Gold complexes with thiosemicarbazones: Reactions of bi- And tridentate thiosemicarbazones with dichloro2-(dimethylaminomethylphenyl-CilgoldCm), [Au(damp-C1A)Cl2]

Article abstract of DOI:10.1039/a908712e

Dichloro[2-(A,A-dimethylaminomethyl)phenyl-C1,A]gold(iii), [Au(damp-C,A)Cl₂] (1), reacts with salicylaldchyde thiosemicarbazone (H₂saltsc), vanilline thiosemicarbaezone (Hvantsc), N-methylpyrrole aldehyde thiosemicarbazone (Hmepyrtsc), pyridoxal methylthiosemicarbazone (H₂pydoxmetsc), 2-diphenylphosphinobenzaldehyde thiosemicarbazone (HPtsc) or variously substituted acetylpyridine thiosemicarbazones (HapRtsc; R = H, Me, Ph) with cleavage of the Au-N bond and protonation of the dimethylamino group. Compounds of general formulae [Au(Hdamp-C¹)CI(L)f (L = Hsaltsc^-, vantsc^-, mepyrtsc¹), [Au(Hdamp-C¹)Cl(L)]²⁺ (L = H₂pydoxmetsc) or [Au(Hdamp-C¹)(L)]²⁺ (L = Ptsc^-, apRtsc^-, R = H, Me, Ph) have been isolated and characterized. The presence of the (T-bonded 2-(dimethylaminomethyl)phenyl ligand is mandatory to prevent reduction of the gold(in) centre. The crystal structures of [Au(Hdanip-C¹)CI(HsaItsc)](PF₆) (3a), [Au(Hdamp-C')Cl(mepyrtsc)]Cl (3c), [Au(Hdamp-C₁)-CI(H₂pydo.xtnetsc)]Cl₂-MeOH (4), [Au(Hdamp-C¹)(apPhtsc)]Cl₂-2 MeOH (5c) and [Au(Hdamp-C')(Ptsc)]Cl₂-1.5MeOH (6) have been elucidated, showing the gold atoms in distorted square-planar co-ordination environments. The potentially O,N,S-tridentate ligands H₂saltsc and H₂pydoxmetsc co-ordinate in a bidentate fashion and do not incorporate the OH groups in the chelating framework, whereas HapRtsc or HPtsc co-ordinate in a tridentate manner. Generally, one or more hydrogen atoms of the heterocyclic ligands and/or the NMe2H+ group form hydrogen bridges in the solid state structures. The preliminary results of antiproliferation tests on tumor cells demonstrate the considerable cytotoxicity of these new gold complexes. The Royal Society of Chemistry 2000.

Full text of DOI:10.1039/a908712e

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Gold complexes with thiosemicarbazones: reactions of bi- and
tridentate thiosemicarbazones with dichloro[2-(dimethylamino-
1
1
methyl)phenyl-C ,N]gold(III), [Au(damp-C ,N)Cl ]
2
a
b
c
c
Ulrich Abram,* Kirstin Ortner,† Ronald Gust and Klaus Sommer
a
Forschungszentrum Rossendorf, Institute of Radiochemistry, c/o Dresden University of
Technology, Institute of Analytical Chemistry, D-01062 Dresden, Germany
University of Tübingen, Institute of Inorganic Chemistry, Auf der Morgenstelle 18,
D-72076 Tübingen, Germany
Freie Universität Berlin, Institute of Pharmacy, Königin-Louise-Str. 2–4, D-14195 Berlin,
Germany
b
c
Received 2nd November 1999, Accepted 22nd December 1999
1
1
Dichloro[2-(N,N-dimethylaminomethyl)phenyl-C ,N]gold(), [Au(damp-C ,N)Cl ] (1), reacts with salicylaldehyde
2
thiosemicarbazone (H saltsc), vanilline thiosemicarbazone (Hvantsc), N-methylpyrrole aldehyde thiosemicarbazone
2
(
Hmepyrtsc), pyridoxal methylthiosemicarbazone (H pydoxmetsc), 2-diphenylphosphinobenzaldehyde thiosemi-
2
carbazone (HPtsc) or variously substituted acetylpyridine thiosemicarbazones (HapRtsc; R = H, Me, Ph) with
cleavage of the Au–N bond and protonation of the dimethylamino group. Compounds of general formulae
1
ϩ
Ϫ
Ϫ
Ϫ
1
2ϩ
[
[
Au(Hdamp-C )Cl(L)] (L = Hsaltsc , vantsc , mepyrtsc ), [Au(Hdamp-C )Cl(L)] (L = H pydoxmetsc) or
2
1 2ϩ Ϫ Ϫ
Au(Hdamp-C )(L)] (L = Ptsc , apRtsc , R = H, Me, Ph) have been isolated and characterized. The presence of
the σ-bonded 2-(dimethylaminomethyl)phenyl ligand is mandatory to prevent reduction of the gold() centre. The
1
1
1
crystal structures of [Au(Hdamp-C )Cl(Hsaltsc)](PF ) (3a), [Au(Hdamp-C )Cl(mepyrtsc)]Cl (3c), [Au(Hdamp-C )-
6
1
1
Cl(H pydoxmetsc)]Cl ؒMeOH (4), [Au(Hdamp-C )(apPhtsc)]Cl ؒ2 MeOH (5c) and [Au(Hdamp-C )(Ptsc)]Cl ؒ
2
2
2
2
1
.5MeOH (6) have been elucidated, showing the gold atoms in distorted square-planar co-ordination environments.
The potentially O,N,S-tridentate ligands H saltsc and H pydoxmetsc co-ordinate in a bidentate fashion and do not
2
2
incorporate the OH groups in the chelating framework, whereas HapRtsc or HPtsc co-ordinate in a tridentate manner.
ϩ
Generally, one or more hydrogen atoms of the heterocyclic ligands and/or the NMe H group form hydrogen bridges
2
in the solid state structures. The preliminary results of antiproliferation tests on tumor cells demonstrate the
considerable cytotoxicity of these new gold complexes.
1
3–20
Introduction
mercury().
Recently, we reported preliminary details of
21
the first gold complexes with this type of ligand. Here, we
describe the synthesis and structural characterization of thio-
semicarbazone complexes of gold() additionally containing
the 2-(dimethylaminomethyl)phenyl (damp ) ligand.
Square-planar gold() complexes with the (damp-C ,N)
ligand have been known since 1984. Key compounds are the
dichloro and diacetato complexes [Au(damp-C ,N)Cl ] (1) and
Thiosemicarbazones (tautomeric forms, see Ia and Ib) and their
Ϫ
1
Ϫ
22
1
2
metal complexes are of considerable interest because of their
1,2
chemical and promising biological properties. They can easily
be modified by variation of the parent aldehyde or ketone
used for the synthesis, particularly with compounds having
additional potential co-ordinating sites (position R) or by sub-
3
stitutions on the terminal N position. Antibacterial, antineo-
4
5
6
plastic, antimalarial and antiviral behaviour has been found.
Relationships are evident between chelate formation in the
7–10
complexes and the in vivo activity.
This makes structural
1
1
[
Au(damp-C ,N)(CH CO ) ] (2) which have recently been
3 2 2
23
studies on thiosemicarbazone complexes interesting. Although
a number of studies dealing with the complex-formation
structurally characterized and show distorted square-planar
co-ordination spheres for the gold atoms. During ligand
11,12
properties of this class of compounds exist,
comparatively
exchange reactions, the chloro or acetato ligands are preferen-
few structural reports are published. They deal with
iron(), cobalt(), nickel(), copper(), palladium(), zinc(),
tin(), tin(), bismuth(), indium(), cadmium() and
23–30
tially replaced.
Only a few examples where the Au–N bond
30
is cleaved have been reported. Protonation of the liberated
N(CH ) group, however, to the best of our knowledge has only
3
2
31
been observed for gold compounds with heterocyclic thiols
32
and diphenylthiocarbazone (dithizone), both ligand types
which are related to the thiosemicarbazones under study here.
†
Present address: University of Zürich, Institute of Inorganic
Chemistry, Winterthurerstr. 190, CH-8057 Zürich, Switzerland.
DOI: 10.1039/a908712e
J. Chem. Soc., Dalton Trans., 2000, 735–744
735
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Table 1 Selected bond lengths (Å) and angles (Њ) in the complexes (3a),
3b) and (3c)
(
a
(
3a)
(3b)
(3c)
Au–C(1)
Au–S(11)
Au–N(15)
Au–Cl(1)
C(12)–N(13)
C(12)–N(14)
N(14)–N(15)
N(15)–C(16)
S(11)–C(12)
2.039(7)
2.247(2)
2.115(6)
2.322(2)
1.364(11)
1.290(10)
1.385(9)
1.290(10)
1.758(8)
2.024(6)
2.249(2)
2.116(5)
2.320(2)
1.336(10)
1.295(8)
1.392(7)
1.276(8)
1.759(7)
2.029(8)
2.248(3)
2.106(7)
2.320(2)
1.356(11)
1.281(11)
1.383(9)
1.295(11)
1.763(9)
C(1)–Au–S(11)
C(1)–Au–N(15)
C(1)–Au–Cl(1)
S(11)–Au–N(15)
S(11)–Au–Cl(1)
N(15)–Au–Cl(1)
87.4(2)
171.8(3)
92.2(2)
84.5(2)
178.70(8)
95.9(2)
90.7(2)
172.2(2)
89.8(2)
84.3(2)
179.44(6)
95.3(2)
88.7(2)
172.6(3)
91.5(2)
84.1(2)
178.8(1)
95.7(2)
D–H
H ؒ ؒ ؒ A D ؒ ؒ ؒ A D–H ؒ ؒ ؒ A
Hydrogen bonds in (3a)
N(8)–H(8) ؒ ؒ ؒ Cl(1)
O(19)–H(19) ؒ ؒ ؒ F(36)
0.75(7) 2.47(8)
0.86(9) 1.92(9)
3.216(8) 168(7)
2.769(9) 167(10)
Fig. 1 Thiosemicarbazone ligands used throughout the experiments.
All ligands are given in their thione form.
Hydrogen bonds in (3c)
N(8)–H(8) ؒ ؒ ؒ Cl(2Ј)
N(13)–H(13A) ؒ ؒ ؒ Cl(2Љ) 1.01
N(13)–H(13B) ؒ ؒ ؒ Cl(2) 0.87
0.87
2.43
2.03
2.48
3.224(8) 151
2.987(8) 157
3.213(9) 142
In a recent paper, some tumor cell toxicity studies of
1
[
Au(damp-C ,N)Cl ], which has structural and electronic
2
analogies to cis-diamminedichloroplatinum(), cis-platin, have
a
Symmetry operations: (Ј) 1 Ϫ x, Ϫy, 1 Ϫ z; (Љ) 1 Ϫ x, Ϫy, 2 Ϫ z. More
details are contained in ref. 21. The atom labelling corresponds to that
given in Fig. 2 for (3a).
30
been reported. This makes further studies dealing with the
ligand exchange behaviour of this complex and the biological
activity of the resulting products interesting.
Here, we present syntheses and structural characterization of
complexes which are obtained from the reaction of [Au(damp-
1
C ,N)Cl ] with the thiosemicarbazones shown in Fig. 1. All
2
ligands are given in their thione form, despite the fact that in
solution thiosemicarbazones probably consist of an equi-
librium mixture of thione (Ia) and thiol (Ib) tautomers.
Results and discussion
Starting from [Au(damp-C ,N)Cl ] and thiosemicarbazones, a
1
2
variety of new gold complexes have been synthesized and struc-
turally characterized. Scheme 1 summarizes the reactions per-
formed and the products obtained. All ligands summarized in
Fig. 1 react with (1) via exchange of the chloro ligands, cleavage
of the Au–N bonds and protonation of the N(CH ) groups.
3
2
3
3
This behaviour has also been observed for reactions with
Fig. 2 ZORTEP representation of the complex cation of (3a).
31,32
heterocyclic thiols or dithizone,
but is unusual with respect
Thermal ellipsoids represent 50% probability.
to the numerous Au(damp) complexes with various mono- or
Ϫ
bidentate ligands which have the general formulae [Au(damp-
gold, whereas Ptsc and the acetylpyridine thiosemicarbazones
1
1
0,2ϩ
1
1
2 0,2ϩ
C ,N)(X)L ]
(X = L or Cl) or [Au(damp-C ,N)L ]
,
exhibit tridentate co-ordination.
Pale yellow crystals of [Au(Hdamp-C )Cl(Hsaltsc)](PF ) (3a)
2
3–30
1
depending on the net charge of the ligands used.
6
The reactions were performed in methanol–acetone solutions
in which the sparingly soluble thiosemicarbazones readily dis-
solve after mixing with a solution of (1). Yellow to orange–red,
air-stable products were obtained after reducing the solvent
volume and/or diffusion of diethyl ether into solutions of the
complexes. The yields are moderate due to serious problems
during the isolation of crystalline compounds (see Experi-
mental). Reduction of the gold() centre and formation of
gold() compounds or elemental gold, however, has not been
observed.
suitable for X-ray analysis were obtained by treating (1) with
one equivalent of H saltsc and KPF . The formation of the
2
6
cationic complex is supported by the occurrence of an intense
ϩ
peak in the FAB mass spectrum of the compound at m/z =
561. The IR spectrum shows an O–H valency vibration at 3410
Ϫ1
cm and suggests that the OH group of the salicylaldehyde
thiosemicarbazone does not contribute to the co-ordination. A
Ϫ1
band at 2677 cm is in accordance with values found previ-
1
ously for monodentate (Hdamp-C ) ligands with protonated
21,31,32
(CH ) N groups
forming hydrogen bonds.
3
2
33
The thiosemicarbazones bind as N,S-chelates with mono-
deprotonation of the co-ordinating back-bone. The only excep-
Fig. 2 shows an ellipsoidal representation of the structure
of the complex cation. Selected bond lengths and angles are
summarized in Table 1. The thiosemicarbazone is only singly
deprotonated and binds to gold via S and N. The almost ideally
square-planar co-ordination sphere of the metal is completed
tion, the co-ordination of H pydoxmetsc as a formally neutral
2
chelating ligand, is explained by the zwitterionic character of
this ligand and will be discussed later. The potential third co-
ordination sites of H saltsc and H pydoxmetsc do not bind to
Ϫ
by Cl and a monodentate Hdamp ligand. The position of the
2
2
7
36
J. Chem. Soc., Dalton Trans., 2000, 735–744

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Scheme 1
gold atom deviates from a least-squares plane formed by the
donor atoms by only 0.003 Å. The Au–N bond is cleaved and
the liberated dimethylamino group is protonated forming an
intramolecular hydrogen bond to Cl(1). This has been verified
by the localization of all hydrogen atoms attached to O or N
atoms in the Fourier maps and refinement of their positions.
Thus, the bonding situation is comparable with that in
Au(damp) complexes with heterocyclic thiols/thiones which
Table 2 Comparison of bond lengths (Å) in selected salicylaldehyde
thiosemicarbazone complexes. The labelling scheme refers to the
IUPAC numbering as shown for I
Formal
1
[
Au(Hdamp-C )- [Sn(Ph)2-
bond
ϩ a
36
2ϩ 37
b
Bond
Cl(Hsaltsc)]
(saltsc)]
[Ni(H saltsc)]
length
2
1
2
3
4
2
C᎐ N
1.29
1.30
1.40
1.30
1.73
1.28
1.36
1.35
1.70
1.22
1.48
1.22
1.81
also contain protonated (CH ) N groups with the N(8)H pro-
3
3
2
N– N 1.39
3
1
4
ton included in hydrogen-bonded networks and differs from
that in [Pt(C H NMe -C ,N)(C H NHMe -C )Br] where the
N᎐ C
1.29
1.76
᎐
2
2
C–S
10
6
2
10
6
2
hydrogen atom is directed strictly towards the metal and an
a
b
This work. Sum of covalency radii.
34
interaction with platinum is suggested.
The bidentate co-ordination of the potentially tridentate
salicylaldehyde thiosemicarbazone ligand is unusual and to our
knowledge only one crystal structure with this bonding mode
3
6
five-co-ordinate [Sn(Ph) (saltsc)],
which has
a
doubly-
2ϩ
2
2Ϫ
deprotonated, tridentate saltsc ligand, and [Ni(H saltsc) ] ,
where the octahedral co-ordination sphere of the metal is
formed by two neutral H saltsc ligands. Only minor differ-
2
2
35
has been reported, [Ru(Hsaltsc) (PPh ) ]. In the present case,
2
3 2
37
the low affinity of gold to oxygen donor ligands may explain
2
Ϫ
this bonding situation. The Hsaltsc ligand has Z configuration
ences can be found between the gold and the tin compounds, in
which the thiol form of the ligand (Ib) predominates, whereas
the C–S bond is shorter in the neutral thiosemicarbazone lig-
ands of the nickel complex. This suggests a higher proportion
of the tautomeric thione form (Ia) in this compound.
The same type of product has been obtained for vanilline
thiosemicarbazone (Hvantsc) and methylpyrrole thiosemi-
carbazone (Hmepyrtsc). We have previously reported the syn-
with respect to the C(12)–C(14) bond which is required for the
formation of the chelate ring, whereas the E configuration is
found for the N(15)–N(16) bond which minimizes steric repul-
sions between the aromatic ring and Cl(1). Despite the expected
delocalization of electron density in the thiosemicarbazone
skeleton, alternating bond lengths are observed. This seems to
be typical for co-ordinated thiosemicarbazones, independent of
their bonding mode. Table 2 compares the values obtained
1
thesis and structure of [Au(Hdamp-C )Cl(vantsc)]Cl (3b) in a
preliminary communication. Therefore, only some basic
1
ϩ
21
for [Au(Hdamp-C )Cl(Hsaltsc)] with the bonding situations in
J. Chem. Soc., Dalton Trans., 2000, 735–744
737

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3
3
Fig. 4 ZORTEP representation of H pydoxmetscؒHCl. Thermal
3
3
2
Fig. 3 ZORTEP representation of the complex cation of (3c).
ellipsoids represent 50% probability.
Thermal ellipsoids represent 50% probability.
structural features of this complex are compared with its
Ϫ
Ϫ
Hsaltsc and mepyrtsc analogues in Table 1. No changes in
the co-ordination sphere of the metal or the thiosemicarbazone
skeleton are evident as a result of changes in the periphery of
the ligands. The largest structural trans influence is expected for
the σ-bonded phenyl ring of (Hdamp) and, thus, the azo-
methine function of the thiosemicarbazone is situated trans to
this position in all compounds. The phenyl rings of the Hdamp
ligands are twisted against the coordination plane by 73Њ for
(
3a), 66Њ for (3b) and 64Њ for (3c).
Orange–red crystals of [Au(Hdamp-C )Cl(mepyrtsc)]Cl (3c)
1
were obtained in very low yields due to the rapid decomposition
of the compound and the formation of a black solid upon
standing. Therefore, the spectroscopic studies were performed
on a product obtained from a reaction mixture from which the
solvent had been removed under vacuum immediately after a
stirring period of 1 h. The identity of this product was checked
by IR spectroscopy on the crystals. Mass and NMR spectra
3
3
Fig. 5 ZORTEP representation of the complex cation of (4).
Thermal ellipsoids represent 50% probability. The labelling scheme of
the damp ligand corresponds to that given in Fig. 2.
tive of pyridoxal (H pydoxmetsc) IIb is examined. This com-
2
pound crystallizes as a hydrochloride when it is prepared under
the same conditions as described for IIa. The introduction of a
methyl substituent at the terminal amino group changes the
situation inside the molecule and another conformation is
favoured. This is supported by the protonation of the hydroxyl
group and the formation of a hydrogen bond between O(23)
and N(15). A crystal structure analysis of pyridoxal methyl-
thiosemicarbazone hydrochloride, which allowed the detection
of the positions of all the acidic hydrogen atoms (Fig. 4), clearly
shows the Z conformation about C(12)–N(14). Table 3 sum-
marizes selected bond lengths and angles which indicate almost
localised double bonds between S(11) and C(12) [1.669(5) Å]
and N(15) and C(16) [1.287(6) Å]. The conformation of the
proligand pre-forms a tridentate O,N,S chelating ligand.
The reaction of H pydoxmetscؒHCl with [Au(damp-C ,N)-
Cl ], however, results in a rotation about the N(15)–C(16)
bond and the formation of a bidentate N,S-chelate. Pale yellow
needles were isolated which contain [Au(Hdamp-C )Cl(H -
pydoxmetsc)]Cl (4) and one molecule of methanol per formula
unit. Fig. 5 contains an ellipsoidal representation of the struc-
ture of the complex cation. Table 3 compares the bond lengths
and angles with those obtained for H pydoxmetscؒHCl. The
1
suggest a composition of [Au(Hdamp-C )Cl(thiosemicarb-
Ϫ1
azonate)]Cl. An infrared band at 2693 cm gives evidence for
the protonation of the dimethylamino group and the formation
of hydrogen bonds. Au–Cl vibrations can be detected at 315
Ϫ1
cm .
A ZORTEP plot of the cation of (3c) is given in Fig. 3.
Important bond lengths and angles are contained in Table 1.
The thiosemicarbazone is singly deprotonated and co-ordinates
in a bidentate fashion via N and S, as described for (3a and b).
The co-ordination sphere is planar with a maximum deviation
of 0.029 Å from a least-squares plane formed by the atoms
S(11), N(15), Cl(1), C(1) and Au. A hydrogen-bonded network
including N(13), N(8) and symmetry-related positions of Cl(2),
stabilizes the solid-state structure of the complex.
1
2
The condensation of 3-hydroxy-5-hydroxymethyl-2-methyl-
pyridine-4-carbaldehyde (pyridoxal) with thiosemicarbazide
yields a hydrophilic thiosemicarbazone which is a versatile pro-
ligand. Metal complexes have been isolated with this tridentate
2
1
2
38,39
40–42
2
ligand as a neutral thione,
thionate,
monoanionic thiolate
or
or as a dianionic thiolate. The proligand crystal-
lizes in the zwitterionic form IIa with the pyridine nitrogen
38,43
41
2
phenolic hydroxyl group and the pyridine nitrogen remain pro-
tonated, resulting in a zwitterionic ligand after deprotonation
of N(14). This co-ordination behaviour is without precedent for
a pyridoxal thiosemicarbazone, but may be understood with
regard to the low tendency of gold to form bonds with oxygen
donors. The S(11)–C(12) bond length of 1.764(13) Å favours
the thiolate co-ordination mode. The rotation about the N(15)–
C(16) bond minimizes steric interactions between the phenyl
ring and the chloro ligands and allows hydrogen bonds between
O(23) and N(14). An additional weak interaction between
H(23) and N(15) leads to a three-centred hydrogen bond. The
4
4
protonated and a non-protonated aromatic phenolic group.
Ϫ
The solid state structure is stabilized by a hydrogen bond
complex cations, the Cl anion and the incorporated methanol
between the NH group and the azomethine nitrogen. This situ-
ation changes when the 4-N-methylthiosemicarbazone deriva-
are involved in an extensive hydrogen-bonding network, as is
illustrated in Fig. 6 and Table 3.
2
7
38
J. Chem. Soc., Dalton Trans., 2000, 735–744

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Table 3 Selected bond lengths (Å) and angles (Њ) in H pydoxmetscؒ
2
HCl and (4)
H pydoxmetscؒHCl
2
(4)
Au–C(1)
Au–S(11)
2.015(12)
2.266(3)
Au–N(15)
Au–Cl(1)
2.130(10)
2.320(3)
S(11)–C(12)
C(12)–N(13)
C(12)–N(14)
N(14)–N(15)
N(15)–C(16)
C(16)–C(17)
1.669(5)
1.339(6)
1.379(6)
1.357(5)
1.287(6)
1.457(6)
1.764(13)
1.334(16)
1.329(15)
1.368(14)
1.305(15)
1.441(17)
C(1)–Au–S(11)
C(1)–Au–N(15)
C(1)–Au–Cl(1)
90.1(3)
174.2(4)
89.0(3)
Fig. 6 Hydrogen-bonding network in (4). Only acidic H atoms are
45
shown for clarity.
S(11)–Au–N(15)
S(11)–Au–Cl(1)
84.1(4)
179.1(1)
96.8(3)
N(15)–Au–Cl(1)
Au–S(11)–C(12)
S(11)–C(12)–N(13)
S(11)–C(12)–N(14)
C(12)–N(14)–N(15)
N(14)–N(15)–Au
N(14)–N(15)–C(16)
N(15)–C(16)–C(17)
96.4(4)
124.6(3)
122.9(3)
118.1(4)
116.2(8)
125.9(9)
115.0(10)
118.5(7)
116.6(10)
130.1(10)
119.0(4)
117.3(4)
D–H
H ؒ ؒ ؒ A D ؒ ؒ ؒ A
D–H ؒ ؒ ؒ A
Hydrogen bonds in H pydoxmetscؒHCl
2
N(20)–H(20) ؒ ؒ ؒ Cl(1)
O(23)–H(23) ؒ ؒ ؒ N(15)
O(23)–H(23) ؒ ؒ ؒ S(11)I
O(26)–H(26) ؒ ؒ ؒ Cl(1)
0.86(7)
0.90(7)
0.90(7)
0.89(7)
1.04(6)
2.22(7)
1.69(7)
2.99(6)
2.24(7)
2.30(7)
3.050(4)
2.553(5)
3.622(3)
3.064(4)
3.280(4)
162(6)
159(6)
129(5)
153(6)
157(5)
169(8)
3
3
II
Fig. 7 ZORTEP representation of the complex cation of (5c).
Thermal ellipsoids represent 50% probability. The labelling scheme of
the damp ligand corresponds to that given in Fig. 2.
N(13)–H(13) ؒ ؒ ؒ Cl(1)
N(14)–H(14) ؒ ؒ ؒ O(26)
III
1.00(10) 1.86(10) 2.852(5)
Hydrogen bonds in (4)
IV
O(30)–H(30) ؒ ؒ ؒ Cl(3)
N(8)–H(8) ؒ ؒ ؒ Cl(2)
N(13)–H(13) ؒ ؒ ؒ Cl(2)
0.84(15) 2.31(15) 3.050(15) 147(18)
0.71(15) 2.34(15) 3.049(11) 170(15)
0.71(14) 2.54(12) 3.170(11) 149(14)
0.84(15) 1.72(16) 2.530(13) 157(17)
0.86(15) 2.39(17) 3.074(14) 137(14)
0.81(17) 2.35(15) 3.095(10) 153(17)
1
ϩ
1
complexes ([Au(damp-C ,N)(apRtsc-S,N)] or [Au(damp-C )-
(
ϩ
apRtsc-S,N,N)] ). Therefore, we performed crystal structure
V
Ϫ Ϫ
analyses of the apHtsc and apPhtsc derivatives, which prove
O(23)–H(23) ؒ ؒ ؒ N(14)
O(23)–H(23) ؒ ؒ ؒ N(15)
the solid-state structures of the complexes to be [Au(Hdamp-
C )(apRtsc-S,N,N)] . The N–H bond in the NH(CH )
group of the damp ligand is, obviously, easily cleaved in nitro-
VI
1
2ϩ
ϩ
O(26)–H(26) ؒ ؒ ؒ Cl(2)
N(20)–H(20) ؒ ؒ ؒ Cl(3)
3 2
IV
0.7(2)
2.4(2)
3.012(13) 152(23)
benzyl alcohol solution under the conditions applied in the
Symmetry operations: (I) 1 Ϫ x, 3 Ϫ y, Ϫ1 Ϫ z; (II) 1 Ϫ x, y, 1 ϩ z;
III) Ϫx, 3 Ϫ y, Ϫz; (IV) Ϫx, 2 Ϫ y, Ϫz; (V) 1 Ϫ x, 1 Ϫ y, 1 Ϫ z; (VI)
1
(
mass spectrometer. [Au(Hdamp-C )(apHtsc)]Cl
2
ؒ0.5H O (5a)
2
1
Ϫ x, 1 Ϫ y, Ϫz.
crystallizes from methanol–diethyl ether solutions which con-
tain small amounts of water. The presence of water favours the
crystallization and the co-crystallized H O contributes to an
2
Thiosemicarbazones of heterocyclic aldehydes or ketones
extended hydrogen-bonding network, as do the chloride anions.
The gold atom deviates from the least-squares plane formed by
the donor atoms only by 0.046 Å. More details on the crystal
structure of (5a) are contained in a preliminary communication
and their metal complexes have been studied extensively
because some of the compounds are cancerostatic. The
biological activities of the proligands are increased on co-
46
21
ordination to iron or copper centres. An S,N,N-chelating
system has been found in all hitherto known cancerostatic thio-
which has been published recently. In Table 4 selected bond
lengths and angles are compared with the values found in
47
1
semicarbazone complexes. We prepared gold complexes of
HapHtsc, HapMetsc and HapPhtsc by reaction of the poten-
tially tridentate proligands with (1). Additionally we used 2-
[Au(Hdamp-C )(apPhtsc)]Cl (5c). The labelling scheme of
2
1
ϩ
[Au(Hdamp-C )(apHtsc)] follows that applied for the phenyl-
substituted compound.
(
diphenylphosphino)benzaldehyde thiosemicarbazone for
An ellipsoidal representation of the cation of (5c) is given in
Fig. 7. The thiosemicarbazone ligand is not completely planar.
The NH phenyl ring is bent out of the co-ordination plane by
15Њ. The S(11)–C(12) bond is surprisingly short at 1.677(8) Å,
whereas C–S bond lengths between 1.76 and 1.79 Å have been
found for all the other complexes discussed. This suggests the
comparison.
The reaction of (1) with HapRtsc gave yellow solids which
are readily soluble in organic solvents. Their IR spectra suggest
Ϫ
Ϫ
triply co-ordinated tsc ligands or chelate-bonded damp lig-
ands due to the lack of Au–Cl vibrations which can clearly be
observed for the complexes with bidentate thiosemicarbazones
in the range between 300 and 330 cm . IR bands between 2600
and 2700 cm , however, give evidence for hydrogen bonds in
the solid-state structures of the complexes. FAB mass spec-
trometric studies of all three gold apRtsc complexes resulted in
the detection of very intense [Au(damp)(apRtsc)] peaks which
Ϫ
co-ordination of apPhtsc as a monoanionic thione, as
Ϫ1
opposed to the thiolate mode which is preferred in the other
complexes. A widespread delocalization of electron density
over the whole ligand skeleton is also supported by the surpris-
ingly short length of the C(12)–N(13) bond. The tridentate co-
Ϫ1
ϩ
ϩ
Ϫ
ordination mode of the apRtsc ligands with two five-
do not allow unambiguous assignment of the structure of the
membered chelate rings leads to visible distortions in the
J. Chem. Soc., Dalton Trans., 2000, 735–744
739

View Article Online
Table 5 Selected interatomic distances (Å) and angles (Њ) for (6)
Table 4 Selected bond lengths (Å) and angles (Њ) in (5a) and (5c)
a
(
5a)
(5c)
Au–C(1)
2.055(6)
2.308(2)
2.092(5)
2.308(2)
1.772(6)
1.323(7)
0.76(8)
C(12)–N(14)
N(14)–N(15)
N(15)–C(16)
C(16)–C(21)
C(20)–C(21)
C(20)–P
1.301(7)
1.372(6)
1.287(7)
1.459(8)
1.411(8)
1.803(6)
Au–S(11)
Au–N(15)
Au–P
S(11)–C(12)
C(12)–N(13)
N(8)–H(8)
Au–C(1)
Au–S(11)
Au–N(15)
Au–N(19)
S(11)–C(12)
C(12)–N(13)
C(12)–N(14)
N(14)–N(15)
N(15)–C(16)
C(16)–C(18)
C(16)–C(17)
N(8)–H(8)
2.043(4)
2.251(1)
2.036(4)
2.081(4)
1.791(5)
1.328(6)
1.314(6)
1.375(5)
1.285(5)
1.473(6)
1.480(6)
0.92(5)
1.915(8)
2.194(2)
1.904(6)
2.035(7)
1.677(8)
1.267(9)
1.318(11)
1.295(8)
1.282(10)
1.366(10)
1.397(11)
0.81(9)
C(1)–Au–S(11)
C(1)–Au–N(15)
C(1)–Au–P
S(11)–Au–N(15)
S(11)–Au–P
91.0(2)
171.9(2)
90.7(2)
84.0(1)
172.89(5)
92.6(1)
95.2(2)
115.8(4)
125.1(5)
C(12)–N(14)–N(15)
N(14)–N(15)–Au
N(14)–N(15)–C(16)
C(16)–N(15)–Au
N(15)–C(16)–C(21)
C(16)–C(21)–C(20)
C(21)–C(20)–P
116.8(5)
118.4(3)
113.6(5)
127.9(4)
131.5(5)
128.4(5)
122.0(4)
111.0(2)
N(15)–Au–P
Au–S(11)–C(12)
S(11)–C(12)–N(13)
S(11)–C(12)–N(14)
C(20)–P–Au
C(1)–Au–S(11)
C(1)–Au–N(15)
96.5(1)
178.6(2)
99.1(2)
89.1(2)
178.6(3)
90.1(2)
C(1)–Au–N(19)
S(11)–Au–N(15)
S(11)–Au–N(19)
N(15)–Au–N(19)
Au–S(11)–C(12)
S(11)–C(12)–N(13)
S(11)–C(12)–N(14)
C(12)–N(14)–N(15)
N(14)–N(15)–Au
C(16)–N(15)–Au
N(15)–C(16)–C(18)
C(16)–C(18)–N(19)
C(18)–N(19)–Au
C(20)–N(19)–Au
C(18)–N(19)–C(20)
N(14)–N(15)–C(16)
84.9(1)
163.6(1)
79.5(2)
84.1(4)
165.9(2)
75.9(3)
94.7(2)
90.0(3)
113.5(3)
126.2(4)
112.3(4)
121.7(3)
117.4(3)
114.7(4)
117.1(4)
111.3(3)
128.9(3)
119.7(4)
120.9(4)
108.1(6)
127.8(6)
115.4(6)
116.6(5)
119.5(5)
116.3(7)
111.9(7)
115.9(5)
128.1(6)
115.9(8)
123.7(6)
a
Values are taken from a preliminary communication reported in ref.
1. The labelling of the atoms has been partially changed to match the
2
labelling scheme given in Fig. 7 for (5c).
square-planar co-ordination environment of Au() resulting in
N(19)–Au–S(11) angles of 163.6(1)Њ in (5a) and 165.9(2)Њ in
(
5c). The σ-bonded phenyl rings of the damp ligands are bent
out of the co-ordination plane of the metal by 66.2Њ in
1
2ϩ
1
[
(
Au(Hdamp-C )(apHtsc)]
and 76.4Њ in [Au(Hdamp-C )-
2ϩ
33
apPhtsc)] to minimize steric interactions.
Fig. 8 ZORTEP representation of the complex cation of (6).
Thermal ellipsoids represent 50% probability. The labelling scheme of
the damp ligand corresponds to that given in Fig. 2.
A more bulky tridentate thiosemicarbazone, HPtsc, can be
47
derived from 2-(diphenylphosphino)benzaldehyde.
HPtsc
reacts with (1) forming a complex having the same basic struc-
Ϫ
1
ϩ
ture as the apRtsc complexes. [Au(Hdamp-C )(Ptsc)]Cl (6) is
able nickel(II) complex, [Ni(Ptsc)(py)] , where the pyridine ring
2
a yellow solid which can be crystallized from methanol–diethyl
ether as a solvate containing 1.5 equiv. MeOH per complex in
the crystal lattice. The compound is stable in air and readily
is also arranged parallel to one of the phosphine phenyl groups
48
(inter-ring distances between 3.1 and 4.2 Å). Thus, weak
interactions between the ring systems in both compounds
cannot completely be ruled out, at least for their solid state
structures.
ϩ
ϩ
soluble in methanol. FAB mass spectrometry shows [M Ϫ H]
ϩ
and [Au(Ptsc)] peaks, as has been observed previously for
the acetylpyridine thiosemicarbazone complexes, and gives evi-
Preliminary tests of the antitumor activity carried out on
human MCF-7 breast cancer cells indicate a high antiprolifer-
ative potency for the new compounds. At a concentration of
5 µM gold complexes with the thiosemicarbazone ligands
1
dence for facile deprotonation of the Au(Hdamp-C ) unit
31
under mass spectrometric conditions. The P resonance of the
thiosemicarbazone is shifted from Ϫ13.2 ppm in the proligand
to ϩ29.2 ppm upon co-ordination to Au().
HapHtsc, HapMetsc, HapPhtsc, HPtsc and H saltsc display
2
An ellipsoidal representation of the complex cation of (6) is
shown in Fig. 8. Selected bond lengths and angles are summar-
ized in Table 5. The distorted square-planar co-ordination
sphere of gold is formed by four different donor atoms. The
metal is situated 0.13 Å outside the least-squares plane formed
by the donor atoms. 2-(Diphenylphosphino)benzaldehyde thio-
semicarbazone is bonded as a monoanionic tridentate ligand
forming 5- and 6-membered chelate rings. Thus, the phenyl ring
which carries the thiosemicarbazone moiety is co-planar with
the co-ordination plane. The damp phenyl ring, however, is
almost perpendicular to this plane (angle between the planes:
exceedingly cytotoxic activity leading to cell death. After an
incubation period of 216 h, τ ranges from Ϫ63.61 to Ϫ65.47%,
thus being more effective than cisplatin (τ = Ϫ2.47%). This
work is presently in progress in our laboratories and the results
49
will be published elsewhere.
Conclusions
Cationic complexes are formed during the reaction of dichloro-
1
[2-(dimethylaminomethyl)phenyl-C ,N]gold() with thiosemi-
carbazones. A main structural feature of the resulting gold()
compounds is the formation of ammonium functions from the
liberated N(CH ) groups.
7
9.9Њ). With this, it is almost parallel to one of the phenyl rings
of the phosphine, as is evident from Fig. 8. The distances
between related carbon atoms of these rings range between 3.4
and 5.3 Å. A similar situation has been observed in a compar-
3
2
All complex molecules are involved in extended hydrogen-
bonding networks with the counter ions and solvent molecules
7
40
J. Chem. Soc., Dalton Trans., 2000, 735–744

View Article Online
Table 6 Comparison of selected bond lengths (Å) and angles (Њ) in the
standard. An Oxford NMR 300 Gemini 2000 (Varian) instru-
gold thiosemicarbazone complexes studied. For labelling scheme, see
31
ment with H PO as internal standard was used to obtain
P
3
4
(
4)
NMR spectra.
(
3a–c), (4)
(5a)
(5c)
(6)
Syntheses
1
Au–C(1)
Au–S(11)
Au–N(15)
2.02–2.04
2.25–2.27
2.11–2.13
2.32
2.04
2.25
2.04
2.08
1.79
1.31
1.38
1.29
1.92
2.19
1.90
2.04
1.68
1.32
1.30
1.28
2.06
2.31
2.09
2.38
1.77
1.30
1.37
1.29
[Au(Hdamp-C )Cl(Hsaltsc)]Cl. Salicylaldehyde thiosemi-
carbazone (100 mg, 0.5 mmol) was suspended in about 3 ml
acetone and added to a solution of [Au(damp-C ,N)Cl ] (200
1
2
Au–Cl/N /P
py
mg, 0.5 mmol) in 3 ml of a methanol–acetone (1:1 v/v) mixture.
A clear yellow solution formed immediately which was stirred
at room temperature for 2 h. The solvent was removed and the
remaining yellow solid dissolved in methanol. Upon slow evap-
oration of the solvent a few tiny crystals were formed which
were not suitable for an X-ray structure analysis. The majority
of the product deposits as a yellow microcrystalline solid which
is readily soluble in methanol, but almost insoluble in acetone
or dichloromethane. Yield: 180 mg (60%). Elemental analysis,
Found: C, 34.4; H, 3.4; N, 9.4; S, 5.4; Cl, 12.1; Calcd. for
C H N AuCl OS: C, 34.2; H, 3.5; N, 9.4; S, 5.4; Cl, 11.9%. IR
S(11)–C(12)
C(12)–N(14)
N(14)–N(15)
N(15)–C(16)
1.76
1.28–1.33
1.37–1.39
1.28–1.31
C(1)–Au–S(11)
S(11)–Au–N(15)
N(15)–Au–Cl/N /P
87.4–90.7
84.1–84.5
95.3–96.8
89.0–92.2
171.8–174.2
178.7–179.4
96.5
84.9
79.5
99.1
178.6
163.6
89.1
90.1
75.9
104.9
178.6
165.9
91.04
84.0
93.6
90.7
171.9
172.9
py
Cl/N /P–Au–C(1)
py
C(1)–Au–N(15)
S(11)–Au–Cl/N /P
py
17
21
4
Ϫ1
2
ϩ
1
(
1
1
νmax/cm ): 3410 (O–H), 2677 (m, N–H , Hdamp-C ), 1601–
1
456 (C᎐C, N᎐N), 324 (s, Au–Cl). H-NMR (dmso-d , ppm):
᎐ ᎐
6
ϩ
0.85 (1H, s, br, NH ), 9.0 (1H, s, OH), 8.17–7.0 (10H, m,
13
phenyl, NH ), 4.67 (2H, s, CH ), 2.95 (6H, m, 2CH ). C-NMR
2
2
3
(
(
dmso-d , ppm): 171.3 (CS), 164.7–116.9 (arom. C), 55.0
6
ϩ
CH ), 42.8, 42.5 (CH , damp). FAB -MS: m/z = 561 {100%,
2
3
ϩ
ϩ
M , [Au(Hdamp)(Hsaltsc)Cl] }, 525 {25%, [Au(Hdamp)-
ϩ
(
Hsaltsc)] }.
which are frequently incorporated into the solid state structures
of the compounds. A comparison of the main structural
features of the complex cations is given in Table 6. The corre-
sponding labelling scheme is briefly depicted in III. Since the
bonding situation is very similar in all compounds, containing
bidentate co-ordinated thiosemicarbazones, it has been sum-
marized and compared with the complexes containing tri-
dentate ligands. Whereas the observed C–S bond lengths prove
the predominant contribution of the tautomeric thiolate form
Ib to the bonding situation in almost all thiosemicarbazonato
complexes discussed, the short C–S bond in (5c) is remark-
able. This can, however, not be exclusively explained by the
occurence of the thione form Ia in this compound, since the
neighbouring C(12)–N(14) bond is not significantly lengthened
and a short C(12)–N(13) bond is observed. Thus, the substitu-
tion of a phenyl ring on N(13) most probably leads to an
extended π-system and increases the electron density in the co-
ordination sphere of the metal. The observed bond angles
around gold and the deviations from an ideal square co-
ordination environment are due to the formation of the restrict-
ing bite angles of the 5-membered chelate rings.
Crystals of the complex suitable for an X-ray structure
Ϫ
determination were obtained for its PF
addition of KPF to
salt (3a) formed via
solution of [Au(Hdamp-C )-
6
1
a
6
Cl(Hsaltsc)]Cl in methanol and slow evaporation of the
solvent.
1
1
[Au(Hdamp-C )Cl(vantsc)]Cl (3b). [Au(damp-C ,N)Cl ] (314
2
mg, 0.79 mmol) and vanilline thiosemicarbazone (177 mg, 0.79
mmol) were suspended in 20 ml methanol and heated under
reflux for 2 h to yield a clear yellow solution. The solvent was
evaporated to dryness, the residue washed with cold acetone and
the orange–red, microcystalline solid dried in vacuo. Yield: 450
mg (90%). Yellow crystals suitable for X-ray diffraction were
obtained by slow evaporation of a methanol solution. Elem-
ental analysis, Found: C, 35.0; H, 4.3; N, 9.2; S, 5.1; Cl, 11.5;
Calcd. for C H N AuCl O S: C, 34.5; H, 3.9; N, 8.9; S, 5.1; Cl,
1
8
23
4
2
2
Ϫ1
ϩ
11.3%. IR (ν /cm ): 3439, 3334 (O–H, N–H), 2686 (N–H ,
Hdamp-C ), 1600–1512 (C᎐C, N᎐N), 452 (Au–C), 316 (s, Au–
Cl). H-NMR (dmso-d , ppm): 10.51 (1H, s, br, NH ), 10.18
max
1
᎐
᎐
1
ϩ
6
(1H, s, OH), 7.96–6.78 (8H, m, phenyl), 7.72 (2H, s, NH ),
2
4.31 (2H, s, CH ), 3.67 (3H, d, OCH ), 2.58 (6H, m, 2CH ).
2
3
3
13
First results from the antiproliferation tests on tumor cells
prove the cytotoxicity of the new gold complexes. These
promising results suggest that an intensification of such studies
would be worthwhile.
C-NMR (dmso-d , ppm): 171.8 (CS), 153.2–117.5 (arom. C),
6
ϩ
63.4 (CH ), 57.8 (OCH ), 44.1, 43.8 (2CH , damp). FAB -MS:
2
3
3
ϩ
ϩ
m/z = 591 {100%, M , [Au(Hdamp)Cl(vantsc)] }, 555 {32%,
[Au(Hdamp)(vantsc)] }.
ϩ
1
1
[
Au(Hdamp-C )Cl(mepyrtsc)]Cl (3c). [Au(damp-C ,N)Cl ]
2
Experimental
(
200 mg, 0.5 mmol) was dissolved in 2 ml of a methanol–
The thiosemicarbazone ligands used were prepared by refluxing
equivalent amounts of thiosemicarbazide, 4-N-methylthio-
semicarbazide or 4-N-phenylthiosemicarbazide (Aldrich) and
the corresponding aldehydes or ketones (Aldrich, Fluka) in
ethanol. They were characterized by their infrared and mass
acetone mixture (1:1, v/v) and solid methylpyrrole thiosemi-
carbazone (91 mg, 0.5 mmol) added. The thiosemicarbazone
rapidly dissolved and a clear red solution was formed which
lightened after stirring for 1 h. The volume was slowly reduced
by evaporation of the solvents and a few orange–red crystals
deposited over a period of 24 h. More product was obtained
by reducing the volume of the mother liquor under vacuum.
However, the solid obtained rapidly decomposed to give a
black powder. Satifactory IR, NMR and mass spectra were
obtained immediately after separation of the solid. Yield: 73 mg,
spectra. Tetrachloroauric acid was a gift from Degussa AG.
1
[
Au(damp-C ,N)Cl ] was synthesized by two transmetallations
2
via [Hg(damp)Cl] following a procedure outlined in ref. 23.
Infrared spectra were recorded for KBr pellets on a Spectrum
1
4
000 (Perkin-Elmer) FT IR spectrometer in the range between
000 and 200 cm . Routine EI and FAB spectra were meas-
Ϫ1 ϩ ϩ
Ϫ1
ϩ
25%. IR 1 (νmax/cm ): 3386, 3251 (N–H), 2693 (N–H ,
ured with a TSQ spectrometer (Finnigan) with nitrobenzyl
Hdamp-C ), 1599–1559 (C᎐C, N᎐N), 451 (Au–C), 315 (s, Au–
1
13
1
ϩ
alcohol as matrix. H and C NMR spectra were recorded in
Cl). H-NMR (dmso-d , ppm): 10.85 (1H, s, br, NH ), 8.2
6
dmso-d with a DRX-250 spectrometer (Bruker) with TMS as
(2H, s, NH ), 7.87–7.0 (8H, m, phenyl), 4.5 (2H, s, CH ),
6
2
2
J. Chem. Soc., Dalton Trans., 2000, 735–744
741

View Article Online
Table 7 X-Ray structure data collection and refinement parameters
H pydoxmetscؒ
HCl
2
(
3a)
(3c)
(4)ؒMeOH
(5c)ؒ2MeOH
(6)ؒ1.5MeOH
Formula
C H AuClF N - C H AuCl N S C H ClN O S C H AuCl N O S
C H AuCl N O S
C H N Cl O1.5PS
31 37 4 2
1
7
21
6
4
16 22
2
5
10 15
4
2
20 31
3
5
3
25 34
2
5
2
OPS
706.8
Ϫ1
M/g mol
584.31
290.77
724.9
736.50
820.54
Crystal dimension/
mm
Crystal system
Space group
Unit cell
0.25 × 0.2 × 0.15
0.3 × 0.1 × 0.5
0.4 × 0.2 × 0.03 0.15 × 0.1 × 0.1
0.25 × 0.25 × 0.15
0.4 × 0.1 × 0.1
Monoclinic
Monoclinic
Triclinic
P1
Triclinic
P1
Monoclinic
Monoclinic
¯
¯
P2 /c
P2 /c
P2 /c
P2 /n
1
1
1
1
a = 12.799(2) Å
b = 10.504(1) Å
c = 16.973(4) Å
a = 12.858(1) Å
b = 12.559(3) Å
c = 12.904(2) Å
a = 7.700(1)
b = 8.050(1)
c = 12.461(1)
α = 74.08(1)
β = 75.85(1)
γ = 64.49(1)
663.2(1)
a = 9.736(2) Å
b = 11.180(1) Å
c = 13.085(2) Å
α = 77.35(1)Њ
β = 84.75(1)Њ
γ = 83.00(1)
1376.3(8)
a = 13.943(3) Å
b = 13.410(4) Å
c = 15.292(3) Å
a = 16.596(3) Å
b = 11.257(1) Å
c = 18.363(3) Å
β = 93.38(1)Њ
β = 97.21(2)Њ
β = 100.05(2)
β = 94.80(1)Њ
3
V/Å
2277.9(8)
4
2067.3(6)
4
2815(1)
4
3418.6(7)
4
Z
2
2
Measurement
temperature/ЊC
Linear absorptionϪ1
coefficient/mm
Measured
20
Ϫ65
Ϫ65
Ϫ120
Ϫ65
Ϫ65
6.804
7.485
4.046
5.742
5.521
4.599
5608
5083
3164
3345
6845
8241
reflections
Independent
reflections/R
R1 (F)/wR2 (F )
4938/0.036
0.0389/0.0811
4487/0.047
0.0494/0.0772
2253/0.063
0.0539/0.1927
3345
6099/0.0264
0.0423/0.0969
7455/0.0301
0.0357/0.0804
int
2
0.0613/0.1234
ϩ
ϩ
ϩ
3
5
.18 (3H, NCH ), 2.75 (6H, m, 2CH ). FAB -MS: m/z =
{100%, [M Ϫ H ], [Au(Hdamp)(apHtsc)] }, 390 {40%,
[Au(apHtsc)] }.
3
3
ϩ
ϩ
ϩ
48 {27%, M , [Au(Hdamp)Cl(mepyrtsc)] }, 512 {15%,
ϩ
[Au(Hdamp)(mepyrtsc)] }.
1
[
Au(Hdamp-C )(apMetsc)]Cl (5b). The compound was pre-
pared as described for (5c) and was isolated in the form of
yellow needles. Yield: 40 mg, 13%. IR (ν /cm ): 3405 (br,
MeOH), 3287, 3147 (N–H), 2684 (NH ), 1597 (C᎐N), 1570,
1548, 1513 (C᎐C), 425 (Au–C). FAB -MS: m/z = 538 {100%,
[M Ϫ H] }, 507 {5%, [M Ϫ H Ϫ (NHMe)] }, 404 {42%,
2
1
1
[
Au(Hdamp-C )Cl(H pydoxmetsc)]Cl (4). [Au(damp-C ,N)-
Cl ] (200 mg, 0.5 mmol) was dissolved in 5 ml of a methanol–
acetone mixture (1:1, v/v) and pyridoxal thiosemicarbazone
127 mg, 0.5 mmol) suspended in a small amount of methanol
was added. After stirring for 1 h the orange–red solution was
decanted from a pale brown solid and reduced in volume by
slow evaporation. Pale yellow crystals of [Au(Hdamp-C )-
Cl(H pydoxmetsc)]Cl ؒMeOH deposited which rapidly
2
2
Ϫ1
2
max
ϩ
ϩ
(
ϩ
ϩ
ϩ
[Au(apMetsc)] }.
1
1
1
[Au(Hdamp-C )(apPhtsc)]Cl (5c). [Au(damp-C ,N)Cl ] (200
2 2
2
2
decomposed when removed from the solvent. Considerable
amounts of an insoluble, finely powdered side-product was
formed, which most probably consists of polymeric, reduced
gold compounds. This prevented the isolation of larger
amounts of (4) in sufficient purity to yield satisfactory
elemental analyses. Samples of the crystalline gold()
mg, 0.5 mmol) was dissolved in 5 ml of a methanol–acetone
mixture (1:1, v/v) and HapPhtsc (135 mg, 0.5 mmol) was added
as a solid in small portions. The thiosemicarbazone dissolved
within a few minutes. After filtration, the orange–red reaction
mixture was overlayered with diethyl ether and kept for crystal-
lization. Yellow crystals deposited on the glass walls which
were filtered off and dried under vacuum. Yield: 95 mg, 28%.
Elemental analysis, Found: C, 41.0; H, 3.5; N, 9.8; S, 4.9; Cl,
10.5; Calcd. for C H N AuSCl : C, 41.2; H, 3.9; N, 10.5; S,
complex for spectroscopic studies were separated manually.
Ϫ1
Yield: ca. 10%. IR (ν /cm ): 3185 (O–H, N–H), 2820–
2
max
ϩ
580 (m, N–H ), 2100–2012 (N᎐C᎐S), 1560–1470 (C᎐C,
23
26
5
2
Ϫ1
N᎐N), 1001 (s, C᎐S), 751 (s, bisubstituted phenyl, damp), 452
4.8; Cl, 10.6%. IR (νmaxϩ/cm ): 3425 (br, Me–OH), 3216, 3179,
᎐
᎐
ϩ
ϩ
(
[
(
Au–C), 326 (s, Au–Cl). FAB -MS: m/z = 620 (35%, M ,
Au(Hdamp)Cl(H pydoxmetsc)] ), 584 (20%, [Au(Hdamp)-
3119 (N–H), 2701 (NH ), 1602 (C᎐N), 1555, 1510 (C᎐C), 455
ϩ
1
(Au–C). H-NMR (dmso-d , ppm): 11.25 (1H, s, NH), 11.12
2
6
ϩ
ϩ
H pydoxmetsc] ).
(1H, s, br, NH ), 8.51–7.2 (13H, m, arom.), 4.54 (2H, m, CH ),
.78 (3H, s, CH ), 2.69 [6H, s, N(CH ) ]. C-NMR (dmso-d6,
2
2
13
2
3
3
2
1
1
[
Au(Hdamp-C )(apHtsc)]Cl (5a). [Au(damp-C ,N)Cl ] (200
ppm): 161.3 (CS), 158.5–120.7 (arom. C), 61.4 (CH ), 42.0
2
2
2
ϩ
mg, 0.5 mmol) was dissolved in 5 ml of a methanol–acetone
mixture (1:1, v/v) and HapHtsc (97 mg, 0.5 mmol) added in 3
ml acetone. The bright yellow solution was stirred at room
temperature for 1 h and overlayered with diethyl ether. Yellow
(CH ), 41.3 (CH ), 14.5 (CH ). FAB -MS: m/z = 600 {65%,
3
3
3
ϩ
ϩ
[M Ϫ H] ], 507 {7%, [M Ϫ H Ϫ (NHPh)] }, 466 {50%,
[Au(apPhtsc)] }.
ϩ
1
1
1
crystals of [Au(Hdamp-C )(apHtsc)]Cl ؒ0.5H O grew within a
[Au(Hdamp-C )(Ptsc)]Cl (6). [Au(damp-C ,N)Cl ] (200 mg,
2 2
2
2
few days. They were separated, washed with cold acetone and
dried. Yield: 225 mg, 75%. Elemental analysis, Found: C, 34.1;
H, 4.0; N, 11.8; S, 5.3; Cl, 11.9; Calcd. for C H N AuSCl :
0.5 mmol) and HPtsc (182 mg, 0.5 mmol) were stirred in 10 ml
of a methanol–acetone mixture (1:1, v/v). After 2 h the bright
yellow solution was filtered and overlayered with the same
17
22
5
Ϫ1
2
1
C, 34.3; H, 3.7; N, 11.8; S, 5.4; Cl, 11.8%. IR (ν /cm ): 3410,
volume of diethyl ether. Yellow crystals of [Au(Hdamp-C )-
max
ϩ
3
277, 3154 (N–H), 2629 (NH ), 1625, 1604 (C᎐C, C᎐N), 488
Au–C). H-NMR (dmso-d , ppm): 11.2 (1H, s, br, NH ), 8.95
2H, s, br, NH ), 8.4–7.4 (8H, m, phenyl), 4.5 (2H, m, CH ), 2.6
6H, s, 2CH ), 2.5 (3H, s, CH ). C-NMR (dmso-d , ppm): 177
(Ptsc)]Cl ؒ1.5MeOH deposited upon standing for a week. More
2
1
ϩ
(
(
(
(
product was obtained by evaporation of the solvent. The com-
plex was washed with cold acetone and dried under vacuum.
Yield: 115 mg, 30%. Elemental analysis, Found: C, 45.4; H, 3.6;
N, 7.4; S, 4.5; Calcd. for C H N AuPSCl : C, 45.6; H, 3.9;
6
2
2
13
3
3
6
CS), 159.8–129.3 (12C, arom. C), 62.2 (CH ), 42.7 (CH ,
2
3
29 30
4
2
ϩ
Ϫ1
ϩ
damp), 42.2 (CH , damp), 14.7 (CH ). FAB -MS: m/z = 524
N, 7.3; S, 4.2%. IR (νmax/cm ): 2773 (NH ), 1623 (s, C᎐N),
3
3
7
42
J. Chem. Soc., Dalton Trans., 2000, 735–744

View Article Online
5 D. L. Klayman, J. P. Scovill, J. F. Bartosevich and C. J. Mason,
1
501 (s, C᎐C), 750 (disubstituted damp-phenyl), 692 (monosub-
᎐
1
J. Med. Chem., 1979, 22, 1367.
stituted phenyl), 434 (Au–C), 340 (Au–P). H-NMR (dmso-d ,
ppm): 8.59 (1H, s, arom.), 8.15 (1H, m, arom.), 7.22–7.82 (17H,
m, arom.), 4.48 (2H, s, CH ), 2.75 (6H, s, 2CH ). C-NMR
6
6
7
C. Shipman, Jr., S. H. Smith, J. C. Drach and D. L. Klayman,
Antiviral Res., 1986, 6, 197.
13
2
3
S. Miertus and P. Filipovic, Eur. J. Med. Chem., 1982, 17 145.
(
(
(
dmso-d , ppm): 172 (CS), 150.9, 135.8–127.7 (arom. C), 62.2
6
31
8 L. A. Saryan, K. Mailer, C. Krishnamurti, W. Atholine and
D. H. Petering, Biochem. Pharmacol., 1981, 30, 1595.
9 A. C. Sartorelli, K. C. Agrawal, A. S. Tsiftsoglou and E. C. Moore,
Adv. Enzyme Regul., 1977, 15, 117.
0 L. P. Scovill, D. L. Klayman, C. Lambrose, G. E. Childs and
J. D. Notsch, J. Med. Chem., 1984, 27, 87.
1 D. X. West, C. S. Carlson, C. P. Galloway, A. E. Liberta and
C. R. Daniels, Transition Met. Chem., 1990, 15, 43 and refs therein.
2 B. S. Garg, M. R. P. Kurup, S. K. Jain and Y. K. Bhoon, Transition
Met. Chem., 1988, 13, 247 and refs. therein.
CH ), 42.9 (CH , damp). P-NMR (dmso-d , ppm): ϩ29.2
2
3
6
ϩ
ϩ
proligand: Ϫ13.2). FAB -MS: m/z = 694 {28%, [M Ϫ H ]},
ϩ
5
59 {9%, [Au(Ptsc)] }.
1
1
1
1
X-Ray structure determinations
The intensities for the X-ray determinations of (3a), (3c), (5c),
(
6) and H pydoxmetscؒHCl were collected on an automated
2
single crystal diffractometer of the CAD4 type (Enraf-Nonius,
Delft) with Mo-Kα radiation (Au complexes) or Cu-Kα radi-
ation (H pydoxmetscؒHCl). The data set for (4) was obtained
on a DIP 2000 Image Plate instrument (Enraf-Nonius) using
standard procedures.
The programs HELENA and DENZO were applied for
data reduction. The structures were solved by Patterson syn-
3 D. X. West, A. E. Liberta, S. B. Padhyé, R. C. Chikate, P. B.
Sonawane, A. S. Kumbhar and R. G. Yerande, Coord. Chem. Rev.,
1993, 123, 49 and refs. therein.
2
1
1
1
4 A. Castineiras, D. X. West, H. Gebremedhim and T. J. Romack,
Inorg. Chim. Acta, 1994, 216, 229.
5 D. X. West, H. Gebremedhim, R. J. Butcher and J. P. Jasinski,
Transition Met. Chem., 1995, 20, 84.
6 D. Kovala-Demertzi, A. Domopolous, M. Demertzis, C. P.
Raptopoulou and A. Terzis, Polyhedron, 1994, 13, 1917.
50
51
52
theses using SHELXS97. Subsequent Fourier-difference map
analyses yielded the positions of the non-hydrogen atoms.
17 D. F. de Sousa, C. A. L. Filqueiras, A. Abras, S. S. Al-Juaid, P. B.
53
Hitchcock and J. F. Nixon, Inorg. Chim. Acta, 1994, 218, 139.
Refinement was performed using SHELXL97. The positions
of all hydrogen atoms bonded to N or O and possibly contribut-
ing to hydrogen bonds were derived from the final Fourier map
and fully refined. All other H atoms were calculated for ideal-
ized positions and treated with the ‘riding model’ option of
SHELXL97. Crystal data and more details of the data collec-
tions and refinements are contained in Table 7.
1
1
2
8 J. S. Casas, A. Castineiras, A. Sanchez, J. Sordo, A. Vazquez-Lopez,
M. C. Rodriguez-Arguelles and U. Russo, Inorg. Chim. Acta, 1994,
2
21, 61.
9 E. Bermejo, A. Castineiras, R. Domingues, R. Carballo, C.
Maichle-Mössmer, J. Strähle and D. X. West, Z. Anorg. Allg. Chem.,
1999, 625, 961 and refs. therein.
0 S. Abram, C. Maichle-Mössmer and U. Abram, Polyhedron, 1998,
1
7, 131.
CCDC reference number 186/1796.
2
1 K. Ortner and U. Abram, Inorg. Chem. Commun., 1998, 1, 251.
2 J. Vicente, M. T. Chicote and M. D. Bermudez, J. Organomet.
Chem., 1984, 268, 191.
See http://www.rsc.org/suppdata/dt/a9/a908712e/ for crystal-
lographic files in .cif format.
2
2
3 J. Mack, K. Ortner, R. V. Parish and U. Abram, Z. Anorg. Allg.
Chem., 1997, 623, 873.
4 J. Vicente, M. T. Chicote, M. D. Bermudez, P. G. Jones and
G. M. Sheldrick, J. Chem. Res., 1985, 72, 954.
In vitro chemosensitivity assay
2
The antiproliferative activity of the gold complexes was tested
on exponentially dividing human MCF-7 breast cancer cells
according to a standardized microtitre assay. The cells were
seeded onto 96-well microtitre plates as a suspension with
25 J. Vicente, M. T. Chicote, M. D. Bermudez and M. J. Sanchez-
54
Santano, J. Organomet. Chem., 1986, 310, 401.
2
6 J. Vicente, M. T. Chicote, M. D. Bermudez, P. G. Jones, C. Fittschen
and G. M. Sheldrick, J. Chem. Soc., Dalton Trans., 1986, 2361.
7 J. Vicente, M. T. Chicote, M. D. Bermudez, M. J. Sanchez-Santano
and P. G. Jones, J. Organomet. Chem., 1988, 354, 381.
5
Ϫ1
1
7 × 10 cells ml . After a 72 h preincubation period, this
2
medium was exchanged for a new one containing the test com-
pound at a concentration of 5 µM. Cell growth was stopped
with glutardialdehyde after different incubation periods (max.
incubation time: 216 h). The cells were then stored at 4 ЊC under
PBS (phosphate buffered saline). Cell biomass was determined
by a crystal violet staining technique as described in ref. 55
combined with UV detection. Cytocidal effect can be expressed
as τ(%) = [(T* Ϫ C )/C ] × 100. C represents the mean optical
28 J. Vicente, M. D. Bermudez, J. Escribano, M. P. Carrillo and
P. G. Jones, J. Chem. Soc., Dalton Trans., 1990, 3083.
2
9 R. V. Parish, J. Mack, L. Hargreaves, J. P. Wright, R. G. Buckley,
A. M. Elsome, S. P. Fricker and B. R. C. Theobald, J. Chem. Soc.,
Dalton Trans., 1996, 69.
3
0 R. V. Parish, B. P. Howe, J. P. Wright, J. Mack, R. G. Pritchard,
R. G. Buckley, A. M. Elsome and S. P. Fricker, Inorg. Chem., 1996,
35, 1659.
0
0
0
density of the cell extract immediately before treatment and T*
the mean optical density of the cell extract after different incu-
bation periods.
31 U. Abram, J. Mack, K. Ortner and M. Müller, J. Chem. Soc., Dalton
Trans., 1998, 1011.
3
3
2 K. Ortner and U. Abram, Polyhedron, 1998, 18, 749.
3 L. Zsolnai and G. Huttner, ZORTEP, a program for the ellipsoidal
representation of crystal structures, University of Heidelberg,
1
995.
Acknowledgements
3
3
3
4 M. F. Davidson, D. M. Grove, G. van Koten and A. L. Spek,
J. Chem. Soc., Chem. Commun., 1989, 1562.
We thank Degussa AG for generously providing us with gold
starting materials and acknowledge grants from the Deutsche
Forschungsgemeinschaft and the Fonds der Chemischen
Industrie. We also thank Professor J. Strähle (Tübingen) for his
kind hospitality and the opportunity to collect the CAD4 X-ray
data sets and Dr Yifan Zheng for collection of the data set for
5 F. Basuli, S.-M. Peng and S. Bhattacharya, Inorg. Chem., 1997, 36,
5
645.
6 M. Zimmer, G. Schulte, X.-L. Luo and R. H. Crabtree, Angew.
Chem., Int. Ed. Engl., 1991, 30, 193.
37 J. S. Casas, A. Sanchez, J. Sordo, A. Vazquez-Lopez, E. E.
Castellano, J. Zukerman-Schpector, M. C. Rodriguez-Argüelles and
U. Russo, Inorg. Chim. Acta, 1994, 216, 169.
8 M. B. Ferrari Belicchi, G. G. Fava, C. Pelizzi, P. Tarasconi and
G. Tosi, J. Chem. Soc., Dalton Trans., 1987, 227.
9 M. B. Ferrari Belicchi, G. G. Fava, C. Pelizzi, G. Pelosi and
P. Tarasconi, Inorg. Chim. Acta, 1998, 269, 297.
(
4) at the Crystallography Laboratory of the University of
3
3
4
Oxford.
References
0 J. S. Casas, E. E. Castellano, M. C. Rodríguez-Argüelles, A.
Sánchez, J. Sordo and J. Zukerman-Schpector, Inorg. Chim. Acta,
1997, 260, 183.
1
D. X. West, S. B. Padhyé and P. B. Sonawane, Structure and Bonding,
vol. 76, Complex Chemistry, Springer, Berlin, 1991.
2
3
S. Padhyé and G. B. Kauffman, Coord. Chem. Rev., 1985, 63, 127.
A. S. Dobek, D. L. Klayman, E. T. Dickson, J. P. Scovill and
C. N. Oster, Arzneim.-Forsch., 1983, 33, 1583.
D. L. Klayman, J. P. Scovill, C. J. Mason, J. F. Bartosevich, J. Bruce
and A. Lin, Arzneim.-Forsch., 1983, 33, 909.
41 M. B. Ferrari Belicchi, G. G. Fava, M. Lanfranchi, C. Pelizzi and
P. Tarasconi, J. Chem. Soc., Dalton Trans., 1991, 1951.
42 M. B. Ferrari Belicchi, G. G. Fava, G. Pelosi, M. C. Rodríguez-
Argüelles and P. Tarasconi, J. Chem. Soc., Dalton Trans., 1995,
3035.
4
J. Chem. Soc., Dalton Trans., 2000, 735–744
743

View Article Online
50 A. Spek, PLATON and HELENA, programs for data reduction and
handling of crystal structure data, University of Utrecht, 1998.
51 Z. Otwinowski and W. Minor, Processing of X-ray diffraction
data collected in oscillation mode. Methods in Enzymology, vol. 276,
ed. C. W. Carter and R. M. Sweet, Academic Press, New York, 1996.
52 G. M. Sheldrick, SHELXS97, a program for the solution of crystal
structures, University of Göttingen, 1997.
53 G. M. Sheldrick, SHELXL97, a program for the refinement of
crystal structures, University of Göttingen, 1997.
54 R. Gust, R. Keilitz, R. Krauser, K. Schmidt and B. Schnur, Arch.
Pharm. Med. Chem., 1999, 332, 261.
4
3 M. B. Ferrari Belicchi, G. G. Fava, C. Pelizzi and P. Tarasconi,
J. Chem. Soc., Dalton Trans., 1992, 2153.
4 M. B. Ferrari Belicchi, G. F. Gasparri, E. Leporati, C. Pelizzi,
P. Tarasconi and G. Tosi, J. Chem. Soc., Dalton Trans., 1986,
4
2
455.
4
4
5 K. Brandenburg, DIAMOND, Informationssystem für Kristall-
strukturen, Bonn, 1997.
6 M. A. Ali, K. K. Dey, M. Nazimuddin, F. E. Smith, R. J. Butcher,
J. P. Jasinski and J. M. Jasinski, Polyhedron, 1996, 15, 3331 and refs.
therein.
7 J. García-Tojal, M. Karmele Urtiaga, R. Cortés, L. Lezama,
M. I. Arriortua and T. Rojo, J. Chem. Soc., Dalton Trans., 1994,
4
55 G. Bernhard, H. Reile, H. Birnböck, T. Spruß and H.
Schönenberger, J. Cancer Res. Clin. Oncol., 1990, 187, 262.
2
233.
48 V. M. Leovac, B. Ribár, G. Argay, A. Kálmán and I. Brceski,
J. Coord. Chem., 1996, 39, 11.
49 K. Sommer, R. Gust, K. Ortner and U. Abram, unpublished results.
Paper a908712e
7
44
J. Chem. Soc., Dalton Trans., 2000, 735–744