| Chemical models were employed to elucidate certain in vivo aspects of siderophore facilitated microbial iron acquisition. Studies described herein include the kinetics and thermodynamics of iron(III) chelation/dechelation reactions, first and second sphere host-guest chemistry relevant to molecular recognition leading to facilitated bulk liquid membrane (BLM) transport and supramolecular assembly formation, and biologically relevant iron(III/II) redox reactions.; The kinetics and thermodynamics of iron chelation/dechelation for the highly charged siderophore mimic tris(L-lysinehydroxamato)iron(III) (+6) cation were studied to examine the effect of electrostatic interactions in the second coordination sphere on reactivity and iron(III) binding affinity in the first coordination sphere. Complex formation rate constants are shown to be dependent on the charge and the shape of the ligand and metal.; Two different model approaches were utilized to investigate molecular recognition and carrier facilitated BLM transport of iron: (1) first coordination sphere recognition through an amphiphilic chelator capable of selectively occupying labile coordination sites on tetradenate and hexadentate siderophore iron complexes; and (2) second coordination sphere recognition through a labile bi-functional molecule which binds tetradenate iron(III) complexes and acts as a guest in a hydrophobic ionophore host. The BLM flux observed was fit to a diffusion-controlled model and data were obtained to illustrate the efficiency of uphill iron complex transport driven by counter-port proton transport. Results obtained illustrate a model for siderophore recognition and transport as well as environmental remediation.; Novel redox active aza crown ethers were investigated as hosts for metal ion, alkyl ammonium, and ferrioxamine B siderophore guests. The reduced form of the aza crown ether forms a significantly more stable assembly with each of the guests, as determined by cyclic voltammetry. These results suggest a redox control for guest binding and release that may be applicable as an external switch in selective membrane transport experiments.; Finally, the effect of an iron(II) chelator on the ascorbate driven reduction of iron sequestered by the iron-overload drug DesferalRTM (ferrioxamine B) was investigated. A mechanism for the observed facilitation of Fe(III/II) reduction by bathophenanthrolinedisulfonate includes ternary complex formation. These results may explain the efficiency and hazards of Desferal/ascorbate therapies in the treatment of iron-overload. |
