Dihydroxamate siderophores

Hou Z, Sunderland CJ, Nishio T, Raymond KN (1996) Preorganization of Ferric Alcaligin, Ee2L3. The Eirst Structure of aEerric Dihydroxamate Siderophore. J Am Chem Soc 118 5148... 

Ledyard KM, Butler A (1997) Structure of Putrebactin, a New Dihydroxamate Siderophore Produced by Shewanella putrefaciens. J Biol Inorg Chem 2 93... 

Nishio T, Tanaka N, Hiratake J, Katsube Y, Ishida Y, Oda J (1988) Isolation and Structure of the Novel Dihydroxamate Siderophore Alcaligin. J Am Chem Soc 110 8733... 

Okujo N, Sakakibara Y, Yoshida T, Yamamoto S. (1994) Structure of Acinetoferrin, a New Citrate-based Dihydroxamate Siderophore from Acinetobacter haemolyticus. BioMetals 7 170... 

The first example of a helical complex with pre-determined chirality was the dinuclear complex [Fe2(rdt)3], where rdtFl2 is the fungal iron chelator rhodotorulic acid, (15), a dihydroxamate siderophore. Several more helical and chiral Fe " " and Fe complexes are documented in the diimine and in the hydroxamate and catechol sections. A doubly looped ( bow tie ) complex has been constructed with the aid of a tris-terimine ligand (Section 5.4.3.5.7). 

Figure 38 5 Short term Fe uptake rates from model iron/ligand complexes hy Trichodesmium colonies collected in the suhtropical Atlantic Ocean. Shown are uptake rates from Fe complexed to a trihydroxamate siderophore (desferrioxamine), a dihydroxamate siderophore (rhodoturulic acid), and a porphyrin (protoporphyrin IX). For comparative purposes, uptake rates were also measured using added inorganic Fe (111). Achilles et al. (2003), Limnology and Oceanography 48 2250-2255.

Rhodotorulic acid (RA), a dihydroxamate siderophore, forms dimeric complexes with iron, aluminium and chromium of the stoichiometry M2(RA)3 at neutral pH 36 188). The coordination chemistry of this siderophore is probably the most complicated of the siderophores. The combination of cis-trans, A and A configurations of two iron miters, connected by three RA molecules, makes 42 non-redundant isomers theoretically possible each can be simulated by molecular models. Recently three different isomers or mixtures of isomers of Cr2RA3 were separated by reversed phase HPLC-chromatography177). The visible spectrum of the most abundant fraction corresponds to the cis isomer the two other fractions are very similar to the visible spectrum of the trans Cr(men)3 isomer. The CD spectra, in comparison with the Cr(men)3 model complex, show two different optical isomers, assigned as A -trans and A -trans. The A isomer preparation seems also to contain a certain amount of the A configuration. This is the first time that two different, kinetically stable optical isomers have been isolated from the metal complexes of a siderophore 177). 

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. 

In addition to structure, the dihydroxamate connecting chain length will affect the affinity of linear siderophores and side-rophore mimics for iron(III) (Table IIIA). If the chain connecting the hydroxamates is long, there will be a significant entropic... 

Fig. 15. Linear dihydroxamic acid siderophore mimics with alkyl connecting chains.

The kinetics of iron(III) dissociation from a series of dihydrox-amate siderophores and siderophore mimics, including rhodo-torulic acid (3) and alcalagin, have been investigated (52,127,128, 177,178). ESI-MS studies show that these systems form multiple species as a function of pH and siderophore/iron ratio (128). The lability of these systems and the resultant multiple species leads to several parallel paths to iron(III) dissociation (177). Both the distribution of structures and kinetics of dissociation were shown to be dependent on the length of the spacer chain between the dihydroxamate donor groups (52,127). 

A multiple-path mechanism has been elaborated for dissociation of the mono- and binuclear tris(hydroxamato)-iron(III) complexes with dihydroxamate ligands in aqueous solution. " Iron removal by edta from mono-, bi-, and trinuclear complexes with model desferrioxamine-related siderophores containing one, two, or three tris-hydroxamate units generally follows first-order kinetics though biphasic kinetics were reported for iron removal from one of the binuclear complexes. The kinetic results were interpreted in terms of discrete intrastrand ferrioxamine-type structures for the di-iron and tri-iron complexes of (288). " Reactivities for dissociation, by dissociative activation mechanisms, of a selection of bidentate and hexadentate hydroxamates have been compared with those of oxinates and salicylates. ... 

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. ... 

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