Role of the azadithiolate cofactor in models for [FeFe]-hydrogenase: Novel structures and catalytic implications

Article abstract of DOI:10.1021/ja103998v

This paper summarizes studies on the redox behavior of synthetic models for the [FeFe]-hydrogenases, consisting of diiron dithiolato carbonyl complexes bearing the amine cofactor and its N-benzyl derivative. Of specific interest are the causes of the low

Full text of DOI:10.1021/ja103998v

Published on Web 11/29/2010
Role of the Azadithiolate Cofactor in Models for
[FeFe]-Hydrogenase: Novel Structures and Catalytic
Implications
Matthew T. Olsen, Thomas B. Rauchfuss,* and Scott R. Wilson
Department of Chemistry, UniVersity of Illinois at Urbana-Champaign,
Urbana, Illinois 61801, United States
Received May 15, 2010; E-mail: rauchfuz@illinois.edu
Abstract: This paper summarizes studies on the redox behavior of synthetic models for the [FeFe]-
hydrogenases, consisting of diiron dithiolato carbonyl complexes bearing the amine cofactor and its
N-benzyl derivative. Of specific interest are the causes of the low reactivity of oxidized models toward
H2, which contrasts with the high activity of these enzymes for H2 oxidation. The redox and acid-base
properties of the model complexes [Fe2[(SCH2)2NR](CO)3(dppv)(PMe3)]+ ([2]+ for R ) H and [2′]+ for
R ) CH2C6H5, dppv ) cis-1,2-bis(diphenylphosphino)ethylene)) indicate that addition of H2 followed
by deprotonation are (i) endothermic for the mixed valence (FeIIFeI) state and (ii) exothermic for the
diferrous (FeIIFeII) state. The diferrous state is shown to be unstable with respect to coordination of
the amine to Fe, a derivative of which was characterized crystallographically. The redox and acid-base
properties for the mixed valence models differ strongly for those containing the amine cofactor versus
those derived from propanedithiolate. Protonation of [2′]+ induces disproportionation to a 1:1 mixture
of the ammonium [H2′]+ (FeIFeI) and the dication [2′]2+ (FeIIFeII). This effect is consistent with substantial
enhancement of the basicity of the amine in the FeIFeI state vs the FeIIFeI state. The FeIFeI ammonium
compounds are rapid and efficient H-atom donors toward the nitroxyl compound TEMPO. The atom
transfer is proposed to proceed via the hydride. Collectively, the results suggest that proton-coupled
electron-transfer pathways should be considered for H2 activation by the [FeFe]-hydrogenases.
Introduction
The catalytic chemistry of hydrogen evolution and oxida-
tion is topical because H2 is a versatile reagent and a
promising carrier of energy.1,2 New approaches to this area
of catalysis have been inspired by the hydrogenase enzymes,
and studies on the [FeFe]-hydrogenases have proven espe-
cially influential.3 We and others have proposed that catalysis
occurs at a single coordination site on one Fe center of the
diiron subunit (Figure 1),4,5 with participation of various
cofactors.
Figure 1. Active site of the oxidized state (Hox) of the [FeFe]-hydrogenase
(left),7,8 showing the azadithiolate cofactor and a vacant site on the distal
iron center.9 Model complex for the Hox state of the active site (right), with
organophosphorus ligands in place of the cyanide and 4Fe-4S cofactors.
Ongoing research in this area focuses on elucidating the
electronic features of the bimetallic site (oxidation state, redox
potentials, asymmetry) and equipping models with the cofactors
required for efficient catalysis. Thus, models have evolved
from the simple Fe2(SR)2(CO)6 to substituted derivatives
Fe2(SR)2(CO)6-xLx, which exhibit the two essential attributes
of hydrogenases, acid-base and redox behavior. Two cofactors
are of functional significance since they enhance the redox or
acid-base properties inherent in the diiron center. First, the
redox-active 4Fe-4S cluster allows the diiron subsite, which
operates via a 1e- couple, to effect 2e- redox reactions, as
required by the H2/2H+ redox couple. Second, and very relevant
to this report, the amine-containing dithiolate cofactor4,5 is
proposed to relay protons to and from the distal Fe.6
(1) Kubas, G. J. Metal Dihydrogen and σ-Bond Complexes; Kluwer
Academic/Plenum: New York, 2001.
(2) Vincent, K. A.; Parkin, A.; Armstrong, F. A. Chem. ReV. 2007, 107,
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130, 16834–16835.
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123, 1596–1601.
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7507–7509.
Synthetic models differ from the diiron site in the protein
in three important ways. First, most models feature organo-
phosphorus ligands such as cis-1,2-C2H2(PPh2)2 (dppv) and
PMe3 in place of the cyanide cofactors. This change enables
9
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J. AM. CHEM. SOC. 2010, 132, 17733–17740 17733

A R T I C L E S
Olsen et al.
Scheme 1. Regiochemistry of Protonation of Tri- and Tetrasubstituted Diiron Azadithiolato Carbonyl Complexes6,9
mechanistic studies without the complications of reactions
at FeCN. Second, with a single exception,10 models omit the
4Fe-4S cofactor that is found in the 6-Fe “H-cluster” (Figure
1). Finally, the model complexes differ from the active site
in the stereochemistry of one of the iron centers. In the
protein, the distal Fe center adopts an “inverted” (also
described as “rotated”11) structure in which a CO ligand
occupies a semibridging position between the two Fe centers.
This stereochemistry exposes a coordination site adjacent to
the amine of the dithiolate cofactor. The inverted structure
is observed in the oxidized models of the type [Fe2(SR)2-
(CO)4L2]+ and [Fe2(SR)2(CO)3L3]+,12-15 but such inverted
structures are rarely observed in reduced diiron models.16,17
Theoretical studies indicate that rotated structures are de-
stabilized by about 10 kcal in model complexes.11
More recent models incorporate the amine cofactor, which
we call azadithiolate (adt ) (SCH2)2NH2-). N-Protonation
of such compounds shifts the reduction potential of the diiron
center by ∼0.5 V and the oxidation potential by ∼0.2 V.18,19
Of relevance to the enymatic mechanism, the complex
Fe2(adt)(CO)2(dppv)2 electrocatalyzes hydrogen evolution
from weaker acids than is possible for the related complexes
lacking the amine, for example, Fe2(pdt)(CO)2(dppv)2 (pdt
) S2(CH2)32-).6 Catalysis by these electron-rich models
proceeds via the intermediacy of an iron hydride, for which
the rates of formation and deprotonation are modified by the
amine. Such amine-complemented models for the Hox state
are ideal systems to explore factors relevant to H2 oxidation.
In the present report, we examine the interplay between the
acid-base behavior of the amine and the redox properties
of the Fe2 centers in Fe2(adt)(CO)3(dppv)(PMe3).9 Protonation
of Fe2(adt)(CO)3(dppv)(PMe3) gives the ammonium deriva-
tive as the only spectroscopically detectable tautomer. Via a
first-order pathway, the ammonium compound tautomerizes
slowly at room temperature in CH2Cl2 solution to the isomeric
“µ-hydride”, which features H- bound to both Fe centers
(Scheme 1).9,20
In contrast to the “trisphosphine” discussed above, the
tetrasubstituted diiron dithiolates form spectroscopically
detectable terminal hydrides. The enzyme is thought to
operate via such terminal hydrides (indicated as t-H), not
µ-hydrides. For [(t-H)Fe2(adt)(CO)2(dppv)2]BF4, the pKCa D Cl
2
2
is between 5.7 and 8.2.6 The terminal hydride and ammonium
tautomers of this complex coexist in comparable amounts in
CH2Cl2 solution (Scheme 1). Indicative of the subtleties of
-
this system is the finding that high concentrations of BF4
shift the equilibrium from the hydride toward the ammonium
tautomer.6
The process by which H2 is activated by diiron dithiolato
complexes came into focus with the finding that H2 is only
slowly oxidized by [Fe2(adt)(CO)3(dppv)(PMe3)]+ (at 1800
psi H2, rate ≈ 10-4 s-1),9 whereas the enzyme from
21
DesulfoVibrio gigas oxidizes H2 at 105 s-1
.
The low
reactivity of mixed valence models toward H2 is generally
understandable because the heterolytic scission of H2 by iron
characteristically requires ferrous centers.1 Theoretical studies
show that the diferrous state of the diiron subsite is well
suited for activation of H2.22 Diferrous µ-hydride complexes
catalyze H-D exchange between H2 and D2O, albeit only
photochemically.23 Diferrous compounds that contain a
vacant coordination site are rare,24,25 but unsaturated mono-
nuclear ferrous complexes have much precedence and often
(10) Tard, C.; Liu, X.; Ibrahim, S. K.; Bruschi, M.; De Gioia, L.; Davies,
S. C.; Yang, X.; Wang, L.-S.; Sawers, G.; Pickett, C. J. Nature 2005,
433, 610–614.
(11) Tye, J. W.; Darensbourg, M. Y.; Hall, M. B. Inorg. Chem. 2006, 45,
1552–1559.
(12) Justice, A. K.; Rauchfuss, T. B.; Wilson, S. R. Angew. Chem., Int.
Ed. 2007, 46, 6152–6154.
(13) Justice, A. K.; De Gioia, L.; Nilges, M. J.; Rauchfuss, T. B.; Wilson,
S. R.; Zampella, G. Inorg. Chem. 2008, 47, 7405–7414.
(14) Liu, T.; Darensbourg, M. Y. J. Am. Chem. Soc. 2007, 129, 7008–
7009.
(15) Thomas, C. M.; Liu, T.; Hall, M. B.; Darensbourg, M. Y. Inorg. Chem.
2008, 47, 7009–7024.
(16) Olsen, M. T.; Bruschi, M.; De Gioia, L.; Rauchfuss, T. B.; Wilson,
S. R. J. Am. Chem. Soc. 2008, 130, 12021–12030.
(20) Barton, B. E.; Zampella, G.; Justice, A. K.; De Gioia, L.; Rauchfuss,
T. B.; Wilson, S. R. Dalton Trans. 2010, 3011–3019.
(21) Fontecilla-Camps, J. C.; Volbeda, A.; Cavazza, C.; Nicolet, Y. Chem.
ReV. 2007, 107, 4273–4303.
(17) Cheah, M. H.; Tard, C.; Borg, S. J.; Liu, X.; Ibrahim, S. K.; Pickett,
C. J.; Best, S. P. J. Am. Chem. Soc. 2007, 129, 11085–11092.
(18) Eilers, G.; Schwartz, L.; Stein, M.; Zampella, G.; De Gioia, L.; Ott,
S.; Lomoth, R. Chem.sEur. J. 2007, 13, 7075–7084.
(19) Ezzaher, S.; Orain, P.; Capon, J.; Gloaguen, F.; Petillon, F.; Roisnel,
T.; Schollhammer, P.; Talarmin, J. Chem. Commun. 2008, 2547, 2549.
(22) Siegbahn, P. E. M.; Tye, J. W.; Hall, M. B. Chem. ReV. 2007, 107,
4414–4435.
(23) Zhao, X.; Chiang, C.-Y.; Miller, M. L.; Rampersad, M. V.; Darens-
bourg, M. Y. J. Am. Chem. Soc. 2003, 125, 518–524.
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17734 J. AM. CHEM. SOC. VOL. 132, NO. 50, 2010

Role of the Azadithiolate Cofactor in Models
A R T I C L E S
form η2-H2 complexes.26,27 Furthermore, amine-complement-
ed mononuclear ferrous phosphine complexes have been
shown to undergo redox-triggered tautomerization (eq 1).28
Figure 2. Structure of the dication in [2′(MeCN)](BF4)2. Thermal ellipsoids
set at the 30% probability level and hydrogen atoms are not shown.
Results
Table 1. Selected Bond Distances (Å) and Angles (deg) for
[2′(MeCN)](BF4)2
Synthesis and Characterization of Diferrous K3-Azadithiolato
Complexes. On a preparative scale and consistent with ample
precedent,12-15 oxidation of Fe2[(SCH2)2X](CO)3(dppv)-
(PMe3) with Fc+ was found to yield the mixed valence FeIIFeI
derivatives (“Hox models”), where X ) CH2, NH, NBn, and
O, for 1, 2, 2′, and 3, respectively (Bn ) CH2C6H5).9,12 These
cationic derivatives were isolated using bulky arylborate
counteranions, which are essential for the stabilization of Hox
models.9 The azadithiolates were found to undergo a second
bond
distance
bonds
angles
Fe(1)-N(1)
Fe(1)-Fe(2)
Fe(1)-C(1)
Fe(2)-N(2)
Fe(1)-S(2)
Fe(2)-S(2)
2.098(8)
3.477(2)
1.753(11)
1.965(10)
2.336(3)
2.323(3)
N(1)-Fe(1)-S(2)
Fe(1)-S(2)-C(36)
Fe(2)-S(2)-C(36)
S(1)-Fe(1)-S(2)
S(1)-Fe(2)-S(2)
P(1)-Fe(1)-P(2)
72.9(2)
80.9(3)
107.7(4)
80.97(11)
81.45(11)
87.24(12)
by a pair of thiolates, are each octahedral. The coordination
spheres of the Fe subsites are described as Fe(CO)2(PMe3)-
(MeCN)(SR)2 and Fe(CO)(dppv)(amine)(SR)2. The S-Fe-N
angles are acute at ∼73°, but the other Fe-ligand bond lengths
and angles are within the normal range (Table 1).
oxidation with FcBArF , and in this way we generated
4
[2′](BArF )2 (FcBArF ) [Fe(C5H5)2]B(C6H3-3,5-(CF3)2)4).
4
4
The initial 31P NMR spectrum at -70 °C indicates that [2′]-
(BArF )2 is diamagnetic and Cs-symmetric. In FTIR spectra
4
The solution properties of [2′(MeCN)]2+ were examined by
variable-temperature 31P NMR spectroscopy. Dissolution of the
crystalline [2′(MeCN)](BF4)2 at -70 °C gave a compound with
the same spectroscopic signature as that obtained by addition
of solutions of [2′](BArF )2, the νCO bands are shifted to
4
higher energy by ∼40 cm-1 from the positions for [2′]+, and
all three bands occur in the terminal carbonyl region (2066,
2008, and 1977 cm-1). When we instead employed the
oxidant FcBF4, a spectroscopically distinct compound was
observed (Supporting Information).
of MeCN to a CD2Cl2 solution of [2′](BArF ) generated at -70
4 2
°C. Over the course of ∼24 h at 20 °C, this species isomerized
to a second symmetrical isomer (two 31P NMR signals) (eq 2,
Treatment of a CD2Cl2 solution of [2′]2+ with MeCN was
Figure 3). Solutions of [2′](BArF ) were found to rapidly and
4 2
found to afford stable adducts, regardless of the counteranion,
irreversibly form an adduct upon treatment with 1 atm of CO.
In contrast, monocation [2′]+ binds CO reversibly, and the
adducts are only observable at low temperatures.9,13 Treatment
of the formula [2′(MeCN)]2+. Although the BArF - salts
4
-
afforded tacky oils, the BF4 salts readily crystallized. The
of [2′](BArF ) with 1800 psi H2 for 30 h gave [2′(µ-H)]+ as
crystallographic analysis of this salt revealed a diiron dithiolate
as expected, but unlike all previously reported azadithiolato
complexes,29-31 the amine is coordinated to Fe (Figure 2). The
Fe· · ·Fe distance of 3.447(2) Å is nonbonding, which is also
uncommon.24,32-34 The two iron centers, which are still linked
4 2
well as smaller amounts of [Fe(H)(CO)3(dppv)]+. Additionally,
[2′]2+ was found to react at low temperatures with PhSiH3 to
give the hydride [2′(µ-H)]+.
(24) van der Vlugt, J. I.; Rauchfuss, T. B.; Wilson, S. R. Chem.sEur. J.
2005, 12, 90–98.
(25) Justice, A. K.; Nilges, M. J.; Rauchfuss, T. B.; Wilson, S. R.; De
Gioia, L.; Zampella, G. J. Am. Chem. Soc. 2008, 130, 5293–5301.
(26) Kubas, G. J. Chem. ReV. 2007, 107, 4152–4205.
(27) Landau, S. E.; Morris, R. H.; Lough, A. J. Inorg. Chem. 1999, 38,
6060–6068.
(28) Henry, R. M.; Shoemaker, R. K.; Dubois, D. L.; Rakowski DuBois,
M. J. Am. Chem. Soc. 2006, 128, 3002–3010.
(29) Lawrence, J. D.; Li, H.; Rauchfuss, T. B.; Be´nard, M.; Rohmer, M.-
M. Angew Chem., Int. Ed. 2001, 40, 1768–1771.
Electrochemical Properties of Diiron Azadithiolates. Diiron
dithiolates of the formula Fe2[(SCH2)2X](CO)3(dppv)(PMe3)
undergo a reversible 1e- oxidation for X ) CH2, NH,
NCH2C6H5, and O (for 1, 2, 2′, and 3; see Figure 4, eq 3, and
(30) Ott, S.; Kritikos, M.; Åkermark, B.; Sun, L.; Lomoth, R. Angew. Chem.,
Int. Ed. 2004, 43, 1006–1009.
(31) Dong, W.; Wang, M.; Liu, X.; Jin, K.; Li, G.; Wang, F.; Sun, L. Chem.
Commun. 2006, 305–307.
9
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A R T I C L E S
Olsen et al.
creased by 130 and 177 mV for 2′ and 2, respectively. This
separation of electrochemical events is commonly observed in
noncoordinating electrolytes,35 and the larger value of ∆E for
2 versus 2′ is attributable to the ability of smaller fluoroanions
such as PF6- to engage in hydrogen-bonding.36 Upon addition
of MeCN to CH2Cl2 solutions of 2′, E2 becomes irreversible,
and two closely spaced cathodic waves are observed at -0.80
and -0.90 V. The strong effect of MeCN is consistent with the
formation of the adduct [2′(MeCN)]2+
.
Figure 3. 31P NMR spectra (CD2Cl2) of a fresh solution of [2′](BArF )2 at
4
-193 K (top), after treatment with CD3CN (middle), and after allowing
the same solution to stand at 293 K for 48 h. Signals at >δ70 are assigned
to dppv and those absorbing at <δ40 are assigned to PMe3.
Acid-Base Reactions. The pKCa D Cl values of the ammonium
compounds [H2′]+ and [H2]+ were measured as 3.3 and 3.2,
2
2
respectively, by titration of 2′ and 2 with [HPMe2Ph]BF4
37
(pKCa D Cl ) 5.7). The pKCa H CN value for [H2′]+ was determined
2
2
3
to be 13.1 by titration with ClCH2CO2H (pKCa H CN ) 15.3). We
3
could not directly determine the corresponding pKa of [H2′]2+
because [2′]+ undergoes quasi-disproportionation upon treatment
with acids, even in solution at -78 °C. The product mixture
consists of equal amounts of the reduced ammonium species
[H2′]+ and the dication [2′]2+ (eq 4, Figure 5).
Figure 4. Cyclic voltammograms of a CH2Cl2 solution of 1 (black) and 2′
(red) illustrative of the effect of the azadithiolate on the second anodic event.
Conditions: 0.001 M 2′, 0.300 M [(C4H9)4N]PF6, CH2Cl2, 20 °C, 0.1 V/s
scan rate.
Table 2). For 2′, the ratios of the oxidation and reduction
currents (ipc/ipa) are >0.9 at a scan rate of 0.100 V/s in
noncoordinating solvents (CH2Cl2). The linear dependence of
ip on (scan rate)0.5 also indicates a diffusion-controlled process.
Oxidations corresponding to the [Fe2(SR)2]+/2+ (FeIIFeI/
FeIIFeII) couple proved highly dependent on the dithiolate
(Figure 4 and eq 3). For the propane- and oxadithiolato
compounds, but not the azadithiolates, a poorly reversible second
oxidation is observed at 0.890 ( 0.040 V more anodic than the
[Fe2(SR)2]0/+ couple. Unlike the amine-free derivatives, the
[Fe2(SR)2]+/2+ couple for the azadithiolates 2 and 2′ occurs at
mild potentials and displays full reversibility. Interestingly ∆E
for 2 is significantly smaller than that for 2′. When noncoor-
The proton-induced quasi-disproportionation of [2′]+ (eq 4)
is driven by the strong oxidizing ability of [H2′]2+. The
requirement of 0.5 equiv of acid for the reaction in eq 2 was
confirmed. Furthermore, >0.5 equiv of H(OEt2)2BArF4 was found
not to affect the product distribution, a result consistent with
the low basicity of [2′]2+, wherein the amine is coordinated to
Fe. In contrast to this behavior, mixed-valence Fe(I)Fe(II)
complexes lacking azadithiolates are unreactive toward
acid. For example, a CH2Cl2 solution of [Fe2(S2C3H6)(CO)3-
(dppv)(PMe3)]BArF was unaffected by treatment with
4
H(OEt2)2BArF at 20 °C.
4
Together with the pKa for [H2′]+, E1/2 for the [H2′]+/2+ couple
would allow us to calculate the pKa of the mixed valence
ammonium cation [H2′]2+. The [H2′]+/2+ couple is irreversible,
dinating [(C4H9)4N]BArF electrolyte was employed, ∆E in-
4
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17736 J. AM. CHEM. SOC. VOL. 132, NO. 50, 2010

Role of the Azadithiolate Cofactor in Models
A R T I C L E S
Table 2. Half-wave Potentials (V) for the [Fe2(SR)2]0/+ and [Fe2(SR)2]+/2+ Couples for Fe2[(SCH2)2X](CO)3(dppv)(PMe3)a
dithiolate
electrolyte
E1 for [Fe2(SR)2]0/+ (∆Ep, V) [ipc/ipa]
E2 for [Fe2(SR)2]+/2+ (∆Ep) [ipc/ipa]
E2 - E1
(SCH2)2NBn (2′)
(SCH2)2NBn (2′)
(SCH2)2NH (2)
(SCH2)2NH (2)
(SCH2)2CH2 (1)
(S2C2H4)
[(C4H9)4N]PF6
[(C4H9)4N]BArF
[(C4H9)4N]PF6
[(C4H9)4N]BArF
[(C4H9)4N]PF6
[(C4H9)4N]PF6
[(C4H9)4N]PF6
[(C4H9)4N]PF6
[(C4H9)4N]PF6
-0.643 (0.118) [>0.9]
-0.715 (0.111) [0.9]
-0.561 (0.095)b
-0.624 (0.075) [>0.9]
-0.609 (0.126) [>0.9]
-0.469 (0.121) [>0.9]
-0.528 (0.139) [>0.9]
Ep/2 ) 0.040 (irrev.)
Ep/2 ) 0.050 (irrev.)
-0.128 (0.147) [>0.9]
-0.070 (0.222) [0.7]c
-0.363 (0.101)b
0.515
0.645
0.198
0.375
0.965
0.930
0.840
4
4
-0.249 (0.175) [0.1]c
0.356 (0.160) [0.2]
0.345 (0.143) [0.5]
0.353 (0.233) [0.1]
(SCH2)2O (3)
[(SCH2)2NBn(H)]+ ([H2′]+)
[(SCH2)2NH2]+ ([H2]+)
a Conditions: 1 mM diiron complex, 100 mM [Bu4N]PF6, CH2Cl2 solution, vs Fc0/+, 0.1 V/s scan rate. Under our experimental conditions, an internal
standard of Fc (1 mM) displayed ∆Ep ≈ 100 mV. The ipa/ipa values for E1 were recorded under conditions where the scan range did not extend to E2.
b The ipc/ipa ratio was not determined. The close separation of the two oxidation steps precludes accurate measurement of this current ratio. c At fast scan
rates the cathodic return wave of E2 becomes broadened making the ipc/ipa value an inaccurate representation of reversibility. At slow scan rates, E2 is
fully reversible.
Figure 5. IR spectra (CH2Cl2 solution) for [2′]+ (top), the products of its
TEMPO faster than did [H2′]+ under similar conditions: the
reaction with 0.5 equiv of H(OEt2)2BArF4 (middle top), [2′](BArF )2 (middle
4
reaction was complete in minutes vs ∼60 min for the Bn
bottom), and [H2′]+ generated by protonation of 2′ with H(OEt2)2BArF
4
(bottom). Component IR bands (CH2Cl2) are as follows: [2′]+ 2017, 1965,
derivative at 199 K.
1867 cm-1; [2′]2+ 2065, 2009, 1977; [H2′]+ 1960, 1925, 1898 cm-1
.
Insights into a possible mechanism of the hydrogen-atom
transfer reactions were provided by experiments with the
terminal hydrides [HFe2[(SCH2)2NR](CO)2(dppv)2]+ and
[HFe2(pdt)(CO)2(dppv)2]+.6 In CH2Cl2 solution, both species
were found to react (t1/2 ≈ 10 min, 199 K) with TEMPO to
give the corresponding mixed-valence Fe(II)Fe(I) derivatives.25
The IR signatures for the diferrous hydride starting materials
and mixed valence products overlap, thus we conducted these
oxidations under an atmosphere of CO, which rapidly affords
the CO adducts that display distinctive IR signatures.25
Scheme 2. Bordwell Calculation at 20 °C of the pKCa D Cl of [H2′]2+
Assuming E1/2 of the [H2′]+/2+ Couple as 0.04 V
2
2
thus precluding accurate determination of E1/2. Nonetheless,
estimating E1/2 as the potential of the anodic wave at half-height
would indicate that 1e- oxidation of [H2′]+ decreases the
basicity of the amine by as much as 109 (CH2Cl2 solution,
Scheme 2).
H-Atom Transfer Reactions. The electron-rich N-protonated
azadithiolato complexes were found to serve as H-atom donors.
Thus, treatment of [H2′]+ with 1 equiv of 2,2,6,6-tetrameth-
ylpiperidin-1-oxyl (TEMPO), an H-atom abstracting agent,38
immediately and quantitatively yielded [2′]+ at 293 °C (eq 5,
R2NO ) TEMPO). This reaction is conveniently monitored by
IR spectroscopy in the νCO region.
When the reaction was monitored by in situ IR spectroscopy
at low temperatures, a transient build-up of 2′ was detected.
This species results from the reversible deprotonation of [H2′]+
by TEMPOH, the product of eq 5.39 At 199 K, the rate of
disappearance of [H2′]+ is 8.13 × 10-3 s-1 M-1. By measuring
the temperature dependence of the rate constant over the range
199-229 K, we determined that ∆Gq is 13.5 kcal/mol (199 K).
The secondary ammonium [H2]+ was observed to react with
Conclusions
The hydrogenases function by coupling or combining
acid-base and redox properties. The present study examined
the interplay of these properties in a diiron model that
contains both a base and a redox center. We report three
unusual findings:
(i) The mildness and reversibility of the FeIIFeI/FeIIFeII
couple in models containing the amine cofactor arises from
the formation of an Fe-N bond. In the absence of the amine,
32e- diferrous dithiolates which are analogues of [Fe2(pdt)-
(CO)3(dppv)(PMe3)]2+, are predicted to be stabilized by
agostic interactions involving the central methylene of the
dithiolate. We expect that amine binding would be stronger
than an agostic interaction, thus stabilizing this oxidation.40,41
(32) Boyke, C. A.; Rauchfuss, T. B.; Wilson, S. R.; Rohmer, M.-M.;
Be´nard, M. J. Am. Chem. Soc. 2004, 126, 15151–15160.
(33) Boyke, C. A.; van der Vlugt, J. I.; Rauchfuss, T. B.; Wilson, S. R.;
Zampella, G.; De Gioia, L. J. Am. Chem. Soc. 2005, 127, 11010–
11018.
9
J. AM. CHEM. SOC. VOL. 132, NO. 50, 2010 17737

A R T I C L E S
Olsen et al.
Figure 6. Free energy changes (vs E(Fc0/+) ) 0 V) for the hydrogenation of mixed-valence and diferrous dithiolato complexes using data obtained for
[Fe2[(SCH2)2NR](CO)3(dppv)(PMe3)]n (n ) +, 2+). The calculation assumes that the proton binds to a base of pKaMeCN ) 10.
Table 3. Estimated Affinities of [2′]+ for H+, H·, and H- (kcal/mol)
The hydride acceptor strength of the diferrous center, e.g.,
in MeCN Solution (20 °C)
[2′]2+ (assuming κ2-adt), -88 kcal/mol, is sufficiently exergonic
∆G(H+)
∆G(H•)
-56
∆G(H-)
-48
that H2 heterolysis is favorable. No biophysical evidence exists,
however, for an unsaturated diferrous state for the enzyme. In
fact, Nature might avoid this state because it would be unstable
with respect to coordination of the amine. The 2e- change
required for exergonic H2 activation can however proceed via
a PCET pathway,42 avoiding formation of the Lewis acidic
diferrous state. In this scenario, the appended 4Fe-4S cluster
is poised to provide the oxidizing equivalent (eq 6). PCET has
recently been proposed for other hydrogen redox reactions.3
15
Our measurements suggest that coordination of the amine
stabilizes the diferrous state by ∼11 kcal/mol as indicated
by ∆EFeIIFeI/FeIIFeII
.
(ii) The FeIFeI ammonium center serves as an efficient H-atom
donor, with concomitant Fe-centered redox. This finding
demonstrates the ability of hydrogenase models and, by implica-
tion, the enzyme to participate in proton-coupled electron
transfer (PCET).
(iii) The basicity of the amine is highly sensitive to the
oxidation state of the underlying diiron centers.
The [FeFe]-hydrogenases are characterized by reduced and
oxidized states, respectively, Hred and Hox, that differ by 1e-.
In terms of enzyme mechanism, the reduced state activates
protons and the oxidized state activates H2. The oxidation state
for the diiron center in Hred remains uncertain but is likely either
a diferrous hydride or a disubferrous ammonium, which would
be readily interconverted.6 As we demonstrated in this work,
Hred and Hox are separated formally as well as operationally
by H•.
Our measurements bear on the mechanism for activation of
H2. In the heterolytic pathway, which is assumed for all
hydrogenases,26 H2 is a source of H-, invariably bound to an
Fe(II), and H+, which is usually bound to an organic base. We
show that the binding of hydride to Fe(II)Fe(I) complexes is
far less favorable than that to Fe(II)Fe(II) derivatives (Figure
6). The hydride acceptor strength of [2′]+, -48 kcal/mol, is
insufficient to compensate for the energy required for the
heterolysis of H2 (Table 3). Thus H2 activation by [2′]+ is
predicted to be unfavorable, even when coupled to the neutral-
ization of the proton by a moderately strong base.
The relevance of PCET pathways is reinforced by the facile
transfer of H• from the ammonium and hydride tautomers of
the diiron dithiolates, [Fe2[(SCH2)2NHR](CO)3(dppv)(PMe3)]+
and [HFe2(SR)2(CO)2(dppv)2]+, respectively.
The κ3-aminodithiolate ligand may be relevant to recent
observations on the [FeFe]-hydrogenases: upon being oxidized
at ∼0 V (vs SHE), the enzyme from DesulfoVibrio desulfuricans
reversibly deactivates to a state that is protected against oxidative
(aerobic) damage.43,44 It is assumed that this protection is
provided by a ligand that occupies the apical site on the distal
(34) van der Vlugt, J. I.; Rauchfuss, T. B.; Whaley, C. M.; Wilson, S. R.
J. Am. Chem. Soc. 2005, 127, 16012–16013.
(35) Geiger, W. E.; Barriere, F. Acc. Chem. Res. 2010, 43, 1030–1039.
(36) Heiden, Z. M.; Rauchfuss, T. B. J. Am. Chem. Soc. 2009, 131, 3593–
3600.
(37) Li, T.; Lough, A. J.; Morris, R. H. Chem.sEur. J. 2007, 13, 3796–
3803.
(38) Anelli, P. L.; Biffi, C.; Montanari, F.; Quici, S. J. Org. Chem. 1987,
52, 2559–2562.
(39) Sen, V. D.; Golubev, V. A. J. Phys. Org. Chem. 2008, 22, 138–143.
(40) Bruschi, M.; Fantucci, P.; De Gioia, L. Inorg. Chem. 2003, 42, 4773–
4781.
(41) Geiger, W. E.; Ohrenberg, N. C.; Yeomans, B.; Connelly, N. G.;
Emslie, D. J. H. J. Am. Chem. Soc. 2005, 125, 8680–8688.
(42) Mayer, J. M. Annu. ReV. Phys. Chem. 2004, 55, 363–390.
(43) Vincent, K. A.; Parkin, A.; Lenz, O.; Albracht, S. P. J.; Fontecilla-
Camps, J. C.; Cammack, R.; Friedrich, B.; Armstrong, F. A. J. Am.
Chem. Soc. 2005, 127, 18179–18189.
(44) van Dijk, C.; van Berkel-Arts, A.; Veeger, C. FEBS Lett. 1983, 156,
340–344.
9
17738 J. AM. CHEM. SOC. VOL. 132, NO. 50, 2010

Role of the Azadithiolate Cofactor in Models
A R T I C L E S
Fe. Although this blocking ligand might be water or hydroxide,2,43
the amine could also serve this protective role.
Hydrogenation of [2′](BArF )2. A solution of [2′](BArF )2 was
4
4
generated by the addition of 5 mL of CH2Cl2 to a mixture of 0.025
g (0.029 mmol) of 2′ and 0.064 g (0.058 mmol) of FcBArF at 20
4
°C. The solution of [2′](BArF )2 was pressurized (Parr bomb) with
4
Materials and Methods
1800 psi H2 for 30
h
to give [2′(µ-H)]+ (~50%) and
Synthetic methods for Fe2[(SCH2)2NBn](CO)3(dppv)(PMe3) have
been recently described.9 In situ IR measurements employed a
[Fe(H)(CO)3(dppv)]+ (∼15%) as verified by 31P and 1H NMR
analysis.49
React-IR 4000 (Mettler-Toledo). Compounds 1,45 2,45 2′,9 3,9
Treatment of [2′](BArF )2 with PhSiH3. A mixture of 0.050 g
4
47
4
FcBArF ,46 and H(OEt2)2BArF
were prepared as previously
(0.058 mmol) [2′](BArF ) and 0.121 g (0.116 mmol) FcBArF4 was
4
4 2
reported. 2,2,6,6-Tetramethylpiperidine 1-oxyl (TEMPO) and
Cp*2Co were purchased from Sigma Aldrich and sublimed before
use. Rate constants were obtained by simulation of experimental
data using the program Kintecus.48
cooled in an acetone/CO2 bath, and to it was added 2 mL of CH2Cl2.
In situ IR spectra indicated the presence of [2′](BArF )2. IR
4
(CH2Cl2): 2066, 2008, 1977. To this mixture was added 0.2 mL of
PhSiH3. After ∼30 min, the [2′](BArF ) had been consumed. After
4 2
Protonation of [Fe2[(SCH2)2NBn](CO)3(dppv)(PMe3)]BArF . To
warming to 20 °C, the sample was found to be spectroscopically
4
1
a solution of 0.025 g (0.029 mmol) of 2′ in 5 mL of CH2Cl2 was
(31P and H NMR, IR, ESI-MS) identical to [Fe2(µ-H)[(SCH2)2-
added a solution of 0.030 g (0.029 mmol) FcBArF in 5 mL of
NBn](CO)3(dppv)(PMe3)]BArF .9
4
4
Oxidation of [Fe2[(SCH2)2N(H)R](CO)3(dppv)(PMe3)]BArF
CH2Cl2. The resulting purple solution was thermally equilibrated
in an acetone/CO2 bath for 10 min. A solution of 0.014 g (0.015
4
with TEMPO (R ) H, Bn). A solution of [2′H]BArF was
4
mmol) of H(OEt2)2BArF in 2 mL of CH2Cl2 was added to the
4
generated at -78 °C by the addition of 0.8 mL of CH2Cl2 to a
mixture of 0.023 g (0.027 mmol) of 2′ and 0.027 g (0.027 mmol)
reaction mixture. The solution immediately became orange in color,
and the IR spectrum indicated the presence of only [2′](BArF )2
of H(OEt2)2BArF . Treatment of this solution with 0.103 g (0.66
4
4
and [H2′]BArF (see Figure 5). The presence of [H2′]+ was
mmol) of TEMPO gave [2′]+. Similar spectra were obtained using
[2H]+ in place of [2′H]+. We independently confirmed by IR
spectroscopy that [2′H]+ was fully deprotonated by 1 equiv of
TEMPOH, the organic product of the H-atom transfer reaction (see
eq 3). In a related experiment, we found that exposure of a solution
of TEMPOH and [2′H]+ to air rapidly gave [2′]+. Precautions were
taken to avoid this facile aerobic oxidation pathway.
4
confirmed by allowing it to isomerize to its µ-H counterpart. Upon
warming to 20 °C, the reaction mixture was filtered through Celite,
and the high-field 1H NMR spectrum (CD2Cl2) confirmed the
presence of [2′(µ-H)]+. Under analogous conditions, a solution of
[1]BArF4 in CH2Cl2 was shown by IR spectroscopy to be unaffected
by the addition of H(OEt2)2BArF , even after warming to 25 °C.
4
[Fe2[(SCH2)2NBn](CO)3(dppv)(PMe3)](BArF ) . Into a J. Young
4 2
[Fe2[(SCH2)2NBn](CO)3(dppv)(PMe3)(MeCN)](BF4)2. Obtain-
ing single crystals of salts derived from [2′]2+ proved challenging.
NMR tube containing 0.010 g (0.012 mmol) of 2′ and 0.025 g
(0.023 mmol) of FcBArF , immersed in liquid N2, was distilled 1
Various counterions (BF4-, SbF6-, BArF -, and BPh4-) and various
4
4
mL of CD2Cl2. The frozen mixture was thawed in an acetone/CO2
bath and mixed, with care not to let the contents leave the cold
bath. The tube was then quickly inserted into a spectrometer probe
precooled to -70 °C. Several hundred scans were necessary for a
well-resolved spectrum, possibly owing to the low solubility of the
salt. 31P NMR (CD2Cl2, -70 °C): δ 77.0 (s, dppv), 44.1 (s, PMe3).
Upon warming the sample, the spectrum became complex (see
Supporting Information).
solvent combinations (slow diffusion at -30 °C of hexanes, Et2O,
or toluene into CH2Cl2 solutions of the respective salts of [2′]2+
)
all afforded amorphous tacky solids. We thus turned to the adduct,
[2′(MeCN)]2+. To a Schlenk tube containing a mixture of 0.050 g
(0.06 mmol) 2′ and 0.032 g (0.12 mmol) of FcBF4, cooled to -78
°C, was added 8 mL of CH2Cl2. The solution was stirred vigorously
for 5 min, and then 0.1 mL of MeCN was added. Stirring was
stopped, and 40 mL of hexane was carefully layered on top of the
reaction mixture and allowed to diffuse at -30 °C. After ∼4 days,
red crystals had formed. The supernatant was filtered off to remove
ferrocene and then the crystalline solid was scrapped from the flask.
Finally, this material was dried in Vacuo, extracted into 5 mL of
CH2Cl2, filtered through Celite, and precipitated as an orange-
colored powder upon the addition of 20 mL of hexanes. IR (CH2Cl2,
cm-1): νCO ) 2065, 2042, 2001, 1974. 31P NMR (CD2Cl2, 20 °C):
δ 73.0 (s, dppv, isomer A), 72.9 (d, dppv, JP-P ) 13 Hz, isomer
A), 21.3 (d, J ) 13 Hz, PMe3, isomer A). 31P NMR (CD2Cl2, 48 h
at 20 °C): δ 79.9 (s, dppv, isomer B), 25.8 (s, PMe3, isomer B).
[Fe2[(SCH2)NBn](CO)3(dppv)(PMe3)(CD3CN)](BArF ) . A so-
4 2
lution of [2′](BArF ) in CD2Cl2 was generated in a J. Young NMR
4 2
tube as described above. The solution was frozen and re-evacuated,
and onto it was distilled 0.1 mL of CD3CN. The tube was thawed
in an acetone/CO2 bath and reinserted into the probe, which was
precooled to -70 °C. 31P NMR (CD2Cl2, -70 °C): δ 73.5 (d, dppv,
JP-P ) 11 Hz, isomer A), 73.0 (s, dppv, isomer A), 20.8 (d, J )
11 Hz, PMe3, isomer A). Chemical shifts vary slightly from the
-
isolated complex due to change in counterion (BF4 vs BArF -).
4
ESI-MS: m/z 432.9 [Fe2[(SCH2)2NBn](CO)3(dppv)(PMe3)]2+), 454.9
[Fe2[(SCH2)2NBn](CO)3(dppv)(PMe3)(CD3CN)]2, 619.4 ([FeCl-
(CO)2(dppv)(PMe3)]+), 900.7 ([Fe2[(SCH2)2NBn]Cl(CO)3(dppv)-
(PMe3)]+).
MS ESI: m/z
)
453.2 ([Fe2[(SCH2)2NBn](CO)3(dppv)-
(PMe3)(MeCN)]2+). The dppv P-Fe-P coupling is not resolved
(J < 5 Hz), instead the dppv signal is broadened (FWHH )14 Hz).
Anal. Calcd (Found) for C43H45B2F8Fe2N2O3P3S2: C, 47.81 (47.09);
H, 4.20 (4.41); N, 2.59 (2.40).
Fe2[(SCH2)2NBn](CO)4(dppv)(PMe3)](BArF ) ([2′CO](BArF ) ).
4 2
4 2
A solution of [2′](BArF )2 in CD2Cl2 was generated in a J. Young
4
valve NMR tube as described above. The solution was frozen, and
the tube was evacuated and then pressurized with 1 atm of CO.
The tube was thawed in an acetone/CO2 bath and then slowly
warmed to 20 °C. 31P NMR (CD2Cl2, 20 °C): δ 68.4 (m, dppv),
68.2 (m, dppv), 15.7 (d, J ) 11 Hz, PMe3). ESI-MS: m/z
446.9 ([Fe2[(SCH2)2NBn](CO)4(dppv)(PMe3)]2+), 619.4 ([FeCl-
(CO)2(dppv)(PMe3)]+), 900.7 ([Fe2[(SCH2)2NBn]Cl(CO)3(dppv)-
(PMe3)]+).
Single crystals were obtained from 8 mL of CH2Cl2 solution of
7 mM [2′](BF4)2, which was generated at -78 °C as described
above and then treated with 5 drops of MeCN. The solution was
then layered with 50 mL of hexane and stored at -30 °C. After 1
week, several red crystals had appeared. Alternatively, a 7 mM
solution of [2′]BF4 was treated with 1 drop of MeCN and then
layered with 50 mL of hexane. After 1 week, a single cluster of
red crystals had formed and were separated from the dark brown
solution.
Crystallography. Structure was phased by dual space methods.
Systematic conditions suggested the ambiguous space group P1. The
space group choice was confirmed by successful convergence of the
(45) Justice, A. K.; Zampella, G.; De Gioia, L.; Rauchfuss, T. B.; van der
Vlugt, J. I.; Wilson, S. R. Inorg. Chem. 2007, 46, 1655–1664.
(46) Le Bras, J.; Jiao, H.; Meyer, W. E.; Hampel, F.; Gladysz, J. A. J.
Organomet. Chem. 2000, 616, 54–66.
j
(47) Brookhart, M.; Grant, B.; Volpe, A. F., Jr. Organometallics 1992,
11, 3920–3922.
(49) Sowa, J. R., Jr.; Zanotti, V.; Facchin, G.; Angelici, R. J. J. Am. Chem.
Soc. 1992, 114, 160.
(48) Ianni, J. Kintecus, V3.962; 2010.
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J. AM. CHEM. SOC. VOL. 132, NO. 50, 2010 17739

A R T I C L E S
Olsen et al.
full-matrix least-squares refinement on F2. The highest peak in the
final difference Fourier map was located 2.6 Å from the nearest
aromatic H atom. This residual density located in a void suggests the
possibility of a partially occupied water solvate. The final map had no
other significant features. A final analysis of variance between observed
and calculated structure factors showed no dependence on amplitude
or resolution. The proposed model includes two disordered positions
for phenyl ring C20-25 of the host cation and two disordered positions
for one of two CH2Cl2 solvate molecules. Phenyl rings were refined
as rigid, idealized groups. A common geometry was imposed on the
disordered CH2Cl2 solvates using effective standard deviations of 0.01
and 0.02 Å for bond lengths and bond angles, respectively. Rigid-
bond restraints (esd 0.01) were imposed on displacement parameters
for all disordered sites, and similar displacement amplitudes (esd 0.01)
were imposed on disordered sites overlapping by less than the sum of
van der Waals radii. Methyl H atom positions were optimized by
rotation about R-C bonds with idealized C-H, R-H and H · · ·H
distances. Remaining H atoms were included as riding idealized
contributors. Methyl H atom U’s were assigned as 1.5 times Ueq of
the carrier atom; remaining H atom U’s were assigned as 1.2 times
carrier Ueq.
Electrochemistry. Cyclic voltammetry experiments were carried
out in a ∼10 mL scintillation vial inside of a glovebox. The working
electrode was a glassy carbon disk (0.3 cm in diameter), the
pseudoreference electrode Ag wire, and the counter electrode Pt
wire. Under our conditions (CH2Cl2 solution), we generally observed
that ∆Ep was ∼0.12 V for the [Fe2]0/+ couple, whereas an equimolar
internal standard of Fc displayed ∆Ep as ∼0.1 V. Potentials were
referenced vs the 0.001 M internal Fc standard.
Acknowledgment. This research was sponsored by NIH. M.T.O.
thanks the NIH for a CBI-Fellowship.
Supporting Information Available: Crystallographic informa-
tion file (cif) for [2′(MeCN)](BF4)2, thermodynamic calculations,
and associated spectra. This material is available free of charge
via the Internet at http://pubs.acs.org.
JA103998V
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17740 J. AM. CHEM. SOC. VOL. 132, NO. 50, 2010