Aza- and oxadithiolates are probable proton relays in functional models for the [FeFe]-hydrogenases

Article abstract of DOI:10.1021/ja8057666

The dithiolate cofactor for the [FeFe]-hydrogenase models, Fe₂(xdt)(CO)₂(dppv)₂ (where xdt = 1,3-propanedithiolate (pdt), azadithiolate (adt), (SCH₂)₂NH, and oxadithiolate (odt), (SCH₂)₂O; dppv = cis-1,2-bis(diphenylphosphino)ethylene) have been probed for their functionality as proton relays enabling formation and deprotonation of terminal hydrides. Compared to the propanedithiolate derivative, the azadithiolate and oxaditiholate show enhanced rates of proton transfer between solution and the terminal site on one Fe center. The results are consistent with the heteroatom of the dithiolate serving a gating role for both protonation and deprotonation. The pK_a of the transiently formed ammonium (pK^CD2Cl2 5.7-8.2) or oxonium (pK^CD2Cl2 -4.7-1.6) regulates the proton transfer. As a consequence, only the azadithiolate is capable of yielding the terminal hydride from weak acids. The aza- and oxadithiolates manifested the advantages of proton relays: the odt derivative proved to be a faster catalyst for hydrogen evolution than the pdt derivative as indicated from cyclic voltammetry plots of i_c/i_p vs [H⁺]. The adt derivative was capable of proton reduction from the weak acid [HPMe₂Ph]BF₄ (pK^CD2Cl2 = 5.7). The proton relay function does not apply to the isomeric bridged-hydrides [Fe₂(xdt)(μ-H)(CO)₂(dppv)₂]⁺, where the hydride is too distant and too basic to interact to be affected by the heteroatomic relay site. None of these μ-H species can be deprotonated. Copyright

Full text of DOI:10.1021/ja8057666

Published on Web 11/21/2008
Aza- and Oxadithiolates Are Probable Proton Relays in Functional Models for
the [FeFe]-Hydrogenases
Bryan E. Barton, Matthew T. Olsen, and Thomas B. Rauchfuss*
School of Chemical Sciences, UniVersity of Illinois, Urbana, Illinois 61801
Received July 23, 2008; E-mail: rauchfuz@uiuc.edu
Scheme 1. Acid-Base Reactions of 1-3
The [FeFe]-hydrogenases are among the very best catalysts known for
the reduction of protons to dihydrogen, with turnover frequencies estimated
to be ∼6000 mol of H2/mol of enzyme per second operating at nearly
Nerstian potentials.1 The question about why the [FeFe]-hydrogenases are
so efficient is topical,2 and the answer is likely related to the incompletely
characterized dithiolate cofactor that bridges the diiron subunit. In 2001,
Nicolet et al. proposed that this dithiolate is the azadithiolate (adt,
(SCH2)2NH), wherein the amine functionality could relay protons to and
from the apical site on the distal Fe center.3 It is known that, unlike typical
amine bases, transition metals can be slow to protonate.4 The adt hypothesis
is attractive because it potentially shows how to couple the kinetic facility
of amine protonation with the redox abilities of iron hydrides. Indeed,
DuBois has demonstrated that amine bases constrained within diphosphine
ligands greatly accelerate both H2 uptake and production for mononuclear
iron and nickel phosphine complexes.5 A recent DFT investigation
suggests that the dithiolate cofactor is the oxadithiolate (odt, (SCH2)2O),
which also merits evaluation since protein crystallography cannot distin-
guish between C, N, and O.6
Efforts to understand and exploit the possible presence of the adt
cofactor have been underway for several years. The amine can be
protonated independently of the diiron site.7,8 However, N-protonation
has little effect on proton reduction by the catalysts of the general
type Fe2(µ-H)(SR)2L6, where µ-H indicates that the hydride bridges
the two Fe centers.9,10
dithiolate). These terminal hydrides undergo reduction at a milder
potential than the isomeric bridging hydride species, are catalytically
competent, and are sufficiently robust to study in detail.13 The crucial
unanswered question is whether a heteroatom in the dithiolate
participates in proton transfer to and from the terminal hydride. To
address this question, we report results that demonstrate a functional
role of oxa- and azadithiolates as proton relays. These experiments
are benchmarked relative to the third crystallographically feasible
dithiolate, propanedithiolate. We prepared Fe2(odt)(CO)2(dppv)2 from
the hexacarbonyl14 and confirmed spectroscopically (odt ) 2-oxopro-
pane-1,3-dithiolate).
Protonation of Fe2(odt)(CO)2(dppv)2 (3) at -78 °C with the strong
acid [H(Et2O)2]BArF4 afforded the terminal hydride [3(t-H)]BArF . 1H
4
and 31P NMR analysis confirmed that protonation occurred at a single
Fe center, characteristic of related derivatives.15 This terminal hydride
was found to isomerize upon warming to give the µ-hydride complex,
[3(µ-H)]BArF (2.6 × 10-4 s-1, -10 °C), a process following
4
unimolecular kinetics. The isomerization rate is similar to that for [2(t-
H)]BArF (1.4 × 10-4 s-1) but is faster than [1(t-H)]BArF (2.5 ×
4
4
Figure 1. Structure of diiron active site of the enzyme from D. desulfu-
ricans showing the dithiolate cofactor (turquoise/yellow).
10-5 s-1).
Odt and Adt Accelerate Deprotonation of [HFe2(xdt)(CO)2(diphos-
phine)2]+. We first compared the facility with which a CD2Cl2 solution
of [3(t-H)]BArF4 deprotonates. At -78 °C, [3(t-H)]BArF4 is unreactive
toward base, but upon warming to ∼0 °C, two products form, [3(µ-
H)]BArF4 and 3, as assayed by 1H and 31P NMR spectroscopy. The
ratio of these two products was unaffected by the concentration of the
base as well as its pKa, as indicated by deprotonations with both strong
and weak bases, respectively, tetramethylguanidine (TMGH+, pKa
The recent discovery that diiron(I) dithiolates initially protonate to
give terminal, not bridging, hydrides opens a new and potentially
significant phase in elucidating the role of the dithiolate cofactor in
the catalysis.11 Terminal hydride ligands12 would be directly adjacent
to the heteroatom in the dithiolate, which is therefore well positioned
as a site for proton relay. We recently demonstrated that protonations
of the electronically symmetrical Fe2(pdt)(CO)2(dppv)2 (1) and
Fe2(adt)(CO)2(dppv)2 (2) yield relatively stable (t1/2 ≈ minutes at 25
°C), terminal hydride derivatives (dppv ) cis-1,2-bis(diphenylphos-
phino)ethylene; pdt ) 1,3-propanedithiolate; adt ) 2-azapropane-1,3-
∼23) and PPh3 ([HPPh3] BF4, pKCD Cl ) 1.6).16 In contrast, [1(t-
H)]BArF4 cannot be deprotonated by any organic base, even at room
temperature, where isomerization to [1(µ-H)]+ eventually occurs.
2
2
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16834 J. AM. CHEM. SOC. 2008, 130, 16834–16835
10.1021/ja8057666 CCC: $40.75
2008 American Chemical Society

C O M M U N I C A T I O N S
correspond to an aqueous pKa of 6.8.16 Catalysis by the amine [2(t-H)]BF4
with strong acids is complicated because protonation occurs at both the
amine and terminally at Fe.7,10,13 Interestingly, for strong acids, [3(t-H)]BF4
is a significantly faster catalyst for hydrogen evolution than is [1(t-H)]BF4,
which suggests that even the weakly basic ether group assists in proton
relay (Figure 2).
The results presented in this paper indicate that the presence of a
heteroatom in the dithiolate bridge strongly facilitates proton transfer
to and from the apical site on Fe, but only to the extent that the acid
can protonate the bridgehead atom. Although both azadithiolate (in 2)
and oxadithiolate (in 3) exhibit relay-like behavior, indicated by
enhanced rates of proton reduction catalysis by 2 and 3, only the
azadithiolate 2 enables hydride formation from weak acids, which is
relevant to catalysis at low overpotentials.18
Acknowledgment. This research was supported by NIH and
PRF. M.T.O. thanks the NIH CBI Training Program for a graduate
fellowship.
Figure 2. Dependence of current (ic/ip) vs [HBF4.Et2O] for [1(t-H)]BF4
and [3(t-H)]BF4 (-20 °C, 1 mM catalyst), where ic is peak catalytic current
and ip is the peak current in the absence of acid.
Deprotonation of [2(t-H)]BArF is however immediate with PBu3
4
Note Added after ASAP Publication. The version published Nov
21, 2008 contained errors in the text, references, and SI. The corrected
version was published Dec 10, 2008.
([HPBu3]BF4, pKCD Cl ) 8.2) even at -90 °C, exclusiVely providing
2. The close similarity of the IR spectra in the νCO region for [1(t-
H)]BArF , [2(t-H)]BArF , and [3(t-H)]BArF suggests that these
2
2
4
4
4
terminal hydrides should have similar thermodynamic acidities.17 The
similar thermodynamic acidities of these three hydrides indicate that
the rate of deprotonation is strongly influenced by the presence of a
heteroatom in the dithiolate (Scheme 1). Not only is deprotonation of
the terminal hydrides strongly affected by the identity of the dithiolate
ligand, the stereochemistry of the hydride also has a profound effect.
The three bridging hydrides, [1(µ-H)]+, [2(µ-H)]+, and [3(µ-H)]+, are
not deprotonated by NEt3 at room temperature.
Supporting Information Available: Preparative and spectroscopic
details. This material is available free of charge via the Internet at http://
pubs.acs.org.
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addition of [NBu4]BF4 to a CH2Cl2 solution of [2H]BArF partially
4
converts the terminal hydride to the ammonium tautomer.
These results are consistent with a mechanism whereby hydride
formation is regulated by the basicity of the heteroatom in the dithiolate:
the amine center in 2 is easily protonated and then quickly relays
protons to Fe. In contrast for complexes with weakly basic oxadithiolate
+
(pKCD Cl (R2OH ) ∼ -4.7 to 1.6) or nonbasic propanedithiolate, the
Fe site can only be protonated by strong acids, even though the
basicities of these diiron centers are very similar.
2
2
Heteroatom-Containing Dithiolates Enhance Proton Reduction
Catalysis. As the azadithiolate exhibits enhanced rates of protonation, this
enhancement could be manifested in catalysis by accelerating the rate of
proton reduction. At -20 °C, where these terminal hydrides are stable,
the hydrides [1(t-H)]BF4, [2(t-H)]BF4, and [3(t-H)]BF4 all catalyze
hydrogen evolution at approximately the same potentials, ∼ -1.5 V vs
Fc/Fc+ (∼ -0.8 V vs NHE). Using [HPMe2Ph]BF4 (pKCD Cl ) 5.7),
however, [2(t-H)]BF4 is catalytically active, but [1(t-H)]BF4 and [3(t-
2
2
H)]BF4 are not. The pKCD Cl of [HPMe2Ph]BF4 has been estimated to
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