Macrocyclic ligand complexes are involved in a variety of fundamental
biological systems. Examples include photosynthesis, which proceeds
due to the magnesium macrocycle chlorophyll, and various electron
transfer reactions which occur in cytochromes.
Nature chooses macrocyclic derivatives which give enhanced kinetic
and thermodynamic stabilities, such that the metal ion is very
firmly held in the central cavity of the ligand, so the biological
function is not impaired by competing demetallation processes.
Some typical macrocyclic ligands are the cyclic amine compounds.
Transition metal complexes of all nitrogen containing
macrocycles show enormous structural variety. Totally unsaturated
ligands may be restricted to square planar geometries. Saturated
ligands, of the type shown, may fold to create conformational
The macrocylic effect
says that a macrocyclic ligand complex is more stable than its
open chain analogue:
show that the effect depends on both enthalpy and entropy.
The magnitude of the macrocyclic effect depends
on the interplay of these factors, and so depends both on the
ligand and the metal center. In the Ni2+ case, the
macrocyclic effect is driven by the enthalpy, whereas in the
Cu2+ case, it is entropy driven.
The different terms are:
Enthalpy: the conformational
nature of the ligand (the macrocycle may be locked in the conformation
in which bonding occurs and therefore no energy needs to be
spent on its rearrangement).
Entropy: the change in
solvation of both the metal center and ligand (as the complex
forms, the solvent needs to rearrange, and this is an entropic
factor, and is different for the cyclic and acyclic ligands)
Kinetic effects of the Macrocyclic Effect
The enhanced stability of a macrocyclic ligand complex may arise
from its rate of dissociation being slow compared to its open
||kf = 4.1x105
||kd = 3x104
||kf/kd = 14
||kf = 2.8x104
||kd = 9
||kf/kd = 3100
In the sulphur complexes above, it is seen that
the rate of dissociation of the macrocycle is very low: the
macrocycle complex is kinetically stabilised,
ie. it is relatively inert.
Synthesis of Macrocyclic Ligands: The Template Effect
A metal ion template reaction is on in which coordination
of at least one reactant molecule to a metal ion is necessary
either for the reaction to proceed, or to change the product distribution
in favour of a specific macrocyclic compound. This means that
the presence of the metal is controlling the synthesis. This is
known as the template effect. An example of its use it the production
of the phthalocyanines, which are used as dye pigments and semiconductors,
and also as the model ligand for biological macrocycles such as
The template effect is demonstrated in two ways,
the thermodynamic and the kinetic template effects.
The Equilibrium (or Thermodynamic)
Template Effect: Complexation to a metal ion stabilizes
one component of a mixture, shifting the equilibrium in favour
of production of a metal complex.
The Equilibrium Template Effect
In the example below, the equilibrium
lies in favour of the thiazoline in the absence of the
Ni2+ ion, whereas the macrocycle complex
is formed in 70% yield in the presence of the Ni2+
The Kinetic Template Effect:
Coordination of reactive groups to a metal ion, which then holds
these groups in the proper geometry, favours an intramolecular
The favoured octahedral coordination
about the metal center drives the reaction to give
the cyclic product.