Natural macrocyclic complexes

Busch, D. H.. K. Farmery, V. Goedken, A. C. Katovic, A. C. Melnyk, C. R. Spevati, and N. Tokel (1971) Chemical Foundations for the Understanding of Natural Macrocyclic Complexes, in Bioinorganic Chemistry—Advances in Chemistry. Vol. 100, American Chemical Society, Washington DC. 

Chemical Foundations for the Understanding of Natural Macrocyclic Complexes... 

The intramolecular version for synthesizing cyclic and polycyclic compounds offers a powerful synthetic method for naturally occurring macrocyclic and polycyclic compounds, and novel total syntheses of many naturally occurring complex molecules have been achieved by synthetic designs based on this methodology. Cyclization by the coupling of an enone and alkenyl iodide has been applied to the synthesis of a model compound of l6-membered car-bomycin B 162 in 55% yield. A stoichiometric amount of the catalyst was used because the reaction was carried out under high dilution conditions[132]. 

S-2.2.2 Neutral Carrier Electrodes hi addition to charged liquid ion exchangers, liquid-membrane electrodes often rely on the use of complex-forming neutral carriers. Much effort has been devoted to the isolation or synthesis of compounds containing cavities of molecular dimensions. Such use of chemical recognition principles has made an enormous impact upon widespread acceptance of ISEs. The resulting neutral carriers can be natural macrocyclic molecules or synthetic crown... 

A very large number of synthetic, as well as many natural, macrocycles have now been studied in considerable depth. A major thrust of many of these studies has been to investigate the unusual properties frequently associated with cyclic ligand complexes. In particular, the investigation of spectral, electrochemical, structural, kinetic, and thermodynamic aspects of macrocyclic complex formation have all received considerable attention. 

The dissociation kinetics of macrocyclic complexes have received considerable attention, especially during investigations of the nature of the macrocyclic effect. Before discussing the dissociation of cyclic ligand species, it is of benefit to consider some aspects of the dissociation of open-chain ligand complexes. 

Most of the kinetic models predict that the sulfite ion radical is easily oxidized by 02 and/or the oxidized form of the catalyst, but this species was rarely considered as a potential oxidant. In a recent pulse radiolysis study, the oxidation of Ni(II and I) and Cu(II and I) macrocyclic complexes by SO was studied under anaerobic conditions (117). In the reactions with Ni(I) and Cu(I) complexes intermediates could not be detected, and the electron transfer was interpreted in terms of a simple outer-sphere mechanism. In contrast, time resolved spectra confirmed the formation of intermediates with a ligand-radical nature in the reactions of the M(II) ions. The formation of a product with a sulfonated macrocycle and another with an additional double bond in the macrocycle were isolated in the reaction with [NiCR]2+. These results may require the refinement of the kinetic model proposed by Lepentsiotis for the [NiCR]2+ SO/ 02 system (116). 

In chelate and macrocyclic complexes, electronic states may exist which are of a delocalized nature they pertain to the system of metal and ligands. Such states are not simply derived from metal d—d states or from free ligand states and transitions involving delocalized states are often quite intense. 

Natural macrocycles displaying antibiotic propenies are also very efficient in the recognition of alkali metal ions. For instance, valinomycin (5 in Fig, 3) gives a strong and selective complex in which a K+ ion is included in the macrocyclic cavity in octahedral environment of six carbonyl oxygens (Fig. 4). 

A great variety of aza macrocycle complexes have been formed by condensation reactions in the presence of a metal ion, often termed template reactions . The majority of such reactions have inline formation as the ring-closing step. Fourteen- and, to a lesser extent, sixteen-membered tetraaza macrocycles predominate, and nickel(II) and copper(II) are the most widely active metal ions. Only a selection of the more general types of reaction can be described here, and some closely related, but non metal-ion-promoted, reactions will be included for convenience. The reactions are classified according to the nature of the carbonyl and amine reactants. 

We see that for the (alkali metal + oxygen macrocycle) complexes, charge and relative size of the ion play an important part in determining the stability of the complex. However, for the (transition metal + aza- or thia-substituted macrocycle) complexes, the nature of the bonding seems to be the important effect. Sten Ahrland16 has used a classification scheme for metal ion acceptors that helps us understand this difference. He designates the metal ion as either hard or soft. The characteristics that determine the assignment are as follows. 

Let us start by considering the reaction of the copper(n) complex 6.49 with formaldehyde. Initially we might expect the diimine 6.50 to be formed, but this ignores the nature of the intermediates. As we saw earlier, the reaction of an amine with an aldehyde initially produces an aminol. Consider the addition of the second molecule of formaldehyde to 6.49. The product will be 6.51, which contains an imine and an aminol (Fig. 6-43). The imine is co-ordinated to a metal ion, and the polarisation effect is likely to increase the electrophilic character of the carbon. The hydroxy group of the aminol is nucleophilic and it is correctly oriented for an intramolecular attack upon the co-ordinated imine. The result is the formation of the copper(n) macrocyclic complex 6.52. 

The nature of the additional nucleophile may be varied. For example, the reaction of the nickel(n) complex 6.56 with formaldehyde and methylamine gives the macrocyclic complex 6.57 (Fig. 6-46). Again, it is not clear whether the first steps of the reaction involve reaction with formaldehyde, followed by attack of amine upon the imine, or initial formation of an electrophile such as H2C=NMe, which attacks 6.56. 

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