Pharmaceutical Analytical Chemistry II

(PHC 103)

Complex formation
Titrations

1
Pharmaceutical Analytical Chemistry II (PHC 103)

The 100 marks of this Course is divided into:

- Midterm : 10 marks
- Quiz : 5 marks
- Attendance and behavior : 5 marks
- Practical exam : 20 marks
- Oral exam : 10 marks
- Written final exam : 50 marks

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3
 Schedule of Practical Analytical Chemistry II (PHC 103) Clinical

.Week No Date Subject

1 18/2/2024 Determination of Ni2+, Zn2+ samples

2 25/2/2024 Determination of Ca2+/Mg2+ mixture
3 3/3/2024 Preparation and standardization of
N KMnO4 0.1
Determination of Oxalic acid sample

4 10/3/2024 Determination of Fe2+/Fe3+ mixture

5 17/3/2024 Determination of H2O2 sample
6 24/3/2024 Determination of I- (by Andrew's method)
31/3/2024
7 Midterm Exam
7/4/2024
8 Practical exam 1
14/4/2024
9 Potentiometric titration of NaOH solution with acetic acid solution

21/4/2024 Conductometric titration of NaOH solution with HCl solution

10

28/4/2024 Revision
11

5/5/2024 ‫إجازة شم النسيم‬

12
12/5/2024
13 Practical Exam 2
4
 Complexometry
Complex formation Titrations
Analytical Chemistry

• What is a complex
• Complex formation
• Co-ordination number
• Types of complexing agents
• Factors affecting stability of
complexes
 Definition
A Complex is a weakly ionizable stable
compound, formed by the reaction of a metal ion
Analytical Chemistry

(Mn+) with an anion or neutral molecule (Ligand).

Complex

where metal ion act as Lewis acid (electron

acceptor) and ligand as Lewis base (electron donor)
forming a coordinate bond
Analytical Chemistry

Example
 Complex formation

  H]
M n+ + [H  O M.(H2O)x
Analytical Chemistry

..
aquo-complex

Therefore Metals form with water Aquo-complex

Complexation reaction is the replacement of

solvent molecules by ligand
[M.(H2O)x] n+
+ L [M.(H2O)x-1 .L]n+
2+
(aq) + 4 NH3(aq) → [Cu(NH3)4]2+(aq) + 4 H2O(l)]Cu(H2O)4[
 Co-ordination number
Analytical Chemistry

Co-ordination number is, the number of bonds

formed by the central metal ion with the ligand.
Typical values of co-ordination number are 2,4 or 6.
Example

[Cu (H2O)4]2+ + 4 NH3 [Cu(NH3)4]2+ + 4H2O

+
Usually double valency of Mn
 Types of complexing agents

1- Unidentate ligands
-
NH3, H2O, halides, CN
Analytical Chemistry

Example : Formation of copper ammine complex

2+
NH3
..

Cu2+ + 4NH3 H3N: Cu :NH 3

..
NH3
 2- Polydentate ligands (Chelating agents)
Analytical Chemistry

- Chelating agents are organic molecules (usually

insoluble in water) containing two or more groups
capable of donating unshared pair of electrons.
- They form ring structure with metal
-Polydentate Ligands are called chelating agents and
the complexes are called chelates
 Examples
A) Bidentate ligands
• Ethylene diamine:
Analytical Chemistry

H2N: :NH 2
H2C CH2
H2N-CH2-CH2-NH 2 + Cu2+ H2C .. Cu
.. CH2
NH2 H2N
 • 8-hydroxyquinoline
Analytical Chemistry

2 + Mg2+ + 2H+
N N
OH :O:
Mg
 • 1,10-O-phenanthrolene:
Analytical Chemistry

2+

N N
+ Fe2+ Fe
N N

3
 b) Tridentate ligand.

e.g. Diethylene triamine

Analytical Chemistry

H2C CH2
H2N-CH NH2
.. 2-CH2-NH-CH
.. 2-CH2-NH
.. 2 NH
NH2
H2C CH2
 c) Tetradentate ligand
Analytical Chemistry

e.g. Triethylene tetramine (Trien)

H2C CH2
NH2 NH CH2
NH2 NH CH2
H2C CH2
 chelates are more stable than complexes
formed by unidentate ligands, due to the
Analytical Chemistry

presence of more than one point of

attachment of ligand to Mn+
 Polydentate ligands are preferable as titrant if
compared with unidentate ligands because:
Analytical Chemistry

1- Polydentate ligands react completely in one step

forming stable complex leading to sharp end point

2- Stepwise formation of complex with unidentate

ligands give no sharp end point due to gradual
increase or stepwise formation of complex.
* Ammonia couldn’t be use as titrant.??
 Factors affecting stability of complex

1- Ability of central metal ion to form complex.

Analytical Chemistry

2- Ability of ligand to form complex.

3- Structure of the final chelate.

4- The pH value.
 1- Ability of central metal ion to form complex.

The higher the acidity (electron deficiency) of

Analytical Chemistry

central metal ion (Mn+) the higher the stability of

the formed complex.
Acidity of Mn+ depends on

• Intensity of + ve charge on Mn+

Q Charge
Intensity of + ve charge on Mn+ F radius
m
Mn+ of small radius and high + ve charge has high ability to
form stable complex.
 2- Ability of ligand to form complex.

It depends on Basicity of ligand and Size of ligand

a- Basicity of ligand
Analytical Chemistry

Basicity of ligand is its electron donating ability.

Therefore ligand must contain electron donating
atom e.g.
N > O > S > X- (I- , Br- , Cl- , F-)
Organic ligands must contain co-ordinate and acidic
groups or both of them.
 Examples of co-ordinate groups
:O: Keto group - NH2 amino group
Analytical Chemistry

.. Ether group - N=O nitroso group

O
..
- OH Alcoholic - OH nitro group N O

-N= Cyclic nitrogen oxime C NOH

 Examples of acidic groups
Analytical Chemistry

- COOH Carboxylic = NH imino group

acid group

- SO3H Sulphonic NOH oxime

C
acid group NOH

- OH Phenolic - OH
 b- Size of ligand
Analytical Chemistry

Large, bulky ligands form less stable complexes

than smaller ones due to steric effect

CH3 H3C
H2N - CH2 - CH2 - NH2
N CH2 CH2 N
Ethylene diamine H3C
Form more stable complexes CH3

form less stable complexes

 3- Structure of the final chelate

It was found that, most stable chelates are formed

Analytical Chemistry

by saturated ligand that forms five-membered ring

or by unsaturated ligand forming six-membered
ring
 EDTA as titrant in complexometric titration

HOOC.H 2C CH2COOH
Analytical Chemistry

N CH2 CH2 N
HOOC.H 2C CH2COOH

ethylenediamine tetra-acetic acid (Complexon III)

 - -
+
Na OOC.H 2C CH 2COO Na+
N CH 2 CH 2 N
H OOC .H 2C CH 2 COO H
Analytical Chemistry

The di-sodium salt of EDTA which is soluble in water forms

soluble chelates and called sequestering agent, therefore it
is the most suitable titrant.
The disodium salt of EDTA is abbreviated by
Na2H2Y

Sequestering agent (soluble chelates)

EDTA form 1:1 stable complexes with metal ions
 In water
Na2H2Y 2Na+ + H2Y2-
Analytical Chemistry

EDTA reacts with different Mn+ producing chelate in the

ratio of 1:1 irrespective to the valency of Mn+

H2Y2- + M2+ MY2- + EDTA titrations are

H2Y2- + 2H
+
MY- + 2H+ done in alkaline or
M3+H Y2- + buffered medium
2
MYo +
M4+ 2H+
+
Mn+ + H2Y2- MY(n-4) + 2H
 From the previous

1- Mn+ displace (2H+) in H2Y2- producing 2 gm. mol. of

Analytical Chemistry

hydrogen.
2- EDTA is not selective reagent
3- The reaction between EDTA and Mn+ is according to M.wt.,
therefore EDTA is used as molar standard.
4- Formation or dissociation of the formed complexes is
affected by pH.
The reversibility of the reaction can be prevented by addition of
buffer or alkali to shift the reaction forward and hence stability of
chelate is increased.
 Stability and stability constant of complex

Stability of a complex is evaluated by its stability

constant (or formation constant). Assume a
Analytical Chemistry

reaction between metal ion (Mn+) and EDTA

(H2Y2-)
Vf
Mn+ + H2Y2- MY (n-4) +
V 2H+
b
 According to the law of mass action
Analytical Chemistry

[My (n  4 ) ][H ]2
K eq 
[Mn  ][H2 Y 2  ]

formation constant (Kf)

or stability constant (Kst.)
 In buffered medium
Analytical Chemistry

(n  4 )
[My ]
K st. 
[Mn  ][H2 Y 2  ]

For a complete complexometric titration the

produced complex should have
Kst ~ 108
1
=
Kinstability Kst