The Application of

Complexometric Titration

An application method of
Inorganic Pharmaceutical Analysis

Lecturer : Dr. Tutus Gusdinar

Pharmacochemistry Research Group
School of Pharmacy
INSTITUT TEKNOLOGI BANDUNG
 H 4Y
tetraprotic acid

MY
chelate
h l t
Complexometric titration curve is plotted of pM versus
volume of titrant, by calculated from pM = - log [M+]

This titration curve can be used for the purpose of :

1) Determination of titration feasibility
2) Choose an appropriate metal indicator

Some of technical application of the titration are :

1) Direct titration
2) Back titration
3) Substitutive titration
4) Indirect titration
5) Selective or specific titration
 COMPLEXOMETRIC CURVE
Calculate such metal ion potent as :
1) pM before the titration
2) pM
M before
b f (at
( t neighbourhood
i hb h d of) f) the
th EEquivalent
i l tP Point
i t
3) pM at the Equivalent Point
pH = 12
4) pM just after the Equivalent Point
Example : pH = 10

pH
H=8

pCa

Metal ionic “buffer”

ml of EDTA
50
 COMPLEXOMETRIC TITRATION FEASIBILITY

The Effective Equilibrium Constant (Keff is as K

required in the reaction) for the most feasible
titration is calculated from stoichiometric reaction.

Example
50 ml of M2+ metal ion solution of 0.01 M is titrated
with Na2EDTA solution of 0.01 M. Calculate Keff after
49.95 ml of Na2EDTA addition where pM changed
by 2 units when 2 drops (0.10 ml) of Na2EDTA titrant
addition.
Before the titration
titration, EDTA is 0.5
0 5 mmoles
At one drop before the Equivalent Point, EDTA will
be 0.4995
0 4995 mmoles
mmoles, and the excess of 0 0.0005
0005
mmoles of M2+(in total volume of 99.95 ml) is 5 x 10-
6 M or pM = 5.30.
5 30
But if ΔpM is 2.0 units the pM = 7.30 or [M2+]= 5 x
10-88 M,
M occurred d after
ft 50.05
50 05 mll off tit
titrantt addition.
dditi
CY = (0.05 x 0.01)/100.05 = 5 x 10-6 M.
[MY2-] = 0.5 mmoles/100 ml = 5 x 10-3 M.
hence
Keff = 5x10-3/(5x10-8)(5x10-6) = K = 2 x 10-3 M

What is the Keff if the ΔpM is only 1.0 unit ?

 FEASIBILITY OF
COMPLEXOMETRIC TITRATION
If the K for a feasible titration was known
known, we can
calculate pH minimum in which the titration is
feasible For example :
feasible.
Zn2+ titrated with Na2EDTA, log Kef > 8.0.
Read from Data Table : log Kabs of ZnY2- = 16.50
logg Kef = log g α4
g Kabs + log
Then Keff at any pH can be calculated :
Keff = 8.06
8 06 at pH = 4
Keff = 10.05 at pH = 5
The titration will be feasible when pH = 4
 METAL ION INDICATOR
Metal ion indicator is a dyestuff forming a
complexed compound with a metal ion, having
different colour of free from a non complex indicator
species. Metal indicators are generally acid-base
indicator Acid-base
indicator. Acid base equilibrium must be calculated
at any type of metal ion indicators.
example : 1) Eriochrom Black T (or EBT)
2) Calmagite
3) Murexide
4) Calcon
 Complexometric curve of Calmagite
pMg pCa
In3-
Reddish
8 orange
8
HIn- HIn2-
red blue H2In- HIn2- In3-
red blue Redish
6 orange
6

4 Mg(OH)
g( )2
White 4

MgIn- precipitate
CaIn-
Red
red
2
2 Ca(OH)2
White precipitate
8 10 12 14 8 10 12
pH pH
 Complexometric Curve of Mg-Calmagite

pKa HIn2- = 12,4

9 II In3-
III Reddish orange
g

a H2In- = 8.1
1
8 IV
HIn2-
7 H2In-
blue
red

pKa
6

pMg Eq Pt =5,26
=5 26 End Pt =5,7
=5 7
5

4 I

3 MgIn-
red Mg(OH)2
2 Whit
White
precipitate
1
0
6 7 8 9 10 11 12 13
pH
BUFFER PROPERTIES OF METAL IONS
M + L ML
metal ion Ligand
g Complex
p

If CL = ligand analytical concentration, then

Keff = (ML)/(M).CL
[M] = 1/Keff . [ML]/CL
log [M] = log 1/Keff + log (ML)/CL
pM = log Keff - log [ML]/CL
pMM = log
l Keff + log l CL/(ML)
(similar to Henderson-Hasselbalch)
When pM “fixed”
fixed to Keff
and metal ion complex molar ratio to
forming ligand concentration
 COMPLEXOMETRIC TITRATION ERROR

titration Error = + ΔpM atau + ΔpL

(
(caused d off ΔpMM = - ΔpL) L)
% Titration Error = 100 x {[L]final – [M]final} / CM
CM = analytical concentration of metal ion total in solution
ΔpM = pMfinal – pMequivalent
or [M]final = [M]equivalent . 10-ΔpM
and [L]final = [L]equivalent.10-ΔpL
Due to [M]equivalent = [L]equivalent
then % Titration Error = 100 [M]equivalen. {10ΔpM – 10-ΔpM} / CM
= 100 . {10ΔpM – 10-ΔpM}/ CM.K’M’L’
if ΔpM < 0,4 (small) then
% titration error = 100. 4.6.ΔpM / CM.K’M’L’
 SELECTIVITY OF COMPLEXON
Complexon selectivity can be maintained by :

1.
1 Adjustment of pH (buffering)
2. Masking
3
3. Demasking
4. Separation
5
5. Extraction
6. Anionization
7
7. Kinetic Masking
8. Metal ion indicator reaction
 1) Selectivity due to pH
Mixture of Bi3+ and Th4+ : Bi3+ is titrated in
acid solution (p
(pH=2)) using
g indicator Xyline
y
Orange + Methylthymol Blue

Mixture of Bi3+ and Pb2+ can be titrated at

pH=2 using indicator Xyline Orange, then
histamine was added up to pH pH=5 5 for
enabling titration of Pb2+
2) Selectivity due to masking
Masking does not result a physical reaction
and not change the initial state
By masking,
masking some of cation mixture can
not react with EDTA and indicator. The
effective masking agent such as CN- forms
complex compound with Cd2+, Zn2+, Hg2+,
Cu2+, Co2+, Ni2+, Ag+, but does not react
g2+, Pb2+, Ca2+, Sr2+),
with earth alcalies ((Mg
then metal ion mixture can be titrated with
Ca2+, Pb2+, Mn2+, Mg2+
3) Selectivity due to demasking
Demasking is a process where masked
compounds are not able to change the
initial state
Cd2+ and Zn2+ which is masked with CN-
can be demasked with chloralhydrate or
mixture of formaldehyde + acetic acid (3:1)
until complexed of [Zn(CN)4]2+ can release
its Zn2+. This technique is usually used
for determining a mixture of Mg2+,
Cu2+, Zn2+.
4) Selectivity due to separation
Precipitation of Ni2+ as NiNi-DMG
DMG
(DMG=dimethylglyoxime) or Cu2+ as CuCNS

5) Selectivity due to extraction

Mixture of Cu2+ and Zn2+ or Pb2+ and Zn2+
with NH4CNS forms Zn-thiocyanate
Zn thiocyanate which
can be extracted with isobuthylmethylketon.
After dissolution of the extract in water, then
Zn2+ can be titrated with Complexon III
6) Selectivity due to anionization
Ortho-phosphate ion can be separated by
using anion exchange resin

7) Selectivity due to kinetic masking

One metal ion is changed to inert, then one

reaction
ti iis slow
l b
butt another
th reactt ffastly.
tl
Such as titration of Cr3+ with Na2EDTA
8)) Selectivity
y due to reaction
of metal ion with its indicator
Metal ion indicator should
1. React to yield a sharp colour change
2. React selectivelly of specifically with metal ion
3. Yield a stable metal-indicator complex compound and
result
lt an intensive
i t i colour
l d
due tto a stability
t bilit off M-Ind
MI d<
M-EDTA
4. pH adjus
p adjusted
ed aat the
e feasible
eas b e titration
a o cocondition
d o
pH=5.3-7.1 pH=10.5-12.5
H2In- HIn2- In3-
red blue orange yellow
pH=7-11
5
5. Have a distinct colour of free indicator from a complex
of Metal – Indicator.
 ERIOCHROME BLACK T (EBT)
metal ion indicator
a chelate complex formed by releasing a
proton from phenolic group, then metal ion
forms a covalent bond with an oxygen
yg atom
and a coordinative covalent bond with a
nitrogen atom

EBT is a triprotic acid molecule, H3In, releasing H+

f
from a sulphonic
l h i group iindependent
d d t tto pH H off th
the
solution, to form H2In- (red). This indicator forms a
gra e red colo
grave colourr stable comple
complex (1:1) ith Mg2+, Ca2+,
(1 1) with
Zn2+, Ni2+
Titration of Na2EDTA should be performed at pH=8- pH 8
10 where the EBT is in HIn2- (blue) form.
 CALMAGITE
(a stable form of EBT)
Properties
P ti and
d reaction
ti are similar
i il tto th
those off EBT :
H3In H2In- + H+
(red)
H2In- HIn2- + H+ pKa2= 8,1
(blue) ( K 2 EBT=6,3)
(pKa 6 3)
HIn- In3- + H+ pKa3=12,4
(orange) ( K 3 EBT=11,6)
(pKa 11 6)

Mg2+ + HIn2- MgIn- + H+

(blue) (red)
A sharp colour change from blue to red
red, titration
should be at pH=8-11.
 OH HO

-O S N N
3

NO2

Eriochrome Black T
H3In
 OH HO

-O S N N
3

CH3

Calmagite
H3In