Iron Center Research Articles

Nature and Redox Properties of Iron Sites in Zeolites Revealed by Mössbauer Spectroscopy.

Iron-containing zeolite-based catalysts play a pivotal role in environmental processes aimed at mitigating the release of harmful greenhouse gases, such as nitrous oxide (N2O) and methane (CH4). Despite the rich iron chemistry in zeolites, only a fraction of iron species that exhibit an open coordination sphere and possess the ability for electron transfer are responsible for activating reagents. In addition, the splitting of molecular oxygen is facilitated by bare iron cations embedded in zeolitic matrices. Mössbauer spectroscopy is the ideal tool for investigating the valency and geometry of iron species in zeolites because it leaves no iron forms silent and provides insights into in-situ processes. This review is dedicated to the utilization of Mössbauer spectroscopy to elucidate the nature of the extra-framework iron centers in ferrierite (FER), beta-structured (*BEA), and ZSM-5 zeolite (MFI) zeolites, which are active in N2O decomposition and CH4 oxidation through using the active oxygen derived from N2O and O2. In this work, a structured summary of the Mössbauer parameters established over the last two decades is presented, characterizing the specific iron active centers and intermediates formed upon iron's interaction with N2O/O2 and CH4. Additionally, the impact of preparation methods, iron loading, and the long-term stability on iron speciation and its redox behavior under reaction conditions is discussed.

The Influence of Heavy Metal Pollution on the Pigment Content in the Assimilation Apparatus of Poplar Cultivars in the Conditions of the Iron Ore Region

Abstract We carried out studies of the translocation of heavy metals in the soils of Kryvyi Rih. The peculiarities of the accumulation of heavy metals in the assimilation apparatus of seven poplar cultivars were clarified. The maximum rates of translocation of heavy metals were detected at the monitoring site of the industrial site of Northern Iron Ore Dressing Combine (henceforth referred to as Pivnichnyi HZK or PivnHZK). In the leaves of poplars “Lvivska,” “Hradizhzka,” and “I-45/51,” cadmium, one of the highly toxic elements, accumulates 25–30 times more than in the leaves of control plants. High rates of accumulation of heavy metals lead to a violation of the functioning of the plant organism at the physiological and biochemical levels, as evidenced by changes in the content of chlorophyll a and b. The amount of the main pigments of photosynthesis in the leaves of poplar cultivars under conditions of environmental pollution with heavy metals is lower than in the control, which indicates the inclusion of plant signaling mechanisms. At the same time, the amount of carotenoids in the organs of assimilation of poplars growing on the industrial sites of Northern and Central Iron Ore Dressing Combines (henceforth referred to as Central HZK or CHZK) increases and indicates the realization of their protective functions. The investigated cultivars can be divided into two groups according to the intensity of changes in pigment content. The first group (with a decrease in chlorophylls up to 2 times and an increase in the amount of carotenoids up to 2.5 times) includes “I-45/51,” “Lvivska,” and “Hradizhzka,” and the second group (with a decrease in chlorophylls by more than 2 times and an increase in the amount of carotenoids by more than 2.5 times) includes “Keliberdynska,” “Robusta,” “Sacrau-59,” and “Tronco.” This fact indicates better adaptation and greater resistance of cultivars of the first group to the action of heavy metals.

The Iron Chaperone Poly C Binding Protein 1 Regulates Iron Efflux through Intestinal Ferroportin in Mice

Iron is an essential nutrient required by all cells but used primarily for red blood cell production. Because humans have no effective mechanism for ridding the body of excess iron, the absorption of dietary iron must be precisely regulated. The critical site of regulation is the transfer of iron from the absorptive enterocyte to the portal circulation via the sole iron efflux transporter, ferroportin (FPN). Here we report that poly(rC)-binding protein 1 (PCBP1), the major cytosolic iron chaperone, is necessary for the regulation of iron flux through FPN in the intestine of mice. PCBP1 binds iron-glutathione complexes in the cytosol of cells and delivers the iron to ferritin, the iron storage protein, to iron centers in enzymes, and to iron-sulfur cluster chaperones. PCBP1 also limits the chemical reactivity of iron, thereby limiting iron-catalyzed oxidative damage in cells. To explore the role of PCBP1 in dietary iron absorption, we developed mice with an inducible, enterocyte-specific deletion of PCBP1. Mice lacking PCBP1 in the intestinal epithelium exhibit low levels of enterocyte iron, poor retention of dietary iron in enterocyte ferritin, and excess efflux of iron through FPN. Kinetic studies of iron transport using a stable isotope ( 57Fe) coupled with a mini-hepcidin that blocks FPN activity demonstrated that PCBP1 deletion had no effect of intestinal iron uptake but caused high rates of iron efflux through FPN. Surprisingly, excess iron efflux occurred despite lower levels of FPN protein in enterocytes and upregulation of the iron regulatory hormone hepcidin. PCBP1 deletion and the resulting unregulated dietary iron absorption led to poor growth, severe anemia on a low iron diet and liver oxidative stress with iron loading on a high iron diet. To investigate the roles of PCBP1 more precisely in enterocytes, we developed 3-D organoid cultures from intestinal epithelium which functionally expressed the major iron trafficking proteins: divalent metal transporter 1, PCBP1, ferritin, transferrin receptor 1 and FPN. Ex vivo culture of wild-type and PCBP1-depleted enteroids demonstrated normal patterns of FPN expression and hepcidin-mediated turnover. However, fluorescence measurements of kinetically labile iron pools in enteroids competent or blocked for FPN iron efflux indicated that PCBP1 dramatically altered efflux activity. PCBP1 functioned as a cytosolic buffer for iron, binding and retaining iron and thereby keeping “free” iron at very low levels. This low concentration of free iron limited its availability for FPN-mediated efflux and allowed hepcidin-mediated changes in FPN levels to regulate the amount of iron exported from the enterocyte. Thus, by binding enterocyte iron, PCBP1 reduces the concentration of unchaperoned, “free” iron to a low level. This low level of cytosolic free iron is necessary for hepcidin-mediated regulation of FPN activity.

Maturation of the [FeFe]‐Hydrogenase: Direct Transfer of the (κ3‐cysteinate)FeII(CN)(CO)2 Complex B from HydG to HydE

Abstract[FeFe]‐hydrogenases efficiently catalyze the reversible oxidation of molecular hydrogen. Their prowess stems from the intricate H‐cluster, combining a [Fe4S4] center with a binuclear iron center ([2Fe]H). In the latter, each iron atom is coordinated by a CO and CN ligand, connected by a CO and an azadithiolate ligand. The synthesis of this active site involves a unique multiprotein assembly, featuring radical SAM proteins HydG and HydE. HydG initiates the transformation of L‐tyrosine into cyanide and carbon monoxide to generate complex B, which is subsequently transferred to HydE to continue the biosynthesis of the [2Fe]H‐subcluster. Due to its instability, complex B isolation for structural or spectroscopic characterization has been elusive thus far. Nevertheless, the use of a biomimetic analogue of complex B allowed circumvention of the need for the HydG protein during in vitro functional investigations, implying a similar structure for complex B. Herein, we used the HydE protein as a nanocage to encapsulate and stabilize the complex B product generated by HydG. Using X‐ray crystallography, we successfully determined its structure at 1.3 Å resolution. Furthermore, we demonstrated that complex B is directly transferred from HydG to HydE, thus not being released into the solution post‐synthesis, highlighting a transient interaction between the two proteins.

Maturation of the [FeFe]-Hydrogenase: Direct Transfer of the (κ3 -cysteinate)FeII (CN)(CO)2 Complex B from HydG to HydE.

[FeFe]-hydrogenases efficiently catalyze the reversible oxidation of molecular hydrogen. Their prowess stems from the intricate H-cluster, combining a [Fe4 S4 ] center with a binuclear iron center ([2Fe]H ). In the latter, each iron atom is coordinated by a CO and CN ligand, connected by a CO and an azadithiolate ligand. The synthesis of this active site involves a unique multiprotein assembly, featuring radical SAM proteins HydG and HydE. HydG initiates the transformation of L-tyrosine into cyanide and carbon monoxide to generate complex B, which is subsequently transferred to HydE to continue the biosynthesis of the [2Fe]H -subcluster. Due to its instability, complex B isolation for structural or spectroscopic characterization has been elusive thus far. Nevertheless, the use of a biomimetic analogue of complex B allowed circumvention of the need for the HydG protein during in vitro functional investigations, implying a similar structure for complex B. Herein, we used the HydE protein as a nanocage to encapsulate and stabilize the complex B product generated by HydG. Using X-ray crystallography, we successfully determined its structure at 1.3 Å resolution. Furthermore, we demonstrated that complex B is directly transferred from HydG to HydE, thus not being released into the solution post-synthesis, highlighting a transient interaction between the two proteins.

Iron‐Catalyzed Stereoconvergent 1,4‐Hydrosilylation of Conjugated Dienes

AbstractStereoconvergent transformation of E/Z mixtures of olefins to products with a single steric configuration is of great practical importance but hard to achieve. Herein, we report an iron‐catalyzed stereoconvergent 1,4‐hydrosilylation reactions of E/Z mixtures of readily available conjugated dienes for the synthesis of Z‐allylsilanes with high regioselectivity and exclusive stereoselectivity. Mechanistic studies suggest that the reactions most likely proceed through a two‐electron redox mechanism. The stereoselectivity of the reactions is ultimately determined by the crowded reaction cavity of the α‐diimine ligand‐modified iron catalyst, which forces the conjugated diene to coordinate with the iron center in a cis conformation, which in turn results in generation of an anti‐π‐allyl iron intermediate. The mechanism of this stereoconvergent transformation differs from previously reported mechanisms of other related reactions involving radicals or metal‐hydride species.

Iron-Catalyzed Stereoconvergent 1,4-Hydrosilylation of Conjugated Dienes.

Stereoconvergent transformation of E/Z mixtures of olefins to products with a single steric configuration is of great practical importance but hard to achieve. Herein, we report an iron-catalyzed stereoconvergent 1,4-hydrosilylation reactions of E/Z mixtures of readily available conjugated dienes for the synthesis of Z-allylsilanes with high regioselectivity and exclusive stereoselectivity. Mechanistic studies suggest that the reactions most likely proceed through a two-electron redox mechanism. The stereoselectivity of the reactions is ultimately determined by the crowded reaction cavity of the α-diimine ligand-modified iron catalyst, which forces the conjugated diene to coordinate with the iron center in a cis conformation, which in turn results in generation of an anti-π-allyl iron intermediate. The mechanism of this stereoconvergent transformation differs from previously reported mechanisms of other related reactions involving radicals or metal-hydride species.

Visible-light-induced C-H Annulation by Metal-decorated Covalent Organic Frameworks with Fe-bipyridyl linkages

The integration of transition metal and photoredox catalyst achieves a harmonious cooperation between sophisticated chemical transformations and judicious utilization of light energy. The previous work was exclusively accomplished through employment of homogeneous transition-metal catalysts or photoredox catalysts. In this study, we present the synthesis of iron-decorated covalent organic frameworks (Fe-COF) and its application on C-H annulation of amides with alkynes by irradiation of visible light. The iron center prompts robust chelation with amides, leading to C-H activation, subsequently. Meanwhile, the photoactive covalent organic framework facilitates visible light absorption and accelerates the C-H activation step. Significantly, isoquinolin-1(2H)-one derivatives with high yield and selectivity were obtained in the presence of Fe-COF under visible light, and highlighting the covalent organic framework's stability and inherent heterogeneous property with repeatable chemical recyclability.

Dioxygen Activation and Reduction by a Soluble Iron Phthalocyanine.

Iron ions in a square-planar coordination can bind molecules at the vacant axial positions and are able to transform them in stoichiometric and catalytic reactions. Nature takes advantage of these properties by incorporating iron into porphyrin systems, which play a key role not only in the binding and transport of oxygen, but also in catalytic oxidation and reduction reactions involving cytochrome P450. Although these systems have been studied extensively, there are still unresolved questions regarding the interplay between the iron ions and the surrounding ligands. Phthalocyanines (Pc) create a similar environment for metal atoms and FePc is known for a long time. However, without axial ligands FePc aggregates leading to solids of low solubility. In this work we used a known six-coordinate iron phthalocyanine derivative with bulky substituents and removed the stabilizing axial ligands. The resulting paramagnetic, four-coordinate compound does not aggregate and dissolves well so that NMR spectroscopy can be employed for studying the molecular structure and the reactivity. Solvent molecules bind weakly to the iron centers and oxygen is reduced in the presence of H-atom donors. The stoichiometric and catalytic reactivity with oxygen was studied in more detail.

Changes in the Surroundings of the Central Iron Atom in Amorphous Alloys

Changes in the Surroundings of the Central Iron Atom in Amorphous Alloys

The Importance of Dynamic Iron Deposition in Projecting Climate Change Impacts on Pacific Ocean Biogeochemistry

AbstractDeposition of mineral dust plays an important role in upper‐ocean biogeochemical processes, particularly by delivering iron to iron‐limited regions. Here we examine the impact of dynamically changing iron deposition on tropical Pacific Ocean biogeochemistry in fully coupled earth system model projections under several emissions scenarios. Projected end‐of‐21st‐century increases in central tropical Pacific dust and iron deposition strengthen with increasing emissions/radiative forcing, and are aligned with projected soil moisture decreases in adjacent land areas and precipitation increases over the equatorial Pacific. Increased delivery of soluble iron results in a reduction in, and eastward contraction of, equatorial Pacific phytoplankton iron limitation and shifts primary production and particulate organic carbon flux projections relative to a high emissions projection (SSP5‐8.5) wherein soluble iron deposition is prescribed as a static climatology. These results highlight modeling advances in representing coupled land‐air‐sea interactions to project basin‐scale patterns of ocean biogeochemical change.

Mechanism of CO2 Reduction to Methanol with H2 on an Iron(II)-scorpionate Catalyst.

CO2 utilization is an important process in the chemical industry with great environmental power. In this work we show how CO2 and H2 can be reacted to form methanol on an iron(II) center and highlight the bottlenecks for the reaction and what structural features of the catalyst are essential for efficient turnover. The calculations predict the reactions to proceed through three successive reaction cycles that start with heterolytic cleavage of H2 followed by sequential hydride and proton transfer processes. The H2 splitting process is an endergonic process and hence high pressures will be needed to overcome this step and trigger the hydrogenation reaction. Moreover, H2 cleavage into a hydride and proton requires a metal to bind hydride and a nearby source to bind the proton, such as an amide or pyrazolyl group, which the scorpionate ligand used here facilitates. As such the computations highlight the non-innocence of the ligand scaffold through proton shuttle from H2 to substrate as an important step in the reaction mechanism.

Nitric oxide inhibits FTO demethylase activity to regulate N6-methyladenosine mRNA methylation

N6-methyladenosine (m6A) is the most abundant internal modification on eukaryotic mRNAs. Demethylation of m6A on mRNA is catalyzed by the enzyme fat mass and obesity-associated protein (FTO), a member of the nonheme Fe(II) and 2-oxoglutarate (2-OG)-dependent family of dioxygenases. FTO activity and m6A-mRNA are dysregulated in multiple diseases including cancers, yet endogenous signaling molecules that modulate FTO activity have not been identified. Here we show that nitric oxide (NO) is a potent inhibitor of FTO demethylase activity by directly binding to the catalytic iron center, which causes global m6A hypermethylation of mRNA in cells and results in gene-specific enrichment of m6A on mRNA of NO-regulated transcripts. Both cell culture and tumor xenograft models demonstrated that endogenous NO synthesis can regulate m6A-mRNA levels and transcriptional changes of m6A-associated genes. These results build a direct link between NO and m6A-mRNA regulation and reveal a novel signaling mechanism of NO as an endogenous regulator of the epitranscriptome.

Characterization of a novel aromatic ring-hydroxylating oxygenase, NarA2B2, from thermophilic Hydrogenibacillus sp. strain N12.

Polycyclic aromatic hydrocarbons (PAHs) are harmful to human health due to their carcinogenic, teratogenic, and mutagenic effects. A thermophilic Hydrogenibacillus sp. strain N12 capable of degrading a variety of PAHs and derivatives was previously isolated. In this study, an aromatic ring-hydroxylating oxygenase, NarA2B2, was identified from strain N12, with substrate specificity including naphthalene, phenanthrene, dibenzothiophene, fluorene, acenaphthene, carbazole, biphenyl, and pyrene. NarA2B2 was proposed to add one or two atoms of molecular oxygen to the substrate and catalyze biphenyl at C-2, 2 or C-3, 4 positions with different characteristics than before. The key catalytic amino acids, H222, H227, and D379, were identified as playing a pivotal role in the formation of the 2-his-1-carboxylate facial triad. Furthermore, we conducted molecular docking and molecular dynamics simulations, notably, D219 enhanced the stability of the iron center by forming two stable hydrogen bonds with H222, while the mutation of F216, T223, and H302 modulated the catalytic activity by altering the pocket's size and shape. Compared to the wild-type (WT) enzyme, the degradation ratios of acenaphthene by F216A, T223A, and H302A had an improvement of 23.08%, 26.87%, and 29.52%, the degradation ratios of naphthalene by T223A and H302A had an improvement of 51.30% and 65.17%, while the degradation ratio of biphenyl by V236A had an improvement of 77.94%. The purified NarA2B2 was oxygen-sensitive when it was incubated with L-ascorbic acid in an anaerobic environment, and its catalytic activity was restored in vitro. These results contribute to a better understanding of the molecular mechanism responsible for PAHs' degradation in thermophilic microorganisms.IMPORTANCE(i) A novel aromatic ring-hydroxylating oxygenase named NarA2B2, capable of degrading multiple polycyclic aromatic hydrocarbons and derivatives, was identified from the thermophilic microorganism Hydrogenibacillus sp. N12. (ii) The degradation characteristics of NarA2B2 were characterized by adding one or two atoms of molecular oxygen to the substrate. Unlike the previous study, NarA2B2 catalyzed biphenyl at C-2, 2 or C-3, 4 positions. (iii) Catalytic sites of NarA2B2 were conserved, and key amino acids F216, D219, H222, T223, H227, V236, F243, Y300, H302, W316, F369, and D379 played pivotal roles in catalysis, as confirmed by protein structure prediction, molecular docking, molecular dynamics simulations, and point mutation.

Effect of magnetic field modification on oxidative stability of myoglobin in sarcoplasm systems

This study aimed to investigate the effect of magnetic fields (0, 3, 6, 12 mT) on the oxidation characteristics of myoglobin (Mb) in the sarcoplasmic protein (SP) system and to understander the underlying mechanism. The metmyoglobin content, Soret band of heme iron porphyrin, protein conformation and molecular weight distribution were measured in different Mb and SP samples. The results showed that the primary oxidation site of hydroxyl radical on Mb was likely to be the porphyrin ring structure and the side chain group of protein rather than the central iron atoms, what’s more, 12 mT magnetic field treatment had an inhibitory effect on the oxidative damage induced by hydroxyl radical.

Implementing Mesoporosity in Zeolitic Imidazolate Frameworks through Clip-Off Chemistry in Heterometallic Iron-Zinc ZIF-8.

Bond breaking has emerged as a new tool to postsynthetically modify the pore structure in metal-organic frameworks since it allows us to obtain pore environments in structures that are inaccessible by other techniques. Here, we extend the concept of clip-off chemistry to archetypical ZIF-8, taking advantage of the different stabilities of the bonds between imidazolate and Zn and Fe metal atoms in heterometallic Fe-Zn-ZIF-8. We demonstrate that Fe centers can be removed selectively without affecting the backbone of the structure that is supported by the Zn atoms. This allows us to create mesopores within the highly stable ZIF-8 structure. The strategy presented, combined with control of the amount of iron centers incorporated into the structure, permits porosity engineering of ZIF materials and opens a new avenue for designing novel hierarchical porous frameworks.

Coordination dynamics of iron center enables the C–H bond activation: QM/MM insight into the catalysis of hydroxyglutarate synthase (HglS)

Hydroxyglutarate synthase (HglS) from Pseudomonas putida is an iron (II) dependent non-heme oxygenase, which is responsible for the biodegradation of 2-oxoadipate (2OA) to D-2-hydroxyglutarate (D-2HG) in plant lysine catabolism. Here detailed mechanisms for the chemical steps involved in decarboxylation and hydroxylation in the biodegradation of 2OA have been explored by extensive MD simulations and QM/MM calculations. Our study revealed the existence of two coordination modes of the Fe(IV)-oxo species during the reactions of HglS, and the “proximal” one is responsible for the C–H bond activation. The reaction initiates with the attack of Fe(III)-superoxo species on 2OA, resulting in the FeII-O-O-2OA species. After the release of CO2 and the subsequent O-O cleavage, the reactions lead to the “distal” Fe(IV)-oxo species. This species can undergo a coordination switch to evolve into the “proximal” conformation of Fe(IV)-oxo, which is the rate-limiting step with an energy barrier of 20.6 kcal/mol. Moreover, residues in the second coordination sphere, including Arg74, Gln266, Val402, and Ser403, not only strengthen the substrate binding but also facilitate the ferryl-flip, leading to the “proximal” Fe(IV)-oxo conformation that is ideal for the C–H bond activation. These findings may expand our understanding of the coordination dynamics of the iron center in HglS enzyme, which has general implications for other non-heme oxygenases.

Exploring the Methane to Methanol Oxidation over Iron and Copper Sites in Metal–Organic Frameworks

The direct oxidation of methane to methanol (MTM) is a significant challenge in catalysis and holds profound economic implications for the modern chemical industry. Bioinspired metal–organic frameworks (MOFs) with active iron and copper sites have emerged as innovative catalytic platforms capable of facilitating MTM conversion under mild conditions. This review discusses the current state of the art in applying MOFs with iron and copper catalytic centers to effectuate the MTM reaction, with a focus on the diverse spectroscopic techniques employed to uncover the electronic and structural properties of MOF catalysts at a microscopic level. We explore the synthetic strategies employed to incorporate iron and copper sites into various MOF topologies and explore the efficiency and selectivity of the MOFs embedded with iron and copper in acting as catalysts, as well as the ensuing MTM reaction mechanisms based on spectroscopic characterizations supported by theory. In particular, we show how integrating complementary spectroscopic tools that probe varying regions of the electromagnetic spectrum can be exceptionally conducive to achieving a comprehensive understanding of the crucial reaction pathways and intermediates. Finally, we provide a critical perspective on future directions to advance the use of MOFs to accomplish the MTM reaction.

Effect of the Ferrocene Nucleus on the Microwave-Accelerated Esterification Reaction

Microwave irradiation has been utilized in the syntheses of a wide variety of organic compounds due to its shorter reaction times and improved selectivities. Since ferrocene is an organometallic compound consisting of an iron center sandwiched between two cyclopentadienyl rings, the iron moiety was expected to efficiently absorb microwave irradiation, thereby resulting in the ferrocene molecules exhibiting an antenna effect. Thus, we herein confirmed this antenna effect by employing an esterification reaction as a model reaction, using both ferrocene and benzene derivatives under microwave irradiation and conventional heating conditions for comparison purposes. It was also found that the reaction could be carried out at lower temperature using ferrocene derivatives.

Fe(III) T1 MRI Probes Containing Phenolate or Hydroxypyridine-Appended Triamine Chelates and a Coordination Site for Bound Water.

Fe(III) complexes containing a triamine framework and phenolate or hydroxypyridine donors are characterized and studied as T1 MRI probes. In contrast to most Fe(III) MRI probes of linear chelates reported to date, the ligands reported here are pentadentate to give six-coordinate complexes with a coordination site for inner-sphere water. The crystal structure of the complex containing unsubstituted phenolate donors, Fe(L1)Cl, shows a six-coordinate iron center and contains a chloride ligand that is displaced in water. Two additional derivatives are sufficiently water-soluble for study as MRI probes, including a complex with a hydroxypyridine group, Fe(L2), and a hydroxybenzoic acid group, Fe(L3). The pH potentiometric titrations give protonation constants of 7.2 and 7.5 for Fe(L2) and Fe(L3), respectively, which are assigned to deprotonation of the bound water. Changes in the electronic absorbance spectra of the complexes as a function of pH are consistent with the deprotonation of phenol pendants at acidic pH values. However, the inner-sphere water ligand of Fe(L2) and Fe(L3) does not exchange rapidly on the NMR timescale at pH 6.0 or 7.4, as shown by variable-temperature 17O NMR spectroscopy. The pH-dependent proton relaxivity profiles show a maximum in relaxivity at a near-neutral pH, suggesting that exchange of the protons of the bound water is an important contribution. Competitive binding studies with ethylenediaminetetraacetic acid (EDTA) show effective stability constants for Fe(L2) and Fe(L3) at pH 7.4 with log K values of 21.1 and 20.5, respectively. These two complexes are kinetically inert in carbonate phosphate buffer at 37 °C for several hours but transfer iron to transferrin. Fe(L2) and Fe(L3) show enhanced contrast in T1-weighted imaging analyses in BALB/c mice. These studies show that Fe(L2) clears through mixed renal and hepatobiliary routes, while Fe(L3) has a similar pharmacokinetic clearance profile to a macrocyclic Gd(III) contrast agent.