Complexation: Classification of complexation: Metal ion or co-ordination complexes : Inorganic type Organic molecular complexes : Quinhydrone type Picric acid type Caffeine and other drug complexes Polymer type Inclusion or occlusion compound Channel lattice type Layer type Monomolecular type Macromolecular type Chelates Olefin type Aromatic type Pi (п) complexes Sigma (б) complexes Sandwich complexes

1. IIIrd Semesester B. pharmacy
Physical Pharmaceutics-I
Unit-IV
Complexation and Protein Binding [Part-1]
(Introduction and Classification and application )
Miss. Pooja D. Bhandare
(Assistant professor)
Kandhar college of pharmacy

2. Complexation:
• Interaction of two or more substances that either based upon donor-
acceptor mechanism or Lewis acid base theory.
• The interaction forces involved are:-
 Covalent bonding
Van der Wall forces
Hydrogen bonding
Ion-dipole, dipole- dipole, dipole induced dipole etc.

3. Classification of complexation:
1. Metal ion or co-ordination complexes :
a. Inorganic type
b. Chelates
c. Olefin type
d. Aromatic type
i. Pi (п) complexes
ii. Sigma (б) complexes
iii. Sandwich complexes

4. 2. Organic molecular complexes :
a. Quinhydrone type
b. Picric acid type
c. Caffeine and other drug complexes
d. Polymer type
3. Inclusion or occlusion compound
a. Channel lattice type
b. Layer type
c. Monomolecular type
d. Macromolecular type

5. Metal ion or co-ordination complexes:
• In metallic complex, metal ion act as central atom & serve as
acceptor.
• Inorganic Complex:-
Eg Hexamine cobalt (III) chloride
Cobalt act as central atom (Coordination no.6)

6. • Chelates :-
Group of metal ion complexes in which substance provide two or more
donor groups to form complex with metal ion.
Eg. EDTA
• Applications :
1. Water Purification (Calcium complex)
2. Antioxidant (complex with iron & Copper)
3. Anticoagulant (Calcium complex)

7. • Olefin Type:
Olefin belongs to family of organic compound called hydrocarbons. They
consist of different molecular combination of two element, carbon and
hydrogen . Another name of olefin is alkene
Olefin ligands are common in organotransition metal chemistry. The first
organotransition metal complex zeise’s salt (K[Pt𝐶𝑙3(𝐶2 𝐻4)]. 𝐻2O) was an
olefin complex

8. •Aromatic Type:
1. Pi (п) complexes : The example of Pi complex is interaction of local
anaesthetic bupivacaine and its structural analogs such as 2,6-
dimethylaniline, and N-methyl-2, 6 dimethylacetanilide, and cocain, with
several electron deficient aromatic moieties.

9. • Sigma б Complexes :
An arenium ion is cyclohexadienyl cation that appears as a reactive
intermediate in electrophilic aromatic substitution. This complex is also
called a Wheland intermediate or a sigma complex.
The smallest arenium ion is the benzenium (𝐶6 𝐻7+), which is protonated
benzene.

10. • Sandwich compound :
A sandwich compound is a metal bound by hepatic covalent bonds to
two arene ligands.
The arenes have the formula 𝐶 𝑛 𝐻 𝑛, substituted derivatives (for example
(𝐶 𝑛 𝐶𝐻3)n and heterocyclic derivatives (for example B𝐶 𝑛 𝐻 𝑛+1).
The most famous example is probably methylcyclopentadienyl magnese
ticarbonyl.

11. Organic Molecular Complexes
Weaker in comparison to metallic complexes
• Involve Vander wall forces.
• Energy involve than 5KCal
• Distance between two molecule is less than 3A◦
Based on donor acceptor mechanism or either charge transfer
mechanism

12. • Quinhydrone type: Obtained by mixing alcoholic solution on
equimolar quantities of benzoquinone and hydroquinone in the form
of green crystals. (In water complex dissociates, green colour
disappears)

13. • Picric acid complex:
Picric acid being strong acid binds to basic drugs.
Eg Picric acid (antiseptic) complex with butesin (anaesthetic) to form
butesin picrate (burn treatment).

14. • Caffine drug Complex:
Caffine form complex with benzocain, tetracaine, procaine.
Intermolecular force involved dipole type.
E.g. Caffine benzocaine complex
• Application:
For solubility and stability enhancement
Taste masking.

15. • Polymer Type :
PEG, CMC contains nucleophilic oxygen which can form complex with
various drug like Salicylic acid, tannic acid, Phenols.
Such type of complexation may lead to incompatibilities
(loss of preservatives, delayed absorption etc.)

16. Inclusion Complexes:
Not based upon donor-acceptor or charge transfer mechanism
Based upon molecular architect of the substance.
In such type of complexation one molecule act as guest and another as
host

17. • Channel Type:
Eg. Complex of urea with α- methyl lipoate
Eg. Of host molecule: Urea, Deoxycholic acid, amylose, thiourea.
• Application
Used for separation of larger molecules which are interfering in
analysis.
Separation of optical isomer

18. • Layer Type :
In complexation if formation of multiple channels occurs termed as
layer complexes.
Eg. Of Host molecule: clay montomorillorite

19. • Clathrates type:
• Cage like structure/lattice in which substance is entrapped

20. • Monomolecular types:
Entrapment of guest molecule in the cavity of host molecule.
Eg. β – cyclodextrin
Application:
Solubility/ dissolution/ stability enhancement

21. • APPLICATION OF COMPLEXATION
• Solubility/ Dissolution enhancement :
• Bioavailability enhancement :
• Modifying reactivity :
• Modifying drug releases:
• Test masking :
• Administration of therapeutic agent :
• Use of ion exchange :
• In diagnosis :

22. • Complexation as a therapeutic tool
• Treatment of poisoning
Arsenic and mercury poisoning
Lead poisoning
Radioactive materials
Dialysis and complexation in poisoining