Terminal hydride in [FeFe]-hydrogenase model has lower potential for H 2 production than the isomeric bridging hydride

Article abstract of DOI:10.1021/ic800030y

Protonation of the symmetrical tetraphosphine complexes Fe ₂(S₂C_nH_2n)(CO)₂(dppv) ₂ afforded the corresponding terminal hydrides, establishing that even symmetrical diiron(I) dithiolates undergo protonation at terminal sites. The terminal hydride [HFe₂(S₂C₃H ₆)(CO)₂(dppv)₂]⁺ was found to catalyze proton reduction at potentials 200 mV milder than the isomeric bridging hydride, thereby establishing a thermodynamic advantage for catalysis operating via terminal hydride. The azadithiolate protonates to afford, [Fe ₂[(SCH₂)₂NH₂](CO) ₂(dppv)₂]⁺, [HFe₂[(SCH ₂)₂NH](CO)₂-(dppv)₂]⁺, and [HFe₂[(SCH₂)₂NH₂](CO) ₂(dppv)₂]²⁺, depending on conditions.

Full text of DOI:10.1021/ic800030y

Inorg. Chem. 2008, 47, 2261-2263
Terminal Hydride in [FeFe]-Hydrogenase Model Has Lower Potential for
H2 Production Than the Isomeric Bridging Hydride
Bryan E. Barton and Thomas B. Rauchfuss*
Department of Chemistry, UniVersity of Illinois at Urbana-Champaign, Urbana, Illinois 61801
Received January 8, 2008
Protonation of the symmetrical tetraphosphine complexes
Fe2(S2CnH2n)(CO)2(dppv)2 afforded the corresponding terminal
hydrides, establishing that even symmetrical diiron(I) dithiolates
undergo protonation at terminal sites. The terminal hydride
[HFe2(S2C3H6)(CO)2(dppv)2]+ was found to catalyze proton reduc-
tion at potentials 200 mV milder than the isomeric bridging hydride,
Figure 1. Structure of the [FeFe]-hydrogenase active site (Fep ) proximal
thereby establishing a thermodynamic advantage for catalysis
operating via terminal hydride. The azadithiolate protonates to
afford, [Fe2[(SCH2)2NH2](CO)2(dppv)2]+, [HFe2[(SCH2)2NH](CO)2-
(dppv)2]+, and [HFe2[(SCH2)2NH2](CO)2(dppv)2]2+, depending on
conditions.
iron center and Fed ) distal iron center).
phine ligands, these diiron dithiolato complexes are basic in
both Lewis and, as we show, Brønsted senses. The Fe2
complexes are protonated by HBF4 · Et2O at room tempera-
ture to afford the expected bridging hydrides [Fe2(S2CnH2n)-
(µ-H)(CO)2(dppv)2]+, [1µΗ]+ and [2µΗ]+. One isomer of
the propanedithiolato derivative, [2µΗ]BF4, was character-
ized crystallographically, which established the location of
the µ-hydrido ligand (Supporting Information).
Recent research has significantly advanced our under-
standing of nature’s most efficient catalysts for hydrogen
production, the [FeFe]-hydrogenases (Figure 1).1 First, the
mixed-valence Hox state has been replicated with synthetic
models providing a coordinatively unsaturated model featur-
ing a vacant coordination site on the distal iron, ap-
proximately trans to the Fe-Fe vector.2,3 Second, unsym-
metrically substituted diiron dithiolatotetracarbonyls have
been shown to protonate at a single Fe site to afford terminal
hydrides that have been characterized by 1H NMR spectros-
copy at low temperatures (∼-75 °C).4 The protonation at a
single Fe center conforms to a mechanism whereby proton
reduction, hydrogen oxidation, and CO inhibition all occur
via substrate binding at a single site on the distal Fe. In this
paper, we describe results that support the single-site
hypothesis for hydrogenogenesis by examining factors that
influence the stability and reactivity of terminal hydrides.
Our starting complexes are the recently described diiron(I)
dithiolates Fe2(S2CnH2n)(CO)2(dppv)2 [n ) 2 (1), 3 (2); dppv
) cis-1,2-bis(diphenylphosphino)ethene].5 With four phos-
When 1 and 2 were protonated at low temperatures, we
1
observed high-field H NMR signals characteristic of hy-
drides (for [1H]BF4, δ -6.1, t, JPH ) 74 Hz; for [2H]BF4,
δ -3.5, t, JPH ) 78 Hz).4,6 These kinetic products were
observed to isomerize to the µ-hydrido isomers upon
warming. The ethanedithiolate, [1H]+, isomerized in minutes
even at -20 °C to [1µΗ]+, whereas the propanedithiolate
[2H]+, derivative proved more stable (t1/2 ∼ 10 min at 20
°C). The slower isomerization of the propanedithiolate (pdt)
derivative is ascribable to the steric clash between dppv and
the middle methylene group of pdt, which inhibits rotation
of the FeH(CO)(dppv) site (eq 1).7
(4) (a) Ezzaher, S.; Capon, J.-F.; Gloaguen, F.; Pétillon, F. Y.; Scholl-
hammer, P.; Talarmin, J.; Pichon, R.; Kervarec, N. Inorg. Chem. 2007,
46, 3426–3428. (b) Morvan, D.; Capon, J.-F.; Gloaguen, F.; Le Goff,
A.; Marchivie, M.; Michaud, F.; Schollhammer, P.; Talarmin, J.;
Yaouanc, J.-J. Organometallics 2007, 26, 2042–2052. (c) Orain, P.-
Y.; Capon, J.-F.; Kervarec, N.; Gloaguen, F.; Pétillon, F.; Pichon, R.;
Schollhammer, P.; Talarmin, J. Dalton Trans. 2007, 3754–3756.
(5) Justice, A. K.; Zampella, G.; De Gioia, L.; Rauchfuss, T. B. Chem.
Commun. 2007, 2019–2021.
*
To whom correspondence should be addressed. E-mail:
rauchfuz@uiuc.edu.
(1) (a) Fontecilla-Camps, J. C.; Volbeda, A.; Cavazza, C.; Nicolet, Y.
Chem. ReV. 2007, 107, 4273–4303. (b) Siegbahn, P. E. M.; Tye, J. W.;
Hall, M. B. Chem. ReV. 2007, 107, 4414–4435. (c) Vignais, P. M.;
Billoud, B. Chem. ReV. 2007, 107, 4206–4272.
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7009.
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J. Am. Chem. Soc. 2005, 127, 16012–16013.
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10.1021/ic800030y CCC: $40.75  2008 American Chemical Society
Inorganic Chemistry, Vol. 47, No. 7, 2008 2261
Published on Web 03/12/2008

COMMUNICATION
The isomerization of the terminal [2H]+ to the bridging
[2µ]+ hydride proceeds via a first-order pathway (k ) 1 ×
10-3 s-1, 25 °C) and was unaffected by solvent polarity or
the presence of CO. These findings are indicative of an
intramolecular process, consistent with isomerization kinetics
previously reported.6 The temperature dependence of the
rates indicate ∆Hq ) 80 kJ/mol and ∆Sq ) -23 J/mol K,
also consistent with an intramolecular process that proceeds
without ligand dissociation.
Figure 2. Cyclic voltammetry (200 mV/s, 0 °C) of a 1 mM solution of
[HFe2(S2C3H6)(CO)2(dppv)2][BF4] as a mixture of terminal and bridging
isomers (a) and the same solution scanned after isomerization (b).
In light of the lability of the tetracarbonyl hydrides recently
described by Schollhammer et al.,4 our results suggest that
the stability of the terminal hydride (vs the bridging hydride)
depends mainly on the basicity of the Fe2 center. The
electronic asymmetry of the Fe2 unit also plays a role because
terminal hydrides have been detected for the protonation of
unsymmetrical Fe2(S2C3H6)(CO)4(PR3)2 isomers but not yet
for the corresponding symmetrical isomers.
Methylene chloride solutions of [2H]+ are unreactive
toward HOTf, showing no tendency to evolve H2, nor did
the FeH group exchange with CD3OD over the course of
3 h. In contrast, the more basic trimethylphosphine derivative
[HFe2(S2C2H4)(µ-CO)(CO)(PMe3)4]+ (νCO ) 1940 and 1874
cm-1 in CH3CN solution) reacts with HBF4 in CH3CN to
afford H2.6 On the basis of νCO, [2H]BF4 is the better
spectroscopic model for the Hred state of the enzyme
(observed: 1964 (s) and 1905 (m) cm-1 vs Hred for D.d.:8
1965, 1916, and 1894 cm-1).
Cyclic voltammetric (CV) studies (CH2Cl2 solution, 0 °C,
vs Ag/AgCl) show that the terminal hydride [2Η]BF4 reduces
at ∼200 mV milder than the isomeric bridging hydride
[2µΗ]BF4 (Figure 2). The reduction current (ip,c) for [2H]BF4
in a CH2Cl2 solution displayed a first-order dependence on
[HBF4], indicative of proton reduction catalysis. For catalytic
proton reduction involving [2H]BF4, we propose the catalytic
cycle depicted in Figure 3. Reduction of [2Η]BF4 is a 1e-
process as indicated by the similarity of the dependence of
ip vs V1/2 for both [2Η]BF4 and its conjugate base 2, which
we have established undergoes a 1e- oxidation to 2+ (the
recently described model of Hox).9 At 0 °C, the [2H]+/0 couple
is reversible even at scan rates as slow as 25 mV/s, which
implies that the reduced hydride has a half-life of at least
several seconds at this temperature. The pathway for hydro-
genogenesis therefore entails protonation of the mixed-
valence hydride [2H]0. We can estimate the pKa of [2H]0 by
the strength of the acids that render the [2H]+/0 couple
irreversible. For these CV titrations, we used phosphonium
acids, for which Morris has established a pKa scale for
Figure 3. Proposed mechanism of hydrogenogenesis by [2H]+.
CD2Cl2 solutions.10 In the presence of [HPPh2Me]BF4
(pKCD Cl ) 3.3), the [2H]+/0 couple was reversible; however,
2
2
the couple became irreversible with the slightly stronger acid
[HPPh3]BF4 (pKCD Cl ∼ 1.6). These experiments show that
2
2
reduction of [2H]+ increases the basicity of the iron hydride
by at least five pKCD Cl units ([2H]+ is unreactive toward
2
2
HBF4, pKCD Cl ∼ -4.7). Tilset et al. have reported that
redox-state changes can change the acidity of hydrides by
more than 20 pKa units in monometallic complexes.11
According to our proposed mechanism, the reduced species
[2H]0 undergoes protonation to release H2, affording 2+.
Under the conditions of the experiment, 2+ would be reduced
to 2, completing the cycle.3 The isomeric bridging hydride
[2µH]+ also catalyzes proton reduction catalysis but at
potentials more negatiVe by 200 mV.
2
2
The azadithiolate Fe2[(SCH2)2NH](CO)2(dppv)2 (3) also
undergoes protonation at -40 °C to give a terminal hydride
[3H]+ (δ -4.2, t, JPH ) 73 Hz). The stereochemistry of the
1
protonation, indicated by the H and 31P NMR data, again
places the hydride in an apical site adjacent to the amine
(8) De Lacey, A. L.; Fernández, V. M.; Rousset, M.; Cammack, R. Chem.
ReV. 2007, 107, 4304–4330.
(10) Li, T.; Lough, A. J.; Morris, R. H. Chem.sEur. J. 2007, 13, 3796–
3803.
(9) Justice, A. K.; Nilges, M.; Rauchfuss, T. B.; Wilson, S. R.; De Gioia,
L.; Zampella, G. J. Am. Chem. Soc. 2008, 130, in press.
(11) Ryan, O. B.; Tilset, M.; Parker, V. D. J. Am. Chem. Soc. 1990, 112,
2618–2626.
2262 Inorganic Chemistry, Vol. 47, No. 7, 2008

COMMUNICATION
the ammonium center is highly acidic, being deprotonated
even by MeOD. The ammonium hydride [3H2]2+ is stable
in a CH2Cl2 solution but released H2 when the protonation
was conducted in a MeCN solution. The acid–base properties
of 3 are clearly sensitive to the medium14 and will be
explored more fully in a future report. Preliminary CV
experiments indicate that [3H]+ is a better catalyst than
[2H]+, in terms of both kinetics and thermodynamics, but
itsthermallabilitycomplicatestheelectrochemicalmeasurements.
In summary, this work supports the following mechanistic
features for the production of H2 by these models for
[FeFe]-hydrogenases:
(i) The protonation of diiron dithiolato complexes can
occur at a single Fe site, even for symmetrical (FeI)2
compounds.
(ii) The terminal hydride is thermodynamically more easily
reduced than the isomeric µ-hydride.
(iii) Isomerization of the terminal hydride is inhibited both
by the basicity of the Fe2 complex as well as by the steric
size of the dithiolate in the models. In the enzyme, terminal-
bridge isomerization may also be inhibited by hydrogen
bonding between CNdistal and a ꢀ-ammonium center of a
nearby, highly conserved lysine residue (358 in CpI and 237
in DdH).15
(iv) Even though terminal hydrides are more readily
protonated than their isomeric bridging hydrides,16 diferrous
terminal hydrides are not necessarily poised for hydrogeno-
genesis. Their hydridic character is, however, enhanced by
several pKa units upon 1e- reduction.
Figure 4. Protonation of Fe2[(SCH2)2NH](CO)2(dppv)2.
and cis to the phosphine ligands. For the related systems,
Fe2[(SCH2)2NAr](CO)6-x(PR3)x, N-protonation occurs rap-
idly,12 which suggests that [3H]+ arises via migration of the
proton from N to Fe.
Compound [3H]+ isomerized to the bridging hydride in
seconds at 0 °C, faster than [2H]+ but more slowly than
[1H]+. As for [2H]+, CD2Cl2 solutions of [3H]+ do not
exchange with CD3OD during the course of the isomeriza-
tion. Double protonation of 3 with H(Et2O)2BArF4 (selected
because it can be accurately weighed) occurred readily to
give the terminal hydride bearing an adjacent ammonium
Acknowledgment. This research was supported by the
National Institutes of Health and the Petroleum Research
Fund.
center, [3H2][BArF ] . This species was characterized by 1H
4 2
Supporting Information Available: Experimental methods,
spectra, and voltammograms and CIF for the crystal structure. This
materialisavailablefreeofchargeviatheInternetathttp://pubs.acs.org.
NMR (high field), 31P NMR, and IR (νCO region) spec-
troscopies. The protonated derivatives of 3 can be accessed
by selective deprotonation of [3H2]2+ (Figure 4).
IC800030Y
Monoiron hydrides exchange intramolecularly with adja-
cent ammonium centers,13 but the rate depends on the relative
(13) Jacobsen, G. M.; Shoemaker, R. K.; Rakowski DuBois, M.; DuBois,
D. L. Organometallics 2007, 26, 4964–4971.
basicities of the amine and the FeH centers. In [3H2][BArF ] ,
4 2
(14) Curtis, C. J.; Miedaner, A.; Ciancanelli, R.; Ellis, W. W.; Noll, B. C.;
Rakowski DuBois, M.; DuBois, D. L. Inorg. Chem. 2003, 42, 216–
227.
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Ott, S.; Lomoth, R. Chem.sEur. J. 2007, 13, 7075–7084. (b) Wang,
F.; Wang, M.; Liu, X.; Jin, K.; Dong, W.; Li, G.; Åkermark, B.; Sun,
L. Chem. Commun. 2005, 3221–3223. (c) Stanley, J. L.; Heiden, Z. M.;
Rauchfuss, T. B.; Wilson, S. R.; De Gioia, L.; Zampella, G.
Organometallics 2007, 27, 119–125.
(15) Nicolet, Y.; Lemon, B. J.; Fontecilla-Camps, J. C.; Peters, J. W. Trends
Biochem. Sci. 2000, 25, 138–143.
(16) Justice, A. K.; Linck, R. C.; Rauchfuss, T. B.; Wilson, S. R. J. Am.
Chem. Soc. 2004, 126, 13214–13215.
Inorganic Chemistry, Vol. 47, No. 7, 2008 2263