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Complexation& Complexes used
in Pharmacy
2016-2017 
3rd Year Pharmacy 
Ligands
Molecule or ion having a lone electron 
pair that can be used to form a bond to a
metal ion
(Lewis base).

coordinate covalent bond: metal- 
ligand bond
monodentate: one bond to metal ion
two bond to metal ion bidentate:
more than two
polydentate:



Example : Octahedral Complex
FeCl3 +3H2O= [Fe(H2O)3Cl3]
Cl 
H2O
Cl 
Fe 
H2O
H2O 
Cl 
Werner Theory
1- Two steps of valiancy are observed 
Primary ( ionizable )and Secondary non- 
ionizable valence.
2-Each metal exhibit a specific maximum 
numbers of secondary valence.
3-The primary valences are filled by 
anions, but secondary valence anions or
neutral.
4- The ligands are arranged (Square 
planner, Tetrahedral, Octahedral )
The most stable complexes are found by 
cations of the transition series with
anions. Why?
The criteria for maximum stability of the 
metal in a complex involving ( + ) charge ,
a small cation radius and unoccupied .
Properties of Ligands
The ligands may be anions or neutral 
molecules .
Neutral atoms arenot found in 
coordination agents.
There are one factor that all ligands have
in common that one non – bonded pairs
of es , which is used to form a
coordination covalent bond with metal.


Table2: Complexation ligands
Neutral ligands
Anionic ligands
NH3
H2O
CN-
NH2R
HOR
S2O3-2
NHR2
ROR
F-
NR3
R2C=O
OH-1
-
RHC=O
Cl-1
Br-1
Bidentate ligands
Ligands have two positions arranged, so 
that both can act simultaneously as donor
sites in a complex
Table 3:Some common bidentate
Ligands
Ethylene diamine
En
NH2CH2CH2NH2
Glycinate
Gly
NH2CH2COO-
Oxalate
-
-ooccoo-
Ethylen diamine
tetraacetic acid
EDTA
-
COO
O OC
N
-
N
-
O OC
Ethylene diamine tetraacetic acid
COO
-
Example ( en + M+2)

M +2

H2N CH2-CH2-NH2 
Importance of Chelation
1- Employ in pharmaceutical and reducing 
agent( Benedict reagent) for sugar test.
2- Drug Therapy ( various types of poisoning 
&Radioactive materials).
3- Titration with complexing agents in 
analytical methods.
4-Has been used to alter the physicochemical 
& biopharmaceutical properties of drugs
5-Chelation is used in solubility & stability of 
products.
Bonding in Complexes
There FOUR theories describe the 
bonding in complexation :
1-Valence bond theory 
2-Crystal field theory 
3-Ligand field theory 
4-Molecular orbital theory( MOT) 
MOT now is used in common. 
Factors affecting the complexation
The solution conditions that effect the 
size of the formation constant are: •
Temperature, • Presence of competing
ions, • pH, and • Ionic strength, stability
….
EX: Cr+3 + 6CN-1 =
Cr24 :
Cr +3
d2 SP3 
Cr( CN)6
4S2 3d4 4p0 
4S0 3d3 4p0 
-3
H3N 

H3N
H3N 
Cr 
H3N
H3N 
H3N 
C ompare between the following
complexes
Fe ( H2O)6 +3 
Fe ( CN)6) -3 
Answer
[Fe ( H2O )6 ] +++ 
magnetic momentum = 5.9 B.M( Bohr 
magnaton )
4s2 3d6 
Fe+++= 4s0 3d5 
(H2O)6 are on sp3d2 high spin complex 
Octahedral structure. 
[Fe( CN)6]-3
D.M= 2 B.M low spin complex 
3d5 octahedral complex structure
d2SP3 

Why Ni(CN)4 is squar plannar
while NiCl4 is tetrahedra
When lighand CN is low spin , the d 
orbital be vacant & form dsp2 hybride is a
squar plannar.
In case of Cl high spin lighand , the d – 
orbital would only have SP3 and form
tetrahedral .
Pharmaceutical Products
1- Ca di Na edetate 
2- Di Na edetate 
3- penicillamine 
4-Dicaperol 
5- Iron injection ( imferone ) 
1-Calciuum di sodium edetate
Calcium Disodium Versenate (edetate 
calcium disodium injection, USP) is a
sterile, injectable, chelating agent in
concentrated solution for intravenous
infusion or intramuscular injection. Each 5
ml ampoule contains 1000 mg of edetate
calcium disodium (equivalent to 200
mg/ml) in water for injection
Chelation therapy should not replace 
effective measures to eliminate or reduce
further exposure to lead.( Plumblism)
It may be used for posioing Cu, Ni , Cd, 
Zn, Cr , & Mn.
It is no value in treatment for Hg,As & Au. 
2-Disodium edetate.
Endrate (Edetate Disodium Injection, 
USP) is a sterile, nonpyrogenic,
concentrated solution of edetate
disodium in water for injection which as a
result of a pH adjustment with sodium
hydroxide contains varying amounts of
disodium and trisodium salts. After
dilution, it is administered by intravenous
infusion
Uses.
Endrate (Edetate Disodium Injection, 
USP) is indicated in selected patients for
the emergency treatment of
hypercalcemia and for the control of
ventricular arrhythmias associated with
digitalis toxicity
3- Penicillamine
. The pharmaceutical form is D- 
penicillamine, as L-penicillamine is toxic (it
inhibits the action of pyridoxine
Uses of penicillamine
In Wilson's disease, a rare genetic 
disorder of copper metabolism,
penicillamine treatment relies on its
binding to accumulated copper and
elimination through urine.
4- Dimercaprol
Dimercaprol (INN) or British anti- 
Lewisite (abbreviated BAL)
Dimercaprol is itself toxic, with a narrow therapeutic
range and a tendency to concentrate arsenic in some
organs. Other drawbacks include the need to administer
it by painful intramuscular injection.[7] Serious side
effects include nephrotoxicity and hypertension
5-Imferon injection
1- Iron defiency ( anemia ) 
Pregnency or Children 
It give by Physician in applying equation to
calculate the dose.
2-Iron replacement ( Blood loss). 

Iron+ Dextran=Complex
Fe(OH)3 given as injection 
Fe+2 
Fe SO4 given orally. 
Fe+2 Lactate orally 