Deferoxamine B: A Natural, Excellent and Versatile Metal Chelator Original paper

What was reviewed?

This review synthesizes chemistry, biology, and clinical applications of the Deferoxamine B metal chelator, a natural trihydroxamate siderophore produced by Streptomyces pilosus and other actinomycetes, with emphasis on its solution equilibria across metals, protein recognition, and therapeutic/diagnostic uses relevant to host–microbe competition for metals. It details protonation behavior, very high-affinity Fe(III) complexation, notable binding to other trivalent and divalent ions (including Pb[II]), and how DFOB’s terminal amine enables conjugation for imaging and drug delivery. Mechanistic sections describe why hydroxamate coordination stabilizes hard cations, how formation constants and pM/K_D values compare across the periodic table, and where DFOB intersects host “nutritional immunity” and microbial siderophore trafficking.

Who was reviewed?

Evidence spans physicochemical measurements (potentiometry, spectrophotometry, SAXS, calorimetry), computational modeling (DFT), and structural biology showing feroxamine B recognition by siderophore transport proteins of Escherichia coli and Staphylococcus aureus, alongside preclinical/clinical contexts where DFOB removes iron, modulates redox injury, and serves as a radiometal chelator. The review also summarizes conjugation to antibodies for ^89Zr immunoPET and notes bacterial infection imaging with ^68Ga-DFOB in Pseudomonas aeruginosa and S. aureus, linking microbial uptake systems to diagnostic specificity.

Most important findings

DFOB’s three bidentate hydroxamates wrap hard metal centers to yield exceptionally stable octahedral or higher-coordinate complexes; Fe(III) binding dominates across pH 1–10, with the amine protonated and not metal-bound. Stability trends extend to Al(III), Ga(III), In(III), Co(III), Mn(III), Zr(IV), Th(IV), and Pu(IV); among divalents, Cu(II) is notably strong, while Pb(II) forms measurable but weaker complexes (pM and K_D values position Pb(II) below Fe(III)/Ga(III) but within biologically relevant chelation). These equilibria mean DFOB can substantially lower free ferric iron at acidic to neutral pH, outcompeting many ligands and impacting microbial metal acquisition, yet it can also bind non-iron cations and thereby alter the “metal economy” at host–microbe interfaces. Protein studies show feroxamine B fits cognate periplasmic binding proteins (FhuD family), explaining bacterial uptake and enabling vectorization of reporters or therapeutics via the terminal amine.

Clinically, DFOB remains foundational for iron-overload therapy and demonstrates antioxidant benefit where iron-driven ROS exacerbate toxicity; the review also reports preliminary protection against lead-induced cardiotoxicity in rats, consistent with DFOB’s ability to buffer redox-active metal stress. In diagnostics, ^68Ga-DFOB targets infections and ^89Zr-DFOB–antibody conjugates enable immunoPET, though Zr(IV) coordination chemistry motivates octadentate DFOB analogues to reduce bone accumulation. Collectively, these findings position DFOB as a bridge between microbial siderophore biology and clinical chelation, with quantifiable speciation parameters valuable for microbiome-signature curation where metal availability, siderophore uptake, and host sequestration shape community states.

Key implications

For clinicians integrating microbiome insights, the review indicates that Deferoxamine B can modulate metal availability that underpins microbial fitness, virulence factor expression, and community competition, while simultaneously serving as a therapeutic chelator and a targeting scaffold for infection imaging. Because siderophore transporters of pathogens recognize feroxamine B, DFOB-based probes can noninvasively report siderophore-active infections, and DFOB derivatives may perturb metal-driven dysbiosis where iron, aluminum, or lead exposures intersect with oxidative stress and barrier injury. The reported formation constants, protein affinities, and in vivo imaging/therapy data provide actionable parameters for designing chelation strategies and for annotating microbiome signatures that hinge on Fe(III) sequestration and cross-metal buffering.