permits the accurate experimental measurement of log Kow, well beyond the range of traditional shake-flask methods (DeVoe et a l . , 1981; Woodburn et a l . , 1984; ). This technique has been used to measure log Kow values for several classes of highly hydrophobic aromatic compounds including polychlorinated biphe'nyls (PCBs) ( M i l l e r et a l . , t984), polybrominated biphenyls (PBBs), polychlorinated dioxins (PCDDs), and polychlorinated furans (PCDFs) (Doucette, 1985, Doucette and Andren, 1987). Using only experimental values determined using a generator-column technique, an accurate and self-consistent set of log Kow values for 64 highly hydrophobic aromatic compounds was developed. This data set, consisting of compounds ranging in log Kow from 2.13 to 8.58 was used to develop and evaluate the six estimation methods described below. METHODS
OF EST IMA'T ION
METHOD A
This method uses e m p i r i c a l l y derived fragment constants ( f ) and s t r u c t u r a l factors (F) to d l r e c t l y calculate the log Kow of a compound from its s t r u c t u r e alone (Hansch and Leo, 1978). log Kow = sum of fragments ( f ) + sum of factors (F) Fragment constants and factors compiled (Hansch and Leo, 1978) for a large number of atoms and groups enable the calculation of log Kow for almost any compound. If an accurate measured value of log Kow is available for a s t r u c t u r a l l y s i m i l a r or "parent" compound, this measured value can be used to calculate the log Kow of the "derivative" by adding or subtracting the appropriate f or F values as shown below. log Kow ( d e r i v a t i v e ) = log
Kow (parent) + fragment ( f ) + factor (F)
Because the interaction terms in the parent molecule are already accounted f o r , this approach is p r e f e r r e d whenever a r e l i a b l e measured value is available (Leo, 1975). This approach is often used for substituted aromatic compounds and is equivalent to the widely used Tr-factor approach (Fujita et e l . , 1964;Fujita, 1966;Hansch et e l . , 1968; and Hansch and Leo, 1979). Recently, computerized versions of Hansch and Leo's method have been developed. Values used in this study, shown in Table 1, were calculated using a program developed by Leo (1985). Table I. Experimentaland predicted log Kowvalues for 65 aromatic compounds.
Compound blphenyl Z-chloroblphenyl 3-chloroblphenyl
1ogKow 1ogKow IogKow 1ogKow IogKow IogKow IogKow (e×p) (Meth A) (Meth B) (Meth C) (Meth D) (Meth E) (Meth F) 3,8g 4.03 3,79 3,69 3.88 4,35 4.52 4.38 4.74 4.56 3.g2 4.q4 4.81 4.90 4.58 4.74 4.56 4.44 4.80 4.g4
347 Table I
(cont.)
4-chloroblphenyl
4.49
4.74
4.56
-
4.44
4.80
4.94
4 , 4 ' - c l l c h l o r oblphenyl
5.53
5.46
5.32
-
5.10
5m23
5m36
3,4-dlchloroblphenyl
5,29
5.46
5.52
-
5. t0
5.24
5.31
2, Z'- dtchlor oblphenyl
4.90
5.46
5.32
-
5.10
5.24
5.28
2,4'-dlchloroblphenyl
5, 14
5.46
5.32
-
5, 10
5.24
5.32
2,5-dlchloroblphenyt
5.16
5.46
5.52
-
5.10
5.24
5.32
2,6-dlchloroblphenyl
4.93
5.46
5.23
5.10
5.24
5.28
2,2',5-trlchloroblphenyl
5.60
6.16
6.00
5.44
5,65
5.71
2,4,5-trlchloroblphenyl
5.81
6.17
5.99
5.47
5.44
5.65
5.69
2 , 4 ' , 5-t rlchloroblphenyl
5.79
6.17
6.00
-
5,44
5.64
5,74
2 , 4 , 6 - t rlchloroblphenyl
5.57
6.17
5.99
-
5.44
5.65
5.71
2,3, 4,5-tetrachloroblphenyl
5.72
6.88
6.74
-
5.89
6.04
6.02
2 , 2 ' , 4', 5, - t e t r a c hloroblphenyl
5.75
6.88
6.67
-
5.89
6.03
6.13
2 , 2 ' , 4 , 5 , 5 ' - p e n t achloroblphenyl
6.50
7.60
7.43
5.88
6.32
6.39
6.50
2,3,4,5,6-pentachloroblphenyl
6.30
7.60
7.43
-
6.32
6.40
6.36
,6,6'-hexachloroblphenyl
6,81
8.31
8,18
-
6.71
6,73
6.80
Z, 2', 4,4', 5 , 5 ' - h e x a c h l o r o b l p h e n y l
2,2,3,3
6.90
8.31
8.18
6.46
6.71
6.73
6.87
2 , 2 ' , 3, 3', 4 , 4 ' - h e x a c h l o r o b l p h e n y l
6.98
8.31
8.16
6.71
6.73
6.76 6.69
2,2", 4 , 4 ' , 6 , 6 ' - h e x a chIoroblphenyl
7.55
8.31
6.16
6.71
6.73
2 , 2 ' , 3,3', 4 , 4 ' , 6-hepta c111oroblphenyl
6.68
9.03
8.94
7.06
7.04
7.16
2 , 2 ' , 3 , 3 ' , 5, 5', 6 , 6 ' - o c t a c h l o r o b l p h e n y l
7.12
9.73
9.69
-
7.39
7.34
7.54
2 , 2 ' , 3 , 3 ' , 4 , 5 , 5 ' , 6 , 6 -nonochloroblphenyl
8.16
10.45
10.44
-
7.68
7.60
7.67 8.20
decachloroblphenyl
8.20
I 1,16
I 1.20
7.73
7,95
7.85
2-bromoblphenyl
4.59
4.89
4.83
-
5.10
5.14
5.05
3-bromoblphenyl
4.85
4.89
4.83
-
5.10
5.14
5.10
4-bromoblphenyl
4.96
4.89
4.83
-
5.10
5.14
5.10
4,4'-dlbromoblphenyl
5,72
5.75
5.85
-
6.14
5,81
5.68
2,2', 4,5,5'-pentabromoblphenyl
7.10
8.06
8.76
8.27
7,55
7.25
decabromoblphenyl
6.58
10.42
13.87
8.46
8.89
7,10
dlbenz o - p - d l o x l n
4.37
4.65
4.14
4.18
4.37
4.70
4.35
2-c h]o r odlbenz o - p - d l o x l n
4,9,1
5.47
4.89
4.98
4.89
5.1'~
4.79
I, 2 , 3 , 4 - t e t r a c h l o r o d l b e n z o - p - d l o x l n
6.20
7.70
7.12
6.86
6,26
6.08
5.91
oct a c hlo rdlbenz o - p - d t o x l n
7.59
I0.56
10.09
7.83
7.65
7.53
7.46
dlbenzofuran
4.31
4.12
4.04
3.66
4.11
4,57
4.13
2 , 8 - d t c h l o rdlbenzoi'uran
5.44
5.65
5.53
5.12
4.92
5.42
5.01
oct achlorocllbenzofuran
7.97
9.96
9.99
7.90
7.51
7.32
7.05
-
4.11
4.71
5.01
4.33
5.06
5.50
2.50
2.56
2.28
2.52
4-methylblphenyl
4.63
4.68
4.33
4 , 4 ' - d l met hv1 blphenvI
5.09
5.33
4.87
benzene
2.13
2.14
2.09
chlorobenzene
2.98
2.84
3.07
3.18
2.82
2.94
1, Z-dlchlorobenzene
3.38
3.57
3.59
-
3.77
3.35
3.31
I ,3-dlchlorobenzene
3.48
3.57
3.59
-
3.77
3.34
3.36
I , 4-dlchlorobenzene
3.36
3.57
3.59
-
3.77
3.34
3,36
I , 2 , 3 - t rlchlorobenzene
4.04
4.28
4.27
-
4.32
3.85
3.69
1 , 2 , 4 - t rlchlorobenzene
3.98
4.28
4.27
-
4.32
3.85
3.73
1,3,5-trlchlorobenzene
4.02
4.28
4.27
-
4.32
3.34
3.78
348
Table 1 (cont.) 1,2,3,4-tetrachlorobenzene
4.55
4.gg
5.02
-
4.65
4.53
4.06
1,2,3,5-tetrachlorobenzene
4.65
4.99
5.02
-
4.85
4.06
4.11 4.11
1,2,4,5-tetrachlorobenzene
4.51
4.99
5.02
-
4.85
4.49
pentachlorobenzene
5.03
5.71
5.77
5.47
5.34
4.86
4.43
he×achlorobenzene
5.47
6.q2
6.53
6.22
5.60
5.22
4.75
toluene
2.65
2.60
2.60
2.93
2.81
2.75
3.01
I ,2-dlmethylbenzene
3.13
3.14
3.14
-
3.06
3.16
3.42
I ,3-dimethylbenzene
3.18
3.14
3.14
-
3.06
3.18
3.50
I ,4-dlmethylbenzene
3.20
3.14
3.14
-
3.06
3.16
3.50
I, 2,3-t rl methylbenzene
3.55
3.58
3.58
3.81
3.51
3.57
3.62
I, 2,4-t ri methyl benzene
3.63
3.58
3.58
-
3.51
3.56
3.82
I, 2,3,4-tet ra methylbenzene
3.98
4.02
4.02
-
3.55
3.97
4.23
1.2,3. S-tetra methylbenzene
4.04
4.02
4.02
-
3.55
3.g6
4.52
he×amethylbenzene
4.61
5.16
5.16
-
4.02
4.75
4.96
bromobenzene
2.98
3.00
3.07
3.05
3.93
2.81
3.10
METHOD B This m e t h o d a l s o c a l c u l a t e s
log Kow
values directly
from
the compound's structure
using t h e a p p r o p r i a t e h y d r o p h o b i c f r a g m e n t c o n s t a n t s o r f - v a l u e s . The f - v a l u e s a r e d e r i v e d f r o m a s t a t i s t i c a l a n a l y s i s of a l a r g e data base of e x p e r i m e n t a l l o g Kow v a l u e s and a r e d e f i n e d as t h e l i p o p h i l i c c o n t r i b u t o r t o t a l l i p o p h i l i c i t y (Nys and R e k k e r , 1 9 7 5 ) .
of a s u b s t i t u e n t p a r t of a s t r u c t u r e to t h e C a l c u l a t i o n of log Kow is b a s e d on t h e
equation"
logKo~= ~ a nf i=l where
an is
a numerical
factor
indicating
the
incidence
of
a given
fragment
in
the
structure. A c o m p i l a t i o n of f - v a l u e s (Nys and R e k k e r , 1973, 1974) p e r m i t s t h e c a l c u l a t i o n of l o g Kow f o r m o s t c o m p o u n d s . The l o g Kow v a l u e s c a l c u l a t e d by t h i s m e t h o d a r e l i s t e d in T a b l e 1. METHOD C This m e t h o d is b a s e d on t h e c o r r e l a t i o n its retention time (RT) determined chromatography (RP-HPLC). In t h i s
b e t w e e n t h e log Kow v a l u e of a c o m p o u n d and
by r e v e r s e - p h a s e high technique, c o m p o u n d s of
performance liquid k n o w n l o g Kow a r e
c o r r e l a t e d to t h e i r RP-HPLC RTs and a r e g r e s s i o n e q u a t i o n is o b t a i n e d . RTs of c o m p o u n d s w i t h u n k n o w n Kow v a l u e s a r e d e t e r m i n e d and t h e i r log Kow v a l u e s a r e c a l c u l a t e d f r o m t h e regression equation. The RP-HPLCRTs used in t h i s s t u d y w e r e d e t e r m i n e d b y S a r n a et a l . ( 1 9 8 4 ) on a W a t e r s uBondpak C18 c o l u m n using a m o b i l e p h a s e of m e t h a n o l - w a t e r ( 8 5 ; 1 5 ) at a f l o w r a t e of 1.0 m L / m i n , c o r r e c t e d f o r t h e v o i d t i m e of t h e s y s t e m , and a d j u s t e d r e l a t i v e t o t h e c o r r e c t e d retention time for catechol. A
plot
of
experimental
l o g Kow vs
log
corrected
RT was
made
for
21
aromatic
349
hydrocarbons (Figure 1), including several PCBs, PCDFs, and PCDDs. Regression analysis yielded the equation: log K o w = - 1 . 8 ? O (log RT) Z+ 7.04 (log RT) + 1.289
(1)
(n = 21, R2 = 0.994) This expresslonwas used to c a l c u ] a t e t h e predicted log Kowvalues shown in Table 1.
10
8
/¢X.o
cm
s @
E
~4
0.0
0,5 HPLC
1.0
Retention
Time
1.5
2.0
( m i n ) ( M e t h o d C)
Figure I. Experimental log Kow versus log corrected HPLC retention time for 21 aromatic compounds, Retention time values determined by Sarna e t a ] . , 1984. METHOD D This method is based on the correlation between the molecular weight of a compound and its experimental log Kowva]ue. The relationship between MW and experimental log Kow for 64 aromatic compounds (shown in Figure 2) was found to be best represented by the following equation: log K o w = - l . 3 5
x 10-5 (MW) Z + 0 . 0 2 1 (MW) + 1.029
(2)
(n = 64, R2 = 0.938)
10
~8 I i
[]
"= []
o
~6 E
~=
4
200
400
Molecular
Figure 2.
600
800
1000
Weight
Experimental log Kowversus Molecular weight for 64 aromatic compounds.
350
Eliminating the two apparent high MW o u t l i e r s (penta and decabromobiphenyl) observed in Figure 2, did not s i g n i f i c a n t l y change the r e g r e s s i o n r e s u l t s as s h o w n i n equation ( 3 ) . log K o w = - I . O 8 E - 5
( M W ) 2 + O.OZO0 ( M W ) + 1.106
(3)
( n = 62 R Z = 0.943)
Equation (2) was used to c a l c u l a t e the log K o w v a l u e s in Table 1. METHOD E
This method is based on a c o r r e l a t i o n between e x p e r i m e n t a l log Kow values and m o l e c u l a r c o n n e c t i v i t y indices (MCI) calculated by the procedure of Kier and Hall (1980). To c a l c u l a t e the MCIs, the s t r u c t u r e of the molecule is drawn out in the hydrogen atom suppressed s k e l e t a l f o r m .
A simple c o n n e c t i v i t y v a l u e ( ~ u )
is then assigned to each
atom of the m o l e c u l a r skeleton. This value is expressed as 11'u - Z maximum valence and h is the number of hydrogens on the atom.
Ii, where Z is the
The f i r s t - o r d e r v a l e n c e - c o r r e c t e d m o l e c u l a r c o n n e c t i v i t y l n d e x ( 1 X V ) is computed as: IxV -- ~ ( ' ~ i
~j)
I
where
It I and'll'j
are the v a l e n c e - c o r r e c t e d connectivity values f o r the adjacent atoms i
and j and n is the number of bonds within the molecule. Additional i n f o r m a t i o n is given b y K i e r and Hall (1976, 1986). Using the e x p e r i m e n t a l log K o w v a l u e s compiled in Table 2 the r e l a t i o n s h i p between MCt and log Kow (shown in Figure 3) was best represented by the r e g r e s s i o n equation: log K o w = - O . 0 4 9 9 (MCI)E+ 1.272 ( M C I ) - 0.0853
(4)
(n= 64, R2 = 0.964) The log K o w v a l u e s calculated using this expression are listed in Table 1.
10 o
v
8
o i
e=
6
E o. ~=
[].
4
2
4
6
8
10
12
Molecular Connectivity Index (MCI)
Figure 3. E x p e r i m e n t a l tog Kow v e r s u s f i r s t o r d e r M o l e c u l a r Connectivity Indexes f o r 64 a r o m a t i c compounds.
351
Method F
This method i n v o l v e s c o r r e l a t i o n
of e x p e r i m e n t a l
log Kow v a l u e s wlth t o t a l
surface
area (TSA) v a l u e s c a l c u l a t e d using a c o m p u t e r p r o g r a m obtained f r o m the Quantum C h e m i s t r y P r o g r a m Exchange, C h e m l s t r y D e p t . , Indiana U n i v e r s i t y , B l o o m i n g t o n , Indiana, and adapted f o r use on a S p e r r y 1100 m a i n f r a m e c o m p u t e r by Loux ( 1 9 8 2 ) . In this p r o g r a m , each atom of a m o l e c u l e is r e p r e s e n t e d by a sphere c e n t e r e d at the e q u i l i b r i u m position of the n u c l e u s . The radius of the sphere is equal to that of the van der Waal r a d i u s . The p r o g r a m c a l c u l a t e s the s u r f a c e area r e p r e s e n t e d by the i n t e r s e c t i o n of all the spheres in the m o l e c u l e . A detailed d e s c r i p t i o n of the m o l e c u l a r s u r f a c e area c a l c u l a t i o n method is provided by P e a r l m a n ( 1 9 8 0 ) . Standard g e o m e t r y , s t a n d a r d i n t e r a t o m i c bond l e n g t h s , and bond angles, supplemented with X-Ray d i f f r a c t i o n data, were used in c o n s t r u c t i n g the m o l e c u l a r s t r u c t u r a l d e t a i l s . The s u b s t i t u t e d benzenes, d l b e n z o - p - d i o x i n s , and d i b e n z o f u r a n s were assumed to have a planar conformation. For the s u b s t i t u t e d b i p h e n y l s , a n o n - p l a n a r c o n f o r m a t i o n was used which gave a maximum c a l c u l a t e d TSA. The methyl groups were a p p r o x i m a t e d as a single sphere of radius Z . 0 A as suggested by Valvanl et al. ( 1 9 8 Z ) . It was also possible to c a l c u l a t e the TSA of the solute m o l e c u l e a f t e r the addition of a suitable solvent radius. C a l c u l a t i o n showed, h o w e v e r , that the addition of a s o l v e n t radius f o r w a t e r did not s i g n i f i c a n t l y i m p r o v e the c o r r e l a t i o n between TSA and log Kow (Doucette, 1985). Thus, TSA v a l u e s r e p o r t e d in this study do not i n c l u d e the s o l v e n t radius c o n t r i b u t i o n . Unlike the p r e v i o u s c o r r e l a t i v e methods presented above, r e g r e s s i o n a n a l y s i s showed that the r e l a t i o n s h i p between TSA and log Kow (shown in Figure 4) is best e x p r e s s e d as a l i n e a r f u n c t i o n where: log Kow= 0.0238 ( T S A ) - 0 . 0 9 9
(5)
(n = 64, R2= 0 . 9 4 3 ) This e x p r e s s i o n was used to c a l c u l a t e the p r e d i c t e d log K o w v a l u e s shown in Table 1.
10
~:
!
8,
O
•~
6 ¸
E 4
g oo
i
i
200
300
400
T o t a l S u r f a c e A r e a (TSA)
Figure 4. E x p e r i m e n t a l log K o w v e r s u s c a l c u l a t e d Total Surface A r e a (/~2).
352
Results and Discussion Comparison and E v a l u a t i o n of the Methods Methods
A
through
F were
used
to
predict
log
Kow v a l u e s
for
the
aromatic
h y d r o c a r b o n s tisted in Table 1. T a b l e 2 l i s ts theHPLC r e t e n t i o n t i m e s , m o l e c u l a r weights, f i r s t o r d e r m o l e c u l a r c o n n e c t i v i t y indexes, and c a l c u l a t e d t o t a l s u r f a c e areas used to develop the c o r r e l a t i v e methods C-F. A v e r a g e a b s o l u t e percent e r r o r and range of e r r o r f o r each method are given in Table 3. The p e r c ent e r r o r is defined by the f o l l o w i n g expression: % e r r o r = { ( p r e d log K o w - exp log K o w ) / e x p log Kow] x 100 (6) Thus, p o s i t i v e ~ e r r o r v a l u e s indicate the p r e d i c t e d is g r e a t e r than the e x p e r i m e n t a l v a l u e , wh i l e negative v a l u e s s h o w t h e opposite. Table 2. M o l e c u l a r weights (MW), M o l e c u l a r Connectivity Index (MCl), Total Surface A r e a , and RP-HPLC r e t e n t i o n t i m e s used to develop c o r r e l a t i o n s f o r Method C-F.
Comoound
loa Kowa Perb
MWc
MCl d
TSA e
HPLC-RTf
biphenyl
3.8g
I
154.2
4.071
19Z.34
0.38
Z-chlorobiphenyl
4.38
I
188.7
4.5g0
Z08.33
0.4Z
3-chloroblphenyl
4.58
1
188.7
4.584
z0g.87
4-chloroblphenyl
4,4g
1
188.7
4.584
zog.87
4 4'-dlchloroblphenyl
5.53
1
Z33.1
5.097
Z27.40
3 4-dlchloroblphenyl
5.zg
I
233.1
5.103
225.41
Z 2'-dlchloroblphenyl
4.90
1
Z33.1
5.103
ZZ4.3Z
Z 4'-dichloroblphenyl
5.14
1
Z33.1
5,103
Z25.86
Z 5-dlchloroblphenyl
5.16
Z
Z33.1
5.10g
ZZ5.85
Z 6-dlchloroblphenyl
4.g3
Z
233.1
5.10g
ZZ4.3Z
Z,Z',5-trlchloroblphenyl
5.60
1
Z57.5
5.6ZI
Z41.84
Z,4,5-trlchloroblphenyl
5.81
1
Z57.5
5.6ZI
Z41.3g
Z,4',5-trlchloroblphenyl
5.7g
1
Z57.5
5.615
Z43.3g
Z,4,6-trlchloroblphenyl
5.57
3
Z57.5
5.6Z1
Z41.84
Z,3,4,5-tetrachloroblphenyl
5.7Z
Z
zgz.o
6.146
Z54.g5
Z,Z',4',5,-tetrachlorobiphenyl
5.73
Z
zgz.o
6.135
z5g,41
Z,Z',4,5,5'-pentachloroblphenyl
6.50
3
3Z6.4
6.652
Z74.95
Z,3,4,5,6-pentachloroblphenyt
6.30
Z
326.4
6.670
Z68.g5
Z,Z',3,3',6,6'-hexachloroblphenyl
6.81
3
360.9
7.183
Z87.38
Z,Z',4,4',5,5'-hexachloroblphenyl
6.go
3
360.g
7.171
Z90.50
Z,Z',3,3',4,4'-hexachlorobipheny]
6.g8
Z
360.g
7.177
Z86.4g
Z,Z',4,q',6,6'-hexachloroblphenyl
7.55
Z
360.g
7.177
Zgl.36
Z,Z',3,3',4,4',6-heptachloroblphenyl
6.68
Z
3g5.3
7.6g6
30Z.48
Z,Z',3,3',5,5',6,6'-octachlorobtphenyl
7.1Z
5
4zg.8
8.ZZ0
318.47
Z,Z',3,3',4,5,5',6,6'-nonochloroblphenyl
8,16
Z
464,2
8.740
33Z.02
O. 74
0.8g
O. 84
I .00
353 (Table Z cont. ) decachlorobiphenyl
8.20
5
4g8.7
g.270
345.59
Z-bromoblphenyl
4.59
5
233.1
4.g80
214.53
3-bromobiphenyl
4.85
5
Z33.1
4.982
216.55
4-bromoblphenyl
4.g6
5
Z33.1
4.982
Z16.55
4,4'-dibromoblphenyl
5.72
5
312.0
5.833
240.83 306.13
1 .
57
I
Z,Z',4,5,5'-pentabromobiphenyl
7. IO
5
548.7
8.643
decabromoblphenyl
8.58
5
943.2
13.250 zgg. 86
dibenzo-p-dlo×In
4.37
5
184.2
4.471
185.55
0.47
Z- c hlorodibe nzo-p-dioxln
4.94
5
218.6
4.980
203.61
O. 63
1, Z, 3,4-tet rachlordlbenzo-p-dlo×In
6.Z0
5
322.0
6.Z01
250.25
1.13
oct achl or dibenzo-p-dio×in
7.59
5
459.8
8.597
314.94
1.67
dlbenzofuran
4.31
5
168.2
4.313
176.25
0.41
Z, 8-dlchlordibenzofur an
5.44
5
Z21.I
5.3Z9
21Z.76
O. 66
oct achlor odlbenzofur an
7.97
5
443.8
8.189
Z97.96
1.80
4- m ethylblphenyl
4.63
5
168.2
4.482
212.88
4,4'-dimethylblphenyl
5.09
5
182.2
4.893
Z33.36
Z.13
Z
78.2
Z.O00
lOg.Z3
2.98
2
11Z.6
Z.508
126.73
1,2-dlchlorobenzene
3.38
2
147.0
3.022
142.23
1,3-dlchlorobenzene
3.48
Z
147.0
3.017
144.24
benzene chlorobenzene
I, 4-dlchlorobenzene
3.38
2
147.0
3.015
144.24
1, Z, 3-t rlchlo robenzene
4.04
Z
181.5
3.537
157.70
1,2,4-trlchlorobenzene
3.98
2
181.5
3.530
159.72
1 ,3,5-trlchlorobenzene
4.02
Z
181.5
3.017
161.75
1,2,3,4-tetrachlorobenzene
4.55
Z
215.g
4.051
173.18
0.18
I, Z, 3,5-tet rachlorobenzene
4.65
Z
215.9
3.757
175.Z0
I ,2,4, 5-tet rachlorobenzene
4.51
2
215.9
4.2Z3
175.20
5.03
Z
250.3
4.657
188.66
0.74
5.47
2
284.8
5.086
202.12
O. 93
g2.1
Z.441
129.70
0.Z5
pentachlorobenzene
he×achlorobenzene toluene
2.65
4
1,2-dimethvlbenzene
3.13
4
106.2
2.837
146.59
1,3-dlmethvlbenzene
3.18
4
106.2
2.853
150.15
3.20
4
106.2
2.832
150.15
1,4-dl methylbenzene
1,2,3-t rlmethylbenzene
3.55
4
1Z0.2
3.Z44
163.49
1 ,2,4-trl methylbenzene
3.63
4
IZ0.2
3.Z38
163.48
1, Z,3,4-tetramethylbenzene
3.98
4
134.2
3.660
180.37
4.04
4
134.2
3.655
183.94
4.61
4
162.3
4.500
210.61
1,2,3, 5-tetramethylbenzene hexamethylbenzene
0.40
354
(Table 2 cont.) bromobenzene
z.98
4
157.0
2.492
133.40
0. Z7
a
e x p e r i m e n t a l log Kow b r e f e r e n c e s f o r e x p e r i m e n t a l log Kowvalues: (1) Woodburn et a l . , a l . , 1984; (3) Doucette a n d A n d r e n , 1987; (4) Wasik et a l . , 1981
1984; (2)
Miller et
Cmolecular weight d f i r s t o r d e r m o l e c u l a r c o n n e c t i v i t y index etotal m o l e c u l a r surface area ( ~ 2 ) f r e v e r s e - p h a s e HPLC retention t i m e from Sarna et al. 1985.
Table 3.
P r e d i c t i v e E r r o r s f o r Estimation Methods A - F .
Method
na
Average~ error
Range of% E r r o r
A (Hansch& Leo) B (Nys & Rekker)
64 64
10.34 10.03
- 4 . 7 to 36.6 - 6 . 5 to 61.6
C (HPLC-RT) D (MW)
21 64
7.01 6.17
-I0.6 to 17. I -14.8 to 31.9
E (MCI)
64
4.19
- 1 6 . 8 to 11.9
F (TSA)
64
6.11
-17.3 to 18.4
aNumber of compounds evaluated. The group contribution methods (A and B) give almost identical r e s u l t s and exhibit the l a r g e s t average % e r r o r s (10.34 and 10.03~). As i l l u s t r a t e d by Figures 6a and b, the e r r o r s seem to i n c r e a s e with increasing log Kow. For example, whlle the e r r o r in estimating the log K o w v a i u e s f o r benzene is less than 1;~, the e r r o r in estimating log Kow f o r decachlorobipheny] is about 36;~. 12 11 v
9
Z8 ~
7
E_s ~
a 2 I
I
2
•
I
3
'
I
4
I
I
5
,
I
6
I
I
7
,
I
8
I
I
I
I
,
I
I
9 10 11 12
estimated leg Kow (Method A)
Figure 5.
Experimental log K o w v e r s u s estimated log Kowusing M e t h o d A .
355
12 11 v
9
Z ~ ~ E_
s 7 6 s
~
4
~
3 2 i
I
2
I
I
3
'
I
4
I
I
5
I
I
6
"
I
'
7
I
I
8
I
9
•
I
'
I
10 11
I
2
estimated log Kow (Method B)
Figure 6.
E x p e r i m e n t a l log K o w v e r s u s estimated log Kow using Method B.
The c o r r e l a t i v e methods (C t h r o u g h F) all r e q u i r e a set of compounds with e x p e r i m e n t a l l y measured log Kow v a l u e s to develop the r e g r e s s i o n equation. These had s m a l l e r average % e r r o r v a l u e s than the two group c o n t r i b u t i o n methods, p a r t i a l l y due to the fact that the compounds used in developing the c o r r e l a t i o n equation were also used in e v a l u a t i n g the method. The r e g r e s s i o n equations developed in Methods C-F are s u m m a r i z e d in Table 4. Table 4, Regression equations used in Methods C-F to c a l c u l a t e log Kow. Method
na
Regression Equation
R2
C
21
log K o w = - l . 8 7 ( R T )
D
64
log K o w = - l . 3 5 x l O
E F
64 64
log K o w = - 0 . 0 5 0 (MCt) 2 + 1,27 (MCI) - 0.085 log K o w = 0.024 (TSA) - 0.099
2 + 7.04(RT) +1.29 - 5 (MW) 2 + 0 . 0 2 1 ( M W ) + 1 . 0 3
0.944 0,932 0.967 0.946
aNumber of compounds used to develop r e g r e s s i o n equation. Method C is p r o b a b l y the most w i d e l y used c o r r e l a t i v e technique f o r e s t i m a t i n g log Kow" It r e q u i r e s no s t r u c t u r a l i n f o r m a t i o n , but the e x p e r i m e n t a l d e t e r m i n a t i o n of RPHPLCRTs can be d i f f i c u l t f o r compounds having high log Kow ( > 6 ) . Retention t i m e - l o g Kow data was a v a i l a b l e f o r o n l y 21 compounds. While previous studies ( i . e . Ellgehausen et a1.,1981; Halky and Young, 1984) have often r e p o r t e d a l i n e a r r e l a t i o n s h i p between log Kow and log RT, Figure 1 shows that the c o r r e l a t i o n obtained here is not l i n e a r . This apparent d i s c r e p a n c y is due to the wide range of log Kow v a l u e s used in this study. For lack of e x p e r i m e n t a l data, most p r e v i o u s studies did not examine the r e l a t i o n s h i p between log Kow and log RT f o r compounds with log Kow v a l u e s g r e a t e r than 5 or 6. If the compounds having log Kow g r e a t e r than 5 are removed f r o m the data set used in this s t u d y , a more l i n e a r r e l a t i o n s h i p is observed. A l s o , in some p r e v i o u s i n s t a n c e s , log
356
Kowvalues estimated by the method ofNys andRekker, were used instead of experimental values. Since group contribution methods tend to overestimate log Kowvalues for more hydrophobic compounds, a more linear relationship would be observed for the relationship between log RT and experimental versus calculated log Kowvalues. The remaining c o r r e l a t i v e methods (D-F) utilize parameters which, to varying degrees, are related to molecular size. The size of the solute molecule is considered to be a major factor in determining its s o l u b i l i t y and partitioning behavior (Langmuir, 1925; Herman, t971, 1972;Amidon et a l . , 1974). Of the estimation techniques, method E, using f i r s t order MCIs, had the smallest average ~ e r r o r ( 4 . 1 9 ) . The f i r s t - o r d e r v a l e n c e - c o r r e c t e d MCI used in this method are easily calculated and require only knowledge of the compound's s t r u c t u r e . The main disadvantages of this method are that the physical meaning of MCIs is d i f f i c u l t to conceptualize and it does not distinguish between isomers. MethodF, using total surface area, gave the second smallest average ~ e r r o r ( 6 . 1 1 ) . This method requires a more detailed knowledge of solute s t r u c t u r a l features, including van der Waals radii, bond lengths and angles, but is more conceptually meaningful than MCI. In addition, the TSA approach has several other advantages. The effects of conformation and solvent radius can be studied. The TSA of a specific portion of a molecule can also be calculated. Thus, the effect of different functional groups can be examined (Amidon et a l . , 1974). While other c o r r e l a t i v e methods were best described by a non-linear equation, the relationship between TSA and log Kow was linear. This may have significant theoretical implications and should be f u r t h e r investigated for other classes of organic compounds. S u r p r i s i n g l y , the c o r r e l a t i o n between MW and log Kow (Method D) showed an average e r r o r ( 6 . 1 7 ) v e r y s i m i l a r to that of Method F. However, molecular weight correlations do not distinguish between isomers, and the range of e r r o r s observed with Method D is much g r e a t e r than the other c o r r e l a t i v e methods. This method can be useful for providing quick estimates of log Kow, since molecular weights are readily available. A l l c o r r e l a t i o n methods require a set of compounds with "known" log Kow values and the accuracy of the method depends on the accuracy of these "known" values. The data set used here to develop and evaluate the estimation methods consisted only of compounds with log Kowvalues measured using generator-column techniques. This data set contains compounds having log Kow values which range from approximately 2 to 8.5 and is b e l i e v e d t o be the most accurate and self-consistent set of log Kowvalues available for these aromatic compounds. Several previous studies, while developing s i m i l a r c o r r e l a t i o n methods have used data sets where estimated tog Kow values are used in place of experimental values. The inaccuracy of this approach has been discussed. When using these c o r r e l a t i o n methods it is also important to consider the range of log Kowvalues employed in developing the c o r r e l a t i o n . Correlative methods are best applied to compounds within the range of standards used to develop the c o r r e l a t i o n . SUMMARY Six methods were used to predict log Kowvalues for a set of aromatic hydrocarbons of environmental i n t e r e s t , including various PCBs, PBBs, PCDFs, and PCDDs. Predicted results were compared with log Kowvalues obtained e x p e r i m e n t a l l y . The group contribution methods of Hansch and Leo (1978) and Nys and Rekker (1973)
357
gave similar results"
both tended to overestimate log Kowvalues to compounds having log
Kow > 5. Correlative methods, using parameters such as RP-HPLC retention times, molecular connectivity indices, and total surface areas to predict log Kow , were more accurate, but required a set of compounds having accurate log Kow values. Because the experimental data used in this study contained compounds with log Kow values ranging from 2 to 8.58, the c o r r e l a t i v e methods were developed and evaluated for compounds having higher log Kow values than previously reported. The method utilizing MCIs gave the smallest average e r r o r and values were easily calculated from s t r u c t u r e alone. TSA gave similar results. While more difficult to compute, TSA values maybe more conceptually meaningful. ACKNOWLEDGEMENTS This work was funded by the University of Wisconsin Sea Grant College Program under grants from the National Sea Grant Program, National Oceanographic andAtomospheric Administration, U.S. Department of Commerce (Grant NA800-AA-D-00086, Project R/MW-21 ), and from the State of Wisconsin. REFERENCES Amidon, G. L., Yalkowsky, S. H., andValvani, S. C. 1975. Solubility of nonelectrolytes in polar solvents. V. Estimation of the solubility of aliphatic monofunctional compounds using a molecular surface area approach. J. Phys. Chem. 79: 2239Z246. DeVoe, H, M i l l e r , M . M . , andWasik, S.P. 1981. Generator columns and high pressure liquid chromatography for determining aqueous solubilities and octanol-water partition coefficients of hydrophobic substances. Nat]. Bur. Std. J. Res. 86" 361366. Doucette, W.J. andAndren, A.W. 1987. Correlation of Octanol/Water Partition Coefficients and Total Molecular Surface Area for Highly Hydrophobic Aromatic Compounds. Environ. Sci. Technol. A c c e p t e d A p r i ] 9, 1987. Doucette, W.J. 1985. Measurement and estimation of octano]/water partition coefficients and aqueous solubilities for halogenated aromatic hydrocarbons. thesis. University of Wisconsin, Madison, WI.
Ph D
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359
McDuffie, B. 1981. Estimation of octanol/water partition coefficients for organic pollutants using reverse-phaseHPLC. Chemosphere 10" 73-83. M i l l e r , M.M., Ghodbane, S., Wasik, S.P., Tewari, Y.B. and Martire, D.E. 1984. Aqueous solubilities, octanol-water partition coefficients, and entropies of melting of chlorinated benzenes and biphenyls. J. Chem. Eng. Data. 29; 184-190. Nys, G. G., and Rekker, R. F. 1974. The Concept of hydrophobic fragmental constants ( f - v a l u e s ) . II. Extension of its applicability to the calculation of lipophilicities of aromatic and heteroaromatic s t r u c t u r e s . Eur. J. Med. Chem. 9: 561-375. Nys, G. G., andRekker, R. F. 1973. Statistical analysis of a series of partition coefficients with special reference to the predictability of folding of drug molecules. The introduction of hydrophobic fragmental constants ( f v a l u e s ) . Chem. Therm. 8: 521-555. Pearlman, R. S. 1980. Molecular Surface Areas and Volumes and Their Use in S t r u c t u r e / A c t i v i t y R e ] a t i o n s h i p s . In Physical Chemical Properties of Drugs. (Ya]kowsky, S. H., Siku]a, A. A . , andValvani, S. C., eds.) Marcel Dekker, Inc., NewYork, NY. 331 pp. Sarna, L . P . , Hodge, P.E., and Webster, G.R.B. t984. Octanol-water partition coefficients of chlorinated dioxins and dibenzofurans by reversed-phase HPLC using several C 14 columns.
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