Synthesis, structural characterization, and antiinflammatory activity of triethylphosphinegold(I) sulfanylpropenoates of the type [(AuPEt 3)2xspa] [H2xspa = 3-(aryl)-2-sulfanylpropenoic acid]: An (H2O)6</su

Article abstract of DOI:10.1021/ic800314p

Gold complexes of the type [(AuPEt₃)₂xspa] were prepared by reacting AuPEt₃Cl in basic media with the 3-(aryl)-2-sulfanylpropenoic acids H₂xspa [x = p, Clp, -o-mp, -p-mp, -o-hp, -p-hp, diBr-o-hp, f, t, -o-py; p

Full text of DOI:10.1021/ic800314p

Inorg. Chem. 2008, 47, 6262-6272
Synthesis, Structural Characterization, and Antiinflammatory Activity of
Triethylphosphinegold(I) Sulfanylpropenoates of the Type
[(AuPEt3)2xspa] [H2xspa ) 3-(Aryl)-2-sulfanylpropenoic acid]: an (H2O)6
Cluster in the Lattice of the Complexes [(AuPEt3)2xspa] · 3H2O
†
†
‡
§
†
,†
´
Elena Barreiro, Jose´ S. Casas, Mar´ıa D. Couce, Angeles Gato, Agust´ın Sa´nchez, Jose´ Sordo,*
Jose´ M. Varela,† and Ezequiel M. Va´zquez Lo´pez‡
Departamento de Qu´ımica Inorga´nica, Facultade de Farmacia, UniVersidade de Santiago de
Compostela, 15782 Santiago de Compostela, Galicia, Spain, Departamento de Qu´ımica
Inorga´nica, Facultade de Ciencias, UniVersidade de Vigo, 36310 Vigo, Galicia, Spain, and
Departamento de Farmacolox´ıa, Facultade de Farmacia, UniVersidade de Santiago de
Compostela, 15782 Santiago de Compostela, Galicia, Spain
Received February 19, 2008
Gold complexes of the type [(AuPEt3)2xspa] were prepared by reacting AuPEt3Cl in basic media with the 3-(aryl)-
2-sulfanylpropenoic acids H2xspa [x ) p, Clp, -o-mp, -p-mp, -o-hp, -p-hp, diBr-o-hp, f, t, -o-py; p ) 3-phenyl, Clp
) 3-(2-chlorophenyl)-, -o-mp ) 3-(2-methoxyphenyl)-, -p-mp ) 3-(4-methoxyphenyl)-, -o-hp ) 3-(2-hydroxyphenyl)-,
-p-hp ) 3-(4-hydroxyphenyl)-, diBr-o-hp ) 3-(3,5- dibromo-2-hydroxyphenyl)-, f ) 3-(2-furyl)-, t ) 3-(2-thienyl)-,
-o-py ) 3-(2-pyridyl); spa ) 2-sulfanylpropenoato], and 2-cyclopentylidene-2-sulfanylacetic acid (H2cpa). The
complexes were characterized by spectroscopic methods (IR, 1H, 13C and 31P NMR) and mass spectrometry, and
the complexes [(AuPEt3)2pspa] · 3H2O, [(AuPEt3)2-p-hpspa]· 3H2O, [(AuPEt3)2tspa)] · 3H2O, and [(AuPEt3)2-o-hpspa]
by X-ray diffractometry. The crystals of the first three complexes contain (H2O)6 clusters hydrogen bonded to
[(AuPEt3)2xspa]2 dimer units, whereas in the -o-hpspa derivative the hydrogen bonds are between the monomer
[(AuPEt3)2-o-hpspa] units. The antiinflammatory activity of the complexes against plantar edema induced by
carrageenan in rats is generally significant, with the values for the o-hpspa and tspa derivatives being particularly
high.
Introduction
Gold compounds are among these drugs.1 The molecular
basis for their therapeutic effects is not well understood, and
although many pathways have been proposed to explain this
behavior, the activity is probably a combination of biological
effects.2 For example, gold can replace Zn(II) from a Zn-
binding site in the neutrophil collagenase, thus inhibiting the
protein,3 or it can interfere with the homeostasis of the Cu(I)
ion by binding to Cu(I)-responsive transcription factors and
other Cu(I)-trafficking proteins.4 Furthermore, gold may also
Rheumatoid arthritis is a disease of unknown origin and
is characterized by persistent inflammation and joint swelling,
functional disability, and increased mortality. Inflammation
occurs first in the synovial membrane that surrounds the
joints and then moves into the synovial cavity between the
bones. Although no curative therapy exists at present, the
disease-modifying rheumatoid arthritis drugs can delay and
sometimes cause remission of the disease.
(1) (a) Messori, L.; Marcon, G. Met. Ions Biol. Syst. 2004, 41, 279. (b)
Eisler, R. Inflammation Res. 2003, 52, 487. (c) Shaw, C. F., III In
Gold: Progress in Chemistry, Biochemistry and Technology; Schmid-
baur, H., Ed.; J. Wiley & Sons: Chichester, U.K., 1999; p. 260. (d)
Fricker, S. P. Gold Bull. 1996, 29, 53. (e) Parish, R. V.; Cottrill, S. M.
Gold Bull. 1987, 20, 3.
* To whom correspondence should be addressed. E-mail: qijsordo@usc.es.
Tel: +34981528074. Fax: +34981547102.
†
Departamento de Qu´ımica Inorga´nica, Facultade de Farmacia, Uni-
versidade de Santiago de Compostela.
‡
Universidade de Vigo.
(2) Gunatilleke, S. S.; Barrios, A. M. J. Med. Chem. 2006, 49, 3933.
(3) Mallya, S. K.; Van Hart, H. E. J. Biol. Chem. 1989, 264, 1594.
(4) Stoyanov, J. V.; Brown, N. L. J. Biol. Chem. 2003, 278, 1407.
§ Departamento de Farmacolox´ıa, Facultade de Farmacia, Universidade
de Santiago de Compostela.
6262 Inorganic Chemistry, Vol. 47, No. 14, 2008
10.1021/ic800314p CCC: $40.75  2008 American Chemical Society
Published on Web 06/18/2008

Triethylphosphinegold(I) Sulfanylpropenoates
affect the ROS generation,5 inhibit T-cell proliferation and
modulate the immune system,6 induce mitochondrial mem-
brane permeability,7 inhibit osteoclast bone resorption,8
inhibit the activation of NF-κB, a transcription factor
responsible for the production of TNFa and other key
inflammatory cytokines,9 as well as inhibit the activity of
cathepsins, a family of highly homologous, cysteine-depend-
ent enzymes implicated in inflammation and joint destruction.2
Gold drugs in clinical use today include the following
thiolates, gold(I) sodium thiomalate, gold(I) thioglucose,
sodium bis(thiosulfato)gold(I) or sodium thiopropanol sul-
fonate-S-gold(I), and triethylphosphine (2,3,4,6-tetra-O-
acetyl-ꢀ-1-D-thiopyranosato-S) gold(I), which is also known
as triethylphosphine(tetraacetato thioglucose)gold(I), as
[(AuPEt3)tatg], and as auranofin, with the latter compound
only administered orally.
Scheme 2
Auranofin is a monomeric lipophilic complex that con-
tains10 a gold(I) center bonded to an S atom (2.29 Å) and a
P atom (2.26 Å) in an almost linear environment (S-Au-P:
174°). This compound, despite the strong binding of the
thiolate and the phosphine, undergoes a considerable number
of ligand exchange reactions.11,12 The thiolate ligand is
rapidly lost in vivo,11 and this is followed by a slower
displacement and concomitant oxidation of the phosphine
to Et3PO.
Besides these exchange reactions, a mild oxidation that
gave gold clusters and disulfide was recently studied for
auranofin and for the equivalent PMe3 derivative.13 This
oxidation process is shown in Scheme 1.
plexes [(AuPPh3)2L] are dinuclear and also contain the
SAu2P2 fragments but do not dimerize. The sulfanylcarboxy-
late ligand contains a second donor group, a carboxylate
group, which from an electrostatic point of view could play
-
the role of the NO3 anion present in the PMe3 auranofin
Scheme 1
analog. However, in our case17 this group is coordinated to
the metal, thus introducing a significant difference with
respect to simple thiolates.
This reaction enabled the synthesis and structural study
of the PMe3 derivative, which proved to be [(AuPMe3)2(µ-
tatg)]2(NO3)2: a dimer containing Au4 clusters formed through
Au-Au interactions between two cationic digold units each
containing a AuS2P2 fragment. This Au4 cluster is also
present in the oxidation products of other Au(I) phosphine
thiolate complexes,14,15 and the isolated digold units were
previously identified16 in acidic solutions of auranofin.
In a previous study17 we prepared triphenylphosphine
Au(I) derivatives of sulfanylcarboxylates H2L. These com-
The role of the phosphine also seems to be significant,
not only because crystallization of the oxidation product was
difficult in auranofin but also because all of the previous
structural data on Au4 tetramers from thiolates relates to
phosphines such as PMe3, PPh3 or other complex phosphine
derivatives but not from PEt3, as highlighted by a search on
CSD.18 Therefore, to gain an insight into the structural
chemistry of such species and to investigate the potential
therapeutic activity of the resulting complexes, we decided
to investigate the reaction of AuPEt3Cl with the 3-(aryl)-2-
sulfanylpropenoic acids (H2xspa) and 2-cyclopentylidene-
2-sulfanylacetic acid (H2cpa) depicted in Scheme 2 (H2L).
The crystal structures of [(AuPEt3)2pspa] ·3H2O (1·3H2O),
[(AuPEt3)2-o-hpspa] (5), [(AuPEt3)2-p-hpspa] · 3H2O (6 ·
3H2O), and [(AuPEt3)2tspa]·3H2O (9·3H2O) were solved by
X-ray diffraction. 1 · 3H2O, 6 · 3H2O, and 9 · 3H2O were
shown to contain tetranuclear Au4 units separated by clusters
of six water molecules, a situation that gave us the op-
portunity to analyze the influence of the environment on the
structural parameters of the cluster. These clusters are absent
in the structure of 5, which only contains dinuclear units.
The antiinflammatory activity of the complexes was tested,
and the o-h-pspa, tspa, and fspa derivatives proved to be the
most active.
(5) Kerimova, A. A.; Atalay, M.; Ysifov, E. Y.; Kuprin, S. P.; Kerimov,
T. M. Pathophysiology 2000, 7, 209.
(6) Hashimoto, K.; Whitehurst, C. E.; Matsubara, T.; Hirohata, K.; Lipsky,
P. E. J. Clin. InVest. 1992, 89, 1839.
(7) Rigobello, M. P.; Scutari, G.; Boscolo, R.; Bindoli, A. Br. J.
Pharmacol. 2002, 136, 1162.
(8) Hall, T. J.; Jeker, H.; Nyugen, H.; Schaeublin, M. Inflammation Res.
1996, 45, 230.
(9) Jeon, K. I.; Byun, M. S.; Jue, D. M. Exp. Mol. Med. 2003, 35, 61.
(10) Hill, D. T.; Sutton, B. M. Cryst. Struct. Commun. 1980, 9, 679.
(11) Shaw, C. F. Chem. ReV. 1999, 99, 2589.
(12) Ahmad, S.; Isab, A. A.; Ali, S.; Al-Arfaj, A. R. Polyhedron 2006, 25,
1633.
(13) Mohamed, A. A.; Chen, J.; Bruce, A. E.; Bruce, M. R. M.; Krause
Bauer, J. A.; Hill, D. T. Inorg. Chem. 2003, 42, 2203.
(14) Chen, J.; Jiang, T.; Wei, G.; Mohamed, A. A.; Homrighausen, C.;
Krause Bauer, J. A.; Bruce, A. E.; Bruce, M. R. M. J. Am. Chem.
Soc. 1999, 121, 9225.
(15) Mohamed, A. A.; Abdou, H. E.; Chen, J.; Bruce, A. E.; Bruce,
M. R. M. Comments Inorg. Chem. 2002, 23, 321.
(16) Boles Bryan, D. L.; Mikuriya, Y.; Hempel, J. C.; Mellinger, D.;
Hashim, M.; Pasternack, R. F. Inorg. Chem. 1987, 26, 4180.
Inorganic Chemistry, Vol. 47, No. 14, 2008 6263

Barreiro et al.
1336 s, νsym(COO); 1454 s, 1415 m, 1381 m, ν(PEt3). NMR (dmso-
d6): H, δ 7.43 (s, 1H, C(3)H), 8.05 (d, 2H, C(5)H, C(9)H), 7.36
Experimental Section
1
Materials and Methods. 2-Chlorobenzaldehyde, 2-methoxy-
benzaldehyde, 4-methoxybenzaldehyde, 2-hydroxybenzaldehyde,
4-hydroxybenzaldehyde, 3,5-dibromo-2-hydroxybenzaldehyde,
2-furancarboxaldehyde, 2-thiophenecarboxaldehyde, 2-pyridinecar-
boxaldehyde, cyclopentanone (all from Aldrich), benzaldehyde
(Probus), rhodanine (Aldrich) and triethylphosphinegold(I) chloride
(Aldrich) were used as supplied.
Elemental analyses were performed with a Fisons 1108 mi-
croanalyser. Mass spectra were recorded on a Kratos MS50TC
spectrometer connected to a DS90 system and operating in FAB
mode (m-nitrobenzyl alcohol, Xe, 8 eV; ca. 1.28 × 10-15 J); ions
were identified by DS90 software, and the data characterizing peaks
for the metalated species were calculated using the isotope 197Au.
IR spectra (KBr pellets or Nujol mulls) were recorded on a Bruker
IFS66V FT-IR spectrophotometer and are reported in the synthesis
section using the following abbreviations: vs ) very strong, s )
(t, 2H, C(6)H, C(8)H), 7.25 (m, 1H, C(7)H), 1.92 (m, 12H,
H(PCH2)), 1.09 (m, 18H, H(PCH3)); 13C, δ 170.9 C(1), 127.4 C(2),
136.8 C(3), 134.4 C(4), 133.6 C(5) and C(9), 127.7 C(6) and C(8),
130.2 C(7), 16.9 (d, J(C-P) ) 37.0 (PCH2)), 8.9 (PCH3); 31P {1H},
δ 39.2 (s). NMR (CDCl3): 1H, δ 8.03 (s, 1H, C(3)H), 8.17 (d, 2H,
C(5)H, C(9)H), 7.37 (m, 2H, C(6)H, C(8)H), 7.23 (m, 1H, C(7)H),
1.81 (m, 12, H(PCH2)), 1.20 (m, 18H, H(PCH3)); 13C, δ - C(1),
127.8 C(2), 139.7 C(3), 136.6 C(4), 131.4 C(5), 127.7 C(6), 128.3
C(7), 18.0 (d, 2J(13C-31P) ) 35.4 (PCH2)), 8.9 (s, PCH3); 31P {1H},
δ 38.7 (s). Single crystals of [(AuPEt3)2pspa] ·3H2O (1·3H2O) were
grown by slow evaporation of the mother liquor.
[(AuPEt3)2Clpspa] (2). H2Clpspa (0.046 g, 0.21 mmol),
AuPEt3Cl (0.150 g, 0.43 mmol), methanol (8 cm3), NaOH (0.017
g, 0.43 mmol), H2O (1 cm3), pale yellow solid. Yield: 82%. (Found:
C 29.6, H 4.0, S 3.7%. Calcd for C21H35O2SClP2Au2: C 29.9, H
4.2, S 3.8%). MS (FAB): the main metalated signals are at
m/z 1157 (15%), [(AuPEt3)3Clpspa]+; 977 (67), 859 (15)
[(AuPEt3)2AuS]+; [(AuPEt3)3S]+; 842 (25), [M]+; 662 (7),
[(AuPEt3)2S]+; 433 (100), [Au(PEt3)2]+ and 315 (87), [Au(PEt3)]+.
IR (cm-1): 1580 vs, νas(COO); 1346 s, νsym(COO); 1458 s, 1413 m,
1
strong, m ) medium, w ) weak, sh ) shoulder, br ) broad. H
and 13C NMR spectra in solution were recorded in dmso-d6 or
CDCl3 at room temperature on a Bruker AMX 300 operating at
300.14 (1H) and 75.40 MHz (13C), using 5 mm o.d. tubes; chemical
shifts, in ppm, are reported relative to TMS using the solvent signal
1
1380 s, ν(PEt3). NMR (CDCl3): H, δ 7.98 (s, 1H, C(3)H), 7.32
1
1
(δ H ) 2.50 ppm; δ 13C ) 39.50 ppm for dmso-d6 or δ H )
7.26 ppm; δ 13C ) 77.00 ppm for CDCl3) as reference, with the
atoms numbered as in Scheme 2. 1H-1H COSY NMR spectra were
recorded, and 1H-13C HMBC (Heteronuclear Multiple Bond
Correlation) and HMQC (Heteronuclear Multiple Quantum Coher-
ence) experiments were performed, using a Varian Inova 400
spectrometer. 31P NMR spectra were recorded at 202.46 MHz on
a Bruker AMX 500 spectrometer using 5 mm o.d. tubes and are
reported in ppm relative to external H3PO4 (85%). Coupling
constants are reported in Hz. All the physical measurements were
carried out by the RIAIDT services of the University of Santiago
de Compostela (USC).
(d, 1H, C(6)H), 7.21 (st, 1H, C(7)H), 7.14 (m, 1H, C(8)H), 7.82
(d, 1H, C(9)H), 1.79 (m, 12H, H(PCH2)), 1.13 (m, 18H, H(PCH3));
13C, δ 170.2 C(1), 126.8 C(2), 134.4 C(3), 136.4 C(4), 134.1 C(5),
128.8 C(6), 128.4 C(7), 125.7 C(8), 132.1 C(9), 17.9 (d, 2J(13C-31P)
) 34.8 (PCH2)), 9.0 (s, PCH3); 31P {1H}, δ 39.7 (s).
[(AuPEt3)2-o-mpspa] (3). H2-o-mpspa (0.045 g, 0.21 mmol),
AuPEt3Cl (0.150 g, 0.43 mmol), methanol (8 cm3), NaOH (0.017
g, 0.43 mmol), H2O (1 cm3), yellow solid. Yield: 84%. (Found: C
31.2, H 4.2, S 3.4%. Calcd for C22H38O3SP2Au2: C 31.5, H 4.6, S
3.8%). MS (FAB): the main metalated signals are at m/z 1153
(15%), [(AuPEt3)3-o-mpspa]+; 977 (84), 859 (13) [(AuPEt3)2AuS]+;
[(AuPEt3)3S]+; 838 (52), [M]+; 662 (22), [(AuPEt3)2S]+; 433 (89),
[Au(PEt3)2]+ and 315 (100), [AuPEt3]+. IR (cm-1): 1570 sh,
νas(COO); 1358 s, νsym(COO); 2834 w, νsym(OCH3); 1457 vs,
1412 m, 1382 s, ν(PEt3). NMR (dmso-d6): 1H, δ 7.59 (s, 1H,
C(3)H), 8.31 (d, 1H, C(6)H), 6.89 (st, 1H, C(7)H), 7.13 (st, 1H,
C(8)H), 6.79 (d, 1H, C(9)H), 3.75 (s, 3H, OCH3), 1.85 (m, 12H,
H(PCH2)), 1.08 (m, 18H, H(PCH3)); 13C, δ - C(1), 119.1 C(2), -
C(3), 125.0 C(4), 157.5 C(5), 110.0 C(6), 129.9 C(7), 127.0 C(8),
Synthesis. The 3-(aryl)-2-sulfanylpropenoic acids were prepared
by condensation of the appropriate aldehyde with rhodanine,
subsequent hydrolysis in an alkaline medium, and acidification with
aqueous HCl.19,20 For the preparation of 2-cyclopentyliden-2-
sulfanylacetic acid, (H2cpa), a ketone (cyclopentanone) was used
in the condensation reaction instead of an aldehyde.21
Complexes were prepared by adding AuPEt3Cl in a 2:1 molar
ratio to a solution of the appropriate sulfanylcarboxylic acid and
NaOH in methanol/water. After stirring for 1 h, the methanol was
evaporated in air or under vacuum. In cases where a solid was
formed it was washed with water and dried in vacuo. In cases where
an oil was obtained (4, 8, 10, 11) it was treated with chloroform,
filtered to remove NaCl, and the solvent was removed and the oil
dried under vacuum.
[(AuPEt3)2pspa] (1). H2pspa (0.038 g, 0.21 mmol), AuPEt3Cl
(0.150 g, 0.43 mmol), methanol (8 cm3), NaOH (0.017 g, 0.43
mmol), H2O (1 cm3), yellow solid. Yield: 86%. (Found: C 30.9, H
4.8, S 3.9%. Calcd for C21H36O2SP2Au2: C 31.2, H 4.5, S 4.0%).
MS (FAB): the main metalated signals are at m/z 1123 (13%),
[(AuPEt3)3pspa]+; 977 (100), [(AuPEt3)3S]+; 859 (14) [(AuPEt3)2-
AuS]+; 808 (39), [M]+; 662 (4), [(AuPEt3)2S]+; 433 (71), [Au-
(PEt3)2]+ and 315 (66), [AuPEt3]+. IR (cm-1): 1573 vs, νas(COO);
2
127.2 C(9), 55.0 C(OCH3), 17.1 (d, J(13C-31P) ) 34.9 (PCH2)),
8.9 (s, PCH3); 31P {1H}, δ 39 (s), 53.8 (s).
[(AuPEt3)2-p-mpspa] (4). H2-p-mpspa (0.045 g, 0.21 mmol),
AuPEt3Cl (0.150 g, 0.43 mmol), methanol (8 cm3), NaOH (0.017
g, 0.43 mmol), H2O (1 cm3), yellow oil. Yield: 85%. (Found: C
31.7, H 4.4, S 3.5%. Calcd for C22H38O3SP2Au2: C 31.5, H 4.6, S
3.8%). MS (FAB): the main metalated signals are at m/z 977 (45%),
[(AuPEt3)3S]+; 859 (12) [(AuPEt3)2AuS]+; 838 (30), [M]+; 524 (3)
[(AuPEt3)H-p-mpspa]+; 433 (62), [Au(PEt3)2]+ and 315 (100),
[AuPEt3]+. IR (cm-1): 1585 vs, νas(COO); 1319 s, νsym(COO);
2834 m, νsym(OCH3); 1455 vs, 1415 vs, 1380 m, ν(PEt3). NMR
(dmso-d6): 1H, δ 7.65 (s, 1H, C(3)H), 7.76 (d, 2H,C(5)H, C(9)H),
6.95 (d, 2H, C(6)H, C(8)H), 3.77 (s, 3H, OCH3), 1.83 (m, 12H,
H(PCH2)), 1.07 (m, 18H, H(PCH3)); 13C, δ 168.5 C(1), 129.4 C(2),
135.6 C(3), 130.9 C(4), 131.6 C(5) and C(9), 113.2 C(6) and C(8),
2
158.5 C(7), 55.0 C(OCH3), 17.3 (d, J(13C-31P) ) 34.9 (PCH2)),
(17) Barreiro, E.; Casas, J. S.; Couce, M. D.; Sa´nchez, A.; Sordo, J.; Varela,
J. M.; Va´zquez-Lo´pez, E. M. Dalton Trans. 2003, 4754.
(18) Allen, F. H. Acta Crystallogr. 2002, B58, 380.
(19) Gra¨nacher, C. HelV. Chim. Acta 1922, 5, 610.
(20) Campaigne, E.; Cline, R. E. J. Org. Chem. 1956, 21, 32.
(21) Brown, F. C.; Bradsher, K.; McCallum, S. G.; Potter, M. J. Org. Chem.
1950, 15, 174.
8.9 (s, PCH3); 31P {1H}, δ 38.6 (s).
[(AuPEt3)2-o-hpspa] (5). H2-o-hpspa (0.042 g, 0.21 mmol),
AuPEt3Cl (0.150 g, 0.43 mmol), methanol (8 cm3), NaOH (0.017
g, 0.43 mmol), H2O (1 cm3), orange solid. Yield: 91%. (Found: C
30.1, H 4.0, S 3.6%. Calcd for C21H36O3SP2Au2: C 30.6, H 4.4, S
6264 Inorganic Chemistry, Vol. 47, No. 14, 2008

Triethylphosphinegold(I) Sulfanylpropenoates
3.9%). MS (FAB): the main metalated signals are at m/z 1139
(7%), [(AuPEt3)3-o-hpspa]+; 977 (100), [(AuPEt3)3S]+; 859 (13)
[(AuPEt3)2AuS]+; 824 (13), [M]+; 662 (17), [(AuPEt3)2S]+; 433
(47), [Au(PEt3)2]+ and 315 (45), [AuPEt3]+. IR (cm-1): 1568 s,
νas(COO); 1335 m, νsym(COO); 1450 vs, 1413 s, 1381 s, ν(PEt3).
NMR (dmso-d6): 1H, δ 7.57 (s, 1H, C(3)H), 8.08 (s, 1H, C(5)OH),
6.80 (d, 1H, C(6)H), 6.95 (st, 1H, C(7)H), 6.72 (st, 1H, C(8)H),
8.15 (d, 1H, C(9)H), 1.87 (m, 12H, H(PCH2)), 1.09 (m, 18H,
H(PCH3)); 13C, δ 169.6 C(1), 120.8 C(2), 125.1 C(3), 127.0 C(4),
155.8 C(5), 116.3 C(6), 129.8 C(7), 118.7 C(8), 126.6 C(9), 18.0
(m, 18H, H(PCH3)); 13C, δ 169.0 C(1), 116.1 C(2), 128.4 C(3),
152.9 C(4), 112.3 C(5), 111.7 C(6), 142.9 C(7), 18.0 (d, 2J(13C-31P)
) 35.3 (PCH2)), 8.9 (s, PCH3);31P {1H}, δ 38.8(s), 54.7 (s).
[(AuPEt3)2tspa] (9). H2tspa (0.041 g, 0.21 mmol), AuPEt3Cl
(0.150 g, 0.43 mmol), methanol (8 cm3), NaOH (0.017 g, 0.43
mmol), H2O (1 cm3), pale yellow solid. Yield: 74%. (Found: C
27.9, H 4.6, S 7.6%. Calcd for C19H34O2S2P2Au2: C 28.0, H 4.2, S
7.9%). MS (FAB): the main metalated signals are at m/z 1129
(20%), [(AuPEt3)3fspa]+; 977 (80), [(AuPEt3)3S]+; 859 (11)
[(AuPEt3)2AuS]+; 814 (54), [M]+; 662 (8), [(AuPEt3)2S]+; 433
(100), [Au(PEt3)2]+ and 315 (82), [AuPEt3]+. IR (cm-1): 1571 vs,
νas(COO); 1331 s, νsym(COO); 1455 s, 1416 m, 1379 m, ν(PEt3).
2
(d, J(13C-31P) ) 34.9 (PCH2)), 8.9 (s, PCH3); 31P {1H}, δ 39.1
(s), 5.8 (s). Single crystals were grown by slow evaporation of a
dmso-d6 solution.
1
NMR (dmso-d6): H, δ 7.86 (s, 1H, C(3)H), 7.31 (d, 1H, C(5)H),
[(AuPEt3)2-p-hpspa] (6). H2-p-hpspa (0.042 g, 0.21 mmol),
AuPEt3Cl (0.150 g, 0.43 mmol), methanol (8 cm3), NaOH (0.017
g, 0.43 mmol), H2O (1 cm3), yellow solid. Yield: 76%. (Found: C
30.1, H 4.6, S 3.6%. Calcd for C21H36O3SP2Au2: C 30.6, H 3.4, S
3.9%). MS (FAB): the main metalated signals are at m/z 1139
(11%), [(AuPEt3)3-p-hpspa]+; 977 (65), [(AuPEt3)3S]+; 859 (9)
[(AuPEt3)2AuS]+; 824 (45), [M]+; 662 (9), [(AuPEt3)2S]+; 433
(100), [Au(PEt3)2]+ and 315 (93), [AuPEt3]+. IR (cm-1): 1565 vs,
νas(COO); 1334 s, νsym(COO); 1453 vs, 1416 m, 1382 m, ν(PEt3).
7.08 (t, 1H, C(6)H), 7.50 (d, 1H, C(7)H), 1.89 (m, 12H, H(PCH2)),
1.11 (m, 18H, H(PCH3)); 13C, δ 169.7 C(1), 126.4 C(2), 128.9 C(3),
141.5 C(4), 128.0 C(5), 125.9 C(6), 127.1 C(7), 17.2 (d, J(C-P)
1
) 35.1 (PCH2)), 9.00 (PCH3). NMR (CDCl3): H, δ 8.16 (s, 1H,
C(3)H), 7.25 (d, 1H, C(5)H), 6.96 (t, 1H, C(6)H), 7.27 (d, 1H,
C(7)H), 1.76 (m, 12H, H(PCH2)), 1.01 (m, 18H, H(PCH3)); 13C, δ
171.3 C(1), 128.9 C(2), 132.2 C(3), 141.3 C(4), 132.2 C(5), 126.0
2
C(6), 127.0 C(7), 18.0 (d, J(13C-31P) ) 35.3 (PCH2)), 8.9 (s,
PCH3); 31P {1H}, δ 39.1 (s), 54.7(s). Single crystals of [(AuPPh3)2-
tspa] ·3H2O (9·3H2O) were grown by slow evaporation of the
mother liquor.
1
NMR (dmso-d6): H, δ 7.28 (s, 1H, C(3)H), 7.76 (d, 2H, C(5)H,
C(9)H), 6.67 (d, 2H, C(6)H, C(8)H), 9.46 (s, 1H, C(7)OH), 1.90
(m, 12H, H(PCH2)), 1.09 (m, 18H, H(PCH3)); 13C, δ 172.8 C(1),
128.3 C(2), 129.9 C(3), 132.4 C(4), 130.7 C(5) and C(9), 114.2
C(6) and C(8), 155.2 C(7), 17.3 (d, J(C-P) ) 33.7 (PCH2)), 9.1
[(AuPEt3)2-o-pyspa] (10). H2-o-pypspa (0.039 g, 0.21 mmol),
AuPEt3Cl (0.150 g, 0.43 mmol), methanol (8 cm3), NaOH (0.017
g, 0.43 mmol), H2O (1 cm3), orange oil. Yield: 74%. (Found: C
30.0, H 4.7, N 1.9, S 3.6%. Calcd for C20H35O2SNP2Au2: C 29.7,
H 4.4, N 1.7, S 3.9%). MS (FAB): the main metalated signals are
at m/z 1124 (2%), [(AuPEt3)3-o-pyspa]+; 977 (23), [(AuPEt3)3S]+;
859 (3) [(AuPEt3)2AuS]+; 809 (10), [M]+; 662 (6), [(AuPEt3)2S]+;
495 (4), [(AuPEt3)H-o-pyspa]+; 433 (100), [Au(PEt3)2]+ and 315
(44), [AuPEt3]+. IR (cm-1): 1556 vs, νas(COO); 1341 s, νsym(COO);
1
(PCH3); 31P {1H}, δ 39.1 (s), 54.2 (s). NMR (CDCl3) H, δ 7.96
(s, 1H, C(3)H), 7.63 (d, 2H, C(5)H, C(9)H), 6.99 (d, 2H, C(6)H,
C(8)H), 9.71 (s, 1H, C(7)OH), 1.81 (m, 12H, H(PCH2)), 1.26 (m,
18H, H(PCH3)); 31P {1H}, δ 38.2 (s). Single crystals of [(AuPEt3)2-
p-hpspa]·3H2O (6·3H2O) were grown by slow evaporation of a
methanol/acetone solution.
[(AuPEt3)2-diBr-o-hpspa] (7). H2diBr-o-hspspa (0.045 g, 0.21
mmol), AuPEt3Cl (0.150 g, 0.43 mmol), methanol (8 cm3), NaOH
(0.017 g, 0.43 mmol), H2O (1 cm3), orange solid. Yield: 85%.
(Found: C 25.9, H 3.6, S 3.4%. Calcd for C21H34O3SBr2P2Au2: C
25.7, H 23.5, S 3.2%). MS (FAB): the main metalated signals are
at m/z 977 (100%), [(AuPEt3)3S]+; 982 (2), [M]+; 662 (13),
[(AuPEt3)2S]+; 433 (18), [Au(PEt3)2]+ and 315 (18), [AuPEt3]+.
IR (cm-1): 1577 vs, νas(COO); 1316 m, νsym(COO); 1439 m, 1401 s,
1
1454 vs, 1431 s, 1380 s, ν(PEt3). NMR (dmso-d6): H, δ 7.47 (s,
1H, C(3)H), 8.55 (d, 1H,C (5)H), 7.78 (st, 1H, C(6)H), 7.20 (st,
1H, C(7)H), 8.63 (d, 1H, C(8)H), 1.90 (m, 12H, H(PCH2)), 1.08
(m, 18H, H(PCH3)); 13C, δ 170.6 C(1), 138.9 C(2), 135.5 C(3),
155.6 C(4), 149.0 C(5), 133.8 C(6), 121.6 C(7), 124.5 C(8), 17.0
2
(d, J(13C-31P) ) 36.3 (PCH2)), 8.9 (s, PCH3); 31P {1H}, δ 38.1
(s).
[(AuPEt3)2cpa] (11). H2cpa (0.034 g, 0.21 mmol), AuPEt3Cl
(0.150 g, 0.43 mmol), methanol (8 cm3), NaOH (0.017 g, 0.43
mmol), H2O (1 cm3), brown oil. Yield: 73%. (Found: C 28.5, H
4.9, N 4.7, S 4.3%. Calcd for C19H38O2SP2Au2: C, 29.0; H, 5.0; S,
4.0%). MS (FAB): the main metalated signals are at m/z 1101
(7%), [(AuPEt3)3cpa]+; 977 (100), [(AuPEt3)3S]+; 859 (13)
[(AuPEt3)2AuS]+; 786 (68), [M]+; 662 (7), [(AuPEt3)2S]+; 471 (3),
[(AuPEt3)Hcpa]+; 433 (38), [Au(PEt3)2]+ and 315 (56), [AuPEt3]+.
IR (cm-1): 1554 vs, νas(COO); 1365 sh, νsym(COO); 1452 vs, 1411
vs, 1380 vs, ν(PEt3). NMR (dmso-d6): 1H, δ 2.68 (m, 2H, C(4)H2),
1.58 (m, 2H, C(5)H2), 1.58 (m, 2H, C(6)H2), 2.58 (m, 2H, C(7)H2),
1.89 (m, 12H, H(PCH2)), 1.08 (m, 18H, H(PCH3));13C δ 169.8 C(1),
122.1 C(2), 151.6 C(3), 36.1 C(4), 27.2 C(5), 25.5 C(6), 34.4 C(7),
1
1383 vs, ν(PEt3). NMR (CDCl3): H, δ 7.79 (s, 1H, C(3)H), 9.91
(s, 1H, C(5)OH), 7.62 (s, 1H, C(7)H), 7.32 (s, 1H, C(9)H), 1.83
(m, 12H, H(PCH2)), 1.17 (m, 18H, H(PCH3)); 13C, δ 169.6 C(1),
124.7 C(2), 133.8 C(3), 126.8 C(4), 150.0 C(5), 110.0 C(6), 139.5
C(7), 111.7 C(8), 136.5 C(9), 18.7 (d, 2J(13C-31P) ) 33.4 (PCH2)),
9.7 (s, PCH3); 31P {1H}, δ 37.8 (s), 56.1 (s).
[(AuPEt3)2fspa] (8). H2fspa (0.037 g, 0.21 mmol), AuPEt3Cl
(0.150 g, 0.43 mmol), methanol (8 cm3), NaOH (0.017 g, 0.43
mmol), H2O (1 cm3), brown oil. Yield: 86%. (Found: C 28.3, H
4.7, S 3.9%. Calcd for C19H34O3SP2Au2: C 28.6, H 4.3, S 4.0%).
MS (FAB): the main metalated signals are at m/z 1113
(24%), [(AuPEt3)3fspa]+; 977 (66), [(AuPEt3)3S]+; 859 (11)
[(AuPEt3)2AuS]+; 798 (46), [M]+; 662 (6), [(AuPEt3)2S]+; 482 (3),
[(AuPEt3)Hfspa]+; 433 (100), [Au(PEt3)2]+ and 315 (76), [Au-
PEt3]+. IR (cm-1): 1580 vs, νas(COO); 1335 m, νsym(COO); 1456 m,
2
17.2 (d, J(13C-31P) ) 34.1 (PCH2)), 8.9 (s, PCH3); 31P {1H}, δ
38.6 (s).
1
X-ray Structure Determination. Single crystals of [(AuPEt3)2-
pspa] · 3H2O (1 · 3H2O), [(AuPEt3)2-o-hpspa] (5), [(AuPEt3)2-p-
hpspa]·3H2O (6·3H2O), and [(AuPEt3)2tspa]·3H2O (9·3H2O) were
mounted on glass fibers for data collection in a Bruker Smart CCD
automatic diffractometer at 293 K using Mo KR radiation (λ )
0.71073 Å). The crystal data, experimental details, and refinement
results are summarized in Table 1. Corrections for Lorentz effects,
1416 m, 1379 m, ν(PEt3). NMR (dmso-d6): H, δ 7.59 (s, 1H,
C(3)H), 7.18 (d, 1H, C(5)H), 6.61 (t, 1H, C(6)H), 7.69 (d, 1H,
C(7)H), 1.85 (m, 12H, H(PCH2)), 1.07 (m, 18H, H(PCH3)); 13C, δ
168.0 C(1), 126.0 C(2), 129.9 C(3), 152.0 C(4), 113.4 C(5), 112.1
C(6), 143.4 C(7), 17.7 (d, J(C-P) ) 34.5 (PCH2)), 9.4 (PCH3).
NMR (CDCl3): 1H, δ 8.0 (s, 1H, C(3)H), 7.11 (d, 1H, C(5)H), 6.45
(t, 1H, C(6)H), 7.40 (d, 1H, C(7)H), 1.83 (m, 12H, H(PCH2)), 1.19
Inorganic Chemistry, Vol. 47, No. 14, 2008 6265

Barreiro et al.
Table 1. Crystal Data For [(AuPEt3)2pspa]·3H2O (1·3H2O), [(AuPEt3)2-o-hpspa] (5), [(AuPEt3)2-p-hpspa]·3H2O (6·3H2O), and [(AuPEt3)2tspa]·3H2O
(9·3H2O)
[(AuPEt3)2pspa]·
3H2O (1·3H2O)
[(AuPEt3)2-p-hpspa]·
3H2O (6·3H2O)
[(AuPEt3)2tspa]·
3H2O·(9·3H2O)
compound
[(AuPEt3)2-o-hpspa] (5)
empirical formula
M
C21H42Au2O5P2S2
862.48
C21H36O3SAu2P2
824.43
C21H42Au2O6P2S
878.42
C19H40Au2O5P2S2
868.50
crystal system
space group
a (Å)
b (Å)
c (Å)
monoclinic
C2/m
15.0355(16)
15.9279(16)
13.5192(14)
90
117.178(2)
90
2880.2(5)
monoclinic
P2(1)/n
11.1140(9)
15.3963(13
16.2397(13)
90
108.265(2)
90
2638.8(4)
triclinic
P1
10.818(2)
11.155(2)
monoclinic
C2/m
14.9284(11)
15.9503(12)
13.3470(13)
90
116.077(2)
90
2854.6(4)
j
13.509(3)
R (°)
111.044(4)
105.415(3)
92.047(4)
1451.0(5)
2
ꢀ (°)
γ (°)
V (Å3)
Z
4
4
4
Dc (Mg. M-3
)
1.989
10.386
2.075
11.325
2.011
10.312
2.021
10.550
M (mm-1
)
crystal size (mm3)
0.28 × 0.22 × 0.22
1.69-28.00
-14 e h e 19
-20 e k e 20,
-17 e l e 17
7741
3259 [R(int) ) 0.0932]
0.0520, 0.1034
0.1978, 0.1308
0.39 × 0.20 × 0.17
1.87-28.00
-14 e h e 14
-16 e k e 20,
-21 e l e 14
16979
6283 [R(int) ) 0.1033]
0.0446, 0.0783
0.1004, 0.0895
0.40 × 0.20 × 0.20
1.97-27.98
-13 e h e 14,
-14 e k e 10,
-17 e l e 16
8039
5647 [R(int) ) 0.0447]
0.0620, 0.1159
0.1370, 0.1530
0.25 × 0.12 × 0.10
1.70-28.03
-19 e h e 13
-18 e k e 21
-15 e l e 17
7720
3235 [R(int) ) 0.0849]
0.0485, 0.0948
0.1974, 0.1197
θ range for data collection (°)
index ranges
reflections collected
unique reflections, R
Final R1, wR2 [I > 2σ(I)]
(All data)
polarization,22 and absorption23 were made. In 1 · 3H2O the
hydrogen atoms of the water molecules were not located so the
hydrogen bonds were determined on the basis of the O · · · O
distances. In 5 the ethyl groups of the triethylphosphine fragments
are disordered, the hydrogen of O(3) was refined. In 6·3H2O the
hydrogen atoms of the water molecules were not located, so the
hydrogen bonds were determined on the basis of the O · · · O
distances. In 9·3H2O the thiophene group is disordered (two
positions). Once again, the hydrogen atoms of the water molecules
were not located.
fragments that, as in similar systems,25–27 are indicative of
cleavage of the Au-S and Au-P bonds. The complexes are
soluble in MeOH, EtOH, acetone, DMSO, and CHCl3 but
are insoluble in water and Et2O.
Description of the Structures. [(AuPEt3)2pspa] · 3H2O
(1 · 3H2O), [(AuPEt3)2-p-hpspa] · 3H2O (6 · 3H2O) and
[(AuPEt3)2tspa] · 3H2O (9 · 3H2O). Crystals of 1 · 3H2O and
9 · 3H2O are both monoclinic, space group C2/m, whereas
j
those of 6 · 3H2O are triclinic, space group P1. The most
significant structural parameters for these compounds are
shown in Tables 2 and 3.
In Vivo Anti-inflammatory Experiments. Animals. Sprague-
Dawley rats weighting 175-200 g were used. For 1 week before
the experiment the animals were maintained in a sound-proofed
room thermostatted at 22 ( 1 °C with an artificial 12 h:12 h light:
dark cycle. Food and sterile water were supplied ad libitum.
Paw Edema Test (Anti-inflammatory Activity). Solutions of
the compounds under investigation in water/polyethylene glycol
(3:2), or vehicle alone, were administered intraperitoneally 30 min
before edema was induced by injection of 0.05 mL of a 1%
suspension of carrageenan in 0.9% sterile saline into the right plantar
aponerurosis of the rat.24 Paw volume was measured with a Ugo
Basile 7140 plethysmometer before and 4 h after the injection of
carrageenan. Anti-inflammatory activity is expressed as percentage
reduction of edema in treated rats in comparison with controls;
values are the mean ( SE of 8-12 rats. To assess statistical contrast
the Student-t test was carried out, and values were considered
statistically significant when P < 0.05.
The three crystals contain [(AuPEt3)2L]2 dimeric units and
water molecules. The dimer units can be seen as consisting
of two monomer units that dimerize through Au(I)-Au(I)
interactions. In the monomeric unit [(AuPEt3)2pspa] (Figure
1) the two gold atoms have equivalent coordinative environ-
ments. Each one is bonded to the S atom of the sulfanyl
group and to the P atom of PEt3; the orientation of the
carboxylate group allows both Au atoms to interact with O(1)
[Au-O(1) 2.992(14) Å, less than the sum of the van der
Waals radii, 3.20 Å].28
The Au · · · Au distances within the unit [Au-Au#1
3.1997(11) Å] are less than the sum of the van der Waals
radii (3.70 Å)28 but each unit is also close to a neighboring
molecule with Au-Au#2 distances of 3.2376(12) Å, which
are again less than the sum of the van der Waals radii. Thus,
the structure can be seen as a dimer of the type Au4S2, as
shown in Figure 2, where the ethyl groups of the phosphine
have been omitted for clarity.
Results and Discussion
The complexes were prepared by adding a solution of
Au(PEt3)Cl in a 2:1 molar ratio to a solution of the
appropriate acid and NaOH in methanol. The FAB+ mass
spectra of these complexes show the [M]+ peak and other
(25) Cookson, P. D.; Tiekink, E. R. T. J. Coord. Chem. 1992, 26, 313.
(26) Cookson, P. D.; Tiekink, E. R. T. J. Crystallogr. Spectrosc. Res. 1993,
23, 231.
(22) SAINT:SAX Area Detector Integration; Bruker AXS, Inc.: Madison,
WI, 1996.
(27) Wilton-Ely, J. D. E. T.; Schier, A.; Mitzel, N. W.; Schmidbaur, H.
J. Chem. Soc., Dalton Trans. 2001, 1058.
(23) Sheldrick G. M. SADABS, Version 2.03; University of Go¨ttingen,
Go¨ttingen, Germany, 2002.
(28) Huheey, J. E.; Keiter, E. A.; Keiter, R. L. Inorganic Chemistry.
Principles of Structure and ReactiVity, 4th ed.; Harper Collins: New
York, 1993.
(24) Winter, C. A.; Risley, E. A.; Nuss, G. W. Proc. Soc. Ext. Biol. Med.
1962, 111, 544.
6266 Inorganic Chemistry, Vol. 47, No. 14, 2008

Triethylphosphinegold(I) Sulfanylpropenoates
Table 2. Selected Bond Lengths (Å) and Angles (°) in
[(AuPEt3)2pspa]·3H2O (1·3H2O) and [(AuPEt3)2tspa]·3H2O (9·3H2O)a
1·3H2O
9·3H2O
(a) Au Environment
2.256(4)
Au-P
2.261(4)
2.350(4)
2.985(13)
3.2423(10)
3.3121(10)
Au-S
2.349(4)
2.992(14)
3.1997(11)
3.2376(12)
Au-O(1)
Au-Au#1
Au-Au#2
P-Au-S
175.40(16)
111.6(3)
65.0(3)
134.38(13)
47.07(9)
57.68(16)
107.35(12)
76.47(11)
140.5(3)
90.0
103.5(5)
103.5(5)
85.86(18)
105.4(14)
107.9(7)
175.06(15)
110.8(3)
66.1(3)
P-Au-O(1)
S-Au-O(1)
P-Au-Au#1
S-Au-Au#1
O(1)-Au-Au#1
P-Au-Au#2
S-Au-Au#2
O(1)-Au-Au#2
Au#1-Au-Au#2
C(2)-S-Au
135.78(11)
46.39(8)
57.10(16)
108.32(10)
75.29(11)
140.4(2)
90.000(1)
104.8(6)
104.8(6)
87.23(17)
102.0(15)
112.3(7)
Figure 1. Crystal structure of the [(AuPEt3)2pspa] unit. Ellipsoids are shown
at the 30% probability level.
C(2)-S-Au#1
Au-S-Au#1
C(1)-O(1)-Au
O(1W)-O(1)-Au
(b) Ligand
1.74(2)
1.12(2)
1.23(2)
1.46(3)
1.41(2)
1.43(2)
S-C(2)
1.73(2)
1.16(2)
1.27(2)
1.53(3)
1.36(2)
1.48(3)
O(1)-C(1)
O(2)-C(1)
C(1)-C(2)
C(2)-C(3)
C(3)-C(4)
O(2)-C(1)-O(1)
O(2)-C(1)-C(2)
O(1)-C(1)-C(2)
C(3)-C(2)-C(1)
C(3)-C(2)-S
122(2)
120(2)
118(2)
117.5(18)
121.4(15)
121.1(15)
133.5(19)
123(3)
115(2)
122(2)
117(2)
126.7(17)
116.1(17)
127(2)
Figure 2. Structural representation of [(AuPEt3)2pspa]2. Ellipsoids are
shown at the 30% probability level. For the sake of clarity, the ethyl groups
of PEt3 are not shown.
C(1)-C(2)-S
C(2)-C(3)-C(4)
a Symmetry transformations used to generate equivalent atoms: #1, x,
-y + 1, z; #2, -x, y, -z.
This Au4S2 core is a fairly common structural motif for
Au(I) sulfur clusters29 but this is a very rare motif in
situations like the ones described in this paper. Specifically,
the Au · · · Au distances are slightly longer than those found
in [(AuPMe3)2(µ-tatg)]2(NO3)2,13 [3.106(7), 3.171(11) Å],
[(AuPPh3)2(µ-SC6H4CH3)]2(PF6)2,14 [3.152(1), 3.173(1) Å],
[(AuPPh3)2(µ-SCH2C6H5)]2(BF4)2,30 [3.060(1), 3.078(1) Å],
and also longer than the ones present in [(AuPPh3)2-
SCH2COO(AuPPh3)]2(BF4)2 and [(AuPPh3)2S-C6H4-
COOH]2(BF4)230 [3.1270(5) and 3.1628(4) Å], the only two
sulfanylcarboxylates described in the literature that contain
this cluster. The latter two compounds have the formation
of the Au4S2 core in common with 1 · 3H2O, but there are
also remarkable differences. For example, in the first case
the existence of a third AuPPh3 group coordinated to the
carboxylate group [Au-O: 2.057(4) Å] moves this group
away from the Au atoms bonded to the S atom. On the other
hand, in the last compound the carboxylate group is
protonated and only interacts with one of the Au atoms
(Au-O: 2.778 Å); besides, this interacts through one
F-H-O hydrogen bond with the tetrafluoroborate anion
present in the structure.
Table 3. Selected Bond Lengths (Å) and Angles (°) in
[(AuPEt3)2-p-hpspa]·3H2O (6·3H2O)a
(a) Au Environment
Au(1)-P(1)
Au(1)-S
Au(1)-Au(2)
Au(1)-O(1)
Au(2)-S
Au(2)-P(2)
Au(2)-O(1)
Au(2)-Au(1)#1
2.268(4)
2.350(3)
3.2000(9)
2.967(13)
2.347(4)
2.263(5)
3.037(13)
3.1864(9)
P(1)-Au(1)-S
P(1)-Au(1)-Au(2)
C(2)-S-Au(1)
P(1)-Au(1)-O(1)
S-Au(1)-O(1)
P(1)-Au(1)-Au(2)#1
S-Au(1)-Au(2)#1
S-Au(1)-Au(2)
P(2)-Au(2)-S
P(2)-Au(2)-O(1)
S-Au(2)-O(1)
Au(1)-S-Au(2)
C(1)-O(1)-Au(2)
C(2)-S-Au(2)
Au(2)#1-Au(1)-Au(2)
S-Au(2)-Au(1)#1
P(2)-Au(2)-Au(1)#1
174.57(14)
133.84(13)
104.0(5)
108.3(3)
67.2(3)
107.15(12)
77.83(8)
47.02(9)
175.48(14)
110.2(3)
65.9(3)
85.90(12)
103.6(11)
105.0(5)
89.86(2)
78.02(8)
106.30(13)
(b) p-hpspa
S-C(2)
1.783(12)
1.221(18)
1.249(17)
1.509(19)
1.360(18)
1.42(2)
O(1)-C(1)-O(2)
O(1)-C(1)-C(2)
O(2)-C(1)-C(2)
C(3)-C(2)-C(1)
C(3)-C(2)-S
C(1)-C(2)-S
C(2)-C(3)-C(4)
123.0(16)
117.6(15)
119.2(16)
118.2(13)
122.7(11)
119.1(11)
133.8(13)
O(1)-C(1)
O(2)-C(1)
C(1)-C(2)
C(2)-C(3)
C(3)-C(4)
(29) Gimeno, M. C.; Laguna, A. ComprehensiVe Coordination Chemistry
II; Elsevier: Oxford, 2004; Vol. 6, p 1058.
a Symmetry transformations used to generate equivalent atoms: #1, -x
+ 1, -y, -z.
(30) Sladek, A.; Schneider, W.; Angermaier, K.; Bauer, A.; Schidbauer,
H. Z. Naturforsch. 1996, 516, 765.
Inorganic Chemistry, Vol. 47, No. 14, 2008 6267

Barreiro et al.
is similar to that found in [(AuPEt3)2pspa]2; however, some
differences do warrant further comment.
The Au-Au distances [3.1997(11), 3.2376(12) for
1 · 3H2O; 3.2003(9), 3.1871(9) for 6 · 3H2O and 3.2423(10),
3.3121(10) Å for 9·3H2O] show that the greater metal-metal
interaction is present in 6 · 3H2O, and it is also in this
compound that the Au4 ring is closest to a square. The Au-O
bond distances [2.992(14) for 1·3H2O; 2.967(13), 3.037(13)
for 6 · 3H2O and 2.985(13) Å for 9 · 3H2O] are all less than
the sum of the van der Waals radii (3.20 Å)28 but these show
a weaker interaction than those previously found in the
[(AuPPh3)2xspa] complexes17 and in 5 (vide infra).
The differences also affect the (H2O)6 cluster. It can be
seen in Figure 5 that the environment of these clusters is
different in the three crystals. Whereas in all cases the three
O atoms of the cluster interact with O(1) and O(2) of the
carboxylate group, thus generating the previously discussed
sheets, the close contacts with other neighboring sheets are
different. In 9·3H2O, besides the C(7)-H(7)-O(1W) inter-
actions [C(7B)-H(7B)-O(1W)#2: 0.93, 2.59, 3.52(10) Å,
179.3°; #2, x, y, z - 1] that are also present in 1 · 3H2O, the
O(2W)#1 atom interacts with the H-atom bonded to the
triethylphosphine methyl group [C(121)-H(12B)-O(2W)#1:
0.97, 2.68, 3.60(2) Å, 157.6°; #1, -x + 1/2, -y + 1/2, -z
+ 1]. In 6 · 3H2O the interaction is with the H atom of the
OH substituent on the phenyl ring of the p-mpspa ligand
[O(3)-H · · · O(1W)#3 : 0.82, 1.79, 2.55(3) Å, 152.4°; #3, x,
y, z - 1], thus leading to an environment with 6 O atoms
for this cluster. These different environments and the
structural packing have an influence on the cluster param-
eters, as shown in Table 4. The O · · ·O bond distances range
from 2.66(3) to 2.83(3) [2.75 Å for the Ih ice (T ) 60 K),
2.85 Å for liquid water]32,33 and the angles [78.9(8) to
92.5(6)°] show the significant distortion of the cluster with
respect to the ideal tetrahedral angle of Ih ice.
Two examples of (H2O)6 clusters that have a chair
conformation and are located between metallic units have
recently been described. One of these structures was identi-
fied in [Cu(L)]2[Mo(CN)8]·3H2O [L ) 1,4-bis(3-aminopro-
pylpiperazine)],34 bonded through hydrogen bonds to the CN
ligands of the [Mo(CN)8]4- fragments that surround it. The
other case is Li6[Ni3V18O42(H2O)12(SO4)] ·24HO,35 which is
bonded through one hydrogen bond to one terminal O atom
of the [V18O42(SO4)] fragment.
In addition, genuine (H2O)6 clusters have been described
that are bonded by hydrogen bonds to other water molecules,
thus generating major entity structures. For example, in
{[Mn(cda)2 ·H2O] ·4H2O}n (H2cda ) 4-hydroxypyridine-2,6-
dicarboxylic acid)36 the cluster is bonded to two acyclic
tetramers to form an (H2O)14 entity, in 1,4-[B(OH)2]2-
Figure 3. Position of the (H2O)6 cluster in the crystal of
[(AuPEt3)2pspa]·3H2O.
The water molecules present in the crystal interact with
one another through hydrogen bonds to form an (H2O)6
cluster with a conformation of the “chair” type, which is
similar to that found in the hexagonal compact structure of
the Ih ice crystal. It was not possible to locate the hydrogen
atoms of the water molecules and thus the hydrogen bonds
must be described on the basis of the O · · · O distances,
2.784(18) Å for O(1W)-O(2W) and 2.80(2) Å for O(2W)-
O(2W)#3; #3 ) -x + 1, y, -z + 1. This cluster is located
in the lattice in the c position in the Wyckoff terminology,
with the pspa2- fragment of the dimer units located in the
symmetry plane in which the two AuPEt3 fragments are
generated by a reflection (Figure 3). The repetition of (H2O)6
clusters and dimer units generates sheets.
Furthermore, at a distance of about 2.6 Å from the cluster
there are two C(7)-H atoms of phenyl rings from one ligand
of neighboring molecules from adjacent sheets. This gives
rise to the environment for the cluster that is represented in
Figure 4. The C-H· · · O parameters for these interactions
[C(7)-H(7) · · · O(1W)#1: 0.93, 2.61, 3.40(3) Å, 143.3°; #1
x, y, z - 1] and for the [C(8)-H(8) · · · O(2)#2: 0.93, 2.58,
3.48(3) Å, 164.3°; #2 -x + 1, y, -z] suggest close
contacts.31
The crystals of 6 · 3H2O and 9 · 3H2O consist of
[(AuPEt3)2xspa]2 units and (H2O)6 clusters, as in 1 · 3H2O.
The general coordinative scheme found in the [(AuPEt3)2-
p-hpspa]2 (Supporting Information, Figure S1) and
[(AuPEt3)2tspa]2 (Supporting Information, Figure S2) units
(32) Jeffrey, G. A. An Introduction to Hydrogen Bonding; Oxford University
Press: New York, 1997.
(33) Kuhs, W. F.; Lehman, M. S. J. Phys. Chem. 1983, 87, 4312.
(34) Mukhopadhyay, U.; Bernal, I. Cryst. Growth Des. 2005, 5, 1687.
(35) Doedens, R. J.; Johannes, E.; Ishaque Khan, M. Chem. Commun. 2002,
62.
(31) Desiraju, G. R.; Steiner, T. The Weak Hydrogen Bond; Oxford
(36) Ghosh, S. K.; Ribas, J.; El Fallah, M. S.; Bharadwaj, P. K. Inorg.
Chem. 2005, 44, 3856.
University Press: Oxford, U.K., 1999; p 29.
6268 Inorganic Chemistry, Vol. 47, No. 14, 2008

Triethylphosphinegold(I) Sulfanylpropenoates
Figure 4. Close environment of the (H2O)6 cluster in [(AuPEt3)2pspa]·3H2O.
Figure 5. Environment of the (H2O)6 clusters in 1·3H2O (A), 6·3H2O (B), and 9·3H2O (C).
Table 4. Structural Parameters of the (H2O)6 Clusters in the Crystals of
dicarboxylic acid) and [Zn(H2biim)2(OH2)2(ina)2] · 4H2O40
1·3H2O, 6·3H2O, and 9·3H2Oa
(H2biim ) 2,2′-biimidazole; ina ) isonicotinate) where the
water molecules are coordinated to the metal atom and are
not free. Another interesting example is found in [CuL(O2C-
CH2-C6H4-pOH)] · 2H2O (H3L ) N,N′-1,3-diylbis(salicyl-
diimino)propan-2-ol)]· 2H2O,41 where the “(H2O)6” ring is
actually formed by two OH groups and by four water
molecules.
interactions
1·3H2O
6·3H2O
9·3H2O
O(1W)-O(2W)
O(2W)-O(2W)#3
O(1W)-O(3W)
O(2W)-O(3W)#4
2.784(18)
2.80(2)
2.67(4)
2.720(19)
2.83(3)
2.66(3)
2.78(3)
O(2W)#1-O(1W)-O(2W)
O(3W)-O(1W)-O(2W)
O(2W)#3-O(2W)-O(1W)
O(1W)-O(2W)-O(3W)#4
O(1W)-O(3W)-O(2W)#4
a Symmetry transformations used to generate equivalent atoms: #1, x,
-y + 1, z; #3, -x + 1, y, -z + 1; #4, 2 - x, 1 - y, 1 - z.
C6H4 · 4H2O37 the (H2O)6 clusters are bonded to others with
an analog or boat conformation to form water sheets, and in
DAN · 2.5H2O (DAN ) 2,4-dimethyl-5-aminobenzo[b]-1,8-
naphthyridine)38 the clusters are bonded through hydrogen
bonds to form chains in which 4- and 6-membered rings are
fused.
81.5(6)
89.8(5)
82.1(7)
92.5(6)
78.9(8)
[(AuPEt3)2-o-hpspa] (5). The crystal is monoclinic, space
group P2(1)/n, and contains [(AuPEt3)2-o-hpspa] units in-
volved in a network of hydrogen bonds. The structure and
the numbering scheme are shown in Figure 6 and significant
structural parameters are listed in Table 5.
In each [(AuPEt3)2-o-hpspa] unit there are two Au atoms,
Au(1) and Au(2), with different coordinative environments.
Au(2) is bonded to the S atom of the deprotonated sulfanyl
group and to the P atom of PEt3, while Au(1) is also
coordinated to one O atom of the carboxylate group [Au-O
(2.585(5)Å)]. This distance is significantly less than the sum
82.4(9)
88.9(8)
Finally, there are “(H2O)6” clusters like those present in
[Pr(pdc)(pdcH)2H2O] · 0.4H2O39 (H2pdc ) pyridine-2,6-
(39) Ghosh, S. K.; Bharadwaj, P. K. Inorg. Chem. 2003, 42, 8250.
(40) Ye, B.-H.; Ding, B.-B.; Weng, J.-Q.; Chen, X.-M. Inorg. Chem. 2004,
43, 6866.
(37) Rodr´ıguez-Cuamatri, P.; Vargas-Diaz, G.; Ho¨pfl, H. Angew. Chem.,
Int. Ed. 2004, 43, 3041.
(38) Custelcean, R.; Afloroaei, C.; Vlassa, M.; Polverejan, M. Angew.
Chem., Int. Ed. 2000, 39, 3094.
(41) Mukherjee, A.; Saha, M. K.; Nethaji, M.; Chakravarty, A. R. New
J. Chem. 2005, 29, 596.
Inorganic Chemistry, Vol. 47, No. 14, 2008 6269

Barreiro et al.
Figure 6. Molecular structure of [(AuPEt3)2-o-hpspa] showing the number-
ing scheme.
Table 5. Selected Bond Lengths (Å) and Angles (°) in
[(AuPEt3)2-o-hpspa] (5)
(a) Au Environment
Au(1)-P(1)
Au(1)-S
Au(1)-Au(2)
Au(1)-O(1)
2.242(3)
2.363(2)
3.1677(5)
2.585(5)
P(1)-Au(1)-S
P(1)-Au(1)-O(1)
S-Au(1)-O(1)
174.24(8)
111.71(14)
74.05(14)
128.83(8)
47.24(5)
103.1(3)
111.1(4)
111.4(7)
109.1(8)
107.39(13)
116.3(5)
Figure 7. Hydrogen bonding interactions in [(AuPEt3)2-o-hpspa].
P(1)-Au(1)-Au(2)
S-Au(1)-Au(2)
C(2)-S-Au(1)
C(11)-P(1)-Au(1)
C(13A)-P(1)-Au(1)
C(15B)-P(1)-Au(1)
O(1)-Au(1)-Au(2)
C(1)-O(1)-Au(1)
and 9 · 3H2O and this one in terms of the Au unit is the
coordination of the carboxylate group and the formation of
dimers.
When the O atom of the carboxylate group acts as a bridge
between two Au atoms (1·3H2O, 6·3H2O, and 9·3H2O) the
ligands are planar, or essentially planar, but in 5 the CSCOO
fragment is not planar [SC(2)C(1)O(1) torsion angle: 18.5(10)°]
andthephenylringdeviatessignificantlyfromtheC(3)C(2)C(1)S
plane [C(9)C(4)C(3)C(2) torsion angle: 3.8(13)°]. This spatial
arrangement allows, or is the result of, the O-H · · ·O
interaction present in the crystal, where hydrogen bonds exist
between the O(3)-H(3) group of the phenyl ring and the
O(1) atom of the carboxylate group of a neighboring
molecule [O(3)-H(3) · · ·O(1)#1 0.73(9), 1.82(9), 2.529(8 Å,
163(10)°], thus leading to a polymeric structure (see Figure
7).
IR Spectroscopy. Comparison of the spectra of these
compounds with those of the free H2L ligands shows the
disappearance of the ν(SH) band (at about 2590-2560 cm-1)
and the replacement of the CO2H bands (at about 1730-1680
and 1320-1210 cm-1) by bands typical of a carboxylate
group. Both of these observations are consistent with
bideprotonation of the ligand.
With respect to the carboxylate bands in the complexes,
νas(COO) and νsym(COO) are close to the positions of these
bands in the IR spectra of the sodium salt of the ligands
{for example 1574, 1576 and 1566 cm-1 [νas(COO)] and
1383, 1373, and 1392 cm-1 [νsym(COO)] for H2pspa, H2fspa
and H2tspa, respectively} and the value of the parameter
[νas(COO) - νsym(COO)] is low compared42 with that of a
monodentate group. This suggests that in the solid the Au-O
interaction is very weak. Note that the situation in the solids
of 1, 6, and 9 could be different to those found by X-ray
Au(2)-S
Au(2)-P(2)
2.335(2)
2.246(3)
P(2)-Au(2)-S
179.82(11)
132.16(10)
47.99(5)
108.5(2)
121.0(10)
110.1(9)
112.4(7)
112.4(7)
116.1(6)
P(2)-Au(2)-Au(1)
S-Au(2)-Au(1)
C(2)-S-Au(2)
C(23B)-P(2)-Au(2)
C(21B)-P(2)-Au(2)
C(25)-P(2)-Au(2)
C(21A)-P(2)-Au(2)
C(23A)-P(2)-Au(2)
(b) o-hpspa
S-C(2)
1.774(7)
1.241(9)
1.227(9)
1.337(9)
1.524(10)
1.353(10)
1.456(10)
O(2)-C(1)-O(1)
O(2)-C(1)-C(2)
O(1)-C(1)-C(2)
C(1)-C(2)-S
C(3)-C(2)-C(1)
C(3)-C(2)-S
123.9(8)
118.1(8)
118.0(7)
117.1(6)
118.0(7)
124.9(6)
121.5(8)
133.0(7)
O(1)-C(1)
O(2)-C(1)
O(3)-C(5)
C(1)-C(2)
C(2)-C(3)
C(3)-C(4)
C(4)-C(9)-C(8)
C(2)-C(3)-C(4)
of the van der Walls radii (3.20 Å),28 less than the Au-O
bond distances previously described in this paper, and similar
to those found in complexes of type [(AuPPh3)2xspa] with
similar ligands.17 This interaction has a significant effect on
the structural parameters of the metal environment. The
parameter that is most markedly affected by the Au-O
interaction is the S-Au-P angle, which is 174.24(8)° for
Au(1) and 179.82(11)° for Au(2). The Au · · · ·Au [3.1677(5)
Å] distance is less than the sum of the van der Walls radii
for gold (3.70 Å)28 and also less than the intramolecular
Au · · · Au distances found in the previous structures.
The structural features of this unit are in contrast with the
cases discussed previously, and they resemble those found
in the [(AuPPh3)2xspa] compounds already described.17 The
main difference between the structures of 1·3H2O, 6·3H2O,
(42) Nakamoto, K. Infrared and Raman Spectra of Inorganic and Coor-
dination Compounds, 5th Ed.; John Wiley: New York, 1997; part B,
p 60.
6270 Inorganic Chemistry, Vol. 47, No. 14, 2008

Triethylphosphinegold(I) Sulfanylpropenoates
crystallography, as could also be the case (vide infra) for 5,
as the crystals were obtained from a dmso-d6 solution and
the solid from methanol/water.
To investigate the formation of OPEt3 we followed the
evolution of the 31P NMR spectrum of 9 using dmso-d6 as
solvent. The 31P spectrum of a recently prepared solution of
9 shows only a signal at 39.1 ppm attributable to
[(AuPEt3)2tspa]. After 20 min a second signal appears at 54.7
ppm, in this case attributable to OPEt3. The amounts of the
different species after 45 min, estimated from the integrated
peaks, are [(AuPEt3)2tspa] 98.5% and OPEt3 1.5%. After 55
days, the 39.1 ppm signal remained and a new weak signal
at 39.5 ppm was identified. This latter signal could be
attributed to the PEt3 coordinated in [(AuPEt3)(Htspa)], with
both species representing about 67%. The OPEt3 signal
remained and this species represented about 10.8%. A new
signal at 51.1 ppm was seen and this was assigned to
1
NMR Spectroscopy. The main modifications in the H
NMR spectra of the H2L ligands upon formation of the
complexes are the disappearance of the C(2)SH (at about 5
ppm) and the CO2H (at about 13 ppm) signals. This is
consistent with deprotonation of both groups. Another
common characteristic of all the spectra, except those of
H2cpa and H2fspa in CDCl3 and H2-o-pyspa derivatives, is
the shift to higher field of the C(3)H signal with respect to
that in the free ligand, suggesting that the S-coordination
found in the solid state, as in other complexes of these
ligands, remains in solution.17,43,44 In addition, all the spectra
show signals due to the PEt3 groups and these are located
around 1.10 and 1.80 ppm for CH3 and CH2, respectively
The spectrum of the [(AuPEt3)2-o-pyspa] complex does
not show the signal due to the NH group, which is present
in the spectrum of the free ligand, and this reflects depro-
tonation of this group and the evolution of the ligand to the
thiol form, with the subsequent coordination of the metal to
this group.
48
[Au(PEt3)2]+ (about 22.4%), an ion also present in the
MS(FAB) spectra.
During the experiment a signal attributable to the free PEt3
was not observed, meaning that the oxidation of this species
is rapid; however, 9 showed a slow rate of decomposition.
Antiinflammatory Activity. The antiinflammatory effect
of the compounds at doses of 2.5 and 5 mg/Kg are shown
in Table 6 and are compared with the control. As can be
seen, the complexes, except 11, are active at a dose of 5
mg/Kg. The activities are higher than those of the ligands
(for example, H2pspa, H2fspa, and H2tspa, at a dose of 5
mg/Kg showed percentages of inflammation of 19.60, 39.25,
7.51% and reduction of 40.10, -19.77, 77.02%, respec-
tively), which is in contrast with previous results on Zn-
metalation of pyrazolones52 and underlines the positive effect
of the metal.
Despite these findings, the influence of the ligand on the
activity of the complexes is evident. On comparing the
activities of the complexes that contain the phenyl, furan,
thiophene, or pyridine ring it can be seen that the best result
is obtained for the thiophene derivative (9) and the worst
for the pyridine derivative (10); however, the introduction
of substituents on the phenyl ring changes the activity, with
hydroxy and chloro substituents in the ortho-position being
the most effective. The additional incorporation of Br atoms
into the o-hydroxyphenyl derivative decreases the activity.
The values of the inflammation reduction for the best
compounds are higher than those of AuPEt3Cl and also
higher than those previously found in other compounds of
Au(I), Au(III), and auranofin in this induced edema.53,54 To
make comparisons with other agents, indomethacin, an
antiinflammatory used as a positive test in studies carried
out under the same conditions,55,56 shows a percentage of
inflammation reduction of 35.87% at the 5 mg/Kg level.
The high antinflammatory activity of some of these
compounds, together with the recent positive data on a
combination therapy for rheumatoid arthritis that includes
In the 13C NMR spectra the signals are shifted with respect
to those of the free ligands because of the coordination to
the metal atom. For [(AuPEt3)2-o-pyspa], the C(2) signal is
significantly shielded and C(3) is deshielded because of the
evolution of the ligand to the thiol form and subsequent
coordination to the Au atom.
The C(1) signal for the pspa, fspa, and tspa complexes in
the dmso-d6 spectra is close to those found in complexes of
the type [(AuPPh3)2L] with equivalent ligands;17 in the latter
compounds the coordination mode of L is similar to that
found for L in 5. The isolation of this complex from a dmso-
d6 solution and the position of the C(1) signal in the spectra
of the other complexes suggest45,46 the possibility of a similar
coordinative mode in this solvent in all of these cases.
The 31P NMR spectra consist of one singlet located at
around 39 ppm, attributed to the coordinated PEt3, and this
is close to the signal found in other complexes with
S-Au-PEt3 fragments.47–50 The 13C and 31P{1H} chemical
shifts and 31P{1H}-13C coupling constants are consistent with
compounds of this type.50 Some spectra show the presence
of a very weak signal at around 54 ppm and this can be
attributed to OPEt3.48 A peak at around -18.6 ppm that could
be assigned to PEt3 was not observed.49,51
(43) Casas, J. S.; Castin˜eiras, A.; Couce, M. D.; Jorge, M. L.; Russo, U.;
Sa´nchez, A.; Seoane, R.; Sordo, J.; Varela, J. M. Appl. Organomet.
Chem. 2000, 14, 421.
(44) Casas, J. S.; Castin˜eiras, A.; Couce, M. D.; Playa´, N.; Russo, U.;
Sa´nchez, A.; Sordo, J.; Varela, J. M. J. Chem. Soc., Dalton Trans.
1998, 1513.
(45) Gajda-Schrantz, K.; Nagy, L.; Kuzmann, E.; Vertes, A.; Holecek, J.;
Lycka, A. J. Chem. Soc., Dalton Trans. 1997, 2201.
(46) Holecek, J.; Lycka, A.; Nadvornik, M.; Handlir, K. Collect. Czech.
Chem. Commun. 1991, 56, 1908.
(51) Isab, A. A.; Hussain, M. S.; Katar, M. N.; Wazeer, M. I. M.; Al-
Arfaj, A. R. Polyhedron 1999, 18, 1401.
(47) Coffer, M. T.; Shaw, C. F., III; Eidsness, M. K.; Watkins II, J. W.;
Elder, R. C. Inorg. Chem. 1986, 25, 333.
(52) Casas, J. S.; Castan˜o, M. V.; Castellano, M. E. E.; Ellena, J.; Garc´ıa-
Tasende, M. S.; Gato, A.; Sa´nchez, A.; Sanjuan, L. M.; Sordo, J. Inorg.
Chem. 2002, 41, 1550.
(48) Isab, A. A.; Hormann, A. L.; Coffer, M. T.; Shaw, C. F., III J. Am.
Chem. Soc. 1988, 110, 3278.
(53) Coppi, G.; Borella, F.; Gatti, M. T.; Comini, A.; Dall’Asta, L. Boll.
Chim. Farm. 1989, 128, 22.
(49) Ahmad, S.; Isab, A. A. J. Inorg. Biochem. 2002, 88, 44.
(50) Kang, J. G.; Cho, H. K.; Park, C.; Yun, S. S.; Kim, J. K.; Broker,
G. A.; Smyth, D. R.; Tiekink, E. R. T. Inorg. Chem. 2007, 46, 8228.
(54) Girard, G. G.; Hill, D. T.; Dimartino, M. J. Inorg. Chim. Acta 1989,
166, 141.
Inorganic Chemistry, Vol. 47, No. 14, 2008 6271

Barreiro et al.
Table 6. Anti-inflammatory Effect of the Compounds Tested against Plantar Edema Induced by Carrageenan
compound
dose(mg/Kg)
animals
% inflammation
% reduction
control
[(AuPEt3)2pspa] (1)
12
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
8
8
9
9
9
9
9
9
32.77 ( 1.89
17.33 ( 1.70a
3.60 ( 0.80a
8.01 ( 1.40a
2.36 ( 0.60a
33.3 ( 2.06
16.64 ( 2.10a
24.05 ( 1.5a
19.12 ( 2.7a
6.04 ( 1.72a
-0.08 ( 1.90a
20.72 ( 0.81a
9.99 ( 1.05a
25.53 ( 1.8a
20.25 ( 3.3a
16.86 ( 1.66a
2.10 ( 2.22a
4.84 ( 1.65a
1.10 ( 1.37a
17.40 ( 1.08a
12.70 ( 1.0a
40.29 ( 1.7
48.7 ( 1.8
2.5
5
2.5
5
2.5
5
2.5
5
2.5
5
2.5
5
2.5
5
2.5
5
2.5
5
2.5
5
2.5
5
2.5
5
47.11 ( 5.3
88.78 ( 2.6
75.5 ( 4.40
92.85 ( 2.06
-1.90 ( 6.20
49.18 ( 6.40
26.56 ( 4.8
41.65 ( 8.4
81.54 ( 5.25
100.24 ( 5.80
36.74 ( 2.48
69.48 ( 3.22
22.06 ( 5.4
38.16 ( 10.2
48.54 ( 5.08
93.56 ( 1.54
85.15 ( 5.04
96.61 ( 4.19
46.86 ( 3.3
61.22 ( 4.0
-2.30 ( 2.60
-2.78 ( 2.80
59.5 ( 4.2
[(AuPEt3)2Clpspa] (2)
[(AuPEt3)2-o-mpspa] (3)
[(AuPEt3)2-p-mpspa] (4)
[(AuPEt3)2-o-hpspa] (5)
[(AuPEt3)2-p-hpspa] (6)
[(AuPEt3)2-diBr-o-hpspa] (7)
[(AuPEt3)2fspa] (8)
[(AuPEt3)2tspa] (9)
[(AuPEt3)2-o-pyspa] (10)
[(AuPEt3)2cpa] (11)
AuPEt3Cl
13.23 ( 1.39a
12.40 ( 1.4a
62.13 ( 4.4
a Significant with respect to the control (P e 0.05).
gold compounds,57 warrants additional testing of the activity
against this illness for the active compounds.
activity is significant, with the o-hpspa and the tspa deriva-
tives being the most active.
Acknowledgment. We thank the Spanish Ministry of
Science and Technology for financial support under projects
BQU2002-04524-CO2-01 and BQU2002-04524-CO2-02,
and the Xunta the Galicia, Spain, for support under projects
PGIDIT03PXIC20306PN and PGIDIT03PXIC30103PN.
Conclusions
The synthesis and the structural study of complexes of
the type [(AuPEt3)2xspa] [where H2xspa ) RsCHdC(SH)s
COOH] enabled the identification of two classes of structures.
One of them consists of [(AuPEt3)2xspa]2 dimers, a tetra-
nuclear unit that contains an Au4 ring, and these are hydrogen
bonded to (H2O)6 clusters. In the other system the dinuclear
motif [(AuPEt3)2xspa] does not dimerize.
The first class of compounds gives the opportunity to
visualize a structural motif present in the oxidation products
of Au(I) phosphine thiolate compounds such as auranofin
and at the same time, because of the use of different R groups
in the precursor acids, enables us to analyze the influence
of different chemical environments on the (H2O)6 cluster
parameters.
Supporting Information Available: Figures S1, S2 containing
crystal structure of [(AuPEt3)2-p-hpspa]2 in 6 · 3H2O and of
[(AuPEt3)2tspa]2 in 9·3H2O (PDF). This material is available free
of charge via the Internet at http://pubs.acs.org. Also, crystal-
lographic data for this paper can be obtained at the Cambridge
Crystallographic Data Centre [CCDC numbers 676684, 676685,
676686 and 676687 for 1 · 3H2O, 5, 6 · 3H2O and 9 · 3H2O
respectively].
IC800314P
(55) Guzma´n, S.; Gato, A.; Calleja, J. M. Phyther. Res. 2001, 15, 224.
(56) Guzma´n, S.; Gato, A.; Lamela, M.; Freire-Garabad, M.; Calleja, J. M.
Phyther. Res. 2003, 17, 665.
The antiinflammatory activities of the compounds prepared
show that, in general, all of them are active but that the
influence of the R substituents on the antiinflammatory
(57) Lehman, A. J.; Esdaile, J. M.; Klinkhoff, A. V.; Grant, E.; Fitzgerald,
A.; Canvin, J. Arthritis Rheum. 2005, 52, 1360.
6272 Inorganic Chemistry, Vol. 47, No. 14, 2008