Synthesis and structure of a biomimetic model of the iron hydrogenase active site covalently linked to a ruthenium photosensitizer

Article abstract of DOI:10.1002/anie.200351192

First synthetic steps towards light-driven hydrogen production have been achieved by covalently linking a [Ru^II(terpy)₂] (terpy=2,2′:6′,2″-terpyridine) photosensitizer to a biomimetic model of the iron hydrogenase active site (see picture). The IR data show that there is little electronic communication between the redox-active metal centers in the ground state.

Full text of DOI:10.1002/anie.200351192

Angewandte
Chemie
Electron-Transfer Processes
Synthesis and Structure of a Biomimetic Model of
the Iron Hydrogenase Active Site Covalently
Linked to a Ruthenium Photosensitizer**
Sascha Ott, Mikael Kritikos, Björn Škermark,* and
Licheng Sun*
Although known for more than 75 years,[1] sulfur-containing
binuclear complexes of iron have recently experienced a
renaissance as interesting synthetic targets as they closely
resemble the active site of iron hydrogenases (FeH), a
naturally occurring class of enzymes which regulate the
production and consumption of hydrogen in microorgan-
isms.[2–5] Crystallographic studies revealed the active site of
the natural system to consist of two iron(i) cations which are
linked by an unusual bridging dithiolate ligand.[6,7] It has been
[*] Prof. Dr. B. Škermark, Dr. L. Sun, Dr. S. Ott
Department of Organic Chemistry
Arrhenius Laboratory, Stockholm University
10691 Stockholm (Sweden)
Fax: (+46)8-154-908
E-mail: bjorn.akermark@organ.su.se
licheng.sun@organ.su.se
Dr. M. Kritikos
Department of Structural Chemistry
Arrhenius Laboratory, Stockholm University
10691 Stockholm (Sweden)
[**] The authors thank Dr. Jonas Bergquist and Charlotte Hagman
(University of Uppsala) for the measurement of the ESI mass
spectrum of 1. Financial support for this work was provided by the
Swedish Energy Agency, the Knut and Alice Wallenberg Foundation,
the Swedish Research Council for Natural Science (NFR), and the
Swedish Research Council (VR).
Angew. Chem. Int. Ed. 2003, 42, 3285 – 3288
DOI: 10.1002/anie.200351192
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3285

Communications
suggested that this ligand contains a nitrogen heteroatom and
possesses the structure SCH2NHCH2S.[8,9] The remaining
primary coordination sphere around the dinuclear iron
active site is occupied by the diatomic ligands CO and CNꢀ,
as well as by a thiol-linked tetranuclear Fe cluster.[6,7,10–12] In
the natural system one coordination site remains vacant to
allow for hydride or hydrogen coordination.[10]
Recently, Rauchfuss and co-workers have shown that a
biomimetic model of FeH can serve as a catalyst for electro-
chemical hydrogen production.[13] In the context of our
interest in photochemical fuel production[14] we became
intrigued by the possibility of covalently linking a biomimetic
model of the iron hydrogenase active site to a ruthenium
photosensitizer in an attempt to afford hydrogen production
by the action of light. The projected process is illustrated in
Figure 1. It commences with the absorption of a photon by the
ruthenium photosensitizer (step 1, Figure 1). The photoex-
cited ruthenium complex is oxidatively quenched by the
dinuclear iron site, which gives rise to a reduced iron species
(step 2, Figure 1). After regeneration of the photosensitizer
(by an external electron donor), this process is repeated to
afford a doubly reduced diiron species which could then drive
the reduction of protons. The possibility of introducing
ligands different from CO on to the iron portion of the
system is of great importance as the redox properties of the
structure can thereby be altered significantly to
Figure 1. Schematic representation for the projected photoinduced
reduction of protons. L=CO, CNꢀ, PX3, or thiolates.
suit the electronic requirements of this process.
We recently prepared a ruthenium(tris)bi-
pyridine type of photosensitizer linked to a
diiron complex, in which the iron atoms are
connected by a dithiol bridge.[15] Herein we
present the synthesis of a novel system in which
a 2-aza-1,3-dithiol-bridged dinuclear iron com-
plex is covalently linked to a ruthenium photo-
sensitizer. The system was designed to fulfil
various aspects: [Ru(terpy)2]2+ (terpy =
2,2’:6’,2’’-terpyridine) was chosen as the photo-
sensitizer because of its geometric advantages
over other Ru complexes with didentate
ligands.[16] An acetylenic linker between the
redox-active termini was selected not only to
Scheme 1. a) p-CH2O, CH2Cl2, RT, 3 h; b) SOCl2, RT, 30 min; c) Li2(SFe(CO)3)2, THF,
ꢀ788C, 5 min, 76%; d) 4’-ethynyl-2,2’:6’,2’’-terpyridine, [PdCl2(PPh)2], CuI, Et3N, tolu-
ene, 408C, 3 h, 57%; e) [RuCl2(terpy)]·DMSO, MeOH, reflux, 4 h, 29%.
gain precise control over their spatial separa-
tion, but also to prolong the lifetime of the
excited state of [Ru(terpy)2]2+[17] so that elec-
tron transfer to the iron portion can occur.
Finally, the dithiolate bridge in the diiron site was chosen to
contain a nitrogen heteroatom, as this arrangement may play
an essential role in the production of hydrogen in the natural
system.[8,9] With this reasoning, 1 was selected as the target
complex.
The diiron portion was established by applying a recently
published procedure for the preparation of some related
complexes.[18] Thus, the lithium salt of diironhexacarbonyldi-
sulfide[19] was treated with N,N-di(chloromethyl)-4-iodoani-
line (2), which in turn was synthesized from p-iodoaniline in
two steps (Scheme 1).[18] Structural analysis of 3 by single-
crystal X-ray diffraction[20] (Figure 2) revealed the familiar
distorted square-pyramidal arrangement around the iron
agreement with other crystal structure data of this type of
complex.[18,21] The arene substituent resides in an axial
position directly above one carbonyl ligand. The p conjuga-
tion between the phenyl ring and the nitrogen p orbital is
somewhat interrupted in the solid state, as evident from a
deviation of the nitrogen atom by 0.164(3) Š from the plane
defined by the C7, C8, and C9 atoms. The sum of the C-N-C
angles around N1 is 3568. The azadithiolate-bridged diiron
species 3 represents the first complex of this kind where the
nitrogen atom is linked to an aromatic system.
The iodo functionality in the iron complex 3 could be
utilized for further elaboration by reaction of the former
complex with 4’-ethynyl-2,2’:6’,2’’-terpyridine[22,23] under the
cross-coupling conditions used by Sonogashira et al.[24] to
ꢀ
nuclei. The Fe Fe bond length of 2.499(1) Š is in good
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Angewandte
Chemie
exhibit three major bands in the CO region at 2076, 2038, and
2001 cmꢀ1. This resemblance indicates that the iron carbonyl
portion is insensitive to the presence of an acetylenic
substituent on the aniline as well as to the terpyridine.
Solutions of 4 in organic solvents are unstable at room
temperature and decompose within minutes upon exposure to
light, presumably as a result of light-induced decarbonylation
followed by intermolecular terpyridine complexation. How-
ever, as a freshly prepared solution in methanol which is kept
in the dark, ligand 4 coordinates readily to the {Ru(terpy)}
fragment,[25] which gives rise to the desired trinuclear complex
1. The IR spectrum of a solution of 1 in CH2Cl2 shows a
pattern in the CO region that is identical to that found for
complexes 3 and 4. This observation indicates there is
negligible electronic communication between the redox-
active ruthenium center and the iron termini. In contrast to
4, solutions of 1 are stable and can be stored under ambient
conditions for extended periods of time.
Whereas the vast majority of reports in the past have
concentrated on ligand-exchange reactions on the Fe-Fe
portion,[2–5] this work represents one of the few examples in
the literature[26] where chemistry is performed on the organic
bridge of an assembled dinuclear iron complex and ultimately
leads to a covalent connection to a ruthenium photosensitizer.
The preparation of 4 with its free terpyridine metal-binding
pocket will enable the incorporation of many different metals,
thus offering an insight into electron-transfer processes in a
biomimetic model of the active site of FeH. The design of 1
allows the exchange of ligands on the iron portion to facilitate
electron transfer from the photoexcited ruthenium complex.
Such a modified molecular assembly could promote the light-
driven reduction of protons. Experimental efforts in these
directions together with in-depth photophysical studies of the
system are currently in progress.
Figure 2. ORTEP (ellipsoids at 30% probability level) view of 3[20]
Selected bond lengths [Š]: Fe1-Fe2 2.4988(8), Fe1-S1 2.2537(10), Fe1-
S2 2.2630(10), Fe2-S1 2.2573(10), Fe2-S2 2.2682(10), Fe1-C1 1.798(4),
Fe1-C2 1.799(3), Fe1-C3 1.795(4), Fe2-C4 1.778(4), Fe2-C5 1.792(4),
Fe2-C6 1.812(4), S1-C7 1.847(4), S2-C8 1.861(4), N1-C7 1.431(5) N1-
C8 1.413(5), N1-C9 1.404(5).
afford the terpyridine-coupled dinuclear iron complex 4. In
the solid state, the iron carbonyl portion of 4 is stable towards
ligand substitution by the polypyridine unit as unambiguously
demonstrated by single-crystal X-ray diffraction studies[20]
(Figure 3). Apart from the ethynylterpyridine fragment, the
crystal structure of 4 closely resembles that of 3. The rigidity
of the system enables the distance from the nitrogen atom
(N2) of the central pyridine ring to the Fe cations to be
calculated as 11.892(3) and 13.996(3) Š. The electronic
similarities between complexes 3 and 4 are further corrobo-
rated by their respective IR spectra, which are alike and
Experimental Section
4: [PdCl2(PPh3)2] (18 mg, 0.025 mmol) and CuI (2 mg, 0.01 mmol)
were added successively to a degassed solution of iodoarene 3
(150 mg, 0.25 mmol) and 4’-ethynyl-2,2’:6’,2’’-terpyridine (73 mg,
0.28 mmol) in triethylamine and toluene (1:1, 20 mL) at 408C. After
the mixture had been stirred in the dark for 3 h at this temperature, it
was concentrated in vacuo and the black residue was subjected to
column chromatography, conducted in the dark (Al2O3, CH2Cl2), to
give 4 as a red solid (102 mg, 0.14 mmol, 57%). Elemental analysis
(%) calcd for C31H18Fe2N4O6S2: C 51.83, H 2.52, N 7.80; found: C
51.70, H 2.62, N 7.67; 1H NMR (300 MHz, CDCl3): d = 8.71 (m, 2H),
8.59 (m, 2H), 8.54 (s, 2H), 7.85 (m, 2H), 7.50 (d, J = 8.7 Hz, 2H), 7.34
(m, 2H), 6.70 (d, J = 8.7 Hz, 2H), 4.30 ppm (s, 4H, NCH2S); 13C NMR
(75 MHz, CDCl3): d = 206.8, 155.7, 155.4, 149.1, 144.7, 136.9, 133.8,
133.7, 123.9, 122.6, 121.2, 115.3, 113.6, 94.1, 87.0, 49.4 ppm; IR
ꢀ1
ꢁ
¼
(CH2Cl2): n˜ = 2214 (C C), 2076, 2038, 2001 cm (C O).
1: [RuCl2(terpy)(DMSO)] (67 mg, 0.14 mmol) was added to a
degassed solution of 4 (100 mg, 0.14 mmol) in methanol (30 mL). The
mixture was refluxed in the dark for 4 h, before the solvent was
removed in vacuo. The remaining brown solid was purified by flash
chromatography on silica gel (solvent: CH3CN:H2O:sat. aq KNO3 =
90:9:1). After removal of the solvent in vacuo and anion exchange
with NH4PF6, the red solid was recrystallized from CH2Cl2/Et2O
(55 mg, 0.04 mmol, 29%). Elemental analysis (%) calcd for
C46H29F12Fe2N7O6P2RuS2: C 41.21, H 2.18, N 7.31; found: C 41.50,
H 2.15, N 7.56; 1H NMR (300 MHz, CD3CN): d = 8.82 (s, 2H), 8.75 (d,
Figure 3. ORTEP (ellipsoids at 30% probability level) view of 4[20]
Selected bond lengths [Š]: Fe1-Fe2 2.5056(7), Fe1-S1 2.2625(9), Fe1-S2
2.2631(9), Fe2-S1 2.2559(9), Fe2-S2 2.2576(8), Fe1-C1 1.778(4), Fe1-C2
1.789(4), Fe1-C3 1.778(4), Fe2-C4 1.784(4), Fe2-C5 1.785(4), Fe2-C6
1.801(4), S1-C7 1.850(3), S2-C8 1.852(3), N1-C7 1.432(4) N1-C8
1.424(4), N1-C9 1.402(4).
Angew. Chem. Int. Ed. 2003, 42, 3285 – 3288
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Communications
J = 8.3 Hz, 2H), 8.49 (m, 4H), 8.42 (t, J = 8.3 Hz, 1H), 7.93 (m, 4H),
[21] J. D. Lawrence, H. Li, T. B. Rauchfuss, M. Benard, M.-M.
Rohmer, Angew. Chem. 2001, 113, 1818 – 1821; Angew. Chem.
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[22] K. T. Potts, D. Konwar, J. Org. Chem. 1991, 56, 4815 – 4816.
[23] V. Grosshenny, F. M. Romero, R. Ziessel, J. Org. Chem. 1997, 62,
1491 – 1500.
[24] K. Sonogashira, Y. Tohda, N. Hagihara, Tetrahedron Lett. 1975,
16, 4467 – 4470.
[25] T. Norrby, A. Börje, B. Škermark, L. Hammarström, J. Alsins,
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Chem. 1997, 36, 5850 – 5858.
7.70 (d, J = 9.0 Hz, 2H), 7.39 (m, 2H), 7.34 (m, 2H), 7.17 (m, 4H),
6.98 (d, J = 9.0 Hz, 2H), 4.50 ppm (s, 4H, NCH2S); 13C NMR
(75 MHz, CD3CN): d = 209.0, 159.6, 159.3, 156.9 (2C), 154.2 (2C),
147.6, 139.8 (2C), 137.7, 135.6, 132.3, 129.3, 128.1, 126.5, 126.1 (2C),
ꢁ
125.4, 117.4, 113.0, 99.7, 87.4, 50.8 ppm; IR (CH2Cl2): n˜ = 2192 (C C),
2077, 2038, 2001 cmꢀ1 (C = O); ESI-MS: Ru-isotopic pattern centered
at m/z = 1197.9 (100%) [MꢀPF6ꢀ]+, calcd for [MꢀPF6ꢀ]+: m/z =
1197.9.
Received: February 17, 2003
[26] S. Salyi, M. Kritikos, B. Škermark, L. Sun, Chem. Eur. J. 2003, 9,
557 – 560.
Revised: May 19, 2003 [Z51192]
Keywords: bioinorganic chemistry · enzyme models ·
.
iron hydrogenase · ruthenium · structure elucidation
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