PB82-141797
Octanol/Water Partition Coefficients and Aqueous
Solubilities of Organic Compounds
(U.S.) National Bureau of Standards
Washington, DC
Prepared for
Environmental Protection Agency
Washington, DC
Dec 81
U.S. tepert&sst eff Ces*5»rcs
nations) Tectaica) Information Semct
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NBSiR 81-2406
U.S. DEPARTMENT OF COMMERCE
National Bureau of Standards
Center for Chemical Physics
Chatnical Thermodynamics Division
WaahSneton. OC 20234
Dscembar 1981
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NBS-M4A IREV. 2->CI
U.S. DEPT. Of COUU.
BIBLIOGRAPHIC DATA
SHtETlSe* instructions)
1. PUBLICATION OR
REPORT NO.
NBSIR-81-2406
2. Performini Otfan. Report No
* u .1 T 21 1 7 ^ f
December 1981
4. TITLE AND SUBTITLE ..•,. . c n
"Octanol/Water Partition Coefficients and Aqueous Solubilities of Organic
Compounds"
s. AUTHORISE Stanley P. Wasik, Yadu B. Tewari, Hichele M. Miller,
and Daniel E. Marti re 356
t. PERFORMING ORGANiZATION (if joint or otter than NBS.
NATIONAL BUREAU OF STANDARDS
DEPARTMENT OF COMMERCE
WASHINGTON, D.C. 20234
see instructions)
095
7. Contract'Cranl No.
1. Type or Report &
Period Covered
Office of Toxic Substances
Environmental Protection Agency
Washington, DC 20460
10. SUPPLEMENTARY NOTES
[~"| Document describe) a computer protram: SF-IBS, FlPS Software Summary, Is attached.
1. ABSTRACT (A 200->vord or fesj factual summary o/ most significant information. II document includes a significant
bibliography of literature survey, mention it here)
A generator column method for measuring the octanol/water partition
coefficient, K , , and the aqueous solubility, C*, is described. When water
is pumped through a generator column packed with solid support coated with
an organic stationary phase, an aqueous solution is generated that 1s in
equilibrium with the stationary phase. The solute concentration in the
elutea aqueous phase was measured either by high pressure liquid
chromatography or by solvent extraction followed by gas chromatographic
analysis.
Aqueous solubilities and octanol/water partition coefficients of organic
solutes, falling Into 7 general chemical classes, have been systematically
determined using the modified generator column method. From thermodynamics
an equation is derived relating KO/W to the volume-fraction-based solute
activity coefficient 1n water (YJ). the latter being determinate from Cs-
For each class of compounds, excellent linear correlations are found between
log K / and log Y", w1th sl°Pes close to the theoretical value of unity.
o/w s
12. KEY WORDS [Six to twelve entries; alphabetical Oi'der; capitalize only proper names; anil separate key words by s«—ucoions)
Activity coefficients; aqueous solubility; gas chromatography; generator
column; high pressure liquid chromatography; and octanol/water partition
coefficients
U. AVAILABILITY
JS_j Unlimited
(~1 For Official Distribution. Do Not Release to N.TIS
r~~) Order From Superintendent of Documents, U.S. Government Princint Office. Washlnfton, D.C.
20402.
ft" Order From National Technical Info-nation Service (NTIS). Springfield, VA. 22161
14, NO. OF
PRINTED PAGES
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15. Price
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NBSIR81-2406
OCTANOL/WATER PARTITION
COEFFICIENTS AND AQUEOUS
SOLUBILITIES OF ORGANIC COMPOUNDS
Stanley P. Wasik, Yadu B. Tewari. Michele M. Miller.
and Daniel E. Martire
U.S. DEPARTMENT OF COMMERCE
National Bureau of Standards
Center for Chemical Physics
Chemical Thermodynamics Division
Washington, DC 20234
December 1981
Prepared for
Office of Toxic Substances
Environmental Protection Agency
Washington, DC 20460
U.S. DEPARTMENT OF COMMERCE. Malcolm SaJdrisa, Secretory
NATIONAL BUREAU OF STANDARDS, Errant Ambter.
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OCTANOL/WATER PARTITION
COEFFICIENTS AND AQUEOUS
SOLUBILITIES OF ORGANIC
COMPOUNDS
Stanley P. Wasik, Yadu B. Tewarl, and
Michele M. Miller
Chemical Thermodynamics Division
Center for Chemical Physics
National Bureau of Standards
Washington, D.C. 20234
and
Daniel E. Marti re
Chemistry Department
Georgetown University
Washington, D.C. 200b7
Under
Interagency Agreement EPA-80—X0985
,-t
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ABSTRACT
A generator column method for measuring the octanol/water partition
coefficient, K , , and the aqueous solubility, c", is described. When water
is pumped through a generator column packed with solid support coated with
an organic stationary phase, an aqueous solution is generated that is in
equilibrium with the stationary phase. The solute concentration in the
eluted aqueous phase was measured either by high pressure liquid
chromatography or by solvent extraction followed by gas chromatographic
analysis.
Aqueous solubilities and octanol/water partition coefficients of organic
solutes, falling into 7 general chemical classes, have been systematically
determined using the modified generator column method. From thermodynamics
an equation is derived relating KQ. to the volume-fraction-based solute
activity coefficient in water (Y*), the latter being determinate from c"
5 5
For each class of compounds, excellent linear correlations are found between
log K and log YI with slopes close to the theoretical value of unity.
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ACKNOWLEDGMENT
The authors gratefully acknowledge the financial support of their
work by the Environmental Protection Agency.
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TABLE OF CONTENTS
Page
ABSTRACT 1
ACKNOWELDGMENT ii
TABLE OF CONTENTS 1ii
LIST OF TABLES v
LIST OF FIGURES vi
DISCLAIMER V11
I. .SUMMARY 1
II. INTRODUCTION 2
III. COMPARISON OF EXPERIMENTAL METHODS 6
IV. EXPERIMENTAL
A. Aqueous Solubility and Partition Coefficients 8
B. Solute Activity Coefficient in Octanol 15
V. VALIDATION
A. Stir-Flask Equilibrations 17
8. Solubility 18
C. Partition Coefficient 18
D. Activity Coefficients 21
VI. RESULTS AND DISCUSSION 24
VII. RECOMMENDATIONS FOR FUTURE RESEARCH
A. Salinity Dependence 40
B. Temperature Dependence 40
C. Head-Space Measurements 41
0. Tests for Other Classes 41
E. Predictive Schemes 42
VIII. REFERENCES 43
ill
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APPENDIX 1 45
APPENDIX II 47
1v
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LIST OF TABLES
Table Page
1 Aqueous Solubility of n-Propylbenzene . . . . 19
2 Octanol/Water Partition Coefficient, K . . of n-Propylbenzene . 2P
3 Activity Coefficients and Octanol/Water Partition Coefficients
of Organic Compounds at 25.0°C 23
4 Aqueous Solubility and Octanol/Uater Partition Coefficients
of Organic Compounds: Aromatic Hydrocarbons 25
4-A Aqueous Solubilities and Octanol/Water Partition Coefficients
of Organic Compounds: Miscellaneous Aromatic Compounds .... 26
5 Aqueous Solubilities and Octanol/Water Partition Coefficients
of Organic Compounds: Unsaturated Hydrocarbons 27
6 Aqueous Solubilities and Octanol/Water Partition Coefficients
of Organic Compounds: Halogenated Hydrocarbons 28
7 Aqueous Solubilities and Octanol/Water Partition Coefficients
of Organic Compounds: Normal Hydrocarbons 29
8 Aqueous Solubilities and Octanol/Water Partition Coefficients
of Organic Compounds: Aldehydes and Ketones 30
9 Aqueous Solubilities and Octanol/Water Partition Coefficients
of Organic Compounds: Esters , . 31
10 Aqueous Solubilities and Octanol/VJater Partition Coefficients
of Organic Compounds: Alcohols . . 32
11 Coefficients of the Regression Equation and the Correlation
Coefficient of the Solutes 33
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LIST OF FIGURES
Figure
1 Generator Column 9
2 Schematic of HPLC System « 11
3 Generator Column and Collecting Vessel 14
4 Experimental Log K . Versus Literature Log KQ/M 35
5 Experimental Log C* Versus Literature Log C* 36
6 Log KQyw Versus Log £w for the Literature Values 38
7 Log K . Versus Log Iw for the Experimental Values .... 39
vl
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DISCLAIMER
Certain cwrenercial equipment, instruments, and materials are identified
in this paper in order to specify adequately the experimental procedure.
In no case does such identification imply recommendation or endorsement by
the National Bureau of Standards, nor does it imply that the material,
instruments, or equipment identified are necessarily the best available
for the purpose.
vii
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I. SUMMARY
A chromatogrrtphic method for measuring the octanol/water partition
coefficient, K . , and the aqueous solubility, c", of hydrophobic substances
O/ W 5
is described. When water is pumped through generator columns containing
a solid support coated with e.n organic stationary phase, an aqueous solution
is generated which is in equilibrium with the stationary phase. When the
organic phase is pure solute, the concentration of the solute in the eluted
aqueous phase is the solute solubility. When the organic phase is octanol
containing a solute of concentration C° and the concentration of the solute
in the aqueous phase is determined to be c", then the octanol/water
partiton coefficient is given as K. = C°/C*. Validation of the generator
column method was made by corr.paring K > and C* values of n-propylbenzene
carefully measured by the conventional shake-flask method with those
measured by the generator column method. Additional validation of the
method was made by analyzing K, and C^ data measured by the generator
column method in terms of the thermodynamically derived equation.
log KQ/w = -log $" - log Y°
where Y° is the solute activity coefficient, on a volume fraction basis, in
octanol as measured by the GC met'iod and $" is the solute volume fraction in
water which is determined from C* data.
Thermodynamic theory predicts that plots of log K,, versus log \\n
I.I/W y_
should Jiave slopes of unity if the data are accurate while the coefficient
of determination gives precision of the measurements. Analysis of the data
for 62 compounds representing seven chemical classes gave slopes in the
range 0.93 to 1.08 with an average coefficient of determination 0.994.
Our studies indicate that the C* ar.d K , data obtained by using the
generator column method agree very well with the shake-flask literature data
obtained experimentally. Thus these results establish that the data are
accurate and the generator column method is a valid method for measuring
Cs and Ko/W
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II. INTRODUCTION
Measurement of the aqueous solubility, C*. and the octanol/water
partition coefficient, K . , are important for determining the fate
and transport of organic chemicals in the environment. K , may be
considered as a quantitative measure of the hydrophobicity of the compound.
In this respect, it has been used to predict bicconcentration of
organic pollutants in trout muscle [Neely et al_., 1974] and for making
other chemical and biological correlations [Leo e_t al_., 1971]. The aqueous
solubility gives an insight into environmental movement and distribution and
the potenti''! for biodegradation by microorganisms in soil surfaces, water,
arid sewage treatment plants as well as other degradation pathways such as
photolysis, hydrolysis, and oxidation.
Octanol/water partition coefficients and aqueous solubilities are
often measured by a sfake-flask method. Solubilities are determined
by shaking the solute with water, allowing the two phases to separate,
and then determining the solute concentration in the aqueous phase by
an appropriate analytical technique. Octanol/water partition coefficients
are determined by shaking a known volume of octanol containing a small
amount of solute with water, allowing the two phases to separate,
and measuring the solute concentration in the aqueous phase, Cw, and
in the octanol phase, C° . K. is determined as the ratio C°/c"
S O/ W S S •
In any shake-flask experiment with a hydrophobic substance,
the solute concentration in the aqueous phase is low. Consequently
the measurement of this concentration can be seriously affected by
the presence of colloidal dispersions (emulsions), adsorption of
the solute onto surfaces of transfer vessels, and loss of a volatile
solute into the atmosphere. These errors can be reduced, but only
at a cost of inconvenience and increased time, by centrifuging or
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replacing the shaking by gentle stirring, by prerinsing the glassware
with the aqueous phase, and by avoiding exposure of the aqueous phase to
the atflRrephere. A rapid, convenient method for preparing equilibrated
aqueous phases without significant errors from such effects would be
desirable.
For this purpose we have adapted the generator column method
described by Hay e£ a_L [1978]. A generator column has a solid support
coated with a solid or liquid stationary phase. When water is pumped
through the column, an aqueous solution is generated which is equilibrated
with the stationary phase. May e£ al_. [1973} used their generator
columns, packed with glass beads, mainly to measure solubilities
of solid polycyclic aromatic hydrocarbons; the only liquid stationary
phase used by the.., was benzene [Hay et^ <*!•, 1978]. We have redesigned
the ge.'.erator column, changed the support to silanized silica in order
to increase the coverage, and extended the stationary phase to hydrocarbon-octane1
mixtures.
In this report we discuss the work done under Interagency Agreement
EPA-80-2095 in the period October 1, 1980 to September 30, 1981. The objective
of this work was to develop and validate a chromatographic method to measure
C* and K . and to make measurements on selected classes of organic compounds
in order to obtain accurate and precise K . and C* values.
In the third section of this report, "Comparison o* the Experimental
Methods," the shake-ftask method is compared with the generator column
method. The advantages and limitations of both methods are discussed.
The fourth section includes experimental details of the generator
column method and the gas-liquid chromatographic method for determination of
activity coefficients and cctanol/water parti ton coefficients of organic
compounds.
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In the fifth section, "Direct Experimental Validation of the Generator
Column Method," the work done to establish a bench-mark C* and KQ/w measurement
for n-propyl benzene is discussed. A detailed error analysis investigating
every experimental parameter was made in order to arrive at the best
and Cw values. These values were then compared with the values measured
by the snake-flask method.
In the sixth section, "Results and Discussion," K and C" values are
given for over 90 compounds representing seven types of organic
compounds. Further validation of the yenerator column method is made by
analyzing the data using linear regression analysis to the thermodynamically
derived equation log K , = c log YJ * d» where c and d are series constants
and i* is the activity coefficient of solutes in water saturated with octanol.
The accuracy and precision of the data is discussed in terms of the value of
the slope, c, and the coefficient of detenvi nation, r , for the regression
analysis of the data to the different chemical classes.
In the seventh section, "Recommendations for Future Work," we
recommend that additional K . and C* measurements be made in aqueous NaCl
solutions and simulated sea water in order to establish the salinity dependence
of these properties. We also recommend that C* measurements be made at different
temperatures in order to establish the temperature dependence of solubility
and that solute activity coefficients be rr-easured by d head-space method
to further validate the generator column method. There is also a need
for KQ. and C* measurement on classes of compounds not studied in this report.
In Appendix I, the thermodynamic derivation is given for the correlating
equation
log KQ/W = - log ** - log Y°
where $* is the volume fraction of solute in water saturated with octanol
and Y? Is the activity coefficient, on a volume fraction basis, of the
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solute in octanol saturated with water.
Appendix II includes the proposed test method for determination
of the aqueous solubility of organic compounds.
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III. COMPARISON OF EXPERIMENTAL METHODS
Generator columns have several advantages over shake-flask methods
for equilibrating water with a liquid organic phase. The flow rate of water
through the column can be made slow enough to avoid colloidal dispersions,
while the large interfacial area between the organic and aqueous phases allows
rapid equilibration. When the column is part of a continuous and closed flow
system, the system walls become equilibrated with the aqueous solution and
errors from adsorption are avoided; also there is no exposure of the solution
to the atmosphere, thus loss of volatile solutes is avoided. Only about 1 ml
of the organic phase is sufficient to load the column, and the column will
generate samples of the aqueous solution of whatever volume is needed for
analysis until the organic phase has been stripped. Once a column has been
loaded with a given organic phase, it is a simple matter to vary other
parameters such as pH or salinity of the aqueous phase to determine these
effects on the aqueous solubilities of organic compounds.
For compounds having relatively large aqueous solubilities (>1.0 H)
and low KQ^w values (<100), there is no particular advantage 1n the
generator column method over the shake-flask method, since colloidal
dispersion and surface adsorption are no longer an experimental problem.
However, the generator column method is still preferred because it is more
convenient to thermostat a generator colics, than •> fUsk that must be shaken.
The generator column method requires no special skill of the operator.
The generator column is easy and Inexpensive to construct and generally
yields reproducible and accurate data at desired temperatures; whereas,
one will require a thermostated centrifuge to obtain accurate results
using the shake-flask method.
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In summary, the generator column method is much better than the shake-flask
in that the measurement time is much less than the shake-flask method.
Although equipment is required to measure the solute concentration in the
two phases (HPLC or GLC) the generator column method with its
closed flow system makes the measurements more convenient and avoids the
intrinsic errors associated with the shake-flask method.
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IV. EXPERIMENTAL
A. Aqueous solubility and partition coefficients
Keagents
The compounds (solutes) for which aqueous solubilities and
octane 1/water partition coefficients (K , 's) were measured were
obtained from various commercial sources with purities >98S. The octanol
was purified by washing successively with 0.1 K H^SO^, 0.1 H NaOHt and
distilled water. It was then dried with CaClg, filtered and distilled
at atmospheric pressure. HPLC grade methanol and water were used to
prepare the mobile phases for liquid chromatography. Ordinary distilled
water was used for the aqueous phase solutions. Octanol saturated with
water (w-octanol) was used for making up the solute in octanol solution.
This solution was made up by stirring 10 mL of water with 250 ml of octanol for
several hours. The lower excess water layer was removed by a siphon. For the
*o/w measuremsnts, a \% (by weight) solute in w-octanol was used for coating
the solid support in the generator colurm.
The design of the generator column and the method used to determine the
solute concentration, c", in the aqueous phase depended on whether the
5
solute absorbed the U.V. For compounds which absorbed in the U.V., high
pressure liquid chromatography, HPLC, was used to determine C*; for compounds
which did not absorb in the U.V., solvent extraction followed by gas
chromatographic analysis was used to determine C*.
Generator Colurn
The design of tne generator column is shown in Figure 1. The column
consists of a 6 mm (outside diameter) Pyrex tube joined to a short enlarged
section of 9 mm Pyrex tubing. To pack the column a plug of silanized glass
wool was inserted at one end of the 6 mm tube. Silanized diatomaceous silica
support (about O.Sg 100-120 mesh Chromosorb W cleaned by Soxhlet extraction
with ethanol and dried) was poured into the tube with tapping and retained
with a second plug of silanized glass wool.
8
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Inlet
20 cm
Glass Wool
Support (100-120 mesh
Chromsorb W)
X>r*—
6 mm
Glass Wool
=-9 mm
Outlet
Figure 1. Generator column used to generate the aqueous phase. The column is 20
cm. long and packed with 100-120 mesh ehromosorb W for the solid support.
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The column was coated with a liquid solute by pulling approximately
2 ml of the liquid through the clean dry support with gentle suction. The
column was coated with a solid solute by dissolving the solute in a volatile
solvent (102 v/v) and then pouring the mixture into the column until all
the solid support was saturated as evident by the appearance of the volatile
solution at the base of the column. The solvent was then distilled off
under reduced pressure.
HPLC Method
The HPLC analytical system is shown schematically in Figure 2. Two
reciprocating piston pumps delivered the mobile phase (water or a methanol-
water mixture) through two 6-port high pressure rotary valves and a
30 X O.b cm C-18 analytical column to an ultraviolet absorption detector
operating at 254 nm. Chromatogram peaks were recorded and integrated with
a recording integrator.
One of the 6-port valves was sample injection valve used for injecting
samples of either the octanol phase for analysis, or standard solutions
of the solute in methanol for determining response factors. The sample loop
volume was determined by a spectrophotometric method using basic chromate
solution which are known tc be suitable as absorption standards [Edlsbury,
1967J. The method consisted of measuring the absorbance at 373 rtm of three
loopfuls of ar» aqueous stock solution of K^CrO^ (1.3% by weight) diluted to 50 ml
with 0.2 percent KOH, and measuring the absorbance of the same stock
solution -\fter diluting 1:500 with 0.2 percent KOH. From these absorbances
the loop volume was calculated to be (35.7 +, 0.1) mL.
The other 6-port valve 1n the system served as a switching valve for
the extractor column which was used to remove solute from the aqueous
solutions. The extractor column was a 6.6 X 0.6 cm stainless steel tube
10
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WeOH
Sample Injection Valvo
Switching Valve
Switching PiitJern:
MPLC
Pumps
Sample Loop
T
Weighing Bottle
or Waste
Extractor Column
Analytical
Column
• • .!• L.
Plollcr
Integrator
UV
Detector
i
?
Waste
Figure 2. Schematic of the HPLC analysis system. The generator column outlet 1s connected at A and
when a known amount of aqueous phase 1s collected in the weighing bottle, the switching
valve 1s switched and the HPLC pumps transfer the mobile phase through the extractor column
and Into the analytical column. The syringe injection Is used for calibration of the UV
detector.
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with stainless steel end fittings containing 5-i.rn frits, filled with
a superficially porous reverse phase packing (Bondapak C,n/Corasil,
Waters Associates). Aqueous solution from a generator column entered
the switching valve through the 1/16 in (1.6 mm) stainless steel tubing
labelled "A" in Figure 2. A water bath was used to thermostat
to +_ 0.05°C the generator column, the switching valve, the extractor
column, and the interconnecting stainless steel tubing.
The procedure for analyzing the aqueous phase was first to flow
the aqueous solution to waste with the switching valve in tne inject
position In order to equilibrate internal surfaces with the solution, thus
insuring that the analyzed sample would not be depleted by solute
adsorption on surfaces upstream from the valve. At the same time, water
was pumped from the HPLC pumps in order to displace methanol from the
extractor column. The switching valve was next cnangei! to the load position
to divert a sample of the solution through the extractor column, and the
liquid leaving this column was collected in a weighing bottle. During
this extraction step, the mobile phase was changed to a methanol-water
mixture to condition the analytical column. After the desired volume
of sample had been extracted, the switching valve was returned to the
Inject position for elution and analysis. Provided that there was no
breakthrough of solute from the extractor column during the extraction
step, the chromatographic peak represented all of the solute in the
sample. The solute concentration in the aqueous phase was calculated
from the peak area and the weight of the extracted liquid collected in
the weighing bottle.
12
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The octanol/water partition coefficient was calculated from the solute
concentration in the octa"ol and aqueous phases by dividing the concentration
in the octanol phase by the concentration in the aqueous phase. The water
flow through the generator column was 2 mL/min. Further experiments
with a generator column at 25°C show that within experimental error
(standard deviation 3» or less) the measured aqueous concentration was
independent of flow rate (in the range 0.5-2 mL/min).
GC Method
In the GC method aqueous solutions from the generator column entered
a collecting vessel (Figure 3) containing a known weight of extracting solvent
which was immiscible in water. The outlet of the generator column was positioned
such that the aqueous phase always entered below the extracting solvent.
After the aqueous phase was collected, the collecting vessel was stoppered
with a 3/8" Teflon Swagelok cap, and the quantity of aqueous phase was determined
by weighing. The solvent and the aqueous phase were equilibrated by either
stirring with a glass enclosed magnet or by rotating the collecting vessel
at the rate of two revolutions per minute for five minutes. It was found
that rotating the collecting vessel for longer than five minutes did not
Increase the amount of solute extracted into the extracting solvent, A small
amount of the solvent was then Injected into a gas chromatograph equipped
with flame ionization detector, and the solvent concentration In aqueous
phase was determined from a calibration '•urve constructed using known
concentrations of the solute. In order to determine the partition coefficient.
Ko/w* samPles of tlie 1* (by weight) solute in n-octanol solution were injected
Into the GC, and concentration of the solute in the octanol phase was
similarly calculated from a calibration curve. As for the HPLC method, our
experimental error 1n the GC method was less than 3%.
13
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Bath
Return
Generator
Column
Inlet
Generator
Column
To Constant
Temperature
Bath
Extracting
Solvent
Figure 3. Generator' column and collecting vessel used for analysis of the
aqueous phase by the GC-solvent extraction method.
14
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B. Solute activity coefficient__1n_ octanpl
The stationary phase in octanol, was coated onto the support material,
Chromosorb W-HP, 100/120 mesh, and the weight percent of coating was
determined by an ashing method. A stainless steel column (1/8" OD) was then
packed with a known amount of the coated support and was connected to a
Hewlett-Packard 5830A gas chromatograph equipped with a flame ionization
detector (FID) for the determination of the solute retention time. The
temperature of the column was controlled by circulating water through a
copper tubing jacket around the column and by a Haake Model FK temperature
regulator which regulated the water temperature to 25.0 + 0.05 °C.
The column inlet pressure, measured with a precalibrated pressure
gauge (range 0-15 PSI), was kept constant during a run by regulating with
a precision valve. In order to measure the carrier gas flow rate the column
was disconnected from the FID, just before and after the experiment, and
a soap bubble flowmeter was connected to the column outlet. The carrier
gas was presaturated with n-octanol in order to reduce bleeding of the
stationary phase.
Since the retention times decreased as the experiment progressed due
to column loss of the n-octanol, toluene was used as a reference retention
time standard and Injected with each solute. The measured retention ti;r.es
were then corrected for bleeding using the reference solute retention time.
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The solute specific retention volumes (V } were calculated by using
the following equation _
„ V V!a
" ' '
a
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V. VALIDATION
Because of the general lack of agreement in reported C^ and K .
s o/w
values, the first steps toward validation of the generator column method
was to compare generator column data with data measured in this laboratory
by the shake-flask method. Propylbenzene was chosen as the compound
to establish a bench mark measurement because it is very stable, absorbs
1n the U.V., has a typical log K . and log C* value, and can be
obtained pure (>99.9 %) from commercial sources.
A. Shake-Flask Equilibrations
For each equilibration about 10 ml of water and about 4 ml of the
organic phase were placed in a closed Pyrex vessel and stirred with a glass
enclosed stirring bar. For the solubility measurements the organic phase
was the pure solute. For the K . measurements the organic phase was
a }% (by weight) octanol solution. All precautions were taken to eliminate
systematic error. All transfer vessels and tubing were prerinsed with
the aqueous phase to avoid solute adsorption on the walls. The equilibration
flask was stoppered at all times to avoid exposing the aqueous phase to the
atmosphere. To prevent emulsion formation in the aqueous phase vigorous
stirring was avoided. Most of the organic layer was confined to a narrow
neck at the top of the vessel. Above the neck was a 3/8-inch tube septum
for sampling the organic layer. The equilibrated aqueous phase was
transferred to the HPLC system for analysis with the aid of nitrogen pressure.
17
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B. Solubility
Table 1 lists our solubility results for propylbenzene. The aqueous
samples were 2-6 nt in volume. The shake-flask and generator column results
for comparable temperatures agree within experimental uncertainty. Our
value at 25°C> 4.3 X 10~4 M, is similar to the values for this temperature
reported by Andrews and Keefer [1950] (4.6 X 10"4 M) and by Hermann [1972]
(5.0 X 10"4 M). The temperature dependence of the solubility suggests
that there is a minimum in the neighborhood of 20°C. Solubility minima
near 18°C have been observed for benzene and its methyl, dimethyl, and
ethyl derivatives [Bohon and Claussen, 1951]. In the case of propylbenzene,
G^l Sill- [1976] predict from the temperature dependence of the heat
of solution that there is a solubility minimum at (18.6 +.0.2) °C which is
consistent with our results.
C. Partition Coefficient
The octanol-water partition coefficient, KQ., was calculated from the
measured propylbenzene concentrations in the equilibrated octanol and
aqueous phases by dividing the concentration in the octanol phase by the
concentration In the aqueous phase.
The volumes of the aqueous phase samples used to obtain the partition
coefficient values listed in Table Z were in the range 1-4 ml for the
shake-flask results and 10-24 ml for the generator column results. The
water flow rate through the generator columns was 2 mL/min. Further
experiments with a generator column at 25°C showed that within experimental
uncertainty (standard deviation 3% or less) the measured aqueous
concentration was Independent of the water flow rate (in the range 0.5-2
rnL/min) and was independent of the volume of sample passed through the
extractor column (in the range 2-24 ml). These experiments show that
under our experiment.! conditions the equilibration was complete in the
-------
Table 1
Aqueous Solubility of n-Propylbenzene
t/°Ca nb C", 10'4 Mc
stir-flask, stirred 16 h
ambient 4 4.27 + 0.06
Generator column
15.0 3 4.26 + 0.05
20.0 2 4.25*0,12
25.0 3 4.32 1 0.02
30.0 3 4.45 + 0.05
Equilibration temperature. Ambient is (23 + 1)°C.
Number of aqueous solution samples analyzed.
cAqueous concentration; the mean value and the confidence limits
at a 95% confidence level are listed.
19
-------
Table 2
Octanol/Uater Partition Coefficient, K. , of n-Propylbenzene
Method Used Cone, of propyl-
benzene 1n octanol
(Moles/ liter)
Stir-flask 0.222
0.223
0.220
Generator column 0.038
0.086
0.223
0.223
0.223
0.223
0.223
0.223
Equilibrium
Temperature
(°C)
23 ±1
23+1
23 + 1
25.0
25.0
25.0
10.0
15.0
20.0
30.0
35.0
Number of Number of
Hours Stirred Octanol
Phase samples
Analyzed
24 4
41 4
44 3
4
4
4
4
4
4
4
4
Number of
Aqueous
Phase Samples
Analyzed
4
3
4
9
4
6
2
2
2
4
3
L°9 *o/w
3,73 £0.02
3.72 +0.01
3.71 +0.01
3.69 +0.01
3.70 +0.01
3.72 +0.01
3.71 +0.01
3.72 +0.01
3.74 + 0.01
3.72 +0.01
3.68 + 0.01
-------
generator column, and that there was no significant breakthrough of
propylbenzene from the extractor column.
Three shake-flask equilibrations with different stirring times were
carried out (Table 2). With increased stirring time, there was a decrease
in the partition coefficient values of about the same size as the experimental
uncertainty. There is good agreement between these values and the generator
column results.
The partition coefficient 1s seen to vary with temperature (Table
2) having a maximum In the vicinity of 20°C. However, further studies are
required to generalize this phenomenon. It Is Interesting to note that while
the solubility and the partition coefficient of propylbenzene both vary
with temperature, their product over the temperature range in which both
quantities were measured (15-30°C) 1s essentially constant (2.26 + 0.05 M).
This suggests that the heat of solution of propylbenzene in octanol Is small.
The partition coefficient measurements at 25°C (Table 2) show a small
but systematic decrease of log KQ/W with decreasing concentration in the
octanol phase. Extrapolation to Infinite dilution gives log K . = 3.69 + 0.01
o/w —
at 25°C. Iwasa ejt al_. [1965] report log KQ/W = 3.68 + 0.01 from shake-flask
measurements at ambient temperature, 1n excellent agreement with our
results.
Activity Coefficients
In Appendix I an expression Is derived showing the relationship of
109 Ko/w with the 8<3UCOUS solubility in term of solute volume fraction
*°9 Ko/w " " '°9 *s " ^°9 Ys
where ** Is the solute volume fraction 1n water saturated with octanol
-------
and Y? is the solute activity coefficient, on a volume fraction basis,
in octanol saturated with water. This equation provides an indirect method
to determine K. from the solute activity coefficient in octanol and its
aqueous solubility.
The solute activity coefficient in octanol, Y? » can be determined from the
retention volume [Conder and Young, 1979] of the solute eluting from a G.C.
column containing octanol saturated with water as the stationary phase.
This method for determination of Kr»w has been documented in our recent
publication [Tewari et al_., in press]. Since Y? "Is measured at infinite
" 5
dilution and $* is also at Infinite dilution, the K , determined using
the above equation is also at infinite dilution.
The value for log Y? determined by the G.C. method for a number of
solutes are listed in Table 3. Using Y° and Y" determined from
the aqueous solubility and solute molar volume, octanol/water partition
coefficients for the solutes were calculated and compared with the
experimental KQ^W. These two quantities are listed in the last two
columns of table 3. An examination of these two columns shows an excellent
agreement between the experimental KQ/W and the calculated K.. Based
on our measurements, there is a complete consistency In the above
equation. Thus these results suggest that our data are precise and
accurate and that the generator column is a valid method for determination
of the aqueous solubility and octanol/water partition coefficient of organic
compounds.
In conclusion, we have demonstrated In this section that the
generator column method for determining C* and K , is a valid and an
accurate method for measuring these quantities.
22
-------
Table 3
Activity Coefficients and Octanol/Water Partition
Coefficients of Organic Compounds at 25.0°C
Solutes
Benzene
Toluene
Ethyl benzene
o-Xylene
m-Xylene
Chlorobenzert
-------
VI. RESULTS AND DISCUSSION
The experimentally determined values of K . and C* and the calculated
^J
values of YS are listed in Tables 4 through 10 for several classes of compounds.
The notations a and b refer, respectively, to the HPLC and GC methods of analysis.
The average experimental uncertainties in KQ,W and C* are around l.OX. An
asterisk is used to indicate that the literature data are calculated values
according to Hansch et al_. (1968). Our results are generally in good agreement
with available experimental literature data obtained by the conventional
shake-flask method.
The present data were subjected to a linear regression of log K . •
c log YJ + d for each class of compound and for all compounds taken together.
The results of these analyses are shown in Table 11.
The present equations are Inadequate to explain K . and C* data of
aromatic solids listed in Table 4A. Analysis of these data 1s, therefore,
not Included in Table 11.
According to equation 9 of Appendix I the slope for each class should be
unity and the negative of the intercept Is log Y° (assumed to be relatively
constant). Examination of Table 11 shows that the slopes are indeed close to
unity, ranging between 0.91 and 1.08. These small deviations are most likely
caused by slight variations 1n log >J within each class (Tewari et aJL, in
press). For example, the average of the difference between log TW and log K .
for the aromatic compounds is 0.55 for those with aliphatic substltuents and 0.68
for those with halogen substltuents, whereas the least-squares value of log
Ys Is 0.77 when all the aromatic compounds are Included. Therefore, the Intercepts
represent only approximate (averaged) values of log Y? for each class.
These findings show ttoit the octanol/water partition coefficient of a
solute may be estimated with reasonable accuracy from knowledge of Its aqueous
24
-------
Table 4
AQUEOUS SOLUBILITIES AND OCTANOL/KATER PARTITION
COEFFICIENTS OF ORGANIC COMWXAOS
rrr
Aromatic Hydrocarbons
Concentration
1091;
Solute
This Study literature Value
IH) IM)
CMorooenzefte 2.62 X 10
2.84 X 10
3.56
This Study-J
2.98*
0/,
Literature
Toluene
Etnylbenzene
o-xylene
•-Kylefvc
p-Xylene
n-Propyl benzene
n-Butylbenzene
n-Pentyl benzene
n-Heiy I benzene
6.28
1.76
2.08
1.51
2.02
4.34
1.03
2.S9
6.27
X
X
X
X
X
X
X
X
X
lO"3
10°
10-3
10-3U)
,0-3(0)
)a-4CO)
,o-«f.b>
10-5U)
,«•»(•)
5.80 X
1.52 X
1.6) X
1.38 X
1.47 X
4.99 X
8.79 X
«
••>
10
10
10
10
10
10
10
-
*
.3
-3(c)
-3(c)
-3{c,
-4(f)
•5(c)
3
3
3
3
3
4
4
S
5
.17
.66
.60
.73
.60
.22
.79
.35
.92
4 Ccl&S
«.* VJ
3.13<*>
J.I|W.
3.20**'
3io(«l*b)
• lo
3.69f'-b>
4.2B(0)
4CA»*»
• W
5«?Z
2.63
3.15
3.12
3.20
3.15
3.63
4.26
—
—
(f)
to-3'''
lo-3'*)
io-2l«)
io-^-»
3.56 2.98(tJ 2.99tf>
3.96 3.28<§) 3.25(f)
3.47 2.67*'* —
3.46 2.7/1*1
3.52 1.961** —
2.50 1.B5'*1
Indicates that the literature daU are calculated values according to Hansch 5J. aJL, 1968.
'*' W>LC eethod of jnalysis.
(b)
(c)
GC neUxxl of analysis.
Sutton and Calder. 197i.
td) NcAulUfe. 1966.
Hansch et.aK, 1968.
Hansch and Lto. 1979.
et »i... 1980.
... and Burger. 1955
(J)
(f)
(9)
(h)
Average standard deviation of log i* M«urenents Is 0.04.
Average standard deviation of log KO/W Masurenents Is 0.04.
25
-------
wuenn JOIMIIITUS. AND OCTA*WWTM MKTIIIOM comictwTS
Of OftSMIC aM>OUIC>S
MlictlUntouf AroMtfc
txnttnt
SOW..
n-Hcplylbwuenc
n-OctyU«um
Hc«Me Otf 1 beftieti*
Aqueous CcACtntritlMi
Thtt study L1t*r«urt
(H) («)
Z.S* X IIT'14'
|.4« X 10'7'*'
I.4S I 10-6(*»
.« ,;»»
.
t.ze
;.u
—
109 "o/*
T«1s Stud/'^' L1ttr«tur«
—
—
4.«1">
(UpMluleive
2.J9 I 10'
*U)
I XT*'*' ~.
Ml I IO*4'*'
J.S1
W
**'*'
p-Fluorut«fiiirl
chlorld*
•-Dlcnlorgocnicnc
•-DtcMarofettucfW
p'DIChlorottflMM
1,Z,)-tricii1«raMnttiit
1 .2 ,4-THmthy IbcfUtnt
i.Cl
*.»
<*> -.
6.40 X
1.90 I 10*Zt*>
2.J.*.Trl««tliyl
*.«
<•>
pJwoo!
,.„
(»)
|*| Indlcim tfwt tlw lUcratw* tftU
-------
Table 5
AQJEOUS SOLUBILITIES AND OCTANOL/WATER PARTITION
COEFFICIENTS OF ORGANIC COMPOUNDS
Unsaturated Hydrocarbons
Solute
1-Hexene
1-Heptene
VOctene
l*Nonene
1-Pentyne
1-Hexyne
Aqueous Concentrations
This Stwdy
(H)
8.28 X 10~^b) 5
1.85 X 10~Atb*
3.65 X 10"5(b) 2
8.85 X 10"6fbJ
1.54 X 10"2tb)
8,37 X 10'3tb)
Literature
value
(H)
on w l/vH^i
• Q7 A III
—
.40 X 10"5
3.98
4.58
5.24
5.81
2.81
3.01
109 Ko/»
Th1s^^ Literature
Study Value
3.47- )J 2.70*e)*
3.99*b)
4.88tb^ 3.70^e^*
5.35^
2.12
-------
Table 6
AQUEOUS SOLUBILITIES AND OCTANOL/WATER PARTITION
COEFFICUNTS Of ORGANIC COMPOUNDS
Halogenated Hydrocarbons
Solute
1-Chlorobutane
1-Cfilcroheptane
I-Bromobutane
l-Brofliopentane
l-Brwnohexane
1 -Brow/heptane
1-Bromooctane
Bremochloromethane
l-8romo-2-chloro-
propane
1-Iodofoeptane
Trichloroethylene
4-Brou»- 1 -butene
Ally! bromide
Aqueous Concentration
This Study Literature
Value
(H) (M)
9.43 X }Q~3M 7.19 X 10*3{e)
1.01 X 10'4(b)
6.34 X 10'3(b) 4.13 X 10'3{e)
8.38 X lfl-4{b)
1.56 X 10'4(b)
3.71 X 10-5(b)
8.65 X 10'6(b)
0.129(b)
1.42 X 10-2(b)
1.55 X 10'2 2.60^*
3.49^>
3.8Qfb>
4.36
2.18
2.53^)
2.53<'>
1.79(4>
(a)
(b)
(e)
Indicates that the literature data are calculated values according to Hansch «t aj... 196«.
HPLC method of analyls.
GC method of analysis.
SutLon and Calder, 1975.
^d) McAullffe. 1966.
te) Hansch et aj... 1963.
f Hansch and Leo, 1979.
Mac Kay et. a\_., 1980.
Reddick and Burner. 1955.
(9)
(h)
(J)
Average standard deviation of log YJ "easurenents Is 0.03.
Average standard deviation of 109 KO/W measurements is 0.03.
28
-------
Table 7
AQUEOUS SOLUBILITIES AND OCTANOL/HATER PARTITION
COEFFICILNTS OF OR3ANIC COMPOUNDS
Normal Hydrocarbons
Aqueous Concentration log y* log K.
Solute
n-Pentane
n-Hexane
n-Heptana
n-Octane
This Study
(M)
5.65 X 10"4(b)
1.43X10"4(b)
3.57 X 10"5(b)
6(b)
9,66 X 10 b
Literature
Value
(M)
5.39 X 10'4(d) ' 4.19
1.13 X 10~4^ 4.73
3.05 X 10~(dJ 5.28
5.97 X 10'6(d) 5.80
This"*
Study
3.62"1'
4.11'"'
4.66'
3.50*
4.00(6'*
(a)
(b)
(c)
(e)
(f)
(9)
(h)
Indicates that the literature data are calculated values according to Hansch et. al., 1968.
HPLC method of analysis.
GC method of analysis.
Sutton and Calder, 1975.
McAullffe, 1966.
Hansch et aj_., 1968.
Hansch and Leo, 1979.
MacKay et al., 1980.
Reddlck and Burger, 1955.
* ' Average standard deviation of log y* measurement? is 0.06.
s
Average standard deviation of log K , measurements Is 0.02.
-------
Table 8
AQUEOUS SOLUBILITIES AND OCTANOL/WATER PARTITION
COEFFICIENTS OF ORGANIC COMPOUNDS
Aldehydes and Ketones
Solute
2-Butanone
3- Pen ta none
2-Heptanone
2-Octanone
2-Nonanone
2-Decanone
Acetal
2-Furaldehyde
Aqueous Concentrations
This Study
(H)
1.89
0.53
3.57 X 10'2
8.85 X 10~3
3(a)
2.61 X 10 J
5.03 X 10"4
0.75
0.81
Literature
Value
(M)
—
0.43
3.79 X 10'2*e)
...
—
—
0.42(h)
0.85(e)
log Y*
0.77
1.25
2.30
2.86
3.35
4.02
0.97
1.17
This")
Study
0.69
0.99{b)
1.98
2.76
3.81
0.52
.52<"
109 Ko/w
Literature
Value
0.29(e)
0.79^*
1.73^>*
...
—
...
— .
—
(b)
(c)
(d)
(e)
(O
(9)
00
(D
Indicates that the literature data are calculated values according to Kansch et al_., 1968.
HPLC method of analysis.
GC method of analysis.
Sutton and Calder, 1975.
HcAullffe. 1966.
Hansch ej^ajk, 1968.
Hansch and Leo, 1979.
HacKay et al... 1980.
Reddick and Burger. 1955.
Average standard deviation of log Y" measurements Is O.OS.
Average standard deviation of log KQ,W measurements is 0.03.
30
-------
Table 9
AQUEOUS SOLUBILITIES AND OCTANOL/WATER PARTITION
COEFFICIENTS OF ORGANIC COMPOUND.-.
Esters
Aqueous Concentrations
Solute
Methyl nonanoate
Methyl decanoate
Ethyl acetate
n-Propyl acetate
n-Butyl acetate
Ethyl prcpionate
2-Bromoethyl
acetate
This Study
(H)
1.33 X 10~*
5(b)
2.05 X 10 3
0.726{b)
0.200tb)
5.77 X 10'*
0.148
fl.2«W
Literature
Value
(H)
—
0.912^
0.185te)
0.203te)
0.187(h)
—
w(1)
S • O/ "
Thls*^ Literature
Study Value
4.58 4.32{b)
5.36 4.41tb)
1.15 0.68{b) 0.73le)*
1.64 1.24^ 1.23<«>*
2.12 1 .82 1 .73
1.77 1.43(b)
11.1 i 11 '^ ' _--.
.DJ 1 . 1 1 -»»
(a)
(b)
* '
Indicates that the literature data are calculated values according to Hansch et^al_., 1968.
HPLC method of analysis.
GC method of analysis.
Sutton and Calder, 1975.
McAuUffe, 1966.
Hansch et aj.., 1968.
Kaii&Ch uiiU Leo, 1979.
MacKay et aj.., 1980.
Reddlck and Burger, 1955.
Average standard deviation of log y" measurements Is 0.04.
Average standard deviation of log K. measurements Is 0.02.
31
-------
Table 10
AQUEOUS SOLUBILITIES AND OCTANOL/WATER PARTITION
COEFFICIENTS OF ORGANIC COMPOUNDS
Alcohols
Solute
Tnls Study
(H)
wH)
Aqueous Concentration Log YS v '
Literature
Value
L°9 K0/w
This")
Study
Literature
Value
1-Butanol
0.854
(b)
1.0
0.785
(b)
0.84v
1-Pentanol
O.U3
(b)
0.249
(h)
1.84
1.53
(b)
1.34
(O*
1-Hexanol
4.14 X 10"
2.28
2.03
(b)
1.84*
1-Heptanol
1.13 X 10
.-21
2.80
2.57
(b)
2.34
(e)*
1-Nonanrl
7.35 X 10'
3.89
3.77
(b)
2 Ethyl-1,3-hexanedlol 1.56 X 10"
3.61
3.22
(b)
(a)
(b)
(c)
(d>
(e)
(f)
(9)
(h)
(1)
(j)
Indicates that the literature data are calculated values according to Hansch ejt al_. , 1968.
HPLC method of analysis.
GC method of analysis.
Sutton and Calder, 1975.
McAultffe. 1966.
Hansch et aj_. , 1968.
Hansch and Leo, 1979.
MacKay et aj[. , 1980.
Reddlck and Burger, 1955.
Average standard deviation of log Y"
Average standard deviation of log
measurements 1s 0.03.
measurements Is 0.03.
32
-------
to
CO
Table 11
Coefficients of the Regression Equation and
the Coefficient of Determination for the Solutes
Type of
Compounds
Aromatic
Hydrocarbons
Unsaturated
Hydrocarbons
Halogenated
Hydrocarbons
Normal
Hydrocarbons
Aldehydes and
Ketones
Esters
Alcohols
All compounds
Number of
Compounds
18
6
13
4
8
7
6
62
Slope {c}
1
1
0
0
1
0
1
0
.056
.024
.907
.972
.079
.932
.030
.944
+ 0.026
+0.061
+ 0.033
+_ 0.016
+ 0.065
+ 0.055
+ 0.011
+0.018
-0.
-0.
-0.
-0.
-0.
-0.
-0.
-0.
Coefficient of 2
Intercept(d) Determination {r )
768
585
323
468
465
285
348
311
i o.ioo
+ 0.267
+ 0.133
+ 0.081
+ 0.155
+ 0.167
+ 0.112
+ 0.066
0.
0.
0.
0.
0.
0.
0.
0.
990
986
986
999
978
982
994
980
-------
solubility, its molar volume and the regression equation for compounds
of its class. Also, this study establishes that the generator column
method coupled with either HPLC or GC modes of analysis provides an accurate
and rapid method for systematic determination of K. and C* for organic
compounds.
Equation 9 of Appendix I was rigorously derived from thermodynamic
principles. Plots of log K, versus log Y^ having slopes of unity are a
strong indication of the accuracy of the data. The scatter or precision of
the data should be reflected in the coefficient of determination obtained from
a linear regression analysis of the data. A coefficient near unity indicates
good precision in the measurements.
The fact that the slopes of the log KQ. versus log y* plots for the
seven different classes of compounds are near unity (Table 11) is a strong
argument in favor of tne generator column method giving accurate Cw and K .
values and 1s a further validation of the method.
It 1s Interesting to analyze literature values of K . and C* 1n the saute
manner and compare these results with those obtained by the generator column
method. In Figure 4 are plotted lo<, KQ,W values measured by the generator
column against literature log KQ.W values measured by the shake-flask method.
The points that are obviously off 1n the literature log KQ/w range of 2 to 4
are alkanes that have been calculated by the group addttivUy method and are
iiOt experimental values.
In Figure 5 are plotted log C* values measured by the generator column
method against literature log C* values measured by the shake-flask method.
Th*1 agreement is much better than that 1n Figure 5 because all the literature
values are experimental values.
34
-------
6.
u»
U1
t—»
ce.
UJ
o.
X
C9
O
5.
~ 4.
3.
2.
1.
r~ » 0,913
Log K. (Exp) -.1.148 Log K,
0/w (Lit) -0.135 0/w
1.
2. 3. 4.
LOG KQ/W (LITERATURE)
5.
6.
Figure 4. Experimental Log KQyw Versus Literature Log
-------
CO
Ul
Cu
X
LJ
C3
O
5.
«! 4.
I rc = 0.993 u
•Log C" (Exp) = -0.970 Log C* (Lit)
5 +0.011
L/ I
1.
2. 3. 4.
- LOG C* (LITERATURE)
Figure 5. Experimental Log C^ Versus Literature Log C
,w
-------
In Figure 6 are plotted literature log K . values versus literature
log 1/C* values. The large scatter in the points indicates the accuracy
and/or the precision of the measurements is not very good. In Figure 7 are
plotted log K , versus log 1/C* where both K . and C* were measured by the
generator column method. The error bars indicate the precision of the
measurements. A linear regression analysis of the data gives a slope of
0.994 with a coefficient of determination of 0.998 indicating that the
measurements are accurate and precise.
In conclusion we feel that the Figures 4 through 7 and the regression
analysis of the data on the seven different groups of compounds show that the
slopes of the log KQ,W versus log Y* Plots and the coefficients of
determination of these plots are all approximately equal to unity. This is
further validation of the generator column method.
37
-------
5.
4.
3.
ts
o
• r2 « 0.903
Log KQ/W • -0.657 Log q +0.993
2.
1.
1.
3.
- Log C*
4.
Figures
Log KQ/W Vers0s -Log C^ for the Literature Values.
-------
CJ
5.
4.
I 3.
g
1.
r » 0.994
Cog KQ/w = -0.891 Log cj + 0.730
I
I
I
1.
2.
Figure 7. Log KQ/w Versus -Log
3. 4. 5.
- Log C*
C^ for cfTe experimental Values,
6.
-------
VII. RECOMMENDATIONS FOR FUTURE RESEARCH
In any research endeavor it is frequently the case that more new
questions are asked than old ones answered. This is the case for this
work. Two studies were initiated that are incomplete: (1) salinity
dependence of K . and Cw and (2) the temperature dependence of K . and
C . Information obtainted from these studies is important for determining
Vr
the rate and transport of organic substances in the environment.
Sal i ni ty Dependence
It can be shown from thermodynamics that the octanol/salt water
partition coefficient K-sw is related to the concentration of the aqueous
salt solution, C$, by equation 1:
log KQ/SW - log K0/w * ks Cs (1)
where k$ 1s the salting out coefficient which is characteristic of the solute.
Thermodynamics also shows that for compounds of similar chemical
structure k$ is related to the solute molar volume 9 by equation 2:
ks » k, + k2 7 (2)
where kj and k~ are series constants* Combining equations 1 and 2
log KQ/SW - log K0/w Mk, + k2 7) Cs (3)
To date we have data on two different classes of compounds, the
n-alcohols and the alkylbenzenes. These data were taken in order to
test equation 3. It would be desirable to have data on other types of
compounds in order to generalize equation 3.
Temperature Dependence
The temperature dependence of aqueous solubility may be expressed as
AH
d log Cj/dO/T) * - -^
AH is the heat of solution, and R Is gas constant. Very little is known
40
-------
about the heats of solution of hydrophobic substances. Since water temperature
varies from -400C (in the artic) to 40°C (near the equator), it is desirable
to study temperature dependence in order to make accurate predictions of the
aqueous solubility of organic compounds.
Head-Space Measurements
During the course of this work it wc-.s realized that it would be
desirable to have another method (other than shake-flask) for measuring
*o/w for volatile P°lap compounds. The shake-flask method gives unreliable
results because of the relative large solubility of water in these compounds.
The head-space method for determining K. [Brinckman and Bellama, 1978]
avoids these experimental errors because there Is no solute-water interface
in these measurements. These results should be very helpful In the development
of a reliable predictive scheme.
Tests for Other Classes
Additional reliable data on monofunctional groups should be generated to
develop a sound prediction scheme. Compounds containing multifunctional
groups should be studied and the results analyzed using additivity rules for
functional groups to assess the effects of steric hindrance. Also, the aqueous
solubility of organic mixtures should be studied in order to develop a sound
predictive scheme for mixtures.
HacKay ejtaU [19&0] have developed an equation which may be used
to predict the aqueous solubility and octanol/water partition coefficient
of rigid (solid) molecules. However, predictions are generally poor.
Here our study will generate data for rigid and flexible molecules in the solid
state and will develop suitable expressions to explain their aqueous solubilities.
In the study Just completed* there was an attempt to choose
compounds to represent a wide selection of chemical types which would be
of environmental interest. Unfortunately one important group of chemicals
41
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was left out, the organometals [Brinc^n and Bel lama, 1978]. The occurrence
of these compounds in water Is known to cause sickness and deaths. It is, therefore,
desirable to determine the ^ueous solubility and octanol/water partition
coefficient for this class of compounds.
This study will, of course, include other classes of compounds
of immediate interest to EPA.
Predictive Schemes
Success of a predictive scheme depends crucially on the accuracy
of the limited experimental data on which the calculations must rest.
Hansch et aV [1968] have developed a predictive scheme based on group
contributions. However, there has been some concern on their reported *
values. Here our goal will be to develop a more comprehensive predictive
scheme. This Is based on the experimental results obtained in this
laboratory and should also include data on compounds containing multifunctional
groups that have not been measured to date. K . and C* measurements should
be made on compounds containing multifunctional groups that have obvious
steric hinderence. KQ. measurements should be taken on compounds of
increasing complexity in order to determine where the group additivity breaks
down.
Using thermodynamics and a simple model, log K . and log cj will be
related to some simple physical properties (such as, solute molar volumes,
boiling points, and carbon numbers). Our preliminary study suggests
that log KQ/w and log cj may be correlated to the solute molar volumes.
Organic pollutants are often multlcomponent mixtures. It is,
therefore, desirable to develop thermodynamic relations which can predict
the aqueous solubility of each component in the mixture. These will be
modeled on hydrocarbon-hydrocarbon systems but may be used to predict
the solubility of complex mixtures such as DOT-kerosene systems.
42
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VIII. REFERENCES
Andrews, L. and R. Keefer. 1950. Cation Complexes of Compounds Containing
Carbon-Carbon Bonds. VIII. Further Studies on the Argentation of
Substituted Benzenes. J. Am. Chem. Soc. 72: 5C34-5037.
Bohon, R. and W. CUussen. 1951. The Solubility of Aromatic Hydrocarbons
in Water. J. Am. Chem. Soc. 73: 1571-1578.
Brinckman, F. and J. Sena^a, eds. 1978. Organoroetals and Organometalloids.
ACS Symposium Series, Washington, D.C. 314-326.
Conder, J. and C. Young. 1979. Solution Thermodynamics, Chapter 5 in Physico-
chemical Measurements by Gas Chromatography. John Wiley and Sons,
New York. 154-221.
DeVoe, H., H. Miller, and S. Waslk. 1981. Generator Columns and High Pressure
Liquid Chromatography for Determining Aqueous Solubilities and
Octanol-Water Partition Coefficients of Hydroohic Substances. N.B.S.
J. Res. 86: 361-366.
Edisbury, 0. 1967. Practical Hints of Absorption Spectrometrv (Ultraviolet
and Visible). Plenum Press, New York.
Gill, S., Nichols, and I. Wadso. 1976. Calorlmetrlc Determination of
Enthalpies of Solution of Slightly Soluble Liquids. J. Chem. Thermo.
8: 445-452.
Hansch, C. and A. Leo. 1979. Substituent Constants for Correlation
Analysis in Chemistry and Bloloqy. John Wiley and Sons, New York.
Hansch, C. and W. Dunn, III. 1972. Linear Relationships Between
Llphophilic Character and Biological Activity of Drugs. J. Pharm.
Sci. 6JL: 1-19.
Hansch, C.. J. Quinlan, and G. Lawrence. 1968. The Linear Free-Enemy
Relationship Between Partition Coefficients and the Aqueous Solubility
of Organic Liquids. J. Org. Chem. 33: 347-350.
43
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Hermann, R. 1972. Theory of Hydrophobic Bonding. II. The Correlation
of Hydrocarbon Solubility in Water with Solvent Cavity Surface
Area. J. Fhys. Chem. 76; 2754-2759.
Iwasa, J., T. Fujita, and C. Hansch. 1965. Substituent Constants for
Aliphatic Functions Obtained from Partion Coefficients. J. Med.
Chem. 8.: 150-153.
Leo, A., C. Hansch, and D. Elkins. 1971. Partition Coefficients and Their
Uses. Chem. Rev. 71_: 525-616.
MacKay, 0., A. Bobra, W. Shiu, S. Yalkowsky. 1980. Relationships Between
Aqueous Solubility and Octanol-Water Partition Coefficients. Chemosphere.
2: 701-711.
May, W., S. Wasik, and D. Freeman. 1978. Determination of the Aqueous
Solubility of Polynuclear Aromatic Hydrocarbons by a Coupled Column
Liquid Chromatographic Technique. Anal. Chem. 50: 175-179.
May, W., S. Wasik, and D. Freeman. 1978. Determination of the Solubility
Behavior of Some Polycycllc Aromatic Hydrocarbons In Water. Anal.
Chem. 50: 997-1000.
McAuliffe, C. 1966. Solubility 1n Water of Paraffin, Cycloparaffln, plefin.
Acetylene, Cycloolefin, and Aromatic Hydrocarbons. 0. Phys. Chem.
70: 1267-1275.
Neely, W., D. Branson, and G. Blau. 1974. Partition Coefficient to Measure
Bioconcentration Potential of Organic Chemicals in Fish. Environ.
Sci. Technol. 8: 1113-1115.
Reddick, J. and W. Burger. 1955. Techniques of Organic Chemistry vol. 2.
Wiley Interscience Inc., New York.
Sutton, C., and J.A. Calder. 1975. Solubility of Alkylcenzenes in Distilled
and Seawater at 25.0°C. J. Chem. Eng. Data. 20; 320-322.
Tewari, Y. M. Miller, and S. Hasik. Calculation of Aqueous Solubility of
Organic Compounds. In press.
44
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APPENDIX I
The octanol/water partion coefficient, K. , is defined as the
ratio of molar concentration of solute s in octanol saturated with water,
C°, to its concentration in water saturated with octanol, C*, under
S 5
equilibrium condition in an octanol/water system:
Ko/wsCs'Cs <')
Furthermore, the chemical potential of the solute in water, u", and in octanol,
ti°, may be expressed by the following equations:
p* - M* + RT In Y" • *J (2)
pj • u* + RT In Y° . *° (3)
where j. is the chemical potential of pure solute, R is the gas constant,
T is the temperature of the system in Kelvin, $w and $° are, respectively,
5 S
the volume fraction of solute in water and in octanol, and yw and Y° are the
solute activity coefficients on a volume fraction basis, where Y approaches
unity as t approaches unity, in water and in octanol, respectively.
Under equilibrium condition, u* = u°, hence
(4)
Similarly for a solute in equilibrium with its aqueous solution (jiw * ys)
the activity coefficient may also be expressed as
*s *s ' t *J
where Y| and ^ are, respectively, the solute activity coefficient and
volume fraction In solute. For a solute of low aqueous solubility YS
45
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approaches unity as $* approaches unity, hence
rs
w ,w
or Y* * ($*) (&)
At infinite dilution solute concentration in aqueous phase
(C*) and in octanol phase (C°) may be expressed by the following
S *
equations
and C. - */?
where V^ and 7° are, respectively, the solute partial molar
volume In water and in octanol.
Combining equations 1, 4, and 7 we get
K » — —
*o/w vo vo
5 w
or log K0/w - log Y" - log Y° * 1°9 r|- (8)
s
But for all practical purposes 9* = y° > v$, the molar volume of
pure solute. Hence equation (8) reduces to
log KQ/W » log YJ - log Y® (9)
46
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APPENDIX II
Proposed Method for Determining
Aqueous Solubility of Organic Compounds
Scope - This method covers the determination of aqueous solubility of
both liquid and solid compounds. There are no restrictions on the type of
compounds.
Summary of Method - Generator columns packed with a solid support and
loaded with an organic substance make it possible to rapidly and conveniently
equilibrate water with the organic phase by coupling the generator column
to an extractor column for high pressure liquid chromatographic analysis
of the aqueous solution. Errors from surface adsorption and loss to the
atmosphere are avoided. Another method for determining the solute
concentration in the aqueous phase is by solvent extraction of the aqueous
pnase followed by gas chromatographic analysis of the solvent extract.
Apparatus
1. Generator column - Two different designs were used depending on whether
the eluted aqueous phase was analyzed by HPLC (Procedure A) or by solvent
extraction followed by GC analysis of solvent extract (Procedure B).
The design of the generator column for procedure A 1s shown in Figure
II-l. The column consists of a 1/4-Inch O.D. Pyrex tube joined to a short
enlarged section of 9mm Pyrex tubing which In turn is connected to another section
of 1/4-Inch O.D, Pyrex tublnq. Connections to inlet Teflon tubing
(1/8-Inch O.D.) and to outlet stainless steel tubing (1/16-inch O.D.) are by
means of stainless steel fittings with Teflon ferrules.
2. Constant temperature bath with circulation pump-bath should be
capable of controlling temperature to * 0.05°C.
47
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Inlet
20 cm
Glass Wool
Support (100-120 mesh
Chromsorb W)
6 mm
— Glass WOOL
mm
~T i
rru
I
Outlet
Figure II-l Generator column.
48
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3. High pressure liquid chromatograph equipped with a UV detector.
4. Extractor column - 6.6 X 0.6 cm stainless steel tube with end fittings
containing 5 urn frits filled with a superficially porous phase packing
(Bondapack C,a/corasil Waters Associates).
5. Two 6-port high pressure rotary valves.
6. The design of the generator column for procedure 8 is shown in
Figure H-2. The column consists of a 1/4-inch Pyrex tube jointed to a short enlarged
enlarged section of 9mm O.D. Pyrex tubing. The outlet end of the 9mm 0.0.
tubing is connected to a long section of 3mm O.D. stairless steel tubing.
'i>e column is enclosed in a water jacket for temperature control.
7. Collecting tube for procedure B (Figure II-2) - 8X3/4 inch
section of Pyrex tubing with a flat bottom 1s connected to a short section of
3/8-inch O.D. Pyrex tubing. The collecting tube Is sealed with a 3/8-inch
Teflon cap fitting.
8. Gas chromatograph with hydrogen flame detector.
Procedure A - HPLC Method
Procedure A covers the determination of the aqueous solubility of
compounds which absorb In the U.V. The HPLC analytical system is shown schematically
In Figure II-3. Two reciprocating piston pumps deliver the mobile phase (water
or methanol-water mixture) through two 6-port high pressure rotary valves and a
30 X 0.6 cm C-18 analytical column to an ultraviolet adsorption detector operating
at 254 nm. Chromatogram peaks are recorded and Integrated with a recording
Integrator.
1. Determination of response factor
a. Prepare known concentrations (mole/L (M)) solute in methanol
(standard solution).
b. Inject samples of standard solution into HPLC system using a
calibrated sample loop.
49
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Bath •*
Return
Collecting
Vessel
Cc Jurnn
Inlet
X
n
Generator
Column
p=
To Constant
Temperature
Bath
Extracting
Solvent
-V/ater Containing Solute
Figure II-2 Design of generator column for GC method.
50
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MeOH
Sample Injection Valve
Switching Valve
Switching Pattern:
Sample Loop
T
Weighing Bottle
or Waste
Extractor Column
Analytical
Column
Load
Inject
Figure I1-3 Schematic of HPLC - generator column flow system.
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c. Adjust organic solvent (nethanol)/water ratio to obtain a reasonable
retention time for solute peak.
d. Obtain an average peak area for several injections of standard
sample at a set absorbance unit full scale (AUFS).
e. Calculate response factor from following equation:
RF « (conc.(H)) (average area)(AUFS)
2. Loading of Generator Column
a. The design of the generator column is shown in Figure INI. The
column consists of a 6mm of Pyrex tube jointed to a short enlarged
section of 9mm Pyrex tubing.
b. To pack the column a plug of silanized glass wool Is inserted into
one end of the 6mm Pyrex tubing. Silanized diatomaceous silica
support (about 0.5g 100-120 mesh chromosorb W cleaned by Soxhlet
extraction with ethanol and dried) is poured into the tube with tapping
and retained with a second plug of silanized glass wool.
c. If the solute is a liquid, the column is loaded by pulling the
liquid solute through the dry support with gentle section. If the
solute Is a solid, a IX solution of the solid in a volatile solvent
is added to the dry packing. The solvent is then distilled off the
column under reduced pressure.
3. Analysis of Solute
a. Pump water to the generator column by means of a minioump.
b. With the switching valve (Figure II-3) In the inject position, pump
water through the generator column at a flow rate of 1 ml/m1n for
approximately 5 minutes.
C. Switch HPLC pump to 100* water.
i. Weigh a 25 mL weighing bottle.
52
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e. Once the water reaches the HPLC detector which is indicated by a negative
reading on the detector, simultaneously place the weighing bottle at
the waste position and turn the switching valve to the load position.
f. Switch HPLC pump back to organic (methanol)/water mixture.
g. After collecting approximately 10 ml of water in weighing bottle
turn the switching valve back to inject position.
h. Replace the weighing bottle with the waste container.
1. Turn on the integrator.
j. Weigh the weighing bottle containing water sample.
k. Determine average area/g. of water collected at a selected AUFS
setting from several collections.
1. Calculate the solute concentration in water by the following
equation:
solute concentration (M) = (RF) (average area/g){AUFS)(997g/L)
(volume of sample loop in L)
Procedure B - GC Method
1. Determination of Calibration Curve
a. Prepare solute standard solutions of varying concentrations
b. Select a column and optimum GC operating conditions for suitable
resolution between the solute and solvent and the solute and
extracting solvent.
c. Inject a known volume of each standard solution into iaiecton
part of GC.
d. Determine average area/ul for each standard solution.
e. Determine linear regression equation of concentration vs area/pi
for 1n the following form
conc(M) • a ££2>+ b
53
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2. Loading of Generator Column
a. Generator column is packed and loaded with solute in the same manner
as for the HPLC method.
b. Approximately 20 cm of straight stainless steel tubing is connected
to the bottom of the generator column and a beaker is placed beneath
the tubing to collect the water.
c. The top of the generator column is connected to a water reservoir
(Figure I1-4) using Teflon tubing.
d. Air or nitrogen pressure (5 P.S.I.) from an air or nitrogen cylinder
is applied to the water reservoir thus forcing water from the reservoir
through the column to the beaker.
e. Water is collected in the oeaker for approximately 10 min. while
the solute concentration In water equilibrates.
3. Collection and Extraction of the Sotute
a. During the equilibration t1met a known weight of extracting solvent
1s added to a collection vessel which contains a glass-enclosed
stirring rod and can be capped. The extracting solvent should completely
cover the bottom of the collection vessel.
b. Record the weight of collection vessel with cap and extracting
solvent.
c. Remove the cap from the collection vessel and place it under the
generator column so that water from the generator column enters below
the level of the extracting solvent (Figure II-2).
d. When the collection vessel Is filled, remove it from under tne
generator column, replace the cap* and weigh the filled vessel.
e. Determine the weight of water collected.
54
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rr "E^r->
( To
Compressed
Gas Cylinder
i i
Water
(ED
To Generator
Column Inlet
Figure II-4 Water reservoir for GC method.
55
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f. Place the collection vessel on a magnetic stirrer and stir the
contents for approximately 30 min. controlling the rate of stirring
so as not to break the meniscus between the extracting solvent
and water layers.
4. Analysis of the solute
a. After stirring remove a known volume of extracting solvent from
the vessel using a microliter syringe and inject into the G.C.
b. Record the peak area/pL injected and from the regression equation
of the calibration line, determine the concentration of solute
In extracting solvent.
c. The concentration of solute in water (H), c" , is determined from
the following equation
where c" is the concentration of solute in extracting solvent
(M), dH 0 and d*s are the densities of water and extracting solvent,
respectively, and ggs and gH Q are the grams of extracting solvent
and water, respectively, contained in the collection vessel.
d. Replicate injections are made from each collection vessel to determine
an average concentration in water for the vessel.
e. At least one additional collection vessel Is prepared 1n a similar
manner for each generator column.
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