Synthesis and Spectroscopic Characterization of High-Spin Mononuclear Iron(II) \u3cem\u3ep\u3c/em\u3e-Semiquinonate Complexes

Two mononuclear iron(II) p-semiquinonate (pSQ) complexes have been generated via one-electron reduction of precursor complexes containing a substituted 1,4-naphthoquinone ligand. Detailed spectroscopic and computational analysis confirmed the presence of a coordinated pSQ radical ferromagnetically coupled to the high-spin FeII center. The complexes are intended to model electronic interactions between (semi)quinone and iron cofactors in biology

Structural, Spectroscopic, and Electrochemical Properties of Nonheme Fe(II)-Hydroquinonate Complexes: Synthetic Models of Hydroquinone Dioxygenases

Using the tris(3,5-diphenylpyrazol-1-yl)borate (Ph2Tp) supporting ligand, a series of mono- and dinuclear ferrous complexes containing hydroquinonate (HQate) ligands have been prepared and structurally characterized with X-ray crystallography. The monoiron(II) complexes serve as faithful mimics of the substrate-bound form of hydroquinone dioxygenases (HQDOs) – a family of nonheme Fe enzymes that catalyze the oxidative cleavage of 1,4-dihydroxybenzene units. Reflecting the variety of HQDO substrates, the synthetic complexes feature both mono- and bidentate HQate ligands. The bidentate HQates cleanly provide five-coordinate, high-spin Fe(II) complexes with the general formula [Fe(Ph2Tp)(HLX)] (1X), where HLX is a HQate(1-) ligand substituted at the 2-position with a benzimidazolyl (1A), acetyl (1B and 1C), or methoxy (1D) group. In contrast, the monodentate ligand 2,6-dimethylhydroquinone (H2LF) exhibited a greater tendency to bridge between two Fe(II) centers, resulting in formation of [Fe2(Ph2Tp)2(μ-LF)(MeCN)]·[2F(MeCN)]. However, addition of one equivalent of “free” pyrazole (Ph2pz) ligand provided the mononuclear complex, [Fe(Ph2Tp)(HLF)(Ph2pz)]·[1F(Ph2pz)], which is stabilized by an intramolecular hydrogen bond between the HLF and Ph2pz donors. Complex 1F(Ph2pz) represents the first crystallographically-characterized example of a monoiron complex bound to an untethered HQate ligand. The geometric and electronic structures of the Fe/HQate complexes were further probed with spectroscopic (UV-vis absorption, 1H NMR) and electrochemical methods. Cyclic voltammograms of complexes in the 1X series revealed an Fe-based oxidation between 0 and −300 mV (vs. Fc+/0), in addition to irreversible oxidation(s) of the HQate ligand at higher potentials. The one-electron oxidized species (1Xoxox) were examined with UV-vis absorption and electron paramagnetic resonance (EPR) spectroscopies

Synthesis and Characterization of Fe(II) β-Diketonato Complexes with Relevance to Acetylacetone Dioxygenase: Insights into the Electronic Properties of the 3-Histidine Facial Triad

A series of high-spin iron(II) β-diketonato complexes have been prepared and characterized with the intent of modeling the substrate-bound form of the enzyme acetylacetone dioxygenase (Dke1). The Dke1 active site features an Fe(II) center coordinated by three histidine residues in a facial geometry—a departure from the standard 2-histidine-1-carboxylate (2H1C) facial triad dominant among nonheme monoiron enzymes. The deprotonated β-diketone substrate binds to the Fe center in a bidentate fashion. To better understand the implications of subtle changes in coordination environment for the electronic structures of nonheme Fe active sites, synthetic models were prepared with three different supporting ligands (LN3): the anionic Me2Tp and Ph2Tp ligands (R2Tp = hydrotris(pyrazol-1-yl)borate substituted with R-groups at the 3- and 5-pyrazole positions) and the neutral PhTIP ligand (PhTIP = tris(2-phenylimidazol-4-yl)phosphine). The resulting [(LN3)Fe(acacX)]0/+ complexes (acacX = substituted β-diketonates) were analyzed with a combination of experimental and computational methods, namely, X-ray crystallography, cyclic voltammetry, spectroscopic techniques (UV–vis absorption and 1H NMR), and density functional theory (DFT). X-ray diffraction results for complexes with the Me2Tp ligand revealed six-coordinate Fe(II) centers with a bound MeCN molecule, while structures of the Ph2Tp and PhTIP complexes generally exhibited five-coordinate geometries. Each [(LN3)Fe(acacX)]0/+ complex displays two broad absorption features in the visible region that arise from Fe(II)→acacX charge transfer and acacX-based transitions, consistent with UV–vis data reported for Dke1. These absorption bands, along with the Fe redox potentials, are highly sensitive to the identity of LN3 and substitution of the β-diketonates. By interpreting the experimental results in conjunction with DFT calculations, detailed electronic-structure descriptions of the complexes have been obtained, with implications for our understanding of the Dke1 active site

Nanosilver induces minimal lung toxicity or inflammation in a subacute murine inhalation model

<p>Abstract</p> <p>Background</p> <p>There is increasing interest in the environmental and health consequences of silver nanoparticles as the use of this material becomes widespread. Although human exposure to nanosilver is increasing, only a few studies address possible toxic effect of inhaled nanosilver. The objective of this study was to determine whether very small commercially available nanosilver induces pulmonary toxicity in mice following inhalation exposure.</p> <p>Results</p> <p>In this study, mice were exposed sub-acutely by inhalation to well-characterized nanosilver (3.3 mg/m³, 4 hours/day, 10 days, 5 ± 2 nm primary size). Toxicity was assessed by enumeration of total and differential cells, determination of total protein, lactate dehydrogenase activity and inflammatory cytokines in bronchoalveolar lavage fluid. Lungs were evaluated for histopathologic changes and the presence of silver. In contrast to published <it>in vitro </it>studies, minimal inflammatory response or toxicity was found following exposure to nanosilver in our <it>in vivo </it>study. The median retained dose of nanosilver in the lungs measured by inductively coupled plasma - optical emission spectroscopy (ICP-OES) was 31 μg/g lung (dry weight) immediately after the final exposure, 10 μg/g following exposure and a 3-wk rest period and zero in sham-exposed controls. Dissolution studies showed that nanosilver did not dissolve in solutions mimicking the intracellular or extracellular milieu.</p> <p>Conclusions</p> <p>Mice exposed to nanosilver showed minimal pulmonary inflammation or cytotoxicity following sub-acute exposures. However, longer term exposures with higher lung burdens of nanosilver are needed to ensure that there are no chronic effects and to evaluate possible translocation to other organs.</p

Synthesis and Spectroscopic Characterization of High-Spin Mononuclear Iron(II) <i>p</i>‑Semiquinonate Complexes

Two mononuclear iron­(II) <i>p</i>-semiquinonate (<i>p</i>SQ) complexes have been generated via one-electron reduction of precursor complexes containing a substituted 1,4-naphthoquinone ligand. Detailed spectroscopic and computational analysis confirmed the presence of a coordinated <i>p</i>SQ radical ferromagnetically coupled to the high-spin Fe^II center. The complexes are intended to model electronic interactions between (semi)­quinone and iron cofactors in biology

Fe(II) Complexes That Mimic the Active Site Structure of Acetylacetone Dioxygenase: O₂ and NO Reactivity

Acetylacetone dioxygenase (Dke1) is a bacterial enzyme that catalyzes the dioxygen-dependent degradation of β-dicarbonyl compounds. The Dke1 active site contains a nonheme monoiron­(II) center facially ligated by three histidine residues (the 3His triad); coordination of the substrate in a bidentate manner provides a five-coordinate site for O₂ binding. Recently, we published the synthesis and characterization of a series of ferrous β-diketonato complexes that faithfully mimic the enzyme–substrate intermediate of Dke1 (Park, H.; Baus, J.S.; Lindeman, S.V.; Fiedler, A.T. <i>Inorg. Chem.</i> <b>2011</b>, <i>50</i>, 11978–11989). The 3His triad was modeled with three different facially coordinating N3 supporting ligands, and substituted β-diketonates (acac^X) with varying steric and electronic properties were employed. Here, we describe the reactivity of our Dke1 models toward O₂ and its surrogate nitric oxide (NO), and report the synthesis of three new Fe­(II) complexes featuring the anions of dialkyl malonates. Exposure of [Fe­(^Me2Tp)­(acac^X)] complexes (where ^R2Tp = hydrotris­(pyrazol-1-yl)­borate with R-groups at the 3- and 5-positions of the pyrazole rings) to O₂ at −70 °C in toluene results in irreversible formation of green chromophores (λ_max ∼750 nm) that decay at temperatures above −60 °C. Spectroscopic and computational analyses suggest that these intermediates contain a diiron­(III) unit bridged by a trans μ-1,2-peroxo ligand. The green chromophore is not observed with analogous complexes featuring ^Ph2Tp and ^PhTIP ligands (where ^PhTIP = tris­(2-phenylimidazoly-4-yl)­phosphine), since the steric bulk of the phenyl substituents prevents formation of dinuclear species. While these complexes are largely inert toward O₂, ^Ph2Tp-based complexes with dialkyl malonate anions exhibit dioxygenase activity and thus serve as functional Dke1 models. The Fe/acac^X complexes all react readily with NO to yield high-spin (<i>S</i> = 3/2) {FeNO}⁷ adducts that were characterized with crystallographic, spectroscopic, and computational methods. Collectively, the results presented here enhance our understanding of the chemical factors involved in the oxidation of aliphatic substrates by nonheme iron dioxygenases

Fe(II) Complexes That Mimic the Active Site Structure of Acetylacetone Dioxygenase: O₂ and NO Reactivity

Acetylacetone dioxygenase (Dke1) is a bacterial enzyme that catalyzes the dioxygen-dependent degradation of β-dicarbonyl compounds. The Dke1 active site contains a nonheme monoiron­(II) center facially ligated by three histidine residues (the 3His triad); coordination of the substrate in a bidentate manner provides a five-coordinate site for O₂ binding. Recently, we published the synthesis and characterization of a series of ferrous β-diketonato complexes that faithfully mimic the enzyme–substrate intermediate of Dke1 (Park, H.; Baus, J.S.; Lindeman, S.V.; Fiedler, A.T. <i>Inorg. Chem.</i> <b>2011</b>, <i>50</i>, 11978–11989). The 3His triad was modeled with three different facially coordinating N3 supporting ligands, and substituted β-diketonates (acac^X) with varying steric and electronic properties were employed. Here, we describe the reactivity of our Dke1 models toward O₂ and its surrogate nitric oxide (NO), and report the synthesis of three new Fe­(II) complexes featuring the anions of dialkyl malonates. Exposure of [Fe­(^Me2Tp)­(acac^X)] complexes (where ^R2Tp = hydrotris­(pyrazol-1-yl)­borate with R-groups at the 3- and 5-positions of the pyrazole rings) to O₂ at −70 °C in toluene results in irreversible formation of green chromophores (λ_max ∼750 nm) that decay at temperatures above −60 °C. Spectroscopic and computational analyses suggest that these intermediates contain a diiron­(III) unit bridged by a trans μ-1,2-peroxo ligand. The green chromophore is not observed with analogous complexes featuring ^Ph2Tp and ^PhTIP ligands (where ^PhTIP = tris­(2-phenylimidazoly-4-yl)­phosphine), since the steric bulk of the phenyl substituents prevents formation of dinuclear species. While these complexes are largely inert toward O₂, ^Ph2Tp-based complexes with dialkyl malonate anions exhibit dioxygenase activity and thus serve as functional Dke1 models. The Fe/acac^X complexes all react readily with NO to yield high-spin (<i>S</i> = 3/2) {FeNO}⁷ adducts that were characterized with crystallographic, spectroscopic, and computational methods. Collectively, the results presented here enhance our understanding of the chemical factors involved in the oxidation of aliphatic substrates by nonheme iron dioxygenases