Enterobactin complexes

Enterobactin (ent), the cycHc triester of 2,3-dihydroxy-A/-benzoyl-l-serine, uses three catecholate dianions to coordinate iron. The iron(III)-enterobactin complex [62280-34-6] has extraordinary thermodynamic stabiUty. For Fe " +ent , the estimated formal stabiUty constant is 10 and the reduction potential is approximately —750 mV at pH 7 (23). Several catecholate-containing synthetic analogues of enterobactin have been investigated and found to have lesser, but still impressively large, formation constants. 

The resolution of tris(catecholato)chromate(III) has been achieved by crystallization with L-[Co(en)3]3+ the diastereomeric salt isolated contained the L-[Cr(cat)3]3 ion.793 Comparison of the properties of this anion with the chromium(III) enterobactin complex suggested that the natural product stereospeeifically forms the L-cis complex with chromium(III) (190). The tris(catecholate) complex K3[Cr(Cat)3]-5H20 crystallizes in space group C2/c with a = 20.796, 6 = 15.847 and c = 12.273 A and jS = 91.84° the chelate rings are planar.794 Electrochemical and spectroscopic studies of this complex have also been undertaken.795 Recent molecular orbital calculations796 on quinone complexes are consistent with the ligand-centred redox chemistry generally proposed for these systems.788... 

Siderophores. If a suitably high content of iron (e.g., 50 pM or more for E. coli) is maintained in the external medium, bacteria and other microorganisms have little problem with uptake of iron. However, when the external iron concentration is low, special compounds called siderophores are utilized to render the iron more soluble.7 11 For example, at iron concentrations below 2 pM, E. coli and other enterobacteria secrete large amounts of enterobactin (Fig. 16-1). The stable Fe3+-enterobactin complex is taken up by a transport system that involves receptors on the outer bacterial membrane.9 12 13 Siderophores from many bacteria have in common with enterobactin the presence of catechol (orftzo-dihydroxybenzene) groups... 

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... 

The three catechol groups of enterobactin are carried on a cyclic serine triester structure. A variety of both cyclic and linear structures are found among other catechol siderophores. " For example, parabactin and agrobactin (Fig. 16-1) contain a backbone of spermidine (Chapter 24). After the Fe -enterobactin complex enters a bacterial cell the ester linkages of a siderophore are cleaved by an esterase. Because of the extremely high formation constant of M for... 

A locally low pH region in the cellular uptake pathway of the ferric enterobactin complex with a resultant shift in the redox potential which would make it available via reduction. 

In addition to preparing the model catecholate complexes of rhodium and chromium, the analogous enterobactin complexes were also prepared and their CD spectra recorded (62). From examination of molecular models it is apparent that either the A-cis or A-cis diastereomers of a metal enterobactin complex are structurally possible. In theory, these diastereomers should be separable by chromatographic techniques analogous to those used for the hydroxamates (vide supra) however, under a variety of conditions only one chromatographic fraction is obtained. We conclude that one isomer predominates to the exclusion of the other. 

All three enterobactin complexes (Fe, Cr, Rh) have identical Rf values for silica gel TLC in 50% chloroform-methanol solvent. 

The high-spin Fe" -enterobactin complex is exceptionally stable thermodynamically having the largest formation constant (ca. 10 ) known for any Fe" complex. A number of synthetic analogues for enterobactin which contain 1,2-dihydroxyphenyl chelating groups have been investigated. One of these, hexadentate l,3,5-tris 2,3-dihydroxybenzoylaminomethyl)benzene (27) has been shown to form a 1 1 [FeL] complex with a formation constant of 10 . ... 

The potentiometric titration curve of ferric enterobactin, shown in Figure 3, has a sharp inflection after the addition of six equivalents of base. Such a break indicates that the six phenolic oxygens from the three dihydroxybenzoyl groups are displaced by ferric ion in the ferric enterobactin complex. This interpretation is further supported by the absorbance maximum at 490 nm (e 5600), which is very similar to simple tris(catecho-lato)iron(III) complexes (, T). The very low pH at which com-plexatlon of enterobactin occurs, with virtually complete complex formation by pH 6, is a strong indication of a very stable complex. However, the titration is prematurely terminated at pH 3.8 by the precipitation of a purple neutral iron complex (whose composition and structure will be discussed later) which makes it impossible to determine the stability consteint of ferric enterobactin from potentiometric data alone. 

Metal-chelate complexes are ubiquitous in biology. Bacteria such as Escherichia coli and Salmonella enterica in your gut excrete the chelator enterobactin (Figure 13-4) to scavenge iron that is essential for their growth. Chelates excreted by microbes to gather iron are called siderophores. The iron-enterobactin complex binds to the bacterial cell surface and is taken into the cell. Iron is then released by enzymatic disassembly of the chelate. To fight bacterial infection, your immune system produces a protein called siderocalin to sequester and inactivate enterobactin. ... 

Figure 13-4 lron(lll)-enterobactin complex. Certain bacteria secrete enterobactin to capture iron and bring it into the cell. Enterobactin is one of several known chelates—designated s/derophores—released by microbes to capture iron to be used by the cell. 

Kvach, J. T., Wiles, T. I., Mellencamp, M. W., and Kochan, I. (1977) Use of transferrin-iron-enterobactin complexes as the source of iron by serum-exposed bacteria. Infection and Immunity 18 439-445. 

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