Siderophore Recognition and Cellular Uptake

4-HOPY and the bis-hydroxamate PIPDMAHA used FoxA and FhuA receptors, while the bis-hydroxamate DOCYDMAHA could potentially enter through a number of receptor proteins. 

A series of model siderophore molecular recognition studies coupled with host-guest carrier facilitated model membrane transport studies was reported (198-202). Three approaches were taken which incorporate (i) second coordination shell host-guest complexation, (ii) ternary complex formation, and (iii) a combination of ternary complex - second coordination shell host-guest complex formation. Examples of these approaches are described below. 

Siderophore-ionophore supramolecular assembly formation via host-guest complexation of the pendant protonated amine arm of ferrioxamine B has been confirmed by X-ray crystallography (Fig. 28) (203). The stability and selectivity of this interaction as a function of ionophore structure, metal ion identity, and counter anion identity were determined by liquid-liquid extraction, isothermal calorimetry, and MS (204 -211). Second-sphere host-guest complexation constants fall in the range 103— 106M-1 in CHC13 and methanol depending on ionophore structure. 

Second coordination shell complexation of hydrophilic ferrioxamine B produces a hydrophobic supramolecular siderophore-ionophore assembly. The hydrophobic characteristic in concert 

BLM transport systems for ferrioxamine B were also devised based on first coordination shell recognition via ternary complex formation utilizing vacant coordination sites on the Fe(III) center (Fig. 29) (199). The tetra-coordinated substrate complex selectively transported was partially dechelated diaqua-ferrioxamine B and coordinately unsaturated di-hydroxamato iron(III) complexes, which utilized a hydrophobic membrane bound bidentate chelator as a carrier for selective transport. Active transport for these systems was accomplished using a pH gradient (199). 

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