Lecture 10: Organic

Solvent-Air and Organic Liquid-Water

Partitioning
Outline
Thermodynamic Background
Organic Liquid-Air Partitioning
Temperature Effects
Octanol-Water System
Evaporation and Dissolution in Organic Mixtures
Solvent-air Equilibrium
Equilibrium between solvents other than water and air can also
be important.
𝐶 1
𝐾
𝐶 𝑝∗ ⁄𝑅𝑇 𝛾 𝑉

Fortunately, the activity coefficients for organic chemicals in

organic solvents are typically quite low (<100) and less variable
than aqueous activity coefficients.

LFERs can be developed relating Kla values, but the quality of

the fits are strongly dependent on the types of intermolecular
interactions that can occur in each liquid phase.
Solvent-water systems
values are generally less variable than
- This means that usually dominates in solvent-water
systems:
𝐶 𝛾 𝑉
𝐾
𝐶 𝛾𝑉

EOC, 3rd Edition, Figure 10.1

Solvents are similar, but different
Why didn’t this work?
•Different solvents capable of
different interactions
•Ex: Apolar hexadecane can
have only vdW interactions with
solutes
•Ex: Octanol can participate in
dispersive, polar, H-acceptor, H-
donor with solutes
•Sum of interactions (octanol)
may not correlate well with vdW
only (hexadecane)

EOC 2nd Edition, Figure 6.4

Intermolecular interactions matter
Class-specific spLFERs needed

log Kia1  a log Kia2  b

Or, ppLFERs of the form:

𝑙𝑜𝑔𝐾 𝑣 𝑉 𝑙 𝐿 𝑠 𝑆 𝑎 𝐴 𝑏 𝐵 𝑐

EOC, 3rd Edition, Figure 10.3

ppLFERs for 25℃

Note: wet vs. dry octanol very similar, but slightly different (see
Table 10.1 and Figure 10.2 for more details on wet vs. dry
solvent systems)

EOC, 3rd Edition, Table 10.2

Organic Solvent-Water Partitioning
Another phase change

Cwater  Csolvent
solvent
[Corganic liquid ]  Vw    w 
K lw      aqueous
[Cwater ]  Vl    l  solution

We are particularly interested when the solvent is octanol

H2 H2 H2
H3C C C C OH
C C C C
H2 H2 H2 H2
Octanol-Water Partition Coefficient (Kow)
Pharmaceutical and medicinal chemists identified octanol as a
model solvent that describes neutral organic chemical uptake
in the body’s lipids

octanol
Octanol
Coct
Kow =
Water Cw

palmitic acid (a lipid)

We will use Kow as a basis to predict:

• Biota-water partitioning (% lipids)
• Soil/Sediment-water partitioning (% organic matter)
Why octanol?
Developed by pharmaceutical
chemists:

Cmortality
– For use in drug uptake
• mortality related to Kow
• tissues are octanol-like
• oral absorption
– drug must first pass through lipid bilayers in the
intestinal epithelium
– drug must be hydrophobic enough to partition Kow
into the lipid bilayer
– drug must be hydrophilic enough to avoid
retention, non-selective effects

Environmental chemists started using Kow for

environmental transport
• sorption to organic matter
• uptake by organisms
• organic matter and organisms are octanol-like
A Useful Parameter
Fathead Minnows Koc an indicator of sorption

EOC, 2nd Edition Figure 9.11

Kramer et al. Toxicology in Vitro, 2009.
Relationship Between Kow and Solubility
log K ow  a logCwsat (L )  b '

Slope ~ -0.7 to -1.1, depending

on compound class
Important Notes
Assume dilute solution and no co-solvent effects
– wsat  w even at saturation, solute molecules not near each other
– octanol present in water does not affect w
– oct  1 to 10 for most compounds

Depending on measurement method, may need to account for:

• Molar volume of octanol
• pure octanol, Voct = 0.16 L mol-1
• water in octanol: 1:4
• Voct = 0.12 L mol-1 (0.13 L mol-1)
– Molar volume of water
• 1 octanol per 12,500 H2Os
• Vw = 0.018 L mol-1
Importance of Kow
Kow can be determined experimentally:
– “shake flask” and measure levels in octanol and water
– limited to Kow < 105
– poor reproducibility among researchers
• DDT: log Kow range of 4.89 to 6.91 in over 60 different papers*

Many log Kow values tabulated (EOC Appendix C)

Need for reliable estimation methods

– Many LFERs and ppLFERs exist to predict Kow
– Can even correlate to chromatographic elution times (i.e., LC)

*Pontolillo and Eganhouse 2001

What affects Kla or Klw?
Temperature? Increase in T always favors air
• Same is NOT true for liquid-water - minor differences in excess enthalpies of solution
(relative to other phase changes) → generally ignore temperature effects

EOC, 3rd Edition, Table 10.3

Estimating Kow
When you don’t have a value. . .
– related to partitioning in other solvents
– related to aqueous solubility and activity coefficients (Table 7.3)

log K ow  a log C ( L)  b '

sat
w

log K ow  a log  w ( L)  b
– related to retention time in reverse-phase liquid chromatography
(need to calibrate with reference compounds for every system)

 t  t0 
log K ow  a log    b ''
 t0 
Application of Kow Cl

Cl Cl
10-6mole of lindane is added to 100 mL separatory
funnel containing 10 mL of octanol and 90 mL of water. Cl Cl

Cl
At equilibrium and 25C, what concentration (M) of
-hexachlorocyclohexane
lindane will be found in the water?

Kow = 103.78
Distribution of Lindane
total moles in water
fw 
total moles in octanol and water
CwVw
fw 
CoVo  CwVw
CwVw
CwVw 1 1
fw     0.0015
CoVo CwVw
  Vo  3.78  10 
K ow    1 10  90   1
CwVw CwVw  Vw   
masslin,w  fw masslin,T  (0.0015)(10 6 mol )  1.5  10 9 mol
masslin,w 1.5  109 mol
Cw    1.7  10 8 M
Vw 0.090 L
 Other ways to Kow
Structural contributions
(similar to Kaw approach)
– LFERs based on Leo and
Hansch (1975), refined by
Meylan and Howard (1995)
– fragments fk
• compounds’ atomic building
blocks
– correction factors cj
• atomic arrangement
• intramolecular interactions

log K ow   nk  f k   n j  c j  0.23
k j

EOC, 3rd Edition, Table 10.4

Don’t forget the correction factors!
Account for possible intramolecular interactions

EOC, 3rd Edition, Table 10.5

Example:2-hexanone O

f or c number contrib total

f(-CH3) 2 0.55 1.1

f(-CH2-) 3 0.49 1.47

f(al-CO-al) 1 -1.56 -1.56

+0.23

log Kow 1.24

log Kow (meas.) 1.38

Which compound has a higher Kow?

CH3

HN CH3

O O
CH2 CH2
O O

A. 1,2-methylenedioxybenzene B. N-methyl-3,4-methylene-
(MDB) dioxymethamphetamine
(MDMA)
 CH3

Estimating Kow HN CH3

O
Starting with a structurally similar chemical CH2
O

f or F number contrib total

1,2-
2.08
methylenedioxybenzene
f(-CH2-) 1 0.49 0.49
f(-CH<) 1 0.36 0.36
f(CH3) 2 0.55 1.1
f(al-NH-) 1 -1.5 -1.5
log Kow 2.53
log Kow (est.) 2.25 (0.54)
General Advice
Draw the structure!
– start from a structurally related compound with known Kow
– assume overall error of 0.3 log Kow
• errors from individual fragments, factors can be summed also
– consult your colleagues and strive for consensus
– And…give up and use a computer program! (several to choose from)
“Hand calculations are not for the faint-hearted or for those
who are poorly versed in chemistry. Even the designers of
the methods use the computer version in order to uniformly
and correctly apply the rules…

An indication of the difficulty in applying Leo’s method

uniformly by hand is that some published estimates of log
Kow can’t be duplicated…”
Baum, E.J., 1998. Chemical Property Estimation: Theory
and Practice. Lewis Publishers, Boca Raton, Florida.
pH Effects on Kow
For monoprotic acids and bases:

Air/Water Partitioning Octanol/Water Partitioning

K aw (HA, A )   0K aw ,HA K ow (HA, A )   0K ow ,HA

K aw (HB  , B )  (1   0 )K aw ,B K ow (HB  , B )  (1   0 )K ow ,B

Major assumption: Ionic form completely soluble in water,

nonvolatile, and insoluble in octanol.
Problems when ionic form (as a salt) becomes insoluble in
water or soluble in octanol.
D often used instead of K
Visualizing Dow

Note log scale

0 and nonzero
“plateau” for
anionic
species
Organic Solvent-Water Mixtures
What happens when organic chemicals interact with highly
water-soluble (or even completely water miscible organic
solvents, CMOSs) solvents in water? (i.e., Cosolvents)
 the solvation properties of water are changed!

Most focus on when the solute is very insoluble (i.e., organic

solids).

For there to be measurable effects (even for very hydrophobic

chemicals), the organic solvent volume fraction must be > 5%
Effects of cosolvents
EOC, 3rd Edition, Figure 10.4
In general, activity coefficient in
CMOS-water decreases exponentially
as a function of volume fraction

Magnitude and dependence on

volume fraction is a function of both
the CMOS and the solute
EOC, 3rd Edition,
Figure 10.5

In general, the
effects are largest
for large apolar
solutes (i.e., PCBs)
Cosolvency and overall impacts
Estimate solubility in co-solvent mixture
· (Eqn. 10-23)
𝛾 , 𝑓, 𝛾 10 ,

– w, CSOM activity coefficient in co-solvent/water mix

– w activity coefficient in pure water
– c “co-solvency power” (depends on fv)
– fv is the fractional volume of co-solvent in water

Overall impact on bulk phase partition constants/coefficients with

water:
𝛾 , (Eqn. 10-26)
𝐾 , 𝑓, 𝐾
𝛾
Organic Liquid Mixtures
Organic liquid mixtures (LNAPLs and DNAPLs)
– petroleum – gasoline, oil, kerosene
– coal tar
– PCBs – Arochlor
Activity in Organic Mixtures
Organic mixtures in equilibrium with gas phase
– Recall the fugacity of an organic compound in an organic liquid:
𝑓 𝛾 𝑥 𝑝∗ (Eqn. 4-14)

– When the liquid is an organic mixture (and recognizing fugacity as

the partial pressure):

𝑝 𝛾 𝑥 𝑝∗ (Eqn. 10-27)

– If org mix = 1, this is Raoult’s Law.

Turns out, this is pretty close for many organic mixtures

(i.e., org mix  1 to 5)
Activity in Organic Mixtures
Organic mixtures in equilibrium with aqueous phases
Assuming no salt effects and no cosolvent effects, the Kmix,w
can be approximated as:
1
𝐾
𝑉 𝛾 𝐶 𝐿 (Eqn. 10-33)

Again, org mix  1 to 5 (often set to 1), but need to estimate molar
volume of the mix:
𝑀
𝑉 ≅ (Eqn. 10-30)
𝜌
• need average mw of organic liquid mixture (e.g., 𝑀 of coal tar is
150 g mol-1)
• no melting costs
– compound is already in liquid phase in organic mixture