{2Fe3S} clusters related to the di-iron sub-site of the H-centre of all-iron hydrogenases

Article abstract of DOI:10.1039/b102244j

The first synthetic {2Fe3S} clusters structurally related to the sub-site of the H-centre of the all-iron hydrogenases are described: tripodal dithiolate thioether ligands allow the synthesis of di-iron pentacarbonyls with differential (2:3) S ligation of the Fe atoms.

Full text of DOI:10.1039/b102244j

{2Fe3S} clusters related to the di-iron sub-site of the H-centre of
all-iron hydrogenases
Mathieu Razavet, Sian C. Davies, David L. Hughes and Christopher J. Pickett*
Department of Biological Chemistry, John Innes Centre, Norwich, UK NR4 7UH.
E-mail: chris.pickett@bbsrc.ac.uk
Received (in Cambridge, UK) 8th March 2001, Accepted 16th March 2001
First published as an Advance Article on the web 17th April 2001
The first synthetic {2Fe3S} clusters structurally related to the
sub-site of the H-centre of the all-iron hydrogenases are
described: tripodal dithiolate thioether ligands allow the
synthesis of di-iron pentacarbonyls with differential (2+3) S
ligation of the Fe atoms.
alised propanedithiol ligand C, Scheme 1.† The ligand reacts
with [Fe3(CO)12] to yield the {2Fe3S}-carbonyl D which has
been fully characterised by X-ray crystallography, Fig. 1(b),
and spectroscopy.‡
There are two independent molecules (plus their mirror
image molecules) in crystals of D. The two molecules are
essentially identical, and in each, the Fe–Fe distance is short,
mean value 2.512(4) Å, indicative of an iron–iron bond. Each
iron atom has five other contacts, in a square pyramidal
coordination pattern, with the iron atom displaced (mean)
0.382(10) Å from the mean base plane towards the apical
carbonyl ligand and 0.322(5) Å towards the thioether S atom. In
each molecule, the normals to the square base planes are
inclined at (mean) 74.7(6)° and the planes are hinged through
the two bridging thiolate sulfur atoms of the S3 ligands; the Fe–
X-Ray crystallographic data for Fe-only hydrogenases isolated
from Desulfovibrio desulfuricans1 and Clostridium pasteur-
ianum2 together with IR evidence show that the active centre of
the enzyme possesses an unprecedented {2Fe3S} sub-site at
which CO and CN ligands are bound.3 The two Fe atoms of the
sub-site share two bridging sulfur ligands of a propanedithiolate
or related unit4 with one of the Fe atoms additionally sulfur
ligated by a cysteinyl ligand bridged to a {4Fe4S} cluster, Fig.
1(a). Molecules with a {2Fe2S} propanedithiolate core and CO/
CN ligation have been synthesised5 which possess structural
elements of the CO inhibited sub-site.6 We now show that
formal backbone modification of the propanedithiolate ligand
allows access to carbonyls with a {2Fe3S} core with differential
S-ligation of the iron atoms, Fig. 1(b).
S
bridging distances have a mean value of 2.254(1) Å. The third S
atom, the thioether S, is coordinated to one of the iron atoms at
a similar, mean distance of 2.254(3) Å and occupies the apical
coordination site. Two carbonyl ligands occupy the base planes
on each iron and one occupies the apical site of the second iron
atom. The S3 ligand thus lies atop the Fe2(CO)5 unit and is
symmetrically arranged (with a pseudo-mirror plane through
the iron atoms and the apical groups) except for the thioether
methyl group which veers to one side or the other of the mirror
plane. Both enantiomers are present in these centrosymmetric
crystals.
The structural similarities between the enzyme sub-site and
the model compound are evident from Fig. 1. The Fe…Fe bond
distance in D and the average bridging Fe–S bond lengths are
similar to those distances estimated from the protein crystallo-
graphic data, which are 2.6 and 2.3 Å, respectively1,2 but the
thioether Fe–S distance in D is shorter than the corresponding
sub-site Fe–Scysteine distance in the enzyme which is ca 2.5 Å.
The benzyl analogue E is obtained by straightforward
modification of the synthesis, Scheme 1. Its crystal structure,
Fig. 2, confirms a conformation very similar to that of D with
only very minor differences in bond angles and dimensions.‡
We have monitored the reaction of complex D with 2
equivalents of cyanide [K+(18-crown-6) salt; MeCN]. This
reveals its conversion within 30 min to a new species F which
shows two distinct CN stretches, three terminal CO bands and a
bridging CO band at 1780 cm21, Scheme 2. F is indefinitely
stable in MeCN at 0 °C but on standing for 18 h at RT it slowly
transforms to a new species G . The IR pattern and frequencies
of G very closely resemble those of [Fe2(CO)4(CN)2-
Fig. 1 (a) Proposed structure of the H-centre of Fe-only hydrogenases; this
is a composite model combining features reported by Peters (PDB code
1FEH) and Nicolet (code 1HFE). (b) View of a molecule of the product
D.
Two thiolate sulfur ligands of the tripodal thiolate A7 are
readily coupled with dimethyl disulfide with formation of a
stable five-membered ring B, Scheme 1. This allows chemistry
to be carried out on the unprotected thiol group. Reaction with
MeI gives the thioether derivative, and subsequent reductive
cleavage of the disulfide bond gives the backbone function-
Scheme 1 Routes to ligands and complexes. Reagents: (a) i, MeI; ii,
LiAlH4; iii, H2SO4; (b) i, PhCH2Br; ii, LiAlH4; iii, H2SO4.
Fig. 2 View of the molecule of the product E.
DOI: 10.1039/b102244j
Chem. Commun., 2001, 847–848
This journal is © The Royal Society of Chemistry 2001
847

31.60(31.59); H, 3.05(3.04); S, 20.8 (21.8)%. Yield 49% (recrystallised
from hexane).
[Fe2(CO)5{PhCH2SCH2C(Me)(CH2S)2]: 1H NMR (400 MHz, CD2Cl2):
2
d 0.90 (3H, s, CH3), 1.70 [2H, d, J 14 Hz, (HHCCCHH)], 1.82 (2H, s,
CH2SCH2Ph), 2.28 [2H, d, 2J 14 Hz, (HHCCCHH)], 4.12 (2H, s, SCH2Ph),
7.40 (5H, m, SCH2C6H5). FTIR (in CH3CN): n(CO) 1925w, 1981s, br,
2046s and 2073vw cm21. EIMS: m/z 508 {M}+, 480{M 2 CO}+, 452{M 2
2CO}+, 424{M
267{Fe2SSCH2Ph}+,
2
3CO}+, 396{M
2
4CO}+, 368{M
2
5CO}+,
231{Fe2SCH2C(Me)CH2S}+,
176{Fe2S2}+,
91{CH2Ph}+. Microanal.: C19H16O5S3Fe2, found(calc.): C, 40.26(40.16);
H, 3.57(3.15); S, 15.9(18.9)%. Yield 73% (recrystallised from MeCN).
‡ Crystal structure analyses. [Fe2(CO)5{MeSCH2C(Me)(CH2S)2}]: crystal
data: C11H12Fe2O5S3, M = 432.1, monoclinic, space group P21/n (equiv. to
no. 14), a
= 18.467(2), b = 10.9622(12), c = 16.906(2) Å, b =
105.267(8)°, V = 3301.6(6) Å3, Z = 8, Dc = 1.739 g cm23, F(000) =
1744, T = 293 K, m(Mo-Ka) = 21.5 cm21, l(Mo-Ka) = 0.71069 Å.
Deep red, irregular fragment of a diamond-shaped plate crystal, sealed in
a capillary. Preliminary photographic examination, then Nonius CAD4
diffractometer. 3528 Unique reflections to qmax
= 21°, the limit of
measurable intensities; 2614 ‘observed’ with I > 2sI. Corrections for slight
deterioration, absorption (semi-empirical y-scan methods) and elimination
of negative net intensities (Bayesian statistical methods). Structure
determination by direct methods in SHELXS8 (A), refinement by full-
matrix least-squares methods, on F2, in SHELXL9 (B). Final wR2 = 0.061,
R1 = 0.046 (B) for all 3528 reflections weighted w = s22(Fo2); for the
Scheme 2 Solution IR time course for reaction of D with cyanide in MeCN
and proposed pathway to the species F and G.
‘observed’ data, R1 = 0.028. Highest difference peaks (ca. 0.24 e Å23
)
close to a carbonyl ligand.
[Fe2(CO)5{PhCH2SCH2C(Me)(CH2S)2}]: crystal data: C17H16Fe2O5S3,
M = 508.2, triclinic, space group P1 (no. 2), a = 9.8755(11), b =
(SCH2CH2S)]22 5 showing a single n(CN) at 2075 cm21
, ,
¯
11.3853(13), c = 10.3912(13) Å, a = 110.555(10), b = 92.983(9), g =
104.374(9)°, V = 1047.2(2) Å3, Z = 2, Dc = 1.612 g cm23, F(000) = 516,
T = 293(1) K, m(Mo-Ka) = 17.1 cm21, l(Mo-Ka) = 0.71069 Å.
Very thin, red-brown plate mounted on a glass fibre. Similar dif-
fractometer procedure and processing, giving 3686 unique reflections to
qmax = 25° (2715 ‘observed’ with I > 2sI). No deterioration correction
necessary. Final wR2 = 0.105 and R1 = 0.053 (B) for all 3686 reflections
Scheme 2. FAB-MS of G shows a strong parent ion at 759 for
{(K+18-crown-6)[Fe2(CO)4(CN)2{MeSCH2C(Me)(CH2S)2}]}.
These preliminary results are consistent with the initial
formation of a CO bridged di-cyanide species F which slowly
isomerises to the metal–metal bonded terminal carbonyl species
G with dissociation of the methyl thioether group, Scheme 2.
This provides the first tentative evidence for the genesis of a
model complex with all the principal structural features of the
CO inhibited form of the natural sub-site: two cyanide groups,
terminal and bridging CO ligands, and a {2Fe3S} core.§
Finally, we see in the preparation of E that a thiolate-
protected rather than -blocked group can been introduced at one
of the iron atoms: this or other S-protection/deprotection
approaches should open up further chemistry of the synthetic
sub-site.
2
weighted w = [s2(Fo2) + (0.0579P)2]21, with P = (Fo2 + 2Fc )/3; for the
‘observed’ data only, R1 = 0.037. Highest difference peaks (to ca. 0.4
e Å23) all in the cluster core region.
CCDC 156989 and 161064. See http://www.rsc.org/suppdata/cc/b1/
b102244j/ for crystallographic data in .cif or other electronic format.
§ Well-resolved IR data for the oxidised CO inhibited H-centre have been
reported recently by De Lacey et al.10 giving: n(CN) at 2096 and 2089
cm21; n(COterminal) at 2016, 1972 and 1963 cm21; and n(CObridging) at 1811
cm21. In this paramagnetic state the di-iron sub-site is magnetically
described as a localised mixed-valence state, though critically whether FeII–
FeIII or FeI–FeII was undecided.11 The data we have at hand for the FeI–FeI
species F show+n(CN) at 2083 and 2077 cm21; n(COterminal) at 1957, 1919
We thank the BBSRC and the John Innes Foundation for
supporting this work. Drs D. J. Evans and J. R. Sanders are
thanked for helpful discussion.
and 1878 cm21; and n(CObridging) at 1780 cm21. Thus Dn(COterminal
)
corresponds to 59, 53 and 85 cm21 respectively with Dn(CObridge) = 31
cm21. These magnitudes are consistent with the oxidised CO-form of the
sub-site having the FeI–FeII configuration (i.e. it is one-electron oxidised
with respect to F) and lends support to the deduction of De Lacey et al. that
proximal iron atom is in the Fe II state {Dn(CO) = 85 cm21} with the less
perturbed distal iron atom {Dn(CO) = 59, 53 cm21} in the FeI state.
Notes and references
1
† Spectroscopic and analytical data. MeC(CH2S)2CH2SH: H NMR (400
MHz, C6D5CD3): d 0.73 (3H, s, CH3), 0.89 (1H, t, 3J 9 Hz, SH), 2.07 (2H,
d, 3J 9 Hz, CH2SH), 2.27 [2H, d, 2J 11.2 Hz, (CHHSSCHH)], 2.48 [2H, d,
2J 11.2 Hz, (CHHSSCHH)]. FTIR (KBr): n(SH) 2551m, br cm21. EIMS:
m/z 166 {M}+, 133 {M 2 SH}+, 119 {M 2 CH2SH}+. Microanal.: C5H10S3,
found(calc.): C, 36.48(36.12); H, 6.14(6.06); S, 57.6(57.9)%. Yield 91%.
1 Y. Nicolet, C. Piras, P. Legrand, C. E. Hatchikian and J. C. Fontecilla-
Camps, Structure, 1999, 7, 13.
2 J. W. Peters, W. N. Lanzilotta, B. J. Lemon and L. C. Seefeldt, Science,
1998, 282, 1853.
3 A. J. Pierik, M. Hulstein, W. R. Hagen, S. P. J. Albracht and K. A.
Bagley, Eur. J. Biochem., 1998, 258, 572.
4 Y. Nicolet, B. J. Lemon, J. C. Fontecilla-Camps and J. W. Peters, TIBS,
138, 25, 2000.
5 A. Le Cloirec, S. P. Best, S. Borg, S. C. Davies, D. J. Evans, D. L.
Hughes and C. J. Pickett, Chem. Commun., 1999, 22, 2285; M. Schmidt,
S. M. Contakes and T. B. Rauchfuss, J. Am. Chem. Soc., 1999, 121,
9736; E. J. Lyon, I. P. Georgakaki, J. H. Reibenspies and M. Y.
Darensbourg, Angew. Chem., Int. Ed., 1999, 38, 3178.
6 B. J. Lemon and J. W. Peters, Biochemistry, 1999, 38, 12969.
7 C. Kolomyjec, J. Whelan and B. Bosnich, Inorg. Chem., 1983, 22,
2343.
1
MeC(CH2SH)2CH2SMe: H NMR (400 MHz, CD2Cl2): d 1.03 (3H, s,
CH3), 1.32 (2H, t, 3J 9 Hz, SH), 2.13 (3H, s, SCH3), 2.63 (2H, s, CH2SCH3),
2.63 [4H, d, 3J 9 Hz, (HSCH2CCH2SH)]. EIMS: m/z 182 {M}+, 101
{CH3C(CH2)2CH2S}+, 87 {CH3C(CH2)CH2S}+, 69 {CH3C(CH2)3}+, 61
{CH3CCH2}+, 47 {CH2SH}+. Microanal.: C6H14S3, found(calc.): C,
39.26(39.56); H, 7.70(7.59); S, 53.0(52.8)%. Yield 55%.
MeC(CH2SH)2CH2SCH2Ph: 1H NMR (400 MHz, CD2Cl2): d 0.90 (3H,
s, CH3), 1.11 (1H, t, 3J 9 Hz, SH), 2.46 (2H, s, CH2SCH2Ph), 2.47 [4H, d,
2J 9 Hz, (HSCH2CCH2SH)], 3.63 (2H, s, SCH2Ph), 7.24 (5H, m,
SCH2C6H5). EIMS: m/z 258 {M}+, 166{CH3C(CH2S)2CH2SH}+,
133{CH3C(CH2S)2CH2}+, 101{CH3C(CH2)2CH2S}+,
69{CH3C(CH2)3}+. Yield 31%.
91{CH2Ph}+,
[Fe2(CO)5{MeSCH2C(Me)(CH2S)2]: 1H NMR (400 MHz, CD2Cl2): d
0.90 (3H, s, CH3), 1.65 [2H, d, 2J 14 Hz, (HHCCCHH)], 2.05 (2H, br,
CH2SCH3), 2.23 [2H, d, 2J 14 Hz, (HHCCCHH)], 2.64 (3H, s, SCH3). FTIR
(in CH3CN): n(CO) 1925w, 1979s, br and 2046s cm21. EIMS: m/z 432
{M}+, 404{M 2 CO}+, 376{M 2 2CO}+, 348{M 2 3CO}+, 320{M 2
4CO}+, 292{M 2 5CO}+, 180{MeC(CH2S)2CH2SMe}+, 176{Fe2S2}+, 61
{CH3CCH2}+. Microanal.: C13H12O5S3Fe2·(0.1C6H14) found(calc.): C,
8 G. M. Sheldrick, Acta Crystallogr., Sect. A, 1990, 46, 467.
9 G. M. Sheldrick, SHELXL - Program for crystal structure refinement,
University of Göttingen, Germany, 1993.
10 A. L. De Lacey, C. Stadler, C. Cavazza, E. C. Hatchikian and V. M.
Fernandez, J. Am. Chem. Soc., 2000, 122, 11232.
11 C. V. Popescu and E. Munck, J. Am. Chem. Soc., 1999, 121, 7877.
848
Chem. Commun., 2001, 847–848