Tetradentate siderophores

Complexes formed by tetradentate siderophores involve stepwise complex formation and therefore, have somewhat different equilibria from their hexadentate analogs. Initial chelation will occur with a tetracoordinate FeL complex forming. A subsequent equilibrium then occurs, where the FeL complexes will react in a 2 1 stoichiometry with free ligands in solution to form a single Fe2L3 complex (coordinated water and charges not shown for clarity). 

In some cases where the siderophore architecture permits, the tetradentate siderophore will form a dimeric Fe2L2 complex with iron instead of the monomeric FeL form. These dimeric complexes are not discernible from their monomer counterparts... 

Thermodynamic Stability Constants for Iron(III)-Tetradentate Siderophore Mimic Complexes, Measured at 25°C... 

The dissociation of iron from a tetradentate siderophore complex is more rapid than from the analogous hexadentate system (3). This may be a reason for some organisms to produce tetradentate siderophores instead of hexadentate siderophores despite the concentration effect noted in Section III. A. As was illustrated in Fig. 19, it is also thermodynamically easier to reduce iron(III) in tetradentate complexes than hexadentate complexes, making it easier to induce release of iron from the complex by a redox mechanism. 

Another factor that relates complex stability and siderophore architecture is the chelate effect. The chelate effect is represented by an increase in complex stability for a multidentate ligand when compared to complexes with homologous donor atoms of lower denticity. The effect can be observed when comparing the stability of complexes of mono-hydroxamate ligands to their tris-hydroxamate analogs, such as ferrichrome (6) or desferrioxamine B (4). However, the increase in stability alone is not sufficient to explain the preponderance of hexadentate siderophores over tetradentate or bidentate siderophores in nature, and the chelate effect is not observed to a great extent in some siderophore structures (10,22,50,51). 

Fig. 14. Schematic representations of linear tetradentate side-rophore (H2L) complexes with different siderophore/iron stoichiometries. Coordinated water not shown for clarity.

Fig. 19. Plot of redox potentials (Ey2) as a function of pFe3+ values for a series of hexadentate, tetradentate, and bidentate hydroxamic acid siderophores and siderophore mimics. Data from Table V. Legend 1 — ferrioxamine E 2 — ferrioxamine B (4) 3 — H.aLjf4 (11) 4 — H >L 36 (12) 5 - coprogen 6 - ferricrocin 7 - ferrichrome (6) 8 - alcaligin 9 -rhodotorulic acid (3) 10 — NMAHA 11 — AHA 12 — Ly-AHA.

Each of the siderophores cited above forms 1 1 complexes with iron(III). In contrast, the dihydroxamate ligand rhodotorulic acid (RA),. is only tetradentate and hence has to form 2 3 complexes with iron at pH 7 36). Another curiosity among the siderophores is the occurrence of thioformin (N-methyl-thioformohydroxamate) which has been isolated from bacterial cultures of Streptomyces and Pseudomonas species. Thioformin acts as an antibiotic and the 3 1 complex with iron involves coordination by three oxygen and three sulfur atoms37. ... 

Perhaps the earliest triple helicate 48 to be characterized, however, is that formed with rhodotorulic acid 46 (HaL ), the dihydroxamate siderophore produced by the yeast Rhodotorula pilimanae [75,76], Subsequently, a related synthetic iron(III) triple helicate 49 based on diprotic tetradentate 1,2-hydroxypyridinone 47 (H2L ) was synthesized (Scheme 5) and characterized by an X-ray structure analysis. 

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