Synthesis and vibrational spectroscopy of 57Fe-labeled models of [NiFe] hydrogenase: First direct observation of a nickel-iron interaction

Article abstract of DOI:10.1039/c4cc04572f

A new route to iron carbonyls has enabled synthesis of ⁵⁷Fe-labeled [NiFe] hydrogenase mimic (OC)₃⁵⁷Fe(pdt)Ni(dppe). Its study by nuclear resonance vibrational spectroscopy revealed Ni-⁵⁷Fe vibrations, as confirmed by calculations. The modes are absent for [(OC)₃⁵⁷Fe(pdt)Ni(dppe)]⁺, which lacks Ni-⁵⁷Fe bonding, underscoring the utility of the analyses in identifying metal-metal interactions.

Full text of DOI:10.1039/c4cc04572f

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Synthesis and vibrational spectroscopy
57
of Fe-labeled models of [NiFe] hydrogenase: first
direct observation of a nickel–iron interaction†
David Schilter,*a Vladimir Pelmenschikov,b Hongxin Wang,cd Florian Meier,b
Leland B. Gee,c Yoshitaka Yoda,e Martin Kaupp,b Thomas B. Rauchfussa and
Stephen P. Cramer*cd
Cite this: Chem. Commun., 2014,
50, 13469
Received 16th June 2014,
Accepted 9th September 2014
DOI: 10.1039/c4cc04572f
www.rsc.org/chemcomm
A new route to iron carbonyls has enabled synthesis of 57Fe-labeled
[NiFe] hydrogenase mimic (OC)357Fe(pdt)Ni(dppe). Its study by nuclear
resonance vibrational spectroscopy revealed Ni–57Fe vibrations, as
confirmed by calculations. The modes are absent for [(OC)357Fe(pdt)-
Ni(dppe)]+, which lacks Ni–57Fe bonding, underscoring the utility of
the analyses in identifying metal–metal interactions.
Despite our extremely low atmospheric concentration of dihydrogen
(B1 ppm), this substrate is a key metabolite of many anaerobic
bacteria.1 In such living systems can be found the most prevalent
enzymes for hydrogen processing, the nickel–iron hydrogenases
([NiFe]–H2ases).1,2 These electrocatalysts specifically mediate the
redox reaction H2 " 2H+ + 2eꢀ at several hundred turnovers
per second.3 Their heterobimetallic active sites exist in several states,
some of which are summarized below (Fig. 1, left and centre).
Fig. 1 Key [NiFe]–H2ase states (left and centre) and two model complexes
(right).
This has recently enabled observation of characteristic Fe–CN/
The active sites feature Ni bound to four cysteinato residues, Fe–CO bending and stretching modes in [NiFe]–H2ase (Ni–A and
two of which bridge to an Fe(CO)(CN)2 fragment. In the Ni–C Ni–R) and the Fe subsite model [Fe(benzenedithiolato)(CN)2CO]2ꢀ 6
.
state, Ni(III)Fe(II) centres bind a bridging hydride (Hꢀ), reductive However, no NRVS studies have reported on metal–metal bonding,
elimination of which affords Ni–L.4 Thus, H+ is abstracted by a which is expected for low-valent clusters like Ni–L and its models.4,7
terminal cys ligand (Fig. 1, centre top), leaving a Ni(I)Fe(II) core
A near-complete [NiFe]–H2ase mimic is the Ni(II)Fe(I) species
[(OC)3Fe(pdt)Ni(dppe)]+ ([1]+, pdt2ꢀ ꢀS(CH2)3Sꢀ; dppe = 1,2-bis-
with a 2eꢀ bond between the metals.4
=
The use of vibrational spectroscopy to study [NiFe]–H2ase is (diphenylphosphino)ethane), a model for Ni–L, albeit with metal
convenient in that its active site features chromophores easily oxidation states reversed (Fig. 1, right).8 This S = 1/2 model is
identifiable by such techniques. Spectral analyses are often aided prepared from (OC)3Fe(pdt)Ni(dppe) (1),9 itself the subject of density
by comparison to data from synthetic models5 whose structures are functional theory (DFT) and resonance Raman investigations.10
well understood. Specificity for 57Fe-coupled modes is afforded Disclosed here is methodology for 57Fe-labeled prototypes
by nuclear resonance vibrational spectroscopy (NRVS, vide infra). [(OC)357Fe(pdt)Ni(dppe)]0/+ ([1]0/+), enabling the study of metal–
metal bonding with NRVS.
The Ni(I)Fe(I) complex 1 is usually accessed by interaction of
a Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana,
(pdt)Ni(dppe) with an Fe carbonyl such as Fe2(CO)9 or Fe(CO)4I2.11–14
IL 61801, USA. E-mail: schilter@illinois.edu
The precursor to these, Fe(CO)5, is not conveniently prepared from
b
¨
¨
Institut fur Chemie, Technische Universitat Berlin, 10623 Berlin, Germany
c Department of Chemistry, University of California, Davis, CA 95616, USA.
E-mail: spjcramer@ucdavis.edu
elemental Fe, a factor that necessitated a new route adaptable to
57Fe incorporation. Thus, metallic Fe was converted to the organo-
soluble FeI2 source Fe2I4(iPrOH)4,15 which, upon combination with
(pdt)Ni(dppe), gave the known diiodide I2Fe(pdt)Ni(dppe).14 While
the diiodide does not bind CO in CH2Cl2, when treated with
AgBF4 it converts to the putative electrophile ‘[IFe(pdt)Ni(dppe)]+’
(or perhaps its dimer), which undergoes carbonylation to afford
d Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley,
CA 94720, USA
e JASRI, SPring-8, Sayo-gun, Hyogo 679-5198, Japan
† Electronic supplementary information (ESI) available: Experimental proce-
dures, spectral data, computational chemistry details, animated vibrational
modes as GIFs. See DOI: 10.1039/c4cc04572f
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Scheme 1
[(OC)3FeI(pdt)Ni(dppe)]+ ([1I]+).14 Reduction with CoCp2 gave 1
in yields comparable to the (pdt)Ni(dppe)/Fe2(CO)9 route.11
In adapting the synthesis to the Ni57Fe target, elemental 57Fe
was oxidized to 57Fe2I4(iPrOH)4,12 which was converted into violet
57
[(OC)3 FeI(pdt)Ni(dppe)]+ (ESI-MS: m/z 829.5 [10I]+ vs. 828.9 [1I]+),
57
with reduction affording green (OC)3 Fe(pdt)Ni(dppe) (10) in 35%
yield (Scheme 1).
Fig. 2 Observed NRVS spectra for [10]+ (thick red lines, (a) and (b)) and 10
(thick blue lines, (a) and (c)) vs. DFT calculated 57Fe PVDOS spectra for [10]+
(thin red line, (b)) and 10 (thin blue line, (c)). Calculated Fe–Ni KED (green) is
given in (b) for [10]+, and in (c) for 10. Key bands observed for 10 are labelled
in (a), with DFT counterparts in (c) indicated by vertical lines. Modes giving
rise to bands with significant Fe–Ni character are marked (*) and shown in
Fig. 3 and Fig. S10 (ESI†). For 0–650 cmꢀ1 spectra, see Fig. S9 (ESI†).
While nCO energies and analytical and 31P{1H} NMR data for 10
are virtually identical to those of natural abundance 1, LI-FDI-MS
(liquid introduction field desorption ionization mass spectrometry)
analyses are telling. Soft ionization of non-polar 10 and 1 allowed
for the detection of parent cations at m/z 702.9 and 701.9, respec-
tively (Fig. S4, ESI†). Oxidation of 10 with FcBF4 afforded mixed-
valent salt [10]BF4, whose EPR signal is broadened relative to that of
[1]BF4 due to hyperfine interactions.
The assignment of vibrational bands was elaborated using
DFT calculations on [10]0/+ as detailed in the ESI;† simulated NRVS
Investigations into Ni–Fe bonding in the new 57Fe-labeled (57Fe PVDOS) and Fe–Ni KED diagrams for [10]+ and 10 are also
variants of the reduced and oxidized complexes (respectively 10 and presented in Fig. 2b and c, respectively. Band positions and inten-
[10]+) were undertaken using NRVS. This technique, enabled by sities in the calculated and observed spectra are largely in agreement
the development of third generation synchrotron sources, insertion (particularly in Fig. 2c; see also Fig. S9, ESI†). In the case of [10]+,
devices and advanced X-ray optics,16–18 involves scanning an some differences are assigned to impurities (10 and/or [10H]+). The
extremely monochromatic (e.g. 0.8 meV) X-ray beam through a band for 10 at 158 cmꢀ1, calculated by DFT at 157 cmꢀ1, indeed
¨
nuclear resonance of a Mossbauer-active isotope (e.g. 14.4 keV for involves stretching of the Fe–Ni bond symmetrical to a Ni–P1 stretch
57Fe). Subsequent relaxation causes the generation/annihilation of (see Fig. 3, and the ESI† for animations). Such a vibrational coupling
phonons, the detection of which reveals all modes in which the 57Fe in the Fe–Ni–P1 triad implicates a strong Fe–Ni interaction, and it
nucleus moves along the direction of the incident X-ray. NRVS has has no complement in the normal modes pool calculated for [1]+.
several advantages over traditional IR and resonance Raman spectro-
While very prominent in NRVS (owing to the large 57Fe displace-
scopies,19 not least in terms of element and isotope specificity ment), the 157 cmꢀ1 band is weaker (B5%) in the Ni–Fe KED
and absence of the optical selection rules, which have allowed for diagram, which reflects relative motion of Fe and Ni. Other Ni–Fe
the resolution of nFe–X (X = S, P, Cl, CO, CN, NO) vibrations stretches, such as those calculated at 266, 311, and 386 cmꢀ1 (see in
in complicated systems.6,13,19,20 This relatively new but powerful Fig. 2c), are considerably stronger (representing 13%, 9%, and 11%
technique in inorganic and biological iron chemistry is applied here total Ni–Fe KED, respectively). Yet only the first two modes can be
to [10]0/+. The analysed spectra in terms of 57Fe partial vibrational associated with bands observed at 262 and 303 cmꢀ1, while the last
density of states (PVDOS) are given in Fig. 2.
one has vanishing NRVS intensity (Fig. 2a). The modes at 266, 311,
Intense bands assigned to nFe–CO and dFe–CO modes were observed and 386 cmꢀ1 have lower 57Fe PVDOS intensity as they involve
at 440–630 cmꢀ1, with full-range NRVS spectra and Fe–C(O) kinetic displacement mostly of Ni (rather than Fe), this movement being
energy distribution (KED) diagrams presented in Fig. S9 (ESI†). evident from the DFT results (Fig. S10, ESI†). Analysis of Fe–Ni
Similar signals were found for [NiFe]–H2ase.6 It was expected that vibrations is further complicated by vibrational coupling to C/P/S
n
Fe–S, dFe–S and nFe–Ni bands, if observable, would lie at low energies atoms, in particular the bridging S donors. Notably, mixed nFe–Ni
(r400 cmꢀ1). Upon comparing data for 10 and [10]+ (Fig. 2a), a sharp modes in the 220–360 cmꢀ1 region involving up to 14% contribution
and prominent NRVS peak at 158 cmꢀ1 for 10 was noticed. This from the Fe–Ni stretch were also reported for 1.10
band, absent from the spectra of [10]+, was tentatively ascribed to
Structural (X-ray diffraction) and DFT studies on unlabeled
vibration of the Ni–Fe bond, such interactions not being significant [1]0/+ have suggested that the reduced Ni(I)Fe(I) species may
in [10]+. Differences in NRVS data of 10 and [10]+ were less marked in feature Ni–Fe bonding,9 while the oxidized Ni(II)Fe(I) does not.8
other spectral regions, although peaks for [10]+ were broader.
This was confirmed by re-analysing bonding in [1]0/+ using ELF,21
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Since the Fe(I) centre in [1]+ is electron poor (average nCO
=
2010 cmꢀ1)8 it cannot supply 2eꢀ for a Fe-Ni coordinate bond.
Another possibility, a covalent Ni–Fe bond, is unlikely due to the
low donicity of Ni(II). The metal centres in [1]+ are distant (our
DFT result: 2.80 Å), while those in electron-rich 1 (average nCO
=
1977 cmꢀ1) are sufficiently proximal (experimental: 2.47 Å,9 DFT:
2.46 Å) for covalent Fe–Ni bonding (see Table S2 and Fig. S3, ESI†
for structural and IR details).
Obtaining direct evidence of metal–metal bonding in molecular
systems is nontrivial, and distances do not guarantee presence/
absence of bonding. For example, EXAFS studies reveal similar
Fe–Ni distances for Ni–L and Ni–C,24 despite Ni not being bonded
to Fe in the latter. This highlights that (i) [NiFe]–H2ase active site
ligation is inflexible (relative to [1]0/+) and that (ii) EXAFS/XRD
studies typically only afford nuclear positions via core electron
density, with bonding electron density between metals being poorly
resolved.25 In rare cases when very high quality single crystal data
are obtained, multipole analysis, followed by topological analysis
of static electron density (versus inspection of difference maps)
can give insights into metal–metal bonding, as exemplified by
(re)investigation of the archetypal Mn2(CO)10.26
Fig. 3 Scaled arrow depiction of nuclear displacements for the normal
mode calculated for 10 at 157 cmꢀ1 (a symmetric Fe–Ni–P1 stretch, see
corresponding 57Fe PVDOS band in Fig. 2c). Key [10]0/+ modes are animated
in the ESI.†
Metal–metal bonding is common in organoiron chemistry, but
it also plays a role in the reduced states of some metalloenzymes,
stabilizing low-valent metal centres poised for substrate activation.7
In addition to [NiFe]–H2ase, Ni–Fe interactions are also proposed
for carbon monoxide dehydrogenase (CODH),7,27 with Ni–Ni
and Fe–Fe bonds being present in acetyl-CoA synthetase (ACS)7
and [FeFe]–H2ase,28 respectively. NRVS is demonstrably effec-
tive in unambiguous identification of low energy 57Fe-coupled
modes.13,20,29 Compared to IR and resonance Raman, it avoids
interference from solvent and ‘fingerprint’ bands, enabling
identification of Fe-coupled vibrations, such as the 158 cmꢀ1
nFe–Ni mode here. The use of NRVS to probe iron–metal modes
in everything from small molecules to iron enzymes is antici-
pated to provide a wealth of information on these catalysts.
While primordial routes to iron carbonyls have been reported
(e.g. the one-pot preparation of (CO)3Fe(pdt)Fe(CO)3 from
FeCl2),30 they are typically limited in scope and reproducibility.
In contrast, the Fe2I4(iPrOH)4/CO/CoCp2 strategy will likely be
generalizable and afford iron carbonyls of relevance to H2ases
and organoiron chemistry in general. With the isolation of
57Fe-labeled [NiFe]–H2ase mimics [10]0/+, the element and isotope
selectivity of NRVS was exploited to obtain the first vibrational
spectroscopic evidence of Fe–Ni interactions. These results serve
as an important benchmark, opening the door to work probing
metal–metal bonding in redox-active H2ase enzymes as well as
related enzymatic and model systems.
ELI-D,22 and QTAIM23 electron density-based methods (Fig. 4;
Fig. S11 and S12, ESI†), all of which indicated a Ni–Fe bond in 1.
Notably, the ELF/ELI-D bond attractor and the bond critical point
found by QTAIM are shifted from the Ni–Fe vector away from the
bridging S atoms, such that Fe(I) is (pseudo)octahedral. Bonding
involves overlap of two singly-occupied d(z2) orbitals and is absent
when Ni is oxidized, with [1]+ featuring a Fe-localized d(z2) SOMO. In
contrast, Ni–L has a SOMO with Ni d(z2) and d(x2 ꢀ y2) character,4
and a 2eꢀ Ni-Fe dative bond (optimized Fe–Ni distance: 2.47 Å).4
While [1]+ and Ni–L have the same electron count for the [NiFe]3+
site, only one has Ni–Fe bonding. A key distinction is Ni geometry,
which is planar in [1]+ but SF4-like in Ni–L.
Thanks are given to Drs Mark J. Nilges and Haijun Yao for
assistance with EPR and LI-FDI-MS, respectively. Financial
support was provided by the National Institutes of Health
(GM061153-10 to T.B.R. and GM-65440 to S.P.C.), U.S. Depart-
ment of Energy Office of Biological and Environmental Research
(DOE OBER) (S.P.C.), and the ‘Unifying Concepts in Catalysis’
initiative of the German Research Council (V.P., F.M., and M.K.).
NRVS experiments performed at SPring-8 BL09XU were funded
by JASRI (beamtime proposal 2013A0032).
Fig. 4 Electron localization function (ELF) analysis of the Ni–Fe bonding
in [1]0/+ (top/bottom). Ni–Fe bond attractor position for [1]0 is indicated by
the localized area in green (center-top), absent for [1]+. See Fig. S11 and
S12 (ESI†) for alternative bonding representations.
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