Synthesis, structural characterization and in vitro cytotoxicity of new Au(III) and Au(I) complexes with thioamides

Article abstract of DOI:10.1039/b909587j

The reactions of tetrachloroauric(III) acid (HAuCl₄) with the thioamides; 2-mercapto-benzothiazole (mbztH) and 5-ethoxy-2-mercapto- benzimidazole (EtmbzimH) lead to the desulfuration of the ligands and the formation of the ionic complexes {[AuCl₄]^-[bztH ₂]⁺} (1), and {[AuCl₄]^-[EtbzimH ₂]⁺(H₂O)} (2) (where bztH₂ ⁺ and EtbzimH₂⁺ are the desulfurated cations of the starting ligands). The reaction of HAuCl₄ with 2-mercapto-nicotinic acid (mnaH₂), however results in the formation of 2-sulfonate-nicotininc acid (C₆H₅NO₅S) (3) with the simultaneous oxidation of the sulfur atom. On the other hand, the reactions of the gold(I) complex [Au(tpp)Cl] (4) (tpp = triphenylphosphine (Ph₃P)) with the thioamides; 2-mercapto-thiazolidine (mtzdH), 2-mercapto-benzothiazole (mbztH) and 5-chloro-2-mercapto-benzothiazole (ClmbztH) in the presence of potassium hydroxide resulted in the formation of the gold(I) complexes of formulae [Au(tpp)(mtzd)] (5), [Au(tpp)(mbzt)] (6) and [Au(tpp)(Clmbzt)] (7) without ligand desulfuration. All complexes have been characterized by elemental analysis, FT-IR, far-FT-IR,¹H-NMR, spectroscopic techniques and X-Ray crystallography. The electrochemical behavior of 1, 2 and 4-7 complexes and the ligands EtmbzimH, mbztH and mnaH₂ was also studied in acetonitrile and DMF using cyclic voltammetry. The results are in support of a mechanism of desulfuration of the ligands by Au(III), involving a first oxidation of S to -SO₃^-, followed by a C-S bond cleavage. This is also supported by PM6 calculations of bond dissociation energies of the various compounds involved. Complexes 1, 2 and 4-7 were tested for in vitro cytotoxicity against leiomyosarcoma cells and the results are discussed in relation with the geometry of the complexes and compared with those of cisplatin and other metals. Complexes 1 and 5 showed higher activity than that of cisplatin, while HAuCl₄ was inactive against sarcoma cells.

Full text of DOI:10.1039/b909587j

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PAPER
www.rsc.org/dalton | Dalton Transactions
Synthesis, structural characterization and in vitro cytotoxicity of new Au(III)
and Au(I) complexes with thioamides†
K. N. Kouroulis,a S. K. Hadjikakou,*a N. Kourkoumelis,b M. Kubicki,c L. Male,d M. Hursthouse,d S. Skoulika,e
A. K. Metsios, f V. Y. Tyurin,g A. V. Dolganov,g E. R. Milaevag and N. Hadjiliadis*a
Received 14th May 2009, Accepted 18th September 2009
First published as an Advance Article on the web 13th October 2009
DOI: 10.1039/b909587j
The reactions of tetrachloroauric(III) acid (HAuCl4) with the thioamides; 2-mercapto-benzothiazole
(mbztH) and 5-ethoxy-2-mercapto-benzimidazole (EtmbzimH) lead to the desulfuration of the ligands
and the formation of the ionic complexes {[AuCl4]-[bztH2]+} (1), and {[AuCl4]-[EtbzimH2]+(H2O)} (2)
+
+
(where bztH2 and EtbzimH2 are the desulfurated cations of the starting ligands). The reaction of
HAuCl4 with 2-mercapto-nicotinic acid (mnaH2), however results in the formation of
2-sulfonate-nicotininc acid (C6H5NO5S) (3) with the simultaneous oxidation of the sulfur atom. On the
other hand, the reactions of the gold(I) complex [Au(tpp)Cl] (4) (tpp = triphenylphosphine (Ph3P))
with the thioamides; 2-mercapto-thiazolidine (mtzdH), 2-mercapto-benzothiazole (mbztH) and
5-chloro-2-mercapto-benzothiazole (ClmbztH) in the presence of potassium hydroxide resulted in the
formation of the gold(I) complexes of formulae [Au(tpp)(mtzd)] (5), [Au(tpp)(mbzt)] (6) and
[Au(tpp)(Clmbzt)] (7) without ligand desulfuration. All complexes have been characterized by
elemental analysis, FT-IR, far-FT-IR,1H-NMR, spectroscopic techniques and X-Ray crystallography.
The electrochemical behavior of 1, 2 and 4-7 complexes and the ligands EtmbzimH, mbztH and mnaH2
was also studied in acetonitrile and DMF using cyclic voltammetry. The results are in support of a
-
mechanism of desulfuration of the ligands by Au(III), involving a first oxidation of S to -SO3 , followed
by a C-S bond cleavage. This is also supported by PM6 calculations of bond dissociation energies of the
various compounds involved. Complexes 1, 2 and 4-7 were tested for in vitro cytotoxicity against
leiomyosarcoma cells and the results are discussed in relation with the geometry of the complexes and
compared with those of cisplatin and other metals. Complexes 1 and 5 showed higher activity than that
of cisplatin, while HAuCl4 was inactive against sarcoma cells.
investigation of gold compounds relates to the square-planar
Introduction
geometry, also found for platinum in cisplatin, since gold(III)
is isoelectronic with platinum(II) and forms similar square-
planar complexes.4 Given the generally reducing mammalian
environment, compounds containing gold(III) may be expected
to be reduced in vivo to gold(I) and this led to the investigation
of possible antitumor properties of gold(I) compounds as well.4
However, appropriate selection of the ligand donor set (e.g. N
or O) can serve to stabilize gold(III) and consequently there is a
rich literature of anti-tumour/cytotoxicity investigations of such
species.4a
Chrysotherapy, is the use of gold compounds in medicine with
many applications.1-3 Gold thiolates are used clinically against
rheumatoid arthritis.1-3 Recently, many gold(III) and gold(I)
compounds were tested for their antitumor activity against
various cancerous cell lines4 and the results have been reviewed
by Tiekink.4a A commonly cited reason for the anti-tumor
aInorganic and Analytical Chemistry, Department of Chemistry, University
of Ioannina, 45110, Ioannina, Greece. E-mail: nhadjis@uoi.gr, shadjika@
uoi.gr; Fax: +30-26510-08786; Tel: +30-26510-08420; Tel: +30-26510-
08374
In the course of our studies on metalotherapeutics we
synthesized and structurally characterized new gold(III) com-
plexes with the thioamides 2-mercapto-benzothiazole (mbztH)
and 5-ethoxy-2-mercapto-benzimidazole (EtmbzimH) of formu-
lae {[AuCl4]-[bztH2]+} (1), and {[AuCl4]-[EtbzimH2]+(H2O)} (2)
bMedical Physics Laboratory, Medical School, University of Ioannina,
Greece
cDepartment of Chemistry, A. Mickiewicz, University, ul. Grunwaldzka 6,
60-780, Poznan, Poland
dDepartment of Chemistry, University of Southampton, Highfield,
Southampton, UK SO17 1BJ
+
+
(where bztH2 and EtbzimH2 are the desulfurated cations of
the starting ligands) (Scheme 1). Also for gold(I) mixed ligand
complexes of [Au(tpp)Cl] (4) with the thioamides 2-mercapto-
thiazolidine (mtzdH), 2-mercapto-benzothiazole (mbztH) and
5-chloro-2-mercapto-benzothiazole (ClmbztH) and tri-phenyl-
phosphine (tpp) of formulae [Au(tpp)(mtzd)] (5), [Au(tpp)(mbzt)]
(6) and [Au(tpp)(Clmbzt)] (7) (Scheme 1). Moreover in the reaction
of HAuCl4 with 2-mercapto-nicotinic acid (mnaH2) the ligand is
oxidized to 2-sulfonate-nicotininc acid (C6H5NO5S) (3).
eSection of Physical Chemistry, Department of Chemistry, University of
Ioannina, 45110, Ioannina, Greece
f
Department of Experimental Physiology, Medical School, University of
Ioannina, 45110, Ioannina, Greece
gChemistry Department, M.V. Lomonosov Moscow State University,
Leninskie Gory, 119992, Moscow, Russia
† CCDC reference numbers 732324 (1), 732325 (2), 733450 (3), 732369 (6)
and 732368 (7). For crystallographic data in CIF or other electronic format
see DOI: 10.1039/b909587j
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potential electrolyses which was performed in acetonitrile were
achieved at the first anodic wave potential of E = 1.3 V. This
support the assumption that the oxidation of mnaH2 ligand also
proceeds the desulfuration step.
Finally, the in vitro cytotoxicity of complexes 1-2 and 4-7 and
HAuCl4 against leiomyosarcoma cells were also evaluated and
the results were compared with analogous Sn(IV), Ag(I), Sb(III)
complexes, reported by our group earlier6 and cisplatin.
Results and discussion
Scheme 1 The ligands used in this study.
General aspects
The use of AuCl4- as a counter ion in complexes 1 and 2 and the
isolation of 2-sulfonate-nicotinic acid (C6H5NO5S; (3)), strongly
indicates that AuCl4 acts rather as a catalyst, while the oxidation
Tetrachloroauric(III) acid (HAuCl4) solution was prepared ac-
cording to the literature by dissolving Au foil into a mixture of
concentrated hydrochloric acid and nitric acid 4:1.7 Complexes
1 and 2 were obtained by reacting 1 mmol of the appropriate
thioamides 2-mercapto-benzothiazole (mbztH) and 5-ethoxy-2-
mercapto-benzimidazole (EtmbzimH) with 0.5 mmol of HAuCl4
solution in methanol/acetonitrile) under reflux for 3 h (Scheme 2,
reaction I). The reaction of 0.5 mmol HAuCl4 with 1 mmol
2-mercapto-nicotinic acid (mnaH2) on the other hand, treated
with an equimolar amount of KOH, resulted in the formation of
2-sulfonate-nicotininc acid (C6H5NO5S) (3) with simultaneous ox-
idation of the sulfur atom (Scheme 2, reaction II). Au(I) complexes
5, 6 and 7 were synthesized by reacting 1 mmol of [Au(tpp)Cl]8
(4) with 1 mmol of the appropriate thioamide 2-mercapto-
thiazolidine (mtzdH), 2-mercapto-benzothiazole (mbztH) or
5-chloro-2-mercapto-benzothiazole (ClmbztH) in the presence
of an equimolar amount of KOH, in methanol/water solution
(Scheme 2, reaction III).
-
is taking place with atmospheric O2 as it was also found in the
case of the oxidation of thioethers by this anion.5 Electrochemical
and computational studies on the other hand, strongly indicate
that oxidation of the ligands at S, takes place prior of the breaking
of the C-S bonds in the final products. Based on these results, a
possible mechanism of the reaction taking place was proposed.
The electrochemical properties of gold(III) complexes
with N,N-dimethyldithiocarbamate (DMDT) and ethylsar-
cosinedithiocarbamate (ESDT) in acetonitrile have been previ-
ously investigated by cyclic voltammetry.4b The reduction of the
gold(III) compounds followed two separated Au(III)/Au(II) and
Au(II)/Au(I) steps leading to the formation of a dimeric gold(II)
species with bridging chlorine atoms.4b This is different than the
behavior of the complexes in the present study, which involves the
Au(III)/Au(I) and Au(I)/Au(0) reduction processes.
The electrochemical behavior of the free ligands EtmbzimH,
mbztH and mnaH2 was also evaluated in CH3CN and DMF
solutions. The results showed that the easiness of ligand’s oxidation
changes in the order: EtmbzimH > mbztH > mnaH2. The
desulfurated product of mnaH2 by means of the controlled
All complexes are air stable powders. Crystals of compounds
1, 2 and 3, suitable for X-ray analysis, were obtained by slow
evaporation of a methanol/acetonitrile (1:1) solution. Crystals
of 5, 6 and 7 were grown from a dichloromethane/toluene (1:1)
solution.
Scheme 2
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The crystal structures of 4 and 5 were also re-determined here
ORTEP diagrams of compounds 1-3 and 6-7 are shown in
Figs. 1-5. Selected bond distances and angles are given in Table 1.
and found identical to the ones previously reported.9-12
Vibrational spectroscopy
The infrared spectra of complexes 1 and 2 show strong vibrational
bands at 3211 (1) and 3279 (2) cm-1, respectively, which are
assigned to n(N-H) stretching vibrations, while no such bands
were observed in the spectra of complexes 5, 6 and 7 indicating
the de-protonation of their ligands. The corresponding n(N-H)
vibration bands are observed at 3111 cm-1 (mbztH), 3084 cm-1
(EtmbzimH), 3107 cm-1 (ClmbztH) and at 3133 cm-1 (mtzdH).13-19
The vibrational thioamide bands I and II, appear at 1446-
1479 cm-1 and 1182-1309 cm-1 respectively in the IR spectra
of complexes 1, 2, 5, 6 and 7 shifted to lower wavenumbers
as compared with the corresponding vibrational bands of the
free ligands mbztH, EtmbzimH, mtzdH and ClbztH shown at
1496-1514 cm-1 and 1248-1319 cm-1 respectively.16-19 Thioamide
bands III-IV, observed at 995-1173 cm-1 and at 652-811 cm-1,
in the spectra of the free ligands,16-19 appear at 1024-1075 cm-1
and 634-789 cm-1 respectively in the spectra of complexes 5, 6
and 7. The absence of the thioamide bands in the spectra of
complexes 1 and 2 indicate the desulfuration of the 2-mercapto-
benzothiazole (mbztH) or 5-ethoxy-2-mercapto-benzimidazole
(EtmbzimH) ligands upon their reaction with Au(III).
The new bands at 365 and 360 cm-1 in the far-IR spectra
of complexes 1 and 2 have been assigned to the n(Au-Cl)
vibrations,20-22 while bands appearing at 279 and 180 (5), 280 and
179 (6) and 279 and 171 (7) cm-1 in the far-IR spectra of complexes
5-7 are attributed to the n(Au-S) and n(Au-P) vibrations.20-22
Crystal and molecular structures of {[AuCl4]-[bztH2]+} (1),
{[AuCl4]-[EtbzimH2]+(H2O)} (2), the 2-sulfonate-nicotininc acid
(3), [Au(tpp)(mbzt)] (6) and [Au(tpp)(Clmbzt)] (7)
Fig. 1 (A) Anisotropic ellipsoid representation of the building block of
complex 1. The ellipsoids are drawn at 50% probability level. (B) Strong
hydrogen bonding interactions.
The structures of compounds 1-3 and 6, 7 were solved by X-ray
diffraction at 120(2) K for 1 and 2, and at r.t. (293(2) K) for 3
and 7.
-
Complexes 1 and 2 are ionic salts containing an [AuCl4 ]
counter anion neutralized by a protonated fragment of the
˚
Table 1 Selected bond lengths (A) and angles (deg) of compounds 1-3 and 6-7
Complex 1
(a) bond lengths
Au1 Cl4
Au1 Cl3
Au1 Cl2
Au1 Cl1
C1 N1
Complex 2
Compound 3
Complex 6
Complex 7
(a) bond lengths
(a) bond lengths
(a) bond lengths
(a) bond lengths
2.2808(13) Au1 Cl2i
2.2765(16) S1-O1
1.444(3) Au1-S22
2.2960(13) Au1-S22
2.2559(11) Au1-P1
2.296(3)
2.259(3)
1.736(14)
1.275(16)
1.393(16)
2.2816(12) Au1 Cl2
2.2867(13) Au1 Cl1i
2.2884(12) Au1 Cl1
2.2765(16) S1-O2
2.2799(16) S1-O3
2.2799(16) S1-C1
1.439(3) Au1-P1
1.437(3) S22-C22
1.808(3) N23-C22
1.343(4) N23-C23A
1.335(4)
1.743(5)
1.298(6)
1.402(6)
S22-C22
N23-C22
N23-C23A
1.308(7)
1.398(6)
1.684(5)
C1 N2
C3 N2
C2 N1
C1 N1
1.322(7)
1.389(6)
1.388(6)
1.333(6)
N2-C1
N2-C3
C1-C6
C7 N1
C1 S1
1.390(4)
(b) angles
(b) angles
(b) angles
S1-C1-C6
S1-C1-N2
N2-C1-C6
(b) angles
126.8(3) S22-Au1-P1
114.7(2) S21-C22-S22
118.4(3) S21-C22-N23
S22-C22-N23
(b) angles
Cl4 Au1 Cl3
Cl4 Au1 Cl2
Cl3 Au1 Cl2
Cl4 Au1 Cl1
Cl3 Au1 Cl1
Cl2 Au1 Cl1
N1 C1 S1
90.31(4)
Cl2i Au1 Cl2
180.0
90.0
90.0
90.0
90.0
180.00(3)
110.4(4)
176.25(5) S22-Au1-P1
176.11(9)
121.5(7)
115.8(11)
178.81(4) Cl2i Au1 Cl1i
117.3(3)
115.9(4)
126.6(4)
S21-C22-S22
S21-C22-N23
89.14(4)
90.45(5)
Cl2 Au1 Cl1i
Cl2i Au1 Cl1
179.20(5) Cl2 Au1 Cl1
90.11(5)
114.4(4)
Cl1i Au1 Cl1
N2 C1 N1
Symmetry transformations used to generate equivalent atoms: (i) -x+1,-y,-z+1
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Fig. 4 (A) Anisotropic ellipsoid representation of complex 6. The
ellipsoids are drawn at 50% probability level. (B) Packing diagram of 6
with short contacts.
Fig. 2 (A) Anisotropic ellipsoid representation of the building block of
complex 2. The ellipsoids are drawn at 50% probability level. The chloride
and oxonium ions and water molecules are not shown for clarity. (B) Strong
hydrogen bonding interactions.
desulfurated thioamide counter part. The Au-Cl bond distances
-
˚
of 2.28-2.29 A agree with those found in other [AuCl4 ]
+
˚
anions (2.27-2.28 A in [C6H11N2][AuCl4] ([C6H11N2] =1-ethyl-
3-methylimidazolium),23a 2.27-2.29
in [C8H15N2][AuCl4]
˚
˚
A
(C8H15N2]+= 1-butyl-3-methylimidazolium)23a and average 2.29 A
in [C1SCNmim][AuCl4] (C1SCNmim= 1-thiocyanomethyl-3-
methylimidazolium chloride).23b The C-N bond distances in the
desulfurated counter parts of complexes 1 and 2 are C1-N1=
˚
˚
˚
1.308(7) A and C7-N1= 1.398(6) A (1) and C1-N2= 1.322(7) A
˚
and C3-N2= 1.389(6) A (2) respectively indicating that nitrogen
participates in a partial double bond.17,19 Moreover the angles
around the C1 atoms were H1-C1-N1= 122.8◦, H1-C1-S1=
122.8◦ and S1-C1-N1= 114.4 (4)◦ in 1 and H1-C1-N2= 124.9◦,
H1-C1-N1= 124.8◦ and N1-C1-N2= 110.4(4)◦ in 2 indicating
sp2 hybridization of the C atom confirming the existence of a
double bond character between C and protonated N atoms in
both complexes (Scheme 3).
Fig. 3 Anisotropic ellipsoid representation of complex 3. The ellipsoids
are drawn at 50% probability level.
Scheme 3
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and 2 and the isolation of compound 3. Thus, in case of complexes
1 and 2, the tetrachloroauronic anion is present in the complex as
a counter anion since the desulfurated thione is protonated. The
stability due to the charge delocalization in case of compound
3 leads to its isolation (see below). Therefore, a reasonable
mechanism for the desulfuration of thione ligands could involve
first the oxidation of thiones by di-oxygen, catalyzed by the
presence of tetrachloroauric(III) anion followed by the C-S bond
cleavage (in the cases of the ligands mbztH and EtmbzimH). In
case of compound 3 the 2-sulfonate-nicotininc acid (C6H5NO5S)
is more stable than the other ligands, due to delocalization of the
charge density, making the bond cleavage more difficult than in
the other two ones. This is confirmed by the electrochemical and
computational studies (see below). This indicates that both of the
other two ligands produce similar intermediates, however ending
up to 1 and 2 complexes, as less stable than 3.
The reactions of 4 with the 2-mercapto-thiazolidine (mtzdH),
2-mercapto-benzothiazole (mbztH) and 5-chloro-2-mercapto-
benzothiazole (ClmbztH) in the presence of potassium hydroxide
produced mixed ligand complexes of formulae [Au(tpp)(mtzd)]
(5), [Au(tpp)(mbzt)] (6) and [Au(tpp)(Clmbzt)] (7). One triphenyl-
phosphine and one thioamide ligand are coordinated to Au(I)
through their P and S atoms respectively. The geometry around
˚
Au(I) is linear with Au-P bond distances of 2.2960(13) A (6) and
˚
˚
2.259(3) A (7) respectively and Au-S bond lengths of 2.2961(13) A
˚
(6) and 2.296(3) A (7) respectively. The S-Au-P angle is almost
180◦ (176.25(5)◦) for (6) and (176.11(9)◦) for (7), respectively). The
variation from 180◦ may be due to the packing of the molecules
in the crystal lattice.Fig. 4B for (6): C133 ◊ ◊ ◊ C22_e = 3.496(7),
˚
C126 ◊ ◊ ◊ C135_f = 3.562(7) A, Translation of Symmetry Code to
Fig. 5 (A) Anisotropic ellipsoid representation of complex 7. The
ellipsoids are drawn at 50% probability level. (B) Packing diagram of 7
with the short contacts.
Equiv. Pos: e = 3/2-x,1/2+y,-1/2-z, f = 3/2-x,-1/2+y,1/2-z
(stacking interactions) and Fig. 5B for (7): Cl25 ◊ ◊ ◊ C132_b =
˚
3.369(13), N23 ◊ ◊ ◊ C115_d = 3.355(19) A, Translation of Sym-
metry Code to Equiv. Pos: b = 3-x,1-y,1-z, d= 3-x,1-y,2-z
i
˚
Hydrogen bonding interactions N1[H1A] ◊ ◊ ◊ Cl2 = 3.257(4) A
(hydrogen bondings).
ii
˚
(1) and N2[H2] ◊ ◊ ◊ Cl3 = 3.050(5) A (2) (symmetry transfor-
mations: (i) -x+1/2, y-1/2, z and (ii) x, y, z+1) stabilize the
supramolecular assemblies of complexes 1 and 2 (Figs. 1B and
2B).
Computational studies
The proposed desulfuration mechanism through the formation of
a sulfonate intermediate derivative in the case of complexes 1 and
2 (Reaction IV), is further supported by PM6 calculations for the
determination of the Bond Dissociation Energy of the C-SO3H
bond.
Compound 3 is a zwitterion. The C-S bond distance is
1.808(3) A indicating a single C-S bond while the C-N (1.34 A) and
˚
˚
˚
C-C (1.39 A) of the ring correspond to a delocalized double bond.
The nitrogen atom is protonated resulting in a positive charge at
N atom while the sulfonic group is negatively charged. The three
S-O bond distances are almost equal with an average S-O bond
˚
length of 1.44 A (Table 1) and they are in agreement with those
-
found in the sulfonate group of H3O+CF3SO3 ·4H2O (average
(IV)
24a
˚
S-O distance of 1.444 A). The S-O bond lengths of 1.437(3)-
˚
˚
1.444(3) A in 3 are shorter than the S-OH (1.56 A) bond distance
The Bond Dissociation Enthalpies (BDE) for the C-S bond
were obtained from the enthalpies of the different species using
the expression: BDE298(R1-R2) = [DfH298(R1) + DfH298(R2)] -
DfH298(R1-R2) where (R1-R2) are the sulfur oxidized forms of the
ligands, R1 are the free ligands and R2 the desulfurized forms of
the ligands (See Scheme 2, Reaction II). Semi-empirical theoretical
methods are especially designed to obtain enthalpy of formation
of chemical systems with minimum computational cost and recent
work has shown their reliability in BDE estimations.25 PM6 gave
the best results in our preliminary testing runs and therefore it was
selected for the calculations. The calculated BDE values for the
˚
found in the sulfuric acid and closer to the S-O (1.43 A) bond
of the sulfuric acid,24b indicating partial double bond distribution
and delocalization of the negative charge.
Natile et al.,5 have previously described the mechanism of
oxidation of diethyl-thioether to its oxo-derivative (Et2SO) upon
the reaction of Et2S with {[AuCl4]-} in acidic media5 and proposed
a mechanism, where the {[AuCl4]-} was not the oxidation agent,
but it was rather acting as a catalyst. Oxidation was caused by
atmospheric di-oxygen which is simultaneously reduced to O2-.
These findings are confirmed here by the formation of complexes 1
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Table 2 Electrochemical properties of complexes of 1-2 and 4-7 in acetonitrilea
Oxidation potentials, (V)
Reduction potentials, (V)
EIp
Compound
EIp
EII
EII
EIII
p
p
p
1
2
4
5
0.57b
0.71b
1.29
0.93
1.15b
1.34b
0.05
0.05
-1.79
-1.99
-0.51
-0.51
—
-1.13
-1.53
—
—
a Peak potentials (V, vs. Ag/AgCl/KCl) were determined from cyclic voltammetric scans. Experimental conditions: Pt electrode, v = 200 mV/s, 293 K,
acetonitrile containing 50 mM TBABF4, Ep denotes peak potential of a chemically irreversible step. b In reverse anodic scan triggered beyond -0.5 V.
C-S bond (Reaction IV) of compound 3 is +310.16 kJ mol-1,
while the corresponding values for 1 and 2 are +148.16 and
+111.96 kJ mol-1 respectively, indicating the easier formation of
the desulfurated mbztH or EtmbzimH ligands in contrast to the
desulfuration of the 2-sulfonate-nicotininc acid.
Electrochemical studies
(i) The complexes 1-2 and 4-7. The electrochemical behavior
of 1-2 and 4-7 was studied inacetonitrile and DMF solutions, using
cyclic voltammetry.4b The redox potentials of these complexes
are summarized in Table 2. The cyclic voltammogram of the
starting compound 4 displays one irreversible wave in acetonitrile
controlled by diffusion (the dependence of I vs. v1/2 has a linear
character26) in the cathodic range at -1.79 V, which is in accordance
with literature data and corresponds to the reduction of complex
RAuPPh3 with simultaneous formation of Au(0) and PPh3.27 In
the anodic range the one-electron irreversible wave at 1.29 V
was observed. Cyclic voltammograms of complex 5 show one
irreversible cathodic wave. For the oxidative scan, an irreversible
wave was observed.
The replacement of the Cl- anion in complex 4 by a thioamide
ligand with poorer electron-accepting ability as in the case of 5
leads to the increase in LUMO energy that results in Au(I)/Au(0)
redox couple shift to a more negative potential as compared
with complex 4. For the anodic scan the one diffusion-controlled
irreversible one-electron wave was observed at 0.93 V, which may
be assigned to ligand oxidation as it has been shown previously
for a series of RAuPPh3.27 This results to considerable shift of
the metal-centered oxidation potential towards the anodic range
and the corresponding metal-centered wave was not observed in
the solvent’s potential window. The electrochemical properties of
Fig. 6 Cyclic voltammograms of 1.1 ¥ 10-3 M complexes 2 (A) and 1
(B) in CH3CN. Experimental conditions: Pt working electrode, 50 mM
complexes 6 and 7 were not studied in acetonitrile because of their
TBABF4, vs. Ag/AgCl/KCl, scan rate v = 0.2 V.
poor solubility.
Cyclic voltammograms of complex 2 in acetonitrile are pre-
sented in Fig. 6(A). Three waves in the cathodic range of potentials
were observed. The first one is irreversible and shows a diffusion
character and corresponds to the transfer of two-electrons, i.e.
the reduction process Au(III)→Au(I). The second one is a one-
electron irreversible wave and the third one, at highest negative
potential, is a one-electron irreversible one. Scheme 4 shows the
steps of redox transformation of complex 2. The first wave may
be assigned to the reduction of complex 2 (step I at 0.05 V), that
results to the destruction of the complex, thus forming AuICl,
Cl- ions and the oxidized form of the ligand. The second wave
at -0.51 V corresponds to the reduction of AuI to Au0. The third
wave can be ligand-centered and shows reduction of the cationic
species to the radical one. After triggering the potential at -1.8 V
the one-electron wave which appears, is assigned to the oxidation
of a product formed during the reduction of 2. In the anodic
range the reverse scan shows three irreversible waves. The third
one at 1.34 V is an one-electron wave and obviously corresponds
to Cl-/Cl0 oxidation.28 The nature of the first and second waves
might be connected with some chemical reactions which take place
in the reduction process of the complex.
The reverse scan after triggering the potential at E < -0.5 V
generates the new peak at 1.4 V. The characteristic triangle
form and a significant discordance between the concentration
of the complex and the current value, indicate the adsorption
character of this wave (Fig. 6A). We propose that this peak
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metry curve is presented in Fig. 7. The values of the anodic and
cathodic peak potentials are listed in Table 3.
Scheme 4
corresponds to the oxidation of adsorbed Au0 on the surface of the
electrode.
Fig. 7 Cyclic voltammetry curve for 1.1 ¥ 10-3 M complex 7 in
DMF. Experimental conditions: Pt working electrode, 50 mM TBABF4,
vs. Ag/AgCl/KCl, scan rate v = 0.2 V/s.
The electrochemical behavior of complex 1 is similar to that
of complex 2 and can also be explained by Scheme 4. In this
case the potential of the third peak is shifted to more positive
potentials compared with complex 2 (DE ª 100 mV, Table 2).
The more negative reduction potential observed for the third
reduction wave in the case of 2 could be readily rationalized
by the presence of the electron-donating alkoxyl substituent in
2-mercaptobenzothiazole ligand, which makes it more electron-
donor and poorer p-acceptor, and hence reduces its reduction
potential. This fact also reinforces the assumption that the nature
of this wave is assigned to the ligand reduction. Similar electro-
chemical behavior was observed in the electrochemical study of the
complexes of Au(III) with 2,2¢-bipyridine and oxygen containing
ligands.29 In cyclic voltammetric experiments, performed with a
Pt-electrode in acetonitrile, cationic species containing the
Au(bipy)3+ moiety and additional oxygen-donor ligands, undergo
two or three cathodic processes. Electroreduction by means of
controlled potential electrolyses of all compounds studied, affords
elemental gold identified by elemental analyses, free bipyridine lig-
and and Cl- species (in the case of complexes with Cl-substituents).
This fact may be considered as an additional evidence of the
proposed reactions in Scheme 4, which is in agreement with the
experimental results obtained.
It should be noted that the presence of the electron-accepting
Cl substituents in the 2-mercaptobenzothiazole ring results in the
shift of peak potentials to more positive values (Table 3). It was
shown previously,27 that the oxidation of complexes Ph3PAuR
(R = Me, Ph, MeO, Cl, Br, I) in acetonitrile proceeds through
the formation of the Ph3PAuR+∑ radical-cation. Decomposition of
these species leads to unstable compounds RAu and the formation
of Au(0) and R, as described in ref. 26. In the case of Ph3PAuCl (4)
no distinct waves in the anodic range appear within the limits of
the solvent potential window (at ª 1.6 V the discharge of solvent
molecules begins). In the cathodic scan the one-electron diffusion-
controlled the irreversible wave was observed at -0.59 V.
The electrochemical behavior of complexes 1, 2 and 4 in DMF
is very similar to the one in acetonitrile: three irreversible waves
in the cathodic range were observed. Therefore, the reduction of
these compounds may be described as in Scheme 4.
(ii) The ligand. The redox properties of the ligands Etmbz-
imH, mbztH and mnaH2 were studied in an attempt to contribute
to the elucidation of the mechanism of the desulfuration process,
caused by Au(III) ions. As follows from cyclic voltammograms
(Fig. 8), all ligands display the irreversible one-electron wave,
controlled by diffusion at anodic range of potentials. The irre-
versibility takes place in the range of scan rate from 50 mV/s to
Cyclic voltammograms of 5-7 in DMF exhibit one irreversible
wave in the cathodic range and three one-electron diffusion-
controlled irreversible waves at the anodic scan. A typical voltam-
Table 3 Electrochemical properties of complexes of 1-2 and 4-7 in DMFa
Oxidation potentials, (V)
Reduction potentials, (V)
Compound
EIp
EII
EIII
—
EIp
EII
EIII
p
p
p
p
1
2
4
5
6
7
0.65
—
—
0.72
0.68
0.82
1.44
1.35
—
1.1
1.05
1.12
-0.66
-0.68
-0.59
-0.68
-0.83
-0.90
-0.93
-0.95
—
—
—
-1.76
—
—
—
—
—
1.42
1.32
1.44
—
—
a Peak potentials (V, vs. Ag/AgCl/KCl) were determined from cyclic voltammetric scans. Experimental conditions: Pt electrode, v = 200 mV/s, 293 K,
acetonitrile containing 50 mM TBABF4, Ep denotes peak potential of a chemically irreversible step.
10452 | Dalton Trans., 2009, 10446–10456
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case of mnaH2 only the oxidized derivative was isolated and
characterized, we made an attempt to obtain the desulfurated
product by means of the controlled potential electrolyses which
was performed in acetonitrile at the first anodic wave potential
of E= 1.3 V. In the NMR-spectrum of the product, the proton
signal of the SH-group disappeared after electrolyses. The signal
of the carboxy group proton on the other hand, was shifted to
lower fields and a widening was observed, obviously, because of
hydrogen bond formation between the carboxy and sulfo groups.
These facts support the assumption that the oxidation of mnaH2
ligand proceeds the desulfuration step.
Biological tests
Complexes 1-2 and 4-7 and HAuCl4 were tested for cytotoxic ac-
tivity against leiomyosarcoma cells from the Wistar rat, polycyclic
aromatic hydrocarbons (PAH, benzo[a]pyrene) carcinogenesis.
Cytotoxic activities for complexes 1-2 and 4-7 and HAuCl4 were
evaluated as percentage of cells surviving after being exposed
to multiple concentrations of a test compound for 24 h time
period. The IC50 values after treatment for 24 h were 1.3
0.9 (1), 0.7 0.1 (2), inactive (4), 0.8 0.4 (5), 2.1 1.3 (6)
and 1.1 0.5 (7) mM respectively, while HAuCl4 was found to
be inactive against leiomyosarcoma cells (IC50= 4-5 mM6), for
cisplatin. Consequently, complexes 2 and 5, containing Au(III) and
Au(I) respectively, were the more active among 1-2 and 4-7. The
IC50 values of these complexes, cisplatin and other metals, against
leiomyosarcoma cells are compared in Table 5. Gold complexes
2 and 5, are less active than the tin complexes {(Ph3Sn)2(MNA)
(Me2CO)} and Ph3Sn(PMT) with IC50 values 0.005 and 0.1 mM
respectively but they show comparable activity with that of
silver(I) complexes (Table 5). Among complexes of the same lig-
and 5-chloro-2-mercapto-benzothiazole, (7, Me2Sn(CMBZT)2, (n-
Bu)2Sn(CMBZT)2, Ph2Sn(CMBZT)2 and Ph3Sn(CMBZT)) the di-
organotin complex Ph2Sn(CMBZT)2 show higher activity and the
same order is followed between gold(I) and organotin complexes 6
and Ph3Sn(MBZT) of 2-mercapto-benzothiazole ligand (Table 5).
Fig. 8 Cyclic voltammograms of ligands: EtmbzimH (I); mbztH (II);
mnaHz (III) (CH3CN, 100 mV/s; Pt; 10-3 M; Ag/AgCl/HCl).
1000 mV/s that is typical for an EC mechanism (electrochemical-
chemical mechanism). The peak potentials are in good agreement
with the well-known literature data and may be assigned to the
SH-group oxidation.28
This fact points out that these compounds exist in tautomeric
forms in acetonitrile solutions and the equilibrium is shifted to the
SH-containing form as the oxidation proceeds (Scheme 5):
Conclusions
Scheme 5
Based on crystallographic and computational results a possible
mechanism for the desulfuration of thioamide ligands upon their
reaction with {[AuCl4]-} ions was proposed.
The values of theanodicpeak potentials are listed in Table 4. The
easiness of ligand’s oxidation changes in the order: EtmbzimH >
mbztH > mnaH2 which correlates with the electronic effects of
substituents in benzene ring. The change of the ethoxy-group for
a H-atom in mbztH results to the shift of the potential to more
positive values. The mnaH2 ligand oxidizes most hardly due to the
strong presence of the strong electron withdrawing carboxy group.
The first step of HAuCl4 reaction with these ligands (as well
as electrochemical oxidation) might be the oxidation of the
SH-group followed by desulfuration (Reaction II). Since in the
The isolation of the stable enough compound 3 and the
final desulfurated complexes 1 and 2 strongly indicate that the
-
-
AuCl4 ions, which catalyzes the oxidation of S to -SO3 by
atmospheric O2, regenerates and acts as a counter ion in 1 and 2.
Both electrochemical and computational results indicate that the
oxidation of S takes place prior to C-S breakage and desulfuration
and justifies the stability of 3, as compared to the sulfonate
derivatives of the other ligands.
-
Table 4 Electrochemical properties of the ligands EtmbzimH, mbztH
and mnaH2 in acetonitrile (Pt, 200 mV/s, 293 K, acetonitrile containing
50 mM TBABF4 V, vs. Ag/AgCl/KCl)
The catalytic role of AuCl4 in the oxidation of thioethers by
atmospheric O2 had also been proposed earlier by Natile et al.5
Au(III) is most probably first reduced to Au(I) and re-oxidized
back to Au(III). This is the case of the electrochemical behavior
of the complexes in this study, where a two electron process for
the reduction of Au(III) to Au(I) was detected. It should be noted
however, that kinetic data would be required to allow a more
definitive conclusion on any proposed mechanism, to be made.
Ligand
Eox, V
EtmbzimH
mbztH
mnaH2
1.02
1.17
1.3
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Table 5 Cytotoxic activity of Au(III)/(I), Ag(I) and Sn complexes as IC50
(mM) values against leiomyosarcoma cells6
400 MHFT-NMR instrument in CDCl3 or DMSO-d6 solutions.
Chemical shifts d are given in ppm using H-TMS as internal
1
reference. Micro Raman spectra (64 scans) were recorded at room
temperature using a low power (~30 mW) green (514.5) mm laser
on a Renishaw In Via spectrometer set at 2.0 resolution. Thermal
studies were carried out on a Shimadzu DTG-60 simultaneous
DTA-TG apparatus, under a N2 flow (50 cm3 min-1) at a heating
rate of 10 ◦C min-1.
Complex
50% inhibitory concentration (IC50) (mM)
Cisplatin
4-5
1
1.3 0.9
0.7 0.1
inactive
0.8 0.4
2.1 1.3
1.1 0.5
0.8
0.7
0.8
0.9
5-7.5
0.6-0.8
0.3-0.5
0.5-0.8
20-60
0.7
1-2
0.1
2
4
5
6
7
Synthesis of compounds {[AuCl4]-[bztH2]+} (1),
a
{[AgCl(TPTP)]4}
[AgCl(TPTP)3]a
[AgBr(TPTP)3]a
[AgI(TPTP)3]a
{[AuCl4]-[EtbzimH2]+(H2O)} (2), the 2-sulfonate-nicotininc acid
(3), [Au(tpp)(mbzt)] (6) and [Au(tpp)(Clmbzt)] (7)
b
Me2Sn(CMBZT)2
Complexes 1 and 2 were synthesized as follows: 1 mmol of the
appropriate thioamide ligand (0.167 g 2-mercapto-benzothiazole
and 0.194 g of 5-ethoxy-2-mercapto-benzimidazole) were dis-
solved in 10 ml methanol. 10 ml acetonitrile solution which
contains 0.5 mmol HAuCl4 1 ml (0.51 M) was then added
to the ligand’s methanolic solution. The resulting solution was
heated for 3 hours under reflux. After cooling the solution was
filtered off. Slow evaporation of the resulting clear solution form
crystals of complexes 1 and 2 suitable for X-ray analysis. Crystals
of compound 3 were obtained derived by slow evaporation of
the solution resulted from mixing 10 ml acetonitrile solution of
0.5 mmol HAuCl4 1 ml (0.51 M) with 10 ml methanolic solution
of 1 mmol of 2-mercapto-nicotinic acid (0.155 g) in the presence
of 1 mmol KOH (1 ml, 1 N).
b
(n-Bu)2Sn(CMBZT)2
b
Ph2Sn(CMBZT)2
Ph3Sn(CMBZT)b
c
Me2Sn(PMT)2
c
(n-Bu)2Sn(PMT)2
c
Ph2Sn(PMT)2
Ph3Sn(PMT)c
Ph3Sn(MBZO)d
Ph3Sn(MBZT)e
1.3-3
1.5-3
f
{(Ph3Sn)2(MNA)(Me2CO)} 0.005
[SbBr3(TU)2]g
23.5 (unpublished results)
a TPTP = tri(p-toly)phosphine. b CMBZTH = 5-chloro-2-mercapto-
benzothiazole. c PMTH
=
2-mercapto-pyrimidine. d MBZOH
=
2-
mercapto-benzoxazole. e MBZT = 2-mercapto-benzothiazole. f H2MNA=
2-mercapto-nicotinic acid. g TU = thiourea.
The precursor [Au(tpp)Cl] (4) was derived from the reaction
between 1 mmol tri-phenyl-phosphine (0.262 g) with 0.5 mmol of
HAuCl4 solution (1 ml, 0.5 M) in 10 ml methanol.5b Crystals of
complex 4 were grown from a 20 ml dichloromethane solution.
Complexes 5, 6 and 7 were synthesized as follows: A suspension of
0.215 mmol of the appropriate thioamide (0.026 g 2-mercapto-
thiazoline for 5, 0.034 g 2-mercapto-benzothiazole for 6 and
0.042 g 5-chloro-2-mercapto-benzimidazole for 7) in distilled
water (5 ml) was treated with a solution of KOH 1 N (1 cm-3,
1 mmol). The resulting clear solution was then added to 5 ml of
a methanolic solution of 0.215 mmol [Au(tpp)Cl] (0.106 g) under
stirring for 2 hours. The white precipitate was then filtered off and
dried. Crystals of complexes 5, 6 and 7 suitable for X-ray analysis
were formed from slow evaporation of a dichloromethane/toluene
solution (1:1) of the above powders.
The formation of the mixed ligand gold(I) complexes of formu-
lae [Au(tpp)(mtzd)] (5), [Au(tpp)(mbzt)] (6) and [Au(tpp)(Clmbzt)]
(7) where no desulfuration of the ligands takes place emphasizes
the possible catalytic role of AuCl4 in the oxidation and desulfu-
ration of the ligands.
Finally, complexes 2 and 5 containing Au(III) and Au(I) showed
the higher in vitro cytotoxicity against leiomyosarcoma cells,
although there is no significant differences on the cytotoxic profile
between the complexes 1, 2, 5, and 7. These complexes were also
found more active than cis-Pt. Complexes 2 and 5 exhibit lower
activity than the corresponding {(Ph3Sn)2(MNA) (Me2CO)} and
Ph3Sn(PMT) complexes, while they show comparable activity with
that of silver(I) complexes (Table 5). Among gold and organotin
complexes of the same ligand, tin complexes are again more active.
-
[1] Yield 31%. m.p. 232-240 ◦C. Found: C, 17.89%; H, 1.08%; N,
2.63%; S, 6.68%. Calc. for C7H8NOSAuCl4: C, 17.70%; H, 1.27%;
N, 2.95%; S, 6.75%. IR (KBr): 3440.00 w, 3208.88 w, 3072.67,
1458.88, 1404.86 m, 1270.38, 766.01 s, 700.21 s. 1H NMR (DMSO-
d6) d 9.34 s, H(NH); 8.12 s, H(CH);; 8.03 m, H(Ar); 7.48 m, H(Ar).
ESI-MS(+): m/z 663, 573, 484, 323, 268, 163. ESI-MS(-): m/z 339.
[2] Yield 54%. m.p. 165-170 ◦C. Found: C, 21.34%; H, 2.72%; N,
5.14%. Calc. for C9H13N2O2AuCl4: C, 20.79%; H, 2.52%; N, 5.39%.
IR (KBr): 3568.88, 3280.00 w, 3130.85 vs, 2955.55 m, 1631.63 s,
1512.53, 1446.53 s, 1348.00, 1294.57 s, 1261.51, 1187.17 s, 1106.27,
1040.60, 815.47 s, 591.76. Far-IR (Polyethylene): 362.12 vs,
239.59 s, 147.78 s, 135.97 s, 89.37 s, 56.99 s. 1H NMR (DMSO-d6)
d 9.31 s, H(NH); 8.28 s, H(CH); 7.69 m, H(Ar); 7.15 m, H(Ar);
4.08 m, H(CH2O); 1.34, H(CH3). ESI-MS(+): m/z 663, 573, 323,
268, 136. ESI-MS(-): m/z 339. ◦
Experimental
Materials and instruments
All solvents used were of reagent grade, while thioamides and
triphenyl-phosphine (Aldrich, Merk) were used with no further
purification. The tetrachloroauric(III) acid (HAuCl4) solution
(0.51 M) was prepared by dissolving 1 g Au foil into 10 ml
mixture of concentrated hydrochloric acid (12 M) and nitric acid
(16 M) 4:1.7 Elemental analyses for C, H, N, and S were carried
out with a Carlo Erba EA MODEL 1108 elemental analyzer.
Infra-red spectra in the region of 4000-370 cm-1 were obtained
in KBr discs. Far-infra-red spectra in the region of 400-50 cm-1
were obtained in polyethylene discs, with a Perkin-Elmer Spectrum
GX FT-IR spectrophotometer. A Jasco Uv/Vis/NIR V 570 series
spectrophotometer was used to obtain the electronic absorption
spectra. The 1H-NMR spectra were recorded on a Bruker AC 250,
[4] Yield 76%. m.p. 236-240 C. Found: C, 43.14%; H, 2.98%.
Calc. for C18H18AuPCl: C, 43.70%; H, 3.06%. IR (KBr): 3433.22 w,
10454 | Dalton Trans., 2009, 10446–10456
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3053.33, 1479.10, 1435.44 s, 1179.39, 1101.89 s, 998.65, 748.00 s,
712.70, 692.90 vs, 546.65 s, 502.31 s. Far-IR (Polyethylene): 330.12
vs, 171.89 s. 1H NMR (CDCl3) d 7.55 m, H(Ar).
SADABS.32 The structures were solved using SIR9233 (1) and
SIR2004 (2)34 and refined using SHELXL-97.35 All non-hydrogen
atoms were refined anisotropically with hydrogen atoms included
in idealized positions and refined using a riding model. Each
formula unit of 2 contains in total five water molecules, one of
which is disordered and one disordered molecule of [H3O]+. There
are also four chloride ions. The presence of the [H3O]+ molecule
means that the charge in the formula unit is balanced. It was only
possible to locate hydrogen atoms for one of the water moieties,
O2. For all other water molecules and the [H3O]+ molecule it was
found impossible to locate the hydrogen atoms because of the use
of X-ray radiation, the presence of the very heavy gold atom and
the low occupancies of water at these positions. For this reason it
is not possible to assign which of the O4 and O5 atoms belongs to
a water molecule and which belongs to the acid, as the assignment
of either atom as the acid would give the correct charge balance. It
is highly probable that the O3, O4 and O5 moieties are involved in
hydrogen bonding, but this is impossible to confirm due to the fact
that the hydrogen atoms in these moieties could not be located.
Intensity data for the crystals of 3, 4 and 5 were collected
on Bruker P4 diffractometer, with graphite monochromatized
[5] Yield 74%. m.p. 160-161 ◦C. Found: C, 43.98%; H, 3.26%; N,
2.64%; S, 10.91%. Calc. for C21H17AuNPS2: C, 43.83%; H, 2.98%;
N, 2.43%; S, 11.14%. IR (KBr): 3053.33, 2915.55 m, 1554.96
vs, 1478.99, 1435.57 vs, 1303.02, 1181.67, 1100.53 s, 1022.00,
996.65 s, 963.11 s, 917.49 s, 750.24 s, 709.30, 692.08 vs, 631.68,
538.10 vs, 502.53 s. Far-IR (Polyethylene): 279.29 vs, 245.94 s,
1
151.08 s, 179.64, 99.43 vs, 75.48 vs. H NMR (CDCl3) d 7.50 m,
H(Ar(Ph3P)); 4.28 m H4(CH2), 3.38 m, H5(CH2). ESI-MS(+): m/z
1036, 721, 600, 578, 573.
[6] Yield 80%. m.p. 157-161 ◦C. Found: C, 48.33%; H, 3.18%; N,
2.39%; S, 9.90%. Calc. for C25H19AuNPS2: C, 48.00%; H, 3.06%;
N, 2.24%; S, 10.25%. IR (KBr): 3048.88, 1478.62, 1433.85 s,
1417.03 vs, 1308.59, 1272.59, 1234.89, 1099.85 s, 1073.00, 993.17,
971.66 vs, 757.12 s, 709.30, 691. 50 vs, 538.59 vs, 501.65 s.%. Far-
IR (Polyethylene): 279.94 s, 178.48, 89.30 m, 38.95 vs.1H NMR
(CDCl3) d 7.60 m, H(Ar(Ph3P)); 7.25 m, H(Ar(BZT)). ESI-MS(+):
m/z 1084, 721, 626, 648, 573.
[7] Yield 86%. m.p. 88-91 ◦C. Found: C, 45.33%; H, 2.98%; N,
2.13%; S, 9.74%. Calc. for C25H18AuNClPS2: C, 45.50%; H, 2.75%;
N, 2.12%; S, 9.72%. IR (KBr): 3051.54, 1479.24, 1435.50 s, 1408.97
vs, 1308.08 m, 1101.22 s, 1065.82, 998.38 vs, 790.99, 750.13 s,
693.40 vs, 537.85 s, 503.93 s. Far-IR (Polyethylene): v 279.11 s,
˚
MoKa radiation (l = 0.71073 A) at 293(2) K. The structures
were solved with SHELXS-9736 and refined with SHELXL-97.35
All non-hydrogen atoms were refined anisotropically. Hydrogen
atoms were located by difference maps and refined isotropically.
Intensity data for the crystals of 6 and 7 were collected
on KUMA KM4CCD four-circle diffractometer37 with CCD
1
170.88 s, 88.85 s, 70.09 s, 54.29 s. H NMR (CDCl3) d 7.56 m,
H(Ar(Ph3P)); 7.14 m, H(Ar(CBZT)). ESI-MS(+): m/z 1118, 721,
682, 660, 573.
˚
detector, using graphite-monochromated MoKa (l = 0.71073 A).
Cell parameters were determined by a least-squares fit.38 All data
were corrected for Lorentz-polarization effects and absorption.38,34
In these gold structures, the large residual electron density peaks
observed are due to the high atomic radius of gold atom.
The structure was solved with direct methods with SHELXS9736
and refined by full-matrix least-squares procedures on F2 with
SHELXL97.35 All non-hydrogen atoms were refined anisotrop-
ically, hydrogen atoms were located at calculated positions and
refined with ‘riding model’ with isotropic thermal parameters fixed
at 1.2 times the Ueq’s of appropriate carrier atom.
Crystallography
Intensity data for the crystals of 1 were collected on a Bruker
KappaCCD diffractometer and for 2 on a Bruker APEXII CCD
diffractometer, both at the windows of a Bruker FR591 rotating
anode (f scans and w scans to fill the asymmetric unit) in the
range 3.1◦–27.5◦ for 1 and 3.2◦–27.5◦ for 2, using graphite-
˚
monochromated MoKa radiation (l = 0.71073 A) at 120(2) K,
controlled by the COLLECT software package.30 The data were
processed by DENZO31 and corrected for absorption by using
Significant crystal data are given in Table 6.
Table 6 Crystal data and the structure refinement details of the compounds
1
2
3
6
7
Empirical formula
Fw
C7H6AuCl4NS
474.95
120(2)
Orthorhombic
Pbca
15.3524(4)
7.7452(2
19.3505(3)
90
C36H53AuCl8N8O10
1238.43
120(2)
Monoclinic
C2/m
22.0808(5)
25.1431(7)
4.8774(1)
90
92.500(2)
90
2705.26(11)
2
1.520
3.168
15931
C6H5NO5S
203.18
293(2)
Triclinic
P-1
6.762(1)
7.840(1)
8.797(1)
63.61(1)
85.35(1)
65.39(1)
376.71(10)
2
C25H19AuNPS2
625.49
293(2)
Monoclinic
P21/n
12.7430(9)
12.9378(7)
13.6063(6)
90
95.993(5)
90
2231.0(2)
4
1.862
6.866
C25H18AuClNS2
634.26
293(2)
Triclinic
P-1
8.8981(4)
11.0221(4)
14.1845(6)
89.145(3)
76.610(4)
83.837(4)
1345.45(10)
2
Temperature (K)
Cryst. System
Space group
˚
a, A
˚
b, A
˚
c, A
a, deg
b, deg
90
90
g, deg
3
˚
V, A
2300.92(9)
8
2.742
13.855
27049
Z
r
calcd, g cm-3
1.791
3.826
1670
1.629
5.793
9926
m, mm-1
Data Collected
27267
Independent Reflections (Rint)
R1, wR2 [I>2s(I)]
2623 (0.058)
0.027, 0.0575
3171 (0.048)
0.043, 0.1054
1358 (0.101)
0.055, 0.1502
5080 (0.028)
0.026, 0.0666
4736 (0.056)
0.068, 0.2069
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Computational studies
12 U. E. I. Horvath, S. Cronje, S. D. Nogai and H. G. Raubenheimer, Acta
Crystallogr., Sect. E: Struct. Rep. Online, 2006, 62, m1644.
13 N. Hadjililiadis and T. Theophanides, Can. J. Spectroscopy., 1971, 16,
135.
The ground state optimizations on the investigated molecules were
carried out without any constraints using the PM6 semiempirical
method39 as this is implemented in MOPAC 2007 program,40
utilizing the eigenvector following algorithm.41
14 N. Hadjiliadis, A. Yannopoulos and R. Bau, Inorg. Chim. Acta, 1983,
69, 109–115.
15 P. C. Zachariadis, S. K. Hadjikakou, N. Hadjiliadis, A. Michaelides,
S. Skoulika, Y. Ming and Y. Xiaolin, Inorg. Chim. Acta, 2003, 343,
361–365.
Electrochemical study
16 G. J. Corban, S. K. Hadjikakou, N. Hadjiliadis, M. Kubicki, E. R. T.
Tiekink, I. S. Butler, E. Drougas and A. M. Kosmas, Inorg. Chem.,
2005, 44, 8617–8627.
17 V. Daga, S. K. Hadjikakou, N. Hadjiliadis, M. Kubicki, J. H. Z. Santos
and I. S. Butler, Eur. J. Inorg. Chem., 2002, 1718–1728.
18 S. K. Hadjikakou, P. Aslanidis, P. Karagiannidis, D. Mentzafos and A.
Terzis, Inorg. Chim. Acta, 1991, 186, 199–204.
19 (a) I. I. Ozturk, S. K. Hadjikakou, N. Hadjiliadis, N. Kourkoumelis,
M. Kubicki, M. Baril, I. S. Butler and Jan Balzarini, Inorg. Chem.,
2007, 46, 8652–8661; (b) M. N. Xanthopoulou, S. K. Hadjikakou, N.
Hadjiliadis, M. Kubicki, S. Skoulika, T. Bakas, M. Baril and Ian S.
Butler, Inorg. Chem., 2007, 46, 1187–1195.
20 E. A. Allen and W. Wilkinson, Spectrochim. Acta, 1972, 2, 2257–2262.
21 I. S. Butler, A. Neppel, K. R. Plowman and C. F. Shaw, J. Raman
Spectrosc., 1984, 15, 310.
All electrochemical measurements were carried out under argon
at room temperature. Cyclic voltammetry experiments were per-
formed in classical three-electrode cell in CH3CN solution with
0.05 M TBABF4 as supporting electrolyte using a model IPC-Win
potentiostat. The number of electrons transferred were determined
by comparing with the height of Fc2+/Fc3+ =0.45 V wave for
the same concentration and coulometrically. A platinum working
electrode with diameter 2 mm, platinum wire auxiliary electrode
and aqueous Ag/AgCl/KCl (sat.) reference electrode were used.
The solvents were routinely distilled and dried prior to use.
22 A. G. Jones and D. B. Powell, Spectrochim. Acta, 30, 563–570.
23 (a) M. Hasan, I. V. Kozhevnikov, M. R. H. Siddiqui, A. Steiner and
N. Winterton, Inorg. Chem., 1999, 38, 5637; (b) D. Zhao, Z. Fei, W. H.
Ang, R. Scopelliti and P. J. Dyson, Eur. J. Inorg. Chem., 2007, 279–284.
24 (a) J.-O. Lundgren, Acta Crystallogr., Sect. B: Struct. Crystallogr. Cryst.
Chem., 1978, 34, 2432–2435; (b) C. E. Housecroft, A. G. Sharpe,
Inorganic Chemistry 3nd edition, Pearson Education, Paperback, 2007,
chapter 16, page 523.
Biological tests
These have been described in detail elsewhere.42
Acknowledgements
25 T. Nishiyama, S. Shiotsu, H. Tsujita, Polymer Degradation and Stability,
2002, 76, 435-439.
This research was carried out in partial fulfilment of the require-
ments for the master thesis of K.N.K. under the supervision of
S.K.H., within the graduate program in Bioinorganic Chemistry.
S.K.H., E.R.M. and N.H. would like to thank a NATO grant
for the exchange of scientists. E.R.M. also thanks RFBR grant
N09-03-00743
26 K. P. Butin, R. D. Rachimov, V. P. Dyadchenko and O. A. Enyukova,
Memalloorganicheskaya khimia, 1989, 2, 1401–1404.
27 J. Heinze, Angew. Chem., Int. Ed. Engl., 1984, 23, 831–918.
28 Ch. Mann and K. Barnes, Electrochemical reactions in nonaqueous
systems, Marcel Dekker, Inc., New York, 1970.
29 G. Sanna, M. I. Pilo, G. Minghetti, M. A. Cinellu, N. Spano and R.
Seeber, Inorg. Chim. Acta, 2000, 310, 34.
30 R. Hooft and B. V. Nonius, Data collection software, 1998.
31 Z. Otwinowski, W. Minor, Methods in Enzymology, 1997 Vol. 276:
Macromolecular Crystallography, part A, pp. 307-326; C. W. Carter, Jr.
& R. M. Sweet, Eds., Academic Press.
References
1 Martidale The Extra Pharmacopoeia, 28th ed.; J. E. F. Raynolds, Ed.;
The Pharmaceutical Press: London, 1982.
32 G. M. Sheldrick, SADABS - Bruker Nonius area detector scaling and
absorption correction - V2.10.
2 S. Miranda, E. Vergara, F. Mohr, D. de Vos, E. Cerrada, A. Mend´ıa
and M. Laguna, Inorg. Chem., 2008, 47, 5641–5648.
3 J. Zou, P. Taylor, J. Dornan, S. P. Robinson, M. D. Walkinshaw and
P. J. Sadler, Angew. Chem., Int. Ed., 2000, 39, 2931–31.
4 (a) E. R. T. Tiekink, Crit. Rev. Oncol. Hematol., 2002, 42, 225–248;
(b) L. Ronconi, L. Giovagnini, C. Marzano, F. Bett`ıo, R. Graziani, G.
Pilloni and D. Fregona, Inorg. Chem., 2005, 44, 1867–1881.
5 G. Annibale, L. Canovese, L. Cattalini and G. Natile, J. Chem. Soc.,
Dalton Trans., 1980, 1017–1021.
33 A. Altomare, G. Cascarano, C. Giacovazzo and A. Guagliardi, J. Appl.
Crystallogr., 1993, 26, 343–350.
34 M. C. Burla, R. Caliandro, M. Camalli, B. Carrozzini, G. L. Cascarano,
L. De Caro, C. Giacovazzo, G. Polidori and R. Spagna, J. Appl.
Crystallogr., 2005, 38, 381–388.
35 G. M. Sheldrick, SHELXL-97, Program for refinement of crystal
structures, University of Go¨ttingen, Germany, 1997.
36 G. M. Sheldrick, SHELXS-97, Program for solution of crystal struc-
tures, University of Go¨ttingen, Germany, 1997.
37 CrysAlisCCD (Version 1.171.29.9) Oxford Diffraction, Wrocław,
Poland, 2006.
6 S. K. Hadjikakou, I. I. Ozturk, M. N. Xanthopoulou, P. C. Zachariadis,
S. Zartilas, S. Karkabounas and N. Hadjiliadis, J. Inorg. Biochem., 2008,
102, 1007–1015, and references therein.
38 CrysAlisRED (Version 1.171.29.9). Oxford Diffraction, Wrocław,
7 B. P. Block, Inorg. Synth., 1953, 4, 14.
Poland, 2006.
8 A. K. Al-Sa’ady, C. A. McAuliffe, R. V. Parish and J. A. Sandbank,
Inorg. Synth., 1985, 23, 191–194.
39 J. J. P. Stewart, J. Mol,. Mod., 2007, 13, 1173–1213.
40 J. J. P. Stewart, MOPAC 2007, Stewart Computational Chemistry,
Colorado Springs, CO, USA, http://OpenMOPAC.net.
41 J. Baker, J. Comput. Chem., 1986, 7, 385.
42 M. N. Xanthopoulou, S. K. Hadjikakou, N. Hadjiliadis, E. R. Milaeva,
J. A. Gracheva, V.-Y. Tyurin, N. Kourkoumelis, K. C. Christoforidis,
A. K. Metsios, S. Karkabounas and K. Charalabopoulos, Eur. J. Med.
Chem., 2008, 43, 327.
9 N. C. Baenziger, W. E. Bennett and D. M. Soboroff, Acta Crystallogr.,
1976, 32, 962–963.
10 M. Khan, C. Oldham and D. G. Tuck, Can. J. Chem., 1981, 59, 2714–
2718.
11 T. A. Grant, J. M. Forward and J. P. Fackler, Z. Kristallogr., 1996, 211,
483.
10456 | Dalton Trans., 2009, 10446–10456
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