Prediction of distribution properties by solubility parameters: Description of the method and application to methylbenzenes

Chemosphere, Vol. 24, No. 4, pp. 453-464, 1992 Printed in Great Britain

PREDICTION

OF OF

DISTRIBUTION THE

METHOD

0045-6535/92 $5.00 + 0.0~ Pergamon Press plc

PROPERTIES

AND

BY

APPLICATION

SOLUBILITY

PARAMETERS:

H.A.J. Govers I* and E.H.G.

Evers 2

IDepartment of Environmental and Toxicological University of Amsterdam, 1018 WV AMSTERDAM,

Chemistry,

Nieuwe Achtergracht

166,

The Netherlands.

2Ministry of Transport and Public Works, Environmental

DESCRIPTION

TO METHYLBENZEMES.

Chemistry Section

9500 EX THE HAGUE,

Tidal Waters Division,

(RWS-DGW),

P.O. Box 20907,

The Netherlands.

ABSTRACT

A combined lation

of

fragment

molar

and thermodynamic

liquid

volume,

heat

stants of organic contaminants. obtained

for

octanol/water

chromatographic

method

of

Accurate, retention

of methylbenzenes.

is presented

vaporization

and

for the calcu-

distribution

to extremely accurate and

Correlation

the

partition

coefficients

con-

results were

coefficient

ranged

n-

from 0.9943

to 0.99997.

INTRODUCTION

A

large

number

understanding relatively water, other phases,

polar

polar hand

and

apolar

n-octanol,

based

Solubility theory

on

phases

et

[5].

comprise

currently

the

one

hand

blood

and

other

sediments,

thermodynamic

[3],

theory

air,

Linear

(multi-) These

theories

of

applied

for

contaminants polar

phases

body

comprise

fluids.

apolar

the

between On

the

chromatographic

hydrogen-bonding

UNIFAC

[i],

the

Hildebrand

as

[2],

the

(LFER)

of the (LSER)

theories

interaction, or

and

Free Energy Relationships apply

a

limited

interactions

related

octanol/water partition coefficient.

453

number

of physically

like the molar volume,

molar heat of vaporization,

molecules

such

Scatchard

constants may

Linear Solvation Energy Relationships

and molar properties

sic molecular volume, neighbouring

On

phases,

(SOLPAR)

[4] and

well-known molecular

of

phases.

are

of organic

of equilibrium or steady state distribution

well-defined

al.

methods

lipids, membranes and other receptors within organisms.

of Flory-Huggins

of Kamlet

and

of distribution

apolar

Parameter

Collander type

lity,

theories

chromatographic

The calculation be

of

and modelling

dipole moment, between

distribution

the intrinpolarizabi-

functional

constants

like

groups the

n-

454

In

addition,

namic

methods

connectivity

less are

[8]

well-defined

applied or

but

often

utilizing

very

molecular

autocorrelation

[9]

in

a

practical

extra-thermody-

fragments direct

[6,7],

molecular

correlation

with

the

hydroxylated

and

p e r t i n e n t d i s t r i b u t i o n constant. For

many

environmental

halogenated

aromatics

partition,

contaminants

distribution

chromatographic

substantially

for

both

retention,

isomers

In

order

order true

to

to

combine

preserve

sound

in the S O L P A R t h e o r y

performance

with

respect

group

of m e t h y l b e n z e n e s .

more

polar

compounds

to

we

molar

several

may

differ isomer

and toxici-

[i0].

focus

with

on

volume

practicality

methods,

and

heat

we d e s c r i b e

distribution we will

(chorobenzenes,

capable of forming h y d r o g e n bonds

air/water

Moreover,

degradibility

base

[ii]. Here,

Elsewhere,

for

binding,

phases.

in reactivity,

resolution,

descriptors

especially

receptor

theoretical

properties

methylated,

pertinent

is rate d e t e r m i n i n g a

isomer

single-component

and

and

differences may explain differences ty as far as d i s t r i b u t i o n

like

constants,

which

of

chlorinated

apply

the m e t h o d of

dioxins)

and

the

results w i t h

as its

apolar

respect

and

in the

vaporization

properties

present

and

to

compounds

(chlorinated phenols).

METHOD Single-component descriptors The

SOLPAR

model

applies

molar

(h) and s o l u b i l i t y p a r a m e t e r temperature

in

Kelvin).

directly

with

mentally

for several

molar

values

property

x

of

liquid

However, these

hundred

(v or h)

volume

(v),

heat

of

vaporization

(6 = [(h-RT)/v] ~ , w i t h R = gas c o n s t a n t and T = the

SOLPAR

descriptors,

of organic

according

model

which

are

compounds.

does

Thus,

to an a d d i t i v e

not

only

rule

provide

measured

we

us

experi-

first model

detailed

the

enough

to

allow for isomer resolution: x =

x0 + nSS o xSS o + nSC 0 xSC 0

In E q u a t i o n of

1 x0,

vaporization)

single rings

+ nS

xS

+ nSS r xSS r

+ nSS m

xSS m

+ nSSp xSSp

+ nSC m

xSC m

xS,

parameters

substituents (e.g.

actions

on

ortho

between

other)

and

second

fixed

XSSr, xSS..,

ortho,

(S),

denoting

substituents meta

and

are

between

with

respect

to

(ortho,

meta

and

para

interactions

or m o i e t y

(i) (9 m o l a r v o l u m e and 9 heat

contributions

interactions

positions

substituent

+ nSCp XSCp and xSC..,

(C).

nS,

of

the

parent

substituents a central para

between nSSr,

the

different

fragment),

with

nSS..,

on

molecule,

respect

interto

substituent and

number of times a c e r t a i n i n t e r a c t i o n occurs for the molecule.

nSC..,

each and a

are the

455 J

Figure i. Numbers

of interactions

the 1,3,6,9-TCDD

in

~_~|/--'C101;v. //

molecule:

Parent = Dibenzo-p-dioxin;

In methylbenzenes skeleton

|

\

! @~~ ]0~

nCl=4;

CICI,

nClClr=l; nClCl°=°; nClClm=l; nClClp=l ; nClO0=3 ; nClOm=4 ; nClOp=l. Not all interactions

CI

/~

9

>

~l~lp

are drawn.

/

el = CH3, the parent

~I~

is benzene and only nCH3, nCH3

~

jCIOD

/k

___/

~

/

C ~Oo~

~j

/

and nCH3CH 3. .. are relevant. In Figure

1 the

number

fragment

of

interactions

1,3,6,9-TCDD

molecule

interactions

is given as an example

is counted.

In methylbenzenes

do not occur and the number of parameters

5 = i0. The model

can be extended

view of isomer resolution.

of the way the

with other contributions,

It enables

SS r and SC...

is reduced to 2 times if necessary

all 13 methylbenzenes

in

to be physically

discriminated. The i0 x-parameters to

( 2 6 ) experimental

number

parameters

of data-points ble. for

h-

will

based

congeners

also

derivation

might be found by linear regression

values

is rather

for several

we

parameter

and

to be derived

and

Therefore,

in methylbenzenes v-

use

based

on

large with

equations

i.

respect

experimental

multicomponent on

Equation data

However,

to the number

are

not

(distribution) derived

the

in

availa-

properties

the

subsequent

section. Additional

empirical

molar volume in the

is

v[c,25°C])

molecular

with

= 12.5872 can

molar volumes v[i,25°C]

be

applied

to

obtain

at 25°C. The molar volume

obtained

the

in order

molar

from

volume

liquid of

the

density

values

of

(in cm3/mol) and molecular

crystalline

phase

(-

[ii]: be

weight.

The molar

(v[I,25°C]),

correlated

latter

in the

phase

via

v[i,25°C] The

may

and heat of vaporization

liquid

weight,

rules

+ 0.97815 v[c,25°C]

easily

Molar

at T°C via = v[I,T°C]

liquid

of

liquid

volumes

(2)

from

x-ray

crystalline

at 25°C can be

density

obtained

from

and

liquid

[ii]: (i + 0.001237

volume

prediction

calculated

(25-T))

of a n-alkane

certain

with

(3) z carbon-atoms,

chromatographic

constants,

which

can

be

is needed calculated

via: v[l,z,25°C]

= 39.485 + 15.698

n = 20; r = 0.9998; Equation the

4 is obtained

number

of

s.e.r.

z

(4)

= 3.134

by linear regression

data-points,

r

the

to experimental

correlation

coefficient

data

[12].

and

s.e.r,

n is the

standard error of regression. The point

heat (Tbp,

of

vaporization

in Kelvin)

via

(cal/mol)

[Ii]:

can

be

calculated

from

the

boiling

J,56

h[i,25°C] The

heat

via

= -2950

+ 23.7 Tbp + 0.020 Tbp 2

of v a p o r i z a t i o n

at

25°C can

be

(5)

obtained

from

values

at

Tbp

(in °C)

[ii]: h[i,25°C]

Finally, can

be

= h[l,Tbp]

the

molar

calculated

mental

data

via

(25-Tbp)

(6)

vaporization

Equation

= 2577

7,

+ 938.03

r = 0.994;

In all

of

of

a

obtained

n-alkane

by

linear

with

z

carbon-atoms

regression

to

experi-

[12]:

h[l,z,25°C] n = 25;

- 13

heat

cases

the

s.e.r.

z

solubility

and R by the e x p r e s s i o n

(7)

= 803 parameter

mentioned

(6)

earlier

can

be

in this

calculated

from

h,

v,

T

section.

Distribution properties The

Scatchard-Hildebrand

statistical of

the

thermodynamic

excess

residual assumed

Gibbs

part to

the

be

molecules. solvent

SOLPAR

With

lattice-model

energy

of

interaction

the

to

8 holds

mean

the at

[2,13] for

mixing

between

geometric

respect

2 Equation

theory

assumed

different the

activity

solutions

liquids.

is

of

high

for

The to

is b a s e d

on a

combinatorial

part

be

zero

molecules

in the

interactions

coefficient

dilution

with

v,

of R

a

in

T

is

identical

solute

and

the

lattice

between

(7)

6,

and

1

in

defined

as

previously:

(6~-62)2vi/RT

in 7 =

From this a

liquid

(8)

equation

or

solid

and the d e f i n i t i o n

substance

p h a s e w one can d i r e c t l y

For

a

certain as

solubility

choice

a

derive

an

apolar

Equation

liquid

of

the

function

parameter

of

phase the

B1

and

Equation

i0

B2

are

this

(ev.

of the solute b e i n g

can

be

applied

In have

case to

of

partition

vapour pressure in P = Equation from

i,

may v a r y 1 and tion

A

an

is

for is

of

allowing

polar

can

volume

be and

of compounds:

between

on

the

the

partition

capacity a

properties

liquid

empirical

of

coefficient

the

phases.

n-octanol/wa-

factors. phase

I and

relation

a gaseous

between

a

pure

phase

we

solute's

of v a p o r i z a t i o n : (ii)

identical

series

liquid

of a series

+ A

identical

process,

e.g.

additional

is a m o d i f i e d

but

for

P and its heat

-Ch/RT ii

coefficient

supercooled)

a member

depending

chromatographic

partitioning

invoke

(k) of a

(i0)

constants

ter or l i q u i d - l i q u i d

and

(9)

log k = B0 + B1 v + B2 v6 B0,

a

9:

system

molar

coefficient

phase

(6w2-6a2)v/RT - 2(6w-6a)v6/RT

in k = In v ~ v a +

written

between

of the p a r t i t i o n

Young for

equation

all

compounds.

compounds.

for

all

in w h i c h

In the

compounds

for d e t a i l e d

our

unmodified

[14].

isomer

In

the

An

constant

approach Young

important

resolution,

C may

the

differ

constant

equation

liquid-gas

is g a s - l i q u i d

A

C equals partichroma-

457

tography.

Via

specific

retention

specific (z+l)

substitution

retention

n-alkane

retention

[14]

volumes

into

of

the van

index RI,

RI/100

of Equations

volume

8 and

and

the

den

the

compound

Dool

one u l t i m a t e l y

ii into the

subsequent

and

and

its

Kratz

arrives

expression

of the

substitution preceding

equation

of

(z)

[15],

the

and

next

defining

the

at:

[A-A z - (6t2/RT)(V-Vz)

+ (26t/RT) (6V-6zVz)

+ (C-l)(h-hz)/RT ]

[- (6t2/RT) (Vz÷1-Vz) +

(26t/RT) (6z.iVz÷1-6zVz) + (C-I) (hz÷1-hz)/RT ]

- z = (12)

Again, index

for

a certain

RI'=

RI/100

choice

- z can

of

the

phase

be writen

as

(6V-6zVz)

+ B3

system,

the

normalized

a multilinear

function

retention

of

compound

and n - a l k a n e properties: RI' = B0 + B1 As

will

be

(V-Vz) + B2

shown

elsewhere,

similar

(h-hz)

(13)

equations

can

be

derived

for

other

partition properties. Derivation and test of parameters

Equations properties

i, at

distribution and the

3,

4,

the

6,

7 plus

appropriate

properties)

subsequent

the

definition

temperatures)

can be used both

calculation

of

and

6

(for

single-component

Equations

i0

for the d e r i v a t i o n

of s i n g l e - c o m p o n e n t

and

and

13

(for

of x-parameters

distribution

proper-

ties. Here,

we

first

experimental

data

indices

reversed-phase

and

developed which out

derive

phase HPLC c a p a c i t y All

calculations

Multilinear STATPAK, regression

of the

heat

capacity

To

for I B M - c o m p a t i b l e

minimization

x-parameters

the

derived

carried was like

and F-test value

out

carried

Analytical,

parameters

of vaporization,

factors. [16].

and B0,

parameters

factors and n - o c t a n o l - w a t e r are

13 m e t h y l b e n z e n e s this

Minimization

B1 ....

out

using

Inc.,

the

Portland,

M24

retention we

have

computers, is carried This

elsewhere. of

normal

coefficients. personal

programme Oregon),

coefficient,

from

coefficients.

calculation

partition

an Olivetti

correlation

(F).

via

via

GC end

personal

on its a v a i l a b i l i t y will be p u b l i s h e d

test

regression

North-west

statistical

SIMPLEX

for both

program and information we

molar

HPLC

computer programm

non-linear

simultaneously Subsequently,

i0 x-parameters

on m o l a r volume,

a GWBASIC

applies

the

computer.

MLINREG

(NWA-

providing

usual

standard

error

of

458

C A L C U L A T I O N S AND R E S U L T S

D e r i v a t i o n of p a r a m e t e r s

The d e r i v e d x - p a r a m e t e r s

for m e t h y l b e n z e n e s

are given in Table

i.

Table i. M o l a r v o l u m e (v) and heat of v a p o r i z a t i o n (h) p a r a m e t e r s at 25°C for methylbenzenes. Definitions: see text. Atom group

v...(cm3/mol)

h...(cal/mol)

Parent (Benzene) CH 3 CH3CH 3 o,m,p

90.390 15.981 -1.233

9500 963 157

The

derivation

experimental index an

on apolar

apolar

and

3

C18 to

known

calculated

based

squalene the

the

heat

0.621

a non-linear

fit

liquid volume,

of

the

phase

calculated

and

data.

of v a p o r i z a t i o n

i0

procedure

Table

2

-28

x-parameters

HPLC

a methanol/water

single-component

fitting

1

heat of vaporization,

at 96°C and r e v e r s e d - p h a s e

SIMPLEX

experimental

cal E q u a t i o n

on

stationary

include

belonging from

is

data of m o l a r

0.210

also

from values

and

capacity

mobile

contains calculated

with the

the

on

Table

2

properties

their

deviations

deviation

via

46

factor

phase.

distribution

together

to

GC retention

of

the

semi-empiri-

5.

Table 2. C a l c u l a t e d molar volume, product of molar volume and solubility parameter, heat of v a p o r i z a t i o n and deviations from experimental data at 25°C for methylbenzenes. Compound

Vcm3/mo I

(*)

~m~ /2cal~/mol

Benzene Mono1,2-Di1,3-Di1,4-Di1,2 3-Tri1,2 4-Tri1,3 5-Tri1,2 3,4-Tetra1,2 3,5-Tetra1,2 4,5-TetraPentaHexa-

90.390 106.371 121.119 122.562 122.973 136.077 137.931 138.963 151.656 153.099 153.510 167.445 182.001

(-0.720) (0.569) (1.741) (1.048) (1.086) (-0.867) (0.149) (0.817) (-2.466) (-1.409)

897.3261 1024.689 1153.785 1152.371 1152.756 1283.809 1282.616 1280.533 1415.139 1413.432 1413.754 1547.351 1682.295

* **

h cal/mol 9500 10463 11583 11427 11398 12704 12519 12392 13797 13641 13612 14891 16142

(*,**) (-637,-1584) (-769,-1372) (-32,-1150) (-40,-1207) (-115,-1210) ( 42, -970) ( 67,-1067) (-59,-1130) ( 801, -842) ( 966, -985) (1205,-1007) ( , -765) ( , -545)

E x p e r i m e n t a l value [12] minus calculated value. If values in parenthesis are missing, p r e d i c t e d values are given which were not used for p a r a m e t e r derivation. S e m i - e m p i r i c a l value of Equation 5 (Tbp from [12]) minus calculated value.

459

Table 3. C a l c u l a t e d GC r e t e n t i o n index and r e v e r s e d - p h a s e factor and d e v i a t i o n of e x p e r i m e n t a l data of m e t h y l b e n z e n e s . Compound

RI

(*)

Log k'

Benzene Mon o 1 2-Di1 3-Di1 4-Di1 2,3-Tri1 2,4-Tri1 3,5-Tri1 2,3,4-Tetra1 2,3,5-Tetra1 2,4,5-TetraPentaHexa-

649 757 885 863 858 i010 986 968 1134 1112 1107 1258 1403 p

(i) (0) (-2) (0) (3) (i) (-i) (-i) (-i) (-i) (-i) (i)

0.150 0.375 0.565 0.604 0.614 0.760 0.809 0.838 0.968 1.007 1.017 1.181 1.358

HPLC

capacity

(**) (-0.001) (0.001) (0.006) (0.001) (0.001) (0.003) (-0.005) (-0.004) (0.002) (-0.004) (-0.009) (0.005) (0.004)

*

E x p e r i m e n t a l v a l u e at 96°C on a s q u a l e n e c o l u m n [17] m i n u s c a l c u l a t e d value. ** E x p e r i m e n t a l v a l u e on a L i C h r o s o r b RP-18 s t a t i o n a r y p h a s e and a 70% (w/w) m e t h a n o l / w a t e r m o b i l e p h a s e [18] m i n u s calc u l a t e d value. P P r e d i c t e d value, not used for p a r a m e t e r derivation.

Table

4

summarizes

distribution

the

main

statistics

properties.

This

Table

for the n o r m a l i s e d

RI

(RI')

of

the

includes

fit

with

correlation

respect

coefficients

index and reverse p h a s e HPLC c a p a c i t y of p a r a m e t e r s for m e t h y l b e n z e n e s .

Prop.

Eqn.

B0 ±

B1 ±

B2xl0 3 ±

B3xI0 3 ±

r

RI'

13 i0

-0.1304 0.0182 0.0231 0.0009

28.12 4.53 -1.154 0.102

-0.3388 0.2822

Log k'

-2.491 0.117 -0.897 0.013

0.9990 0.014 0.99997* 0.99995 0.004

Table small

1

coefficient

shows

compared

considered

as

Table

The

to

2

and

shows

that

1%,

triplets.

large

systematic

the

to

calculated is

slightly

sequence

of

values

calculated

from the e x p e r i m e n t a l methodical

Our

factor

s.e.r.

statis-

F

n

1340

12

47522

13

CH3-CH 3 all

interaction three

additive

parameters

types

in turn

fragment

are

can be

schemes

using

as parameter.

which

The

4%

property.

para-

simple

corrections

of CH3-groups

about

both

of RI'

small

about

this

meta-

instead

and that

experimental

isomer

for RI

to o r t h o - i n t e r a c t i o n s

only the n u m b e r

v al u e

that

the

and RI.

Table 4. GC r e t e n t i o n tics in the d e r i v a t i o n

* Correlation

to

calculated

heat value,

errors values

molar higher

is

volume than

reproduced

of v a p o r i z a t i o n which for are

fits

correctly has

is d i f f i c u l t

the

the

experimental

experimental

experimental

systematically

a mean to

inaccuracy.

for

all

three

deviation

judge

in v i e w

determinations about

I000

of of of

cal/mol

460

higher

and

better

match

the

experimental

data

than

the

values

obtained

via

E q u a t i o n 5. From T a b l e

3 it can be

ties are

surprisingly

the

same

order

and

capacity

correct

as the

factors;

sequences

This h i g h

i n f e r r e d that

close

experimental about

of v a l u e s

performance

our c a l c u l a t e d

to the e x p e r i m e n t a l

0.1%

inaccuracies

and

0.5%

method

distribution

is also

proper-

The d e v i a t i o n s

for b o t h

retention

respectively.

is c a l c u l a t e d w i t h i n

of our

data.

In

all t h r e e

reflected

both

are of indices

cases

the

isomer triplets.

in the

statistics

of

Table 4. RI and Log k' c o r r e l a t i o n c o e f f i c i e n t s amount to ~ 0.99990. In all cases l e a v i n g out either v, v6 or h s i g n i f i c a n t l y w o r s e n s the fit.

Test of the derived parameters

The based dent

results

presented

on a fit test

of

above,

is c a r r i e d

out by the

from the d e r i v e d parameters, utilized

statistically

application

data.

of v and v6

significant, A more

values,

are

indepen-

calculated

For this p u r p o s e we c a l c u l a t e d the normal

and the p a r t i t i o n c o e f f i c i e n t n - o c t a n o l / w a t e r

method.

The

experimental

data

on

triplet s e q u e n c e s w h i c h d i f f e r s u b s t a n t i a l l y ter derivation.

very

46 e x p e r i m e n t a l

factor on a p o l a r alumina s t a t i o n a r y p h a s e plus a p e n t a n e / w a -

ter m o b i l e p h a s e HPLC

to

for the p r e d i c t i o n of p r o p e r t i e s w h i c h w e r e not

for p a r a m e t e r derivation.

phase c a p a c i t y

the

though

i0 x - p a r a m e t e r s

these

d e t e r m i n e d by

properties

from those u t i l i z e d

show

isomer

for parame-

They w e r e c a l c u l a t e d via linear r e g r e s s i o n b a s e d on E q u a t i o n

i0. The results are s u m m a r i z e d in Table 5 and 6. Table 5. C a l c u l a t e d normal phase c a p a c i t y factor, p a r t i t i o n c o e f f i c i e n t o c t a n o l / w a t e r and d e v i a t i o n s from e x p e r i m e n t a l data for m e t h y l b e n z e n e s . Compound

Log k'

(*)

Log Kow

Benzene Mono1,2-Di1,3-Di1,4-Di1,2,3-Tri1,2,4-Tri1,3,5-Tri1,2,3,4-Tetra1,2,3,5-Tetra1,2,4,5-TetraPentaHexa-

-0.585 -0.465 -0.258 -0.354 -0.375 -0.055 -0.174 -0.251 0.122 0.023 0.002 0.294 0.560

(-0.006 (-0.013 ( 0.012 ( 0.037 (-0.001 ( 0.0251 (-0.037 (-0.026 (-0.0331 (-0.041 ( 0.056 ( 0.054 (-0.029

2.21 2.76 3.18 3.31 3.35 3.61 3.78 3.89 p 4.09 4.23 4.27 p 4.59 p 4.95

* ** *** P

(**)

(***)

(-0.03) (-0.06) (0,04) (0.00) (-0.03) (0.06) (0.02)

(0.02 (0.04 (0.03 (0.02 (0.04 (0.02 (0.02

(0.ii) (-0.02)

(0.i0) (0.05)

(-0.09)

(0.26)

n-

E x p e r i m e n t a l v a l u e on an alumina s t a t i o n a r y p h a s e and a n-pent a n e / w a t e r 99.5% (w/w) m o b i l e phase [19] m i n u s c a l c u l a t e d value. Experimental value (HPLC, m e a n value) [20,21] m i n u s c a l c u l a t e d value. E r r o r in m e a n e x p e r i m e n t a l value. P r e d i c t e d value, not u s e d for p a r a m e t e r testing.

46

Table 6. N o r m a l p h a s e c a p a c i t y factor and p a r t i t i o n c o e f f i c i e n t n o l / w a t e r s t a t i s t i c s for the t e s t of p a r a m e t e r s for m e t h y l b e n z e n e s . Prop.

Eqn.

Log k'

i0

Log Kow

i0

With

B0

B1

B2

+

_+

_+

-2.735 0.130 0.344 0.290

-0.05854 0.00885 0.08818 0.02060

0.008292 0.001338 -0.006801 0.002401

respect

results

are

the

slightly

phase c a p a c i t y three

to

times

prediction

less a c c u r a t e

factors of T a b l e

the

of

experimental

the

r

s. e. r.

F

n

0.9943

0.038

432

13

0.9971

0.07

597

i0

normal

compared

phase

to the c a l c u l a t i o n

3 and 4. The s.e.r.

inaccuracy

and

two

results

experimental

quite

satisfactory

values

rent m e c h a n i s m s ,

in the two

which

a s o r p t i o n process,

are

in v i e w

data.

of d r a s t i c

chromatographic

involved.

(0.037)

w h i l e the reserve phase

phase

the

of reversed-

are

met

However,

and the

the

between quite

system might

system r e s e m b l e s

in

we c o n s i d e r

differences

systems

The normal

factors

a m o u n t s to about

reversals

p r e d i c t e d v a l u e s w i t h r e s p e c t to the e x p e r i m e n t a l these

capacity

n-octa-

the

diffe-

resemble

a true p a r t i t i -

on process. The

latter

partition

suggestion

coefficient

than the normal mental

inaccuracies

confirmed

by

n-octanol/water,

phase

on r e v e r s e d - p h a s e

is

capacity

for this

HPLC.

which

factor.

The

partition

In a d d i t i o n

the

results

is

predicted

s.e.r

constant

obtained

(0.07)

with

the

more

accurately

is close

to experi-

measured

no r e v e r s a l s

for

via

a method

respect

based

to e x p e r i m e n -

tal data occur. In b o t h improvement

cases

the u t i l i z a t i o n

of

prediction

the

of both v and v6 p r o v i d e

compared

to

the

for a s i g n i f i c a n t

utilization

of

only

one

of

these descriptors.

CONCLUSION

In

this

(SOLPAR) volume (GC

study

approach

and h e a t

retention

partition excellent obtained method ring

it

is

can

shown

AND

that

predict

of v a p o r i z a t i o n ) index,

normal

DISCUSSION

and

a

accuracies.

requires

Complete

accuracies three

6 as a f u n c t i o n

close

descriptors of v and h.

fragment

reversed-phase

or to

the

(v, v6

complete

experimental and

h)

It is suited

thermodynamic (molar

distribution

HPLC

capacity

of m e t h y l b e n z e n e s

almost

and

properties

and m u l t i - c o m p o n e n t

coefficient n-octanol/water)

with

combined

single-component

liquid

properties factors

and

w i t h g o o d and often

isomer ones.

or even

for series

only

resolution Basically two,

is the

conside-

of c o m p o u n d s

with

not too m a n y d i f f e r e n t s u b s t i t u e n t s on the p a r e n t m o l e c u l a r skeleton. The m e t h o d has a d v a n t a g e s molecular connectivity

[8],

over c o m p l e t e l y e x t r a - t h e r m o d y n a m i c fragment m e t h o d s

[6,7]

models

like

or the t h e o r e t i c a l l y

less

462

satisfactory The

combination

latter

physical

models

of heats

are

significance

of f o r m a t i o n

sometimes

equally

of the descriptors.

and i n f o r m a t i o n

accurate,

Moreover,

but

indices

do

not

[22].

preserve

our d e s c r i p t o r s p o t e n t i -

ally can be a p p l i e d for all types of d i s t r i b u t i o n properties. The

accurate

enables tion

of

ments.

prediction

the u t i l i z a t i o n experimental We

can

suggest

be

better

partition

and

the

coefficient

a possible

identification

improvement

of this p r o p e r t y via

B0 + B1 Log k'. W i t h

to

the

of our m e t h o d as an a d d i t i o n a l

methods

for the d e t e r m i n a t i o n

B1 Log k' + B2 v

of

(or B2 v6)

empirical

d e p e n d e n c e of Log Kow on Log k'

This

improvements

measure-

HPLC

relation

i0 a r e l a t i o n

m i g h t be an improvement.

than

for the evalua-

erroneous

well-known

the e m p i r i c a l

r e f e r e n c e to our E q u a t i o n

founded

tool of

of the

n-octanol/water

method

Log Kow =

Log Kow = B0 +

improvement

based

on

a

seems

parabolic

[23].

Our m e t h o d w i l l be d e v e l o p e d further along three lines. Firstly,

it

properties

has

like

and r e c e p t o r

to

be

aqueous

binding

tested

for

solubilty,

constants.

the

prediction

sediment

Moreover,

of

sorption,

the

other

distribution

Henry's

systematic

Law

constant

variation

of phase

p r o p e r t i e s can be s t u d i e d and its impact on d i s t r i b u t i o n properties. Secondly,

it

has

to

be

tested

on

other

series

of

compounds,

more p o l a r and c a p a b l e of forming ions or h y d r o g e n bonds. to be

studied

parameters)

to w h a t

can

be

degree

parameters

transferred

to

for m e t h y l b e n z e n e s

other

series l i k e

which

In a d d i t i o n (like

chlorinated

are

it has

CH3-CH3... methylben-

zenes. Finally,

in o r d e r

thermodynamic macroscopic like

part

to

introduce

single-component

molecular

complete

of our m e t h o d w o u l d

intrinsic

descriptors

volume

physical

require

and

v

significance

a further

and

h

from

intermolecular

the

extra-

explanation

of the

molecular

properties

interactions

in

the

liquid phase.

REFERENCEE

I.

Fredenslund,

Estimation

of

A.,

R.L.

Activity

Jones

and J.M.

Coefficients

in

Prausnitz.

1975.

Nonideal

Group-Contribution

Liquid

Mixtures.

AIChE

Journal 2 1 : 1 0 8 6 - 1 0 9 9 . 2. 3.

Barton, A.F°M.

J.M.

Eantiuste.

1988.

S t a t i o n a r y Phases. 4.

1975. S o l u b i l i t y Parameters.

Fernandez-Eanohez,

Chiou,

mental

C.T.

A.

Chem.

Fernandez-Tortes,

Solubility

J. Chromatoqr.

1981.

Chemistry.

Chemicals.

E°,

Parameters

Of

R e v i e w s 75:731-753.

J.A.

Garcia-Dominguez

Gaschromatographic

In Jitendra,

Mixed

457:55-71.

P a r t i t i o n C o e f f i c i e n t and W a t e r S o l u b i l i t y

C u r r e n t Developments,

and

Saxena Vol.l,

and

Fasley,

Fisher, pp.

eds.

Hazard

117-153.

in Environ-

Assessment

of

463

5.

Kamlet,

Taft.

M.J.,

1988.

Technol. 6. 7.

8.

C.

Donnelly,

and

A.

Carr,

Energy

Leo.

J.R.,

of

W.D.

1979.

D. Mackay,

M.H.

Relationships

Abraham

(44).

and R.W.

Environ.

Sci.

J. Chromatogr.

Sabljic,

A.

1985.

with

Broto,

P.,

perception,

G.

Substituent

Constants

for

Correlation

Wiley, New York.

Munslow,

Structure

R°K.

Mitchum

Retention

Index

and for

G.W.

Sovocool.

Chlorinated

1987.

Dibenzo-p-

392:51-63. Calculation

gy. C h l o r i n a t e d Benzenes. 9.

P.W.

in C h e m i s t r y and BioloqT.,

Correlation dioxins.

Doherty,

Solvation

22:503-509.

Hansch,

Analysis

R.M.

Linear

of R e t e n t i o n

J. Chromatogr.

Moreau

and

autocorrelation

C.

Indices

Vandijcke°

descriptor

by M o l e c u l a r

Topolo-

319:1-8.

and

1984.

sar

Molecular

studies.

Eur.

structures:

J.

Med.

Chem.

19:71-78. I0.

Parsons,

J.

Relationships 11. Govers,

H.A.J.,

Vaporization, dioxins.

and

H.A.J.

Govers.

for B i o d e g r a d a t i o n . R.

Molar

LUijk

Volume

1990.

and E.H.G.

and

Quantittative

Ecotoxicol.

Environ.

Evers.

Solubility

1990.

Parameter

Structure-Activity

Safety.

19:212-227.

Calculation of

of Heat of

Polychlorodibenzo-p-

C h e m o s p h e r e 3/4:287-294.

12. Weast,

R.C.

1988.

CRC H a n d b o o k of C h e m i s t r y and Physics,

CRC Press,

Boca

Raton. 13.

Abrams,

Liquid

D.S.

Mixtures:

and

J.M.

A New

Prausnitz.

Expression

C o m p l e t e l y M i s c i b l e Systems. 14.

Ber~nejo,

Parameter Tech.

J.

and

M.D.

of Low V o l a t i l e

Biotechnol.

Retention

Guillen.

1987.

Compounds

from Gas

Index

System

Fredenslund,

A.,

J.

E q u i l i b r i a U s i n q UNIFAC. 17.

Macak,

retention toqr. 18.

J.,

V.

of

Partly

of or

The

Estimation

of

the

Chromatographic

Solubility

Data.

J.

Chem.

Programmed

Gas-

1963. A G e n e r a l i z a t i o n of

Including

Linear

Temperature

J. Chromatogr.

Gmehling

Elsevier,

Navibach,

indices

J.H.,

P.

and

P.

11:463-471.

Rasmussen.

1977.

Vapor-Liquid

Amsterdam.

Buryan

of a l k y l b e n z e n e s

J.

Kri2

Aromatic Hydrocarbons J. Chromatoqr. 19.

Thermodynamics

Energy

and

S.

on their

Sindler.

molecular

1982.

Dependence

structure.

J.

of

Chroma-

234:285-302.

Knox,

Kriz,

mance

Gibbs

37:101-109.

Liquid P a r t i t i o n C h r o m a t o g r a p h y . 16.

Statistical

Excess

A I C h E Journal 21:116-128.

15. Dool, H. v a n den, and P.D. Kratz. The

1975.

for the

J.,

Liquid

and

Eluted

E. Adamcova.

1988.

Retention

Relationships

from Capped and U n c a p p e d O c t a d e c y l

for

Silica gels.

447:13-27. J.

Puncocharcva,

Chromatography

L. v o d i c k a of

and J.

Alkylbenzenes

on

Vareka.

1988.

Alumina.

High-Perfor-

J.

Chromatogr.

437:177-183. 20.

Hammers,

W.E.,

G.J.

Liquid C h r o m a t o g r a p h h y Coefficients

Meurs

and C.L.

de Ligny.

1982.

Correlations

C a p a c i t y R a t i o Data on L i c h r o s o r b RP-18

in the O c t a n o l - w a t e r System. J. Chromatoqr.

Between

and P a r t i t i o n

247:1-13.

464

21.

Sherblom,

water

P.M.

Partition

and

R.P.

Eganhouse.

Coefficients

and

1988.

Correlations

Reversed-Phase

C h r o m a t o g r a p h y C a p a c i t y Factors. J. Chromatoqr.

454:37-50.

22.

Garcia-Raso.

Baura-Calixto,

Formation-

Gas

F.,

A.

Chromatographic

carbons and A l k y l b e n z e n e s . 23.

Sarna,

Garoia-Raso

L.P.,

and

Retention

J. Chromatogr.

P.E. H o d g e and G.R.B.

J.

Between

Octanol-

High-Performance

Relationships

1985.

Liquid

Heats

for A l i p h a t i c

of

Hydro-

322:35-42.

Webster.

1984.

Octanol-Water

Partiti-

on C o e f f i c i e n t s of C h l o r i n a t e d Dioxins and Dibenzofurans

by R e v e r s e d - P h a s e

HPLC

Using

13:975-983.

(Received in Germany 13 September 1991; accepted 10 December 1991)

Several

C18

Columns.

Chemosphere