Synthetic models of the reduced active site of superoxide reductase

Article abstract of DOI:10.1021/ic025517l

We report the synthesis, structural and spectroscopic characterization, and magnetic and electrochemical studies of a series of iron(II) complexes of the pyridyl-appended diazacyclooctane ligand L⁸py₂, including several that model the square-pyramidal [Fe^II(Nhls)₄(S_cys)] structure of the reduced active site of the non-heme iron enzyme superoxide reductase. Combination of L⁸py₂ with FeCl₂ provides [L⁸py₂FeCl₂] (1), which contains a trigonal-prismatic hexacoordinate iron(II) center, whereas a parallel reaction using [Fe(H₂O)₆](BF₄)₂ provides [L⁸py₂Fe(FBF₃)]BF₄ (2), a novel BF₄^--ligated square-pyramidal iron(II) complex. Substitution of the BF₄^- ligand in 2 with formate or acetate ions affords distorted pentacoordinate [L⁸py₂Fe(O₂CH)]BF₄ (3) and [L⁸py₂Fe(O₂CCH₃)]BF₄ (4), respectively. Models of the superoxide reductase active site are prepared upon reaction of 2 with sodium salts of aromatic and aliphatic thiolates. These model complexes include [L⁸py₂Fe(SC₆H₄-p- CH₃)]BF₄ (5), [L⁸py₂Fe(SC₆H₄-m- CH₃)]BF₄ (6), and [L⁸py₂Fe(SC₆H₁₁)]BF₄ (7). X-ray crystallographic studies confirm that the iron(II)-thiolate complexes model the squarepyramidal geometry and N₄S donor set of the reduced active site of superoxide reductase. The iron(II)-thiolate complexes are high spin (S = 2), and their solutions are yellow in color because of multiple charge-transfer transitions that occur between 300 and 425 nm. The ambient temperature cyclic voltammograms of the iron(II)thiolate complexes contain irreversible oxidation waves with anodic peak potentials that correlate with the relative electron donating abilities of the thiolate ligands. This electrochemical irreversibility is attributed to the bimolecular generation of disulfides from the electrochemically generated iron(III)-thiolate species.

Full text of DOI:10.1021/ic025517l

Inorg. Chem. 2002, 41, 3935−3943
Synthetic Models of the Reduced Active Site of Superoxide Reductase
Jason A. Halfen,* Heather L. Moore, and Derek C. Fox
Department of Chemistry, UniVersity of Wisconsin-Eau Claire, 105 Garfield AVenue,
Eau Claire, Wisconsin 54702
Received January 28, 2002
We report the synthesis, structural and spectroscopic characterization, and magnetic and electrochemical studies
of a series of iron(II) complexes of the pyridyl-appended diazacyclooctane ligand L8py2, including several that
II
model the square-pyramidal [Fe (N ) (S )] structure of the reduced active site of the non-heme iron enzyme
his 4 cys
superoxide reductase. Combination of L8py2 with FeCl2 provides [L8py2FeCl2] (1), which contains a trigonal-prismatic
hexacoordinate iron(II) center, whereas a parallel reaction using [Fe(H O)6](BF ) provides [L8py2Fe(FBF )]BF (2),
2
4 2
3
4
a novel BF --ligated square-pyramidal iron(II) complex. Substitution of the BF - ligand in 2 with formate or acetate
4
4
ions affords distorted pentacoordinate [L8py2Fe(O CH)]BF (3) and [L8py2Fe(O CCH )]BF (4), respectively. Models
2
4
2
3
4
of the superoxide reductase active site are prepared upon reaction of 2 with sodium salts of aromatic and aliphatic
thiolates. These model complexes include [L8py2Fe(SC H -p-CH )]BF (5), [L8py2Fe(SC H -m-CH )]BF (6), and
6
4
3
4
6
4
3
4
8
[L py2Fe(SC H )]BF (7). X-ray crystallographic studies confirm that the iron(II)−thiolate complexes model the square-
6
11
4
pyramidal geometry and N S donor set of the reduced active site of superoxide reductase. The iron(II)−thiolate
4
complexes are high spin (S ) 2), and their solutions are yellow in color because of multiple charge-transfer
transitions that occur between 300 and 425 nm. The ambient temperature cyclic voltammograms of the iron(II)−
thiolate complexes contain irreversible oxidation waves with anodic peak potentials that correlate with the relative
electron donating abilities of the thiolate ligands. This electrochemical irreversibility is attributed to the bimolecular
generation of disulfides from the electrochemically generated iron(III)−thiolate species.
Introduction
tolerate the dioxygen coproduct formed during superoxide
dismutation. Structural studies of the reduced SOR (SORRed
)
Nature has devised several pathways for the detoxification
of superoxide (O2 ) in biological systems.1 The most familiar
active site reveal an iron(II) ion bound by a square-pyramidal
array of four equatorial histidine imidazoles and a single,
axial cysteine thiolate ligand (Figure 1).4 Superoxide is
proposed to bind to the metal center trans to the cysteinate
ligand; single electron transfer from the iron and subsequent
protonation of the bound peroxide generates hydrogen
peroxide and the iron(III) form of the enzyme.5 As part of
our examination of metal-mediated superoxide detoxification
pathways in biology, we have targeted synthetic models of
SORRed for preparation, characterization, and reactivity
studies.
-
routes involve superoxide dismutases, a diverse group of
metalloenzymes that mediate the conversion of superoxide
to both hydrogen peroxide and dioxygen.2 An alternative
pathway to superoxide dismutation is the one-electron
reduction of superoxide, a process mediated by the recently
characterized group of metalloenzymes known as superoxide
reductases (SORs).3 These non-heme iron enzymes are
produced by anaerobes and microaerophiles that cannot
* To whom correspondence should be addressed. E-mail: halfenja@
uwec.edu. Phone: 715-836-4360. Fax: 715-836-4979.
(1) (a) Fridovich, I. J. Exp. Biol. 1998, 201, 1203-1209. (b) Fridovich,
I. J. Biol. Chem. 1997, 272, 18515-81517. (b) Fridovich, I. Annu.
ReV. Biochem. 1995, 64, 97-112.
(2) (a) Lyons, T. J.; Gralla, E. B.; Valentine, J. S. Met. Ions Biol. Sys.
1999, 36, 125-177. (b) Lah, M. S.; Dixon, M. M.; Pattridge, K. A.;
Stallings, W. C.; Fee, J. A.; Ludwig, M. L. Biochemistry 1995, 34,
1646-1660. (c) Hsu, J.-L.; Hsieh, Y.; Tu, C. K.; O’Connor, D.; Nick,
H. S.; Silverman, D. N. J. Biol. Chem. 1996, 271, 17687-17691. (d)
Youn, H.-D.; Kim, E.-J.; Roe, J.-H.; Hah, Y. C.; Kang, S.-O. Biochem.
J. 1996, 318, 889-896.
(3) (a) Jenney, F. E., Jr.; Verhagen, M. F. J. M.; Cui, X.; Adams, M. W.
W. Science 1999, 286, 306-309. (b) Jovanovic, T.; Ascenso, C.;
Hazlett, K. R. O.; Sikkink, R.; Krebs, C.; Litwiller, R.; Benson, L.
M.; Moura, I.; Moura, J. J. G.; Radolf, J. D.; Huynh, B. H.; Naylor,
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A.; Coronado, M. A. J. Biol. Inorg. Chem. 1997, 2, 680-689. (b)
Yeh, A. P.; Hu, Y.; Jenner, F. E., Jr.; Adams, M. W. W.; Rees, D. C.
Biochemistry 2000, 39, 2499-2508. (c) Clay, M. D.; Jenney, F. E.,
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M. K. J. Am. Chem. Soc. 2002, 124, 788-805.
10.1021/ic025517l CCC: $22.00 © 2002 American Chemical Society
Published on Web 06/14/2002
Inorganic Chemistry, Vol. 41, No. 15, 2002 3935

Halfen et al.
that biologically relevant ferrous complexes are readily
prepared using L8py2 as a supporting ligand. Of particular
significance is the isolation and structural characterization
of a number of square-pyramidal Fe(II)-thiolate complexes
that model the structural and magnetic properties of SORRed
.
Experimental Section
Materials and Methods. Reagents were obtained from com-
mercial sources and used as received unless noted otherwise.
Solvents were purified according to standard methods. The tet-
radentate ligand L8py2 was prepared from 1,5-diazacyclooctane
dihydrobromide as described previously.6 Because of the hazards
associated with the use of hydrazine in the published, large scale
synthesis of 1,5-diazacyclooctane,8 we present an alternative
synthesis that avoids the use of this toxic material. Sodium thiolates
were prepared by the reaction of the aryl- or alkylthiol with NaH
in THF and isolated as white powders. All reactions were conducted
and products were handled under an inert atmosphere using standard
Schlenk techniques, or in a Vacuum Atmospheres inert atmosphere
glovebox. NMR spectra were obtained using a JEOL Eclipse 400
spectrometer at room temperature. 1H and 13C{1H} chemical shifts
are reported versus TMS and are referenced to residual solvent
peaks. Electronic absorption spectra were measured using a Hewlett-
Packard 8453 spectrophotometer (190-1100 nm range). Electro-
chemical experiments were conducted with a BAS CV50 poten-
tiostat, using a platinum disk working electrode, an SCE reference
electrode, and a platinum wire auxiliary electrode. Cyclic voltam-
mograms were obtained in CH3CN (0.1 M n-Bu4NClO4) with an
analyte concentration of 1 mM. Under these experimental condi-
tions, the ferrocene/ferrocenium redox couple was observed at +461
mV (∆Ep ) 96 mV) with ipa/ipc ) 0.92. Elemental analyses were
performed by Galbraith Laboratories or by Atlantic Microlabs.
Figure 1. Reduced active site of superoxide reductase as determined by
X-ray crystallography (ref 4b).
Scheme 1
1,3-Bis(p-toluenesulfonyl)-1,3-diaminopropane. To a solution
of K2CO3 (201.4 g, 1.456 mol) in water (0.6 L) was added 1,3-
diaminopropane (54.31 g, 0.733 mol). A solution of p-toluene-
sulfonyl chloride (277.9 g, 1.457 mol) in THF (1.2 L) and added
to the diamine solution over a period of 3 h. The heterogeneous
mixture was stirred overnight and then divided into two equal
portions. Each portion was poured into 1 L of ice water, causing
the crude product to precipitate. The mixture was filtered and the
solid washed with cold water and then dried under vacuum.
Recrystallization from a minimum of hot CH3CN provided the pure
product as a colorless crystalline solid, 219.4 g (78%), mp 137-
We recently described the synthesis of a pyridyl-appended
diazacyclooctane ligand, L8py2 (Scheme 1), and its use in
the preparation of Cu(II) catalysts for olefin aziridination.6
Examination of Ni(II) and Co(II) complexes of L8py2 has
revealed that the tetradentate ligand most often occupies the
four equatorial coordination sites of square-planar or square-
pyramidal transition metal complexes.7 Herein, we describe
the coordination chemistry of L8py2 with Fe(II) and report
o
138 °C (lit. 138-140 C).9 1H NMR (400 MHz, CD3CN) δ 7.67
(d, J ) 8.4 Hz, 4H), 7.36 (d, J ) 7.7 Hz, 4H), 5.48 (br t, J ) 5.3,
2H), 2.79 (dt, J ) 5.3 Hz, 4H), 2.41 (s, 6H), 1.53 (br pentet, J )
6.9 Hz, 2H) ppm; 13C{1H} NMR (100 MHz, acetone-d6) δ 142.9,
138.1, 129.6, 126.9, 40.4, 29.8, 20.6 ppm.
(5) (a) Coulter, E. D.; Emerson, J. P.; Kurtz, D. A., Jr.; Cabelli, D. E. J.
Am. Chem. Soc. 2000, 122, 11555-11556. (b) Lombard, M.; Fonte-
cave, M.; Touati, D.; Nivie`re, V. J. Biol. Chem. 2000, 275, 115-121.
(c) Lombard, M.; Houee-Levin, C.; Touati, D.; Fontecave, M.; Nivie`re,
V. Biochemistry 2001, 40, 5032-5040. (d) Nivie`re, V.; Lombard, M.;
Fontecave, M.; Houee-Levin, C. FEBS Lett. 2001, 497, 171-173. (e)
Emerson, J. P.; Coulter, E. D.; Cabelli, D. E.; Phillips, R. S.; Kurtz,
D. M., Jr. Biochemistry 2002, 41, 4348-4357. (f) Mathe´, C.; Mattioli,
T. A.; Horner, O.; Lombard, M.; Latour, J.-M.; Fontecave, M.; Nivie`re,
V. J. Am. Chem. Soc. 2002, 124, 4966-4967.
1,3-Bis(p-toluenesulfonyloxy)propane. A solution of p-tolu-
enesulfonyl chloride (450.6 g, 2.36 mol) in pyridine (1 L) was
prepared and cooled to 3 °C. A solution of 1,3-propanediol (60.68
g, 0.797mol) in pyridine (165 mL) was added dropwise over 3 h,
while maintaining the temperature of the mixture between 5 and
-10 °C. The heterogeneous mixture was stored at -20 °C
overnight. Slow addition of ice water (2 L) caused the crude product
to precipitate. The solid was collected by filtration and washed with
(6) L8py2 ) 1,5-bis(2-pyridylmethyl)-1,5-diazacyclooctane: Halfen, J. A.;
Fox, D. C.; Mehn, M. P.; Que, L., Jr. Inorg. Chem. 2000, 39, 4913-
4920.
(8) Mills, D. K.; Font, I.; Farmer, P. J.; Hsiao, Y.-M.; Tuntulani, T.;
Buonomo, R. M.; Goodman, D. C.; Musie, G.; Grapperhaus, C. A.;
Maguire, M. J.; Lai, C.-H.; Hatley, M. L.; Smee, J. J.; Bellefeuille, J.
A.; Darensbourg, M. Y. Inorg. Synth. 1997, 32, 89-97.
(7) (a) Du, M.; Shang, Z.-L.; Leng, X.-B.; Bu, X.-H. Polyhedron 2001,
20, 3065-3071. (b) Bu, X.-H.; Fang, Y.-Y.; Shang, Z.-L.; Zhang,
R.-H.; Zhu, H.-P.; Liu, Q.-T. Acta Crystallogr. 1999, C55, 39-40.
(c) Halfen, J. A.; Fox, D. C.; Moore, H. L. To be submitted.
(9) Searle, G. H.; Geue, R. J. Aust. J. Chem. 1984, 37, 959-970.
3936 Inorganic Chemistry, Vol. 41, No. 15, 2002

Synthetic Models of Superoxide Reductase
cold water (1 L). Recrystallization from a minimum of hot CH3-
CN provided the pure product as a colorless crystalline solid, 201.2
g (67%), mp 92-93 °C (lit. 91-93 °C).9 1H NMR (400 MHz,
CDCl3) δ 7.73 (d, J ) 8.4 Hz, 4H), 7.34 (d, J ) 7.7 Hz, 4H), 4.23
(t, J ) 5.9 Hz, 4H), 2.45 (s, 6H), 1.99 (pentet, J ) 6.1 Hz, 2H)
ppm; 13C{1H} NMR (100 MHz, CDCl3) δ 145.4, 132.6, 130.0,
128.0, 65.9, 28.6, 21.8 ppm.
[L8py2Fe(O2CH)]BF4 (3). To a stirred solution of L8py2 (0.0504
g, 0.170 mmol) in CH3OH (2 mL) was added [Fe(H2O)6](BF4)2
(0.0699 g, 0.207 mmol). This mixture was stirred until a homo-
geneous, light yellow solution was obtained. Sodium formate
(0.0178 g, 0.261 mmol) was then added, and a pale yellow color
was generated. After 30 min, the solvent was removed under
vacuum, producing a pale yellow solid. This solid was extracted
into CH2Cl2, the mixture filtered through Celite, and the filtrate
evaporated under vacuum. The solid thus produced was recrystal-
lized from CH2Cl2/Et2O to provide pale yellow crystals of the
product, 0.0361 g (44%). Anal. Calcd for C19H25BF4FeN4O2: C,
47.14; H, 5.21; N, 11.57. Found: C, 47.35; H, 5.12; N, 11.55.
[L8py2Fe(O2CCH3)]BF4 (4). To a stirred solution of L8py2
(0.0651 g, 0.220 mmol) in CH3CN (3 mL) was added [Fe(H2O)6]-
(BF4)2 (0.0762 g, 0.226 mmol) followed by sodium acetate (0.0240
g, 0.292 mmol). The color of the mixture slowly changed from
light pink to yellow. After stirring overnight, the solvent was
removed under vacuum, and the resulting solid was extracted into
CH2Cl2. The mixture was then filtered and the filtrate evaporated
to dryness. Recrystallization of the crude yellow solid from CH3-
CN/Et2O provided yellow crystals of the product, 0.0670 g (61%).
Anal. Calcd for C20H27BF4FeN4O2: C, 48.22; H, 5.46; N, 11.25.
Found: C, 48.91; H, 5.75; N, 11.57.
[L8py2Fe(SC6H4-p-CH3)]BF4 (5). To a stirred solution of L8-
py2 (0.0510 g, 0.172 mmol) in CH3OH (2 mL) was added [Fe-
(H2O)6](BF4)2 (0.0592 g, 0.175 mmol). This mixture was stirred
until a homogeneous, light yellow solution was obtained. Sodium
4-methylbenzenethiolate (0.0402 g, 0.275 mmol) was then added,
and a dark yellow color was immediately generated, followed
rapidly by the deposition of a yellow microcrystalline precipitate.
The mixture was filtered and the solid recrystallized from CH2-
Cl2/Et2O to provide yellow crystals of the product, 0.0747 g (77%).
Anal. Calcd for C25H31BF4FeN4S: C, 53.04; H, 5.58; N, 9.96.
Found: C, 52.34; H, 5.49; N, 9.91.
[L8py2Fe(SC6H4-m-CH3)]BF4 (6). To a stirred solution of L8-
py2 (0.0497 g, 0.168 mmol) in CH3OH (2 mL) was added [Fe-
(H2O)6](BF4)2 (0.0628 g, 0.186 mmol). This mixture was stirred
until a homogeneous, light yellow solution was obtained. Sodium
3-methylbenzenethiolate (0.0395 g, 0.271 mmol) was then added,
and a dark yellow color was immediately generated, followed
rapidly by the deposition of a yellow microcrystalline precipitate.
The mixture was filtered, and the solid recrystallized from CH2-
Cl2/Et2O to provide yellow crystals of the product, 0.0651 g (69%).
Anal. Calcd for C25H31BF4FeN4S: C, 53.04; H, 5.58; N, 9.96.
Found: C, 52.34; H, 5.74; N, 10.05.
[L8py2Fe(SC6H11)]BF4 (7). To a stirred solution of L8py2 (0.0654
g, 0.221 mmol) in CH3OH (4 mL) was added [Fe(H2O)6](BF4)2
(0.0775 g, 0.230 mmol) followed by sodium cyclohexanethiolate
(0.0450 g, 0.326 mmol). The color of the solution changed quickly
to yellow, and a small amount of a yellow solid was deposited.
After stirring 30 min, the volume of the mixture was reduced under
vacuum, causing additional yellow solid to be deposited. The light
yellow supernatant was decanted from the solid, which was dried
and then redissolved in CH2Cl2. This yellow solution was filtered
through a plug of glass wool; vapor diffusion of Et2O into the yellow
filtrate provided the product as yellow crystals, 0.0573 g (47%).
Anal. Calcd for C24H35BF4FeN4S: C, 52.00; H, 6.36; N, 10.11.
Found: C, 50.92; H, 6.19; N, 10.29.
1,5-Bis(p-toluenesulfonyl)-1,5-diazacyclooctane. Sodium metal
(7.19 g, 0.3127 mol) was dissolved in dry, degassed methanol to
form a solution of sodium methoxide. To this solution was added
1,3-bis(p-toluenesulfonyl)-1,3-diaminopropane (59.69 g, 0.156 mol),
and the resulting solution refluxed under N2 for 2 h. After cooling,
the solvent was removed under reduced pressure and the white
residue thoroughly dried under vacuum. Anhydrous DMF (1 L)
was added to the solid and the mixture heated to 100 °C under N2.
To this mixture was added a solution of 1,3-bis(p-toluenesulfony-
loxy)propane (59.91 g, 0.156 mol) in anhydrous DMF (0.6 L) over
the course of 2.5 h. The resulting amber solution was heated at
100 °C for 3 h and then cooled to room temperature. Slow addition
of water (2 L) to the amber solution caused the crude product to
precipitate. The solid was collected and washed successively with
water (0.5 L), ethanol (0.5 L), and Et2O (0.5 L) to provide the
product as an off-white microcrystalline solid, 48.23 g (73%), mp
214-216 °C (lit. 218 °C).10 1H NMR (400 MHz, CDCl3) δ 7.67
(d, J ) 8.4 Hz, 4H), 7.30 (d, J ) 8.1 Hz, 4H), 3.26 (t, J ) 5.9 Hz,
8H), 2.42 (s, 6H), 2.03 (pentet, J ) 5.7 Hz, 4H) ppm; 13C{1H}
NMR (100 MHz, CDCl3) δ 143.4, 135.7, 129.8, 127.0, 46.9, 30.0,
21.6 ppm.
1,5-Diazacyclooctane dihydrobromide. A mixture of 1,5-bis-
(p-toluenesulfonyl)-1,5-diazacyclooctane (47.73 g, 0.113 mol) and
phenol (42.57 g, 0.452 mol) was dissolved in 33% HBr/HOAc (500
mL) under N2 and heated to 90 °C. Care should be exercised as
significant outgassing of HBr occurs while heating. After 18 h, the
mixture was cooled to 60 °C, an additional portion of 33% HBr/
HOAc (100 mL) was added, and the mixture was then reheated to
90 °C for 2 h. After cooling to room temperature, the precipitate
was separated by filtration, washed with Et2O (250 mL), and dried
under vacuum to yield the product, 26.59 g (85%), mp > 250 °C.
1H NMR (400 MHz, D2O) δ 3.44 (t, J ) 5.6 Hz, 8H), 2.30 (pentet,
J ) 5.7 Hz, 4H) ppm; 13C{1H} NMR (100 MHz, D2O) δ 44.1,
21.1 ppm. The solid thus obtained was used for the synthesis of
L8py2 without further purification.6
[L8py2FeCl2] (1). A solution of FeCl2 (0.0745 g, 0.452 mmol)
in CH3CN (2 mL) was added to a solution of L8py2 (0.0931 g,
0.314 mmol) in CH3CN (2 mL), and after stirring for several
minutes, a yellow-orange precipitate was deposited. The precipitate
was washed with CH3CN (2 mL) and Et2O (5 mL) and dried under
vacuum. Recrystallization from CH2Cl2/Et2O provided the product
as yellow-orange crystals, 0.0542 g (41%). Anal. Calcd for C18H24-
Cl2FeN4: C, 51.09; H, 5.72; N, 13.24. Found: C, 50.81; H, 5.76;
N, 13.11.
[L8py2Fe(FBF3)]BF4 (2). A solution of L8py2 (0.0921 g, 0.311
mmol) in CH3CN (2 mL) was treated with [Fe(H2O)6](BF4)2 (0.1467
g, 0.435 mmol), generating a very light pink solution. After 30
min, Et2O (5 mL) was added to the solution, causing the deposition
of a light red oil. The supernatant was removed from the oil, and
additional Et2O (5-10 mL) was added to the clear supernatant,
causing a colorless precipitate to form. Recrystallization from CH3-
CN/Et2O provided colorless crystals of the product, 0.0695 g (43%).
Anal. Calcd for C18H24B2F8FeN4: C, 41.11; H, 4.60; N, 10.65.
Found: C, 41.15; H, 4.70; N, 10.74.
X-ray Crystallography. Single crystals were mounted in thin-
walled glass capillaries and transferred to an Enraf-Nonius CAD4
X-ray diffractometer for data collections at 25 °C using graphite
monochromated Mo KR (λ ) 0.71073 Å) radiation. Unit cell
constants were determined from a least squares refinement of the
(10) Houser, R. P.; Young, V. G., Jr.; Tolman, W. B. J. Am. Chem. Soc.
1996, 118, 2101-2102.
Inorganic Chemistry, Vol. 41, No. 15, 2002 3937

Halfen et al.
Table 1. Summary of X-ray Crystallographic Data for Complexes
1-4a
Table 2. Summary of X-ray Crystallographic Data for
Iron(II)-Thiolate Complexes 5-7a
1
2
3
4
5
6
7
empirical
formula
fw
cryst syst
space group
a (Å)
C
18H24
-
C
18H24B2-
F8FeN4
C
19H25B-
C
20H27B-
empirical formula
C25H31BF4-
FeN4S
C25H31BF4-
FeN4S
C24H35BF4-
FeN4S
554.28
monoclinic
C2/m
17.532(3)
12.157(1)
14.028(3)
90
112.18(2)
90
Cl2FeN4
F4FeN4O2
F4FeN4O2
423.16
monoclinic
C2/c
22.786(6)
7.8401(5)
13.805(4)
90
126.94(2)
90
1971.1(8)
4
525.88
orthorhombic monoclinic
484.09
498.12
monoclinic
P21/n
16.325(4)
8.093(1)
17.075(5)
90
96.72(3)
90
2240.4(9)
4
fw
562.26
562.26
cryst syst
space group
a (Å)
triclinic
P1h
triclinic
P1h
Pnnm
16.948(1)
11.274(2)
12.141(1)
90
90
90
2319.8(5)
4
1.506
P21/c
11.889(2)
13.666(2)
14.078(2)
90
109.22(2)
90
2159.8(6)
4
1.489
10.396(2)
11.091(2)
13.142(6)
89.93(3)
111.04(3)
114.00(3)
1339.4(7)
2
10.791(1)
10.971(2)
13.262(2)
91.74(1)
110.55(1)
115.04(1)
1302.0(3)
2
b (Å)
c (Å)
b (Å)
c (Å)
R (deg)
â (deg)
γ (deg)
V (Å3)
Z
R (deg)
â (deg)
γ (deg)
V (Å3)
Z
2768.6(8)
4
1.330
calcd (Mg‚m-3
)
1.426
1.477
d
calcd (Mg‚m-3
)
1.394
1.434
d
cryst size (mm3)
0.52 × 0.32 × 0.50 × 0.45 × 0.52 × 0.38 ×
cryst size
0.40 × 0.35 × 0.48 × 0.30 × 0.35 × 0.32 × 0.42 × 0.30 ×
0.15 0.12 0.30 0.08
1.044 0.727 0.756 0.731
(mm3)
0.10
0.690
0.40
0.710
0.36
0.666
abs coeff (mm-1
2 Θ max (deg)
)
abs coeff
(mm-1
)
50.14
1.0-0.8984
4911
50.04
1.0-0.9386
4855
49.98
1.0-0.9160
2651
2 Θ max (deg) 49.96
transmission
range
49.96
1.0-0.9240
52.06
1.0-0.9225
52.08
1.0-0.8829
transmission range
no. reflns collected
no. indep reflns
no. obsd reflns
no. variables
1.0-0.9154
4643
4590
2560
no. reflns
collected
no. indep reflns 1734
no. obsd reflns 1339
no. variables
R1 (wR2)b
[I > 2σ(I)]
GOF (F2)
1779
2144
4457
4564
2591
4020
1782
325
325
193
R1 (wR2)b [I > 2σ(I)] 0.0755 (0.1702) 0.0396 (0.0947) 0.0599 (0.1443)
2144
1489
187
0.0543
(0.1442)
1.030
0.550,
-0.478
4248
2721
336
0.0633
(0.1260)
1.010
0.303,
-0.282
4407
2931
289
0.0686
(0.1408)
1.031
0.596,
-0.393
GOF (F2)
1.014
1.032
1.024
diff peaks (e-‚Å-3
)
0.630, -0.393 0.552, -0.384 0.330, -0.267
141
0.0313
a See Experimental Section for additional data collection, reduction, and
(0.0726)
structure solution and refinement details. b R1 ) ∑||Fo| - |Fc||/∑|Fo|; wR2
1.039
0.216,
) [∑[w(Fo - Fc )2]]1/2 where w ) 1/σ2(Fo ) + (aP)2 + bP.
2
2
2
diff peaks
(e-‚Å-3
)
-0.240
a See Experimental Section for additional data collection, reduction, and
two equivalent positions with occupancies 77(1)% and 23(1)%, and
the BF4 counterion is rotationally disordered over two positions
structure solution and refinement details. b R1 ) ∑||Fo| - |Fc||/∑|Fo|; wR2
-
2
2
2
) [∑[w(Fo - Fc )2]]1/2 where w ) 1/σ2(Fo ) + (aP)2 + bP.
with occupancies 71(1)% and 29(1)%. The refinements of 4-6
proceeded without complication. A crystallographic mirror plane
bisects the cation in 7. The carbon atoms of the cyclohexyl group
exhibit high anisotropic displacement parameters, reflecting the
room-temperature data collection for this complex. The BF4- anion
in 7 is also disordered over two equally occupied orientations;
geometric constraints were applied to the atoms of this ion.
setting angles of 25 intense, high angle reflections. Intensity data
were collected using the ω/2θ scan technique to a maximum 2θ
value of 50-52°. Absorption corrections were applied based on
azimuthal scans of several reflections for each sample. The data
were corrected for Lorentz and polarization effects and converted
to structure factors using the teXsan for Windows crystallographic
software package.11 Space groups were determined based on
systematic absences and intensity statistics. Successful direct-
methods solutions were calculated for each compound using the
SHELXTL suite of programs.12 Any non-hydrogen atoms not
identified from the initial E-map were located after several cycles
of structure expansion and full matrix least squares refinement on
F2. Hydrogen atoms were added geometrically. All non-hydrogen
atoms were refined with anisotropic displacement parameters, while
hydrogen atoms were refined using a riding model with group
isotropic displacement parameters. Relevant crystallographic in-
formation for the compounds is summarized in Tables 1 and 2,
and selected bond interatomic distances and angles are provided
in Tables 3 and 4. Complete crystallographic data for each
compound are provided as Supporting Information in CIF format.
Neutral molecules of 1 reside on a crystallographic 2-fold axis.
The propylene chains of the diazacyclooctane backbone are
disordered over two equally occupied orientations. A crystal-
lographic mirror plane bisects both the cation and the uncoordinated
BF4- counterion in 2. This ion is rotationally disordered over two
equally occupied orientations. Geometric constraints were applied
to the uncoordinated anion, and the anisotropic displacement
parameters for the atoms of this ion were restrained to fit a rigid
bond approximation. The formate ligand in 3 is disordered over
Results and Discussion
Synthesis. The primary reactions conducted as part of this
study are illustrated in Scheme 1. Among the complexes
initially targeted for synthesis were those that contain an iron-
(II) ion bound by both the tetradentate ligand L8py2 as well
as by some other, labile group(s) that could be readily
replaced by a more biologically relevant thiolate coligand.
The first such complex, [L8py2FeCl2] (1), was isolated as
yellow-orange crystals upon combination of L8py2 with
anhydrous FeCl2 in CH3CN. While 1 does contain labile
chloride ligands, it proved to be an ineffective precursor for
further synthetic studies, as demonstrated by its reaction with
sodium formate. This reaction did not result in simple
substitution of a chloride ligand by a formate ion; rather,
the sole iron-containing product of this reaction was [L8py2-
FeCl]2[Fe2Cl6], isolated as light yellow crystals and identified
by X-ray crystallography.13 The isolation of this product, co-
deposited with colorless crystals of the free ligand L8py2,14
indicates that conversion of 1 to its monochloride-ligated
derivative is thermodynamically favored over substitution
of the precursor’s chloride ligand(s).
(11) TeXsan for Windows, V 1.02; Molecular Structure Corporation, Inc.:
The Woodlands, TX.
(12) SHELXTL, V. 5.1 for Windows NT; Bruker AXS: Madison, WI.
A more viable synthetic precursor was identified in [L8-
py2Fe(FBF3)]BF4 (2), isolated as colorless crystals from the
3938 Inorganic Chemistry, Vol. 41, No. 15, 2002

Synthetic Models of Superoxide Reductase
Table 3. Significant Interatomic Distances (Å) and Angles (deg) for
Complexes 1-4
Table 4. Significant Interatomic Distances (Å) and Angles (deg) for
Iron(II)-Thiolate Complexes 5-7
1
2
5
6
Fe-N1
Fe-N2
Fe-Cl1
2.334(2)
2.305(2)
2.4283(8)
Fe-N1
Fe-N2
Fe-F1
2.205(4)
2.166(4)
1.967(4)
Fe-N1
Fe-N2
Fe-N3
Fe-N4
Fe-S1
2.241(5)
2.212(6)
2.185(5)
2.197(5)
2.323(3)
Fe-N1
Fe-N2
Fe-N3
Fe-N4
Fe-S1
2.225(2)
2.217(2)
2.182(2)
2.171(2)
2.3060(9)
N1-Fe-N1A
N1-Fe-N2
76.4(1)
71.40(8)
130.88(8)
91.75(6)
133.78(6)
155.3(1)
83.82(6)
84.91(6)
125.25(5)
B1-F1
1.39(1)
1.341(8)
1.353(8)
1.35(1)
88.5(2)
77.6(1)
145.6(1)
114.6(1)
107.2(2)
98.6(1)
B1-F2
N1-Fe-N2A
N1-Fe-Cl1
N1-Fe-Cl1A
N2-Fe-N2A
N2-Fe-Cl1
N2-Fe-Cl1A
Cl1-Fe-Cl1A
B1-F3
N1-Fe-N2
N1-Fe-N3
N1-Fe-N4
N1-Fe-S1
N2-Fe-N3
N2-Fe-N4
N2-Fe-S1
N3-Fe-N4
N3-Fe-S1
N4-Fe-S1
Fe-S1-C19
80.6(2)
75.3(2)
147.3(2)
104.1(2)
136.8(2)
77.0(2)
111.2(2)
105.8(2)
109.2(2)
106.1(2)
97.6(2)
N1-Fe-N2
N1-Fe-N3
N1-Fe-N4
N1-Fe-S1
N2-Fe-N3
N2-Fe-N4
N2-Fe-S1
N3-Fe-N4
N3-Fe-S1
N4-Fe-S1
Fe-S1-C19
80.01(8)
75.54(8)
147.24(8)
105.36(6)
136.00(8)
77.80(8)
112.05(6)
104.92(8)
109.44(6)
107.17(6)
95.25(9)
B1-F4
N1-Fe-N1A
N1-Fe-N2
N1-Fe-N2A
N1-Fe-F1
N2-Fe-N2A
N2-Fe-F1
Fe-F1-B1
133.1(4)
3
4
Fe-N1
Fe-N2
Fe-N3
Fe-N4
Fe-O1
Fe‚‚‚O2
C19-O1
C19-O2
2.214(4)
2.195(3)
2.140(4)
2.198(4)
1.987(5)
2.85(1)
Fe-N1
Fe-N2
Fe-N3
Fe-N4
Fe-O1
Fe‚‚‚O2
C19-O1
C19-O2
2.202(4)
2.195(4)
2.159(4)
2.215(4)
2.009(4)
2.565(4)
1.265(6)
1.240(6)
7
Fe-N1
Fe-N2
Fe-S1
2.228(4)
2.189(4)
2.259(2)
N1-Fe-N1A
N1-Fe-N2
N1-Fe-N2A
N1-Fe-S1
N2-Fe-N2A
N2-Fe-S1
Fe-S1-C11
79.4(2)
1.223(8)
1.209(8)
76.1(2)
140.8(1)
108.9(1)
105.3(2)
107.8(1)
100.9(4)
N1-Fe-N2
N1-Fe-N3
N1-Fe-N4
N1-Fe-O1
N2-Fe-N3
N2-Fe-N4
N2-Fe-O1
N3-Fe-N4
N3-Fe-O1
N4-Fe-O1
O2‚‚‚Fe-O1
O2‚‚‚Fe-N1
O2‚‚‚Fe-N2
O2‚‚‚Fe-N3
O2‚‚‚Fe-N4
O1-C19-O2
81.2(1)
77.2(2)
140.6(1)
129.0(2)
146.3(1)
76.1(1)
101.5(2)
105.3(2)
112.3(2)
87.3(2)
48.5(2)
82.7(2)
111.7(2)
91.0(2)
135.7(2)
122.7(7)
N1-Fe-N2
N1-Fe-N3
N1-Fe-N4
N1-Fe-O1
N2-Fe-N3
N2-Fe-N4
N2-Fe-O1
N3-Fe-N4
N3-Fe-O1
N4-Fe-O1
O2‚‚‚Fe-O1
O2‚‚‚Fe-N1
O2‚‚‚Fe-N2
O2‚‚‚Fe-N3
O2‚‚‚Fe-N4
O1-C19-O2
81.0(2)
78.2(1)
133.1(1)
133.6(2)
148.6(2)
74.6(2)
96.5(2)
103.5(2)
114.9(2)
89.0(2)
55.1(1)
84.0(1)
115.3(1)
85.7(1)
142.7(1)
120.2(5)
Most significant is the ability of 2 to be transformed into
structural models of SORRed via its reaction with aromatic
or aliphatic thiolates. For example, reaction of 2 with the
sodium salts of para- or meta-methylbenzenethiolate pro-
vided yellow-orange crystals of [L8py2Fe(SC6H4-p-CH3)]BF4
(5) and [L8py2Fe(SC6H4-m-CH3)]BF4 (6), respectively. These
compounds were conveniently isolated in pure form by
filtration from the crude reaction mixture. In a similar
manner, reaction of 2 with sodium cyclohexanethiolate
produced yellow crystals of [L8py2Fe(SC6H11)]BF4 (7). The
alkylthiolate ligation of this complex closely models the
cysteine thiolate ligand present in SORRed. Crystallographic
analyses confirm that these thiolate-ligated iron(II) complexes
replicate the structure of the SORRed active site.
reaction of L8py2 with [Fe(H2O)6](BF4)2 in CH3CN. This
compound is noteworthy not only because it contains a labile
η1-BF4- ligand but also because this tetrafluoroborate ligand
is able to compete so effectively with other, more strongly
donating H2O and CH3CN ligands for a vacant (axial) coor-
dination position on the iron center. Facile substitution of
the tetrafluoroborate ligand was demonstrated by the reaction
of 2 with carboxylate ions. Mixing 2 with sodium formate
in CH3OH produced pale yellow crystals of [L8py2Fe(O2-
CH)]BF4 (3), while a parallel reaction with sodium acetate
generated yellow crystals of [L8py2Fe(O2CCH3)]BF4 (4).
Structural Characterization. X-ray crystallographic data
for the complexes are collected in Tables 1 and 2, while
significant interatomic distances and angles are compiled in
Tables 3 and 4. Full listings of positional and anisotropic
displacement parameters, as well as complete tables of
interatomic distances and angles in CIF format, are provided
as Supporting Information.
(13) X-ray crystallographic data for [L8py2FeCl]2[Fe2Cl6], C36H46Cl8-
Fe4N8: triclinic, P1h, with a ) 8.358(2) Å, b ) 10.968(2) Å, c )
12.938(3) Å, R ) 77.29(3)°, â ) 85.48(3)°, γ ) 77.41(3)°, V )
1128.6(4) Å3, and Z ) 1 at 25 °C. Full matrix least squares refinement
on F2 provided current residuals R1 ) 0.0530, wR2 ) 0.1481, and
GOF ) 1.031 for 1641 reflections with I > 2σ(I) and 163 variables.
Full details of the structure determination will be reported elsewhere.
(14) X-ray crystallographic data for L8py2, C18H22N4: triclinic, P1h, with a
) 6.259(1) Å, b ) 11.198(3) Å, c ) 13.047(3) Å, R ) 113.28(2)°, â
) 94.18(2)°, γ ) 90.02(2)°, V ) 837.3(3) Å3, and Z ) 2 at 25 °C.
Full matrix least squares refinement on F2 provided current residuals
R1 ) 0.0587, wR2 ) 0.1516, and GOF ) 1.015 for 1604 reflections
with I > 2σ(I) and 199 variable parameters. Full details of the structure
determination will be reported elsewhere.
The X-ray crystal structure of 1 reveals a hexacoordinate
iron(II) ion bound by tetradentate L8py2 as well as by two
chloride ions (Figure 2). The iron(II) center adopts an
uncommon trigonal prismatic geometry, presumably because
of unfavorable steric interactions that would occur between
the two chloride ligands and the propylene chains of the
macrocyclic backbone if the complex were to adopt a more
regular, octahedral geometry. Indeed, the six-membered
chelate rings in 1 both adopt chair conformations, presumably
to minimize these steric interactions. The metal-ligand bond
Inorganic Chemistry, Vol. 41, No. 15, 2002 3939

Halfen et al.
Figure 3. Thermal ellipsoid representations (35% probability level), with
partial atom labeling schemes, of the cationic portions of 3 and 4. Hydrogen
atoms are omitted for clarity.
are significantly displaced from the position normally oc-
cupied by a metal-axial ligand bond in a square-pyramidal
transition metal complex (Figure 3). These deviations from
ideal geometry are most apparent in the O(1)-Fe-N(1) bond
angles, 129.0(2)° in 3 and 133.6(2)° in 4, which are
significantly perturbed from the ideal value of 90°. The
distorted geometries adopted by these complexes presumably
reflect weak binding of the second carboxylate oxygen atoms
to the iron centers. Weak interactions between the iron
centers and the dangling carboxylate oxygen atoms are
indicated by the Fe-O(2) distances (2.85(1) Å in 3 and
2.565(4) Å in 4), the small amount of C-O bond length
alternation in the carboxylate ions (∆C-O ) 0.014(8) Å for
3 and 0.025(6) Å for 4), and also the lengths of the Fe-
N(4) bonds, which are approximately trans to the Fe‚‚‚O(2)
interactions. In both complexes, the Fe-N(4) bonds are
elongated relative to the Fe-N(3) bonds (by 0.058(4) Å in
3 and 0.056(4) Å in 4), a bond length asymmetry that is
absent in the remainder of the pentacoordinate complexes
described herein. The asymmetric bidentate coordination of
the carboxylate ions in 3 and 4, in conjunction with the
Figure 2. Thermal ellipsoid representations (35% probability level), with
partial atom labeling schemes, of 1 and 2. Hydrogen atoms and uncoordi-
nated BF4 ions are omitted for clarity.
-
lengths in 1 are uniformly longer than those identified for
the remainder of the complexes reported herein, reflecting
the high coordination number of the iron center in this
complex. These structural features contrast with those of the
cation present in 2 (Figure 2) in which the tetradentate L8-
py2 ligand occupies four equatorial coordination sites of the
square-pyramidal iron(II) complex, complemented by an η1-
-
BF4 ligand bound in one axial position. Inspection of the
six-membered chelate rings in 2 reveals that one of them
-
(opposite the BF4 ligand) adopts a boat conformation;
similar coordination-number-dependent chelate ring confor-
mations in tetradentate ligands derived from diazacyclooctane
have been discussed previously.15 The iron(II) ion in 2 resides
0.59 Å above the plane of the four basal nitrogen donors,
-
-
ligation of the poor donor BF4 in their common precursor
2, may reflect significant Lewis acidity of the iron(II) center
in complexes of L8py2.
displaced toward the axial BF4 group. The Fe-F bond
length, 1.967(4) Å, is shorter than that present in the only
other iron-tetrafluoroborate complex structurally character-
ized to date, [Fe(η1-BF4)(CO)(depe)2]BF4 (Fe-F ) 2.081-
(6) Å), presumably because 2 lacks an additional donor group
The ultimate targets of the current synthetic study were
pentacoordinate iron(II)-thiolate complexes, and three such
compounds, 5-7, were isolated in forms amenable to
crystallographic analysis (Figure 4). These iron(II)-thiolate
complexes share a common structural motif: all contain a
regular, square-pyramidal iron(II) center, with a basal plane
of four nitrogen donors provided by the tetradentate L8py2
ligand, complemented by an axial aryl- or alkylthiolate donor.
As was the case in the other square-pyramidal iron(II)
complexes described previously, the iron(II) ions in the
thiolate complexes are displaced from the basal plane of four
nitrogen donors toward the axial thiolate ligands (by 0.67,
0.67, and 0.69 Å, in 5, 6, and 7, respectively). The Fe-S
bond lengths in the iron(II)-thiolate complexes are some-
-
trans to its BF4 ligand.16 As expected, the terminal B-F
bonds are shorter than that present in the B-F-Fe unit.
Complex 2 has proven to be a versatile starting material for
the synthesis of numerous pentacoordinate iron(II) complexes
of L8py2.
The X-ray crystal structures of formate complex 3 and
acetate complex 4 reveal iron(II) complexes with distorted
pentacoordinate geometries, in which the Fe-O(1) bonds
(15) Buonomo, R. M.; Reibenspies, J. J.; Darensbourg, M. Y. Chem. Ber.
1996, 129, 779-784.
(16) depe ) 1,2-bis(diethylphosphino)ethane: Landau, S. E.; Morris, R.
H.; Lough, A. J. Inorg. Chem. 1999, 38, 6060-6068.
3940 Inorganic Chemistry, Vol. 41, No. 15, 2002

Synthetic Models of Superoxide Reductase
the structural and electronic differences between the por-
phyrin ligands and L8py2. The structure of the Schiff base
complex is quite similar to those of 5-7, although the N2O2
basal donor set provided by the 5-NO2salen2- ligand fails
to replicate the array of biological donor groups present in
the SOR active site. Also relevant to the iron(II)-thiolate
complexes reported herein are two non-heme iron(II) com-
plexes with N4S donor sets, [(TPA)Fe(SC6H2-2,4,6-(CH3)3)]-
20
ClO4 and [FeSMe2N4(tren)]PF6, the latter of which is
- 21
oxidized to a stable Fe(III) analogue by O2 . While the
trigonal-bipyramidal geometries of these two complexes do
not replicate the square-pyramidal structure of SORRed, the
latter compound does model SOR reactivity.
Physical, Spectroscopic, and Electrochemical Properties
of SOR Model Complexes. The metal-ligand bond lengths
identified by X-ray crystallography suggest that the iron-
(II)-thiolate complexes contain high-spin (S ) 2) iron(II)
ions.22 These assignments were confirmed by solid-state
magnetic susceptibility measurements (Table 5), which
provided magnetic susceptibilities ranging from 4.52 to 5.27
µB for the complexes described previously. Of particular
significance is that the S ) 2 ground state of these iron-
(II)-thiolate complexes replicates that of SORRed.
3b,4c With
the exception of tetrafluoroborate-ligated complex 2, the iron-
(II) complexes of L8py2 are yellow in color, the result of
electronic transitions in the high-energy region of the visible
spectrum (Table 5). The electronic absorption spectra of the
iron(II)-thiolate complexes are complex, because of multiple
overlapping transitions between 300 and 425 nm; such
complexity is not apparent in the optical spectra of complexes
2-4, which lack axial thiolate ligation. For example, the
UV-vis spectrum of 7 (Figure 6), whose axial cyclohex-
anethiolate ligand best models the cysteinate donor present
in SORRed, was fit by four overlapping Gaussian transitions
centered at 254 nm (7000 M-1 cm-1), 305 nm (830 M-1
cm-1), 340 nm (1800 M-1 cm-1), and 424 nm (300 M-1
cm-1). While a detailed analysis of these visible spectroscopic
features is not supported by the available data, it seems
reasonable to suggest that one or more of these transitions
may result from a thiolate-to-iron(II) LMCT transition, as
recently identified for SORRed; in the enzyme from Pyro-
coccus furiosus, charge-transfer transitions involving the iron-
Figure 4. Thermal ellipsoid representations (35% probability level), with
partial atom labeling schemes, of the cationic portions of 5-7. Hydrogen
atoms are omitted for clarity.
what sensitive to the nature of the thiolate ligands, spanning
a range of 2.259(2)-2.323(3) Å in the three complexes
described herein. The Fe-S bond length in 7 is the shortest
in this series, perhaps reflecting the increased electron-
donating ability of the aliphatic thiolate relative to the
aromatic thiolates. With their square-pyramidal geometries,
basal planes of four neutral nitrogen donors, and vacant
coordination sites trans to their axial thiolate ligands, iron-
(II)-thiolate complexes 5-7 model the [FeII(Nhis)4(Scys)]
structure of SORRed.4 Specific comparisons between the
metrical parameters of SORRed and its synthetic models are
provided in Figure 5.
(17) (a) Schappacher, M.; Ricard, L.; Weiss, R.; Montiel-Montoya, R.;
Gonser, E.; Bill, E.; Trautwein, A. X. Inorg. Chim. Acta 1983, 78,
L9-L12. (b) Schappacher, M.; Ricard, L.; Fischer, J.; Weiss, R.;
Montiel-Montoya, R.; Bill, E.; Trautwein, A. X. Inorg. Chem. 1989,
28, 4639-4645. (c) Caron, C.; Mitschler, A.; Riviere, G.; Ricard, L.;
Schappacher, M.; Weiss, R. J. Am. Chem. Soc. 1979, 101, 7401-
7402.
(18) 5-NO2salen ) 1,2-bis-(5-nitrosailcylidineamino)ethane: Mukherjee,
R. N.; Abrahamson, A. J.; Patterson, G. S.; Stack, T. D. P.; Holm, R.
H. Inorg. Chem. 1988, 27, 2137-2144.
The compounds with structures most closely related to
5-7 are square-pyramidal iron(II)-thiolate complexes,
including several porphyrin-supported iron(II)-thiolate spe-
cies,17 as well as the Schiff-base-ligated complex Et4N[(5-
NO2salen)Fe(SC6H4-p-CH3)].18 The porphyrin-ligated com-
pounds model the high-spin ferrous state of the heme enzyme
cytochrome P-450,19 and as a result, detailed comparisons
between these complexes and 5-7 are tenuous because of
(19) Sono, M.; Roach, M. P.; Coulter, E. D.; Dawson, J. H. Chem. ReV.
1996, 96, 2841-2887.
(20) TPA ) tris(2-pyridylmethyl)amine: Zang, Y.; Que, L., Jr. Inorg.
Chem. 1995, 34, 1030-1035.
(21) SMe2N4(tren) ) 3-{2-[bis(2-aminoethyl)amino]ethylimino}-2-meth-
ylbutane-2-thiol: Shearer, J.; Nehring, J.; Lovell, S.; Kaminsky, W.;
Kovacs, J. A. Inorg. Chem. 2001, 40, 5483-5484.
(22) (a) Blakesley, D. W.; Payne, S. C.; Hagen, K. S. Inorg. Chem. 2000,
39, 1979-1989. (b) Diebold, A.; Hagen, K. S. Inorg. Chem. 1998,
37, 215-223.
Inorganic Chemistry, Vol. 41, No. 15, 2002 3941

Halfen et al.
Figure 5. Core structures of SORRed and its synthetic models 5-7, with significant metrical details noted. Bond lengths and angles for SORRed are taken
from refs 4b (single-crystal X-ray, high-occupancy iron site “A”) and 4c (EXAFS).
Table 5. Magnetic Susceptibility, UV-Vis Spectroscopic, and
The oxidation potentials of iron(II)-thiolate complexes
5-7 are uniformly lower than those of 2, 3, or 4, reflecting
Electrochemical Data
b
complex
µ
eff (µB)a
λ
max, nm (ꢀ, M-1 cm-1
)
E
pa (mV)c
increased electron densities at the iron(II) centers in the
thiolate complexes relative to those in the tetrafluoroborate
and carboxylate complexes. Moreover, the anodic peak
potentials of the thiolate complexes reflect the relative
electron-donating abilities of the bound thiolate ligands. Thus,
the oxidation potential of 7, which contains the most electron
rich, aliphatic thiolate ligand, is lower than those of 5 and
6, which contain less electron rich, aromatic thiolate ligands.
The irreversibility of all of these oxidative processes suggests
that the electrochemically generated iron(III)-thiolate com-
plexes undergo decomposition in solution, preventing their
facile electrochemical reduction to the original iron(II)-
thiolate state. We speculate that this reaction is a bimolecular
process in which two iron(III)-thiolate complexes undergo
an internal redox reaction to form 2 equiv of an unidentified
iron(II) complex and 1 equiv of a disulfide. In support of
this notion, chemical oxidation of 5 with AgPF6 in CH2Cl2
produced p-tolyl disulfide, identified by GC/MS analysis of
the resultant solution; similar reactivity was observed previ-
ously for the Schiff base-ligated iron(II)-thiolate complex
Et4N[(5-NO2salen)Fe(SC6H4-p-CH3)].18 Finally, while 5-7
are irreversibly oxidized at room temperature, the cyclic
voltammogram of 7 at -20 °C reveals an electrochemically
reversible (∆Ep ) 87 mV) but chemically quasireversible
(ipc/ipa ) 0.6) redox couple with E°′ ) 470 mV versus SCE.
Thus, chemical oxidation of 7 to its (metastable) Fe(III)-
thiolate redox partner may be possible under conditions of
reduced temperatures and/or high dilution. Efforts to generate
and characterize such a species are ongoing.
2
3
4
5
4.85
4.92
4.52
5.27
261 (9600), sh 332 (790)
262 (8000), 364 (420)
261 (6400), 374 (440)
255 (14000), sh 309 (3400),
sh 405 (820)
269 (13000), sh 305 (3100),
sh 402 (570)
254 (7000), sh 305 (830),
340 (1800), sh 424 (300)
+1228
+941
+844
+615
6
7
4.98
4.70
+655
+565
a Solid-state magnetic susceptibility determined at room temperature.
b Measured in CH3CN (sh ) shoulder). c Measured in CH3CN with 0.1 M
Bu4NClO4. Potentials are quoted versus SCE at a scan rate of 100 mV‚sec-1
.
Figure 6. Electronic absorption spectrum of 7 in CH3CN.
(II) center occur at 295 nm (identified by MCD) and 320
nm.4c Examination of 5-7 by MCD and resonance Raman
spectroscopy may clarify the nature of the optical transitions
observed in these iron(II)-thiolate complexes.
The redox chemistry of iron(II)-thiolate complexes 5-7
was probed using electrochemical methods. At room tem-
perature, 5-7 exhibit irreversible oxidation processes in their
cyclic voltammograms (Table 5), with anodic peak potentials
(Epa) that are uniformly higher than that of the reversible
Fe(II)/Fe(III) redox potential of SOR (E° ) -33(4) mV
versus SCE for the SOR from Treponema pallidum, -2(10)
mV versus SCE for the SOR from P. furiosus).3b,4c The
divergence among the redox potentials of 5-7 and those of
SOR is at least partially rooted in the different solvent
systems used for the electrochemical measurements (CH3-
CN for 5-7; aqueous, pH ) 7.5-7.8 buffer for SOR).3b,4c
Unfortunately, the low solubility of 5-7 in water precludes
determination of their redox potentials in aqueous solution.
Summary
We have prepared and characterized a family of iron(II)-
thiolate complexes that model the square-pyramidal [FeII-
(Nhis)4(Scys)] structure and high-spin, S ) 2 electronic ground
state of the reduced active site of superoxide reductase.
Electrochemical studies at ambient temperature reveal that
the oxidized forms of these complexes are unstable relative
to the formation of organic disulfides and thus indicate that
further tuning of the structural and/or electronic properties
of this family of model compounds is necessary to replicate
the facile one-electron redox cycling that is characteristic of
the enzyme. Ongoing synthetic, spectroscopic, and reactivity
studies of compounds that model SORRed may provide
3942 Inorganic Chemistry, Vol. 41, No. 15, 2002

Synthetic Models of Superoxide Reductase
significant insights into superoxide detoxification pathways
in biological systems.
sity of Wisconsin-Eau Claire. We thank Prof. Lawrence Que,
Jr., for helpful discussions.
Supporting Information Available: Complete X-ray crystal-
lographic information in CIF format. This material is available free
of charge on the Internet at http://pubs.acs.org.
Acknowledgment. Funding in support of this work was
provided by the National Science Foundation (CHE-
0078746), the Camille and Henry Dreyfus Foundation (Henry
Dreyfus Teacher-Scholar Award to J.A.H.), and the Univer-
IC025517L
Inorganic Chemistry, Vol. 41, No. 15, 2002 3943