Iron(IV) complexes with tetraazaadamantane-based ligands: synthesis, structure, applications in dioxygen activation and labeling of biomolecules.

4,6,10-Trihydroxy-1,4,6,10-tetraazaadamantane (TAAD) has been shown to form a stable Fe(IV) complex having a diamantane cage structure, in which the metal center is coordinated by three oxygen atoms of the deprotonated ligand. The complex was characterized by X-ray diffraction analysis, HRMS, NMR, FT-IR, Mössbauer spectroscopy and DFT calculations, which supported the d4 configuration of iron. The Fe(IV)-TAAD complex showed excellent performance in dioxygen activation under mild conditions serving as a mimetic of the thiol oxidase enzyme. The nucleophilicity of the bridgehead nitrogen atom in TAAD provides a straightforward way for the conjugation of Fe(IV)-TAAD complexes to various functional molecules. Using this approach, steroidal and peptide molecules having an iron(IV) label have been prepared for the first time. In addition, the Fe(IV)-TAAD complex was covalently bound to a polystyrene matrix and the resulting material was shown to serve as a heterogeneous catalyst for aerobic oxidation of thiols to disulfides.

Combining Structural with Functional Model Properties in Iron Synthetic Analogue Complexes for the Active Site in Rabbit Lipoxygenase.

Iron complexes that model the structural and functional properties of the active iron site in rabbit lipoxygenase are described. The ligand sphere of the mononuclear pseudo-octahedral cis-(carboxylato)(hydroxo)iron(III) complex, which is completed by a tetraazamacrocyclic ligand, reproduces the first coordination shell of the active site in the enzyme. In addition, two corresponding iron(II) complexes are presented that differ in the coordination of a water molecule. In their structural and electronic properties, both the (hydroxo)iron(III) and the (aqua)iron(II) complex reflect well the only two essential states found in the enzymatic mechanism of peroxidation of polyunsaturated fatty acids. Furthermore, the ferric complex is shown to undergo hydrogen atom abstraction reactions with O-H and C-H bonds of suitable substrates, and the bond dissociation free energy of the coordinated water ligand of the ferrous complex is determined to be 72.4 kcal·mol-1. Theoretical investigations of the reactivity support a concerted proton-coupled electron transfer mechanism in close analogy to the initial step in the enzymatic mechanism. The propensity of the (hydroxo)iron(III) complex to undergo H atom abstraction reactions is the basis for its catalytic function in the aerobic peroxidation of 2,4,6-tri(tert-butyl)phenol and its role as a radical initiator in the reaction of dihydroanthracene with oxygen.

Unmasking Steps in Intramolecular Aromatic Hydroxylation by a Synthetic Nonheme Oxoiron(IV) Complex.

In this study, a methyl group on the classic tetramethylcyclam (TMC) ligand framework is replaced with a benzylic group to form the metastable [FeIV (Osyn )(Bn3MC)]2+ (2-syn; Bn3MC=1-benzyl-4,8,11-trimethyl-1,4,8,11-tetraazacyclotetradecane) species at -40 °C. The decay of 2-syn with time at 25 °C allows the unprecedented monitoring of the steps involved in the intramolecular hydroxylation of the ligand phenyl ring to form the major FeIII -OAr product 3. At the same time, the FeII (Bn3MC)2+ (1) precursor to 2-syn is re-generated in a 1:2 molar ratio relative to 3, accounting for the first time for all the electrons involved and all the Fe species derived from 2-syn as shown in the following balanced equation: 3 [FeIV (O)(LPh )]2+ (2-syn)→2 [FeIII (LOAr )]2+ (3)+[FeII (LPh )]2+ (1)+H2 O. This system thus serves as a paradigm for aryl hydroxylation by FeIV =O oxidants described thus far. It is also observed that 2-syn can be intercepted by certain hydrocarbon substrates, thereby providing a means to assess the relative energetics of aliphatic and aromatic C-H hydroxylation in this system.

Kirkendall Effect Boosts Phosphorylated nZVI for Efficient Heavy Metal Wastewater Treatment.

Removal of non-biodegradable heavy metals has been the top priority in wastewater treatment and the development of green technologies remains a significant challenge. We demonstrate that phosphorylated nanoscale zero-valent iron (nZVI) is promising for removal of heavy metals (NiII , CuII , CrVI , HgII ) via a boosted Kirkendall effect. Phosphorylation confines tensile hoop stress on the nZVI particles and "breaks" the structurally dense spherical nZVI to produce numerous radial nanocracks. Exemplified by NiII removal, the radial nanocracks favor the facile inward diffusion of NiII and the rapid outward transport of electrons and ferrous ions through the oxide shell for surface (NiII /electron) and boundary (NiII /Fe0 ) galvanic exchange. Accompanied by a pronounced hollowing phenomenon, phosphorylated nZVI can instantly reduce and immobilize NiII throughout the oxide shell with a high capacity (258 mg Ni g-1 Fe). For real electroplating factory wastewater treatment, this novel nZVI performs simultaneous NiII and CuII removal, producing effluent of stable quality that meets local discharge regulations.

Probing the Mechanism for 2,4'-Dihydroxyacetophenone Dioxygenase Using Biomimetic Iron Complexes.

In this study, we report the synthesis and characterization of [Fe(T1Et4iPrIP)(2-OH-AP)(OTf)](OTf) (2), [Fe(T1Et4iPrIP)(2-O-AP)](OTf) (3), and [Fe(T1Et4iPrIP)(DMF)3](OTf)3 (4) (T1Et4iPrIP = tris(1-ethyl-4-isopropyl-imidazolyl)phosphine; 2-OH-AP = 2-hydroxyacetophenone, and 2-O-AP- = monodeprotonated 2-hydroxyacetophenone). Both 2 and 3 serve as model complexes for the enzyme-substrate adduct for the nonheme enzyme 2,4'-dihydroacetophenone (DHAP) dioxygenase or DAD, while 4 serves as a model for the ferric form of DAD. Complexes 2-4 have been characterized by X-ray crystallography which reveals T1Et4iPrIP to bind iron in a tridentate fashion. Complex 2 additionally contains a bidentate 2-OH-AP ligand and a monodentate triflate ligand yielding distorted octahedral geometry, while 3 possesses a bidentate 2-O-AP- ligand and exhibits distorted trigonal bipyramidal geometry (τ = 0.56). Complex 4 displays distorted octahedral geometry with 3 DMF ligands completing the ligand set. The UV-vis spectrum of 2 matches more closely to the DAD-substrate spectrum than 3, and therefore, it is believed that the substrate for DAD is bound in the protonated form. TD-DFT studies indicate that visible absorption bands for 2 and 3 are due to MLCT bands. Complexes 2 and 3 are capable of oxidizing the coordinated substrate mimics in a stoichiometric and catalytic fashion in the presence of O2. Complex 4 does not convert 2-OH-AP to products under the same catalytic conditions; however, it becomes anaerobically reduced in the presence of 2 equiv 2-OH-AP to 2.

Design and Syntheses of New Antibiotics Inspired by Nature's Quest for Iron in an Oxidative Climate.

This Account describes fundamental chemistry that promoted the discovery of new antibiotics. Specifically, the NH acidity of simple hydroxamic acid derivatives facilitated the syntheses of novel ß-lactams (oxamazins and monobactams), siderophore mimics that limit bacterial iron uptake and bacterially targeted sideromycins (siderophore-antibiotic conjugates). The development of resistance to our current limited set of antibiotic scaffolds has created a dire medical situation. As recently stated, "if you weren't taking antibiotic resistance seriously before, now would be a good time to start." A project commissioned by the British government (https://amr-review.org/) has released estimates of the near-future global toll of antibiotic resistance that are jaw-dropping in their seriousness and scale: 10 million deaths per year and at least $100 trillion in sacrificed gross national product. The 2020 COVID pandemic confirmed that infectious disease problems are no longer localized but worldwide. Many classical antibiotics, especially ß-lactams, previously provided economical cures, but the evolution of antibiotic destructive enzymes (i.e., ß-lactamases), efflux pumps, and bacterial cell wall permeability barriers has made many types of bacteria, especially Gram-negative strains, resistant. Still, and in contrast to other therapies, the public expectation is that any new antibiotic must be inexpensive. This creates market limitations that have caused most major pharmaceutical companies to abandon antibiotic research. Much needs to be done to address this significant problem.The critical need for bacteria to sequester essential iron provides an Achilles' heel for new antibiotic development. Although ferric iron is extremely insoluble, bacteria need micromolar intracellular concentrations for growth and virulence. To this end, they biosynthesize siderophores (Gr. iron bearer) and excrete them into their environment, where they bind iron with high affinity. The iron complexes are recognized by specific outer-membrane transporters, and once actively internalized, the iron is released for essential processes. To conserve biosynthetic energy, some bacteria recognize and utilize siderophores made by competing strains. As a counter-revolution in the never-ending fight for survival, bacteria have also evolved sideromycins, which are siderophores conjugated to warheads that are lethal to rogue bacteria. While none are now used therapeutically, natural sideromycins called albomycins have been used clinically, and others have been shown to be well tolerated and active in animal infection models. Herein we describe practical methods to synthesize new antibiotics and artificial sideromycins with the generalized structure shown above (siderophore-linker drug). Utilizing the molecular-recognition-based siderophore/sideromycin bacterial assimilation processes, it is possible to design both broad spectrum and exquisitely narrow spectrum (targeted) sideromycins and even repurpose older or more classical antibiotics. Relevant microbiological assays, in vivo animal infection studies, and the recent FDA approval of cefiderocol demonstrate their effectiveness.

Synthesis and Reactivity of Iron Complexes with a Biomimetic SCS Pincer Ligand.

Recent experimental evidence suggests that the FeMoco of nitrogenase undergoes structural rearrangement during N2 reduction, which may result in the generation of coordinatively unsaturated iron sites with two sulfur donors and a carbon donor. In an effort to synthesize and study small-molecule model complexes with a one-carbon/two-sulfur coordination environment, we have designed two new SCS pincer ligands containing a central NHC donor accompanied by thioether- or thiolate-functionalized aryl groups. Metalation of the thioether ligand with Fe(OTf)2 gives 6-coordinate complexes in which the SCS ligand binds meridionally. In contrast, metalation of the thiolate ligand with Fe(HMDS)2 gives a four-coordinate pseudotetrahedral amide complex in which the ligand binds facially, illustrating the potential structural flexibility of these ligands. Reaction of the amide complex with a bulky monothiol gives a four-coordinate complex with a one-carbon/three-sulfur coordination environment that resembles the resting state of nitrogenase. Reaction of the amide complex with phenylhydrazine gives a product with a rare κ1-bound phenylhydrazido group which undergoes N-N cleavage to give a phenylamido complex.

Tailoring Viruslike Mesoporous FeSe2 Hedgehogs for Controlled Drug Delivery and Synergistic Tumor Suppression.

To enhance affinity to their hosts, many organisms have evolved to be spiky. This strategy has been inspiring in many fields, but in drug delivery, the feasibility has not yet been extensively explored due to the lack of suitable nanocarriers. Herein, viruslike mesoporous FeSe2 hedgehogs with exceptional photothermal and catalytic performances have been tailored and explored for synergistic tumor therapy. The viruslike topology makes these hedgehogs highly prone to be internalized by cells. By uploading doxorubicin (Dox) into the hollow spikes and encapsulating the hedgehogs with photothermal-meltable gelatin, controlled surface morphology transition from quasi-spherical to spiky and accompanied Dox release have been achieved, with the assistance of the strong photothermal effect of FeSe2 hedgehogs. These integrated features allow specific and controlled drug delivery, leading to synergistic tumor suppression and immunogenic tumor cell death. These results provide new insights into the tailoring of drug carriers relying on their intrinsic physical features.

Enhanced Redox Reactivity of a Nonheme Iron(V)-Oxo Complex Binding Proton.

Acid effects on the chemical properties of metal-oxygen intermediates have attracted much attention recently, such as the enhanced reactivity of high-valent metal(IV)-oxo species by binding proton(s) or Lewis acidic metal ion(s) in redox reactions. Herein, we report for the first time the proton effects of an iron(V)-oxo complex bearing a negatively charged tetraamido macrocyclic ligand (TAML) in oxygen atom transfer (OAT) and electron-transfer (ET) reactions. First, we synthesized and characterized a mononuclear nonheme Fe(V)-oxo TAML complex (1) and its protonated iron(V)-oxo complexes binding two and three protons, which are denoted as 2 and 3, respectively. The protons were found to bind to the TAML ligand of the Fe(V)-oxo species based on spectroscopic characterization, such as resonance Raman, extended X-ray absorption fine structure (EXAFS), and electron paramagnetic resonance (EPR) measurements, along with density functional theory (DFT) calculations. The two-protons binding constant of 1 to produce 2 and the third protonation constant of 2 to produce 3 were determined to be 8.0(7) × 108 M-2 and 10(1) M-1, respectively. The reactivities of the proton-bound iron(V)-oxo complexes were investigated in OAT and ET reactions, showing a dramatic increase in the rate of sulfoxidation of thioanisole derivatives, such as 107 times increase in reactivity when the oxidation of p-CN-thioanisole by 1 was performed in the presence of HOTf (i.e., 200 mM). The one-electron reduction potential of 2 (Ered vs SCE = 0.97 V) was significantly shifted to the positive direction, compared to that of 1 (Ered vs SCE = 0.33 V). Upon further addition of a proton to a solution of 2, a more positive shift of the Ered value was observed with a slope of 47 mV/log([HOTf]). The sulfoxidation of thioanisole derivatives by 2 was shown to proceed via ET from thioanisoles to 2 or direct OAT from 2 to thioanisoles, depending on the ET driving force.

Mono-, Di- and Tetra-iron Complexes with Selenium or Sulphur Functionalized Vinyliminium Ligands: Synthesis, Structural Characterization and Antiproliferative Activity.

A series of diiron/tetrairon compounds containing a S- or a Se-function (2a-d, 4a-d, 5a-b, 6), and the monoiron [FeCp(CO){SeC1(NMe2)C2HC3(Me)}] (3) were prepared from the diiron µ-vinyliminium precursors [Fe2Cp2(CO)( µ-CO){ µ-η1: η3-C3(R')C2HC1N(Me)(R)}]CF3SO3 (R = R' = Me, 1a; R = 2,6-C6H3Me2 = Xyl, R' = Ph, 1b; R = Xyl, R' = CH2OH, 1c), via treatment with S8 or gray selenium. The new compounds were characterized by elemental analysis, IR and multinuclear NMR spectroscopy, and structural aspects were further elucidated by DFT calculations. The unprecedented metallacyclic structure of 3 was ascertained by single crystal X-ray diffraction. The air-stable compounds (3, 4a-d, 5a-b, 6) display fair to good stability in aqueous media, and thus were assessed for their cytotoxic activity towards A2780, A2780cisR, and HEK-293 cell lines. Cyclic voltammetry, ROS production and NADH oxidation studies were carried out on selected compounds to give insights into their mode of action.

Iron(II) Spin Crossover Complexes with 4,4'-Dipyridylethyne-Crystal Structures and Spin Crossover with Hysteresis.

Three new iron(II) 1D coordination polymers with cooperative spin crossover behavior showing thermal hysteresis loops were synthesized using N2O2 Schiff base-like equatorial ligands and 4,4'-dipyridylethyne as a bridging, rigid axial linker. One of those iron(II) 1D coordination polymers showed a 73 K wide hysteresis below room temperature, which, upon solvent loss, decreased to a still remarkable 30 K wide hysteresis. Single crystal X-ray structures of two iron(II) coordination polymers and T-dependent powder XRD patterns are discussed to obtain insight into the structure property relationship of those materials.

Synthesis of Quercetin-Metal Complexes, In Vitro and In Silico Anticholinesterase and Antioxidant Evaluation, and In Vivo Toxicological and Anxiolitic Activities.

The level of acetylcholine, a neurotransmitter essential for processing memory and learning, is lower in the brains of patients with Alzheimer's disease due to the higher concentration of the enzyme acetylcholinesterase. The main compounds used for Alzheimer's treatment are acetylcholinesterase inhibitors. Quercetin coordination complexes with the metal ions Cu+2, Zn+2, Ni+2, Co+2, and Fe+2 were synthesized to investigate their potential use against Alzheimer's disease, by evaluating the inhibition of acetylcholinesterase in vitro and in silico, as well as the antioxidant activity, toxicity, and anxiolytic action in the zebrafish (Danio rerio) model. The organic complexes were characterized by UV-Vis and FT-IR. The spectral information suggested that coordination of metals occurs with the carbonyl group and OH linked to the C-3 carbon of quercetin. The quercetin-Fe (QFe) complex presented the best antioxidant and antiacetylcholinesterase actions, and these results were confirmed by molecular docking. In the toxicity and locomotor evaluation, the quercetin molecules and the synthesized complexes, mainly QCu and QZn derivatives, showed the highest degree of inhibition of the fish's locomotor activity, suggesting a possible anxiolytic action. Then, quercetin complexes with metals, mainly with Fe+2, represent valuable compounds and deserve more investigation as promising agents against Alzheimer's disease.

A Synthetic Model of Enzymatic [Fe4S4]-Alkyl Intermediates.

Although alkyl complexes of [Fe4S4] clusters have been invoked as intermediates in a number of enzymatic reactions, obtaining a detailed understanding of their reactivity patterns and electronic structures has been difficult owing to their transient nature. To address this challenge, we herein report the synthesis and characterization of a 3:1 site-differentiated [Fe4S4]2+-alkyl cluster. Whereas [Fe4S4]2+ clusters typically exhibit pairwise delocalized electronic structures in which each Fe has a formal valence of 2.5+, Mössbauer spectroscopic and computational studies suggest that the highly electron-releasing alkyl group partially localizes the charge distribution within the cubane, an effect that has not been previously observed in tetrahedrally coordinated [Fe4S4] clusters.

Spectroscopic and Reactivity Comparisons between Nonheme Oxoiron(IV) and Oxoiron(V) Species Bearing the Same Ancillary Ligand.

This work directly compares the spectroscopic and reactivity properties of an oxoiron(IV) and an oxoiron(V) complex that are supported by the same neutral tetradentate N-based PyNMe3 ligand. A complete spectroscopic characterization of the oxoiron(IV) species (2) reveals that this compound exists as a mixture of two isomers. The reactivity of the thermodynamically more stable oxoiron(IV) isomer (2b) is directly compared to that exhibited by the previously reported 1e--oxidized analogue [FeV(O)(OAc)(PyNMe3)]2+ (3). Our data indicates that 2b is 4 to 5 orders of magnitude slower than 3 in hydrogen atom transfer (HAT) from C-H bonds. The origin of this huge difference lies in the strength of the O-H bond formed after HAT by the oxoiron unit, the O-H bond derived from 3 being about 20 kcal·mol-1 stronger than that from 2b. The estimated bond strength of the FeIVO-H bond of 100 kcal·mol-1 is very close to the reported values for highly active synthetic models of compound I of cytochrome P450. In addition, this comparative study provides direct experimental evidence that the lifetime of the carbon-centered radical that forms after the initial HAT by the high valent oxoiron complex depends on the oxidation state of the nascent Fe-OH complex. Complex 2b generates long-lived carbon-centered radicals that freely diffuse in solution, while 3 generates short-lived caged radicals that rapidly form product C-OH bonds, so only 3 engages in stereoretentive hydroxylation reactions. Thus, the oxidation state of the iron center modulates not only the rate of HAT but also the rate of ligand rebound.

Aging effects on the stabilisation and reactivity of iron-based nanoparticles green synthesised using aqueous extracts of Eichhornia crassipes.

Aging effects play a crucial role in determining applications of green-synthesised iron-based nanoparticles in wastewater treatment from laboratory scale to practical applications. In this study, iron-based nanoparticles (Ec-Fe-NPs) were synthesised using the extract of Eichhornia crassipes and ferric chloride. Scanning electron microscopy (SEM) revealed that the fresh Ec-Fe-NPs were spherical and had a narrow particle size range (50 to 80 nm). X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) demonstrated that the Ec-Fe-NPs were mainly amorphous in nature and consisted of Fe0, FeO, Fe2O3 and Fe3O4. As they aged, the particle size of the liquid Ec-Fe-NPs gradually increased and then tended to stabilise. Ec-Fe-NPs that were aged for 28 days were only 19% less efficient than fresh material at removing Cr(VI). Extracts aged up to 28 days were also tested, and their antioxidant capacity was found to be 15.4% lower than that of the fresh extracts. Furthermore, the removal efficiency of Cr(VI) using iron-based nanoparticles synthesised with the aged extracts was 67.2%. Finally, the active components of the extracts, which were responsible for the reactivity and stability of the iron-based nanoparticles, were identified by liquid chromatography-mass spectrometry. Overall, green-synthesised iron-based nanoparticles show promise for Cr(VI) removal from wastewater in practical applications.

A New Approach in Cancer Treatment: Discovery of Chlorido[N,N'-disalicylidene-1,2-phenylenediamine]iron(III) Complexes as Ferroptosis Inducers.

Chlorido[N,N'-disalicylidene-1,2-phenylenediamine]iron(III) complexes generate lipid-based ROS and induce ferroptosis in leukemia and neuroblastoma cell lines. The extent of ferroptosis on the mode of action is regulated by simple modifications of the substituents at the 1,2-phenylenediamine moiety. In HL-60 cells, the unsubstituted lead exclusively caused ferroptosis. For instance, a 4-F substituent shifted the mode of action toward both ferroptosis and necroptosis, while the analogously chlorinated derivative exerted only necroptosis. Remarkably, cell-death in NB1 neuroblastoma cells was solely induced by ferroptosis, independent of the used substituents. The effects were higher than that of the therapeutically applied drug cisplatin. These data clearly demonstrate for the first time that not only iron ions but also iron salophene complexes are potent ferroptosis inducers, which can be optimized as antitumor agents.

Water-Dispersible and Biocompatible Iron Carbide Nanoparticles with High Specific Absorption Rate.

Magnetic nanoparticles are important tools for biomedicine, where they serve as versatile multifunctional instruments for a wide range of applications. Among these applications, magnetic hyperthermia is of special interest for the destruction of tumors and triggering of drug delivery. However, many applications of magnetic nanoparticles require high-quality magnetic nanoparticles displaying high specific absorption rates (SARs), which remains a challenge today. We report here the functionalization and stabilization in aqueous media of highly magnetic 15 nm iron carbide nanoparticles featuring excellent heating power through magnetic induction. The challenge of achieving water solubility and colloidal stability was addressed by designing and using specific dopamine-based ligands. The resulting nanoparticles were completely stable for several months in water, phosphate, phosphate-buffered saline, and serum-containing media. Iron carbide nanoparticles displayed high SARs in water and viscous media (water/glycerol mixtures), even after extended exposition to water and oxygen (SAR up to 1000 W·g-1 in water at 100 kHz, 47 mT). The cytotoxicity and cellular uptake of iron carbide nanoparticles could be easily tuned and were highly dependent on the chemical structure of the ligands used.

Flower-like Fe7S8/Bi2S3 superstructures with improved near-infrared absorption for efficient chemo-photothermal therapy.

Although various photothermal therapy (PTT) nanoagents have been developed in recent years, the rational design and easy synthesis of a PTT nanoplatform with improved near-infrared (NIR) absorption have remained challenging. Herein, via a facile one-pot solvothermal strategy, hydrophilic nanosheet-assembled flower-like Fe7S8/Bi2S3 superstructures were fabricated successfully. Such nanoflowers exhibit improved NIR absorption, which is 1.54 times higher than that of pure Bi2S3 nanosheets at a wavelength of 808 nm. Attractively, these nanoflowers could serve as a drug delivery carrier with controlled release under pH/NIR stimuli and display a fascinating chemo-photothermal synergetic therapeutic effect both in vitro and vivo. The resulting nanoflowers may open up a way for the design of other nanoagents with an improved NIR absorption and chemo-photothermal cancer therapy effect.

Effects of Thiolate Ligation in Monoiron Hydrogenase (Hmd): Stability of the {Fe(CO)2}2+ Core with NNS Ligands.

In this work, we report the effects of NNS-thiolate ligands and nuclearity (monomer, dimer) on the stability of iron complexes related to the active site of monoiron hydrogenase (Hmd). A thermally stable iron(II) dicarbonyl motif is the core feature of the active site, but the coordination features that lead to this property have not been independently evaluated for their contributions to the {Fe(CO)2}2+ stability. As such, non-bulky and bulky benzothiazoline ligands (thiolate precursors) were synthesized and their iron(II) complexes characterized. The use of non-bulky thiolate ligands and low-temperature crystallizations result in isolation of the dimeric species [(NNS)2Fe2(CO)2(I)2] (1), [(NPhNS)2Fe2(CO)2(I)2] (2), and [(MeNNS)2Fe2(CO)2(I)2] (3), which exhibit dimerization via thiolato (µ2-S)2 bridges. In one particular case (unsubstituted NNS ligand), the pathway of decarbonylation and oxidation from 1 was crystallographically elucidated, via isolation of the half-bis-ligated monocarbonyl dimer [(NNS)3Fe2(CO)]I (4) and the fully decarbonylated and oxidized mononuclear [(NNS)2Fe]I (5). The transformations of dicarbonyl complexes (1, 2, and 3) to monocarbonyl complexes (4, 6, and 7) were monitored by UV/vis, demonstrating that 1 and 3 exhibit longer t1/2 (80 and 75 min, respectively) than 2 (30 min), which is attributed to distortion of the ligand backbone. Density functional theory calculations of isolated complexes and putative intermediates were used to corroborate the experimentally observed IR spectra. Finally, dimerization was prevented using a bulky ligand featuring a 2,6-dimethylphenyl substituent, which affords mononuclear iron dicarbonyl complex, [(NPhNSDMPh)Fe(CO)2Br] (8), identified by IR and NMR spectroscopies. The dicarbonyl complex decomposes to the decarbonylated [(NPhNSDMPh)2Fe] (9) within minutes at room temperature. Overall, the work herein demonstrates that the thiolate moiety does not impart thermal stability to the {Fe(CO)2}2+ unit formed in the active site, further indicating the importance of the organometallic Fe-C(acyl) bond in the enzyme.

Paramagnetic nanoemulsions with unified signals for sensitive 19F MRI cell tracking.

As a promising cell tracking technology, 19F MRI suffers from low sensitivity. Here, fluorinated nanoemulsions with a unified 19F signal and paramagnetic relaxation enhancement were developed as 19F MRI cellular tracers with high stability, size controllability, biocompatibility, cellular uptake, and dual-modality for sensitive in vivo RAW264.7 cell tracking.