Iron is necessary for life, & iron availability plays a major role in bacterial virulence. In times of iron deficiency, bacteria secrete siderophores: low molecular weight molecules which efficiently bind iron for cellular uptake. Understanding bacterial recognition and transport of iron-siderophore complexes is important to understanding bacterial pathogenicity. Iron (III) forms labile complex with siderophores, which often results in rapidly- isomerizing complexes with changing geometries. Since bacterial siderophore receptors are shape-specific, these isomerization reactions could affect transport of iron into the cell. In this proposal, the recognition and transport of ferric siderophore complexes with the newly-isolated siderophores amonabactin and alcaligin will be examined. Amonabactin will be synthesized using D- (natural structure) or L-form amino acids, and the effects of the geometrically opposite inert metal complexes on bacterial iron uptake will be examined. Ferric alcaligin complexes rapidly isomerize, so the uptake of non-isomerizing inert metal alcaligin complexes will also be studied. The isomerization mechanisms will also be examined using siderophore model complexes containing inert Cr(III), Co(III), and Ga(III) ions, which isomerize in protic solvents. Incorporating Ga (III) enables study of these complexes by NMR spectroscopy. In addition, hydroxamate- containing enterobactin analogs will be synthesized and their iron-binding abilities tested. Studying these systems will aid in the design of iron- sequestering drugs to treat iron overload and to help prevent bacterial pathogenesis.
| Fiedler, Dorothea; Pagliero, Daniela; Brumaghim, Julia L et al. (2004) Encapsulation of cationic ruthenium complexes into a chiral self-assembled cage. Inorg Chem 43:846-8 |
