Ion Exchange Chromatography overview

ION CHROMATOGRAPHY

See

ION EXCHANGE: Ion Chromatography Instrumentation; Ion Chromatography Applications; Chelation
Ion Chromatography; Isotope Separation

ION EXCHANGE

Contents

Overview

Principles

Ion Chromatography Instrumentation

Ion Chromatography Applications

Chelation Ion Chromatography

Isolation of Biopolymers

Isotope Separation

Overview

P R Haddad

, University of Tasmania, Hobart, TAS,

Australia

This article is a revision of the previous-edition article by J. Inczedy,
pp. 2267–2273,

& 1995, Elsevier Ltd.

Introduction

Ion exchangers are solid materials or liquid solutions
which are able to take up (or absorb) positively or
negatively charged ions from aqueous electrolyte
solutions and at the same time release other ions
of equivalent amount into the aqueous solution.
According to the electric charge of the ions taking
part in the ion exchange process, one can speak
about cation and anion exchangers. Ion exchangers
which are able to interact with both types of ions are
called amphoteric.

The ideal ion exchange process proceeds stoichio-

metrically, i.e., the ratio of the ions exchanged be-
tween the two phases is strictly determined by their
charges. A clear distinction can be made between ion
exchange and adsorption or liquid–liquid extraction
processes, in which molecules are transferred from
the aqueous phase into the solid, or organic solvent
phase, without releasing any other species into the
aqueous solution.

Ion-exchange processes are important in biological

systems of living organisms. They are important not

only from the point of view of selective secretion of
some biological substances, but also in the transport
mechanism of certain ions crossing cell membranes,
and also in the signal expansions in nerve systems.

Ion exchange processes have importance also in

agriculture, because the ion-exchange properties of
the natural silicates present in the soils highly inﬂu-
ence the composition of the interstitial liquid avail-
able for the feeding of the plants.

Synthetic ion exchangers have proved to be very

useful tools both in industry and in the laboratory,
because by means of ion exchangers the concentra-
tion of certain ions in solution can be changed very
easily without unwanted disturbances of the total
composition of the electrolyte, and also selective
separations, extractions, and enrichment procedures
can be carried out with them.

History

Key events in the development of ion exchangers and
also that of their analytical applications are tabulated
in chronological order in Table 1.

Types of Ion Exchangers

The current synthetic ion exchange materials can be
classiﬁed according to their form into the following
main groups:

solid beads or particles,

solid membranes,

solid sheets (papers or layers), and

440

ION EXCHANGE

/ Overview

organic

solvent

solutions

ion

exchange

compounds (liquid ion exchangers).

The conventional ion exchangers belong to the

ﬁrst group. (The ﬁbrous or powder solid ion ex-
changers are of much less importance.) These ion
exchangers can be classiﬁed according to their chemi-
cal compositions (matrices), and to their functional
groups as follows:

1. Ion-exchange resins with condensation type
(phenol-formaldehyde) or with polymerization type
(styrene-divinylbenzene copolymer or methacrylate-
divinyl-benzene copolymer, etc.) matrix. The strongly
acidic cation exchangers have sulfonic acid groups, the
weakly acidic cation exchangers carboxylic or phos-
phonic acid groups. The strongly basic anion exchangers
usually have quaternary ammonium groups, while the
weak exchangers have primary, secondary, or tertiary
amine groups. Chelating resins have chelate-forming
functional groups containing O, N, or S donor atoms.
Amphoteric ion-exchange resins have both acidic (cat-
ion exchanger) and basic (anion exchange) groups.
2. Cellulose-based ion exchangers. Their chemical
structure is a hydrophilic cellulose network having
acidic (carboxylmethyl, sulfoethyl, etc.) or basic
(amino-ethyl, diethylaminoethyl, etc.) groups.
3. Dextran- or agarose-based ion exchangers. The ma-
trix is cross-linked hydrophilic dextran or agarose and
the attached functional groups are acidic or basic, sim-
ilar to those mentioned for the cellulose ion exchangers,
for cation and anion exchangers, respectively.

4. Inorganic ion exchangers. Inorganic cation ex-
changers include the zeolites (crystalline hydrated
aluminosilicates) and acid salts of polyvalent metal
ions (like zirconium phosphate, titanium tungstate,
nickel hexacyanoferrate(II), etc.), salts of some
hetero-polyacids (ammonium molybdophosphate,
etc.). The hydrous oxides of tri- and tetravalent
metal ions show cation and anion exchange proper-
ties depending on the nature of the metal ion and on
the pH of the solution.
5. Surface-functionalized ion exchangers. Surface-
functionalized ion exchangers are produced for
high-performance ion exchange chromatography as
column packing materials. Usually they are spherical
beads with an inert core (styrene divinylbenzene co-
polymer or silica) and a thin surface layer of ion ex-
changer properties, having acidic or basic functional
groups serving as cation or anion exchangers, re-
spectively. The functional groups can be chemically
bonded directly onto the matrix of the ion-exchange
material or can be attached physically to the matrix
as very small, chemically functionalized latex parti-
cles. The composite ion exchangers have much lower
exchange capacity than the ion-exchange resins, but
their hydrodynamic and mass transfer properties are
much more favorable for rapid, high-performance
chromatographic separations.
6. Ion exchange papers and layers. For ion-exchange
paper chromatography, papers are impregnated
with ion-exchange reagents, or ﬁnely distributed ion-
exchange resin powder is embedded into the paper,
or the paper itself is prepared from cellulose ion
exchanger. For ion-exchange thin-layer chromato-
graphy, the sheets are usually prepared from ion-
exchange resin powder of very low particle size and
ﬁxed by an inert adhesive material.
7. Ion-exchange membranes. Ion-exchange mem-
branes are ﬁlms or thin (0.1–0.6 mm) ion-exchange
sheets with appropriate mechanical properties, and
with proper porosity and low electrical resistance.
8. Liquid ion exchangers. Liquid ion exchangers are
solutions of high molecular mass organic acids (cat-
ion exchangers) or bases (anion exchangers) which
are sparingly soluble in water but readily solu-
ble in less polar organic solvents and by which ions
can be extracted from aqueous solutions.
9. Monolithic ion exchangers. A monolithic ion ex-
changer is formed from a continuous bed of silica or
polymer (rather than discrete particles) in which in-
terconnecting and cross-linked strands of material
form a uniform, porous structure. This structure is
then functionalized to produce anion or cation
exchangers. Monolithic materials have low ﬂow
resistance and can therefore be operated at high ﬂow
rates.

Table 1

Development of ion exchangers and of their analytical

applications

1850

Observation of the ion-exchange properties of soils

1858

Zeolites: natural ion-exchangers in the soils

1917

Determination of ammonia in urine using a synthetic

zeolite

1935

Condensation type ion-exchange resins

1942

Polymerization type cation-exchange resins

1947

Polymerization type anion-exchange resins

1947

Chromatographic separation of rare earths

1948

Specific ion-exchange resin for potassium

1949

Oxidation–reduction functional groups in resins

1948

Liquid anion exchangers

1950

Liquid cation exchangers

1950

Ion-exchange membranes

1951

Chromatographic separation of amino acids

1956

Cellulose-based ion exchangers

1957

Dextran-based ion exchangers

1967

Surface-coated silica ion exchangers for

chromatography

1975

Conductivity detector system and surface-coated

resins for ‘ion-chromatography’

1975

Crown groups in resins

1997

Monolithic ion exchangers

ION EXCHANGE

/ Overview

441

The Properties of Solid Ion
Exchangers

The physical and chemical properties of solid ion
exchangers are crucial to their characterization. Of
the physical properties, color and density are the
most important. For the granular products, particle
size, particle size distribution, the shape of the par-
ticles, the bulk density, porosity, compressibility, me-
chanical stability, and the volume change caused by
acidiﬁcation or alkalinization are important. For
high-performance chromatographic separations, uni-
formity, regular spherical form, low compressibility,
and low volume change of the particles on solvation
are important. For the characterization of the ion-
exchange membranes, the thickness and resistance
against pressure change are also guiding properties.

The most important data for chemical characteri-

stics are as follows:

the ion-exchange capacity (referred to unit volume
or mass);

the nature of the functional groups;

the water uptake;

the structural porosity and rigidity of the matrix;
and

the chemical stability (against acidic/alkaline so-
lutions as well as against oxidants and reductants;
against radiation induced decomposition, etc.).

The ‘capacity’ of the ion exchanger expresses the

amount of exchangeable singly charged ions either
per unit mass or per unit volume. The determination
of the capacity is usually carried out by acidimetric
titration. For the chelating resins, the capacity may
be determined by the uptake of copper(II) ions
referred to unit mass or volume.

The afﬁnities of the exchangeable ions to the ﬁxed

sites depend highly on the ‘nature of the functional
groups’. The ratio of the adsorption strength of simi-
lar ions gives the selectivity of the ion exchangers.

As the ion exchange occurring in aqueous solu-

tions is always accompanied with the transport of
water molecules, the ‘water uptake’ is an important
feature of ion exchangers. The inner porosity, the
number of available exchange sites for ions of higher
size, and the exchange rate of ions at the gel type
ion-exchange resins depend strongly on the water
content and swelling properties of the resin. With the
so-called macroporous resins, the extent of swelling
is lower due to their more rigid structure.

Inorganic ion exchangers exhibit a rigid network

in which the number of available sites depends
strongly on the diameter of the inner channels and on
the size of the hydrated or less hydrated counterions.

For the long-term use of ion exchangers, their

‘chemical stability’ is an important characteristic
which means that during the repeated depletion–
regeneration cycles they should preserve their ex-
change capacities, without degradation of the me-
chanical and physical properties and without
releasing any soluble organic compounds into the
contacting solutions. For nuclear purposes, stability
against radiation is also an important characteristic.

Ion-Exchange Equilibria

The exchange process of two cations (or anions) A
and B taking place between two immiscible phases
can be described by the following equation (the
possible transfer of solvent molecules is neglected):

þ z

¼ X

þ z

½I

where z

and z

denote the charges on the two ions,

respectively. The fraction of the ion exchanger
equivalent to one singly charged counter ion is de-
noted by X. At equilibrium

ð %a

ða

ð %a

ða

½1

where

%a and a denote the activities in the ion exchanger

and in the contacting liquid phase, respectively. K

the thermodynamic equilibrium constant. In the cal-
culation and also in the prediction of thermodynamic
equilibrium constant values, difﬁculties arise from the
fact that the activities inside the ion exchanger phase
are not measurable, and the values of the mass action
ratio expressed in terms of concentrations

ðK

c
B

; see

eqn [2]) usually depend on the mole ratio of the ions
inside the ion exchanger phase:

½B

½A

½B

½2

The mass action ratio can be expressed also in terms of
equivalent fractions, denoted by

%x and x in the ion

exchanger and in the contacting liquid phase,
respectively:

x
B

ð %x

ðx

ð %x

ðx

½3

where

½B

½A

þ z

½B

½4

½A

þ z

½B

½5

442

ION EXCHANGE

/ Overview

½B

½A

þ z

½B

½6

½A

þ z

½B

½7

The ‘selectivity ratio’ (separation factor) of the two

ions, independently of their charge, is as follows:

½B

½A

½B

½A

½8

where D

and D

are the distribution ratios of ion B

and ion A (see later). The larger the value of a

B/A

, the

larger the selectivity of the ion exchanger for the
preference of B ions over A ions. The relationship
between K

and K

is as follows:

c
B

ð %f

ðf

¼ K

T
B

½9

and f

, f

are the activity coefﬁcients for the A, B

ions in the ion exchanger and in the liquid phase,
respectively. The relation between K

and K

x
B

¼ K

c
B

½10

¼ z

[A]

þ z

[B]

) is the total concentration in

the ion exchanger, C(

¼ z

[A]

þ z

[B]

) is the total

concentration in the contacting liquid phase ex-
pressed in terms of equivalents per volume unit and
assuming a binary mixture. The subscripts R and aq
refer

the

exchanger

and

aqueous

phase,

respectively:

¼ a

½11

If z

¼ z

, the relation is very simple:

c
B

¼ K

x
B

¼ a

½12

and the thermodynamic equilibrium constant can be
calculated formally from the following relation if
K

values are known at various

ln K

T
B

ln K

c
B

þ ln

ðf

½13

In analytical chemistry, mainly the K

c
B

and a

B/A

values are used for informatory calculations. The
hydrogen ion is normally used as a reference for cat-
ions and the chloride ion for anions. Both K

and

values depend not only on the nature of the

exchanging ions, but also on the nature of the ion

exchanger. As reference resin, Dowex 50

8 is

usually proposed for cation and Dowex 1

for anion exchangers. Many attempts have been
made to assess the selectivity of ion exchangers,
and to explain factors inﬂuencing it. The main
factors include the charge of the ion being exchanged
(the ‘electroselectivity effect’), the size of the ion
being exchanged, and the chemical nature and
steric arrangement of the functional group on the
resin.

Distribution ratio. The distribution of an ionic

species between the ion exchanger and the contacting
phase is an important term in ion-exchange chro-
matography, because the migration rate of the ion on
the chromatographic column and hence the position
of the peak of the component in the chromatogram is
controlled by the distribution ratio.

For a metal ion, M

½M

½14

The distribution ratio depends on the concentration
of the competing ion in the electrolyte, E

(e.g.,

NaCl or HCl):

½M

½E

2
aq

½M

½E

2
R

½15

½M

¼ K

½E

2
R

½E

2
aq

½16

If the M

metal ion is present in low concentration

and the E

‘eluent’ ion in medium concentration, the

resin is practically in E-ion form and [E

]

is very

close to Q (capacity of the resin), and K

can be

regarded as constant:

¼ K

c
M

½E

2
aq

½17

or in logarithmic form:

log D

¼ log K

c
M

þ 2 log Q 2 log ½E

½18

There is a linear relation between the logarithm of
the distribution ratio of the metal ion and the
logarithm of the concentration of the competing elu-
ent ion. The slope of the line corresponds to the ratio
of the charges on the two ions (2/1). The distribution
ratio of multicharged ions increases steeply with
decreasing concentration of the singly charged eluent
ion. It is interesting to note that the equation is valid
not only in the case if Q is constant (i.e., the same
ion exchanger is used) but also in the case if the
concentration of the eluent is constant but the
capacity of the ion exchanger is changing.

ION EXCHANGE

/ Overview

443

The D

value of the metal ion can be inﬂuenced

not only by the change of the eluent ion concentra-
tion but also by changing the actual value of the
ion-exchange concentration constant. By using
complex-forming agents, which form complexes of
zero or of opposite charge with the metal ion, a
conditional ion exchanger constant can be comput-
ed, which is of lower value than that of the original
one. If a complex-forming agent, H

L, is added to

the solution, which forms complexes according to
the equations

þ L

½II

þ 2L

½III

and the protonation of the ligand takes place ac-
cording to the reactions

þ H

½IV

þ H

0
2

½V

the conditional constant for the M

ion-ex-

change will be

ðLÞ

½19

where

ðLÞ

¼ 1 þ

ðHÞ

½20

ðHÞ

¼ 1 þ ½H

þ ½H

½21

If the pH, and the analytical concentration of the
ligand, C

, and [E

] are known, the conditional

constant value using eqn [19] and the conditional
distribution ratio can be calculated too.

Similar calculations can be carried out for plan-

ning separations of metal ions, or of organic acids
etc. using either solid or liquid ion exchangers, if the
ion-exchange concentration constants, the corre-
sponding protonation and complex formation con-
stants are known.

Beside the ion-exchange process, ‘absorption of

electrolytes’ also takes place if the ion exchanger is in
contact with electrolyte solutions. The extent of the
invasion of the ions depends on the concentration of
the electrolyte in the solution and on the density of
the ionic sites in the ion exchanger phase. The dis-
tribution of the electrolyte between the two phases is
governed by Donnan equilibrium, and is signiﬁcant
only in solutions of higher than 0.1 mol l

concen-

tration. At lower concentration the electrolyte is
‘excluded’ from the ion exchanger phase. For a
single–single charge electrolyte of composition EY,

the concentration of Y

in the ion exchanger phase

can be estimated from the following equation:

½EY

2
aq

¼ ½Y

þ ½Y

2
R

½22

The second term on the right-hand side can be negle-
cted, and eqn [22] is simpliﬁed:

½Y

½EY

2
aq

½23

The ion-exclusion phenomenon is used in ‘ion-
exclusion chromatography’ for separation of ions
of different characters or charges.

Absorption of nonelectrolytes can take place from

solution. The extent of the absorption depends on the
matrix properties of the ion exchanger and on the
electrolyte concentration of the liquid phase. The phe-
nomenon is used for separation of nonelectrolytes and
weak electrolytes by ‘salting out chromatography’.

Ion-Exchange Kinetics

As a general rule, the rate of ion-exchange processes
is controlled by the diffusion of the exchanging ions.
In a few cases the exchange rate is inﬂuenced by slow
chemical reactions.

The rate controlling steps for solid ion exchangers

are in general

transport of the counterions across a thin liquid
ﬁlm (Nernst ﬁlm) covering the surface of the ion
exchanger and

diffusion of the ions inside the solid ion exchanger
phase.

In the mass transfer kinetics of the liquid–liquid

ion exchanger processes, the contacting surface area
and also the diffusion rate of the ions in the liquid
phases are the controlling factors. The process can be
highly accelerated by agitation.

For solid ion exchangers, considering spherical

particles and for the simple ion exchange of isotopic
species, if the process is controlled only by the dif-
fusion of the ions in the thin ﬁlm solution phase the
fractional attainment of equilibrium as a function of
time t can be expressed as follows:

¼ 1 e

ð3dc=rdQÞt

½24

where d and c are the diffusion coefﬁcient and concen-
tration of the ion in the solution phase, r is the radius of
the ion exchanger solid particle, d is the thickness of the
liquid ﬁlm, which can be inﬂuenced by agitation, and Q
is the capacity of the ion exchanger. The half time (until
F

¼ 0.5) of the process is given by

¼ 0:023rdd

½25

444

ION EXCHANGE

/ Overview

For a reaction that is controlled solely by diffusion
within the solid particle, the equation is

¼ 1

ð %dp

Þt

½26

where %

d is the diffusion coefﬁcient of the ion in the ion

exchanger phase. The half time

¼ 0:03r

= %d

½27

depends only on the particle size and diffusion coefﬁ-
cient but not on the concentration.

Since the diffusion coefﬁcients of simple ions

in aqueous solutions at room temperature are
B10

, while the diffusion coefﬁcients in-

side the usual ion exchanger resins are in the range of
10

, ﬁlm diffusion is rate control-

ling only at very small particle size (10

mm) and at

low concentration. High concentration, large particle
size, compact ion exchanger phase (strongly cross-
linked polymer), and less mobile, large ions favor
inner diffusion control.

Application Techniques

Ion-exchange processes using solid ion exchangers
are usually carried out either by a batch or column
technique.

Since in the batch procedure the ion exchange

comes to equilibrium, quantitative exchange of ions
from a solution can be obtained only in the case if the
exchange reaction is highly favored (K

is high) or

multicharged ions are absorbed from singly charged
ion-containing solution of low concentration, and
the ion exchanger is in a fairly large excess.

Using ﬁxed bed ion-exchange column techniques,

the quantitative exchange of ions can also be attained
in those cases where the selectivity conditions are not
very favorable. In these cases the length of the col-
umn and ﬂow rate must be chosen properly.

Applications

Applications of the solid ion exchangers in the ana-
lytical laboratory can be grouped into the following
classes:

1. procedures based on the total ion-exchange

principle,

2. chromatographic separations, and
3. use of ion exchangers as carriers.

For the procedures belonging to class 1, mainly col-
umn techniques, but in a few cases batch techniques
also, can be used.

In ‘inorganic analysis’ the most important appli-

cations are as follows:

titrimetric determination of the salt content of
solutions, by transforming them either into acid or
base;

preparation of standard solution of acids and
bases (e.g., preparation of carbonate-free alkali
hydroxide solution);

dissolution of weakly soluble salts (like gypsum);

removal of interfering ions: either cations, or an-
ions, or both; and

enrichment of ions of low concentration; collec-
tion of metal ion impurities from large volumes
of drinks or from natural waters. The adsorbed
metal ions can be eluted thereafter with a small
volume of a suitable electrolyte solution for sub-
sequent determination. For selective adsorption of
certain metal ions, the presence of chelate-forming
functional groups can also be useful.

In quantitative analysis based mainly on column

chromatographic techniques, elution methods are
preferred. The displacement chromatographic sepa-
rations are useful for preparative purposes. The
chromatographic procedures are useful for separa-
tion of metal ions from each other using cation ex-
change column or in their anionic complex ion form
using an anion exchanger column. For the separation
of ions of nonmetallic elements (Cl

, Br

, HPO

etc.), an anion exchanger column is used.

For the detection of the separated ions, spectro-

photometric and other spectroscopic detection meth-
ods are used.

If the distribution ratio of the analyte is fairly high

4100), but that of the accompanying ions are

low, separation with selective sorption (solid phase
extraction) can be achieved.

Ion-exchange resins are useful as carriers for

storing reagents or indicators, and to facilitate their
use in laboratory work.

In ‘organic analysis’, the procedures based on total

ion exchange are used for transformation of salts to
acids or to bases; for removal of electrolytes from the
solution of nonionic compounds; for isolation and
separation of ionic or ionizable compounds from in-
terfering substances; and group separation of com-
ponents of a mixture containing acidic, basic, and
less polar components.

Using chromatographic techniques, mixtures of

acids, amines, aldehydes, ketones, amino acids, sugars
etc. can be analyzed. If salting out and ion-exclusion
chromatographic techniques are included, quite a
wide range of organic compounds can be separated
and determined. By the use of dextran-based packing

ION EXCHANGE

/ Overview

445

materials, ionizable bioactive compounds of higher
molar mass can be analyzed chromatographically.

In organic analysis, the ion exchangers can be used

as carriers for preparation of solid reagents (e.g.,
diazo reagents or enzymes).

Liquid Ion Exchangers

Liquid ion exchangers are useful for extraction of
metal ions, free acids, or bases from aqueous solu-
tions. The collected ions can be back-extracted using
an electrolyte of proper composition for the deter-
mination after the separation of the phases.

Ion-Exchange Membranes

Ion-exchange membranes can be used as electrodes
for electrometric titration of the salt content of wa-
ter, or in electrodialysis cells for separation of ions of
different charge or of different mobility.

The ion-exchange sheets or papers containing ion-

exchange groups (or being impregnated) can be used
for separation of inorganic and organic ions or ioni-
zable compounds using a buffer solution as eluent
and using established thin layer or paper chro-
matographic techniques.

Columns ﬁlled with resins containing functional

groups with oxidizing–reducing properties can be

used as columns, for the quantitative oxidation or
reduction of certain components of an aqueous so-
lution (e.g., reduction of iron(III) traces to iron(II)
using Variamine Blue reductor).

See also: Ion Exchange: Principles; Ion Chromato-
graphy Instrumentation; Ion Chromatography Applications.
Membrane Techniques: Dialysis and Reverse Osmosis.