Complexation is a chemical process in which molecules or molecular assemblies are formed by the combination of substrates (S) and ligands (L). Most often complex (S_mL_n) formation is a reversible process:
$$ m.S+n.L⇄S_mL_n $$

where m substrate molecules, associate with n ligand molecules to form a complex of m:n stoichiometry. In this context, complex formation, complexation, binding, association, and chelation are often synonymous.

The intermolecular forces involved in the formation of complexes are:

1. Ionic Bonds: Attraction between positively and negatively charged ions.
2. Hydrogen Bonds: Attraction between a hydrogen atom bonded to an electronegative atom (like oxygen, nitrogen, or fluorine) and another electronegative atom.
3. Van der Waals Forces: Weak attractions due to transient partial charges in molecules.
4. Dipole-Dipole Interactions: Attractions between the positive end of one polar molecule and the negative end of another.
5. Coordination Bonds: Bonds between a central metal atom and ligands where both electrons in the bond come from the ligand.​

The Rationale of Complexation

The complex formation changes the physicochemical properties of its constituents, both of the substrate and the ligand, including their aqueous solubility, molar absorptivity, NMR chemical shifts, adsorption to solid surfaces, partitioning behavior, conductivity, chemical reactivity and/or pKa values. By studying such properties, for example of the substrate as a function of the ligand concentration, the complex can be identified and quantitatively described. Furthermore, the methods of chemical kinetics and thermodynamics can be applied to describe the formation and dissociation of a complex. Although most frequently, substrate and ligand molecules are associated by weak chemical forces, there are complexes where bonds are quite strong and formation of some metal complexes are virtually irreversible. Complexes are usually broadly classified into two groups based on the type of S-L bonding involved, namely coordination complexes and molecular complexes.

Complexes, or coordination compounds, according to the classic definition, result from a donor–acceptor mechanism or a Lewis acid–base reaction between two or more different chemical constituents.

Classification OF Complexes

Complexes can be broadly divided into two classes based on whether the acceptor component is a metal ion or an organic molecule. These are classified according to one possible arrangement in Table 1. A third class, inclusion/occlusion compounds, involves the entrapment of one compound within the molecular framework of another and is also included in the table.

Reference:

• Sinko, P. (2011). Martin’s Physical Pharmacy and Pharmaceutical Sciences. Baltimore, : Lippincott Williams & Wilkins, a Wolters Kluwer business.
• Felton. L. (2013). Remington Essentials of Pharmaceutics. London. UK: Pharmaceutical Press.