Ligand design macrocyclic systems

While this work did not involve the use of macrocyclic ligands, the classification system used reveals several principles which are pertinent to macrocycle-metal ion binding. Further study is required to determine if Ais system can be extended to the rational design of macrocyclic ligands. 

Several model systems related to metalloenzymes such as carboxypeptidase and carbonic anhydrase have been reviewed. Breslow contributed a great deal to this field. He showed how to design precise geometries of bis- or trisimidazole derivatives as in natural enzymes. He was able to synthesize a modified cyclodextrin having both a catalytic metal ion moiety and a substrate binding cavity (26). Murakami prepared a novel macrocyclic bisimidazole compound which has also a substrate binding cavity and imidazole ligands for metal ion complexation. Yet the catalytic activities of these model systems are by no means enzymic. 

Like other tetraaza metallo(I) complexes, the nickel(I) macrocyclic ions are powerful and labile reducing agents. A point of some interest in these systems is to design a complex couple for which the nickel(I) state is accessible at reasonable potentials. Provided the tetraaza macrocyclic ligand maintains close to planar microsymmetry, reorganizational barriers for a low-spin d8-d9 system might be expected to be small (194). 

In this article the design, synthesis and d-block metal ion chemistry of some more recent examples of covalently-linked, macrocyclic ligand systems are discussed. The use of macrocyclic rings in such systems is not surprising given that the resulting macrocyclic complexes often exhibit both enhanced kinetic and thermodynamic stabilities and hence tend to retain their integrity under a variety of conditions - a lesson that nature knows well. 

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