Light-Driven Hydrogen Evolution Reaction Catalyzed by a Molybdenum-Copper Artificial Hydrogenase.

Orange protein (Orp) is a small bacterial metalloprotein of unknown function that harbors a unique molybdenum/copper (Mo/Cu) heterometallic cluster, [S2MoS2CuS2MoS2]3-. In this paper, the performance of Orp as a catalyst for the photocatalytic reduction of protons into H2 has been investigated under visible light irradiation. We report the complete biochemical and spectroscopic characterization of holo-Orp containing the [S2MoS2CuS2MoS2]3- cluster, with docking and molecular dynamics simulations suggesting a positively charged Arg, Lys-containing pocket as the binding site. Holo-Orp exhibits excellent photocatalytic activity, in the presence of ascorbate as the sacrificial electron donor and [Ru(bpy)3]Cl2 as the photosensitizer, for hydrogen evolution with a maximum turnover number of 890 after 4 h irradiation. Density functional theory (DFT) calculations were used to propose a consistent reaction mechanism in which the terminal sulfur atoms are playing a key role in promoting H2 formation. A series of dinuclear [S2MS2M'S2MS2](4n)- clusters, with M = MoVI, WVI and M'(n+) = CuI, FeI, NiI, CoI, ZnII, CdII were assembled in Orp, leading to different M/M'-Orp versions which are shown to display catalytic activity, with the Mo/Fe-Orp catalyst giving a remarkable turnover number (TON) of 1150 after 2.5 h reaction and an initial turnover frequency (TOF°) of 800 h-1 establishing a record among previously reported artificial hydrogenases.

Structural correlations of nitrogenase active sites using nuclear resonance vibrational spectroscopy and QM/MM calculations.

The biological conversion of N2 to NH3 is accomplished by the nitrogenase family, which is collectively comprised of three closely related but unique metalloenzymes. In the present study, we have employed a combination of the synchrotron-based technique of 57Fe nuclear resonance vibrational spectroscopy together with DFT-based quantum mechanics/molecular mechanics (QM/MM) calculations to probe the electronic structure and dynamics of the catalytic components of each of the three unique M N2ase enzymes (M = Mo, V, Fe) in both the presence (holo-) and absence (apo-) of the catalytic FeMco clusters (FeMoco, FeVco and FeFeco). The results described herein provide vibrational mode assignments for important fingerprint regions of the FeMco clusters, and demonstrate the sensitivity of the calculated partial vibrational density of states (PVDOS) to the geometric and electronic structures of these clusters. Furthermore, we discuss the challenges that are faced when employing NRVS to investigate large, multi-component metalloenzymatic systems, and outline the scope and limitations of current state-of-the-art theory in reproducing complex spectra.

Understanding the Electronic Structure Basis for N2 Binding to FeMoco: A Systematic Quantum Mechanics/Molecular Mechanics Investigation.

The FeMo cofactor (FeMoco) of Mo nitrogenase is responsible for reducing dinitrogen to ammonia, but it requires the addition of 3-4 e-/H+ pairs before N2 even binds. A binding site at the Fe2/Fe3/Fe6/Fe7 face of the cofactor has long been suggested based on mutation studies, with Fe2 or Fe6 nowadays being primarily discussed as possibilities. However, the nature of N2 binding to the cofactor is enigmatic as the metal ions are coordinatively saturated in the resting state with no obvious binding site. Furthermore, the cofactor consists of high-spin Fe(II)/Fe(III) ions (antiferromagnetically coupled but also mixed-valence delocalized), which are not known to bind N2. This suggests that an Fe binding site with a different molecular and electronic structure than the resting state must be responsible for the experimentally known N2 binding in the E4 state of FeMoco. We have systematically studied N2 binding to Fe2 and Fe6 sites of FeMoco at the broken-symmetry QM/MM level as a function of the redox-, spin-, and protonation state of the cofactor. The local and global electronic structure changes to the cofactor taking place during redox events, protonation, Fe-S cleavage, hydride formation, and N2 coordination are systematically analyzed. Localized orbital and quasi-restricted orbital analysis via diamagnetic substitution is used to get insights into the local single Fe ion electronic structure in various states of FeMoco. A few factors emerge as essential to N2 binding in the calculations: spin-pairing of dxz and dyz orbitals of the N2-binding Fe ion, a coordination change at the N2-binding Fe ion aided by a hemilabile protonated sulfur, and finally hydride ligation. The results show that N2 binding to E0, E1, and E2 models is generally unfavorable, likely due to the high-energy cost of stabilizing the necessary spin-paired electronic structure of the N2-binding Fe ion in a ligand environment that clearly favors high-spin states. The results for models of E4, however, suggest a feasible model for why N2 binding occurs experimentally in the E4 state. E4 models with two bridging hydrides between Fe2 and Fe6 show much more favorable N2 binding than other models. When two hydrides coordinate to the same Fe ion, an increased ligand-field splitting due to octahedral coordination at either Fe2 or Fe6 is found. This altered ligand field makes it easier for the Fe ion to acquire a spin-paired electronic structure with doubly occupied dxz and dyz orbitals that backbond to a terminal N2 ligand. Within this model for N2 binding, both Fe2 and Fe6 emerge as possible binding site scenarios. Due to steric effects involving the His195 residue, affecting both the N2 ligand and the terminal SH- group, distinguishing between Fe2 and Fe6 is difficult; furthermore, the binding depends on the protonation state of His195.

The E3 state of FeMoco: one hydride, two hydrides or dihydrogen?

Hydrides are present in the reduced states of the iron-molybdenum cofactor (FeMoco) of Mo nitrogenase and are believed to play a key mechanistic role in the dinitrogen reduction reaction catalyzed by the enzyme. Two hydrides are present in the E4 state according to 1H ENDOR and there is likely a single hydride in the E2 redox state. The 2-hydride E4 state has been experimentally observed to bind N2 and it has been speculated that E3 may bind N2 as well. However, the E3 state has not been directly observed and very little is known about its molecular and electronic structure or reactivity. In recent computational studies, we have explored the energy surfaces of the E2 and E4 by QM/MM modelling, and found that the most stable hydride isomers contain bridging or partially bridging hydrides with an open protonated belt sulfide-bridge. In this work we systematically explore the energy surface of the E3 redox state, comparing single hydride and two-hydride isomers with varying coordination and bridging vs. terminal sulfhydryl groups. We also include a model featuring a triply protonated carbide. The results are only mildly dependent on the QM-region size. The three most stable E3 isomers at the r2SCAN level of theory have in common: an open belt sulfide-bridge (terminal sulfhydryl group on Fe6) and either 2 bridging hydrides (between Fe2 and Fe6), 1 bridging-1-terminal hydride (around Fe2 and Fe6) or a dihydrogen ligand bound at the Fe2 site. Analyzing the functional dependency of the results, we find that functionals previously found to predict accurate structures of spin-coupled Fe/Mo dimers and FeMoco (TPSSh, B97-D3, r2SCAN, and B3LYP*) are in generally good agreement about the stability of these 3 E3 isomers. However, B3LYP*, similar to its parent B3LYP method, predicts a triply protonated carbide isomer as the most stable isomer, an unlikely scenario in view of the lack of experimental evidence for carbide protonation occurring in reduced FeMoco states. Distinguishing further between the 3 hydride isomers is difficult and this flexible coordination nature of hydrides suggests that multiple hydride isomers could be present during experimental conditions. N2 binding was explored and resulted in geometries with 2 bridging hydrides and N2 bound to either Fe2 or Fe6 with a local low-spin state on the Fe. N2 binding is predicted to be mildly endothermic, similar to the E2 state, and it seems unlikely that the E3 state is capable of binding N2.

Ionization energies of metallocenes: a coupled cluster study of cobaltocene.

Open-shell transition metal chemistry presents challenges to contemporary electronic structure methods, based on either density functional or wavefunction theory. While CCSD(T) is the well-trusted gold standard for maingroup thermochemistry, the accuracy and robustness of the method is less clear for open-shell transition metal chemistry, requiring benchmarking of CCSD(T)-based protocols against either higher-level theory or experiment. Ionization energies (IEs) of metallocenes provide an interesting test case with metallocenes being common redox reagents as well as playing roles as redox mediators and cocatalysts in redox catalysis. Using highly accurate ZEKE-MATI experimental measurements of gas phase adiabatic (5.3275 ± 0.0006 eV) and vertical (5.4424 ± 0.0006 eV) ionization energies of cobaltocene, we systematically assessed the accuracy of the local coupled-cluster method DLPNO-CCSD(T) with respect to geometry, reference determinant, basis set size and extrapolation schemes, PNO cut-off and extrapolation, local triples approximation, relativistic effects and core-valence correlation. We show that PNO errors are controllable via the recently introduced PNO extrapolation schemes and that the expensive iterative triples (T1) contribution can be made more manageable by calculating it as a smaller-basis/smaller PNO-cutoff correction. The reference determinant turns out to be a critical aspect in these calculations with the HF determinant resulting in large DLPNO-CCSD(T) errors, likely due to the qualitatively flawed molecular orbital spectrum. The BP86 functional on the other hand was found to provide reference orbitals giving small DLPNO-CCSD(T) errors, likely due to more realistic orbitals as suggested by the more consistent MO spectrum compared to HF. A protocol including complete basis set extrapolations with correlation-consistent basis sets, complete PNO space extrapolations, iterative triples- and core-valence correlation corrections was found to give errors of -0.07 eV and -0.03 eV for adiabatic- and vertical-IE of cobaltocene, respectively, giving close to chemical accuracy for both properties. A computationally efficient DLPNO-CCSD(T) protocol was devised and tested against adiabatic ionization energies of 6 different metallocenes (V, Cr, Mn, Fe, Co, Ni). For the other metallocenes, the iterative triples (T1) and PNO extrapolation contributions turn out to be even more important. The results give errors close to the experimental uncertainty, similar to recent auxiliary-field quantum Monte Carlo results. The quality of the reference determinant orbitals is identified as the main source of uncertainty in CCSD(T) calculations of metallocenes.

The Spectroscopy of Nitrogenases.

Nitrogenases are responsible for biological nitrogen fixation, a crucial step in the biogeochemical nitrogen cycle. These enzymes utilize a two-component protein system and a series of iron-sulfur clusters to perform this reaction, culminating at the FeMco active site (M = Mo, V, Fe), which is capable of binding and reducing N2 to 2NH3. In this review, we summarize how different spectroscopic approaches have shed light on various aspects of these enzymes, including their structure, mechanism, alternative reactivity, and maturation. Synthetic model chemistry and theory have also played significant roles in developing our present understanding of these systems and are discussed in the context of their contributions to interpreting the nature of nitrogenases. Despite years of significant progress, there is still much to be learned from these enzymes through spectroscopic means, and we highlight where further spectroscopic investigations are needed.

The E2 state of FeMoco: Hydride Formation versus Fe Reduction and a Mechanism for H2 Evolution.

The iron-molybdenum cofactor (FeMoco) is responsible for dinitrogen reduction in Mo nitrogenase. Unlike the resting state, E0 , reduced states of FeMoco are much less well characterized. The E2 state has been proposed to contain a hydride but direct spectroscopic evidence is still lacking. The E2 state can, however, relax back the E0 state via a H2 side-reaction, implying a hydride intermediate prior to H2 formation. This E2 →E0 pathway is one of the primary mechanisms for H2 formation under low-electron flux conditions. In this study we present an exploration of the energy surface of the E2 state. Utilizing both cluster-continuum and QM/MM calculations, we explore various classes of E2 models: including terminal hydrides, bridging hydrides with a closed or open sulfide-bridge, as well as models without. Importantly, we find the hemilability of a protonated belt-sulfide to strongly influence the stability of hydrides. Surprisingly, non-hydride models are found to be almost equally favorable as hydride models. While the cluster-continuum calculations suggest multiple possibilities, QM/MM suggests only two models as contenders for the E2 state. These models feature either i) a bridging hydride between Fe2 and Fe6 and an open sulfide-bridge with terminal SH on Fe6 (E2 -hyd) or ii) a double belt-sulfide protonated, reduced cofactor without a hydride (E2 -nonhyd). We suggest both models as contenders for the E2 redox state and further calculate a mechanism for H2 evolution. The changes in electronic structure of FeMoco during the proposed redox-state cycle, E0 →E1 →E2 →E0 , are discussed.

Carbon Monoxide Binding to the Iron-Molybdenum Cofactor of Nitrogenase: a Detailed Quantum Mechanics/Molecular Mechanics Investigation.

Carbon monoxide (CO) is a well-known inhibitor of nitrogenase activity. Under turnover conditions, CO binds to FeMoco, the active site of Mo nitrogenase. Time-resolved IR measurements suggest an initial terminal CO at 1904 cm-1 that converts to a bridging CO at 1715 cm-1, and an X-ray structure shows that CO can displace one of the bridging belt sulfides of FeMoco. However, the CO-binding redox state(s) of FeMoco (En) and the role of the protein environment in stabilizing specific CO-bound intermediates remain elusive. In this work, we carry out an in-depth analysis of the CO-FeMoco interaction based on quantum chemical calculations addressing different aspects of the electronic structure. (1) The local electronic structure of the Fe-CO bond is studied through diamagnetically substituted FeMoco. (2) A cluster model of FeMoco within a polarizable continuum illustrates how CO binding may affect the spin-coupling between the metal centers. (3) A QM/MM model incorporates the explicit influence of the amino acid residues surrounding FeMoco in the MoFe protein. The QM/MM model predicts both a terminal and a bridging CO in the E1 redox state. The scaled calculated CO frequencies (1922 and 1716 cm-1, respectively) are in good agreement with the experimentally observed IR bands supporting CO binding to the E1 state. Alternatively, an E2 state QM/MM model, which has the same atomic structure as the CO-bound X-ray structure, features a semi-bridging CO with a scaled calculated frequency (1718 cm-1) similar to the bridging CO in the E1 model.

Synthesis, Characterization, and Reaction Studies of Pd(II) Tripeptide Complexes.

The aqueous synthesis of Pd(II) complexes with alkylated tripeptides led to the hydrolysis of the peptides at low pH values and mixtures of complexed peptides were formed. A non-aqueous synthetic route allowed the formation and isolation of single products and their characterization. Pd(II) complexes with α-Asp(OR)AlaGly(OR), ß-Asp(OR)AlaGly(OR), and TrpAlaGly(OR) (R = H or alkyl) as tri and tetradentate chelates were characterized. The tridentate coordination mode was accompanied by a fourth monodentate ligand that was shown to participate in both ligand exchange reactions and a direct removal to form the tetradentate coordination mode. The tetradentate coordination revealed a rare a hemi labile carbonyl goup coordination mode to Pd(II). Reactivity with small molecules such as ethylene, acids, formate, and episulfide was investigated. Under acidic conditions and in the presence of ethylene; acetaldehyde was formed. The Pd(II) is a soft Lewis acid and thiophilic and the complexes abstract sulfur from episulfide at apparent modest catalytic rates. The complexes adopt a square planar geometry according to a spectroscopic analysis and DFT calculations that were employed to evaluate the most energetically favorable coordination geometry and compared with the observed infrared and NMR data.

Quantum Mechanics/Molecular Mechanics Study of Resting-State Vanadium Nitrogenase: Molecular and Electronic Structure of the Iron-Vanadium Cofactor.

The nitrogenase enzymes are responsible for all biological nitrogen reduction. How this is accomplished at the atomic level, however, has still not been established. The molybdenum-dependent nitrogenase has been extensively studied and is the most active catalyst for dinitrogen reduction of the nitrogenase enzymes. The vanadium-dependent form, on the other hand, displays different reactivity, being capable of CO and CO2 reduction to hydrocarbons. Only recently did a crystal structure of the VFe protein of vanadium nitrogenase become available, paving the way for detailed theoretical studies of the iron-vanadium cofactor (FeVco) within the protein matrix. The crystal structure revealed a bridging 4-atom ligand between two Fe atoms, proposed to be either a CO32- or NO3- ligand. Using a quantum mechanics/molecular mechanics model of the VFe protein, starting from the 1.35 Å crystal structure, we have systematically explored multiple computational models for FeVco, considering either a CO32- or NO3- ligand, three different redox states, and multiple broken-symmetry states. We find that only a [VFe7S8C(CO3)]2- model for FeVco reproduces the crystal structure of FeVco well, as seen in a comparison of the Fe-Fe and V-Fe distances in the computed models. Furthermore, a broken-symmetry solution with Fe2, Fe3, and Fe5 spin-down (BS7-235) is energetically preferred. The electronic structure of the [VFe7S8C(CO3)]2- BS7-235 model is compared to our [MoFe7S9C]- BS7-235 model of FeMoco via localized orbital analysis and is discussed in terms of local oxidation states and different degrees of delocalization. As previously found from Fe X-ray absorption spectroscopy studies, the Fe part of FeVco is reduced compared to FeMoco, and the calculations reveal Fe5 as locally ferrous. This suggests resting-state FeVco to be analogous to an unprotonated E1 state of FeMoco. Furthermore, V-Fe interactions in FeVco are not as strong compared to Mo-Fe interactions in FeMoco. These clear differences in the electronic structures of otherwise similar cofactors suggest an explanation for distinct differences in reactivity.

Insensitivity of Magnetic Coupling to Ligand Substitution in a Series of Tetraoxolene Radical-Bridged Fe2 Complexes.

The elucidation of magnetostructural correlations between bridging ligand substitution and strength of magnetic coupling is essential to the development of high-temperature molecule-based magnetic materials. Toward this end, we report the series of tetraoxolene-bridged FeII2 complexes [(Me3TPyA)2Fe2(RL)]n+ (Me3TPyA = tris(6-methyl-2-pyridylmethyl)amine; n = 2: OMeLH2 = 3,6-dimethoxy-2,5-dihydroxo-1,4-benzoquinone, ClLH2 = 3,6-dichloro-2,5-dihydroxo-1,4-benzoquinone, Na2[NO2L] = sodium 3,6-dinitro-2,5-dihydroxo-1,4-benzoquinone; n = 4: SMe2L = 3,6-bis(dimethylsulfonium)-2,5-dihydroxo-1,4-benzoquinone diylide) and their one-electron-reduced analogues. Variable-temperature dc magnetic susceptibility data reveal the presence of weak ferromagnetic superexchange between FeII centers in the oxidized species, with exchange constants of J = +1.2(2) (R = OMe, Cl) and +0.3(1) (R = NO2, SMe2) cm-1. In contrast, X-ray diffraction, cyclic voltammetry, and Mössbauer spectroscopy establish a ligand-centered radical in the reduced complexes. Magnetic measurements for the radical-bridged species reveal the presence of strong antiferromagnetic metal-radical coupling, with J = -57(10), -60(7), -58(6), and -65(8) cm-1 for R = OMe, Cl, NO2, and SMe2, respectively. The minimal effects of substituents in the 3- and 6-positions of RLx-• on the magnetic coupling strength is understood through electronic structure calculations, which show negligible spin density on the substituents and associated C atoms of the ring. Finally, the radical-bridged complexes are single-molecule magnets, with relaxation barriers of Ueff = 50(1), 41(1), 38(1), and 33(1) cm-1 for R = OMe, Cl, NO2, and SMe2, respectively. Taken together, these results provide the first examination of how bridging ligand substitution influences magnetic coupling in semiquinoid-bridged compounds, and they establish design criteria for the synthesis of semiquinoid-based molecules and materials.

Dissociation of the FEBID precursor cis-Pt(CO)2Cl2 driven by low-energy electrons.

In this study, we present experimental and theoretical results on dissociative electron attachment and dissociative ionisation for the potential FEBID precursor cis-Pt(CO)2Cl2. UHV surface studies have shown that high purity platinum deposits can be obtained from cis-Pt(CO)2Cl2. The efficiency and energetics of ligand removal through these processes are discussed and experimental appearance energies are compared to calculated thermochemical thresholds. The present results demonstrate the potential effectiveness of electron-induced reactions in the deposition of this FEBID precursor, and these are discussed in conjunction with surface science studies on this precursor and the design of new FEBID precursors.

Caught in the Hinact : Crystal Structure and Spectroscopy Reveal a Sulfur Bound to the Active Site of an O2 -stable State of [FeFe] Hydrogenase.

[FeFe] hydrogenases are the most active H2 converting catalysts in nature, but their extreme oxygen sensitivity limits their use in technological applications. The [FeFe] hydrogenases from sulfate reducing bacteria can be purified in an O2 -stable state called Hinact . To date, the structure and mechanism of formation of Hinact remain unknown. Our 1.65 Šcrystal structure of this state reveals a sulfur ligand bound to the open coordination site. Furthermore, in-depth spectroscopic characterization by X-ray absorption spectroscopy (XAS), nuclear resonance vibrational spectroscopy (NRVS), resonance Raman (RR) spectroscopy and infrared (IR) spectroscopy, together with hybrid quantum mechanical and molecular mechanical (QM/MM) calculations, provide detailed chemical insight into the Hinact state and its mechanism of formation. This may facilitate the design of O2 -stable hydrogenases and molecular catalysts.

Computational Mechanistic Study of [MoFe3S4] Cubanes for Catalytic Reduction of Nitrogenase Substrates.

Molybdenum-dependent nitrogenase is the most active biological catalyst for dinitrogen reduction. This reaction is catalyzed by a [MoFe7S9C] cofactor (FeMoco). FeMoco can be described as a double-cubane, with [MoFe3S3] and [Fe4S3] parts, bound via an interstitial carbide and three bridging sulfides. Model compounds have been synthesized since early studies of the enzyme and Coucouvanis and co-workers demonstrated that [MoFe3S4] cubanes are active catalysts for many substrates catalyzed by nitrogenase. These reactions include hydrazine reduction to ammonia and cis-dimethyldiazene reduction to methylamine. Experiments implicated molybdenum as the binding site but the mechanisms have not been studied by theoretical calculations before. Here we present a DFT study of the catalytic reaction mechanisms of hydrazine and cis-dimethyldiazene reduction with a [MoFe3S4] cubane. Like in the experiments, molybdenum is revealed as the likely substrate binding site, likely due to the labile ligand on Mo. For the hydrazine mechanism, a reduction event is centered on Fe, specifically on the Fe antiferromagnetically coupled to the mixed-valence pair. After protonation of the distal hydrazine nitrogen, the N-N bond can be cleaved to yield NH3 and a Mo-bound -NH2 intermediate. This is followed by another protonation/reduction step to give an -NH3 intermediate, and finally substituted by the substrate to complete the cycle. The computed mechanisms shed light on the bimetallic cooperativity in these systems where the reduction steps are localized on Fe while the substrate binds to Mo and the reductions require only a free coordination site (on Mo) and a favorable reduction event (to Fe). Although both substrates easily displace the weakly bound acetonitrile ligand, one reduction event is required for hydrazine activation and N-N bond cleavage to give an integer-spin -NH2 intermediate. An integer-spin -NH2 intermediate has been observed as a common intermediate for the enzyme reduction of hydrazine and diazene, suggesting a possible link to the enzyme chemistry.

The role of the dihedral angle and excited cation states in ionization and dissociation of mono-halogenated biphenyls; a combined experimental and theoretical coupled cluster study.

We present a combined theoretical and experimental study on the ionization and primary fragmentation channels of the mono-halogenated biphenyls; 2-chlorobiphenyl, 2-bromobiphenyl and 2-iodobiphenyl. The ionization energies (IEs) of the 2-halobiphenyls and the appearance energies (AEs) of the principal fragments are determined through electron impact ionization, while quantum mechanical calculations at the coupled cluster level of theory are used to elucidate the observed processes and the associated dynamics. The primary fragmentation channels are the direct loss of the halogen upon ionization, the loss of the respective hydrogen halides (HX) as well as loss of the hydrogen halide and an additional hydrogen. We find that the dihedral angle strongly influences the relative potential energy of the neutral and the cation on their respective ground state surfaces, an effect caused by the strong influence of the nuclear motion on the conjugation between the phenyl rings. For the principal dissociative ionization channels from the mono-halogenated biphenyls we reason that these can not be described as statistical decay from the ground state cation, but must rather be understood as direct, state-selective processes from specific excited cationic states characterized through local ionization of either the halogenated or the non-substituted phenyl ring.

X-ray Absorption Spectroscopy Combined with Time-Dependent Density Functional Theory Elucidates Differential Substitution Pathways of Au(I) and Au(III) with Zinc Fingers.

A combination of two elements' (Au, Zn) X-ray absorption spectroscopy (XAS) and time-dependent density functional theory (TD-DFT) allowed the elucidation of differential substitution pathways of Au(I) and Au(III) compounds reacting with biologically relevant zinc fingers (ZnFs). Gold L3-edge XAS probed the interaction of gold and the C-terminal Cys2HisCys finger of the HIV-1 nucleocapsid protein NCp7, and the Cys2His2 human transcription factor Sp1. The use of model compounds helped assign oxidation states and the identity of the gold-bound ligands. The computational studies accurately reproduced the experimental XAS spectra and allowed the proposition of structural models for the interaction products at early time points. The direct electrophilic attack on the ZnF by the highly thiophilic Au(I) resulted in a linear P-Au-Cys coordination sphere after zinc ejection whereas for the Sp1, loss of PEt3 results in linear Cys-Au-Cys or Cys-Au-His arrangements. Reactions with Au(III) compounds, on the other hand, showed multiple binding modes. Prompt reaction between [AuCl(dien)]2+ and [Au(dien)(DMAP)]3+ with Sp1 showed a partially reduced Au center and a final linear His-Au-His coordination. Differently, in the presence of NCp7, [AuCl(dien)]2+ readily reduces to Au(I) and changes from square-planar to linear geometry with Cys-Au-His coordination, while [Au(dien)(DMAP)]3+ initially maintains its Au(III) oxidation state and square-planar geometry and the same first coordination sphere. The latter is the first observation of a "noncovalent" interaction of a Au(III) complex with a zinc finger and confirms early hypotheses that stabilization of Au(III) occurs with N-donor ligands. Modification of the zinc coordination sphere, suggesting full or partial zinc ejection, is observed in all cases, and for [Au(dien)(DMAP)]3+ this represents a novel mechanism for nucleocapsid inactivation. The combination of XAS and TD-DFT presents the first direct experimental observation that not only compound reactivity, but also ZnF core specificity, can be modulated on the basis of the coordination sphere of Au(III) compounds.

Low energy electron-induced decomposition of (η5-Cp)Fe(CO)2Mn(CO)5, a potential bimetallic precursor for focused electron beam induced deposition of alloy structures.

The production of alloyed nanostructures presents a unique problem in focused electron beam induced deposition (FEBID). Deposition of such structures has historically involved the mixing of two or more precursor gases in situ or via multiple channel gas injection systems, thereby making the production of precise, reproducible alloy compositions difficult. Promising recent efforts to address this problem have involved the use of multi-centred, heterometallic FEBID precursor species. In this vein, we present here a study of low-energy electron interactions with cyclopentadienyl iron dicarbonyl manganese pentacarbonyl ((η5-Cp)Fe(CO)2Mn(CO)5), a bimetallic species with a polyhapto ligand (Cp) and seven terminal carbonyl ligands. Gas phase studies and coupled cluster calculations of observed low-energy electron-induced reactions were conducted in order to predict the performance of this precursor in FEBID. In dissociative electron attachment, we find single CO loss and cleavage of the Fe-Mn bond, leading to the formation of [Mn(CO)5]-, to be the two dominant channels. Contributions through further CO loss from the intact core and the formation of [Mn(CO)4]- are minor channels. In dissociative ionization (DI), the fragmentation is significantly more extensive and the DI spectra are dominated by fragments formed through the loss of 5 and 6 CO ligands, and fragments formed through cleavage of the Fe-Mn bond accompanied by substantial CO loss. The gas phase fragmentation channels observed are discussed in relation to the underlying processes and their energetics, and in context to related surface studies and the likely performance of this precursor in FEBID.

QM/MM Study of the Nitrogenase MoFe Protein Resting State: Broken-Symmetry States, Protonation States, and QM Region Convergence in the FeMoco Active Site.

Nitrogenase is one of the most fascinating enzymes in nature, being responsible for all biological nitrogen reduction. Despite decades of research, it is among the enzymes in bioinorganic chemistry whose mechanism is the most poorly understood. The MoFe protein of nitrogenase contains an iron-molybdenum-sulfur cluster, FeMoco, where N2 reduction takes place. The resting state of FeMoco has been characterized by crystallography, multiple spectroscopic techniques, and theory (broken-symmetry density functional theory), and all heavy atoms are now characterized. The cofactor charge, however, has been controversial, the electronic structure has proved enigmatic, and little is known about the mechanism. While many computational studies have been performed on FeMoco, few have taken the protein environment properly into account. In this study, we put forward QM/MM models of the MoFe protein from Azotobacter vinelandii, centered on FeMoco. By a detailed analysis of the FeMoco geometry and comparison to the atomic resolution crystal structure, we conclude that only the [MoFe7S9C]1- charge is a possible resting state charge. Further, we find that of the three lowest energy broken-symmetry solutions of FeMoco, the BS7-235 spin isomer (where 235 refers to Fe atoms that are "spin-down") is the only one that can be reconciled with experiment. This is revealed by a comparison of the metal-metal distances in the experimental crystal structure, a rare case of spin-coupling phenomena being visible through the molecular structure. This could be interpreted as the enzyme deliberately stabilizing a specific electronic state of the cofactor, possibly for tuning specific reactivity on specific metal atoms. Finally, we show that the alkoxide group on the Mo-bound homocitrate must be protonated under resting state conditions, the presence of which has implications regarding the nature of FeMoco redox states as well as for potential substrate reduction mechanisms.

Revisiting the Mössbauer Isomer Shifts of the FeMoco Cluster of Nitrogenase and the Cofactor Charge.

Despite decades of research, the structure-activity relationship of nitrogenase is still not understood. Only recently was the full molecular structure of the FeMo cofactor (FeMoco) revealed, but the charge and metal oxidation states of FeMoco have been controversial. With the recent identification of the interstitial atom as a carbide and the more recent revised oxidation-state assignment of the molybdenum atom as Mo(III), here we revisit the Mössbauer properties of FeMoco. By a detailed error analysis of density functional theory-computed isomer shifts and computing isomer shifts relative to the P-cluster, we find that only the charge of [MoFe7S9C]1- fits the experimental data. In view of the recent Mo(III) identification, the charge of [MoFe7S9C]1- corresponds to a formal oxidation-state assignment of Mo(III)3Fe(II)4Fe(III), although due to spin delocalization, the physical oxidation state distribution might also be interpreted as Mo(III)1Fe(II)4Fe(2.5)2Fe(III), according to a localized orbital analysis of the MS = 3/2 broken symmetry solution. These results can be reconciled with the recent spatially resolved anomalous dispersion study by Einsle et al. that suggests the Mo(III)3Fe(II)4Fe(III) distribution, if some spin localization (either through interactions with the protein environment or through vibronic coupling) were to take place.

Proton Shuttling and Reaction Paths in Dissociative Electron Attachment to o- and p-Tetrafluorohydroquinone, an Experimental and Theoretical Study.

Here we present a combined experimental and theoretical study on the fragmentation of o- and p-tetrafluorohydroquinone upon low energy electron attachment. Despite an identical ring-skeleton and identical functional groups in these constitutional isomers, they show distinctly different fragmentation patterns, a phenomenon that cannot be explained by distinct resonances or different thermochemistry. Using high-level quantum chemical calculations with the computationally affordable domain localized pair natural orbital approach, DLPNO-CCSD(T), we are able to provide a complete and accurate description of the respective reaction dynamics, revealing proton shuttling and transition states for competing channels as the explanation for the different behavior of these isomers. The results represent a "schoolbook example" of how the combination of experiment and modern high-level theory may today provide a thorough understanding of complex reaction dynamics by computationally affordable means.