A new bis(imidazolyl)(alkylthiolate) tripodal ligand and the spontaneous formation of a disulfide-linked, hydroxo-bridged dinuclear zinc complex.

Article abstract of DOI:10.1039/b207770a

The new sterically encumbered, tripodal N2S(alkylthiolate) ligand, LIm2SH, has been synthesized and used to prepare [(LIm2S)ZnCH3], which upon protonolysis under acidic conditions leads to the synthesis of a novel dinucleating ligand and a zinc dimer with

Full text of DOI:10.1039/b207770a

A new bis(imidazolyl)(alkylthiolate) tripodal ligand and the spontaneous
formation of a disulfide-linked, hydroxo-bridged dinuclear zinc complex†
Vivek V. Karambelkar,a Divya Krishnamurthy,a Charlotte L. Stern,b Lev N. Zakharov,c Arnold L.
Rheingoldc and David P. Goldberg*a
a Department of Chemistry, The Johns Hopkins University, 3400 N. Charles Street, Baltimore, Maryland
21218, USA. E-mail: dpg@jhu.edu
b X-ray Crystallography Facility, Northwestern University, Evanston, Illinois 60208, USA
c
Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, USA
Received (in Cambridge, UK) 8th August 2002, Accepted 8th October 2002
First published as an Advance Article on the web 28th October 2002
The new sterically encumbered, tripodal N2S(alkylthiolate)
characteristic singlet at 21.31 ppm for the Zn–CH3 group, and
reflects the expected Cs symmetry for this complex. Identifica-
tion of 2 was confirmed by FAB-MS ([M + Na]+ = 685.3). The
Zn–CH3 peak at 21.31 ppm for 2 is shifted further upfield than
most of the known four-coordinate Zn–CH3 complexes.4,5 Such
a large upfield shift can be attributed to a combination of having
an electron-donating alkylthiolate ligand attached to zinc and
ring current effects caused by the phenyl substituents in close
proximity.11
ligand, LIm SH, has been synthesized and used to prepare
2
[(LIm S)ZnCH3], which upon protonolysis under acidic
2
conditions leads to the synthesis of a novel dinucleating
ligand and a zinc dimer with an unusual structure.
Tripodal ligands have been employed in the synthesis of a vast
number of transition metal complexes. Perhaps the most well-
known of these systems are the tris(pyrazolyl)borates, whose
remarkable versatility is only hampered by their restriction to an
all-nitrogen (N3) donor set.1 We have an ongoing interest in the
synthesis of mixed N,S donor ligands and their divalent metal
complexes (NxSy–MII) as models for certain metalloenzymes
(e.g. peptide deformylase).2–4 Alkylthiolate (RS2) donors2–10
are particularly challenging to synthesize and employ because
of their tendency to form polymeric coordination compounds.
Here we report the synthesis of a new sterically encumbered
Reaction of 2 with an excess of H2O in either toluene for 6
days or in CH3CN at 50 °C for 3 h resulted in the formation of
1
a new species (3) (Scheme 1) which was characterized by H
NMR and FAB-mass spectroscopies. The NMR spectrum of
this new product lacked the upfield Zn–CH3 peak, and revealed
two new singlets at 2.95 and 3.87 ppm assigned to inequivalent
CH3 substituents on the Ph2ImMe groups based on a similar
pattern for a crystallographically characterized (LIm S)2Zn2Br2
2
tripodal N2S(alkylthiolate) ligand, LIm SH (1), which contains a
complex.12 The presence of inequivalent imidazole rings
predicts that the gem-dimethyl groups should be diastereotopic,
which is confirmed by the different singlets at 2.62 and 2.06
ppm. The FAB-mass spectrum reveals a peak at 1231.4, which
2
rare combination of both biomimetic imidazole and alkylth-
iolate donors. With LIm SH in hand, a new zinc alkyl complex,
2
(LIm S)ZnCH3 (2), was synthesized. Examination of the re-
2
corresponds to [M + H]+ for the formula [(LIm S)2Zn] (3). These
2
activity of 2 has led to the formation of a novel disulfide-linked,
hydroxo-bridged dinuclear zinc complex. The structure of this
complex has some interesting implications for designing
models of bimetallic enzymes that cleave DNA/RNA.
data indicate that there has been a rearrangement of the ligand
to an N,S bonding mode and redistribution to give an [N2S2Zn]
complex.
The synthesis of 1, which can be routinely prepared on a 5
gram scale, was accomplished as described in the supplemen-
tary information (ESI†). We prepared the zinc(II)–alkyl com-
plex 2 by addition of 1 to 1.4 equivalents of Zn(CH3)2 in toluene
Interestingly, protonolysis of 2 under acidic conditions leads
to a very different product. When 2 was reacted with aqueous
HBF4
in
acetonitrile,
the
dinuclear
complex
[(LIm S)2Zn2(CH3CN)2(m-OH)](BF4)3 (4) was obtained and
crystallographically characterized.‡ The structure revealed a
hydroxide-bridged zinc dimer.13 In addition, a disulfide bond
had formed, linking the two ligands into a larger organic
framework.14,15 Moreover, the generality of this transformation
was demonstrated by the reaction of 2 with CF3SO3H in
CH3CN, which led to the formation of the same disulfide-linked
dimer (5). An ORTEP diagram of the cation in 5 is shown in Fig.
1.‡
2
1
(86% yield, Scheme 1). The H NMR spectrum of 2 shows a
Scheme 1 Reagents and conditions: (a) 1.4 Zn(CH3)2, toluene, rt, 3 h, (b) 30
H2O, toluene, rt, 6 d, (c) 2 HBF4 (aq.) or 2 CF3SO3H, CH3CN, rt, 24 h.
† Electronic supplementary information (ESI) available: synthesis and
characterisation of compounds 1–5. See http://www.rsc.org/suppdata/cc/
b2/b207770a/
Fig. 1 Thermal ellipsoid plot of the cation in 5 (45% probability). Hydrogen
atoms are omitted for clarity.
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CHEM. COMMUN., 2002, 2772–2773
This journal is © The Royal Society of Chemistry 2002

For 5·CF3SO3H·(CH3CN)2: C86H84F12N12O15S6Zn2, M = 2076.75, T =
173(2) K, monoclinic, C2/c, a = 28.5067(16), b = 14.7799(8), c =
26.0837(15) Å, b = 122.981(10)°, V = 9218.8(9) Å3, Z = 4, Dc = 1.496
g cm23, m = 0.750 mm21. X-Ray diffraction intensities were collected on
a Bruker SMART APEX CCD diffractometer (T = 173(2) K, Mo-Ka
The sulfur atoms in the disulfide unit for 4 (5) are well out of
bonding range (Zn(1)–S(1) 3.395(2) (3.359(1) Å), Zn(1)–S(1)A
3.652(2) (3.621(1) Å)).16 In addition to the m-OH ligand, the
pseudotetrahedral zinc atoms are each coordinated by two
imidazoles from LIm S and a labile CH3CN solvent molecule.
2
radiation, 28570 reflections collected of which 10778 independent (Rint
=
The Zn–N(imidazole) bond lengths of 1.983(6) (1.976(5)) and
1.989(6) (1.991(5) Å) and the Zn–N(CCH3) bond length of
2.025(7) (2.025(5) Å) for 4 (5) are unremarkable.13,17 The Zn–
OH bond length of 1.915(2) (1.919(2) Å) for 4 (5) closely
matches those found for other Zn–O(H)–Zn compounds, such
0.049)).
SADABS absorption corrections were applied. The structure was solved
using direct methods and completed by subsequent difference Fourier
syntheses and refined by full matrix least-squares procedures on reflection
intensities (F2). In the crystal structure of 5 there is a CH3CN disordered
solvate molecule. The solvent content was verified by the SQUEEZE
program (A. L. Spek Acta Crystallogr., Sect. A, 1990, 46, C-34); correction
of the X-ray data for 5 (177 electron/cell) was very close to the required
value (176 electron/cell). All non-H atoms were refined with anisotropic
displacement coefficients. All hydrogen atoms were placed in the structure
factor calculations at idealized positions. One triflate ion is disordered and
was refined with isotropic thermal parameters and restrictions on its
geometry. Based on charge balance considerations, this site is a composite
of CF3SO32 and CF3SO3H (the presence of CF3SO3H as a solvate is well-
precedented, see for example: W. Schuh, H. Wachtler, G. Laschober, H.
Kopacka, K. Wurst and P. Peringer, Chem. Commun., 2000, 1181–1182).
Final R indices [I > 2s(I)]: R1 = 11.41, wR2 = 28.52. All software and
sources of scattering factors are contained in the SHELXTL (5.10) program
package (G.Sheldrick, Bruker XRD, Madison, WI). CCDC 191658.
See http://www.rsc.org/suppdata/cc/b2/b207770a/ for crystallographic
data in CIF or other electronic format.
as [L3Zn–O(H)–ZnL3](ClO4)3 (L
= 5-tert-butylpyrazole),
where d(Zn–OH) = 1.90, 1.91 Å,13 and is considerably shorter
than the Zn–m(OH2) distance of 2.27–2.32 Å found in a rare
aquo-bridged zinc complex.18 Given that both 4 and 5 are
synthesized from the reaction of 2 with HBF4 or CF3SO3H, one
might expect a protonated m-OH2 bridge instead of an OH2
bridge to be favored. However, the structural evidence unambi-
guously identifies a hydroxide bridge. In support of these results
is the fact that a search of the Cambridge Database19 reveals
only three m-OH2 zinc complexes.18,20,21 Complexes 4 and 5 are
freely soluble in acetonitrile and nitromethane, and NMR
spectra in either of these solvents are consistent with the
dinuclear structure determined from X-ray crystallography.
These data indicate the dimers 4 and 5 are stable in solution. A
plausible mechanism for the synthesis of the dimer involves the
1 S. Trofimenko, Scorpionates-The Coordination Chemistry of Poly-
pyrazolylborate Ligands, Imperial College Press, River Edge, NJ,
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2 S. Chang, V. V. Karambelkar, R. D. Sommer, A. L. Rheingold and D.
P. Goldberg, Inorg. Chem., 2002, 41, 239–248.
initial formation of an (LIm S)ZnOH complex, followed by
2
dimerization through the OH bridge, which in turn brings the
sulfur atoms near each other and poised for oxidation by
exogenous O2 to a disulfide.
It is fortuitous that the reaction of 2 with strong acid leads to
the synthesis of the disulfide-linked, dinucleating ligand of
complex 4 (5), since there is interest in the design of polydentate
ligands that can form bimetallic structures for various bio-
mimetic and catalytic applications.22–24 The polydentate ligand
in 4 (5) accommodates a structural motif that may be of
potential utility in modelling certain enzymes that cleave DNA/
RNA, such as alkaline phosphatase, the 3A,5A-exonuclease
domain of DNA polymerase I, and certain ribozymes.25–27 For
these enzymes a bimetallic mechanism has been proposed
which requires 1) two metal ions spaced ~ 3.9 Å apart in order
to bind the phosphate diester substrate in the appropriate
geometry and 2) an exchangeable site on each metal that lies in
the plane of the M–O–M unit to simultaneously bind the
attacking nucleophile and leaving group. The second require-
ment has been difficult to fulfill with small-molecule model
systems.22–24 Complex 4 (5) has some relevant structural
features in this regard; the metal ions are separated by 3.697
(3.645 Å), and the two labile CH3CN solvent molecules occupy
exchangeable sites that lie in the plane of the M–O(H)–M unit.
Thus the disulfide ligand may be useful in preparing other
dimetallic complexes that bind and cleave phosphate diesters.
3 S. Chang, V. V. Karambelkar, R. C. diTargiani and D. P. Goldberg,
Inorg. Chem., 2001, 40, 194–195.
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12 V. V. Karambelkar, C. Stern and D. P. Goldberg, unpublished results.
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¯
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We thank the National Institutes of Health (GM 62309) for
generous support of this work.
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Notes and references
‡
Crystal data: for 4·H2O: C78H79B3F12N10O4S2Zn2, M = 1672.83, T =
24 N. H. Williams, A. Lebuis and J. Chin, J. Am. Chem. Soc., 1999, 121,
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6498–6502.
153(2) K, monoclinic, C2/c, a = 28.526(10), b = 14.601(5), c = 25.161(9)
Å, b = 121.576(5)°, V = 8928(5) Å3, Z = 4, Dc = 1.308 g cm23, m =
0.668 mm21; 10690 reflections collected of which 5598 independent (Rint
=
0.1065). Final R indices [I > 2s(I)]: R1 = 12.48, wR2 = 35.47. CCDC
191657.
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