Ferric ion (hydr)oxo clusters in the “Venus flytrap” cleft of FbpA : Mössbauer, calorimetric and mass spectrometric studies

Isothermal calorimetric studies of the binding of iron(III) citrate to ferric ion binding protein from Neisseria gonorrhoeae suggested the complexation of a tetranuclear iron(III) cluster as a single step binding event (apparent binding constant K appITC = 6.0(5) × 105 M−1). High-resolution Fourier transform ion cyclotron resonance mass spectrometric data supported the binding of a tetranuclear oxo(hydroxo) iron(III) cluster of formula [Fe4O2(OH)4(H2O)(cit)]+ in the interdomain binding cleft of FbpA. The mutant H9Y-nFbpA showed a twofold increase in the apparent binding constant [K appITC = 1.1(7) × 106 M−1] for the tetranuclear iron(III) cluster compared to the wild-type protein. Mössbauer spectra of Escherichia coli cells overexpressing FbpA and cultured in the presence of added 57Fe citrate were indicative of the presence of dinuclear and polynuclear clusters. FbpA therefore appears to have a strong affinity for iron clusters in iron-rich environments, a property which might endow the protein with new biological functions

Physicochemical characterization of ferric pyrophosphate citrate

Iron deficiency is a significant health problem across the world. While many patients benefit from oral iron supplements, some, including those on hemodialysis require intravenous iron therapy to maintain adequate iron levels. Until recently, all iron compounds suitable for parenteral administration were colloidal iron–carbohydrate conjugates that require uptake and processing by macrophages. These compounds are associated with variable risk of anaphylaxis, oxidative stress, and inflammation, depending on their physicochemical characteristics. Ferric pyrophosphate citrate (FPC) is a novel iron compound that was approved for parenteral administration by US Food and Drug Administration in 2015. Here we report the physicochemical characteristics of FPC. FPC is a noncolloidal, highly water soluble, complex iron salt that does not contain a carbohydrate moiety. X-ray absorption spectroscopy data indicate that FPC consists of iron (III) complexed with one pyrophosphate and two citrate molecules in the solid state. This structure is preserved in solution and stable for several months, rendering it suitable for pharmaceutical applications in solid or solution state

2-Phenoxypyridyl Dinucleating Ligands for Assembly of Diiron(II) Complexes: Efficient Reactivity with O[subscript 2] to Form (μ-Oxo)diiron(III) Units

A series of 2-phenoxypyridyl and 2-phenoxyimino ligands, H[subscript 2]L[superscript R,R′] [2,2′-(5,5′-(1,2-phenylenebis(ethyne-2,1-diyl))bis(pyridine-5,2-diyl))diphenol, where R = H, Me, or t-Bu, and R′ = H or Ph] and H[subscript 2]BIPS[superscript Me,Ph] [(3,3′-(1E,1′E)-(3,3′-sulfonylbis(3,1-phenylene)bis(azan-1-yl-1-ylidene))bis(methan-1-yl-1-ylidene)bis(5-methylbiphenyl-2-ol)], were synthesized as platforms for nonheme diiron(II) protein model complexes. UV−vis spectrophotometric studies and preparative-scale reactions of L[superscript R,R′] or BIPS[superscript Me,Ph], where L[superscript R,R′] and BIPS[superscript Me,Ph] are the deprotonated forms of H[subscript 2]L[superscript R,R′] and H[subscript 2]BIPS[superscript Me,Ph], respectively, with iron(II) revealed that the presence of sterically protective o-phenol substituents is necessary to obtain discrete dinuclear species. The reaction of L[superscript Me,Ph] with iron(II) in tetrahydrofuran (THF) afforded the doubly bridged compound [Fe[subscript 2](L[superscript Me,Ph])[subscript 2](THF)[subscript 3]] (1), which was characterized in the solid state by X-ray crystallography. A large internal cavity in this complex facilitates its rapid reaction with dioxygen, even at −50 °C, to produce the thermodynamically stable [Fe[subscript 2](μ-O)(L[superscript Me,Ph])[subscript 2]] (2) species. Reaction of [superscript 18]O[subscript 2] instead of [superscript 16]O[subscript 2] with 1 led to a shift in the Fe−O−Fe vibrational frequency from 833 to 798 cm[superscript −1], confirming the presence of the (μ-oxo)diiron(III) core and molecular oxygen as the source of the bridging oxo group. The L[superscript Me,Ph] ligand is robust toward oxidative decomposition and does not display any reversible redox activity.National Institute of General Medical Sciences (U.S.) (Grant GM032134