7- Partitioning Between Bulk

Phases: General Aspects and

Modeling Approaches
 7.1 Introduction
Partitioning of chemical i between two phases:

i in phase 2 i in phase 1 (4-19)

“reactant” “product”

𝑐𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 𝑜𝑓 𝑖 𝑖𝑛 𝑝ℎ𝑎𝑠𝑒 1 (4-20)

𝐾!"# =
𝑐𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 𝑜𝑓 𝑖 𝑖𝑛 𝑝ℎ𝑎𝑠𝑒 2

(4-29)

𝑙𝑜𝑔𝐾!"# = 𝑐𝑜𝑛𝑠𝑡 + 𝑎 4 Δ"#𝐺!

Thermodynamic cycle

Organic solvent (l) – air (a) partition constant of a

compound i can be derived from organic solvent –
water (w) and air-water partition constant
7.2 Molecular Interactions Governing Bulk Phase
Partitioning of Organic Chemicals
Table 7.1 Classification of Organic Chemicals According to Their Interaction Abilities
Compound Interaction Examples

Apolar only van der Waals alkanes, chlorobenzenes,

PCBs

Monopolar van der Waals alkenes, alkynes,

+ H-accepting (e-donating) alkylaromatic compounds,
ethers, ketones, esters
aldehydes
Monopolar van der Waals chloroform,
+ H-donating (e-accepting) dichloromethane

Bipolar van der Waals primary amines, secondary

+ H-accepting (e-donating) amines, carboxylic acids,
+ H-donating (e-accepting) alcohols
ideal gas (a) (no interactions) Partitioning of a compound i from
i an ideal gas phase (air, “a”) into
insertion of i
Step 2
into cavity: ΔGi liquid a bulk liquid phase (“l”)

formation of a
Step 1
cavity: ΔGcavity

bulk liquid (ℓ )

Δa ℓ Gi = ΔGcavity + ΔGi liquid

Fig. 7.1
 (7-2)

Divide both free energy terms into van der Waals component (vdW) and into a H-
bonding component (H)

(7-3)

Each free energy term is composed of an enthalpy and an entropy component

Four cases can be distinguished

Case 1: Only vdW interactions important: ∆GHcavity = 0; ∆GHiliquid = 0

e.g., solvent = i=

Case 2: H-bonding affects only cavity formation: ∆GHiliquid = 0

e.g., solvent = i=

Case 3: H-bonding affects only interaction between i and bulk liquid

phase: ∆GHcavity= 0

e.g., solvent = i=

Case 4: all terms are important

e.g., solvent = i=
 Box 7.2 – Estimating Molar (Molecular) Volume
from Structures (page 221)
-Several different approaches to calculate molar volume
-McGowan proposed simple method: 1) every atom has characteristic
atomic volume, 2) subtract 6.56 cm3/mol per bond (any bond)

C :16.35 H: 8.71 O:12.43 N:14.39 P:24.87 F:12.48

Cl:20.96 Br:26.21 I:34.53 S:22.91 Si:26.83 (cm3/mol)

e.g., molar volume of benzene: H

H C H
C C
6 carbons, 6 hydrogens, 12 bonds (double bond counts as 1 bond) C C
H C H
Vi = (6 x 16.35 + 6 x 8.71 - 12 x 6.56)cm3/mol = 71.6 cm3/mol H
Case 1 – only vdW are important: any organic
compound i partitioning between air and any
apolar liquid phase (e.g., hexadecane)
 Fig. 7.2 a) logarithm of the
hexadecane-air partition
constants versus molar volume

molar volume (cm3/mol)

Case 1:
-Most organic compounds partition favorably from air into apolar
liquid (Kihexadecane-air > 1) – if only vdW forces play a role, free energy
required to forming cavity is smaller than free energy gain from
inserting compound into cavity

-Compounds of similar size but of different classes can have very

different Kihexadecane-air (e.g., phenanthrene (7.68) vs decane (4.69)).
Rigid PAHs seem to have higher Kihexadecane-air compared to aliphatic
compounds. “more intense vdW interactions” and less loss of
freedom (entropy) than flexible alkanes

- within a set structurally closely related compounds (homologues

or congerners) a linear correlations between Kihexadecane-air and Vi
(molar volume) is observed. Smallest slopes for siloxanes and
fluorotelomers – weakest vdW interactions
Case 1 (continued):
-large rigid organic compounds very strongly partition from air into
hexadecane (e.g., benzo(a)pyrene : logKhexadecane-air =11.74),
PCB153(logKihexadecane-air =9.59) à high tendency of these
compounds to partition into apolar or weakly monopolar biological
materials in environment (e.g., waxes, lipids)
Case 2 - H-bonding only affecting cavity formation: apolar
compound partitioning between air and a bipolar liquid (e.g.,
water)
- partitioning constant will be smaller than in Case 1 (∆Gcavity is
higher, no additional energy is gained)

Table 7.2
Case 3 – H-bonding affects only interaction between i and solvent:
transfer of monopolar compound from air into a monopolar liquid
phase (opposite polarity) - ∆GHcavity = 0, additional energy is gained
from H-bonding upon insertion of i into cavity à larger Kisolvent-air
than in case 1
e.g., i: pyridine (H-acceptor), bulk solvent: chloroform (H-donor)

Cl
H C Cl
N Cl
pyridine
chloroform
Case 4 – all possible energetic combinations
bipolar bulk phase solvents: n-octanol and water
n-octanol has moderate ∆GHcavity
water has extraordinarily high ∆GHcavity
 12 12
(a) (b)
log Ki hexadecane–air (LaLh–1)
10 10 Fig.7.2
8 8

log Ki octanol–air (LaLo–1)

6 6

4 4

2 2

0 0

–2 –2

–4 –4
0 50 100 150 200 250 300 0 50 100 150 200 250 300

12 12
(c) (d)
10 10

8 8
log Ki octanol–water (LwLo–1)
log Ki water–air (LaLw–1)

6 6

4 4

2 2

0 0

–2 –2

–4 –4
0 50 100 150 200 250 300 0 50 100 150 200 250 300

molar volume (cm3 mol–1) molar volume (cm3 mol–1)

aliphatic amines chlorobenzenes polycyclic aromatic hydrocarbons

1-alkanols chlorinated phenols polychlorinated biphenyls
alkanes fluorotelomers siloxanes
carboxylic acid esters ketones
Compare 7.2a with 7.2b)

molar volume (cm3/mol) molar volume (cm3/mol)

-Similar slopes for compound classes

-Different absolute values
-Similar slopes for compound classes à vdW term in Eq.7.3 is
similar

- different absolute values à difference in ∆GHiliquid ; bipolar

group increases Kioa vs Kihexadecane-air (e.g., alkanes vs ketones vs
alcohols)(chlorobenzenes vs chlorophenols)
Fig. 7.2c:
-very different dependence on
size for Kiwater-air no increase
of K with size à cavity cost
and additional vdW
interactions increase with size
(exception: PAHs)
 Liquid Organic Phase-Water Partitioning
Partitioning between two bulk phases

(7-4)

where

we can relate organic liquid-water partition constant to the corresponding organic

liquid-air and water-air partition constant
 Fig.7.2d octanol-water partition
constant vs molar volume

-Increasing size favors partitioning into octanol

- 7.2b similar to 7.2d:
-however polar compounds: much larger Koa than Kow (e.g., alkyl alcohol)
àreason: cavity costs partly compensated for bipolar molecules (in
water as the solvent)
- apolar compounds: smaller K than K
oa ow
 Some General Conclusions

- Most organic compounds generally favor bulk organic phases over

water or air. Extend of partitioning determined by molecular size,
entropic contributions, vdW and H-bonding properties as well as
properties of bulk phase
- For Kioa and Kiow: series of structurally related compounds show
linear correlation (between logKioa (∆12G) and size) => free energy
relationship. Slope of correlations depends on vdW interaction
abilities and entropic aspects.
7.3 Quantitative Approaches to Estimate Bulk Phase Partition
Constants: Linear Free Energy Relationships (LFERs)

For many environmentally relevant matrices, partitioning

constants are not available à need to estimate (e.g., air-lipid,
air – natural organic matter partitioning)
General approaches to estimate these partitioning constants: try
to express free energy of transfer (∆12Gi):
 Fragment Contribution Methods

Δ"#𝐺! = 7 Δ"#𝐺$%&'( )* ! + 𝑠𝑝𝑒𝑐𝑖𝑎𝑙 𝑖𝑛𝑡𝑒𝑟𝑎𝑐𝑡𝑖𝑜𝑛 𝑡𝑒𝑟𝑚 (7-6)

$%&'(

Expressed in terms of partition constants:

logK"# = 7 ∆logK $%&'( )* !"# + 𝑠𝑝𝑒𝑐𝑖𝑎𝑙 𝑖𝑛𝑡𝑒𝑟𝑎𝑐𝑡𝑖𝑜𝑛 𝑡𝑒𝑟𝑚

$%&'( (7-7)

-Special interaction term describes intramolecular interactions and

stereochemical aspects between different parts of the molecule
-Fragment contribution approach allows estimation of Ki12 solely on structure
-Good estimations can be expected if only small changes in structure
-Computer models based on this approach (Absolv, SPARC, EPI Suite)
 Single-Parameter Linear Free Energy Relationship
(sp-LFER)
(7-8)

Usually one of the phases is the same (e.g., 2=4-water; 1 and 3 two different organic
phases

(7-9)

Slope, a and intercept, b are determined in linear correlation of a set of compounds

with known partition constants in both systems

sp-LFER works reasonably well for compounds with similar intermolecular interactions
during partitioning
 Fig.7.3a) hexadecane-air vs octanol-air, b) hexanedecane-water vs octanol water

12 12
(a) (b)

1
1:

1:
10 10

log Ki hexadecane–water (LwLh–1)

log Ki hexadecane–air (LaLh–1)

8 8

6 6

4 4

2 2

0 0

–2 –2

–4 –4
–4 –2 0 2 4 6 8 10 12 –4 –2 0 2 4 6 8 10 12

log Ki octanol–air (LaLo–1) log Ki octanol–water (LwLo–1)

alkanes ketones siloxanes

chlorobenzenes carboxylic acid esters fluorotelomers
polychlorinated biphenyls aliphatic amines polycyclic aromatic hydrocarbons
chlorinated phenols 1-alkanols
-No single sp-LFER can fit all data points well in Fig. 7.3a,b

-However, subset of closely related compounds can be well

described by sp-LFER (nice correlations)

-Applications of sp-LFER: predict organic matter – water partitioning

from octanol-water partitioning (Chapter 13)
 Poly-Parameter Linear Free Energy Relationships
(pp-LFERs)
Abrahams model comprises five terms for organic liquid – air partitioning and
organic liquid – water partitioning

(7-10)

(7-11)

Capital letters are compound (solute) descriptors of i that are relevant for the
partitioning process (Abraham’s parameter)
Vi: size of compound
Ei: “vdW-stickiness” (excess molar refraction)
Ai: H-donor property
Bi: H-acceptor property
Si: dipolarity/polarizability
Li: log Kihexadecane-air
-the better of a H-acceptor the larger Bi (www.ufz.de/lserd/ )
 Example of pp-LFER application:
(7-13)

𝑙𝑜𝑔𝐾!)+ = 2.41 𝑉! + 0.43 𝐿! − 1.41 𝑆! − 0.18 𝐴! − 3.45 𝐵! + 0.34

𝑙𝑜𝑔𝐾!)+ = 3.88 𝑉! + 0.57 𝐸! − 1.06 𝑆! − 0.05 𝐴! − 3.45 𝐵! + 0.03

(7-14)
(for both equations: 314 chemicals, r2=0.99, S.D.=0.15)
 Fig. 7.4 Predicted vs experimental Kow of test set
12
aliphatic amines

1
1:
10 1-alkanols
predicted log Ki octanol–water (LwLo–1)

alkanes
8
carboxylic acid
esters
6
chlorobenzenes
chlorinated phenols
4
fluorotelomers
2 ketones
polycyclic aromatic
0 hydrocarbons
polychlorinated
–2 biphenyls
siloxanes
–4
–4 –2 0 2 4 6 8 10 12
experimental log Ki octanol–water (LwLo–1)
 𝑙𝑜𝑔𝐾!"# = 2.41 𝑉! + 0.43 𝐿! − 1.41 𝑆! − 0.18 𝐴! − 3.45 𝐵! + 0.34

First two terms favor partitioning into octanol (positive sign) – hydrophobic effect

Next three terms (polar terms) are always negative (Si, Ai, Bi are (mostly) positive
values)
Bi term is the most important of the polar term – largest coefficient (3.45)
Where to find Abraham Parameters:
- Appendix C of the textbook that you can
download by going through the website of the
textbook (free)

- Using the UFZ website: www.ufz.de/lserd/

google: “ufz lfer “
www.ufz.de/lserd/
Use CAS RN as input (Chemical Abstract System Registration Number), you can find CAS
numbers often in Wikipedia (format: xxxx – xx – x) e.g, Lindane : 58-89-9

you can also find them in Scifinder (data base of CAS), you have access to Scifinder through
the College Library website, you need to create an account, go through “database” - link