The Crystal structure of ferrioxamine E

Abstract

The crystal structure of ferrioxamine E, Caa^sNsOgFe-l.S^O, has been determined with single-crystal x-ray diffraction. The crystals are triclinic, space group P\, two molecules per unit cell with dimensions a = 19.77 (1) A, b = 10.512 (2) k,c = 8.029 (2) A, a = 106.84 (2)°, ß = 93.91 (2)°, and y = 97.74 (3)°. The intensity data (3963) were collected on an automatic diffractometer. The structure, determined by the heavy-atom method, was refined by least-squares methods. The final R was 0.076 for all data. The Fe3+ ion is coordinated in a cis configuration to three hydroxamate groups. The molecule is quite flat with a total thickness of 3.6 A. The peptide carbonyl bonds are approximately perpendicular to the plane of the molecule and all point in the same direction.Most aerobic microorganisms contain compounds which solubilize and transport iron(III). These low molecular weight compounds are called siderochromes. The subject has recently been reviewed by Neilands1 and Emery.2 The stability constants of deferrisiderochromes, the ligands, with iron(III) are of the order of 1030, while they have little or no affinity for iron(II). The compounds are separated into families in which the iron binding atoms may be furnished by hydroxamic acid groups, carboxylic acid and hydroxyl group, or catechol residues. All siderochromes contain peptide linkages which are not coordinated to the iron-(III) atom. The families are ferrioxamines, ferrichromes, enterobactins, fusarinines, rhodotoluric acids, and aerobactins. Many of the compounds show either growth-factor or antibiotic activity.The first isolation and characterization of a siderchrome was performed by Neilands for ferrichrome.3 The compound showed potent growth-factor activity. An important discovery was also the fact that deferrisiderochromes are produced in high yield in the medium when the organisms are grown under conditions of low iron stress.4,5 This observation together with the high stability constants of siderochromes and other evidence led Neilands to suggest that these compounds act as cellular transport agents for iron in aerobic microorganisms.6 At the present time there is also substantial evidence for a process of "active" transport of siderochromes across the membrane into the cell.1,7The ferrioxamines are metabolic products of actinomycetes and were originally isolated and characterized as ferrioxamines A, B, C, Di, D2, E, F, and G by a group of workers in Switzerland.8,9 All ferrioxamines are trihydroxamates and the deferrioxamines are either cyclic (D2 and E) or linear. The chemical structures of the ferrioxamines are known. The structures were established by degradation methods and chemical syntheses by Keller-Schierlein,

Main group (IIIA or 13) complexes of benzohydroxamic acid and the crystal structure of tris(benzohydroxamato)indium(III)

“…This contrasts directly with the fac geometry found for the Ga analogue (14). As observed previously in structures of Ga3+ (14), SnJ+ (18-21), Fe3+ (22)(23)(24)(25)(26)(27), Cr3+ (28), and zn2+ (29) . Correction for differences in effective ionic radii (30) shows that the hydroxamate moiety makes a stronger chelate with In3+ than with sn3+, in which complexes the Sn-0 bonds are relatively much longer, especially Sn-O(C) (1 8-21).…”

“…G a ( b~)~ (14) and Cr(bz), (28) are the only structurally characterized metal hydroxamates to have the difference between M -O ( C ) and M-0(N] as small as it is in the present structure (0.014, 0.022, 0.039 A); in the Cr complex, this was ascribed to a crystal-field effect (28) that is not available to Ga or I n ( b~)~. The u p a l difference between M -4 ( C ) and M -O ( N ) is 0.05-0.1 1 A (14,(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)29). Because all possible hydrogen bond donors in the In(bz), structure are so utilized (e.g., the N-H), there is likely an addition of electron density to the N -0 , causing this bond to be anomalously short relative to other values.…”

“…In the latter the In bond to the 0-N (In--O(l)), which is hydrogen bonded to the ethanol molecule, is notably longer than the other two. Can In the ferric ion structures, a similarly corrected comparison shows a weaker M -O ( C ) interaction, but a comparable M-O(N) bond (22)(23)(24)(25)(26)(27). G a ( b~)~ (14) and Cr(bz), (28) are the only structurally characterized metal hydroxamates to have the difference between M -O ( C ) and M-0(N] as small as it is in the present structure (0.014, 0.022, 0.039 A); in the Cr complex, this was ascribed to a crystal-field effect (28) that is not available to Ga or I n ( b~)~.…”

The structure of ferrioxamine D1–ethanol–water (1/2/1)

“…Despite the wide interest, the structural results of ferrioxamines are limited. The only reported crystal structures are those of ferrioxamine E (van der Helm & Poling, 1976) and deferriferrioxamine E (Hossain, van der Helm & Poling, 1983). Because of its kinetic lability, the structural features of ferrioxamine B could not be characterized from solution studies, but it has been shown that the more stable Cr 3+ complex of deferriferrioxamine B (and also of D ~) exists as a mixture of two geometrical isomers, with eis and trans configuration (Leong & Raymond, 1975).…”

Structures of alumichrome A and ferrichrome A at low temperature

“…The absorption corrections were calculated with the program of Coppens, Leiserowitz & Rabinovich (1965), employing a Gaussian method and a 6 x 6 x 6 grid. Each structure factor was assigned a weight (van der Helm & Poling, 1976).…”