War. Res. Vol. 31, No. 6, pp.

1471-1481, 1997
~ Pergamon © 1997 ElsevierScienceLtd
All rights reserved. Printed in Great Britain
PII:S0043-1354(96)00395-8 0043-1354/97 $17.00 + 0.00

PREDICTING HENRY'S LAW CONSTANT A N D THE EFFECT

OF' TEMPERATURE ON HENRY'S LAW CONSTANT

N. N I R M A L A K H A N D A N @~*, R. A. B R E N N A N ~ and R. E. S P E E C E @~
tCivil, Agricultural and Geological Engineering Department, New Mexico State University, NM 88003,
U.S.A. and 2Civil and Environmental Engineering Department, Vanderbilt University, TN 37235, U.S.A.

(First received January 1996; accepted in revised form November 1996)

Abstract--Air-water partitioning data for a wide range of organic chemicals are used to validate a three-
variable quantitative structure-activity relationship (QSAR) model for Henry's law constant, H. The
predictive ability of the basic model, developed from a training set of 180 chemicals, is now demonstrated
on 105 new chemicals of similar molecular structure. This basic model is then extended to cover additional
chemicals ef diverse molecular features. The predictive ability of the final model is demonstrated on a
new testing set of 70 chemicals featuring multiple structural components and polyfunctional groups.
Spanning over 10 orders of magnitude, the log H values predicted by the QSAR model for 462 compounds
are found to agree with the reported experimental values with r 2 > 0.95 at p = 0.0005. A new QSAR model
for estimating H as a function of temperature, T, is also proposed. The predictive ability of this H - T
model is demonstrated using experimental data for 18 chemicals over a temperature range of 1(~55~C.
© 1997 El,;evier Science Ltd.

Key words--Henry's law, QSAR model, Henry's law constant, ai~water partitioning

INTRODUCTION constant at a given temperature. The above

When a solute is introduced into an air-water binary
system, it distributes itself between the two phases so
as to re-establish thermodynamic equilibrium. This
distribution phenomenon has been modeled using
Henry's law. The modern thermodynamic theory of
Henry's law, its experimental determination, and its
significance in air-water partitioning have been well
documented in literature and textbooks. F o r dilute
solutions of nonelectrolytes, a practical and "strict"
form of Henry's law can be formulated by equating
the chemical potential of the solute in the liquid phase
to that in the gas phase, leading to the following
expression (Pierotti, 1963):
In = ~-~+ ~+ In . (1)
Here, P2 is the partial pressure of the solute in the gas
phase, and Xz is the mole fraction of the solute in the
liquid phase; R is the ideal gas law constant; T is the
absolute temperature; and v, is the molar volume of
the solvent. The first two terms on the right-hand side
of the equation quantify the partial molar Gibbs free
energy for cavity formation and interaction, respect-
ively, and the last term is a measure of the pure
solvent effect. The ratio (pz/x2) has been termed the
Henry's law constant, H, which can be seen to be a
*Author to whom all correspondence should be addressed
[Fax: + 1 505 646 6049; e-mail: nkhandan@nmsu.edu].
formulation is generally valid for x,_ < 0.03 and total
pressure < 2 atm.
In essence, H can be considered as the ratio of the
gas phase content of the solute to the liquid phase
content. This basic concept of partitioning has been
defined and interpreted in the science and engineering
literature in several different forms, causing consider-
able confusion and discussion (see Letters to the
Editor, 1987). For example, in certain atmospheric
chemistry and physical chemistry applications, H is
considered to be the inverse of the above ratio. One
of the more c o m m o n forms of H, as used in the
environmental engineering field, is obtained by
expressing p2 and x2 as concentrations (mass/volume),
yielding a non-dimensional form of Henry's law
constant. In this paper, H is reported in this
non-dimensional concentration ratio form.
Partitioning of organic solutes in air-water binary
systems has been recognized as an important
phenomenon in many applications. Chemical process
engineering, environmental remediation, and fate and
transport of organic chemicals in the ecosphere are
some areas where H data are crucial inputs. With new
environmental regulations, the need for reliable H
data has become even more critical. Under the Clean
Air Act Amendments of 1990, assessing and
controlling air emissions of more than 350 synthetic
organic chemicals (SOCs) has emerged a pressing
issue. The National Emission Standards for Haz-
ardous Air Pollutants under this Act requires
profound reductions in process and fugitive emissions

1471
1472 N. Nirmalakhandan et al.
of SOCs from many chemical processes, treatment
facilities and storage operations. Essential steps
involved in meeting this challenge include calcu-
lations of mass balance and mass transfer at
air-water interfaces, process modifications, solvent
substitution etc., where H data at different tempera-
tures are key inputs.
In spite of the importance of H in several such
applications, experimental data are not readily
available for many chemicals. In a critical review of
H data published in the literature, Mackay and Shiu
(1981) reported only 40 experimentally measured
data for 167 organic chemicals of environmental
concern. Additional experimental data are becoming
available, but at a fraction of the rate at which new
chemicals are being introduced. Even for the few
common chemicals for which experimentally deter-
mined H data exist, considerable differences can be
noted among the reported data from different
sources. In a comparison of experimental H data for
65 common organic solvents from different sources,
we found the average factor of variability between
different data sources to be typically 2.56 (Nir-
malakhandan, 1988).
Because of the large number of chemicals in
current use, the discrepancies among the reported
experimental data, and the severe analytical limi-
tations on the experimental determination of H
values, researchers, regulators and end users are
interested in developing and using rapid estimation
methods for H. Two approaches have emerged for
the estimation of H values. In the first approach, H
is estimated from a ratio of the vapor pressure to the
aqueous solubility of the solute (s-vp model). The
rationale behind this approach and its validity have
been well discussed in the literature (Mackay and
Shiu, 1981; Burkhard et al., 1985; Ashworth et al.,
1986). It is obvious that errors in aqueous solubility
and vapor pressure data will propagate into the H
values estimated by this model. Burkhard et al. (1985)
have, for example, evaluated such errors in the
prediction of H values of PCB congeners, and
concluded that the average factor of error, AFE,
could range from 3 to 4, with a worse-case maximum
of around 5. (AFE is defined as the ratio of the
predicted H value to the experimental value; if the
ratio is less than 1, then the reciprocal is used.) We
found this method resulted in A F E values of 2-3 for
the more common solvents (Nirmalakhandan, 1988).
However, whenever reliable experimentally measured
s-vp data are available, this approach will yield
excellent results (Meylan and Howard, 1991).
In the second approach, quantitative structure-
activity relationship (QSAR) techniques are used to
develop models to predict H (QSAR models). This
technique is based on the premise that the
physical/chemical/biological properties and activities
of organic molecules are a function of their molecular
structures. To apply this technique, experimentally
measured H data for a selected number of chemicals
and their corresponding molecular descriptors are
assembled to form a "training" set. Then, statistical
techniques are applied to develop a QSAR model
relating the experimental H data to the descriptors.
To validate the resulting QSAR model, a "testing"
set of chemicals with known H values can be used to
verify the H values predicted by the model. Given the
variability in the reported experimental H data and
the uncertainty and the data requirements of the s-vp
model, we feel that if H could be predicted for "new"
chemicals (i.e. chemicals not included in formulating
the models) with an A F E less than 3, then the QSAR
model could be considered excellent and satisfactory,
and acceptable when A F E is less than 4.
The QSAR model offers certain advantages over
the s-vp model. It does not normally require
experimental inputs, in that the model parameters are
calculated or estimated directly from the molecular
structure of the solute. This provides rapid estimation
of H values for "new" chemicals. In addition, a
robust and validated QSAR model for H can be used
to reconcile and corroborate contradictory inter-
laboratory data. When used with the s-vp model, the
QSAR model can aid in establishing realistic values
not only for H, but also for s and vp as well. The
objective of this paper is to present a QSAR model
for H, and document its predictive ability.
RELATED WORK
Hine and Mookerjee (1975) were among the first to
report a structure-property relationship to fit H data.
(In their study, the reciprocal of H was reported.)
They proposed two schemes to relate molecular
features to H data: a bond contribution scheme, and
a group contribution scheme. In the first scheme, H
data of 263 chemicals were analyzed by a least-square
method to establish 34 bond contribution factors. In
the second scheme, data of 212 chemicals were
analyzed to establish 49 fragment contribution
factors. The model based on bond contributions
fitted the log H data with a standard deviation, SD,
of 0.41, while the model based on group contri-
butions fitted with SD = 0.15, albeit for a smaller
number of chemicals. The H values used in these
regressions agreed with the fitted values with an A F E
of 2.61 and 1.28 for the two schemes, respectively.
(Several chemicals were excluded from the regression
analysis due to very high errors). The predictive
ability of this approach, however, was not evaluated
for "new" chemicals.
In our earlier work (Nirmalakhandan and Speece,
1988), we used a subset of the compilation of Hine
and Mookerjee (1975) to develop a QSAR model that
fitted the H data of 180 chemicals ranging over seven
log units, with r 2 = 0.98. We then demonstrated the
predictive ability of this model by comparing the H
values predicted for 20 "new" chemicals against the
reported H values with r2= 0.98. This study also
 Predicting Henry's law constant 1473

included results of several tests that further validated
the statistical robustness of the model.
Meylan and Howard (1991) have recalculated and
expanded the bond. contribution factors of Hine and
Mookerjee (1975) to 59. Their model fitted the
training set of 345 chemicals with r 2 = 0.94 and SD
of 0.45. To improve the quality of fit, they derived
correction factors for certain chemical classes which
increased the r 2 to 0.97 and decreased the SD to 0.34.
(Since they did not publish the predicted values, we
could not determine the corresponding AFE). They
demonstrated the predictive ability of their approach
on a testing set of 74 chemicals of complex structures.
The predicted values agreed well with the experimen-
tal values with r2 = 0.965 and SD = 0.46; based on
the predicted values reported by them, we found the
AFE for this testing set to be 4.39. Meylan and
Howard (1991) compared their approach against our
earlier model (Nirmalakhandan and Speece, 1988)
and concluded the two to be similar in overall
accuracy.
Russell et al. (1992) used a subset of 63 chemicals

Table 1. Prediction of H for chemicals of "similar" structures

Log H Log H

Chemical Found Predicted Error Chemical Found Predicted Error

Aliphatic hydrocarbons Aliphatic alcohols
1 Methane 1.46 1.39 0.07 1 3-Methylbutan- 1-ol -4.47 -4.05 -0.42
2 2-Methylbutane 1.75 1.68 0.07 2 2-Methylpropan-2-ol -3.28 -3.26 -0.02
3 2,3-Dimethylbutane 1.72 1.84 -0.12 3 Pentan-3-ol - 3.19 - 3.28 0.09
4 2-Methylhexane 2.15 1.89 0.26 4 3-Methylbutan- 1-ol -3.24 -3.23 -0.01
5 3-Methylhexane 1.99 1.88 0.11 5 Nonan-l-ol -2.85 -2.88 0.03
6 2,2-Dimethylpentane 2.11 1.99 0.12 6 Decan- 1-ol - 2.67 - 2.77 0.10
7 2,3-Dimethylpentane 1.85 1.93 -0.08 7 Prop-2-en-l-ol -3.69 -3.94 0.25
8 3,3-Dimethylpentane 1.88 1.96 -0.08 Aromatics
9 3-Methylheptane 2.18 1.98 0.20 1 lsopropylbenzene -0.22 -0.36 0.14
l0 2,3,4-Trimethylpenl:ane 1.88 2.10 -0.22 2 1,2,3-Trimethylbenzene - 0.89 - 0.31 - 0.58
l1 n-Nonane 2.30 2.03 0.27 3 1,3,5-Trimethylbenzene -0.66 -0.30 -0.36
12 2,2,5-Trimethylhexane 2.15 2.26 - 0.11 4 1,4-Diethylbenzene -0.69 -0.29 -0.40
13 n-Decane 2.32 2.14 0.18 5 Allylbenzene -0.55 -0.85 0.30
14 Cyclopropane 0.55 0.65 -0.10 6 2-Ethyltoluene -0.76 -0.37 -0.39
15 n-Propylcyclopentane 1.56 1.20 0.36 7 4-Ethyltoluene -0.70 -0.37 -0.33
16 n-Pentylcyclopenta:ae 1.87 1.41 0.46 8 Isobutylbenzene 0.12 -0.24 0.36
17 cis-1,2-Dimethylcyclohexane 1.16 0.97 0.19 9 sec-Butylbenzene -0.33 0.61 -0.94
18 trans-l,4-Dimethylcyclohexane 1.55 1.26 0.29 10 4-isopropyltoluene -0.50 -0.21 -0.29
19 Cyclohepta- 1,3,5-triene -0.73 -0.32 -0.41 11 n-Pentylbenzene - 0.17 - 0.20 0.03
20 2-Methylpent-l-ene 1.08 1.33 -0.25 12 n-Hexylbenzene -0.03 -0.09 0.06
21 Heptene 1.22 1.38 - 1.16 13 Styrene -0.91 -0.96 0.05
22 (E)-Hept-2-ene 1.23 1.38 -0.15
23 Non-l-erie 1.51 1.59 -0.08 Halogenated aromatics
1 Fluorobenzene -0.59 -1.09 0.50
2 Benzotrifluoride -0.18 -1.68 1.50
3 1,2,4-Trichlorobenzene -0.82 -1.61 0.79
Halogenated hydrocarbons 4 1,3,5-Trichlorobenzene -0.57 - 1.61 1.04
1 1,1,1,2-Tetrachloroethane -0.94 - 1.13 0.19 5 1,2,3,5-Tetrachlorobenzene -1.19 -1.90 0.71
2 2-Chlorobutane 0.00 -0.02 0.02
6 1,2,4,5-Tetrachlorobenzene -0.98 - 1.90 0.92
3 2-Chloro-2-methylpropane 0.80 0.11 0.69
7 2-Chlorotoluene -0.84 -0.88 0.04
4 1,4-Dichlorobutane - 1.70 -0.44 - 1.26
8 4-Bromotoluene - 1.02 - 1.11 0.09
5 1-Chlorohexane 0.00 0.12 - 0.12
9 Iodobenzene - 1.28 -0.97 -0.31
6 l-Chloroheptane 0.21 0.22 -0.01
7 l-Chloroprop-2-ene -0.42 -0.64 0.22 Polyaromatic hydrocarbons
8 I-Bromo-2-methylpropane - 0.02 - 0.33 0.31 1 1,3-Dimethylnaphthalene - 1.81 - 2.67 0.86
9 2-Bromo-2-methylpropane -0.62 -0.11 -0.51 2 1,4-Dimethylnaphthalene -2.07 -2.68 0.61
10 I-B romo-3-methy]butane 0.15 -0.24 0.39 3 2,3-Dimethylnapthalene -2.04 -2.52 0.48
11 l-Bromopentane -0.07 -0.30 0.23 4 2,6-Dimethylnaphthalene - 1.93 -2.67 0.74
12 l-Bromohexane 0.13 - 0.19 0.32 5 1-Ethylnaphthalene -1.76 -2.74 0.98
13 l-Bromoheptane 0.25 -0.09 0.34 6 Indane -I.07 -1.16 0.09
14 l-Bromooctane 0.38 0.01 0.37 Phenols
15 I-lodopentane -0.10 -0.15 0.05 1 2,3-Dimethylphenol -4.52 -5.06 0.54
16 l-lodohexane 0.06 -0.05 0.11 2 2,4-Dimethylphenol -4.41 -5.06 0.65
17 1-Iodoheptane 0.20 0.06 0.14 3 2,5-Dimethylphenol -4.34 -5.06 0.72
4 2,6-Dimethylphenol - 3.86 - 5.06 1.20
5 3,4-Dimethylphenol -4.77 - 5.06 0.29
Esters~acids 6 3,5-Dimethylphenol -4.60 -5.06 0.46
I n-Pentylacetate -- 1.84 - 1.71 - 0.13 7 3-Ethylphenol - 4.59 - 5.13 0.54
2 Methyltrimethylacetate - 1.76 - 1.66 - 0.10 8 4-Ethylphenol -4.50 -5.13 0.63
3 n-Pentylpropanoate - 1.55 - 1.74 0.19 9 4-n-Propylphenol -4.33 -5.03 0.70
4 i-Butylpropionate - 1.17 - 1.67 0.50 10 4-tert-Butylphenol -4.34 --4.78 0.44
5 Ethylhexanoate -1.64 -1.63 -0.01 11 2-Fluorophenol -3.88 -5.72 1.84
6 Isobutylisobutano~te - 1.24 - 1.51 0.27 12 4-Fluorophenol -4.54 -5.72 1.18
7 Hexylformate - 1.08 -1.61 0.53 13 2-Chlorophenol -3.34 -5.65 2.31
8 Amyl formate -1.26 -1.84 0.58 14 3-Chlorophenol -4.85 -5.65 0.80
9 Methyloctanoate - 1.50 - 2.07 0.57 15 4-Chlorophenol - 5.16 - 5.65 0.49
10 Ethylbcnzoate -2.67 -2.73 0.06 16 4-Chloro-3-methylphenol -4.98 -5.50 0.52
11 Pentanoic acid -4.52 -4.73 0.21 17 4-Bromophenol -5.23 -5.87 0.64
12 Hexanoic acid -4.56 -4.62 0.06 18 2-1odophenol -4,55 -5.59 1.04
1474 N. Nirmalakhandan et al.

2-

< 0-

-2- ~~¢rFF F FF

-4-

~1~ H H
-6-
Line of perfect prediction
-8 • I ' I ' I ' I I

-8 -6 -4 -2 0 2 4

log H F o u n d f r o m literature

A- 23 Aliphatic hydrocarbons E- 13 Aromatics

B- 17 HalogenatedHCs F- 9 Halogenated aromatics
C- 12 Esters/acids G- 6 Polyaromatie H C s
D- 7 Alcohols H- 18 Phenols
Fig. 1. Comparison between reported and predicted log H values for 105 organic chemicals of "similar"
structures.

from the compilation of Hine and Mookerjee (1975), End users of structure-property models would
and reported another model to estimate H with often prefer to apply these models to predict H values
F = 0.978 and SD = 0.375. The model parameters for chemicals for which experimental data are not
included five variables: number of heavy atoms, two readily available. Unless the predictive ability of such
different measures of charged partial surface area and models is demonstrated on " n e w " chemicals with
two different measures of atomic charge. They used an diverse molecular features that were not used in the
external testing set of seven chemicals to demonstrate original model development, end-users would be
the predictive ability of their model. Based on the reluctant to apply them confidently to new chemicals.
comparative values reported by them, we found the In this paper, we present additional data to
agreement between the experimental and predicted demonstrate the predictive ability of the basic model
values to be good with r 2 = 0.92 and A F E = 2.6. reported by us earlier (Nirmalakhandan and Speece,
A b r a h a m et al. (1994) reported a model based on 1988) and an extension to this model which enables
the linear solvation energy relationship (LSER) H values to be estimated for a wider range of
approach. In this model, H data in the form of gas chemicals. In addition, a new Q S A R model is
solubility were correlated for 408 chemicals with a presented that enables, for the first time, H values to
high degree of fit using five solvatochromic be estimated at different temperatures, directly from
parameters: excess molar refraction, dipolarity/polar- the molecular structures of the chemicals.
izability, effective hydrogen-bond acidity, effective
hydrogen-bond basicity, and M c G o w a n character- BASIC MODEL FOR H
istic volume. This study did not demonstrate the
predictive ability of the model on " n e w " chemicals. The basic model proposed by us (Nirmalakhandan
However, the model parameters in this model enable and Speece, 1988) was derived from equation (I) in
one to evaluate, at a molecular level, the various which the energy terms associated with the cavity
factors involved in air-water partitioning. formation and the solute-solvent interactions were
modeled using a combination of a polarizability
Table 2. Contributions to polarizability parameter parameter, @, the molecular connectivity index, 'Xv,
Atom Contribution Group/bond Contribution and a hydrogen bonding index, L This approach
Carbon 0.577 Aldehyde - 1.192 yielded the following three-variable model for the
Hydrogen - 0.12 Ketone - 1.433 non-dimensional concentration form of H at 25°C:
Oxygen - 0.825 Amine - 3.106
Hydroxyl - 3.701 Nitro -2.223 log H = 1.29 + 1.005@ -- 0.468 ~v _ 1.258 I (2)
Chlorine -0.187 Pyridine -2.511
Bromine -- 0.222 --
Iodine 0.407 Cyclic - 0.952 n = 180; r = 0.99; r 2 = 0.98; SE = 0.262.
Fluorine -0.57 Double bond -0.859
Sulfur -0.535 Triple bond -0.109 The polarizability parameter, @, was derived from
 Predicting Henry's law constant 1475

Table 3. Fitting o f H data to chemicals with " n e w " structures

Log H Log H

Chemical Found Calculated Error Chemical Found Calculated Error

Aldehydes Nitro compounds
1 Formaldehyde -2.02 -2.66 0.64 I Acetonitrile -2.85 - 1.85 - 1.00
2 Acetaldehyde - 2.57 - 2.56 - 0.01 2 1-Cyanobutane -2.67 -1.57 - 1.10
3 Propionaldehyde - 2.52 - 2.47 -0.05 3 1-Cyanopropane -2.58 - 1.68 -0.90
4 Butyraldehyde -2.33 -2.37 0.04 4 Nitromethane -2.95 -2.26 -0.69
5 Isobutyraldehyde -2.10 -2.31 0.21 5 Nitroethane -2.72 -2.18 -0.54
6 Pentanal -2.22 -2.26 0.04 6 l-Nitropropane -2.45 -2.07 -0.38
7 Hexanal -2.06 -2.16 0.10 7 2-Nitropropane - 2.30 -2.01 -0.29
8 Heptanal - 1.96 -2.05 0.09 8 l-Nitrobutane -2.27 - 1.96 -0.31
9 Octanal -1.68 -1.95 0.27 9 l-Nitropentane -2.07 -1.85 -0.22
10 Nonanal -1.52 - 1.84 0.32 10 Benzonitrile -3.09 -2.57 -0.52
11 (e)-But-2-enal -3.10 -2.82 -0.28 11 Nitrobenzene - 3.02 - 3.91 0.89
12 (e)-Hex-2-enal -2.70 -2.62 -0.08 12 2-Nitrotoluene - 2.63 - 3.76 1.13
13 (e)-Oct-2-enal -2.52 -2.41 -0.11 t3 3-Nitrotoluene -2.53 -3.76 1.23
Ketones
1 Propanone -2.79 --2.71 -0.08 Pyridines
2 Butanone -2.72 -2.61 -0.11 1 Pyridine -3.44 -3.65 0.21
3 Pentan-2-one -2.58 -2.46 -0.12 2 2-Methylpyridine - 3.40 - 3.51 0.11
4 Pentan-3-one - 2.50 - 2.49 -0.01 3 3-Methylpyridine -3.50 -3.51 0.01
5 3-Methylbutan-2-one -2.38 -2.41 0.03 4 4-Methylpyridine -3.62 -3.51 -0.11
6 Hexan-2-one -2.41 -2.36 -0.05 5 2,3-Dimethylpyridine -3.54 -3.37 -0.17
7 4-Methylpentan-2-one -2.24 -2.29 0.05 6 2,4°Dimethylpyridine -3.57 -3.36 -0.21
8 Heptan-2-one -2.23 -2.25 0.02 7 2,5-Dimethylpyridine - 3.46 - 3.36 - 0.10
9 Heptan-4-one -2.14 -2.28 0.14 8 2,6-Dimethylpyridine -3.37 -3.37 0.00
10 Octan-2-one - 2.11 - 2.15 0.04 9 3,4-Dimethylpyridine -3.83 -3.36 -0.47
11 Nonan-2-one - 1.83 -2.04 0.21 10 3,5°Dimethylpyridine -3.55 -3.36 -0.19
12 Nonan-5-one - t.94 -2.07 0.13 11 2-Ethylpyridine - 3.18 - 3.43 0.25
13 Decan-2-one - 1.72 -2.53 0.81 12 3-Ethylpyridine -3.37 -3.43 0.06
14 Undecan-2-one -1.58 -1.84 0.26 13 4-Ethylpyridine - 3.47 - 3.43 -0.04
15 3,3-Dimethylbutan-2-one -2.28 -2.29 0.01 14 2-Chloropyridine -3.22 -4.57 1.35
16 2,4-Dimethylpenta:a-3-one -2.01 -2.17 0.16 15 3-Chloropyridine 2.94 -4.56 1.62
16 3-Formylpyridine -5.21 -4.97 -0.24
Amines 17 4-Formylpyridine -5.14 -4.97 -0.17
1 Methylamine -3.34 -3.14 -0.20
18 3-Acetylpyridine -6.06 -4.83 - 1.23
2 Ethylamine - 3.30 - 3.06 - 0.24
19 4-Acetylpyridine -5.59 -4.83 -0.76
3 n-Propylamine -3.22 -2.95 -0.27
4 n-Butylamine -3.11 -2.84 -0.27
5 n-Pentylamine -3.00 -2.74 -0.26 Sulfonated compounds
6 n-Hexylamine -2.90 -2.64 -0.26 1 Dimethylsulfide - 1.18 - 1.21 0.03
7 n-Heptylamine 2.78 -2.53 -0.25 2 Diethylsulfide - 1.07 -0.86 -0.21
8 n-Octylamine - 2.68 - 2.42 - 0.26 3 Dipropylsulfide -0.94 -0.65 -0.29
9 Dimethylamine - 3.15 - 3.13 - 0.02 4 Di-isopropylsulfide -0.88 -0.46 -0.42
10 Di-n-propylamine -2.68 -2.76 0.08 5 Methylthiobenzene -2.00 - 1.75 -0.25
11 Di-isopropylamine -2.36 -2.65 0.29 6 Phenylmethylsulfide 2.00 - 1.75 -0.25
12 Di-n-butylamine -2.38 -2.55 0.17 7 Methylethylsulfide - 1.10 - 1.04 - 0.06
13 Trimethylamine -2.35 -3.07 0.72 8 Diethyldisulfide - 1.07 -0.75 -0.32
14 Triethylamine -2.36 -2.91 0.55 9 Dimethyldisulfide -I.31 -1.06 -0.25
15 N-Methylaniline -3.44 -3.83 0.39
16 N,N-DimethylanilJne -2.53 -3.78 1.25
17 2,6-Dimethylaniline -3.82 -3.55 -0.27

atomic and structural contributions based on an
approach similar to that proposed by Ketelaar
(Horvath, 1982). The molecular connectivity index,
~Xv, was calculated based on the approach proposed
by Kier and Hall (1976, 1986) and modified according
to Nirmalakhandan (1988). A sample calculation
illustrating this nlodified algorithm is shown in the
Appendix. The hydrogen bonding index, I, is assigned
a value of 1 for the chemicals that contained an
electronegative element attached directly to a carbon
atom holding a hydrogen atom. Acetylinfc com-
pounds and aromatic compounds with partially
substituted hydrogen atoms were also assigned 1. For
all the other chemicals, I was assigned a value of 0.
VALIDATION OF THE BASIC MODEL FOR H
In our earlier study, the basic model was validated
using 20 chemicals that were not included in the
model development. In this paper, we now use H data
from the compilation of Abraham et al. (1994) for
additional test chemicals that were not used in the
development of our basic model.
Prediction o f H data for chemicals with "similar"
structures
As a first step in the validation process, we selected
chemicals that are similar in molecular features to
those used in developing the basic model. From the
compilation of Abraham et al. (1994), we found 105
chemicals from eight different congeneric families
meeting this criterion. (Table 1). The reported H
values agreed well with those predicted by our basic
model with r: = 0.953 as shown in Fig. 1. In this set,
the predictions for phenolic and fluorinated com-
1476 N. Nirmalakhandan et al.

p o u n d s a r e p o o r . F o r e x a m p l e , in t h e c a s e o f m o r e in line w i t h t h e o t h e r s i m i l a r c h e m i c a l s . ( U s i n g
2 - c h l o r o p h e n o l , t h e predictive e r r o r is h i g h at 2.31; the other s-vp model a value of -0.43 was obtained.)
t h e r e p o r t e d e x p e r i m e n t a l v a l u e is - 3 . 3 4 while t h a t If 2-chlorophenol and 2-fluorophenol are excluded,
p r e d i c t e d b y t h e Q S A R m o d e l is - 5 . 6 5 , w h i c h is t h e overall A F E for t h e r e m a i n d e r o f t h e c h e m i -
cals = 3.52, w i t h 7 0 % of the predictions of
Table 4. Prediction of H for chemicals with "mixed" structures A F E < 3.0. T h i s a g r e e m e n t s u p p o r t s t h e r a t i o n a l e o f
Log H o u r a p p r o a c h , t h e validity o f t h e b a s i c m o d e l , a n d t h e
significance o f t h e m o d e l p a r a m e t e r s in a i r - w a t e r
Chemical Found Predicted Error
partitioning.
1 Benzaldehyde -2.95 -3.25 0.30
2 4-Methylbenzaldehyde -3.13 -3.11 -0.02
3 3-Hydroxybenzaldehyde -6.97 -7.87 0.90 Fitting of H data for chemicals with "new" structures
4 4-Hydroxybenzaldehyde -6.48 -7.87 1.39
5 Acetophenone - 3.36 - 3.12 - 0.24 C o n t i n u i n g t h e a p p r o a c h , we n o w e x t e n d t h e b a s i c
6 4-Methylacetophenone -3.45 -2.97 -0.48 m o d e l ' s a p p l i c a b i l i t y to c h e m i c a l families t h a t
7 Cyclopentanone -3.45 -3.25 -0.20 c o n t a i n a t o m i c a n d s t r u c t u r a l f e a t u r e s t h a t were
8 Cyclohexanone - 3.60 - 3.14 - 0.46
9 Methylcyclopropylketone - 3.38 - 3.20 -0.18 c o m p l e t e l y a b s e n t in t h e o r i g i n a l t r a i n i n g set.
10 Methylcyclohexylketone -2.86 -2.89 0.03 C h e m i c a l families t h a t were n o t r e p r e s e n t e d a r e
11 4-Methoxyacetophenone - 3.23 - 3.51 0.28
12 N,N-Dimethylformamide -5.73 -5.73 0.00 aldehydes, ketones, pyridines, amines, sulfonated and
13 2-Chloroaniline -3.60 -4.13 0.53 n i t r o c o m p o u n d s . S u c h c h e m i c a l s were n o t i n c l u d e d
14 3-Chloroaniline -4.27 -4.12 -0.15 in o u r b a s i c m o d e l d e v e l o p m e n t d u e to lack o f
15 4-Chloroaniline -4.33 -4.12 -0.21
16 2-Methoxyaniline -4.49 -4.57 0.08 e x p e r i m e n t a l d a t a for a sufficient n u m b e r o f
17 3-Methoxyaniline -5.35 -4.57 -0.78 c h e m i c a l s . A b r a h a m et al. (1994) h a v e n o w r e p o r t e d
18 4-Methoxyaniline -5.49 -4.57 -0.92 d a t a for 87 s u c h c h e m i c a l s . U s i n g t h e s e n e w d a t a as
19 2-Nitroaniline -5.41 -6.05 0.64
20 3-Nitroaniline -6.49 -6.04 -0.45 a t r a i n i n g set, o p t i m i z e d c o n t r i b u t i o n s to ~ were first
21 4-Nitroaniline -7.54 -6.04 - 1.50 established for aldehydes, ketones, pyridines, amines
22 o-Toludine -4.06 -3.69 -0.37
23 p-Toludine -4.09 -3.69 -0.40 a n d n i t r o c o m p o u n d s ( T a b l e 2). U s i n g t h e s e • v a l u e s
24 Cyclohexylamine -3.37 -3.48 0.11 in t h e s a m e b a s i c m o d e l t h a t w a s d e v e l o p e d earlier,
25 1-Naphthylamine -5.34 -6.06 0.72 l o g H v a l u e s were t h e n c a l c u l a t e d for t h e s e 87
26 2-Naphthylamine -5.48 -6.05 0.57
27 Benzamide - 8.07 - 7.31 -0.76 c h e m i c a l s . T h e r e p o r t e d a n d t h e c a l c u l a t e d log H
28 Cyclopentanol -4.03 -4.04 0.01 v a l u e s for this t r a i n i n g set a r e listed in T a b l e 3, f r o m
29 Cycloheptanol -4.02 -3.82 -0.20 which the quality of the agreement between the two
30 2-Methoxyethanol -4.96 -4.57 -0.39
31 2-Ethoxyethanol -4.91 -4.27 -0.64 c a n be s e e n to be s a t i s f a c t o r y , w i t h o v e r a l l
32 2-Propoxyethanol -4.70 -4.16 -0.54 A F E = 3.57 a n d 8 0 % of the predictions of
33 2-Butoxyethanol -4.59 -4.05 -0.54
34 2-Methoxyphenol -4.09 -6.10 2.01 A F E < 3.0.
35 3-Methoxyphenol -5.62 -6.09 0.47
36 l-Naphthol -5.63 -6.57 0.94
37 2-Naphthol -5.95 -6.62 0.67 Prediction of H data for chemicals with "mixed"
38 Benzylalcohol -4.86 -5.23 0.37 structures
39 2-Phenylethanol -4.98 - 5.12 0.14
40 3-Phenylpropanol -5.08 -5.02 -0.06 T o d e m o n s t r a t e t h e p r e d i c t i v e ability o f this final
41 3-Cyanophenol -7.08 -8.91 1.83
42 4-Cyanophenol - 7.46 - 8.91 1.45 m o d e l , we f o r m u l a t e d a t e s t i n g set o f c h e m i c a l s t h a t
43 2-Nitrophenol -3.36 -7.57 4.21 contained combinations of molecular features which
44 3-Nitrophenol -7.06 -7.57 0.51 were r e p r e s e n t e d in t h e t r a i n i n g set i n d i v i d u a l l y . F o r
45 4-Nitrophenol - 7.81 - 7.57 - 0.24
46 3-Cyanopyridine -4.95 -5.48 0.53 example, 4-methylbenzaldehyde consists of a combi-
47 4-Cyanopyridine -4.42 -5.48 1.06 n a t i o n o f a n a r o m a t i c ring a n d a n a l d e h y d e g r o u p ,
48 Quinoline -4.20 -4.92 0.72 w h e r e a s t h e s e t w o s t r u c t u r a l f e a t u r e s were rep-
49 2-Methylpyrazine - 4.04 - 3.89 - 0.15
50 2-Ethylpyrazine -4.00 -3.83 -0.17 r e s e n t e d in t h e t r a i n i n g set s e p a r a t e l y . Similarly,
51 2-1sobutylpyrazine - 3.70 - 3.55 - 0.15 methylcyciopropylketone has a combination of a
52 N-Methylpiperidine -2.85 --2.74 -0.11
53 Diethylether -I.17 -0.62 -0.55 cycle a n d a k e t o n e s t r u c t u r e . D a t a for a t o t a l o f 72
54 Methylpropylether - 1.22 -0.57 -0.65 s u c h c h e m i c a l s w e r e a v a i l a b l e f r o m A b r a h a m et al.
55 Di-n-Propylether -0.85 -0.40 -0.45 (1994) to test t h e p r e d i c t i v e ability o f t h e final m o d e l .
56 Di-lsopropylether -0.39 -0.30 -0.09
57 Di-n-butylether -0.61 -0.20 -0.41 T h e s e c h e m i c a l s a r e listed in T a b l e 4, a n d t h e
58 Dimethylether - 1.40 -0.74 -0.66 comparison between the reported and predicted log
59 Methylethylether - 1.54 -0.67 -0.87 H v a l u e s is i l l u s t r a t e d in Fig. 3. T h e a g r e e m e n t
60 Methyl-tert-butylether - 1.62 -0.33 - 1.29
61 Methylphenylether - 1.80 - 1.47 -0.33 b e t w e e n t h e t w o is s a t i s f a c t o r y , w i t h r 2 = 0.881.
62 Ethylphenylether - 1.63 - 1.41 -0.22 Again, the predictions for the phenolic compounds--
63 Divinylether - 0.15 - 0.70 0.55
64 Methanethiol - 0.99 - 0.86 - 0.13 2-nitrophenol, 2-methoxyphenol, 3-cyanophenol and
65 Ethanethiol -0.95 -0.68 -0.27 4-cyanophenol--are poor. In the case of 4-nitroani-
66 Propanethiol -0.78 -0.58 -0.20 line, t h e r e p o r t e d e x p e r i m e n t a l v a l u e w a s - 7 . 5 4
67 Butanethiol -0.73 -0.47 -0.26
68 Thiophenol -1.87 -I.40 -0.47 while t h e p r e d i c t e d v a l u e is - 6 . 0 4 . U s i n g t h e s - v p
69 Morpholine -5.26 -4.40 --0.86 m o d e l a v a l u e o f - 5.06 c a n b e c a l c u l a t e d w h i c h m a y
70 N-Methylmorpholine -4.64 -4.62 -0.02 be r e a s o n a b l e . W i t h t h e e x c l u s i o n o f t h e s e c h e m i c a l s ,
 Predicting Henry's law constant 1477

<

.~ -4-

"
-6- a A a
~ -7-
~ A A
~~ -8- /
.9 -9- ~ a
-I0 j , , , , , , , , ,

-10 -9 -8 -7 -6 -5 -4 -3 -2 -1 0
Log H Found from Literature
Fig. 2. Comparison between reported and predicted log H values for 70 chemicals with "mixed"
structures.

4
O Training set 1
n = 180
2- o Training set 2
n= 87
o- A Testing set 1
n = 20
< × set2
-2-
I . + n=
Testing set 3
70
-4-
"X
oo
[×
~~ 0 -6-
o

-8-
j~++% + d%~2.Niffophcnol
-I0 I I I I I I
-11 -8 -6 -4 -2 0 2

log H Found from Literature

Fig. 3. Comparison of log H values from literature vs. QSAR model for chemicals in training and testing
sets.

5
4
3
o 2
L.

0 -- r--
O
O
8

"ii
O

Training Training Testing Testing Testing

set 1 set 2 set I set 2 set 3
Fig. 4. Notched box plots of predictive errors in log H values for chemicals in training and testing sets.
1478 N. N i r m a l a k h a n d a n et al.

Table 5. Chemicals used in deriving equations (4) and (5)

Parameter A Parameter B

Chemical Code °Z ';C Exp. Calc. Exp. Calc.

1 Methylene chloride A 2.70 1.60 10.2 11.7 3645 3932
2 Chloroform B 3.57 1.96 11.8 12.5 4046 4088
3 2-Chlorobutane C 4.28 2.34 15.1 12.2 4499 4055
4 1,2-Dichloropropane D 4.28 2.44 12.4 11.0 4333 3869
5 1,3-Dichloropropane E 4.12 2.60 9.9 8.2 3917 3421
6 1,2,3-Trichloropropane F 4.99 3.07 7.4 7.7 3477 3372
7 1,4-Dichlorobutane G 4.82 3.10 6.6 6.3 3128 3156
8 l-Chlorobutane H 4.12 2.50 11.3 9.3 3482 3607
9 Toluene 1 4.38 2.41 11.3 11.9 3751 4020
10 Chlorobenzene J 4.38 2.47 9.6 11.2 3466 3908
11 o-Chlorotoluene M 5.30 2.89 10.0 11.6 3545 4000
12 Ethylenedichloride N 3.41 2.10 8.9 9.9 3539 3677
13 Carbon tetrachloride O 4.50 2.26 15.0 14.4 4438 4412
14 Benzene P 3.46 2.00 11.8 11.4 3964 3910
15 s-Tetrachloroethane Q 5.15 2.95 7.7 10.0 3547 3747
16 l,l-Dichloroethylene R 3.20 1.48 15.9 16.1 4618 4628
17 l,l,2-Trichloroethane S 4.28 2.51 9.0 10.2 3690 3739
18 l,l,l-Trichloroethane T 4.50 2.20 14.5 15.1 4375 4523
19 Trichloroethylene U 4.07 2.07 14.7 14.1 4647 4357
20 Tetrachloroethylene V 5.00 2.51 15.5 14.3 4735 4421

the overall A F E is 3.81, with 60% of the predictions represented by the notch; and values below the 10th
of A F E < 3.0. and above the 90th percentile are plotted as points.
The log H values determined from the QSAR These results support the claim that the proposed
model for the entire data set of 462 chemicals are QSAR model can be used to predict H values for a
compared against the reported values in Fig. 3. These range of chemicals similar to those analyzed here,
data include the original training set of 180 that was typically with an AFE less than 4.
used to develop the basic model in Meylan and
Howard (1991) (Training set 1), the testing set of 20
used in Meylan and Howard (1991) (Testing set 1), MODELING THE EFFECT OF TEMPERATURE ON
the testing set listed in Table 1 with "similar" HENRY'S CONSTANT
structures (Testing set 2), the training set with "new"
Equation (1) was adapted to model the effect of
structures listed in Table 3 (Training set 2), and the
temperature on H. Assuming that the variations of
testing set with "mixed" structures listed in Table 4
Go, G~ and, v~ are negligible over a small range of
(Testing set 3). The distributions of the errors for
temperatures as in environmental applications, the
these five data sets are illustrated in Fig. 4 by notched
following form of equation (1) can be deduced:
box plots, where the 10th, 25th, 50th, 75th and 90th
percentiles are indicated by the horizontal lines; the B
lnH=A-~+CIn T. (3)
95% confidence interval around the median is

1.00
Lines represent QSAR predictions;

"5',

'=' 0.I0,

E
0 0

0.01 , 0 . . I . . . . I . . . . I . . . . I . . . . I . . . .

0 5 10 15 20 25 30
Temperature [aC]
Fig. 5. C o m p a r i s o n b e t w e e n Q S A R - p r e d i c t e d a n d e x p e r i m e n t a l ( L e i g h t o n a n d C a l o , 1981) H d a t a . A:
c a r b o n t e t r a c h l o r i d e ; B: o - c h l o r o t o l u e n e ; C: c h l o r o b e n z e n e ; D: 1 , 2 - d i c h l o r o p r o p a n e ; E: 1 , 3 - d i c h l o r o -
propane.
 Predicting Henry's law constant 1479

Table 6. Comparisonbetweenreported (Gossett, 1981)and predicted H valuesat various temperatures

DimensionlessHenry'slaw constant
at temperatureof:
10.3°C 17.5°C 24.8°C 34.6°C AFE
cis-1,2-Dichloroethylene Observed 0.07 0.11 0.17 0.22
[°X = 3.15; tXv = 1.64; Predicted 0.28 0.41 0.59 0.94
A = 13.9; B = 4287] Factor o f error 3.83 3.71 3.55 4.34 3.86
10.3°C 17.5°C 24.8°C 34.6°C

Vinylchloride Observed 0.63 0.81 1.14 1.42

[°x = 2.28; ~X~ = 1.06; Predicted 0.71 1.05 1.54 2.51
A = 15.7; B = 4539] F a c t o r o f error 1.12 1.30 1.36 1.77 1.39
9.6°C 17.5°C 24.8°C 34.6°C

1,1 -Dich loroethane Observed 0.11 0.16 0.23 0.32

[°x = 3.57; ~;t~ = 1.88; Predicted 0.22 0.33 0.47 0.73
A = 13.5; B = 4239] Factor o f error 2.03 2.00 2.03 2.29 2.09
10.3°C 17.5°C 24.8°C 34.6°C

Chloroel:hane Observed 0.28 0.35 0.45 0.61

[°;t = 2.70; '~ = 1.50; Predicted 0.20 0.28 0.40 0.62
A = 12.9; B = 4120] Factor o f error 1.43 1.26 1.14 1.01 1.21
9.6°C 17.5°C 24.8°C 34.6°C

Dichloromethane Observed 0.05 0.05 0.09 0.13

[°X = 2.70; 'Xv = 1.60; Predicted 0.11 0.16 0.23 0.35
A = 11.7; B = 3935] F a c t o r o f error 2.26 2.97 2.54 2.69 2.62
10.3°C 17.5°C 24.8°C 34.6°C

Chloromethane Observed 0.17 0.24 0.36 0.49

[°x = 2.0; '~= 1.13; Predicted 0.25 0.35 0.50 0.78
A = 13.:!; B = 4144] F a c t o r o f error 1.46 1.44 1.39 1.59 1.47
Overall A F E = 2.10

Several workers have proposed empirical results of a
similar form to model the H - T relationship, using
experimentally mea.sured H data at different tempera-
tures with corresponding A and B values for the
tested chemicals, but the practical utility of such
models is severely limited to only those few chemicals
tested. In this study, we have used such experimental
data to derive QSAR models for A and B, so that
they could be estimated for similar untested chemicals
directly from their molecular structures. This enables
the H - T relationship to be predicted for a wider
range of chemicals.
A data set reported by Leighton and Calo (1981)
for 20 chemicals was used as a training set to develop
QSAR models for the parameters in equation (3)
(original H data reported by Leighton and Calo
(1981) were in the atm/mole fraction form; they were
converted to the non-dimensionalconcentration ratio
form in this study). Because of the limited availability
of experimental data and the marginal contribution
of the third term, C, in equation (3), only the first two
terms, A and B, were modeled. This data set
contained measured H values for benzene, toluene,
and 18 chlorinated aliphatics over a temperature
range of 1-27°C, and the A and B values calculated
from them by Leighton and Calo (1981). The
following equations were derived in this study to
model A and B in terms of molecular connectivity
indexes:
A = 14.97 + 5.78 02( - 11.79 lXv
n = 20; r = 0.879; r2= 0.772; RMS = 1.46
B = 4346 + 947 °x - 1855 ~Xv (5)
n = 20; r = 0.813; r 2 = 0.661; RMS = 298.
The chemicals used, their X values, and the
comparison between the reported and calculated A
and B values are shown in Table 5. Using A and B
values calculated from these equations, H values were
then estimated for five selected chemicals over a
temperature range of 1-25°C. As seen in Fig. 5, these
calculated values agree well with the measured H
values. The agreement between the measured and
calculated H values for the 20 chemicals ranging in
temperature from 1-27°C was satisfactory, with an
overall r 2= 0.86 for the 170 data points and an
overall AFE of 1.74.
To demonstrate the predictive ability of this H - T
model, data sets reported by Gossett (1985) and
Hulscher et al. (1991) were used as testing sets.
Gossett's data set contained H data for six "new"
chemicals over a temperature range of 10-35°C.
These measured values are compared with the H
values predicted at various temperatures in Table 6.
The agreement can be seen to be good, with
an AFE of 2.10 for this set. The comparison between
the observed values of Hulscher et al. (1991)
and those predicted over a temperature range of
10-55°C for 12 "new" chemicals is shown in Table 7.
(4) While the three chlorinated biphenyls in this set are
 T a b l e 7. C o m p a r i s o n between reported (Hulscher et al.) a n d Q S A R - p r e d i c t e d H values at various temperatures
Dimensionless Henry's law constant at temperature of:

14.8°C 20.1 ° C 22.1 ° C 24.2'~C 34.8°C 50.5°C AFE

1,2,3,4-Tetrachlorobenzene Observed 2.03 × 10 -2 2 . 1 4 x 10 2 2 . 7 8 × 10 -2 2.88 × 10 -2 5.01 × 10 -2 1.03 × 10 - I
[°X = 7.15; ~X~ = 3.92; Predicted 3.76 × 10 -2 4 . 7 8 × 10 2 5.23 x 10 -2 5.73 × 10 -2 8.95 × 10 -2 1.64 × 10 - I
A = 10.08; B = 3845] Factor of error 1.85 2.24 1.88 1.99 1.79 1.59 1.89
Pentachlorobenzene Observed 1.57 x 10 2 2.03 × 10 -2 2.78 × 10 -2 2.71 × 10 -2 4.86× 10 2 1.03 × 10 ,
[0~ = 8.07; ~ X ' = 4.57; Predicted 1.15 x 10 -2 1.43 x 10 _2 1.56 × 10 -2 1.69 × 10 -2 2.54x 10 2 4 . 4 2 × 10 2
A = 7.73; B = 3511] Factor of error 1.36 1.42 1.79 1.60 1.91 2.33 1.74
Hexachlorobenzene Observed 9 . 8 9 × 10 3 1 . 2 4 × 10 -2 1.91 × 10 2 2 . 1 2 × 10 -2 3 . 4 6 x 10 -2 8 . 1 0 × 10 -2
[°X = 9.0; ~X~ = 5.08; Predicted 7.63 x 10 -3 9.48 × 10 -3 1.03 × 10 2 1.11 × 10 -2 1.66 x 10 -2 2 . 8 6 × 10 -2
A = 7.10; B = 3446] Factor of error 1.30 1.30 1.86 1.90 2.08 2.83 1.88
10.4°C 20.0°C 30.1 ° C 34.9°C 42.1 ° C 47.9°C 48.4°C

2,5-Dichlorobiphenyl Observed 6.85 × l 0 -3 1.22 × 10 : 2 . 3 2 × 10 z 3.22 × 10 -2 4.71 × 10 -2 6 . 2 2 × 10 -2

[o;( = 8.62; 'X~ = 5.09; Predicted 2.38 × l 0 -3 3.39 × 10 3 4.81 x 10 3 5.63 x 10 3 7.07 × 10 -3 8.43 × 10 -3
A = 4.78; B = 3067] Factor of error 2.88 3.59 4.82 5.72 6.66 7.37 5.17
2,4,4'-Trichlorobiphenyl Observed 3.70 × 10 3 8.73 × 10 3 1.89 × 10 -2 1 . 9 7 × 10 -2 2.71 × 10 -2 4 . 5 3 x 10 -2 4 . 5 9 × 10 2 Z
[02( = 9.54; ';(~ = 5.60; Predicted 1.55 × 10 -3 2 . 1 9 × 10 3 3.07 × 10 -3 3.58 × 10 -3 4 . 4 7 × 10 -3 5.31 × 10 -3 5.39 × 10 _3 Z
A = 4.09; B = 2992] Factor of error 2.39 3.99 6.14 5.50 6.06 8.54 8.51 5.44
2,2',5,5'-Tetrachlorobiphenyl Observed 3.66 × 10 -3 6.75 × 10 -3 1.49 × 10 2 1.52 × 10 2 2.63 × 10 2 4.11 × 10 2 4 . 5 3 × 10 -z
[°X = 10.46; 'X'= 6.12; Predicted 9.53 × 10 _4 1.33 × 10 -3 1.85 × 10 3 2.15 × 10 3 2 . 6 7 × 10 3 3.15 × 10 3 3.20 × 10 -3
A = 3.27; B = 2899] Factor of error 3.84 5.07 8.03 7.07 9.86 13.03 14.17 7.82
lO.O°C 20.0°C 35.0°C 40.1 ° C 45.0°C 55.0°C

Fiuoranthene Observed 1.11 × 10 -4 2 . 6 4 x 10 -4 6 . 3 9 × 10 -4 9 . 1 7 x 10 4 2 . 2 2 × 10 -3 2 . 2 9 × 10 -3

[°X = 8.77; 'X ~ = 5.56; Predicted 2.88 × 10 -4 3 . 8 2 x 10 -4 5 . 6 4 × 10 -4 6.38 × 10 -4 7.16 x 10 -4 8 . 9 6 × 10 -4
A = 0.11; B = 2337] Factor of error 2.60 1.45 1.13 1.44 3.10 2.56 2.05
Benzo(b)fluoranthene Observed 1.07 × 10 5 2 . 1 0 × 10 5 4 . 6 6 x 10 -5 5.82 × 10 -5 7.89 × 10 5 1.36 x 10 4
[°X = 10.85; ~ l ~ = 6.90; Predicted 4 . 0 9 x 10 5 5 . 1 0 × 10 5 6 . 9 0 × 10 5 7 . 5 9 × 10 -5 8.31 × 10 -5 9 . 8 9 × 10 -5
A = - 3.67; B = 1821] Factor of error 3.84 2.43 1.48 1.31 1.05 1.38 1.91
Benzo(k)flnoranthene Observed 9 . 3 8 × 10 -6 1.77 × 10 -5 4 . 1 9 × 10 -5 5.32 × 10 5 7.51 × 10 -5 1.48 × 10 -4
[~X = 10.93; 'X ~ = 6.97; Predicted 3.45 x 10 -5 4 . 2 6 x 10 -5 5 . 7 2 x 10 -5 6.28 × 10 5 6 . 8 5 × 10 -5 8 . 1 2 × 10 -5
A = - - 4 . 0 3 ; B = 1767] Factor of error 3.67 2.41 1.36 1.18 1.10 1.83 1.92
Benzo(a)pyrene Observed 9 . 3 8 x 10 6 1 . 4 0 x 10 - s 2 . 9 0 × 10 -5 3.55 × 10 -5 4 . 1 7 × 10 -5 8 . 7 9 × 10 -5
[~X = 10.93; 'Z~ = 6.97; Predicted 3.45 × 10 5 4 . 2 6 x 10 -5 5.72 x 10 -5 6.28 × 10 -5 6.85 × 10 -5 8 . 1 2 × 10 -5
A = - 4 . 0 3 ; B = 1767] Factor of error 3.67 3.04 1.97 1.77 1.64 1.08 2.20
Benzo(ghi)perylene Observed 8 . 1 0 × 10 -6 1.11 × 10 -5 2 . 0 4 × 10 -5 2.08 × 10 -5 2 . 5 0 x 10 5 3 . 2 0 × 10 -5
[°X = ! 1.93; 'X ~ = 7.72; Predicted 7 . 7 4 × 10 -6 9 . 0 8 × 10 -6 1.13 × 10 -5 1.21 × 10 -5 1.30 x 10 -5 1.47 × 10 -5
A = - 7.09; B = 1323] Factor of error 1.05 1.22 1.80 1.71 1.93 2.18 1.65
lndeno(1,2,3-cd)pyrene Observed 7.67 × 10 -6 1.19 x 10 5 2.23 × 10 5 2.35 × 10 5 2 . 9 2 × 10 -5 3 . 8 6 × 10 5
[°X = ! 1.93; 'X ~ = 7.72; Predicted 7 . 7 4 × 10 6 9.08 × 10 -6 1.13 × 10 5 1.21 × 10 -5 1.30 × 10 -5 1.47 × 10 5
A = - 7.09; B = 1323] Factor of error 1.01 1.31 1.97 1.94 2.26 2.63
1.85
Overall AFE = 2.96
 Predicting Henry's law constant 1481

not well predicted, the overall A F E is satisfactory at Kier L. B. and Hall L. H. (1986) Molecular Connectivity in
2.96. Structure-Activity Analysis. Research Studies, London.
Leighton D. T. and Calo J. M. (1981) Distribution
CONCLUSIONS coefficients of chlorinated hydrocarbons in dilute
air-water systems for groundwater contamination appli-
A QSAR model for predicting Henry's constant cations. J. Chem. Eng. Data 6, 87-96.
Letters to Editor (1987) Environ. Sci. Technol. 21, 828.
values directly from the molecular structure of Mackay D. and Shiu W. Y. (1981) A critical review of
chemicals has been developed. The quality of the Henry's law constants for chemicals of environmental
predictions made by this model was shown to be concern. J. Phys. Chem. Ref. Data 1@(4), 1175-1199.
satisfactory for a wide variety of chemicals that were Meylan W. M. and Howard P. H. (1991) Bond contribution
method for estimating Henry's law constant. Environ.
not included in the model development. The overall fit
Toxicol. Chem. 10, 1283-1293.
o f this model for 462 chemicals, spanning an H range Nirmalakhandan N. (1988) Prediction of aqueous solubility
of 10 orders o f magnitude, was found to be good, with and Henry's constant from molecular structures. PhD
r 2 exceeding 0.95. A Q S A R model for predicting H as dissertation, Drexel University, Philadelphia, PA.
a function o f temperature was also developed using Nirmalakhandan N. and Speece R. E. (1988) QSAR Model
for predicting Henry's constant. Environ. Sci. Technol.
the limited number of data reported in the literature. 22, 1349-1361.
This H - T model predicted H values for 18 " n e w " Pierotti R. A. (1963) The solubility of gases in liquids. J.
chemicals over 10-55°C fairly well. It should be noted Phys. Chem. 67, 1840-1845.
that the shortcomings of the H - T model stem from Russell C. J., Dixon S. L. and Jurs P. C. (1992)
Computer-assisted study of the relationship between
two sources. Firs~L, the inadequacy of the Q S A R
molecular structure and Henry's law constant. Anal.
models, equations (4) and (5). Second, the values for Chem. 64, 1350-1355.
A and B used in developing these two equations; these
values were in turn calculated by regression analysis
APPENDIX
o f the experimental H - T data and thus contain some
built-in uncertaintiles. Additional experimental H - T Algorithm for calculation of molecular connectivity
data for a wider range of chemicals would enable this indexes:
model to be strengthened. Based on the validations l Zv = ~ -05
Hvl.v2
I
demonstrated in this study, the proposed models where n is the number of subgraphs containing single bonds,
could be expected to predict acceptable H data and vl and v2 are the valence values at the terminal points
directly from the molecular structures for chemicals of each bond. For carbon atoms, values are equal to the
similar to those included in the training sets. number of bonds at each atom. For hetero atoms, the
valence values are given in Nirmalakhandan (1988).
Example calculation for ethyl acetate, CH3COOCH:CH3.
Acknowledgements This work was supported in part
by US Air Force Office of Scientific Research under an Step 1: Draw hydrogen-suppressed molecular skeleton and
Award for Science and Engineering Research Training label each node
(ASERT), Grant F49620-94-1-0366; Project Manager, Dr
W. Kozumbo.
1 3
REFERENCES
Abraham M. H., Andonian-Haftvan J., Whiting G. S., Leo
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that influence the solubility of gases and vapors in water
at 298 K, and a new method for its determination. J.
Chem. Soc. Perkir~ Trans. 2, 1777-1791.
I10
Ashworth R. A., Howe G. B., Mullins M. E. and Rogers T. 6
N. (1986) Air-wat,:r partitioning coefficients of organics Step 2: For each node, assign valence nodal values
in dilute aqueous solutions. Presented at AIChE Summer
Node ID 1 2 3 4 5 6
National Meeting, Boston, MA.
Burkhard L. P., Armstrong D. E. and Andren A. W. (1985) Atom C C O C C O
Henry's law constants for the polychlorinated biphenyls. Valence value, v 1 4 6 2 l 6
Environ. Sci. Technol. 19, 590-596. Step 3: Identify subgraphs containing one bond each
Gossett J. M. (1985) Air Force Engineering and Services Subgraph ID 1 2 3 4 5
Center Report ESL TR-85-38. Terminal node IDs 1,2 2,3 3,4 4,5 2,6
Hine J. and Mookerjee P. K. (1975) The intrinsic
hydrophyllic character of organic compounds: corre- Step 4: For each subgraph, calculate HvLv2where vl and v2
lations in terms of structural contributions. J. Org. Chem. are the terminal valence values
40, 292-298. Subgraph ID l 2 3 4 5
Horvath A. (1982) Halogenated Hydrocarbons. Marcel Hv,.~2 4 24 12 2 24
Dekker, New York.
Step 5: Calculate the contribution from each subgraph
Hulscher T. E. M., wmder Velde L. E. and Bruggeman W.
A. (1992) Temperature dependence of Henry's law Subgraph ID 1 2 3 4 5
constants for sele:ted chlorobenzenes, polychlorinated H~i°~ 0.50 0.20 0.29 0.71 0.20
biphenyls, and polycyclic aromatic hydrocarbons. Envi- Step 6: Determine the summation of the contributions from
ron. Toxicol. Chem. 11, 1595-1603. subgraphs to 'Zv
Kier L. B. and Hall L. H. (1976) Molecular Connectivity in
Chemistry and Drug Design. Academic Press, New York. giving 'Xv = ~ HvLv2-°5= 1.90 for ethyl acetate.
I