Dimeric and trimeric homo- and heteroleptic hydroxamic acid macrocycles formed using mixed-ligand Fe(III)-based metal-templated synthesis.
J Inorg Biochem
; 177: 344-351, 2017 12.
Article
en En
| MEDLINE
| ID: mdl-28797801
Macrocyclic hydroxamic acids coordinate Fe(III) with high affinity as part of siderophore-mediated bacterial iron acquisition. Trimeric hydroxamic acid macrocycles, such as desferrioxamine E (DFOE), are prevalent in nature, with fewer dimeric macrocycles identified, including putrebactin (pbH2), avaroferrin (avH2), bisucaberin (bsH2) and alcaligin (alH2). This work used metal-templated synthesis (MTS) to pre-assemble complexes between one equivalent of Fe(III) and two equivalents of 4-((4-aminobutyl)(hydroxy)amino)-4-oxobutanoic acid (BBH) or 4-((5-aminopentyl)(hydroxy)amino)-4-oxobutanoic acid (PBH). Following peptide coupling, the respective Fe(III) complexes of pbH2 or bsH2 were formed, which analysed by LC-MS under acidic pH as [Fe(pb)]+ ([M]+, m/zobs 426.1) or [Fe(bs)]+ ([M]+, m/zobs 454.2). The mixed-ligand 1:1:1 Fe(III):BBH:PBH system furnished [Fe(pb)]+ and [Fe(bs)]+, together with chimeric [Fe(av)]+ ([M]+, m/zobs 440.2). The deviation from the expected 1:2:1 distribution of [Fe(pb)]+:[Fe(av)]+:[Fe(bs)]+ to 1:3.2:1.6 suggested the MTS-mediated formation of dimeric macrocycles could be influenced by steric effects in the pre-complex and/or cavity size, as governed by the monomer. 21-Membered avH2 defined the lower boundary of the optimal architecture. Mixed-ligand MTS between Fe(III):PBH-d4:ret-PBH at 1:1.5:1.5, where ret-PBH=3-(6-amino-N-hydroxyhexanamido)propanoic acid, gave four Fe(III)-loaded trimeric hydroxamic acid macrocycles in a distribution of 1.0:3.0:2.9:1.1 that closely matched the expected distribution 1:3:3:1 for a system without any kinetic and/or thermodynamic bias. Apo-macrocycles pbH2, avH2 and bsH2 were produced upon incubation with diethylenetriaminepentaacetic acid (DTPA) and co-eluted with a biosynthetic mixture of the native macrocycles. The work has demonstrated the utility of single- and mixed-ligand MTS for producing a variety of homo- and heteroleptic dimeric hydroxamic acid macrocycles as Fe(III) complexes and free ligands.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Péptidos Cíclicos
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Succinatos
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Compuestos Férricos
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Putrescina
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Ácidos Hidroxámicos
Idioma:
En
Revista:
J Inorg Biochem
Año:
2017
Tipo del documento:
Article
País de afiliación:
Australia
Pais de publicación:
Estados Unidos