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Iron Hydride Detection and Intramolecular Hydride Transfer in a Synthetic Model of Mono-Iron Hydrogenase with a CNS Chelate Gummadi Durgaprasad,† Zhu-Lin Xie,† and Michael J. Rose* Department of Chemistry, The University of Texas at Austin, Austin, Texas 78712, United States S Supporting Information *
ABSTRACT: We report the identification and reactivity of an iron hydride species in a synthetic model complex of monoiron hydrogenase. The hydride complex is derived from a phosphine-free CNS chelate that includes a Fe−CNH(O) bond (carbamoyl) as a mimic of the active site iron acyl. The reaction of [(OCHNNpySMe)Fe(CO)2(Br)] (1) with NaHBEt3 generates the iron hydride intermediate [(OCHNNpySMe)Fe(H)(CO)2] (2; δFe−H = −5.08 ppm). Above −40 °C, the hydride species extrudes CH3S− via intramolecular hydride transfer, which is stoichiometrically trapped in the structurally characterized dimer μ2(CH3S)2-[(OCHNNPh)Fe(CO)2]2 (3). Alternately, when activated by base (tBuOK), 1 undergoes desulfurization to form a cyclometalated species, [(OCNHNCPh)Fe(CO)2] (5); derivatization of 5 with PPh3 affords the structurally characterized species [(OCNHNC)Fe(CO)(PPh3)2] (6), indicating complex 6 as the common intermediate along each pathway of desulfurization.
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he enzyme monoiron hydrogenase (HMD) catalyzes a hydride transfer from dihydrogen (H2) to tetrahydromethenylmethanopterin (H4MPT+), which serves as a C1 carrier during the methanogenic reduction of carbon dioxide (CO2).1 This metalloenzyme (also called Hmd: H4MPT dehydrogenase) plays an obligate role in the metabolism of CO2 to methane (CO2 → CH4) in the absence of bioavailable nickel (i.e., in the absence of [NiFe] hydrogenase). Although there are other H2-activating enzymes, there are no other known biological examples of H2 activation by a mononuclear iron site. The active site of HMD exhibits a unique array of nonproteinaceous ligands (Scheme 1), including the cis-
reduction has spurred the synthesis of structural models of a HMD active site by Hu et al.3 and Song et al.,4 as well as functional studies by Meyer et al.5 One key intermediate in the catalytic cycle has been proposed as an iron(II) hydride,6 although such a species has not yet been detected in any enzymatic study. Thus, the identification and study of such a reactive species is of keen interest. Recent reports in the iron catalysis literature contain several examples of H2 activation and hydride transfer, wherein the catalytically active iron(II) is supported by ligation of one or two carbonyl ligands. The reported hydride transfer catalysts likely proceed through intermediates analogous to a putative fac-{Fe(H)(CO)2}+ fragment possibly encountered during enzymatic catalysis, although a concerted H2 cleavage mechanism is also possible.6b The iron dicarbonyl hydride motif has been observed in the nonbiomimetic pincer system in the complex [(PNHNNHP)Fe(H)(CO)2]+.7 However, there are no reports of a biomimetic, phosphine-free {Fe(H)(CO)2}+ unit. Herein, we report the identification of such a complex. In relation to the iron acyl motif found in the enzyme active site, we have utilized the related carbamoyl ligation of type {Fe−C(O)NH},8 in which the organometallic Fe−C(O) unit is retained. Pickett and co-workers reported complexes containing a “ferracyclic carbamoyl” unit,9,10 which served as
Scheme 1. Possible Mechanism of Heterolytic Splitting of H2 Performed by HMD6
dicarbonyls and the bidentate pyridone−acyl unit, which presents an organometallic Fe−C σ bond.2 The active site exhibits no redox activity, and only activates H2 in the presence of a substrate.1 The exact role of each donor moiety remains unclear, although the dicarbonyl motif enforces a low-spin, iron(II) configuration. The desire to develop inexpensive ironbased catalysts for hydrogenation, hydride transfer, and CO2 © XXXX American Chemical Society
Special Issue: Small Molecule Activation: From Biological Principles to Energy Applications Part 3 Received: July 30, 2015
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DOI: 10.1021/acs.inorgchem.5b01733 Inorg. Chem. XXXX, XXX, XXX−XXX
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Inorganic Chemistry structural models of the active site. To provide a more robust and stable framework for reactivity and hydride transfer studies, the ligand used herein presents a biomimetic CNS donor set in a single chelate. Reaction of the amino-appended N/S ligand with [Fe(CO)4(Br)2] in Et2O from −25 to −5 °C generates a copious yellow precipitate, accompanied by vigorous extrusion of carbon monoxide (CO) gas. Purification of this solid by chromatography through Al2O3 affords the carbamoyl bromide adduct [(OCHNNpySMe)Fe(CO)2(Br)] (1). The solid-state IR of 1 exhibits ν(CO) features at 2034 and 1974 cm−1 (enzyme = 2011 and 1944 cm−1). Solutions of 1 in tetrahydrofuran (THF)-d8 are remarkably stable in the presence of air or moisture (hours to days) and exhibit features (δN−H = 9.96 ppm; δS−CH3 = 2.60 ppm) consistent with the ligand coordinated to low-spin iron(II). To emulate an iron hydride intermediate as proposed for the enzymatic mechanism, complex 1 was treated directly with a hydride source. A pale-yellow THF-d8 solution of 1 was mixed with ∼1 equiv of NaHBEt3 at −70 °C. The resulting 1H NMR spectrum obtained at −70 °C (Figure 1) exhibits a notable peak
Scheme 2. Reactivity of Characterized Complexes 1−3, 5, and 6, as Well as Proposed Intermediate [4]
Figure 2. ORTEP diagram (30% ellipsoids) of 3. Hydrogen atoms except NH are omitted for clarity. Selected bond distances (Å) and angles (deg): Fe2−C1 = 1.939(2), Fe2−N2 = 2.083(2), Fe2−S1 = 2.3287(7), Fe2−S2 = 2.3679(7), Fe2−C14 = 1.751(3), Fe−C13 = 1.763(3); N1−C1−O1 = 119.0(2), Fe2−C1−N1 = 109.90(17), Fe2− C1−O1 = 130.9(2). Figure 1. Variable-temperature 1H NMR spectra (−70 to −10 °C, 400 MHz) for the reaction of 1 in THF-d8 with ∼1 equiv of NaHBEt3 to form the iron hydride species 2.
phenyl ring is twisted away from the core of the dimer. Notably, the Fe−C(O)NH carbamoyl unit [Fe−C = 1.939(2) Å] and the cis-dicarbonyl fragments remain essentially undisturbed. The bridging methyl thiolate units arrange the Fe−S distances at 2.3287(7) and 2.3679(7) Å, which fixes the two iron(II) ions at a distance of ∼3.54 Å within the Fe2S2 diamond core. The solid-state IR exhibits four red-shifted ν(CO) features at 2013, 1991, 1965, and 1923 cm−1 (see the Supporting Information, Figure S2) due to conversion of the neutral thioether(s) to the anionic thiolate(s). It is important to note that the conversion from the hydride species 2 to dimeric 3 is stoichiometric, suggesting a controlled reaction pathway of intramolecular hydride transfer, followed by dimerization. To investigate the possibility of the hydride acting as a base (NH-activating agent) in the reaction, complex 1 was treated with a strong base. The reaction of a yellow solution of 1 in THF with tBuOK at room temperature rapidly generates a dark-red solution and a beige precipitate (KBr). Subsequently, extraction of the product into C6D6 affords a 1H NMR spectrum (Figure 3, inset) indicative of a single species in solution. The resulting stable, yellow solid exhibits a red-shifted IR spectrum consistent with cis-dicarbonyl ligation, evidenced by ν(CO) = 2003 and 1940 cm−1 (Figure 3). The observation of a NH proton in the 1H NMR spectrum of this isolated species shifted upfield to 7.35 ppm (for 1, δNH = 9.96 ppm in THF-d8), as well as the lack of a thioether resonance near δCH3 ≈ 2.60 ppm and the aforementioned desulfurization, led to
at −5.08 ppm, attributable to a Fe−H species. This resonance exhibits an intermediate value compared with other reported iron(II) carbonyl hydrides, such as [(PNHNNHP)Fe(H)(CO)2]+ (δFe−H = −7.47 ppm) and [(PNNP)Fe(H)(CO)] (δFe−H = −2.25 ppm).7,11 The Fe−H resonance is accompanied by a downfield shift in the NH feature to 11.66 ppm (parent 1; δN−H = 9.96 ppm). The presence of the shifted (but not absent) NH resonance provides evidence that H2 is not eliminated, precluding the formation of a dearomatized intermediate at low temperature. On this basis, we assign the structure of the iron hydride intermediate as [(OCNHNPySMe)Fe(H)(CO)2] (2 in Scheme 2). The variable-temperature NMR study indicates that the hydride species 2 is stable between −70 and −40 °C. Above −40 °C, the Fe−H resonance decreases, indicating transformation to another species; this product was not readily identified by 1H NMR spectroscopy. To remedy this problem, a THF solution of 1 was treated with ∼1 equiv of NaHBEt3 at room temperature. Following the removal of THF and extraction into C6D6, the yellow product was redissolved in fluorobenzene/pentane to afford the dimeric species μ2(CH3S)2-[(OCNHNPh)Fe(CO)2]2 (3) as a structurally characterized complex (Figure 2). In this complex, the CAr−S bond found in 1 has been cleaved, and the resulting (protonated) B
DOI: 10.1021/acs.inorgchem.5b01733 Inorg. Chem. XXXX, XXX, XXX−XXX
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Inorganic Chemistry
the precursor [(iPr2PNHNNHPiPr2)Fe(CO)2]+ with zinc dust.7 Relatedly, Milstein and Huang individually reported the isolation of dearomatized complexes of the type [(PNP)M(CO)(H)(L)]+ (M = Fe, Ru) by analogous treatment with a base.12,13 It was desirable to prove that the five-coordinate cyclometallate 5 served as a common intermediate for both structurally characterized products (3 and 6). As such, a THF solution of 5 was treated with ∼1 equiv of thiophenol (PhSH) at room temperature. Following solvent exchange to C6D6, the 1 H NMR spectrum (see the Supporting Information, Figure S6) and the characteristic four-peak IR spectrum [ν(CO) = 2017, 1998, 1964, 1932 cm−1; see the Supporting Information, Figure S2] were similar to structurally characterized 3, indicating the formation of μ2-(PhS)2-[(OCNHNPh)Fe(CO)2]2 (3′). This reaction confirms 5 as the common intermediate along each pathway of desulfurization (tBuOK or NaHBEt3). In conclusion, we have studied the reactivity of an iron hydride intermediate (2) in a synthetic model of HMD. This Fe−H species promotes C−Sthioether bond cleavage and the formation of an iron(II) cyclometalate. However, the equatorial arrangement of the present CNS donor set is distinct from the facial CNS motif found in the active site.14 Future work will address this issue and incorporate the biomimetic thiolate and methylene−acyl unit to more accurately model the active site.
Figure 3. IR and 1H NMR (inset) spectra for 5 in the aromatic region. IR: ν(CO) 2003, ν(CO) 1940, ν(HNCO) 1606, ν(CNpy) 1579.
formulation of this species as the putative five-coordinate CNC pincer [(OCNHNCPh)Fe(CO)2] (5). To confirm the ligand binding mode of the putative cyclometalate 5, the complex was derivatized with PPh3 for structural characterization. The reaction of 5 with excess PPh3 in benzene afforded yellow crystals of [(OCNHNC)Fe(CO)(PPh3)2] (6; Figure 4). Crystallographic analysis confirms (i)
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ASSOCIATED CONTENT
* Supporting Information S
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.inorgchem.5b01733. X-ray crystallographic data in CIF format (CIF) Spectra and synthetic details (PDF)
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AUTHOR INFORMATION
Corresponding Author
Figure 4. Two ORTEP views (50% ellipsoids) of 6. PPh3 is truncated for clarity; all hydrogen atoms except NH are omitted for clarity. Selected bond distances (Å) and angles (deg): Fe−C11 = 2.009(2), Fe−C12 = 2.008(2), Fe−C13 = 1.725(2), Fe−N1 = 1.9540(18), Fe− P1 = 2.2531(6), Fe−P2 = 2.2525(6); C11−Fe−C12 = 159.36(9), N1−Fe−C13 = 174.36(9), P1−Fe−P2 = 174.92(3).
*E-mail:
[email protected]. Author Contributions †
These authors contributed equally to this work.
Notes
The authors declare no competing financial interest.
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desulfurization of the ligand framework and (ii) concomitant cyclometalation of the former C−S(CH3) carbon directly to the iron(II) center. Pseudooctahedral 6 again retains the Fe−C( O)NH carbamoyl unit, as well as one carbonyl; the remaining axial sites are occupied by PPh3. To determine the fate of the extruded sulfur unit, an analogous reaction was performed in the presence of PMe3 as a [S] scavenger. Extraction of the mixture into CDCl3 afforded a 31P NMR resonance at 30.3 ppm (Me3PS), as well as a gas chromatography−mass spectrometry peak at m/z 109 ([M + H+]) and a high-resolution mass spectrometry peak at m/z 108.0163 ([M+]; see the Supporting Information, Figures S16−S18). Thus, we conclude that the base-assisted extrusion product is elemental sulfur. We postulate the formation of the de-aromatized species [(OCNNS)Fe(CO)2] ([4] in Scheme 2). Recent work has shown the feasibility of dearomatized iron complexes such as [4] involving metal/ligand cooperativity during catalysis with pincer complexes. For example, Kirchner and co-workers reported that the dearomatized pincer complex [(iPr2PNNNHPiPr2)Fe(CO)2]+ is formed upon treatment of
ACKNOWLEDGMENTS The authors gratefully acknowledge the Robert A. Welch Foundation (F-1822) and the ACS Petroleum Research Fund (PRF 53542-DN13) for financial support.
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REFERENCES
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DOI: 10.1021/acs.inorgchem.5b01733 Inorg. Chem. XXXX, XXX, XXX−XXX
