COMPLEXATION

A complex is a species formed by the reversible or irreversible association of

two or more interacting molecules or ions. In the context of this course, it will
be used to characterize the covalent or noncovalent interactions between two
or more compounds that are capable of independent existence.

Complexes or coordination compounds result from a donor–acceptor

mechanism or Lewis acid–base reaction between two or more different
chemical constituents.

Any nonmetallic atom or ion, whether free or contained in a neutral molecule

or in an ionic compound, that can donate an electron pair can serve as the
donor.

The acceptor, or constituent that accepts a share in the pair of electrons, is

frequently a metallic ion, although it can be a neutral atom.

Intermolecular forces involved in the formation of complexes are

1- The van der Waals forces of dispersion.

2- Dipolar, and induced dipolar types.
3- Hydrogen bonding provides a significant force in some molecular
complexes.
4- Coordinate covalence is important in metal complexes.

Classification of Complexes
I. Metal ion complexes
A. Inorganic type
B. Chelates
C. Olefin type
D. Aromatic type
1. Pi (π) complexes
2. Sigma (σ) complexes
3. “Sandwich” compounds
II. Organic molecular complexes
A. Quinhydrone type
B. Picric acid type
C. Caffeine and other drug complexes
D. Polymer type
III. Inclusion/occlusion compounds
A. Channel lattice type
B. Layer type
C. Clathrates
D. Monomolecular type
E. Macromolecular type

Ligands: (Ligare – Latin-To bind)

Ligands are ions or molecules that contain one or more pairs of electrons that
can be shared with the metal.
Coordination number:
The number of coordinate bonds formed by ligands with central metal atom or
ion.
I.A. Inorganic Complexes
The ammonia molecules in hexamminecobalt (III) chloride, as the compound
[Co(NH3)6]3+ Cl3 - is called, are known as the ligands and are said to be
coordinated to the cobalt ion. The coordination number of the cobalt ion, or
number of ammonia groups coordinated to the metal ions, is six.

Other complex ions belonging to the inorganic group include [Ag(NH3)2] + ,

[Fe(CN)6] 4-, and [Cr(H2O)6] 3+ . Each ligand donates a pair of electrons to
form a coordinate covalent link between itself and the central ion having an
incomplete electron shell. For example, Ligands such as H2Ö H3 , Cl - donate a
pair of electrons in forming a complex with a metal ion, and the electron pair
enters one of the unfilled orbitals on the metal ion.

I. B. Chelates:
Chelation is the process of formation of two or more separate coordinate bonds
between a polydentate ligand and a single central atom.
EDTA has two donor nitrogen and acts as a bidentate ligand. When a drug
forms a metal chelate, the solubility and absorption of both drug and metal ion
may be affected and drug chelation can lead to either increased or decreased
absorption.

EDTA

EDTA has a total of six points (4+2) for attachment of

metal ions.
e.g The synthetic chelating agent ethylenediamine tetraacetic acid has been
used to tie up or sequester iron and copper ions so that they cannot catalyze the
oxidative degradation of ascorbic acid in fruit juices and in drug preparation.
Applications of chelating agents:
1. EDTA is used to remove calcium ions from hard water.
2. Oxidative degradation of drug preparation and ascorbic acid in fruit juice
can be prevented by chelation with EDTA.
3. EDTA is also used as an invitro anticoagulant.
4. EDTA is used to detoxify poisonous metal agents such as mercury, arsenic
and lead.
5. EDTA is used to remove colour impurities from antibiotic preparations.
I.C. Olefin complex:
Interactions of aqueous solutions of metal ions (such as iron, mercury, silver
etc) with olefin such as ethylene, form water soluble olefin complex.
These complexes are generally used as catalysts in the manufacture of bulk
drugs, intermediates and in drug analysis.
Orbital bond Energy
s σ k
p π l
d δ m
f n
I. D. Aromatic complex:
The interaction of metal ion with aromatic molecule (such as benzene, toluene,
xylene) form aromatic complexes.

(i) Pie-bonded aromatic complex: (Non-covalent) Some aromatic compounds

form a pie bond with metal ion to produce a complex. E.g Iodine reacts with
benzene to give red colour solution.
(ii) Sigma-bonded aromatic complex: (covalent) - Some aromatic compounds
form a sigma bond with metal ion to produce a complex.
(iii) Sandwich aromatic compounds: Compounds in which a metal atom is
located between the faces of two parallel and planar (or nearly so) ring
structures, e.g. bis(η5-cyclopentadienyl)iron (ferrocene), dibenzenechromium.
The best known members are the metallocenes of the formula M(C5H5)2 where
M = Cr, Fe, Co, Ni, Pb, Zr, Ru, Rh, Sm, Ti, V, Mo, W, Zn. These species are also
called bis(cyclopentadienyl)metal complexes.
Ferrocene is an organometallic compound of the general class metallocene with
the molecular formula Fe(η5-C5H5)2. In this molecule, iron is sandwiched
between two cyclopentadienyl rings.

The symmetry of ferrocene is D5d, in which the two,

planar, cyclopentadienyl rings are staggered with respect to each other.⁎ Each
ring has a delocalised π-system built from the pz orbitals on carbon. Both rings
bond symmetrically to the iron through each of the five carbon atoms, in what
is termed an η5
II. Organic molecular complex:
Components are organic molecules and these are held together by weaker
forces or hydrogen bonding.
Classification of organic molecular complex
1. Quinhydrone types
2. Picric acid types
 3. Drug and caffeine complexes
4. Polymer types

Quinhydrone types
• The molecular complex of this type is obtained by mixing alcoholic solutions
of equimolar quantities of hydroquinone and benzoquinone. Complex settles as
green crystals. Hydrogen bonding contributes in stabilizing the complex.

Picric acid types

• Picric acid, being a strong acid, forms organic molecular complexes with weak
bases, whereas it combines with strong bases (anesthetic activity of butesin) to
yield salts.
Drug and caffeine complexes
• Drugs such as benzocaine, procaine and tetracaine form complexes with
caffeine.
• A number of acidic drugs are known to form complexes with caffeine.
Polymer types
Many pharmaceutical additives such as polyethylene glycols (PEGs),
carboxymethyl cellulose (CMC) contain nucleophilic oxygen. These can form
complexes with various drugs. E.g. Polymers: carbowaxes, pluronics etc. Drugs:
tannic acid, salicylic acid, phenols etc.
Carboxyl methylcellulose (CMC) + Amphetamine = poorly absorbed complex
(tablet additive – drug interaction).