Sonny C. Lee

Kinetics and mechanistic analysis of an extremely rapid carbon dioxide fixation reaction

Carbon dioxide may react with free or metal-bound hydroxide to afford products containing bicarbonate or carbonate, often captured as ligands bridging two or three metal sites. We report the kinetics and probable mechanism of an extremely rapid fixation reaction mediated by a planar nickel complex [NiII(NNN)(OH)]1- containing a tridentate 2,6-pyridinedicarboxamidate pincer ligand and a terminal hydroxide ligand. The minimal generalized reaction is M-OH + CO2 → M-OCO2H; with variant M, previous rate constants are ≲103 M-1 s-1 in aqueous solution. For the present bimolecular reaction, the (extrapolated) rate constant is 9.5 × 105 M-1 s-1 in N,N′-dimethylformamide at 298 K, a value within the range of kcat/KM≈105–108 M-1 s-1 for carbonic anhydrase, the most efficient catalyst of CO2 fixation reactions. The enthalpy profile of the fixation reaction was calculated by density functional theory. The initial event is the formation of a weak precursor complex between the Ni-OH group and CO2, followed by insertion of a CO2 oxygen atom into the Ni-OH bond to generate a four center Ni(η2-OCO2H) transition state similar to that at the zinc site in carbonic anhydrase. Thereafter, the Ni-OH bond detaches to afford the Ni(η1-OCO2H) fragment, after which the molecule passes through a second, lower energy transition state as the bicarbonate ligand rearranges to a conformation very similar to that in the crystalline product. Theoretical values of metric parameters and activation enthalpy are in good agreement with experimental values [ΔH‡ = 3.2(5) kcal/mol].

Developments in the Biomimetic Chemistry of Cubane-Type and Higher Nuclearity Iron-Sulfur Clusters

A prior thematic issue of Chemical Reviews in 20041 provides broad coverage of the field of biomimetic inorganic chemistry. One principal objective of this field, which is a component of the continually burgeoning multidisciplinary enterprise that is bioinorganic chemistry, is the synthesis of analogues of mononuclear and polynuclear sites in proteins which convey information of significance in interpreting the physical and chemical properties of such sites. This article focuses on polynuclear analogues, specifically higher nuclearity, biomimetic metal-sulfur clusters. Many synthetic and biological clusters can be designated as either strong-field or weak-field. Strong-field clusters are formed by first transition series elements with π-acceptor ligands and by second and third series elements regardless of ligation, and manifest properties arising from large splittings of the d-orbital manifold at individual metal sites. Such species are subsumed under a restrictive definition of clusters as containing two or more metal atoms where direct and substantial metal-metal bonding is present.2 A broader definition now normally employed leads to recognition of weak-field clusters. These species contain σ/π-donor ligands that induce smaller d-orbital splittings favoring individual metal sites with high-spin configurations, magnetic interactions among these individual sites, paramagnetic molecular ground states, and labile ligand binding. These clusters contain first transition series elements. Prominent examples of metals in native weak-field cluster sites include (but are not limited to) Mn3–6 (catalases, photosystem II), non-heme Fe7–10 (O2 carriers, oxygenases, reductases, hydrogenase), Fe-S11–14 (electron transfer, nitrogenase, numerous nonredox functions), Ni15,16 (urease), and Ni-Fe17–19 (hydrogenase). The only exceptions to the weak-field designation are Fe sites in [FeFe]- and [NiFe]-hydrogenases, which occur as the fragments Fe(CO)(CN)(μ2-CO) and Fe(CO)(CN)2(μ2-H), respectively. We also note that the weak-field/strong field distinction does not strictly apply to zinc and copper complexes because ZnII and CuI are necessarily diamagnetic, CuII has a spin-doublet ground state, and CuIII is uniformly diamagnetic. However, all but CuIII manifest the substitutional lability associated with the weak-field case. As examples of weak-field clusters, structures of selected protein-bound sites 1–8 containing Mn, non-heme Fe, Fe-S, Ni, and Ni-Fe (Ni site) are provided in Figure 1. Because of the restricted scope of this article, a selected bibliography of summary accounts of the biomimetic chemistry of mono- and polynuclear sites is presented in Table 1. Citations are in the period 2004–2013 and do not include the contents of the previous thematic issue.1 We note in particular a book devoted to bioinorganic synthesis,20 a treatment of biosynthetic inorganic chemistry involving manipulation of protein-bound sites,21 and biomimetic research on sulfur-ligated sites.22 Other examples of weak-field metal sites in proteins are found in this issue. Figure 1 Schematic structures of illustrative weak-field protein-bound clusters: O2-evolving center in photosystem II (1), [FeFe]-hydrogenase (2), [NiFe]-hydrogenase (3); dinuclear (4), trinuclear cuboidal (5), and tetranuclear cubane-type (6) iron-sulfur clusters; ... Table 1 Selected Bibliography of Biomimetic Inorganic Chemisty: 2004–2013 The purview of this article is the biomimetic chemistry of metal-sulfur clusters as confined to post-2004 advances of homo- and heterometallic iron-sulfur clusters of nuclearity four and higher. The emphasis is on the synthetic approaches to such clusters, some of which in their native condition are implicated directly in numerous enzymological processes.

Speculative synthetic chemistry and the nitrogenase problem.

There exist a limited but growing number of biological metal centers whose properties lie conspicuously outside the realm of known inorganic chemistry. The synthetic analogue approach, broadly directed, offers a powerful exploratory tool that can define intrinsic chemical possibilities for these sites while simultaneously expanding the frontiers of fundamental inorganic chemistry. This speculative application of analogue study is exemplified here in the evolution of synthetic efforts inspired by the cluster chemistry of biological nitrogen fixation.

[Fe4S4]q Cubane Clusters (q = 4+, 3+, 2+) with Terminal Amide Ligands

Bis(trimethylsilyl)amide-ligated iron-sulfur cubane clusters [Fe(4)(mu(3)-S)(4)(N{SiMe(3)}(2))(4)](z) (z = 0, 1-, 2-) are accessible by the reaction of FeCl(N{SiMe(3)}(2))(2)(THF) (1) with 1 equiv of NaSH (z = 0), followed by reduction with either 0.25 (z = 1-) or 1 equiv (z = 2-) of Na(2)S as needed. The anionic clusters are obtained as the sodium salts [Na(THF)(2)][Fe(4)S(4)(N{SiMe(3)}(2))(4)] and [Na(THF)(2)](2)[Fe(4)S(4)(N{SiMe(3)}(2))(4)]; in the solid state, these two clusters both possess a unique contact ion pair motif in which individual sodium ions each coordinate to a cluster core sulfide, an adjacent amide nitrogen, and two THF donors. The monoanionic cluster can also be prepared as the lithium salt [Li(THF)(4)][Fe(4)S(4)(N{SiMe(3)}(2))(4)] by the reaction of 1 with 1:0.5 LiCl/Li(2)S. The characterization of the three-membered redox series allows an analysis of redox trends, as well as a study of the effects of the amide donor environment on the [Fe(4)S(4)] core. Bis(trimethylsilyl)amide terminal ligation significantly stabilizes oxidized cluster redox states, permitting isolation of the uncommon [Fe(4)S(4)](3+) and unprecedented [Fe(4)S(4)](4+) weak-field cores.

Selective Syntheses of Iron−Imide−Sulfide Cubanes, Including a Partial Representation of the Fe−S−X Environment in the FeMo Cofactor

The dinuclear precursors Fe(2)(N(t)Bu)(2)Cl(2)(NH(2)(t)Bu)(2), [Fe(2)(N(t)Bu)(S)Cl(4)](2-), and Fe(2)(NH(t)Bu)(2)(S)(N{SiMe(3)}(2))(2) allowed the selective syntheses of the cubane clusters [Fe(4)(N(t)Bu)(n)(S)(4-n)Cl(4)](z) with [n, z] = [3, 1-], [2, 2-], [1, 2-]. Weak-field iron-sulfur clusters with heteroleptic, nitrogen-containing cores are of interest with respect to observed or conjectured environments in the iron-molybdenum cofactor of nitrogenase. In this context, the present iron-imide-sulfide clusters constitute a new class of compounds for study, with the Fe(4)NS(3) core of the [1, 2-] cluster affording the first synthetic representation of the corresponding heteroligated Fe(4)S(3)X subunit in the cofactor.

A Biomimetic Approach to Oxidized Sites in the Xanthine Oxidoreductase Family : Synthesis and Stereochemistry of Tungsten(VI) Analogue Complexes

Two series of square pyramidal (SP) monodithiolene complexes, [M (VI)O 3- n S n (bdt)] (2-) and their silylated derivatives [M (VI)O 2- n S n (OSiR 3)(bdt)] (-) ( n = 0, M = Mo or W; n = 1, 2, M = W), synthesized in this and previous work, constitute the basic molecules in a biomimetic approach to structural analogues of the oxidized sites in the xanthine oxidoreductase enzyme family. Benzene-1,2-dithiolate (bdt) simulates native pyranopterindithiolene chelation in the basal plane, tungsten instead of the native metal molybdenum was employed in sulfido complexes to avoid autoreduction, and silylation models protonation. The complexes [MO 3(bdt)] (2-) and [MO 2(OSiR 3)(bdt)] (-) represent inactive sites, while [MO 2S(bdt)] (2-) and [MOS(OSiR 3)(bdt)] (-), with basal sulfido and silyloxo ligands, are the first analogues of the catalytic sites. Also prepared were [MOS 2(bdt)] (2-) and [MS 2(OSiR 3)(bdt)] (-), with basal sulfido and silyloxo ligands. Complexes are described by angular parameters which reveal occasional distortions from idealized SP toward a trigonal bipyramidal (TBP) structure arising from crystal packing forces in crystalline Et 4N (+) salts. Miminized energy structures from DFT calculations are uniformly SP and reproduce experimental structures. For example, the correct structure is predicted for [WO 2S(bdt)] (2-), whose basal and apical sulfido diastereomers are potentially interconvertible through a low-lying TBP transition state for pseudorotation. The lowest energy tautomer of the protonated form is calculated to be [WOS(OH)(bdt)] (-), with basal sulfido and hydroxo ligands. Computational and experimental structures indicate that protein sites adopt intrinsic coordination geometries rather than those dictated by protein structure and environment.

Iron–Amide–Sulfide and Iron–Imide–Sulfide Clusters: Heteroligated Core Environments Relevant to the Nitrogenase FeMo Cofactor

Heteroligated cluster cores consisting of weak-field iron, strongly basic nitrogen anions, and sulfide are of interest with respect to observed and conjectured environments in the FeMo cofactor of nitrogenase. Selective syntheses have been developed to achieve such environments with tert-butyl-substituted amide and imide core ligands. A number of different routes were employed, including nominal ligand substitution and oxidative addition reactions, as well as novel transformations involving the combination of different cluster precursors. New cluster products include precursor Fe(2)(μ-NH(t)Bu)(2)[N(SiMe(3))(2)](2) (6), Fe(2)(μ-NH(t)Bu)(2)(μ-S)[N(SiMe(3))(2)](2) (7), which has a rare confacial bitetrahedral geometry previously unknown in iron chemistry, [Fe(2)(μ-N(t)Bu)(μ-S)Cl(4)](2-) (2), and cuboidal [Fe(4)(μ(3)-N(t)Bu)(3)(μ(3)-S)Cl(4)](-) (8), [Fe(4)(μ(3)-N(t)Bu)(2)(μ(3)-S)(2)Cl(4)](2-) (9), and [Fe(4)(μ(3)-N(t)Bu)(μ(3)-S)(3)Cl(4)](2-) (10), as well as selenide-substituted derivatives Fe(2)(μ-NH(t)Bu)(2)(μ-Se)[N(SiMe(3))(2)](2) (7-Se) and [Fe(4)(μ(3)-N(t)Bu)(μ(3)-Se)(3)Cl(4)](2-) (10-Se). The imide-sulfide clusters complete the compositional sets [Fe(2)(μ-N(t)Bu)(n)(μ-S)(2-n)Cl(4)](2-) (n = 0-2) and [Fe(4)(μ(3)-N(t)Bu)(n)(μ(3)-S)(4-n)Cl(4)](z) (n = 0-4), represented previously only by the all-imide and all-sulfide core congeners, and they share chemical and physical properties with the parent homoleptic core species. All imide-sulfide cores are compositionally stable and show no evidence of core ligand exchange over days in solution. Beyond structural differences, the impact of mixed core ligation is most evident in redox potentials, which show progressive decreases of -435 (for z = 1-/2-) or -385 mV (for z = 2-/3-) for each replacement of sulfide by the more potent imide donor, and a corresponding effect may be expected for the interstitial heteroligand in the FeMo cofactor. Cluster 10 presents an [Fe(4)NS(3)] core framework virtually isometric with the isostructural [Fe(4)S(3)X] subunit of the FeMo cofactor, thus providing a synthetic structural representation for this portion of the cofactor core.

Reactivity of a Sterically Hindered Fe(II) Thiolate Dimer with Amines and Hydrazines

The sterically hindered Fe(II) thiolate dimer Fe(2)(mu-STriph)(2)(STriph)(2) (1; [STriph](-) = 2,4,6-triphenylbenzenethiolate) reacts with primary amines ((t)BuNH(2), aniline) and N(2)H(4) to form the structurally characterized addition complexes Fe(STriph)(2)(NH(2)(t)Bu)(2), Fe(2)(mu-STriph)(2)(STriph)(2)(NH(2)Ph)(2), and Fe(2)(mu-eta(1):eta(1)-N(2)H(4))(2)(N(2)H(4))(4)(STriph)(4) in high yield. Chemical and NMR spectroscopic evidence indicate that the binding of these nitrogen donors is labile in solution and multispecies equilibria are likely. With arylhydrazines, 1 catalytically disproportionates 1,2-diphenylhydrazine to aniline and azobenzene, and it rearranges 1-methyl-1,2-diarylhydrazines to give, after treatment with alumina, mononuclear, trigonal bipyramidal Fe(III) complexes of composition Fe(ISQ)(2)(STriph), where [ISQ](-) denotes an appropriately substituted bidentate o-diiminobenzosemiquinonate ligand. Complex 1 shows no reaction with hindered 1,2-dialkylhydrazines (isopropyl or tert-butyl) or tetrasubstituted 1,2-dimethyl-1,2-diphenylhydrazine.

Iron L2,3-Edge X-ray Absorption and X-ray Magnetic Circular Dichroism Studies of Molecular Iron Complexes with Relevance to the FeMoco and FeVco Active Sites of Nitrogenase

Herein, a systematic study of a series of molecular iron model complexes has been carried out using Fe L2,3-edge X-ray absorption (XAS) and X-ray magnetic circular dichroism (XMCD) spectroscopies. This series spans iron complexes of increasing complexity, starting from ferric and ferrous tetrachlorides ([FeCl4]−/2–), to ferric and ferrous tetrathiolates ([Fe(SR)4]−/2–), to diferric and mixed-valent iron–sulfur complexes [Fe2S2R4]2–/3–. This test set of compounds is used to evaluate the sensitivity of both Fe L2,3-edge XAS and XMCD spectroscopy to oxidation state and ligation changes. It is demonstrated that the energy shift and intensity of the L2,3-edge XAS spectra depends on both the oxidation state and covalency of the system; however, the quantitative information that can be extracted from these data is limited. On the other hand, analysis of the Fe XMCD shows distinct changes in the intensity at both L3 and L2 edges, depending on the oxidation state of the system. It is also demonstrated that the XMCD intensity is modulated by the covalency of the system. For mononuclear systems, the experimental data are correlated with atomic multiplet calculations in order to provide insights into the experimental observations. Finally, XMCD is applied to the tetranuclear heterometal–iron–sulfur clusters [MFe3S4]3+/2+ (M = Mo, V), which serve as structural analogues of the FeMoco and FeVco active sites of nitrogenase. It is demonstrated that the XMCD data can be utilized to obtain information on the oxidation state distribution in complex clusters that is not readily accessible for the Fe L2,3-edge XAS data alone. The advantages of XMCD relative to standard K-edge and L2,3-edge XAS are highlighted. This study provides an important foundation for future XMCD studies on complex (bio)inorganic systems.

Light-Atom Influences on the Electronic Structures of Iron–Sulfur Clusters

Ligand K-edge X-ray absorption spectroscopy was used to study dimeric and tetrameric Cl-terminated Fe-S clusters with variable numbers of S(2-) substituted by N(t)Bu(2-) (N(t)Bu(2-) = tertbutylimido) ligands to gain insights into the functional role of the interstitial light atom in the iron-molybdenum cofactor (FeMoco) of nitrogenase. These studies are complemented by time-dependent density functional theory analysis to quantify the relative effects on Fe-S and Fe-Cl bonding. The results show that N(t)Bu(2-) substitution dramatically affects the electronic structure of dimeric clusters, while the impact on tetrameric clusters is small. Strong agreement between experiment and theory merited extension of this analysis to hypothetical clusters with S(2-) substituted by N and C-atom donor ligands as well as FeMoco itself. These results show that very strong electron donors are required to appreciably modulate the electronic structure of tetrameric (or larger) iron sulfur clusters, pointing to a possible role of the central C(4-) in FeMoco.