Microbial iron transport and mobilization is achieved using very powerful low-molecular-weight complexing agents which solubilize ferric ion through the formation of pseudo-octahedral complexes of high-spin Fe3+. These compounds, called siderophores, are manufactured by microorganisms specifically in response to their need for iron, an essential element for growth. The availability of iron to pathogens has been directly linked to the onset of disease in a number of illnesses associated with microbial infection. Transport of the iron occurs via several different mechanisms, as found either between different microorganisms or as parallel systems within one microorganism. We continue to use the replacement of kinetically labile Fe(III) by kinetically inert ions such as Cr(III) or Rh(III) in order to produce metal siderophore complexes of known and stable geometry to be used as biological probes of the transport process. Similarly, use of Ga(III) as a substitute for Fe(III) produces complexes of approximately the same thermodynamic stability and kinetic lability, but of dramatically different redox behavior. Thus Ga(III) substituted compounds can be used as specific probes for parts of the transport and uptake process which depend upon redox behavior. The synthesis of chelating agents which at least in part mimic particular siderophores can be designed so as to test for which parts of the siderophore are critical in the recognition process associated with microbial receptor proteins. Finally, the fundamental coordination chemistry and solution thermodynamic and ligand exchange behavior of the siderophores and their analogs will continue to be characterized as fundamental aspects of the biochemistry of this important class of compounds. In particular, the ligand exchange kinetics in non-aqueous media approximating the hydrophobic environment of the cell membrane will be examined for any significant difference from the aqueous ligand exchange behavior.
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