Analysis of Bridgehead Effects on [FeFe]-Hydrogenase Active Site:
Steric Bulk at Nitrogen versus Carbon
Danielle J. Crouthers, David G. Munoz, Jason A. Denny, and Marcetta Y. Darensbourg*
Texas A&M University, College Station, TX 77843
Essential Features of
[FeFe]-Hydrogenase Active Site
1H
and 13C Variable Temperature NMR
13C
NMR
CD2Cl2
1H
NMR
CD2Cl2
• Open Site: site for proton oxidative addition or
dihydrogen binding
• Azadithiolate Linker: relays protons to and from
the iron distal to the 4Fe4S cluster
• Diatomic Ligands: stabilize the redox states of
the irons
• 4Fe4S Cluster: redox active shuttle of electrons
20
°
0
°
-10
°
-20
°
-30
°
-40
25 ° C
0
°°
-10
-30 °
Comparison of Carbon and Nitrogen
2
Bridgehead
NH
Complex
Pdt
dmpdt
NH
NMe
NtBu
NPh
NMe
ν(CO) IR
(cm-1)
2076, 2035, 2005, 1992, 1981
2075, 2034, 2005, 1992, 1980
2075, 2036, 2007, 1990, 1981
2075, 2036, 2002, 1990, 1984
NtBu
Fe-Fe (Å)
2.5105(8)
2.4939(4)
2.5150(3)
2.4924(7)
2075, 2036, 2002, 1994, 1982 2.5172(9)
2074, 2039, 1999, 1990, 1981 2.5047(6)
Torsionb
(°)
0.0(2)
6.5(2)
0.00(9)
0.0(4)
C/N-Fec
3.498
3.735
3.481
3.587
118.46
123.66
6.1(2)
20.1(2)
3.320
3.48
Synthesis of Azadithiolate Disubstituted
Complexes
-40 °
-50 °
2PMe3
Fe
Fe
C ba
O
N
O
C
ap
Fe
ba
OC
Complex
Fe-Fe (Å)
pdt(PMe3)2
dmpdt(PMe3)2
NMe(PMe3)2
NtBu(PMe3)2
NPh(PMe3)2
2.5554(2)
2.5690(7)
2.526(1)
2.5860(2)
2.573(4)
CO
S S
C ba
O
ΔG‡
ΔG‡
(kJ/mol (kcal/mol
)
)
edt
50.7
12.1
0 °C
pdt
43.5
10.4
-60 °C
dmpdt -87 °C
31
7.4
NMe
45.7
10.9
-40 °C
NtBu
46
11
-30 °C
NPh
disulfide -60 °C
38.3
9.2
Complex
Tcoal
<
7.4
ΔG‡
calculate
d
14.3
12.1
10.0
Fe
CO
CO
13.8
15.0
11.4
11.5
<
 The energy barriers are calculated using
datafrom 13C VTNMR, looking at peak separation
and the coalescence temperature.
 Analysis of the carbon bridgehead complexes
finds that steric bulk on the bridgehead lowers
the energy for rotation however, steric bulk at
the nitrogen bridgehead has little effect for
R=alkyl and a greater effect for R=phenyl.
<
9.2
10.4
<
10.9
<
11
12.1
Electrochemical Studies
The diiron complexes were studied in
acetonitrile with addition of acetic
acid. The complexes exhibit an
increase in current with addition of
acetic acid at two events past the
first reduction. The nitrogen
bridgehead complexes show a 2- fold
increase in the current compared to
the carbon bridgehead complexes at
the first catalytic event. NtBu shows
a 1.5-fold increase compared to the
other
hexacarbonyl
complexes
studied at the second catalytic event.
DMPDT
PDT
NMe
NtBu
Second Catalytic Peak Comparison
Conclusions
 Incorporation of nitrogen in the bridgehead has no effect on the vibrational spectra compared
to carbon and only a minimal effect on the solid state molecular structure.
 Addition of steric bulk to a carbon bridgehead increases the torsion angle of the complex
however addition of steric bulk to a pyramidal nitrogen has little effect on the torsion angle due
to the direction the steric bulk is pointed. Steric bulk on a planar nitrogen increases the torsion
angel similar to the carbon bridgehead complexes.
 Analysis of the hexacarbonyl complexes does not reveal any correlation between the Fe(CO)3
rotor fluxionality and catalytic efficiency.
C/N--Fec
(Å)
3.449
3.731
3.396
3.298
3.428
CO
Energy Barrier for CO Site Exchange3,4
Comparison of Disubstituted Structures
Torsionb
(°)
9.1(5)
28.9(3)
2.1(3)
1.0(9)
10(2)
CO
R
3PMe3
Flap Anglea
(°)
129.9
135.74
122.24
118.46
121.28
CO
S S
C ap
ba
OC
°
First Catalytic Peak Comparison
1PMe3
O
°
-70
°
-80
NPh
Flap Anglea
(°)
137.09
135.74
131.95
122.26
N
°
-50
°
-60
-20 °
 [FeFe]-hydrogenases are key enzymes in energy metabolism, catalyzing the reversible interconversion of
protons and electrons into hydrogen under mild conditions (pH = 7; E = - 400 mV).1
 The synthesis of small molecule models of the [FeFe]-H2ase active site is driven by the desire to better
understand a unique biological system capable of producing hydrogen at rates comparable to platinum.
Questions: Can [FeFe]-hydrogenase active site models define the role of nitrogen at the bridge head? Is
there a correlation between the Fe(CO)3 rotor fluxionality and catalytic efficiency?
R
References
Acknowledgements
1) Pandy, A. S. et al. J. Am. Chem. Soc. 2008, 130, 4533.
MYD Research Group
2) Li, H. et al. J. Am. Chem. Soc. 2002, 124, 726.
$$$$$$$$$$$$$$$$$$$$
3) Singleton, M. L. et al. C. R. Chimie 2008, 11, 861.
National Science Foundation
4) Lyon, E. J. et al. J. Am. Chem. Soc. 2001, 123, 3268.
Robert A. Welch Foundation