Macrocyclic Ligands - Web del Profesor

their guests more strongly and are, in sequence, the spherands
> cryptaspherands ≈ cryptands > hemispherands > crown
ethers. 116
A useful correlation of enthalpy–entropy considerations for
complexation has been shown by Inoue, Liu, and Hakushi. 113
The treatment reflects enthalpy–entropy relationships for
given types of ligands. The general concept is that as the
enthalpic contributions become strong, a higher level of
organization is obtained, which will result in unfavorable
entropy changes. For a given type of system with similar
entropic versus enthalpic considerations, the T�S and �H
values determined for a series of ligands should thus exhibit
a linear relationship. This is found for the macrocyclic crown
ethers, the cryptands, lariat ethers, and bis-crown ethers, as
well as the acyclic polyethers known as podands. The slopes
are all positive with high correlation coefficients. Gokel has
suggested that these slopes can be used to assess the ligand
flexibility: glymes and podands (0.86) > crown ethers (0.76)
> cryptands (0.51). 119
4.5.2 Lariat Ethers
The lariat ethers (19) and (20) known to date consist
of macrocycles with many different types of podand
groups, and much of their complexation chemistry involves
electrostatic binding of guests. Reviews of both structural and
thermodynamic aspects of the lariat ethers can be found. 120–122
The trends are noted to be relatively similar for both the
carbon-pivot and nitrogen-pivot types of lariat ethers. Binding
strengths and selectivities are dependent on ring size and in
general increase as ligand size increases. Strong selectivities
are noted for the potassium ion, as in the crown ethers.
4.5.3 Spherands and Hemispherands
The spherands (21) were specifically designed using the
concept of ‘preorganization’ wherein the oxygen donors are
arranged in an enforced spherical cavity. Totally prearranged
(spherand) and partially arranged (hemispherand, (22))
complexes are possible. 118 Due to the structural restraints
imposed by the rigidly joined phenyl rings, the spherands are
considered to be highly ‘preorganized’ binding sites. In these
macrocycles the lone pair of electrons will always be pointed
toward the center of the macrocyclic cavity.
4.5.4 Calixarenes
The calixarenes (23) are also highly preorganized
molecules which are capable of forming different
conformational isomers. The conformational flexibility is
determined by the size of the ring, with the preferred conformation
becoming more planar as the ring size increases. 37
5 APPLICATIONS
MACROCYCLIC LIGANDS 17
As macrocyclic chemistry has developed, the variety and
scope of the applications of these molecules have continued
to multiply. This concluding section is an attempt to provide
an overview of only three of the applications of synthetic
macrocycles. A particularly insightful treatment can be
found in the Nobel Lecture of Jean-Marie Lehn, 123 which
describes the concept of supramolecular chemistry from
simple recognition, to cation and anion receptors, multiple
recognition, catalysis, transport, and molecular devices.
5.1 Ion Transport
Ion transport, especially cation transport, was one of the
early focal points in macrocyclic chemistry, revolving primarily
around the crown ethers and cryptands. Later efforts have
been to provide switches to control the rates of cation transport.
Two examples of the types of switches that have been
developed include photo switches using cryptands, 124 and
electrochemical switches using anthraquinone-derived lariat
ethers. 125
Related to transport capabilities is the use of synthetic
macrocycles in analytical chemistry. Because of their selective
complexation of a variety of cations, the crown ethers and
related macrocycles have been widely used for separations
and analyses. 126
While transport efforts have largely involved metal
cations, more recent developments have led to the use of
macrocycles for transport of more complex molecules such as
nucleosides. 127
5.2 Catalysis
Catalysis can be broken down into a number of areas,
depending on the substrate and the catalytic reaction. One of
the prime areas of the initial effort in catalysis has been small
molecule activation, such as oxygen with a number of transition
metal ion macrocycles 128,129 and carbon dioxide, the latter
particularly with cobalt(I) and nickel(I) macrocycles. 130,131
Once the polyammonium macrocycles were found to be able
to recognize substrates other than metal ions, other catalysis
applications evolved. For example, phosphoryl transfer catalysis
with simple polyammonium macrocycles has become
quite accessible. 132
5.3 Magnetic Resonance Imaging
Macrocyclic complexes have gained recognition in
magnetic resonance imaging. 133,134 In order to be effective
imaging agents, complexes must provide a significant
enhancement in the proton relaxation rates of water,
as well as be nontoxic, and thermodynamically stable.
Hence, macrocyclic ligands with pendant carboxylates, such