Macrocycle-facilitated metal ion

Two possible roles for the metal ion in a template reaction have been delineated (Thompson Busch, 1964). First, the metal ion may sequester the cyclic product from an equilibrium mixture such as, for example, between products and reactants. In this manner the formation of the macrocycle is promoted as its metal complex. The metal ion is thus instrumental in shifting the position of an equilibrium - such a process has been termed a thermodynamic template effect. Secondly, the metal ion may direct the steric course of a condensation such that formation of the required cyclic product is facilitated. This process has been called the kinetic template effect. 

One of the first examples of metal ions facilitating macrocycle formation was the synthesis of metal phthalocyanines (95) from 1,2-dicyanobenzene or 2-cyanobenzamide (Scheme 53).229-231 This example of macrocycle synthesis has been applied to a very wide range of metal salts of various valencies, and is of great commercial interest. As this area of chemistry has been reviewed frequently and is dealt with in Chapter 21.1, only a brief consideration of the most important template reactions will be presented here. 

Antibodies were generated against a bent A-alky 1 mesoporpbyrin, which is a known inhibitor of the enzyme ferrochelatase. Ferrochelatase catalyzes the insertion of Fe(II) into protoporphyrin, as part of the heme biosynthetic pathway (Lavallee, 1988). Antibody 7G12 was found to catalyze the insertion of divalent metal ions into porphyrins, with a rate similar to thatfound for ferrochelatase (Cochran and Schultz, 1990). The structural data presented below supports the hypothesis that the transition state for porphyrin metallation involves a distortion of the macrocyclic ring system to facilitate metal insertion, and that this bent porphyrin acts as a good transition-state mimic in the development of catalytic antibody 7G12. 

Process in which the presence of a metal ion facilitates the formation of a macrocycle by bringing together the reacting strands and leading to one-pot syntheses... 

One of the first examples of metal ions facilitating macrocycle formation was the synthesis of metal phthalocyanines (95) from 1,2-dicyanobenzene or 2-cyanobenzamide (Scheme 53). 

Much of the work in this area concentrates on metal-free macrocycles, often with the nitrogen atoms of the macrocycle functionalized as amides [82], Reduction of these amides to facilitate complexation to a metal ion destroys the mesomorphism. 

A less obvious part of the template concept is that, once formed, the products of these template reactions are not dependent on the template that guided in their generation. Thus, the macrocyclic ligands formed by template reactions of the kind shown in Fig. 2 can be removed from their metal ions and moved to other chemical applications. The great promise of the template effect rests on that fact. Templates facilitate the synthesis of complicated molecular architectures composed solely of the light atoms typical of organic molecules. 

Reaction 3. This reaction has been described as a "Redox-Switch" mechanism. The metal ion in its lower oxidation state first forms an "outer sphere" complex with the corrin macrocycle, followed by a two electron transfer of the complexed metal ion to a two electron acceptor. Oxidation of the complexed metal ion facilitates carbanion transfer from the cobalt to the complexed metal. 

The technique is applied to link non-cyclic ligsons together to form macrocyclic systems. The ligson heteroatoms have weak donor properties, so that centres such as transition and rare earth element, alkali, and alkaline metal ions are not able to play a template role in synthesis from the relevant species. The metalloids are able to form covalent bonds to weak donors and are thus suitable for the realisation of the required reactions. Organo-element compounds of appropriate metals are used for covalent-template synthesis. These combine the coordination ability of metals and the substitution ability of organic moieties, and therefore facilitate the wide range of chemical conversions involved in template processes. The basic feature of the reactions considered here is the weakness of bonds between matrix and ligsons, so that the synthesis of the free macrocyclic compound may be completed by release of the template. 

Neutral macrocyclic ethers have been used to facilitate the transport of cations across liquid membranes. It has been found that the anion desolvation energy barrier is one of the more important factors in controlling the rate of transfer across the membrane. a-Carboxy-a>-hydroxypolyethers containing ethylene and 1,2-phenylene units can transport metal-ions from aqueous alkali metal hydroxide to an aqueous solution of hydrochloric add through a liquid membrane of hexan-l-ol. However, unlike natural carboxylic ionophores, active transport against the alkali metal-ion concentration gradient could not be observed. ... 

Heat treatment can facilitate bonding of the metal ions to the surface nitrogen of a graphite particle surface. The graphite particle surface serves as the catalyst support. It is believed that the inner core structure of the N4 macrocycle remains after pyrolysis and then acts as a catalytic center towards the ORR. The better electrochemical stability of the centers has been assumed to be the result of electronic integration into a stable carbon particle [39]. 

Phthalocyanine compounds contain macrocyclic conjugated pi-electron systems and metal ions in the central void. These phthalocyanine structures are very similar to porphyrins, one of the most important compounds in biochemistry. Accordingly, phthalocyanine compounds are expected to facilitate interesting catalysis and multielectron processes. Almost all metal and semi-metal ions can be incorporated in the central void of the phthalocyanine molecule, and the characteristics of such phthalocyanine compounds can be modified by the metal ions. About seventy metals are known to incorporate in the phthalocyanine molecule. 

Kudo, Y., Y. Takeda, and H. Matsuda, On the facilitating effect of neutral macrocyclic ligands on ion transfer across the interface between aqueous and organic solutions. Part 2. Alkali-metal ion complexes with hydrophilic crown ethers, J Electroanal Chem, Vol. 396, (1995) p. 333. 

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