Pyrrole thioamide complexes of the d8 metals platinum(II), palladium(II) and gold(III)

Article abstract of DOI:10.1016/j.ica.2019.119282

Reactions of the cycloaurated gold(III) complexes [AuCl₂(2-benzylpyridyl)] and [AuCl₂(C₆H₄CH₂NMe₂)] with a set of pyrrole-2-thioamide ligands, containing various substituents on the pyrrole ring, gave a series of new gold(III) pyrrole thioamide complexes. X-ray crystal structures on two complexes indicate that the pyrrole thioamide ligand is coordinated through the deprotonated pyrrole nitrogen, as well as the sulfur atom of the deprotonated thioamide group, forming five-membered chelate ring complexes. In both complexes, the two highest trans-influence donor atoms (C and S) are mutually cis. Related sets of platinum(II) and palladium(II) pyrrole thioamide complexes were similarly prepared by reactions of cis-[PtCl₂(PPh₃)₂] and [PdCl₂(dppe)] (dppe = Ph₂PCH₂CH₂PPh₂)] respectively. The complexes were characterised by NMR and IR spectroscopies, and ESI mass spectrometry. A preliminary investigation of the activity of a selection of compounds towards A549 (adenocarcinomic human alveolar basal epithelial) cells was also carried out.

Full text of DOI:10.1016/j.ica.2019.119282

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Research paper
Pyrrole thioamide complexes of the d8 metals platinum(II), palladium(II) and
gold(III)
Haiming Tang, Graham C. Saunders, Xiaochuan Ma, William Henderson
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S0020-1693(19)31348-9
https://doi.org/10.1016/j.ica.2019.119282
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Please cite this article as: H. Tang, G.C. Saunders, X. Ma, W. Henderson, Pyrrole thioamide complexes of the d8
metals platinum(II), palladium(II) and gold(III), Inorganica Chimica Acta (2019), doi: https://doi.org/10.1016/j.ica.
2019.119282
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Correspondence to:
Professor W. Henderson,
Chemistry,
School of Science,
University of Waikato,
Private Bag 3105,
Hamilton 3240,
New Zealand
e-mail w.henderson@waikato.ac.nz
Pyrrole thioamide complexes of the d8 metals platinum(II),
palladium(II) and gold(III)
Haiming Tang,a Graham C. Saunders,a Xiaochuan Mab and William Henderson*,a
a Chemistry, School of Science, University of Waikato, Private Bag 3105, Hamilton, New
Zealand 3216
b State Key Laboratory of Radiation Medicine and Protection, School for Radiological and
Interdisciplinary Sciences (RAD-X) & Collaborative Innovation Center of Radiation
Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123,
China
Received:
1

ABSTRACT
Reactions of the cycloaurated gold(III) complexes [AuCl2(2-benzylpyridyl)] and
[AuCl2(C6H4CH2NMe2)] with a set of pyrrole-2-thioamide ligands, containing various
substituents on the pyrrole ring, gave a series of new gold(III) pyrrole thioamide
complexes. X-ray crystal structures on two complexes indicate that the pyrrole thioamide
ligand is coordinated through the deprotonated pyrrole nitrogen, as well as the sulfur
atom of the deprotonated thioamide group, forming five-membered chelate ring
complexes. In both complexes, the two highest trans-influence donor atoms (C and S) are
mutually cis. Related sets of platinum(II) and palladium(II) pyrrole thioamide complexes
were similarly prepared by reactions of cis-[PtCl2(PPh3)2] and [PdCl2(dppe)] (dppe =
Ph2PCH2CH2PPh2)] respectively. The complexes were characterised by NMR and IR
spectroscopies, and ESI mass spectrometry. A preliminary investigation of the activity of
a selection of compounds towards A549 (adenocarcinomic human alveolar basal
epithelial) cells was also carried out.
Keywords: Pyrrole; Thioamide; X-ray structures; Platinum; Palladium; Gold
2

1. Introduction
Sulfur-nitrogen donor ligands are a highly attractive ligand class, because of the
combination of hard and soft donor atoms, potentially allowing coordination – in a diverse
range of binding modes – to a wide range of metal centres. For example, the coordination
chemistry of N-heterocyclic thionate ligands has been summarised in two reviews by
Raper.[1,2] Pyridine-derived thioamide ligands have attracted attention, because of the built-
in ancillary ligand properties of the pyridine group. A wide range of synthesised and
characterised pyridyl thioamide complexes include those of ruthenium and
osmium,[3,4,5,6,7,8,9] gold,[10,11] palladium,[12,13,14] copper and nickel.[15] While a
common theme in many of the recent studies concerns biological activity, especially of
ruthenium and osmium arene derivatives,[6-9] pyridine thioamide complexes of palladium
[16] and ruthenium(II) [17,18,19] have also been studied for their catalytic potential.
We subsequently wished to investigate thioamide ligands derived from other nitrogen-
containing heterocycles, and were interested in the possibility of utilising the pyrrole group,
where the heterocyclic NH could potentially be deprotonated, furnishing a dianionic ligand.
To the best of our knowledge, there are no reports on gold and platinum group complexes
containing pyrrole-derived thioamide ligands, though deprotonated pyrrole complexes of
gold,[20] palladium [21,22,23,24] and platinum [24,25] are all well established. In this
contribution, we report the synthesis and characterisation of a series of complexes of this
type, together with a preliminary study on their biological activity.
2. Results and discussion
2.1. Synthesis and characterisation of pyrrole thioamide ligands
3

Using the methodology by Bullock and Abraham (Scheme 1),[26] three compounds
(1a, 1b and 1c) were prepared by refluxing (solvent-free) the respective pyrrole with an
excess of phenyl isothiocyanate. After work-up and isolation, compounds 1b and 1c were
obtained by recrystallisation from ether/heptane, which is in line with the literature
procedure. However, compound 1a was isolated in a much lower yield, because of the much
longer reaction time required, and the larger number of steps involved in the workup.
The analogous 4-nitrophenyl compounds 1d-1f were synthesised in an analogous
manner to 1a-1c, using an excess of 4-nitrophenyl isothiocyanate and the pyrrole. The
reaction was stirred until TLC analysis (ethyl acetate: dichloromethane: hexane = 1:20:20)
indicated the complete consumption of the starting pyrrole. Compound 1d was purified by
crystallisation from heptane, but compounds 1e and 1f were both purified by chromatography
(silica gel; eluting with ethyl acetate: dichloromethane: petroleum ether = 1:3:5).
The identity of 1f was unambiguously confirmed by the determination of its single-
crystal X-ray structure. The ORTEP diagram and atom numbering scheme are shown in
Figure 1, and selected bond lengths and angles are summarised in Table 1. The pyrrole N-C
distances N(1)-C(4) and N(1)-C(1) are different, 1.380(2) Å and 1.355(2) Å respectively, as a
result of different substituents (electron-withdrawing or electron-donating) on the pyrrole
ring. The C=S bond length of 1f is 1.6775(17) Å, which is longer than the pyrrole thioamide
N,N’-diphenyl-1H-pyrrole-2,5-dithiocarboxamide [1.664(3) Å].[27] The three bond angles
around C(9) are 121.89(13)° for S(1)-C(9)-C(4), 124.10(13)° for S(1)-C(9)-N(2) and
114.01(14)° for C(4)-C(9)-N(2). Interestingly, except for the ethyl group, all the atoms are
almost coplanar. The molecule forms a dimer in the solid state, Figure 2, via interactions of
the thiocarbonyl group and the pyrrole NH and CH3 substituent hydrogens.
1
All of the pyrrole thioamide ligands show a multiplet in their H NMR spectra in the
range δ 7.24–8.66 ppm for the phenyl protons, and triplets around δ 1.07 ppm and quartets δ
4

2.40 ppm for the ethyl protons in the compounds 1c and 1f. In addition, ligands 1a-1f show
two singlet peaks in the region 9.42–9.78 and 8.53–8.76 ppm in their 1H NMR spectra, which
are assigned to the pyrrole NH and CSNH protons respectively. This was confirmed by a
COSY NMR spectrum of 1a, which displays couplings between the pyrrole NH proton and
pyrrole CH protons. In comparison to 1a, for compound 1b, the pyrrole NH and CSNH
resonances are shifted upfield at 9.50 and 8.54 ppm, presumably due to the electron-donating
effect of the methyl groups on the pyrrole ring.
All compounds were characterised by ESI mass spectrometry in CH3OH and gave
intense [M+H]+ ions at a low capillary exit voltage (80 V) at m/z values that agreed well with
predicted values. The exception was ligand 1d, which gave only a weak [M+Na]+ ion.
Furthermore, the compounds were also investigated in negative ion mode. The expected [M-
H]- ion of compounds 1a-1c and 1e-1f was observed at a low capillary exit voltage.
In the IR spectra of the ligands 1a-1f, absorption bands at 703–796 and 3285–3383
cm-1 are assigned to thioamide group νC=S vibrations and the pyrrole group νN-H, respectively.
Additionally, in the cases of compounds 1d-1f, absorption bands due to the asymmetric νNO
2
and symmetric νNO are observed at 1505-1512 and 1333-1339 cm-1 respectively.[28]
2
2.2. Synthesis of platinum(II) and gold(III) pyrrole thioamide complexes
Reactions of the cycloaurated gold(III) complex [AuCl2(2-benzylpyridyl)] with
equimolar amounts of the pyrrole-derived thioamide ligands 1a-1f in the presence of
trimethylamine in refluxing methanol gave, after cooling and filtration, the complexes 2a-2f
in moderate to good yields (57-88%), Scheme 2. These complexes were found to show good
solubility in chloroform and dichloromethane, but were poorly soluble in methanol. In a
similar fashion, the reaction of [AuCl2(C6H4CH2NMe2)] with pyrrole-derived thioamide
ligands 1a and 1d-1f in a 1:1 molar ratio in the presence of trimethylamine yielded
5

complexes 3a and 3d-3f (Scheme 2). Complexes 3d to 3f were obtained in significantly
higher yield than compound 3a. In addition, 3a has good solubility in methanol, chloroform
and dichloromethane, but complexes 3d-3f are only soluble in chloroform and
dichloromethane.
A series of complexes containing the Pt(PPh3)2 or Pd(dppe) (dppe =
Ph2PCH2CH2PPh2) moieties were also synthesised by analogous procedures, starting from
cis-[PtCl2(PPh3)2] or [PdCl2(dppe)] respectively.
2.3. X-ray crystal structure determinations of pyrrole thioamide complexes
To confirm the binding mode of the pyrrole thioamide ligand to the metal centre in
these d8 complexes, X-ray crystal structure determinations were carried out on the gold
complexes 2b and 3d. The molecular structures of 2b and 3d are shown in Figures 3 and 4
respectively, and selected bond lengths and angles are given in Tables 2 and 3.
In both complexes the gold atom is in an approximately square-planar coordination
environment, with τ4 parameters of 0.118 (2b) and 0.097 (3d). The τ4 parameter can be used
to provide a coordination geometry metric for four-coordinate transition metal complexes
[29] compared to theoretical values of 0 for a perfect square plane to 1 for a perfect
tetrahedron. The gold atom is coordinated with the nitrogen of the deprotonated pyrrole
group, the sulfur atom of the thioamide, and the σ-C and N of the cycloaurated ligand, with
the pyrrole-derived thioamide ligand forming a five-membered chelate ring. In both
structures 2b and 3d, the S and C donor atoms show antisymbiosis,[30] with the two highest
trans-influence donor atoms (C and S) mutually cis. This is similar to other closely related
cycloaurated gold(III) complexes [31] containing S,N [32,33,34,35] or S,O [36] donor
ligands.
6

The C-S bond lengths of the complexes are relatively long [2b 1.803(6); 3d 1.789(5)
Å], which represent a C-S single bond [37,38,39,40,41] and contrasts the C=S bond distance
of 1f [1.6775(17) Å]. Additionally, the exocyclic C(9)-N(2) distances [2b 1.284(8); 3d
1.280(6) Å] are as expected for a C-N double bond (1.27-1.29 Å) [42,43] and are
significantly shorter than the corresponding C-N bond distance in 1f [1.362(2) Å]. Together,
these bond length data indicate that the pyrrole thioamide ligand is coordinated in the
deprotonated thiol(ate) tautomeric form. In both structures, the exocyclic imine phenyl
substituent is approximately perpendicular to the metallacyclic ring, presumably to minimise
steric interaction between the ortho phenyl hydrogen and the sulfur atom.
In 2b, the interplanar angle between the N(1)-Au(1)-S(1) and C(4)-C(9)-S(1) planes is
13.69°, indicating that the five-membered Au(1)-N(1)-C(4)-C(9)-S(1) ring is slightly
puckered. The corresponding angle in 3d is smaller (10.40°).
The benzylpyridyl ligand of complex 2b has the typical boat conformation, as
observed in other structural determinations of complexes containing this moiety. An example
of this is the starting complex [AuCl2(2-benzylpyridyl)].[44] In 2b, this puckering also
minimises steric interaction of the benzylpyridyl ligand with the methyl substituent adjacent
to the pyrrole nitrogen, and such steric interaction may also be responsible for the slightly
greater deviation from square planarity of complex 2b. Complex 2b also crystallises with
dichloromethane in the lattice, which participates in a weak C-H…S intermolecular
interaction.
2.4. Spectroscopic characterisation of pyrrole thioamide complexes
1
In their H NMR spectra the singlet peaks corresponding to –NH protons of the free
ligands disappear upon complex formation. Interestingly, compared to the pyrrole-derived
thioamide ligands, the 1H NMR spectra of the gold complexes 2 and 3 show the signals of the
7

pyrrole CH protons shifted downfield, whereas the same signals were shifted upfield in the
platinum complexes 4 and palladium complexes 5. This effect is most likely due to the high
electronegativity of gold [45,46], compared to the lower electronegativity of platinum and
palladium, which are coordinated by electron-donating phosphine ligands which provide a
shielding effect on neighbouring protons.
As expected, the 31P{1H} NMR spectrum of the triphenylphosphine platinum complex
4a shows an AB pattern for two inequivalent PPh3 ligands, with two resonances at δ 19.5 and
1
2
13.5. The J(PtP) coupling constants are 2843 and 3178 Hz, respectively, while the J(PP)
1
coupling is 24 Hz. In comparison, the analogous compound 4d has similar J(PtP) coupling
constants of 2893 and 3167 Hz. The difference in coupling constants is consistent with strong
thiolate and weaker pyrrole nitrogen donors. In contrast, the coupling constants of 4e (3081
and 3094 Hz) and 4f (3084 and 3092 Hz) are fairly similar to each other, but significantly
different to 4a and 4d. The more balanced coupling constants in 4e and 4f may be due to the
presence of alkyl substituents on the pyrolle ligands in these complexes, increasing their -
31
donor strength. The palladium complexes 5 also showed two signals in their P{1H} NMR
spectra with coupling between the two phosphorus atoms. The dppe palladium complexes
show the expected substantial downfield shift of the phosphorus atoms, which is well-known
to be an indicator of phosphine chelation in dppe complexes.[47]
In the IR spectra, the free ligand νC=S and pyrrole νN-H absorption bands are lost upon
coordination to the metal centre. The νC-S band of the suite of complexes 2, 3, 4 and 5
generally shifts to medium energy in the region 1279–1393 cm-1. The symmetric and
asymmetric νNO modes are observed at 1298-1396 (νsNO2) cm-1 and 1464-1586 (νasNO ) cm-1
2
2
in those complexes containing the 4-nitrophenyl substituent.
The electrospray ionisation (ESI) mass spectra of the palladium complexes 5 and the
gold complexes 2 and 3 all give the expected intense [M+H]+ ions at a relatively high
8

capillary exit voltage (160 V), without any observed fragmentation. This is consistent with
the presence of two metallacyclic rings that are relatively resilient towards fragmentation. In
contrast, the mass spectra of platinum complexes 4 give, in addition to an intense [M+H]+ ion
at the expected m/z values, the additional fragment ion of [M-PPh3+H]+, at a capillary exit
voltage of 160 V.
2.5. Biological activity
The toxicities of compounds 2c-f, 3a, 3d, 3e, 4a, 4d-f, 5d and 5f were evaluated
toward A549 cells (adenocarcinomic human alveolar basal epithelial cells) by MTT assay.
Due to their poor solubility in water, 2a, 2b, 3f, 5a and 5e were not tested. Compared to a
control, where the cells were allowed to grow without any treatment, it was found that
compounds 2d, 3d and 4a caused a significant reduction in A549 cell viability at 100 μM
concentration. Therefore, compounds 2d, 3d and 4a were selected for further investigation,
and evaluated at a range of concentrations (3-100 μM). Inspection of the data given in Figure
4 reveals that treatment with 4a at 25 μM seems to have moderate toxicity on A549 cells,
while the complexes 2d and 3b show moderate toxicity at concentrations >50 μM. The
antiproliferative activities of the ligands 1a-f were also studied against the same cell line, but
they showed no obvious cytotoxicity.
3. Conclusions
In this work, a range of novel gold, platinum and palladium complexes have been
synthesised using pyrrole-thioamide ligands, and were characterised by NMR, MS and FTIR.
X-ray structure determinations of two gold complexes confirms that the gold atom is bound
to the ligand via the nitrogen of the deprotonated pyrrole group and the sulfur of the
9

deprotonated thioamide. We are currently investigating other precious metal complexes of
these ligands and results will be reported in due course.
4. Experimental
4.1. Materials and instrumentation
The following materials were used as supplied from Sigma Aldrich: pyrrole, phenyl
isothiocyanate, 4-nitrophenyl isothiocyanate. 2,4-Dimethylpyrrole and 3-ethyl-2,4-
dimethylpyrrole were used as supplied from Tokyo Chemical Industries (TCI). Aqueous
trimethylamine solution (BDH) was used as supplied. All solvents were AR grade, and
petroleum spirits refers to the fraction of boiling range 30-60 °C. The complexes [AuCl2(2-
benzylpyridyl)] [48] and [AuCl2(C6H4CH2NMe2)] [49] were prepared by the literature
procedures. The complexes cis-[PtCl2(PPh3)2] and [PdCl2(dppe)] were prepared by ligand
substitution of the [MCl2(cod)] complex (M = Pd [50], or M = Pt [51], cod =1,5-cyclo-
octadiene) with the molar amount of phosphine in CH2Cl2, and the product precipitated with
petroleum spirits.
All reactions were carried out without any attempts to exclude air or moisture.
Elemental microanalyses were carried out by the Campbell Microanalytical Laboratory,
University of Otago, Dunedin, New Zealand. ESI mass spectra were recorded in methanol
solution on a Bruker MicrOTOF instrument that was calibrated using a solution of sodium
formate; a capillary exit voltage in the range 60-180 V was used; m/z values were calculated
using ChemBioDraw Ultra 12.0. NMR spectra were recorded in CDCl3 on a Bruker AVIII
400 instrument using Topspin 3.0 software; signals were referenced relative to residual non-
deuterated solvent peaks or external H3PO4 (for 31P NMR spectra). Coupling constants (J) are
reported in Hz. Infrared spectra were recorded as KBr disks on a PerkinElmer Spectrum 100
10

FT-IR spectrophotometer. Melting points were determined on a Reichert-Jung hot-stage
apparatus and are uncorrected.
4.2. Synthesis of N-phenyl-1H-pyrrole-2-carbothioamide 1a
This compound has been synthesised previously,[26] using a slightly different
procedure, and characterised by melting point and elemental analysis. A mixture of pyrrole (5
g, 0.075 mol) and phenyl isothiocyanate (11 g, 0.082 mol) was heated to reflux for 19 h.
When the reaction mixture became very viscous, cold heptane (20 mL) was added; the
product solidified when scratched with a glass rod. The black solid was dissolved in diethyl
ether (100 mL) and the insoluble solid was removed by filtration. Heptane (100 mL) was
added to the diethyl ether extract, resulting in precipitation of a black oil. Decanting the
solution from the oil, and filtering through filter paper gave an orange solution. Additional
heptane (100 mL) was added to the residue. A yellow solid (720 mg, 5%) was precipitated,
filtered and washed with heptane. 1H NMR: δ (ppm) 9.89 (s, 1H), 8.78 (s, 1H), 7.73 (d, J 7.6
Hz, 2H), 7.46 (m, 2H), 7.31 (m, 1H), 7.08 (m, 1H), 6.67 (s, 1H), 6.36 (m, 1H). ESI MS:
positive-ion [M+H]+, m/z 203.071, calculated m/z 203.056; [M+Na]+, m/z 225.054, calculated
m/z 225.056; negative-ion [M-H]-, m/z 201.084, calculated m/z 201.056. IR: 703 (νC=S), 3341
(νN-H) cm-1.
4.3. Synthesis of 1b and 1c
Compounds 1b and 1c were prepared in the same manner as 1a; these have been synthesised
and characterised by melting point and elemental analysis previously.[26]
3,5-Dimethyl-N-phenyl-1H-pyrrole-2-carbothioamide 1b
11

Yield 35%. 1H NMR: δ (ppm) 9.95 (s, 1H), 8.56 (s, 1H), 7.71 (d, J 8.4, 2H), 7.44 (m, 2H),
7.30 (m, 1H), 5.59 (d, J 2.8, 1H), 2.48 (s, 3H), 2.30 (s, 3H). ESI MS: positive-ion [M+H]+,
m/z 231.088, calculated m/z 231.088; negative-ion [M-H]-, m/z 229.014, calculated m/z
229.088. IR: 749 (νC=S), 3349 (νN-H) cm-1.
4-Ethyl-3,5-dimethyl-N-phenyl-1H-pyrrole-2-carbothioamide 1c
1
Yield 38%. H NMR: δ (ppm) 9.94 (s, 1H), 8.53 (s, 1H), 7.68 (d, J 8.0, 2H), 7.41 (m, 2H),
7.23 (m, 1H), 2.39 (q, 5H), 2.24 (s, 3H), 1.07 (t, 3H). ESI MS: positive-ion [M+H]+, m/z
259.156, calculated m/z 259.119; negative-ion [M-H]-, m/z 257.045, calculated m/z 257.119.
IR: 750 (νC=S), 3285 (νN-H) cm-1.
4.4. Synthesis of N-(4-nitrophenyl)-1H-pyrrole-2-carbothioamide 1d
A mixture of 4-nitrophenyl isothiocyanate (400 mg, 2.22 mmol) and pyrrole (950 mg,
14.16 mmol) was refluxed with stirring for 5 h until TLC analysis (eluting with ethyl
acetate/dichloromethane/n-hexane 1:20:20) indicated the complete consumption of 4-
nitrophenyl isothiocyanate. A dark yellow suspension formed during the course of addition of
cold heptane (5 mL). The precipitate (385 mg, 70%) was filtered and washed with heptane (3
mL). M.p. 130-136 °C. Found: C, 53.71; H, 3.67; N, 17.08%. C11H9N3O2S requires C, 53.43;
H, 3.67; N, 16.99%. 1H NMR: δ (ppm) 9.75 (s, 1H), 8.87 (s, 1H), 8.30 (d, J 9.2, 2H), 8.05 (d,
J 9.2, 2H), 7.13 (m, 1H), 6.76 (m, 1H), 6.38 (m, 1H). ESI MS: positive-ion [M+Na]+, m/z
270.036, calculated m/z 270.042; negative-ion [M-H]-, m/z 245.982, calculated m/z 246.042.
IR: 760 (νC=S), 3383 (νN-H), 1505 (νasNO ), 1339 (νsNO2) cm-1.
2
4.5. Synthesis of 3,5-dimethyl-N-(4-nitrophenyl)-1H-pyrrole-2-carbothioamide 1e
12

A mixture of 4-nitrophenyl isothiocyanate (250 mg, 1.39 mmol) and 2,4-dimethyl-
1H-pyrrole (792 mg, 8.33 mmol) was refluxed with stirring for 5 h until TLC analysis
(eluting with ethyl acetate/dichloromethane/n-hexane 1:20:20) indicated the complete
consumption of 4-nitrophenyl isothiocyanate. The mixture was evaporated to afford the crude
product which was chromatographed on silica gel (ethyl acetate/dichloromethane/petroleum
ether 1:3:5) to give 1e (212 mg, 56%) as a brown solid. M.p. 170-176 °C. Found: C, 57.00;
1
H, 4.84; N, 15.10%. C13H13N3O2S requires C, 56.71; H, 4.76; N, 15.26%. H NMR (CDCl3):
δ (ppm) 9.50 (s, 1H), 8.70 (s, 1H), 8.30 (d, J 9.2, 2H), 8.04 (d, J 9.2, 2H), 5.96 (d, J 2.8, 1H),
2.51 (s, 3H), 2.32 (s, 3H). ESI MS: positive-ion [M+H]+, m/z 276.088, calculated m/z
276.073; negative-ion [M-H]-, m/z 274.010, calculated m/z 274.073. IR: 796 (νC=S), 3321 (νN-
H), 1512 (νasNO ), 1333 (νsNO2) cm-1.
2
4.6. Synthesis of 4-ethyl-3,5-dimethyl-N-(4-nitrophenyl)-1H-pyrrole-2-carbothioamide 1f
A mixture of 4-nitrophenyl isothiocyanate (200 mg, 1.11 mmol) and 3-ethyl-2,4-
dimethyl-1H-pyrrole (547 mg, 4.44 mmol) was refluxed with stirring for 2 h until TLC
analysis (eluting with ethyl acetate/dichloromethane/n-hexane 1:20:20) indicated the
complete consumption of 4-nitrophenyl isothiocyanate. Pentane (5 mL) was added, resulting
in precipitation of a dark brown solid. The crude product was filtered and washed with
pentane (3 mL). The solid was chromatographed on silica gel (ethyl
acetate/dichloromethane/petroleum sprits 1:3:5) to give 1f (150 mg, 45%) as a black
crystalline solid. M.p. 188-190 °C. Found: C, 59.36; H, 5.73; N, 13.71%. C15H17N3O2S
requires C, 59.38; H, 5.65; N, 13.85%. 1H NMR: δ (ppm) 9.42 (s, 1H), 8.66 (s, 1H), 8.27 (d, J
9.2, 2H), 8.00 (d, J 9.2, 2H), 2.42 (q, 5H), 2.26 (s, 3H), 1.07 (t, 3H). ESI MS: positive-ion
[M+H]+, m/z 304.272, calculated m/z 304.104; negative-ion [M-H]-, m/z 302.035, calculated
m/z 302.104. IR: 747 (νC=S), 3325 (νN-H), 1510 (νasNO ), 1333 (νsNO2) cm-1.
2
13

4.7. Synthesis of 2a
A suspension of [AuCl2(2-benzylpyridyl)] (50 mg, 0.115 mmol) in methanol (10 mL)
was added in one portion to a stirred solution of N-phenyl-1H-pyrrole-2-carbothioamide 1a
(26 mg, 0.126 mmol) in methanol (10 mL), and the mixture was heated to 50 °C. Aqueous
trimethylamine (5 drops, excess) was added and the reaction mixture was refluxed for 2 h. A
light green solid precipitated out after 10 min. reaction. The product was filtered, washed
with methanol (3 mL) and water (3 mL) and dried under vacuum. Yield 57 mg, 88%. M.p.
190-196 °C. Found: C, 48.70; H, 3.18; N, 7.34%. C23H18AuN3S requires C, 48.86; H, 3.21;
1
N, 7.43%. H NMR: δ (ppm) 9.03 (dd, J 5.6, 1H), 8.09 (t, 1H), 7.80 (d, J 7.6, 1H), 7.62 (t,
1H), 7.50 (dd, J 7.6, 1H), 7.33 (m, 2H), 7.10 (m, 7H), 6.66 (m, 1H), 6.44 (m, 1H), 4.50 (d, J
14.8, 1H), 4.05 (d, J 14.8, 1H). ESI MS: positive-ion [M+H]+, m/z 566.109, calculated m/z
566.089. IR: 1588 (νC=N), 1393 (νC-S) cm-1.
The following complexes were prepared by the same method as for 2a.
4.8. Synthesis of 2b
[AuCl2(2-benzylpyridyl)] (50 mg, 0.115 mmol) with 3,5-dimethyl-N-phenyl-1H-
pyrrole-2-carbothioamide 1b (44 mg, 0.140 mmol) and trimethylamine (5 drops, excess) in
methanol (20 mL) gave an orange powder (46 mg, 73%). M.p. 186-190 °C. Found: C, 49.72;
1
H, 3.73; N, 6.91%. C25H22AuN3S requires C, 50.59; H, 3.74; N, 7.08%. H NMR: δ (ppm)
8.93 (dd, J 5.6, 1H), 8.01 (t, 1H), 7.77 (d, J 7.6, 1H), 7.58 (d, J 7.6, 1H), 7.49 (m, 1H), 7.34
(m, 2H), 7.10 (m, 6H), 5.99 (s, 1H), 4.58 (d, J 14.8, 1H), 4.06 (d, J 14.8, 1H), 2.45 (s, 3H),
1.70 (s, 3H). ESI MS: positive-ion [M+H]+, m/z 594.131, calculated m/z 594.120. IR: 1563
(νC=N), 1308 (νC-S) cm-1.
14

4.9. Synthesis of 2c
[AuCl2(2-benzylpyridyl)] (50 mg, 0.115 mmol) with 4-ethyl-3,5-dimethyl-N-phenyl-
1H-pyrrole-2-carbothioamide 1c (33 mg, 0.126 mmol) and trimethylamine (5 drops, excess)
in methanol (25 mL) gave a yellow ochre powder (60 mg, 84%). M.p. 192-196 °C. Found: C,
1
52.27; H, 4.27; N, 6.65%. C27H26AuN3S requires C, 52.17; H, 4.22; N, 6.76%. H NMR: δ
(ppm) 8.89 (dd, J 5.6, 1H), 8.00 (t, 1H), 7.75 (d, J 7.6, 1H), 7.46 (m, 1H), 7.31 (m, 2H), 7.07
(m, 6H), 4.55 (d, J 14.4, 1H), 4.04 (d, J 14.4, 1H), 2.41 (m, 5H), 1.61 (s, 3H), 1.06 (t, 3H).
ESI MS: positive-ion [M+H]+, m/z 622.177, calculated m/z 622.151. IR: 1574 (νC=N), 1325
(νC-S) cm-1.
4.10. Synthesis of 2d
[AuCl2(2-benzylpyridyl)] (50 mg, 0.115 mmol) with N-(4-nitrophenyl)-1H-pyrrole-2-
carbothioamide 1d (31mg, 0.126 mmol) and trimethylamine (5 drops, excess) in methanol
(25 mL) gave a yellow powder (46 mg, 66%). M.p. 196-200 °C. Found: C, 45.09; H, 2.88; N,
1
9.16%. C23H17AuN4O2S requires C, 45.25; H, 2.81; N, 9.18%. H NMR: δ (ppm) 9.02 (d, J
5.6, 1H), 8.20 (m, 2H), 8.13 (t, 1H), 7.83 (d, J 8.0, 1H), 7.65 (t, 1H), 7.47 (dd, J 7.6, 1H), 7.16
(m, 6H), 6.68 (m, 1H), 6.45 (m, 1H), 4.52 (d, J 14.8, 1H), 4.09 (d, J 14.8, 1H). ESI MS:
positive-ion [M+H]+, m/z 611.080, calculated m/z 611.074. IR: 1558 (νC=N), 1333 (νC-S), 1504
(νasNO ), 1390 (νsNO2) cm-1.
2
4.11. Synthesis of 2e
[AuCl2(2-benzylpyridyl)] (50 mg, 0.115 mmol) with 3,5-dimethyl-N-phenyl-1H-
pyrrole-2-carbothioamide 1e (35 mg, 0.126 mmol) and trimethylamine (5 drops, excess) in
methanol (25 mL) gave an orange powder (42 mg, 57%). M.p. 194-196 °C. Found: C, 47.02;
15

H, 3.35; N, 8.76%. C25H21AuN4O2S requires C, 47.03; H, 3.32; N, 8.77%. 1H NMR: δ (ppm)
8.91 (dd, J 5.6, 1H), 8.21 (m, 1H), 8.06 (t, 1H), 7.78 (d, J 7.2, 1H), 7.50 (m, 2H), 7.13 (m,
4H), 7.00 (m, 1H), 5.99 (s, 1H), 4.56 (d, J 14.8, 1H), 4.07 (d, J 14.8, 1H), 2.40 (s, 3H), 1.69
(s, 3H). ESI MS: positive-ion [M+H]+, m/z 639.104, calculated m/z 639.105. IR: 1572 (νC=N),
1333 (νC-S), 1503 (νasNO ), 1311 (νsNO2) cm-1.
2
4.12. Synthesis of 2f
[AuCl2(2-benzylpyridyl)] (50 mg, 0.115 mmol) with 4-ethyl-3,5-dimethyl-N-(4-
nitrophenyl)-1H-pyrrole-2-carbothioamide 1f (38 mg, 0.126 mmol) and trimethylamine (5
drops, excess) in methanol gave an orange powder (65 mg, 57%). M.p. 202-204 °C. Found:
1
C, 48.62; H, 3.82; N, 8.38%. C27H25AuN4O2S requires C, 48.65; H, 3.78; N, 8.41%. H
NMR: δ (ppm) 8.92 (dd, J 5.6, 1H), 8.22 (m, 2H), 8.06 (t, 1H), 7.80 (d, J 8.0, 1H), 7.52 (m,
2H), 7.17 (m, 4H), 7.02 (m, 1H), 4.59 (d, J 14.4, 1H), 4.09 (d, J 14.4, 1H), 2.41 (m, 5H), 1.67
(s, 3H), 1.09 (t, 3H). ESI MS: positive-ion [M+H]+, m/z 667.090, calculated m/z 667.136. IR:
1563 (νC=N), 1328 (νC-S), 1499 (νasNO ), 1309 (νsNO2) cm-1.
2
4.13. Synthesis of 3a
A solution of [AuCl2(C6H4CH2NMe2)] (50 mg, 0.124 mmol) in methanol (10 mL)
was added in one portion to a stirred solution of N-phenyl-1H-pyrrole-2-carbothioamide 1a
(28 mg, 0.137 mmol) in methanol (10 mL), and the mixture was heated to 50 °C. After
aqueous trimethylamine (5 drops, excess) was added, the reaction mixture was heated to
reflux for 2 h. After cooling to room temperature, water (2 mL) was added, resulting in
precipitation of a yellow solid. The product was filtered and washed with petroleum spirits (3
mL), yield 38 mg, 58%. M.p. 158-160 °C. Found: C, 44.51; H, 4.02; N, 7.63%. C20H20AuN3S
requires C, 45.20; H, 3.79; N, 7.91%. 1H NMR: δ (ppm) 7.38 (m, 3H), 7.21 (m, 2H), 7.11 (m,
16

6H), 6.54 (q, 1H), 4.35 (s, 2H), 3.38 (s, 6H). ESI MS: positive-ion [M+H]+, m/z 532.120,
calculated m/z 532.104. IR: 1566 (νC=N), 1390 (νC-S) cm-1.
4.14. Synthesis of 3d
[AuCl2(C6H4CH2NMe2)] (50 mg, 0.124 mmol) with N-(4-nitrophenyl)-1H-pyrrole-2-
carbothioamide 1d (34 mg, 0.137 mmol) and trimethylamine (5 drops, excess) in methanol
gave a brownish yellow powder (53 mg, 74%). M.p. 198-202 °C. Found: C, 41.37; H, 3.18;
N, 9.64%. C20H19AuN4O2S requires C, 41.67; H, 3.32; N, 9.72%. 1H NMR: δ (ppm) 8.22 (m,
2H), 7.30 (d, J 7.76, 1H), 7.22 (m, 2H), 7.15 (m, 2H), 7.10 (m, 2H), 6.97 (br, 1H), 6.53 (q,
1H), 4.32 (s, 2H), 3.39 (s, 6H). ESI MS: positive-ion [M+H]+, m/z 577.183, calculated m/z
577.089. IR: 1578 (νC=N), 1331 (νC-S), 1504 (νasNO ), 1391 (νsNO2) cm-1.
2
4.15. Synthesis of 3e
[AuCl2(C6H4CH2NMe2)] (50 mg, 0.124 mmol) with 3,5-dimethyl-N-phenyl-1H-
pyrrole-2-carbothioamide 1e (38 mg, 0.137 mmol) and trimethylamine (5 drops, excess) in
methanol gave a brown powder (57 mg, 73%). M.p. 172-178 °C. Found: C, 43.36; H, 3.75;
N, 9.06%. C22H23AuN4O2S requires C, 43.71; H, 3.84; N, 9.27%. 1H NMR: δ (ppm) 8.15 (m,
2H), 7.21 (m, 1H), 7.19 (m, 2H), 7.08 (m, 3H), 6.10 (s, 1H), 4.26 (s, 2H), 3.30 (s, 6H), 2.49
(s, 3H), 2.40 (s, 3H). ESI MS: positive-ion [M+H]+, m/z 605.242, calculated m/z 605.121. IR:
1569 (νC=N), 1331 (νC-S), 1502 (νasNO ), 1306 (νsNO2) cm-1.
2
4.16. Synthesis of 3f
[AuCl2(C6H4CH2NMe2)] (40 mg, 0.099 mmol) with 4-ethyl-3,5-dimethyl-N-(4-
nitrophenyl)-1H-pyrrole-2-carbothioamide 1f (33 mg, 0.109 mmol) and trimethylamine (5
drops, excess) in methanol gave a brown powder (38 mg, 60%). M.p. 164-170 °C. Found: C,
17

45.50; H, 4.22; N, 8.76%. C24H27AuN4O2S requires C, 45.57; H, 4.30; N, 8.86%. 1H NMR: δ
(ppm) 8.16 (m, 2H), 7.22 (m, 3H), 7.12 (m, 3H), 4.27 (s, 1H), 3.31 (s, 6H), 2.47 (m, 5H),
2.40 (d, J 3.2, 3H), 1.12 (t, 3H). ESI MS: positive-ion [M+H]+, m/z 633.290, calculated m/z
633.152. IR: 1561 (νC=N), 1332 (νC-S), 1503 (νasNO ), 1390 (νsNO2) cm-1.
2
4.17. Synthesis of 4a
A mixture of cis-[PtCl2(PPh3)2] (100 mg, 0.126 mmol) with N-phenyl-1H-pyrrole-2-
carbothioamide 1a (28 mg, 0.139 mmol) and trimethylamine (5 drops, excess) in methanol
gave 4a as a light yellow powder (67 mg, 58%). M.p. 290-292 °C. Found: C, 61.22; H, 4.10;
N, 3.18%. C47H38N2P2PtS requires C, 61.36; H, 4.16; N, 3.05%. 31P{1H} NMR, δ (ppm) 19.4
1
2
1
2
1
[d, J(PtP) 2849, J(PP) 24], δ 13.4 [d, J(PtP) 3177, J(PP) 24]. H NMR: δ (ppm) 7.40 (m,
6H), 7.37 (m, 6H), 7.30 (m, 5H), 7.15 (m, 15H), 6.97 (m, 2H), 6.85 (m, 1H), 6.69 (m, 1H),
6.00 (s, 1H), 5.70 (m, 1H). ESI MS: positive-ion [M+H]+, m/z 920.217, calculated m/z
920.188. IR: 1557 (νC=N), 1281 (νC-S) cm-1.
4.18. Synthesis of 4d
A mixture of cis-[PtCl2(PPh3)2] (100 mg, 0.126 mmol) with N-(4-nitrophenyl)-1H-
pyrrole-2-carbothioamide 1d (34 mg, 0.139 mmol) and trimethylamine (5 drops, excess) in
methanol gave 4d as a light orange powder (72 mg, 59%). M.p. decomp. > ca. 282 °C turns
black. Found: C, 58.37; H, 3.77; N, 4.33%. C47H37N3O2P2PtS requires C, 58.50; H, 3.86; N,
1
2
1
4.35%. 31P{1H} NMR, δ (ppm) 19.2 [d, J(PtP) 2900, J(PP) 24], δ 12.6 [d, J(PtP) 3163,
1
2J(PP) 24]. H NMR: δ (ppm) 7.99 (m, 2H), 7.45 (m, 6H), 7.41 (m, 6H), 7.33 (m, 6H), 7.17
(m, 12H), 7.03 (m, 2H), 6.64 (s, 1H), 6.02 (m, 1H), 5.72 (m, 1H). ESI MS: positive-ion
18

[M+H]+, m/z 965.204, calculated m/z 965.173. IR: 1531 (νC=N), 1329 (νC-S), 1504 (νasNO ),
2
1396 (νsNO2) cm-1.
4.19. Synthesis of 4e
A mixture of cis-[PtCl2(PPh3)2] (100 mg, 0.126 mmol) with 3,5-dimethyl-N-(4-
nitrophenyl)-1H-pyrrole-2-carbothioamide 1e (38 mg, 0.139 mmol) and trimethylamine (5
drops, excess) in methanol (25 mL) gave 4e as an orange powder (63 mg, 50%). M.p. 220-
224 °C. Found: C, 59.03; H, 4.11; N, 4.36%. C49H41N3O2P2PtS requires C, 59.27; H, 4.16; N,
1
2
1
4.23%. 31P{1H} NMR, δ (ppm) 15.8 [d, J(PtP) 3088, J(PP) 24], δ 7.1 [d, J(PtP) 3100,
2J(PP) 24]. 1H NMR: δ (ppm) 7.91 (m, 2H), 7.52 (m, 6H), 7.34 (m, 6H), 7.20 (m, 12H), 7.12
(m, 6H), 6.90 (m, 2H), 5.43 (dd, J 3.6, 1H), 2.42 (s, 3H), 1.46 (s, 3H). ESI MS: positive-ion
[M+H]+, m/z 993.519, calculated m/z 993.204. IR: 1527 (νC=N), 1333 (νC-S), 1498 (νasNO ),
2
1298 (νsNO2) cm-1.
4.20. Synthesis of 4f
A mixture of cis-[PtCl2(PPh3)2] (80 mg, 0.101 mmol) with 4-ethyl-3,5-dimethyl-N-(4-
nitrophenyl)-1H-pyrrole-2-carbothioamide 1f (34 mg, 0.111 mmol) and trimethylamine (5
drops, excess) in methanol gave 4f as a dark orange powder (75 mg, 73%). M.p. 222-224 °C.
Found: C, 59.98; H, 4.46; N, 4.23%. C51H45N3O2P2PtS requires C, 59.99; H, 4.44; N, 4.12%.
1
2
1
2
31P{1H} NMR, δ (ppm) 16.1 [d, J(PtP) 3090, J(PP) 23], δ 7.2 [d, J(PtP) 3084, J(PP) 23].
1H NMR: δ (ppm) 7.90 (m, 2H), 7.52 (m, 6H), 7.33 (m, 6H), 7.24 (m, 12H), 7.12 (m, 6H),
6.89 (m, 2H), 2.40 (s, 3H), 1.98 (q, 2H), 1.42 (s, 3H), 1.98 (t, 3H). ESI MS: positive-ion
[M+H]+, m/z 1021.157, calculated m/z 1021.236. IR: 1520 (νC=N), 1323 (νC-S), 1542 (νasNO ),
2
1299 (νsNO2) cm-1.
19

4.21. Synthesis of 5a
A mixture of [PdCl2(dppe)] (50 mg, 0.087 mmol) with N-phenyl-1H-pyrrole-2-
carbothioamide 1a (19 mg, 0.096 mmol) and trimethylamine (5 drops, excess) in methanol
gave an orange powder (35 mg, 56%). M.p. 172-176 °C. Found: C, 62.17; H, 4.63; N, 4.11%.
C37H32N2P2PdS requires C, 63.03; H, 4.57; N, 3.97%. 31P{1H} NMR, δ (ppm) 56.9 [d, 2J(PP)
29], δ 50.4 [d, 2J(PP) 29]. 1H NMR: δ (ppm) 7.71 (m, 8H), 7.40 (m, 12H), 7.15 (m, 2H), 7.03
(m, 2H), 6.82 (m, 2H), 6.18 (s, 1H), 5.94 (s, 1H), 2.33 (m, 4H). ESI MS: positive-ion
[M+H]+, m/z 705.133, calculated m/z 705.080. IR: 1551 (νC=N), 1279 (νC-S) cm-1.
4.22. Synthesis of 5d
[PdCl2(dppe)] (50 mg, 0.087 mmol) with N-(4-nitrophenyl)-1H-pyrrole-2-
carbothioamide 1d (24 mg, 0.096 mmol) and trimethylamine (5 drops, excess) in methanol
gave a red powder (53 mg, 81%). M.p. 270-276 °C. Found: C, 59.05; H, 4.07; N, 5.72%.
C37H31N3O2P2PdS requires C, 59.25; H, 4.17; N, 5.60%. 31P{1H} NMR, δ (ppm) 58.0 [d,
2J(PP) 29], δ 51.5 [d, 2J(PP) 28]. 1H NMR: δ (ppm) 8.05 (m, 2H), 7.77 (m, 4H), 7.67 (m, 4H),
7.41 (m, 12H), 7.06 (m, 2H), 6.74 (s, 1H), 6.18 (m, 1H), 5.94 (m, 1H), 2.37 (m, 4H). ESI MS:
positive-ion [M+H]+, m/z 750.073, calculated m/z 750.065. IR: 1544 (νC=N), 1324 (νC-S), 1586
(νasNO ), 1386 (νsNO2) cm-1.
2
4.23. Synthesis of 5e
[PdCl2(dppe)] (50 mg, 0.087 mmol) with 3,5-dimethyl-N-phenyl-1H-pyrrole-2-
carbothioamide 1e (26 mg, 0.096 mmol) and trimethylamine (5 drops, excess) in methanol
gave a dark red powder (56 mg, 83%). M.p. 190-196 °C. Found: C, 59.34; H, 4.51; N, 5.75%.
C39H35N3O2P2PdS requires C, 60.20; H, 4.53; N, 5.40%. 31P{1H} NMR, δ (ppm) 61.8 [d,
2J(PP) 32], δ 47.3 [d, 2J(PP) 34]. 1H NMR: δ (ppm) 7.89 (m, 6H), 7.64 (m, 4H), 7.49 (m, 8H),
20

7.40 (m, 4H), 6.94 (m, 2H), 5.69 (d, J 3.4, 1H), 2.37 (s, 3H), 2.21 (m, 4H), 1.48 (s, 3H). ESI
MS: positive-ion [M+H]+, m/z 778.112, calculated m/z 778.096. IR: 1511 (νC=N), 1279 (νC-S),
1464 (νasNO ), 1327 (νsNO2) cm-1.
2
4.24. Synthesis of 5f
[PdCl2(dppe)] (50 mg, 0.087 mmol) with 4-ethyl-3,5-dimethyl-N-(4-nitrophenyl)-1H-
pyrrole-2-carbothioamide 1f (29 mg, 0.096 mmol) and trimethylamine (5 drops, excess) in
methanol gave a dark red powder (55 mg, 79%). M.p. 220-226 °C. Found: C, 60.37; H, 4.95;
31
N, 5.53%. C41H39N3O2P2PdS requires C, 61.08; H, 4.88; N, 5.21%. P{1H} NMR, δ (ppm)
61.6 [d, 2J(PP) 34], δ 47.3 [d, 2J(PP) 34]. 1H NMR: δ (ppm) 7.88 (m, 3H), 7.67 (m, 4H), 7.46
(m, 8H), 7.36 (m, 4H), 7.06 (t, 2H), 6.89 (d, J 8.2, 2H), 6.79 (t, 1H), 2.40 (s, 3H), 2.22 (m,
6H), 1.45 (s, 3H), 0.87 (t, 4H). ESI MS: positive-ion [M+H]+, m/z 806.143, calculated m/z
806.127. IR: 1544 (νC=N), 1308 (νC-S), 1494 (νasNO ), 1326 (νsNO2) cm-1.
2
4.25. X-ray structure determinations of 1f, 2b•0.75CH2Cl2 and 3d
Black crystals of 1f were obtained by rotary evaporation of an ethyl
acetate/dichloromethane/hexane 1:3:5 solution. Orange crystals of 2b•0.75CH2Cl2 and yellow
crystals of 3d were obtained by slow diffusion of diethyl ether into a dichloromethane
solution of the compounds at room temperature.
Intensity data were obtained on an Agilent SuperNova, Single source at offset, Atlas
diffractometer with graphite-monochromated Cu—Kα radiation and corrected for absorption
using a multi-scan procedure.[52] Using Olex2,[53] the structures were solved with the
Olex2.solve [54] structure solution program using Charge Flipping and refined with the
21

Olex2.refine [54] refinement package using Gauss–Newton minimisation. The peak electron
densities of 2b and 3b lie close to Au(1) (within 1.1 Å).
Crystallographic details are presented in Table 4.
4.26. Biological assays
The MTT assay was used to examine the cytotoxic effect of the compounds toward
human A549 cells, which are used as models for the study of lung cancer. Cells were seeded
in a complete growth medium in 96-well plates (Costar Corning, NY), at a density of 1 ×
104 cells/well, and grown for 24 h before treatment. The growth medium was then substituted
with fresh medium containing the compounds to be tested at appropriate concentrations.
After incubation for 24 h, cells were washed with PBS three times and 100 μL of fresh
culture medium containing MTT (5 mg/mL) was added to each well. Cells were continually
incubated for another 4 h before the media with MTT were removed. Furthermore, 150 μL of
DMSO was added to each well and incubated at 37 °C for 10 min. The absorbance of each
sample at 490 nm was measured using a microplate reader (Perkin-Elmer, Victor X4).
Acknowledgements
We thank the University of Waikato for financial support of this work, and Pat Gread, Wendy
Jackson and Dr. Judith Burrows for technical assistance. The biological assay work was
partially supported by the National Natural Science Foundation of China (31700875), the
National Science Foundation of Jiangsu Province (BK20160311), the Postdoctoral Science
Foundation of China (2016M590496), Collaborative Innovation Center of Radiological
22

Medicine of Jiangsu Higher Education Institutions, Jiangsu Provincial Key Laboratory of
Radiation Medicine and Protection, and a project funded by the Priority Academic Program
Development of Jiangsu Higher Education Institutions (PAPD).
Disclosure statement
No potential conflict of interest
Supplementary material
CCDC 1948345 - 1948347 contain the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/data_request/cif. Supplementary data to this article can be found
online at http://............
23

Table 1 Selected bond lengths (Å) and angles (°) for 1f, with esds in parentheses.
Atoms
Lengths (Å)
Atoms
Angles (°)
N(1)-C(4)
C(4)-C(9)
C(9)-S(1)
C(9)-N(2)
N(2)-C(11)
N(1)-C(1)
1.380(2)
1.437(2)
1.6775(17)
1.362(2)
1.404(2)
1.355(2)
N(1)-C(4)-C(9)
C(4)-C(9)-S(1)
S(1)-C(9)-N(2)
C(9)-N(2)-C(11)
C(4)-C(9)-N(2)
119.95(15)
121.89(13)
124.10(13)
134.31(15)
114.01(14)
24

Table 2 Selected bond lengths (Å) and angles (°) for the complex 2b•CH2Cl2, with esds in
parentheses
Atoms
Lengths (Å)
Atoms
Angles (°)
Au(1)-N(1)
Au(1)-N(4)
Au(1)-C(31)
Au(1)-S(1)
S(1)-C(9)
2.062(6)
2.090(5)
2.043(7)
2.2630(15)
1.803(6)
1.284(8)
N(4)-Au(1)-C(31)
C(31)-Au(1)-S(1)
S(1)-Au(1)-N(1)
N(1)-Au(1)-N(4)
S(1)-Au(1)-N(4)
N(1)-Au(1)-C(31)
Au(1)-N(1)-C(4)
Au(1)-S(1)-C(9)
87.1(2)
90.71(19)
85.07(15)
98.0(2)
170.68(16)
172.6(3)
117.9(4)
99.4(2)
N(2)-C(9)
Table 3 Selected bond lengths (Å) and angles (°) for the complex 3d, with esds in
parentheses
Atoms
Lengths (Å)
Atoms
Angles (°)
Au(1)-N(1)
Au(1)-N(4)
Au(1)-C(21)
Au(1)-S(1)
S(1)-C(9)
2.080(4)
2.144(4)
2.028(5)
2.2797(11)
1.789(5)
1.280(6)
N(4)-Au(1)-C(21)
C(21)-Au(1)-S(1)
S(1)-Au(1)-N(1)
N(1)-Au(1)-N(4)
S(1)-Au(1)-N(4)
N(1)-Au(1)-C(21)
Au(1)-N(1)-C(4)
Au(1)-S(1)-C(9)
81.17(18)
90.84(14)
85.61(12)
102.57(16)
170.73(11)
175.62(19)
117.2(3)
N(2)-C(9)
99.64(17)
25

Table 4 Crystal and refinement data for the compounds 1f, 2b•0.75CH2Cl2 and 3d
Complex
1f
2b•0.75CH2Cl2
3d
Formula
C15H17N3O2S
303.39
C25.75H23.5AuCl1.5N3S
657.21
C20H19AuN4O2S
576.43
Molecular Weight
T/K
100.05(16)
Triclinic
P-1
111(15)
99.95(13)
Monoclinic
P21/n
Crystal system
Space group
a (Å)
Triclinic
P-1
6.9323(4)
8.5240(6)
12.5071(8)
89.096(5)
79.418(6)
82.735(5)
720.64(8)
2
10.3271(5)
12.0211(6)
12.2148(5)
118.107(5)
98.606(4)
105.272(4)
1221.73(13)
2
15.0999(2)
8.23711(15)
15.1811(2)
90
b (Å)
c (Å)
α (°)
β (°)
92.8016(14)
90
γ (°)
V (Å3)
1885.96(5)
4
Z
Dcalc (g cm-3)
Residual electron density
(max, min e Å-3)
Tmax,min
1.398
1.786
2.030
0.360, -0.401
4.437, -2.216
1.698, -1.597
1.000, 0.672
2798
0.793, 0.622
4783
0.816, 0.454
3659
No. of unique reflections
No. of observed
reflections [I>2σ(I)]
R [I>2σ(I)]
wR2 (all data)
Goodness of Fit
2347
4433
3233
0.0371
0.0946
1.032
0.0456
0.1240
1.037
0.0263
0.0739
1.068
26

HN
H
N
S
H
N
C
N
S
R
1a
1d
R = H
R = NO2
HN
H
N
(R = H or NO2)
H
N
R
Reflux
S
R
1b
1e
R = H
H
N
R = NO2
HN
H
N
S
R
1c
R = H
1f
R = NO2
Scheme 1 Syntheses of pyrrole-derived thioamide ligands 1a-1f
27

R4
R4
N
S
N
S
Au
Au
N
N
N
R3
N
R3
R1
R1
R2
R2
R1
R2
R3
R4
R1
R2
R3
R4
2a
2b
2c
2d
H
H
H
Et
H
H
H
3a
3d
3e
3f
H
H
H
H
Et
H
H
H
Me
Me
H
Me
Me
H
H
H
NO2
NO2
NO2
H
Me
Me
Me
Me
NO2
2e
2f
Me
Me
H
Me
Me
NO2
NO2
Et
Scheme 2 Gold(III) complexes containing pyrrole thioamide ligands
28

R4
N
S
L
M
N
L
R3
R1
R2
M
L
R1
H
R2
H
R3
H
R4
4a
4d
4e
4f
Pt
PPh3
PPh3
PPh3
PPh3
dppe
dppe
dppe
dppe
H
Pt
H
H
H
NO2
NO2
NO2
H
Pt
Me
Me
H
H
Me
Me
H
Pt
Et
H
5a
5d
5e
5f
Pd
Pd
Pd
Pd
H
H
H
NO2
NO2
NO2
Me
Me
H
Me
Me
Et
Scheme 3 Platinum(II) and palladium(II) complexes containing pyrrole thioamide ligands
29