Enterobactin model ligand

The catechol-type ligand appears to be restricted to siderochromes derived from prokaryotic microorganisms. Klebsiella oxytoca, an organism closely related to members of the genus Aerobacter, forms the 2,3-dihy-droxy-N-benzoyl derivates of serine and threonine in three day cultures (72). It is not known if the latter amino acid occurs in trimers but examination of space-filling CPK models does indicate that enterobactin could accomodate a methyl substituent on the carbon of the serine residue. Catechols occur in higher protist organisms but their formation... 

Recently the naturally occurring powerful iron sequestering agent enterobactin has provided a model for the development of ligands which show high formation constants with Ga3+ and... 

It can be seen from molecular models that two diastereoisomers are possible for the ferric enterobactin complex, A-cis and A-cis. These are not mirror images because of the optical activity of the ligand. The similarity of the roles played by the ferrichromes and enterobactin lent additional speculative interest to the preferred absolute configuration of the iron complex (20). The structural studies of the tris catechol complexes (vide infra) and the spectroscopic properties of the chromic... 

Siderophores,hexadentate tris-catecholate and tris-hydroxamate ligands, are produced by many microorganisms to facihtate iron uptake. Several synthetic models, such as trencam (35) and licams (36), for the tris-catecholate enterobactin (37) do not quite match its affinity for iron(ni) (Table 8). Similar tris-hydroxamate ligands model naturally occurring ferrichromes and desferrioxamines (e g. dfo, (38)). 

Figure 9 Possible protonation schemes of tris(catecholate) metal complexes. In path 1, the metal complex undergoes a series of two overlapping one-proton steps to generate a mixed salicylate-catecholate coordination. Further protonation results in the precipitation of a tris(salicylate) complex (e.g. enterobactin, MECAM). This differs from path 2, in which a single two-proton step dissociates one arm of the ligand to form a bis(catecholate) chelate. Path 3 incorporates features of paths 1 and 2. In this model, the metal again imdergoes a series of two overlapping one-proton reactions. However, unlike the case of path 1, the second proton displaces a catecholate arm, which results in a bis(catecholate) metal complex...

There are two catecholate siderophores which may be chosen as model compounds for synthesis the cyclic enterobactin and the linear parabactin precursor N. N8-bis(2,3-dihydroxybenzoyl)spermidine. Both of these natural products are capable of the rapid removal of iron from transferrin, the human iron transport protein 89-90). The synthesis of these and other catecholate ligands routinely requires protection of the phenolic oxygens (for example, by methyl, benzyl or acetyl groups). Very few preparations of catechol-containing siderophores have appeared in which the unprotected 2,3-dihydroxybenzoyl group is used in the synthesis 91,92). 

As with hydroxamate siderophores, simple tris(catecholato) metallate(lll) complexes have served as models for enterobactin. Unlike hydroxamate, catecholate is a symmetric, bidentate ligand. Consequently, there are no geometrical isomers of simple tris(catecholato) metal complexes, and only A and A optical isomers are possible. However all siderophore catecholates are substituted asymmetrically on the catechol ring, such that geometric isomers may in principle exist. However, in the case of enterobactin molecular models show only the more symmetric cis chelate is possible, as the A or A form. 

As with the hydroxamate siderophores, our initial approach has been to study simple tris(catecholato)metallate(III) complexes as models for the tricatecholate siderophore enterobactin. Unlike hydroxamates, catecholate is a symmetric, bidentate ligand. 

Fig. 6. Conformational model of chelated enterobactin (66). Bonds and atoms at the cycloester triseryl backbone are marked with heavier lines. Hydrogen atoms are not shown. A left-handed propeller configuration is shown for the ligands around the metal ion center, but this has not yet been established experimentally...

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