Electrochemical and chemical oxidation of gold(I) thiolate phosphine complexes: Formation of gold clusters and disulfide [4]

Full text of DOI:10.1021/ja991986j

J. Am. Chem. Soc. 1999, 121, 9225-9226
Electrochemical and Chemical Oxidation of Gold(I)
9225
Thiolate Phosphine Complexes: Formation of Gold
Clusters and Disulfide
Jinhua Chen,§ Tong Jiang,§ Gang Wei,§ Ahmed A. Mohamed,§
Craig Homrighausen,† Jeanette A. Krause Bauer,†
Alice E. Bruce,*,§ and Mitchell R. M. Bruce*,§
Departments of Chemistry
UniVersity of Maine, Orono, Maine 04469-5706
UniVersity of Cincinnati, Cincinnati, Ohio 45221-0172
ReceiVed June 14, 1999
The biological activity of gold-sulfur complexes is well
established and has led to the development of highly effective
antiarthritis drugs, as well as complexes that show antitumor
activity and inhibition of the HIV virus.1 However, the targets
and mechanisms of action of gold complexes remain elusive.
Since rheumatoid arthritis has an oxidative pathology,2-4 we have
been studying the oxidative reactivity and electronic structure of
complexes of the form LAu(SC6H4CH3) and LL[Au(SC6H4CH3)]2,
where L and LL are mono- and bisphosphines.5-14 These
complexes are related to the antiarthritis drug, Auranofin, which
contains gold(I) coordinated to triethylphosphine and tetraacetyl-
thioglucose. The study reported below demonstrates that mild
oxidation of gold-sulfur complexes produces gold clusters and
disulfide by way of an electron-transfer mechanism that occurs
with unexpected n values. These results suggest an oxidative
reactivity for gold-sulfur centers that has not been previously
recognized.
The results of cyclic voltammetry experiments for LAu(SC6H4-
CH3) and LL[Au(SC6H4CH3)]2 [L ) PPh3; LL ) dppe, dppp,
dppb, dpppn] show two irreversible anodic processes at +0.8 (
0.1 V and +1.6 ( 0.1 V (vs SCE).9,15 Constant potential
electrolysis experiments on Ph3PAu(SC6H4CH3) show n values
of 0.5 and >2 for the first and second oxidations, respectively.
Similarly, n values obtained for the dinuclear complexes, LL-
[Au(SC6H4CH3)]2, are approximately 1 and >4 for the first and
Figure 1. ORTEP drawing of the cationic portion of [(PPh3)4Au4(µ-
SC6H4CH3)2](PF6)2 (1) (50% probability ellipsoids). For clarity, only the
ipso-carbons of the phenyl rings (designated R) are shown. Selected
distances (Å) and angles (deg): Au(1)-P(1), 2.275(2); Au(1)-S(1),
2.342(2); Au(1)-Au(2), 3.152(1); Au(1)-Au(2A), 3.173(1); P(1)-Au-
(1)-S(1), 174.59(5).
second oxidations, respectively. The nonintegral n value of 0.5
for the first oxidation of Ph3PAu(SC6H4CH3) is unexpected insofar
as complete oxidation of a single type of redox center, i.e.,
phosphine, gold, or thiolate, would lead to an n value of 1 or
greater. The same logic suggests that an n value of 1.0 for the
dinuclear complexes, LL[Au(SC6H4CH3)]2, is half of the expected
value. These results suggest that a chemical reaction occurs
following the first oxidation.
1
Monitoring the first oxidation for Ph3PAu(SC6H4CH3) by H
NMR during constant potential electrolysis experiments16 reveals
that disulfide, (SC6H4CH3)2, forms in significant quantities.17
Chemical titration experiments on Ph3PAu(SC6H4CH3) using the
mild oxidant, (Cp2Fe)PF6,18 also confirms the nonintegral n values
and the formation of significant quantities of disulfide. Chemical
oxidation afforded the opportunity to isolate the products of the
first oxidation process. Reaction of 0.5 mmol of Ph3PAu(SC6H4-
CH3) and 0.25 mmol of (Cp2Fe)PF6 in CH2Cl2 resulted in
formation of [(Ph3P)4Au4(µ-SC6H4CH3)2](PF6)2 (1), (SC6H4CH3)2,
and Cp2Fe.19 X-ray quality crystals of 1 were obtained from a
CH2Cl2/Et2O solution.20 Figure 1 shows the ORTEP drawing of
1, which can be thought of as consisting of two monocationic
Au2(PPh3)2(µ-SC6H4CH3)+ units that dimerize via Au(I)-Au(I)
interactions to form a tetranuclear cluster. The four Au atoms
form a square with angles about Au(1) and Au(2) near 90° (Au-
(2)-Au(1)-Au(2A) ) 87.5°, Au(1)-Au(2)-Au(1A) ) 92.5°).
The structure is similar to that of [Au2(PPh3)2(µ-SCH2Ph)]2(NO3)2
reported by Wang and Fackler.21 The structural patterns and
§ University of Maine.
† University of Cincinnati.
(1) Shaw, C. F., III. In Gold: Progress in Chemistry, Biochemistry and
Technology; Schmidbaur, H., Ed.; John Wiley & Sons: Chichester, 1999; pp
250-308.
(2) Shaw, G. F., III; Schraa, S.; Gleichmann, E.; Grover, Y. P.; Dunemann,
L.; Jagarlamudi, A. Metal-Based Drugs 1994, 1, 354-362.
(3) Takahashi, K.; Griem, P.; Goebel, C.; Gonzalez, J.; Gleichmann, E.
Metal-Based Drugs 1994, 1, 483-496.
(4) Smith, W. E.; Reglinski, J. Metal-Based Drugs 1994, 1, 497-507.
(5) DiLorenzo, M.; Ganesh, S.; Tadayon, L.; Bruce, M. R. M.; Bruce, A.
E. Metal-Based Drugs, in press.
(6) Foley, J.; Fort, R. C. J.; McDougal, K.; Bruce, M. R. M.; Bruce, A. E.
Metal-Based Drugs 1994, 1, 405-417.
(7) Foley, J. B.; Bruce, A. E.; Bruce, M. R. M. J. Am. Chem. Soc. 1995,
117, 9596-9597.
(8) Foley, J. B.; Gay, S. E.; Turmel, C.; Wei, G.; Jiang, T.; Narayanaswamy,
R.; Foxman, B. M.; Vela, M. J.; Bruce, A. E.; Bruce, M. R. M. Metal-Based
Drugs, in press.
(9) Jiang, T.; Wei, G.; Turmel, C.; Bruce, A. E.; Bruce, M. R. M. Metal-
Based Drugs 1994, 1, 419-431.
(16) Conditions for electrolysis: Pt mesh electrode, +1.0 V, saturated KPF6/
CD3CN.
(10) Jones, W. B.; Yuan, J.; Narayanaswamy, R.; Young, M. A.; Elder, R.
C.; Bruce, A. E.; Bruce, M. R. M. Inorg. Chem. 1995, 34, 1996-2001.
(11) Mohamed, A. A.; Bruce, A. E.; Bruce, M. R. M. In The Chemistry of
Organic DeriVatiVes of Gold and SilVer; Patai, S., Rappaport, Z., Eds.; John
Wiley & Sons: Chichester, 1999; pp 313-352.
(17) Bromine oxidation of a related complex containing a propanedithiol
ligand, LLAu2(pdt), also leads to formation of disulfide and LL(AuBr)2. See
ref 9.
(18) The oxidation potential for Cp2Fe0/+ in [Bu4N][PF6]/CH2Cl2 is +0.46
V vs SCE. See: Connelly, N. G.; Geiger, W. E. Chem. ReV. 1996, 96, 877-
910.
(12) Mohamed, A. A.; Bruce, A. E.; Bruce, M. R. M. Metal-Based Drugs,
in press.
(13) Narayanaswamy, R.; Young, M. A.; Parkhurst, E.; Ouellette, M.; Kerr,
M. E.; Ho, D. M.; Elder, R. C.; Bruce, A. E.; Bruce, M. R. M. Inorg. Chem.
1993, 32, 2506-2517.
(19) The disulfide, (SC6H4CH3)2, forms in 48% yield based on starting gold
complex and was characterized by comparison of its 1H NMR spectrum with
an authentic sample (Aldrich). 1H NMR (CDCl3, ppm): δ 7.37 (d); 7.09 (d);
2.31 (s).
(20) X-ray data (293 K): colorless needles of 1 from CH2Cl2/Et2O,
orthorhombic (Pbca), a ) 18.6416(2) Å, R ) 90°, b ) 18.8457(4) Å, â )
90°, c ) 24.1510(4) Å, γ ) 90°, V ) 8484.6(2) Å3, Z ) 4, R ) 0.0365, GOF
) 0.804.
(14) Schwerdtfeger, P.; Bruce, A. E.; Bruce, M. R. M. J. Am. Chem. Soc.
1998, 120, 6587-6597.
(15) The gold(I) complexes were prepared as described in ref 13. dppe )
diphenylphosphinoethane, dppp ) diphenylphosphinopropane, dppb ) di-
phenylphosphinobutane, dpppn ) diphenylphosphinopentane.
10.1021/ja991986j CCC: $18.00 © 1999 American Chemical Society
Published on Web 09/18/1999

9226 J. Am. Chem. Soc., Vol. 121, No. 39, 1999
Communications to the Editor
bonding in digold(organo)sulfonium salts have been discussed
previously.21-25
A sequence of reactions producing the stoichiometry that is
consistent with the observed nonintegral n value of 0.5 for the
mononuclear gold(I) complex is illustrated in Scheme 1. One-
electron oxidation of Ph3PAu(SC6H4CH3) results in homolytic
cleavage of the Au-S bond and formation of Ph3PAu+ and thiyl
•
radical, SC6H4CH3, which rapidly dimerizes to produce disul-
fide.26 Previous studies on the electronic structure of gold(I)
thiolate phosphine complexes have assigned the HOMO orbitals
of these complexes as having significant sulfur character.10,13,14
The cation, Ph3PAu+, reacts with a molecule of the starting
mononuclear gold(I) complex to form a digold complex with
thiolates bridging two gold(I) centers, which then dimerizes via
Au-Au bonds to form the observed tetragold cluster. The last
step in the mechanism is supported by an independent synthesis
of the tetragold cluster. Thus, treatment of Ph3PAu(SC6H4CH3)
with Ph3PAu+ yields [(PPh3)4Au4(µ-SC6H4CH3)2]2+
.
Figure 2. ORTEP drawing of the cationic portion of [(dppe)2Au4(µ-
SC6H4CH3)2](PF6)2 (2) (50% probability ellipsoids). For clarity, only the
ipso-carbons of the phenyl rings (designated R) are shown. Selected
distances (Å) and angles (deg): Au(1)-P(1), 2.274(2); Au(1)-S(1A),
2.328(3); Au(1)-Au(2), 2.961(1); P(1)-Au(1)-S(1A), 173.88(9).
Scheme 1 (L ) Ph3P, R ) C6H4CH3)
-1e
LAuSR
-8 LAu+ + RS•
RS• f 1/2RSSR
Further support for Schemes 1 and 2 is provided by comparison
of the electrochemistry of the neutral vs cluster complexes.
According to the schemes, one-electron oxidation of PPh3Au-
(SC6H4CH3) and dppe[Au(SC6H4CH3)]2 converts the complexes
to gold clusters and disulfide. Assuming the chemical reactions
after one-electron oxidation (+0.8 V) are fast, cyclic voltammo-
grams of PPh3Au(SC6H4CH3) and dppe[Au(SC6H4CH3)]2 should
contain the appropriate gold cluster and disulfide, in the potential
region >+0.8 V. Additionally, if one-electron oxidation of PPh3-
Au(SC6H4CH3) and dppe[Au(SC6H4CH3)]2 results in oxidation
of terminal thiolates, these redox processes may be absent in 1
and 2, since the clusters contain only bridging thiolates. Cyclic
voltammetry experiments show that the first oxidation of PPh3-
Au(SC6H4CH3) and dppe[Au(SC6H4CH3)]2 at +0.8 V is, indeed,
absent in 1 and 2. Furthermore, bulk electrolysis experiments on
1 at +1.0 V show n ≈ 0. Cyclic voltammetry experiments also
show that 1, 2, and (SC6H4CH3)2 all oxidize at +1.6 V,
approximately the same potential as the second oxidation of PPh3-
Au(SC6H4CH3) and dppe[Au(SC6H4CH3)]2.
The oxidative reactivity of gold-sulfur complexes suggests
some intriguing possibilities for the biochemistry of gold. For
example, oxidation of gold complexes bound to cysteine-rich
proteins may lead to formation of disulfide bonds that would cause
substantial changes in reaction chemistry. Recently, we reported
that the oxidative reactivity of Auranofin is similar to that of Ph3-
PAuSC6H4CH3.12 Preliminary experiments in our laboratory
suggest that mild oxidation of Auranofin also results in formation
of disulfide and a gold cluster.28
LAu+ + LAuSR f 1/2[L4Au4(µ-SR)2]2+
-1e
2LAuSR
-8 1/2RSSR + 1/2[L4Au4(µ-SR)2]2+
Oxidation of the dinuclear complex, dppe[Au(SC6H4CH3)]2 (0.4
mmol), with (Cp2Fe)PF6 (0.4 mmol) resulted in formation of
[(dppe)2Au4(µ-SC6H4CH3)2](PF6)2 (2), (SC6H4CH3)2, and Cp2Fe.
X-ray quality crystals of 2 were obtained from a CH2Cl2/Et2O
solution.27 Figure 2 shows the ORTEP drawing of 2, which can
be thought of as consisting of two monocationic dppeAu2(µ-
SC6H4CH3)+ units which dimerize to form a tetranuclear cluster.
The Au4S2 core adopts a chair configuration with a gold single
bond between Au(1)-Au(2) ) 2.961(1) Å and a sulfur-bridged
nonbonded Au‚‚‚Au interaction of 3.844 Å. A consistent sequence
of reactions producing the stoichiometry and observed n values
of 1.0 for oxidation of the dinuclear gold complexes is illustrated
in Scheme 2.
Scheme 2 (LL ) dppe, R ) C6H4CH3)
-1e
LL(AuSR)2
-8 [LLAu2(SR)]+ + RS•
RS• f 1/2RSSR
[LLAu2(SR)]+ f 1/2[(LL)2Au4(µ-SR)2]2+
Acknowledgment. We thank Professor Paul Sharp for helpful
discussions and R. Narayanaswamy, C. Turmel, and R. Morrison for their
technical assistance. X-ray data were collected through the Ohio Crystal-
lographic Consortium, funded by the Ohio Board of Regents 1995
Investment Fund (CAP-075), located at the University of Toledo,
Instrumentation Center in A&S, Toledo, OH 43606. Alfa Aesar (Johnson
Matthey) is acknowledged for a generous loan of HAuCl4.
LL(AuSR)2
-81/2RSSR + 1/2[(LL)2Au4(µ-SR)2]2+
-1e
(21) Wang, S.; Fackler, J. P., Jr. Inorg. Chem. 1990, 29, 4404-4407.
(22) Kuzmina, L.; Baukova, A.; Churakov, A.; Kuzmin, V.; Dvortsova,
N. Koord. Khim. 1997, 23, 301.
(23) Lopez-de-Lurzuriaga, J. M.; Sladek, A.; Schneider, W.; Schmidbaur,
H. Chem Ber./Recl. 1997, 130, 641-646.
Supporting Information Available: Experimental details for the
chemical titration experiments, syntheses, cyclic voltammograms, spec-
troscopic data (PDF). X-ray crystallographic files, in CIF format, are also
available for 1 and 2. This material is available free of charge via the
Internet at http://pubs.acs.org.
(24) Canales, F.; Concepcion Gimeno, M.; Laguna, A.; Jones, P. G. J. Am.
Chem. Soc. 1996, 118, 4839-3835.
(25) Sladek, A.; Schneider, W.; Angermaier, K.; Bauer, A.; Schmidbaur,
H. Z. Naturforsch., B 1996, 51, 765-772.
(26) Andrieux, C. P.; Hapiot, P.; Pinson, J.; Save´ant, J.-M. J. Am. Chem.
Soc. 1993, 115, 7783-7788.
(27) X-ray data (270 K): colorless striated plates of 2‚2H2O from CH2-
Cl2-Et2O, monoclinic (P21/c), a ) 14.0845(3) Å, R ) 90°, b ) 13.2873(2)
Å, â ) 97.516(1)°, c ) 19.6109(3) Å, γ ) 90°, V ) 3638.55(11) Å3, Z ) 2,
R ) 0.0530, GOF ) 1.002.
JA991986J
(28) Mohamed, A. A.; Chen, J.; Bruce, A. E.; Bruce, M. R. M., unpublished
data.