Carrier-Facilitated Bulk Liquid Membrane Transport of Iron(III)−Siderophore Complexes Utilizing First Coordination Sphere Recognition

Abstract

Carrier-facilitated bulk liquid membrane (BLM) transport from an aqueous source phase through a chloroform membrane phase to an aqueous receiving phase was studied for various hydrophilic synthetic and naturally occurring Fe(III)-siderophore complexes using first coordination sphere recognition. Iron transport systems were designed such that two cis coordination sites on a hydrophilic Fe(III) complex are occupied by labile aquo ligands, while the other four coordination sites are blocked by strong tetradentate ligands (siderophores). The labile aquo coordination sites can be "recognized" by a liquid membrane-bound hydrophobic bidentate ligand, which carries the hydrophilic Fe(III)-siderophore complex across the hydrophobic membrane to an aqueous receiving phase. The system is further designed for uphill transport of Fe(III) against a concentration gradient, driven by anti-port H(+) transport. Three tetradentate siderophore and siderophore mimic ligands were investigated: rhodotorulic acid (H(2)L(RA)), alcaligin (H(2)L(AG)), and N,N'-dihydroxy-N,N'-dimethyldecanediamide (H(2)L(8)). Flux values for the transport of Fe(L(x))(OH(2))(2)(+) (x = RA, AG, 8) facilitated by the hydrophobic lauroyl hydroxamic acid (HLHA) membrane carrier were the highest when x = 8, which is attributed to substrate lipophilicity. Ferrioxamine B (FeHDFB(+)) was also selectively transported through a BLM by HLHA. The process involves partial dechelation of ferrioxamine B to produce the tetradentate form of the complex (Fe(H(2)DFB)(OH(2))(2)(2+)), followed by ternary complex formation with HLHA (Fe(H(2)DFB)(LHA)(+)) and transport across the membrane into the receiving phase. Uphill transport of ferrioxamine B was confirmed by increased flux as [H(+)](source phase) < [H(+)](receiving phase). The membrane flux of ferrioxamine B occurs near neutral pH, as evidence that ternary complex formation and ligand exchange are viable processes at the membrane/receptor surface of microbial cells.

Hard and Soft X-ray Absorption Spectroscopic Investigation of Aqueous Fe(III)−Hydroxamate Siderophore Complexes

“…7 Although the importance of Fe-siderophore complexes in the cellular transport of iron, treatment of siderosis, and sequestration of actinides from radioactive waste repositories has been established, the coordination environment and the structures of metal-siderophore complexes in aqueous solutions are not well-understood. [9][10][11] A previous structural analysis of these complexes was limited to the isolated crystalline compounds in the dry state. 12 The identification of the structure and speciation of Fe(III)-siderophore complexes as a function of pH in aqueous solutions is necessary in understanding the role of siderophores in the aforesaid processes.…”

Carrier-facilitated bulk liquid membrane transport of iron(iii) hydroxamate complexes utilizing a labile recognition agent and amine recognition in the second coordination sphere

“…7 relates the flux (mol cm Ϫ2 s Ϫ1 ) to the extraction constant (K ex ), the diffusion coefficient of the complex assembly in the membrane solvent (D mem ), the diffusion layer or membrane thickness (l ), the carrier concentration in the membrane phase ([DC18C6] org ), and the iron complex ([Fe(L 8 )(H x L y ) z ] aq source ) and anion ([ClO 4 Ϫ ] aq source ) concentrations in the aqueous source phase. 11,12 The correlation between flux and K ex predicted by eqn. 7 is observed for the ternary complexes reported here and ferrioxamine B, as illustrated in Fig.…”

“…However, complete compartmentalization of the iron in the receiving phase in these experiments is not possible due to the lipophilicity of the Fe(L 8 )(OH 2 ) 2 ϩ complex. The Fe(L 8 )(OH 2 ) 2 ϩ complex has a pK a of 6.36 32 and the neutral/deprotonated species will partition to a limited extent into the membrane phase 11 and diffuse back into the source phase. A similar iron transport system using a more hydrophilic tetradentate ligand, such as rhodotorulic acid or alcaligin, 11,35-44 could be used to completely compartmentalize the iron.…”

“…We have used hexadentate Fe() chelates with proton-facilitated partial ring opening and Fe() complexes with tetradentate ligands to illustrate the efficacy of this model approach. 11 For second coordination sphere molecular recognition, two strategies for BLM transport may be envisioned. Both strategies utilize a hydrophobic host in the membrane phase which recognizes a guest moiety in the second coordination sphere of the Fe() complex.…”

“…11,20,21 Flux data points represent the average of 1-3 individual replications. Uncertainties in individual flux values are in the 5-10% range.ESI-MS spectra were obtained using an Agilent 1100 Series LC/MSD Ion Trap mass spectrometer.…”