Two-State Reactivity in Iron-Catalyzed Alkene Isomerization Confers σ-Base Resistance.

A low-coordinate, high spin (S = 3/2) organometallic iron(I) complex is a catalyst for the isomerization of alkenes. A combination of experimental and computational mechanistic studies supports a mechanism in which alkene isomerization occurs by the allyl mechanism. Importantly, while substrate binding occurs on the S = 3/2 surface, oxidative addition to an η1-allyl intermediate only occurs on the S = 1/2 surface. Since this spin state change is only possible when the alkene substrate is bound, the catalyst has high immunity to typical σ-base poisons due to the antibonding interactions of the high spin state.

A Dimeric Hydride-Bridged Complex with Geometrically Distinct Iron Centers Giving Rise to an S = 3 Ground State.

Structural and spectroscopic characterization of the dimeric iron hydride complex [Ph2B(tBuIm)2FeH]2 reveals an unusual structure in which a tetrahedral iron(II) site (S = 2) is connected to a square planar iron(II) site (S = 1) by two bridging hydride ligands. Magnetic susceptibility reveals strong ferromagnetic coupling between iron centers, with a coupling constant of J = +110(12) cm-1, to give an S = 3 ground state. High-frequency and -field electron paramagnetic resonance (HFEPR) spectroscopy confirms this model. A qualitative molecular orbital analysis of the electronic structure, as supported by electronic structure calculations, reveals that the observed spin configuration results from the orthogonal alignment of two geometrically distinct four-coordinate iron fragments held together by highly covalent hydride ligands.

Magnetization Slow Dynamics in Ferrocenium Complexes.

The single-molecule magnet (SMM) properties of a series of ferrocenium complexes, [Fe(η5 -C5 R5 )2 ]+ (R=Me, Bn), are reported. In the presence of an applied dc field, the slow dynamics of the magnetization in [Fe(η5 -C5 Me5 )2 ]BArF are revealed. Multireference quantum mechanical calculations show a large energy difference between the ground and first excited states, excluding the commonly invoked, thermally activated (Orbach-like) mechanism of relaxation. In contrast, a detailed analysis of the relaxation time highlights that both direct and Raman processes are responsible for the SMM properties. Similarly, the bulky ferrocenium complexes, [Fe(η5 -C5 Bn5 )2 ]BF4 and [Fe(η5 -C5 Bn5 )2 ]PF6 , also exhibit magnetization slow dynamics, however an additional relaxation process is clearly detected for these analogous systems.

Protonation Studies of Molybdenum(VI) Nitride Complexes That Contain the [2,6-(ArNCH2)2NC5H3]2- Ligand (Ar = 2,6-Diisopropylphenyl).

[Ar2N3]Mo(N)(O- t-Bu) (1), which contains the conformationally rigid pyridine-based diamido ligand [2,6-(ArNCH2)2NC5H3]2- (Ar = 2,6-diisopropylphenyl), is a catalyst for the reduction of dinitrogen with protons and electrons. Various acids have been added in order to explore where and how the first proton adds to the complex. The addition of adamantol to 1 produces a five-coordinate bis(adamantoxide), [HAr2N3]Mo(N)(OAd)2 (2a), in which one of the amido nitrogens in the ligand has been protonated and the resulting aniline nitrogen in the [HAr2N3]- ligand is not bound to the metal. The addition of [Ph2NH2][OTf] to 1 produces {[HAr2N3]Mo(N)(O- t-Bu)}(OTf) (3), in which an amido nitrogen has been protonated, but the aniline in the [HAr2N3]- ligand remains bound to the metal. Last, the addition of (2,6-lutidinium)BArF4 (BArF4 = {B(3,5-(CF3)2C6H3)4}-) to 1 yields {[Ar2N3]Mo(N)(LutH)(O- t-Bu)}BArF4, in which LutH+ is hydrogen-bonded to the nitride in the solid state and in dichloromethane with Keq = 412 ± 94 and Δ G = -3.6 ± 0.8 kcal at 22 °C. A similar hydrogen-bonded adduct was formed through the addition of (2-methylpyridinium)BArF4 to 1, but the addition of (pyridinium)BArF4 to 1 leads to the formation of (inter alia) {[HAr2N3]Mo(N)(O- t-Bu)}(BArF4), in which the amide nitrogen has been protonated. The addition of cobaltocene to 3 or {[Ar2N3]Mo(N)(LutH)(O- t-Bu)}(BArF4) leads only to the re-formation of 1. X-ray structural studies were carried out on 2a, 3, and {[Ar2N3]Mo(N)(LutH)(O- t-Bu)}(BArF4).

Sulfide Homeostasis and Nitroxyl Intersect via Formation of Reactive Sulfur Species in Staphylococcus aureus.

Staphylococcus aureus is a commensal human pathogen and a major cause of nosocomial infections. As gaseous signaling molecules, endogenous hydrogen sulfide (H2S) and nitric oxide (NO·) protect S. aureus from antibiotic stress synergistically, which we propose involves the intermediacy of nitroxyl (HNO). Here, we examine the effect of exogenous sulfide and HNO on the transcriptome and the formation of low-molecular-weight (LMW) thiol persulfides of bacillithiol, cysteine, and coenzyme A as representative of reactive sulfur species (RSS) in wild-type and ΔcstR strains of S. aureus. CstR is a per- and polysulfide sensor that controls the expression of a sulfide oxidation and detoxification system. As anticipated, exogenous sulfide induces the cst operon but also indirectly represses much of the CymR regulon which controls cysteine metabolism. A zinc limitation response is also observed, linking sulfide homeostasis to zinc bioavailability. Cellular RSS levels impact the expression of a number of virulence factors, including the exotoxins, particularly apparent in the ΔcstR strain. HNO, like sulfide, induces the cst operon as well as other genes regulated by exogenous sulfide, a finding that is traced to a direct reaction of CstR with HNO and to an endogenous perturbation in cellular RSS, possibly originating from disassembly of Fe-S clusters. More broadly, HNO induces a transcriptomic response to Fe overload, Cu toxicity, and reactive oxygen species and reactive nitrogen species and shares similarity with the sigB regulon. This work reveals an H2S/NO· interplay in S. aureus that impacts transition metal homeostasis and virulence gene expression. IMPORTANCE Hydrogen sulfide (H2S) is a toxic molecule and a recently described gasotransmitter in vertebrates whose function in bacteria is not well understood. In this work, we describe the transcriptomic response of the major human pathogen Staphylococcus aureus to quantified changes in levels of cellular organic reactive sulfur species, which are effector molecules involved in H2S signaling. We show that nitroxyl (HNO), a recently described signaling intermediate proposed to originate from the interplay of H2S and nitric oxide, also induces changes in cellular sulfur speciation and transition metal homeostasis, thus linking sulfide homeostasis to an adaptive response to antimicrobial reactive nitrogen species.

Spectroscopic and Computational Studies of Spin States of Iron(IV) Nitrido and Imido Complexes.

High-oxidation-state metal complexes with multiply bonded ligands are of great interest for both their reactivity as well as their fundamental bonding properties. This paper reports a combined spectroscopic and theoretical investigation into the effect of the apical multiply bonded ligand on the spin-state preferences of threefold symmetric iron(IV) complexes with tris(carbene) donor ligands. Specifically, singlet (S = 0) nitrido [{PhB(ImR)3}FeN], R = tBu (1), Mes (mesityl, 2) and the related triplet (S = 1) imido complexes, [{PhB(ImR)3}Fe(NR')]+, R = Mes, R' = 1-adamantyl (3), tBu (4), were investigated by electronic absorption and Mössbauer effect spectroscopies. For comparison, two other Fe(IV) nitrido complexes, [(TIMENAr)FeN]+ (TIMENAr = tris[2-(3-aryl-imidazol-2-ylidene)ethyl]amine; Ar = Xyl (xylyl), Mes), were investigated by 57Fe Mössbauer spectroscopy, including applied-field measurements. The paramagnetic imido complexes 3 and 4 were also studied by magnetic susceptibility measurements (for 3) and paramagnetic resonance spectroscopy: high-frequency and -field electron paramagnetic resonance (for 3 and 4) and frequency-domain Fourier-transform (FD-FT) terahertz electron paramagnetic resonance (for 3), which reveal their zero-field splitting parameters. Experimentally correlated theoretical studies comprising ligand-field theory and quantum chemical theory, the latter including both density functional theory and ab initio methods, reveal the key role played by the Fe 3dz2 (a1) orbital in these systems: the nature of its interaction with the nitrido or imido ligand dictates the spin-state preference of the complex. The ability to tune the spin state through the energy and nature of a single orbital has general relevance to the factors controlling spin states in complexes with applicability as single molecule devices.

Two-state reactivity in C-H activation by a four-coordinate iron(0) complex.

The ground state structure of [Ph2B(tBuIm)2Fe(CO)2]- is trigonal pyramidal (S = 1), with a thermally accessible square planar (S = 0) geometry. Experimentally calibrated electronic structure calculations provide evidence for two-state reactivity, with C-H oxidative addition on the singlet surface providing an iron(ii) product (S = 0).

Arrested α-hydride migration activates a phosphido ligand for C-H insertion.

Bulky tris(carbene)borate ligands provide access to high spin iron(ii) phosphido complexes. The complex PhB(MesIm)3FeP(H)Ph is thermally unstable, and [PPh] group insertion into a C-H bond of the supporting ligand is observed. An arrested α-hydride migration mechanism suggests increased nucleophilicity of the phosphorus atom facilitates [PPh] group transfer reactivity.

Dehydrogenation of hydrocarbons with metal-carbon multiple bonds and trapping of a titanium(II) intermediate.

Reacting (PNP)Ti[double bond, length as m-dash]CH(t)Bu(CH2(t)Bu) with 2,2'-bipyridine (bipy) in cyclohexane or heptane results in dehydrogenation, cleanly producing cyclohexene and 1-heptene, respectively, and a Ti(II) intermediate that is trapped by bipy to produce [(PNP)Ti(III)(CH2(t)Bu)(bipy˙(-))] (1). This titanium(ii) intermediate reduces the bipy ligand upon coordination to form a Ti(III) center, where the unpaired electron is antiferromagnetically coupled to the electron of the reduced [bipy˙(-)] π-radical moiety, giving an overall diamagnetic species. Complex 1 has been characterized by NMR and UV-vis spectroscopies as well as single crystal X-ray diffraction studies.

Room temperature dehydrogenation of ethane, propane, linear alkanes C4-C8, and some cyclic alkanes by titanium-carbon multiple bonds.

The transient titanium neopentylidyne, [(PNP)Ti≡C(t)Bu] (A; PNP(-)≡N[2-P(i)Pr2-4-methylphenyl]2(-)), dehydrogenates ethane to ethylene at room temperature over 24 h, by sequential 1,2-CH bond addition and ß-hydrogen abstraction to afford [(PNP)Ti(η(2)-H2C═CH2)(CH2(t)Bu)] (1). Intermediate A can also dehydrogenate propane to propene, albeit not cleanly, as well as linear and volatile alkanes C4-C6 to form isolable α-olefin complexes of the type, [(PNP)Ti(η(2)-H2C═CHR)(CH2(t)Bu)] (R = CH3 (2), CH2CH3 (3), (n)Pr (4), and (n)Bu (5)). Complexes 1-5 can be independently prepared from [(PNP)Ti═CH(t)Bu(OTf)] and the corresponding alkylating reagents, LiCH2CHR (R = H, CH3(unstable), CH2CH3, (n)Pr, and (n)Bu). Olefin complexes 1 and 3-5 have all been characterized by a diverse array of multinuclear NMR spectroscopic experiments including (1)H-(31)P HOESY, and in the case of the α-olefin adducts 2-5, formation of mixtures of two diastereomers (each with their corresponding pair of enantiomers) has been unequivocally established. The latter has been spectroscopically elucidated by NMR via C-H coupled and decoupled (1)H-(13)C multiplicity edited gHSQC, (1)H-(31)P HMBC, and dqfCOSY experiments. Heavier linear alkanes (C7 and C8) are also dehydrogenated by A to form [(PNP)Ti(η(2)-H2C═CH(n)Pentyl)(CH2(t)Bu)] (6) and [(PNP)Ti(η(2)-H2C═CH(n)Hexyl)(CH2(t)Bu)] (7), respectively, but these species are unstable but can exchange with ethylene (1 atm) to form 1 and the free α-olefin. Complex 1 exchanges with D2C═CD2 with concomitant release of H2C═CH2. In addition, deuterium incorporation is observed in the neopentyl ligand as a result of this process. Cyclohexane and methylcyclohexane can be also dehydrogenated by transient A, and in the case of cyclohexane, ethylene (1 atm) can trap the [(PNP)Ti(CH2(t)Bu)] fragment to form 1. Dehydrogenation of the alkane is not rate-determining since pentane and pentane-d12 can be dehydrogenated to 4 and 4-d12 with comparable rates (KIE = 1.1(0) at ~29 °C). Computational studies have been applied to understand the formation and bonding pattern of the olefin complexes. Steric repulsion was shown to play an important role in determining the relative stability of several olefin adducts and their conformers. The olefin in 1 can be liberated by use of N2O, organic azides (N3R; R = 1-adamantyl or SiMe3), ketones (O═CPh2; 2 equiv) and the diazoalkane, N2CHtolyl2. For complexes 3-7, oxidation with N2O also liberates the α-olefin.

Evidence for the existence of terminal scandium imidos: mechanistic studies involving imido-scandium bond formation and C-H activation reactions.

The anilide-methyl complex (PNP)Sc(NH[DIPP])(CH(3)) (1) [PNP(-) = bis(2-diisopropylphosphino-4-tolyl)amide, DIPP = 2,6-diisopropylphenyl] eliminates methane (k(avg) = 5.13 × 10(-4) M(-1) s(-1) at 50 °C) in the presence of pyridine to generate the transient scandium imido (PNP)Sc═N[DIPP](NC(5)H(5)) (A-py), which rapidly activates the C-H bond of pyridine in 1,2-addition fashion to form the stable pyridyl complex (PNP)Sc(NH[DIPP])(η(2)-NC(5)H(4)) (2). Mechanistic studies suggest the C-H activation process to be second order overall: first order in scandium and first order in substrate (pyridine). Pyridine binding precedes elimination of methane, and α-hydrogen abstraction is overall-rate-determining [the kinetic isotope effect (KIE) for 1-d(1) conversion to 2 was 5.37(6) at 35 °C and 4.9(14) at 50 °C] with activation parameters ΔH(‡) = 17.9(9) kcal/mol and ΔS(‡) = -18(3) cal/(mol K), consistent with an associative-type mechanism. No KIE or exchange with the anilide proton was observed when 1-d(3) was treated with pyridine or thermolyzed at 35 or 50 °C. The post-rate-determining step, C-H bond activation of pyridine, revealed a primary KIE of 1.1(2) at 35 °C for the intermolecular C-H activation reaction in pyridine versus pyridine-d(5). Complex 2 equilibrated back to the imide A-py slowly, as the isotopomer (PNP)Sc(ND[DIPP])(η(2)-NC(5)H(4)) (2-d(1)) converted to (PNP)Sc(NH[DIPP])(η(2)-NC(5)H(3)D) over 9 days at 60 °C. Molecular orbital analysis of A-py suggested that this species possesses a fairly linear scandium imido motif (169.7°) with a very short Sc-N distance of 1.84 Å. Substituted pyridines can also be activated, with the rates of C-H activation depending on both the steric and electronic properties of the substrate.