Macrocyclic Ligands - Web del Profesor

HO O O OH
+
Cl O O Cl
Scheme 9
Spherands and hemispherands (21)and(22) are synthesized
by ring closure reactions of aryllithium with Fe(acac)3, often
using high dilution techniques. 36
Calixarenes (23) are obtained from base-catalyzed condensations
of p-substituted phenols with formaldehyde. 37
4 THERMODYNAMICS AND STRUCTURAL
ASPECTS
4.1 Introduction
4.1.1 The Macrocyclic Effect
This term refers to the amazing stability of macrocyclic
ligands. It was initially described in studies of tetraaza
macrocycles with copper(II). 63 For polyaza macrocycles this
effect has been attributed to both entropic and enthalpic
considerations and considerable controversy raged for a
number of years as to which was the predominant factor. 64,65
The conflicting reports are now realized to be extremely
dependent on the experimental methods used for the
determination of the thermodynamic parameters. Two main
types of technique have been employed, each of which has its
strengths and weaknesses: the calorimetric titration method
and the use of the temperature variation of the stability
constants. The controversy has been largely settled by more
recent studies. 66,67 Important contributions to the enthalpic
term are now attributed to a number of factors, including
solvation and conformation changes upon bond formation.
Likewise, the entropic considerations include the number of
species present and particularly solvation effects. Detailed
discussions of the historical development can be found. 13,17
Related to the macrocyclic effect are the decreased rates
of dissociation observed for macrocyclic complexes. Busch
and co-workers have coined a term to describe these longterm
stabilities incurred by synthetic macrocycles: multiple
juxtapositional fixedness. The premise is that straight-chain
ligands can undergo dissociative displacements in consecutive
steps starting at one end of the ligand and finishing with the
opposite end. This is not the case for macrocyclic ligands, for
which each dissociated donor is still held in proximity to the
metal ion by the rest of the ligand framework. 68
O
O
O
O
O
O
MACROCYCLIC LIGANDS 9
The macrocyclic effect has been observed for polyaza,
polythia, and polyoxa, as well as mixed donor atom,
macrocycles. 69
4.1.2 Selectivity
The selectivity of a macrocycle for either a metal ion or
another substrate is critically dependent on the structure of
the macrocycle and electronic effects, i.e. the types of donor
atoms. Some of the important aspects are described below.
1. The number of binding sites is perhaps one of the
most crucial influences on the binding properties of the
substrate. Electronic effects of the binding of macrocycles
with substrates are charge, polarity, and polarizability
of the binding sites. For metal ion binding, this means
ion pair interactions for negatively charged ligands,
ion–dipole and ion–induced dipole interactions for
neutral ligands, and the hard–soft acid–base criteria.
Nitrogen, phosphorus, and sulfur donors are noted for
their complexation of transition metal ions. Oxygen is
more likely to complex alkali or alkaline earth metal ions.
2. The arrangement of the binding sites should be such as to
maximize the potential ligand–metal ion interactions. In
this regard the selection of spacers between donor atoms
to allow for the formation of five- and six-member chelate
rings has been the most utilized.
3. The preferred conformations of the macrocycles dictate
its propensity to bind a metal ion internally or externally
to the cavity. The propensity of the lone pair to point in
or out of the cavity is also a deciding factor. Hence, it is
not always a foregone conclusion that the metal ion will
be bound within the macrocyclic cavity.
4. The identity of the macrocyclic framework also plays
a major role in structure. For example, saturated
hydrocarbon chains provide considerably more flexibility
than incorporated aromatic units. Likewise the presence
of other functional groups, such as amides or esters, serve
to stiffen the macrocyclic framework. Decreasing the
flexibility of the macrocycle by adding selected ‘shaping
groups’ is the theory behind preorganization, so important
in the cavitands. Another method of creating rigidity is to
increase the dimensionality of the macrocycle, inherent in
cryptand selectivities.
5. The size of the macrocyclic cavity also plays a large role in
governing the flexibility of the ligand, and its propensity
for metal ion binding.
Since the focus of this article is primarily on transition metal
chemistry, the structural aspects related to complexation of
transition metals will be emphasized, and other aspects of
complexation will only be briefly treated.
In addition to the traditional measurement of thermochemical
properties, molecular mechanics calculations are now
available to supplement and correlate with experimental findings.
An extensive review which links the large data base of