N2S2Ni metallothiolates as a class of ligands that support organometallic and bioorganometallic reactivity

Article abstract of DOI:10.1002/anie.200461747

It hinges on the ligand: The electron-donor ability of NiN ₂S₂ ligands is compared to that of traditional diphosphine and diimine ligands. Structural comparison of NiN₂S₂ and o-phenanthroline (phen) complexes of {W(CO)₄} and (PdX₂) units shows asymmetry imposed by the hinge bonding of the NiN₂S ₂ S donors (see superimposed structures) which favors stereo- and regioselective substrate addition.

Full text of DOI:10.1002/anie.200461747

Angewandte
Chemie
Nickel Complexes
N2S2Ni Metallothiolates as a Class of Ligands that
Support Organometallic and Bioorganometallic
Reactivity**
Marilyn V. Rampersad, Stephen P. Jeffery,
Joseph H. Reibenspies, Cesar G. Ortiz,
Donald J. Darensbourg, and Marcetta Y. Darensbourg*
That Cys-X-Cys tripeptide linkages can serve as tetradentate
N2S2 ligands, utilizing carboxamido nitrogen and cysteinyl
sulfur atoms as donors in metalloenzyme active sites, has
recently been verified in several protein crystal structures.[1–5]
It was further discovered that the nickel-bound Cys-Gly-Cys
NiN2S2 moiety of acetyl coA synthase binds through biden-
tate bridging thiolate groups to a second nickel center which
mediates the organometallic reactions required of the bio-
catalyst (the assembly of CH3 , CO, and SRꢀ into the
+
[1,2]
=
acetyl coA thioester CH3C( O)SR).
The (Cys-Gly-
Cys)Ni unit joins a host of synthetic NiN2S2 complexes that
are known to form multimetal clusters through m-SR inter-
actions. Natureꢀs control of binuclearity in the construction of
an organometallic catalyst presents the intriguing possibility
that the NiN2S2 complexes might be suitable for development
as a novel class of ligands for organometalllic chemistry and
catalysis. To this end we have characterized a series of NiN2S2
complexes, four of which are shown in Figure 1, according to
their electron-donating ability and stereochemical fea-
Figure 1. NiN2S2 complexes used as S-donor ligands; bme-daco=1,5-
(1,5-diazacyclooctane)di(ethylthiolate), bme*-daco=di(2-methyl-2-pro-
pylthiolate, bme-Me2pda=N,N’-dimethyl-2,9-diazanonanedithiolate,
ema4ꢀ =2,7-dioxo-3,6-diazaoctanedithiolate.
[*] M. V. Rampersad, S. P. Jeffery, Dr. J. H. Reibenspies, C. G. Ortiz,
Prof. Dr. D. J. Darensbourg, Prof. Dr. M. Y. Darensbourg
Department of Chemistry
Texas A&M University
College Station, TX 77843 (USA)
Fax: (+1)979-845-0158
E-mail: marcetta@mail.chem.tamu.edu
[**] We gratefully acknowledge the financial support from the National
Science Foundation (CHE 01-11629 and CHE 02-34860) and the
Robert A. Welch Foundation.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
Angew. Chem. Int. Ed. 2005, 44, 1217 –1220
DOI: 10.1002/anie.200461747
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Communications
tures.[6–9] These characteristics are contrasted to the classical
ligands of organometallic chemistry, diphosphines and di-
imines. The results are presented herein along with an
organometallic reaction principle that models steps in ace-
tyl coA synthase as well as CO/olefin copolymerization
catalysis.
According to Equation (1), NiN2S2 derivatives of tungsten
tetracarbonyl were prepared from the labile-ligand complex,
cis-[(piperidine)2W(CO)4].[10] Vibrational mode assignments
and n(CO) stretching frequencies are listed in Table 1.
fNiN2S2g þ cis-½ðpipÞ2WðCOÞ4ꢁ !
ð1Þ
cis-½ðNiN2S2Þ2WðCOÞ4ꢁ þ 2 HNC5H10
Table 1: IR data for [{NiN2S2}W(CO)4] and [(L2)W(CO)4] complexes.[a]
NiN2S2 or L2
(A11)
(B1)
(A21)
(B2)
(bme-daco)Ni
(bme*-daco)Ni
(bme-Me2pda)Ni
[Ni(ema)]2ꢀ
dmpm[b]
1995
1996
1993
1986
2007
2006
2000
1871
1871
1876
1853
1885
1887
1863
1853
1857
1843
1837
1885
1870
1852
1819
1816
1826
1791
1863
1830
1809
Figure 2. Ball-and-stick molecular structures of a) [Ni(bme-Me2pda)-
W(CO)4], b) [Ni(ema)W(CO)4]2ꢀ, c) [Ni(bme*-daco)W(CO)4], and
d) [(o-phenathroline)W(CO)4]. The dihedral angle is for the intersection
of the best planes of NiN2S2 and WS2C2.
bipy[c] or o-phen[d]
pip[e]
[a] n(CO) cmꢀ1, DMF solution spectra; assignments under C2v symmetry.
[b] dmpm=dimethyl phosphinomethane. [c] bipy=bipyridine. [d] o-
phen=o-phenanthroline. [e] pip=piperdine.
WS2C2 are identical, 1078, for the relatively flat [Ni(ema)]2ꢀ
and the Ni(bme-Me2pda) metallothiolate ligands, however,
the steric bulk of the geminal dimethyl groups on the carbon a
to the thiolate sulfur in the [(bme*-daco)Ni] complex opens
the hinge to 1368. The Ni···W separations of [Ni-
Of note is the similarity of the n(CO) values for the
W(CO)4 derivatives containing neutral NiN2S2 units; the
corresponding n(CO) values for species with the dianionic
complex, [Ni(ema)W(CO)4]2ꢀ are shifted negatively from
these by 8 to 35 cmꢀ1, dependent on the vibrational mode
compared. Thus as might be expected and as indicated by the
CO stretching frequencies, this dianionic ligand transfers
more electron density to the W(CO)4 unit than the neutral
NiN2S2 ligands.
(ema)W(CO)4]
(2.928 ꢁ),
[Ni(bme-Me2pda)W(CO)4]
(3.033 ꢁ), and [Ni(bme*-daco)W(CO)4] (3.389 ꢁ), reflect
the different hinge angles of the complexes. There is some
deviation from linearity of the CO groups closest to the
NiN2S2 plane, however the observed angles do not correlate
with steric bulk of the ligands. Note that the analogous CO
groups in the phenanthroline derivative of {W(CO)4} also
bend away from the position of the substituent ligand, despite
the fact that there is no possibility of a steric or lone-pair assist
to this deformation.
Also listed in Table 1 are the n(CO) values for cis-
[(pip)2W(CO)4] and representative classical bidentate P- and
N-donor ligands in [(LL)W(CO)4] complexes. From this data
_
we conclude that the electron-donating ability of neutral
NiN2S2 S-donor ligands towards the {W(CO)4} fragment is
greater than that of diphosphines, and closer in donor ability
to the o-phen and bipy ligands. The dianionic NiN2S2 ligand
derived from the ema tetraanion is a significantly better
donor. The electron-donating ability of these ligands to the
W(CO)4 moiety is:[Ni(ema)]2ꢀ > {NiN2S2}0 > phen > (pip)2 >
bipy > dmpm. The molecular structures of three
[{NiN2S2}W(CO)4] complexes are presented as ball and stick
drawings in Figure 2; for comparison, the structure of [(o-
phenanthroline)W(CO)4] is also shown.[11] The orientation
chosen for these depictions stresses the most prominent
structural feature of the nickel dithiolates: the dihedral angle
or hinge at the Ni(m-S)2W linkage that generates distinct
asymmetry to the molecule. Thus, the C2v symmetry used to
assign the n(CO) IR spectra holds only for the atom donor
sets in the first coordination sphere; the overall symmetry
from the molecular structure is Cs. The dihedral angles
defined by the intersection of best planes of NiN2S2 and
Listed in Figure 2 are the S-W-S angles, the “bite angles”
of the NiN2S2 bidentate ligands. The largest, 75.18 is for the
rigid ema ligand; the more flexible, neutral ligands have bite
angles of around 708. In addition, the S-Ni-S angles of the
tungsten-bound ligand, show only minor decreases from those
S-Ni-S angles in the free ligand (Figure 1 and Figure 2). As
ꢀ
ꢀ
the S W bonds are longer than the S Ni bonds, the S-W-S
bite angles are from 15–228 smaller than the corresponding
S-Ni-S angles of the free NiN2S2 ligands.
As the electron-donor abilities and the relatively flat form
of the NiN2S2 ligands mimic diimine ligands we sought a
model reaction for the purpose of contrasting organometallic
reactivity supported by diimine and NiN2S2 ligands. A logical
choice is the classical CO insertion process of interest in CO/
olefin copolymerization catalysis. This reaction also serves as
a biomimic of the CO insertion process of acetyl coA
synthase. While the exogenous (that is, as related to the
NiN2S2 moiety) nickel center is the active metal in both
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Angewandte
Chemie
processes, the palladium analogue offers greater stability
and the chance for isolating intermediates. The tmeda
ligand-displacement route developed by Boersma,
Van Koten, et al. for the preparation of diphosphine and
diimine derivatives of {NiMe2} and {PdMe2} units, was
used for the preparation of [Ni(bme-daco)PdMe2]
Scheme 1.[12] In CH3CN, the red-pink product obtained is
[Ni(bme-daco)PdMe2] as evidenced by mass spectral
analysis. Unfortunately, high-quality crystals were not
forthcoming. Crystals suitable for X-ray diffraction studies
were acquired from the reaction performed in CH2Cl2.
These crystals analyzed as the chloro-methyl derivative
[Ni(bme-daco)Pd(Me)Cl] whose molecular structure is
shown as a thermal ellipsoid plot in Scheme 1. In it, the
NiN2S2 unit from [(bme-daco)Ni] (Ni-1), binds to palla-
dium through bridging sulfur interactions forming a
square-planar {S2Pd(Me)Cl} unit in which the methyl
Scheme 2. a) Reaction of [(Ni-1)PdMe2] with acid and CO. b) IR spectra of
the reaction product and of the 13C-labeled product which agrees well with the
calculated isotope-shift bands.
Isotopic labeling was also used to explore the exchange
reaction of bound with free 13CO in [(Ni-1)Pd(CO)-
+
{C( O)Me}] in CH2Cl2. Under a 13CO atmosphere over the
=
course of 30 min at ꢀ788C, the IR spectrum of the solution
showed approximately 75% enrichment of the terminal CO
position while the acetyl 12CO band remained the major
species. Nevertheless, there was some build-up of a shoulder
on the lower energy side of the 1722 cmꢀ1 band which
indicated minor incorporation of 13CO into the acetyl
position.
The facile nature of the terminal CO exchange with free
13CO at ꢀ788C deserves comment. As the processes which
might create an open site, chelate ring-opening or CO
dissociation, are expected to have activation barriers that
could not be overcome at such low temperatures, we assume
that CO exchange proceeds by an associative process. A
similar five-coordinate intermediate would also account for
the deinsertion process that is required for the apparent
incorporation of some of the 13C label into the acetyl site. On
Scheme 1. Displacement of tmeda from [(tmeda)PdMe2] by
[Ni(bme-daco)] in CH2Cl2 and MeCN. The crystal structure of the prod-
uct obtained in CH2Cl2 is also shown; tmeda=N,N,N’,N’-tetramethyl-
1,2-ethanediamine.
and chlorine atoms are disordered; they were modeled with
50% occupancy of each site. The dihedral angle between the
two square planes is 101.38, and the Ni···Pd separation is
2.802 ꢁ.
ꢀ
the other hand, the strength of the Pd S bond in the NiS2Pd
ꢀ
chelate system is unknown and the breaking of one NiS2 Ni
bond in the theoretical model of acetyl coA synthase was
computed as a probably route for creating the open site
required for CO uptake and catalysis.[14] Further discussion at
this time would just be speculation.
In accordance with the method of Brookhart et al., for the
generation of an open site on an analogous [(o-phenanthro-
line)PdMe2][13] complex Scheme 2 depicts the reactivity of
[(Ni-1)PdMe2] with acid (HBAr’4; Ar’ = 3,5-(CF3)2C6H3 in
CH2Cl2 at ꢀ308C. On cooling this solution to ꢀ788C, purging
with CO produced a compound with n(CO) infrared bands at
2110 and 1722 cmꢀ1, assigned to a terminal and an acetyl CO
group, respectively, consistent with the structure proposed in
Scheme 2. With 13C-labeled CO (95% enriched), shifts in
both the terminal and the acetyl CO positions match the
calculated predictions of n(13CO) bands, supporting the
In 1995, Holm and Tucci demonstrated an essential
feature of acetyl coA synthase, the coupling of a thiolate
and a nickel-bound acetyl group using the [(bipy)NiMe2]
complex which readily reacts with a RSH source forming
[(bipy)NiMe(SR)] with subsequent thioester formation upon
introduction of CO gas.[15] NaSMe was added to [(Ni-
+
=
1)Pd(CO){C( O)Me}] in CH2Cl2 at ꢀ308C. On warming
the dark red solution to 228C, over the course of 1 h, the IR
spectrum showed diminished bands for the carbonyl groups of
the NiPd complex and growth of a band at 1686 cmꢀ1,
assignment (Scheme 2 b). For the analogous [(o-phen)Pd-
+
=
(CO){C( O)Me}] , the n(CO) bands are at 2127 (terminal
CO) and 1745 cmꢀ1, (acetyl C O),
which reflects the
consistent with that of a pure sample of MeSC( O)Me.
[13]
=
=
poorer electron-donating ability of o-phen compared with
Ni-1 towards the Pd2+ center, as also seen with the {W(CO)4}
probe moiety.
Whether the formation of the thioester occurred by nucleo-
philic attack of the ꢀ[SR] or reductive elimination of the
acetyl requires further study.
Angew. Chem. Int. Ed. 2005, 44, 1217 –1220
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Communications
analysis (%) calcd for C18H28N2Ni1O4S2W1: C 33.6, H 4.39, N 4.36;
found: C 32.1, H 4.49, N 4.49. UV/Vis in DMF solution: lmax(e) = 306
(5002), 372 (1382), 420 (1480), 504 nm (495).
These results suggest the NiN2S2 complexes which model a
soft bidentate binding site for redox-active exogenous nickel
centers in nature should also be considered as a new class of
synthetic ligands for organometallic chemistry. An intriguing
aspect of the ligands to be developed is the extensive
Received: August 21, 2004
stereochemical potentiality, best illustrated by the overlay of
Keywords: acetyl coA synthase · bioinorganic chemistry ·
insertion · nickel · S ligands
+
=
the [(Ni-1)Pd(Me)Cl] with the [(phen)Pd(CO){C( O)Me}]
.
complex, Figure 3.[13] One face of the square planar d8 Pd
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Figure 3. Cerius model overlay of [(Ni-1)Pd(Me)Cl] (white) with the
[(phen)Pd(CO){C( O)Me}]+ (gray) ion.
=
[7] M. Y. Darensbourg, I. Font, M. Pala, J. H. Reibenspies, J. Coord.
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2682.
active metal center is flanked by the square plane of the
NiN2S2 ligands in [(Ni-1)Pd(Me)Cl], while the other is open.
Substrates approaching the open site are expected to
experience strong orientational preferences due to this
feature and hence lead to regioselectivity. Chirality can also
be introduced into the ligands at several places.
In conclusion, the n(CO) frequencies probed by the
{W(CO)4} and Pd-acetyl moieties indicate that NiN2S2 ligands
are much better electron donors than conventional diphos-
phines and diimines, yet with the capability of stabilizing low-
oxidation-state metals, such as W0 and PdII. The NiN2S2
complex serves as a ligand to a Pd-alkyl metal center that
undergoes CO addition and insertion reactions similar to
those of Brookhartꢀs catalyst. Moreover, the reactivity of the
[NiN2S2Pd-alkyl] complex with CO and an ꢀ[SR] source to
produce a thioester is the first example of a heterobimetallic
complex that is able to mimic the final step mediated by the
acetyl coA synthase enzyme active site.
[11] H. Jinshun, C. Qingong, W. Manfong, L. Shimei, J. Struct. Chem.
1985, 26, 69 – 71.
[12] W. De Graaf, J. Boersma, J. J. Smeets, A. L. Spek, G. Van Koten,
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[13] F. C. Rix, M. Brookhart, P. S. White, J. Am. Chem. Soc. 1996, 118,
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[14] C. E. Webster, M. Y. Darensbourg, P. A. Lindahl, M. B. Hall, J.
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[15] G. C. Tucci, R. H. Holm, J. Am. Chem. Soc. 1995, 117, 6489 –
6496.
Experimental Section
See Supporting Information for all additional syntheses. CCDC-
253549–253552 contain the supplementary crystallographic data for
this paper. These data can be obtained free of charge via
www.ccdc.cam.ac.uk/conts/retrieving.html (or from the Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge CB21EZ,
UK; fax: (+ 44)1223-336-033; or deposit@ccdc.cam.ac.uk).
[Ni(bme*-daco)W(CO)4]: The yellow [W(CO)4(pip)2] (0.12 g,
0.26 mmol) was dissolved in CH2Cl2 (20 mL) and heated to 408C for
10 min under an N2 atmosphere. To this was added dropwise a lilac-
purple solution of [Ni(bme*-daco)] (0.09 g, 0.26 mmol) dissolved in
CH2Cl2 (10 mL). The resulting red-brown solution was heated for an
additional 10 min at 408C, and then stirred at 228C ultimately
producing a brown precipitate. The solvent and piperidine were
removed under vacuum and the brown solid washed with benzene
(25 mL ꢂ 2) and diethyl ether (25 mL ꢂ 2). The solid was extracted
with CH2Cl2 and orange-red crystals were obtained from vapor
diffusion of hexane into this solution, yield 0.11 g (65%) elemental
1220
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Angew. Chem. Int. Ed. 2005, 44, 1217 –1220