1. Complexation& Complexes used in Pharmacy
3rd Year Pharmacy

2. 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
bidentate: two bond to metal ion
polydentate: more than two bonds to a metal
ion possible

3. Example : Octahedral Complex FeCl3 +3H2O= [Fe(H2O)3Cl3]
H2O H2O

4. 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 )

5. 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 .

6. 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.

7. Table2: Complexation ligands
Anionic ligands
Neutral ligands
CN-
H2O
NH3
S2O3-2
HOR
NH2R F-
ROR
NHR2
OH-1
R2C=O
NR3
Cl-1
RHC=O -
Br-1

8. Bidentate ligands
Ligands have two positions arranged, so that both can act simultaneously as donor sites in a complex

9. Table 3:Some common bidentate Ligands
NH2CH2CH2NH2 En
Ethylene diamine
NH2CH2COO-
Gly
Glycinate
-ooccoo- -
Oxalate
EDTA
Ethylen diamine tetraacetic acid

10. Example ( en + M+2)
M +2
H2N CH2-CH2-NH2

11. 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.

13. 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.

14. 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 ….

15. EX: Cr+3 + 6CN-1 = Cr( CN)6 -3 Cr24 : 4S2 3d4 4p0 Cr +3 4S0 3d3 4p0
d2 SP3

16. H3N
H3N H3N Cr
H3N H3N

17. C ompare between the following complexes
Fe ( H2O)6 +3
Fe ( CN)6) -3

18. 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.

19. [Fe( CN)6]-3 D.M= 2 B.M low spin complex
3d5 octahedral complex structure
d2SP3

20. 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 .

21. Pharmaceutical Products
1- Ca di Na edetate
2- Di Na edetate
3- penicillamine
4-Dicaperol
5- Iron injection ( imferone )

22. 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

24. 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.

25. It is no value in treatment for Hg,As & Au.

26. 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

28. 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

29. 3- Penicillamine
. The pharmaceutical form is D- penicillamine, as L-penicillamine is toxic (it inhibits the action of pyridoxine

30. 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.

32. 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

33. 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).

34. Iron+ Dextran=Complex
Fe(OH)3 given as injection
Fe+2
Fe SO4 given orally.
Fe+2 Lactate orally