Synthesis of Bioactive N-Acyclic Gold(I) and Gold(III) Diamino Carbenes with Different Ancillary Ligands

Article abstract of DOI:10.1002/ejic.201900606

A series of gold(I) and gold(III) N-acyclic diamino carbene (ADC) complexes with different ancillary ligands have been synthesized. The chloride carbene derivatives [Au{C(NHR)(NHCH₂py)}Cl] (R = Cy, R = naphthyl, R = xylyl) have been obtained by reaction of 2-picolylamine with the corresponding [AuCl(CNR)]. The gold(I) thiolate derivatives [Au{C(NHR)(NHCH₂py)}(Spy)] were prepared by reaction of the chlorido complexes with 2-mercaptopyridine (2-HSpy) in presence of potassium carbonate. The phosphane derivative [Au(pyCH₂NH₂)(PPh₃)](OTf) was obtained by reaction of freshly prepared [Au(OTf)(PPh₃)] with 2-picolylamine. The phosphane-carbene complexes [Au{C(NHR)(NHCH₂py}(PPh₃)](OTf) were obtained from the reaction of picolylamino species with the isocyanide. The gold(III) derivative cis-[Au(C₆F₅)₂(pyCH₂NH₂)](ClO₄) was obtained by the reaction of 2-picolylamine with freshly [Au(C₆F₅)₂(Et₂O)₂](ClO₄). The reaction of the former with CNCy led to complex cis-[Au(C₆F₅)₂{C(NHCy)(NHCH₂py)}]ClO₄ by a nucleophilic attack of the isocyanide to the amine ligand, thus producing a bidentate C,N acyclic carbene ligand. Cytotoxic studies against the tumor human cell lines Jurkat (T-cell leukaemia), MiaPaca2 (pancreatic carcinoma), A549 (lung carcinoma) and MDA-MB-231 (breast carcinoma) showed moderate to good cytotoxic activity for some of the complexes.

Full text of DOI:10.1002/ejic.201900606

DOI: 10.1002/ejic.201900606
Full Paper
Diamino Carbenes
Synthesis of Bioactive N-Acyclic Gold(I) and Gold(III) Diamino
Carbenes with Different Ancillary Ligands
Sara Montanel-Pérez,[a] Raquel Elizalde,[a] Antonio Laguna,[a] M. Dolores Villacampa,*[a] and
M. Concepción Gimeno*[a]
Dedicated to Professor Cristian Silvestru on the occasion of his 65th birthday.
Abstract: A series of gold(I) and gold(III) N-acyclic diamino tained from the reaction of picolylamino species with the iso-
carbene (ADC) complexes with different ancillary ligands have cyanide. The gold(III) derivative cis-[Au(C6F5)2(pyCH2NH2)](ClO4)
been synthesized. The chloride carbene derivatives was obtained by the reaction of 2-picolylamine with freshly
[Au{C(NHR)(NHCH2py)}Cl] (R = Cy, R = naphthyl, R = xylyl) have [Au(C6F5)2(Et2O)2](ClO4). The reaction of the former with CNCy
been obtained by reaction of 2-picolylamine with the corre- led to complex cis-[Au(C6F5)2{C(NHCy)(NHCH2py)}]ClO4 by a nu-
sponding [AuCl(CNR)]. The gold(I) thiolate derivatives cleophilic attack of the isocyanide to the amine ligand, thus
[Au{C(NHR)(NHCH2py)}(Spy)] were prepared by reaction of the producing a bidentate C,N acyclic carbene ligand. Cytotoxic
chlorido complexes with 2-mercaptopyridine (2-HSpy) in pres- studies against the tumor human cell lines Jurkat (T-cell leukae-
ence of potassium carbonate. The phosphane derivative mia), MiaPaca2 (pancreatic carcinoma), A549 (lung carcinoma)
[Au(pyCH2NH2)(PPh3)](OTf) was obtained by reaction of freshly and MDA-MB-231 (breast carcinoma) showed moderate to good
prepared [Au(OTf)(PPh3)] with 2-picolylamine. The phosphane- cytotoxic activity for some of the complexes.
carbene complexes [Au{C(NHR)(NHCH2py}(PPh3)](OTf) were ob-
Introduction
activity has been reported about acyclic gold(I) and gold(III)
carbene derivatives.[5] The search in cancer therapy of new al-
ternatives to platinum-based drugs, which present serious side
effects and generation of resistance,[6] has conducted to the
chemical community to find new metallic drugs with different
biological behavior and different biological targets to the plati-
num chemotherapeutics. Among them, gold derivatives are
now thoroughly investigated, especially after the discovery of
the great activity of auranofin against rheumatoid arthritis.[7]
Taking into account all these facts, and the great stability of
ADC gold derivatives it is surprising that this type of complexes
has been until now neglected in the literature. Additionally, the
presence of different ancillary ligands such as phosphanes or
thiolates may greatly enhance antitumor activity. This is in
agreement with the existence of many complexes bearing
phosphane and/or thiolate groups as auxiliary ligands, as partic-
ular examples of the wide group of gold complexes with anti-
tumor activity.[8]
With this idea in mind, we have synthesized a series of neu-
tral or cationic acyclic diamino carbene gold(I) and gold(III) de-
rivatives. Chloride, thiolate or triphenylphosphane ligands com-
plete the expected di-coordinated linear geometry around the
gold metal atom in the final complexes. Two pentafluorophenyl
groups and a new bidentate C,N N-acyclic diamino carbene li-
gand, complete the square-planar geometry in the gold(III) de-
rivative. The in vitro antitumor activity of some of them has
been tested against the tumor human cell lines Jurkat (T-cell
leukaemia), MiaPaca2 (pancreatic carcinoma), A549 (lung carci-
Isocyanides are an important class of compounds widely used
as building blocks in organic chemistry. They can react with
both electrophiles and nucleophiles. Coordination of isocyan-
ides to a metal center greatly enhances their electrophilic char-
acter. Isocyanide gold(I) derivatives show in general an impor-
tant electrophilic character through the carbon atom of the iso-
cyanide group. It permits the synthesis of acyclic diamino carb-
ene complexes by reaction with amines. In general, the coordi-
nation of the isocyanide group to metals facilitates the addition
of nucleophiles to the carbon atom of the isocyanides.[1] The
gold(I) acyclic diamine carbene complexes (ADCs) are showing
interesting properties, especially in catalysis, as reflects the high
volume of papers published about that in the last years.[2] These
acyclic carbenes are good σ-donor ligands with attractive con-
formational flexibility and a wide N-Ccarbene–N angle that en-
hances their catalytic possibilities.[1,2ab,3] On the other hand, the
related N-heterocyclic gold(I) carbenes (NHCs) have been thor-
oughly investigated in medicine, especially as antitumor agents
showing several of them promising activity.[4] In contrast, as far
as we are aware, only some scarcely examples of the antitumor
[a] Departamento de Química Inorgánica, Instituto de Síntesis Química y
Catálisis Homogénea (ISQCH), CSIC-Universidad de Zaragoza,
50009 Zaragoza, Spain
E-mail: dvilla@unizar.es, gimeno@unizar.es
ORCID(s) from the author(s) for this article is/are available on the WWW
under https://doi.org/10.1002/ejic.201900606.
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noma) and MDA-MB- 231 (breast carcinoma) and compared the
results with those of cisplatin.
One characteristic of these N-acyclic carbene derivatives is
the presence in their solutions at room temperature of confor-
mational isomers or rotamers. It is a consequence of the elec-
tronic delocalization along with the C-N bonds of the carbene
group, that hinder the rotation around these bonds at room
temperature, unless in the NMR time scale (Figure 1).[2g,11]
Results and Discussion
Synthesis and Characterization
All the complexes synthesized are air- and moisture-stable
white solids. They have been characterized by means of IR, NMR
spectroscopy and mass spectrometry. Assignments of the 1H
NMR and 13C NMR signals were made on the basis of 2D 1H
COSY and HSQC spectra. Complete spectroscopic information
of the complexes has been collected in the Experimental Sec-
tion.
The isocyanide complexes [AuCl(CNR)] (R = Cy (1), 2-naphthyl
(2) or xylyl (xylyl = 2,6-dimethylphenyl)) (3), previously synthe-
sized,[9] were prepared by the reaction of [AuCltht] (tht = tetra-
hydrothiophene)[10] and an equimolecular amount of the corre-
sponding isocyanide CNR. Spectroscopic information of com-
plexes 1–3 is collected in the Experimental Section. The reac-
tion of [AuCl(CNR)] (1–3) (R = cyclohexyl (Cy), 2-naphthyl, xylyl)
with equimolecular amounts of 2-picolylamine gives complexes
4–6, respectively. The nucleophilic addition of the amine to the
carbon center of the isocyanide group produces the formation
of the corresponding mononuclear gold(I) acyclic diamino carb-
enes (Scheme 1).
Figure 1. Different structural conformations for ADCs.
1
In the H NMR spectra of complexes 4 and 5, three and two
isomers, respectively, could be identified. The relative ratio of
the isomers, 4 (1:0.6:0.2) or 5 (1:0.8), could be quantified with
the protons of the CH2 of the 2-picolylamine group, which ap-
pear in a clear region of the spectra. In the H NMR spectrum
of complex 6, a major isomer was identified with only a small
amount of a second one (Figure 2).
1
Complexes 7–8 (Scheme 2) were synthesized by the reaction
between the carbene (5, 6) gold(I) chloride and the thiol 2-
mercaptopyridine (2-HSpy) in the presence of potassium carb-
onate. Infrared spectra of complexes show, among others, one
band corresponding to the Au–S vibration at ca. 400 cm–1 and
the absorptions from NH at ca. 3200 cm–1 and 3000 cm–1. In
the ESI+ mass spectra the fragments [M + H]+ appear at m/z =
569 (100 %) (7), 547 (2 %) (8) and [M – py]+ at 463 (100 %) (8).
The 1H NMR of the ADC derivatives 7 and 8 appeared as a
mixture of two and three rotamers, respectively. Integration of
Scheme 1. Synthesis of chloro-gold(I) ADC complexes 4–6.
The IR spectra of complexes 4–6 show the characteristic
ν(Au–Cl) vibration of a gold(I) atom coordinated to a chloride
ligand at 321, 324 or 308 cm–1, respectively, remarkably lower
than those present in the chloride gold(I) isocyanide starting
materials infrared spectra, in which these signals appear at ca.
350 cm–1 (see experimental section). This is in good accordance
with the stronger σ electron donor properties of carbene than
isocyanide ligand. In the ESI+ mass spectra the fragments [M –
Cl]+ appear at m/z (%) = 414 (100) (4), 458(100) (5), 436(100)
(6).
Scheme 2. Synthesis of thiolate-gold(I) ADC complexes 7–8.
Figure 2. 1H NMR spectrum of complex 4.
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the signals of CH2 protons gave a relative ratio of isomers of ular amount of 2-picolylamine (Scheme 4). The reaction of com-
1:0.7 for 7 and 1:0.2:0.3 for 8.
plex 13, cis-[Au(C6F5)2(2-picolylamine)]ClO4, with an equimolec-
ular amount of the isocyanide CNCy gave compound 14 with a
bidentate C^N acyclic diamino carbene ligand. IR spectra of the
complexes show the absorptions corresponding to the penta-
fluorophenyl groups at around 1500, 960, 815 and 795 cm–1
With the aim to prepare gold(I) derivatives with carbene and
phosphane ligands, we synthesized the precursor complex 9
bearing a phosphane and a pyridylamine ligands (Scheme 3). It
has a nucleophilic NH2 group capable of reacting with isocyan-
ide groups to lead P–Au-Cacyclic-carbene complexes. Complex 9
was synthesized by the reaction of an equimolar amount of 2-
picolylamine and freshly prepared [Au(OTf)(PPh3)]. The coordi-
nation through the pyridine nitrogen to the gold atom is pro-
posed. The IR spectrum shows a band corresponding to the
amine NH2 group at 3205 cm–1 and the absorptions arising
from the trifluoromethanesulfonate anion at 1279, 1251, 1223,
1148 and 1027 cm–1. In the ESI+ mass spectra the fragment
[M – OTf]+ appears at m/z = 567 (100 %). The 1H NMR spectrum
shows the resonances for the 2-picolylamine ligand and the
phenyl rings in the appropriate ratio. The 31P{1H} NMR spectrum
is one singlet at 30.9 ppm.
and those of the ClO4 anion at around 1060 and 620 cm–1.
–
Two different pentafluorophenyl groups, with free rotation in
the ring, can be identified in the 19F NMR spectra of 13 and 14.
1
The H NMR spectrum of complex 14 displays the absorptions
for the 2-picolylamine and the cyclohexyl groups in an appro-
priate ratio. The ESI+ spectra show the cation molecular peak
[M – ClO4]+ at m/z = 639 (100 %) (13), 748 (100 %) (14).
Scheme 4. Synthesis of gold(III) complexes 13–14.
Crystal Structural Discussion
The molecular structures of complexes 4, 6 and 10 (Figure 3)
have been confirmed by X-ray diffraction.
Scheme 3. Synthesis of phosphane-gold(I) ADC complexes 10–12.
Three carbene triphenylphosphane gold(I) derivatives were
synthesized by the reaction of complex 9 with the equimolec-
ular amount of the corresponding isocyanide group CNR (R =
Cy (10), 2-naphthyl (11), xylyl (12)) (Scheme 3). Infrared spectra
of the complexes display, among others signals, two bands at
ca. 3250 and 3050 cm–1 corresponding to the NH groups of the
carbene N-C-N core. The ESI+ spectra show the cation molecular
peak [M – OTf]+ at m/z = 676 (100 %) (10), 720 (100 %) (11),
698 (100 %) (12).
Two rotamers were identified in the 1H NMR spectrum of
each complex. Again, the relative ratio of isomers in each deriv-
ative could be assessed with the CH2 signals which appear as a
doublet by coupling with the NH proton, 1:0.7 (10), 1:0.6 (11),
1:0.9 (12). The 31P{1H} NMR spectra of complexes 10 and 12
present a unique broad resonance corresponding to the phos-
phorus of triphenylphosphane at 40 and 40.5 ppm, respectively;
complex 11 showed two thin signals at 39.5 and 39.0 ppm that
may be attributed to the rotamers. In all the cases, the chemical
shift is higher than that of the starting material, showing the
stronger σ donor capability of the carbene ligand than 2-picolyl-
amine.
Gold(I) complexes 4, 6 and 10 crystallize in the monoclinic
(C2/c), orthorhombic (Ibca) and monoclinic (P21/n) systems, re-
spectively. One of the syn,anti-diastereomer, in which steric in-
fluence of the N-substituents is low, crystallizes in all the com-
plexes. Gold(I) atoms are in the almost linear geometry ex-
pected for gold(I) derivatives, defined by the Ccarbene and the
chloride (4, 6) or the P of the triphenylphosphane (10). The
chloride, 4 and 6, derivatives show aurophilic interactions with
Au···Au distances of 3.4085 (7) Å and 3.3631 (6) Å, respectively.
Besides, dimers form chains through classical H bonds between
the NH amide groups and the pyridine nitrogen atom of differ-
ent molecules (Figure 4). In 4 the N(2)–H(2)···N(3) [x + 1/2,
–y + 2, z] distance is 2.254 Å with an angle of 148.24° and in 6
the N(1)–H(1)···N(3) [–x + 1, –y + 2, –z] distance is 2.149 Å with
an angle of 160.02°. Similar intermolecular interactions were
found in the related gold(I) carbene derivative [AuCl{C(NEt2)-
(NH2Py-2}][12] obtained from 2-pyridilisocyanide derivative.
There are not aurophilic interactions in complex 10, probably
because of the bulkiness of the PPh3 group prevents the short
distances between the gold atoms. However, the molecules are
associated in dimers through H bonds between one NH amide
Moreover, two gold(III) derivatives 13 and 14 have been syn- group and the pyridine nitrogen atom of the neighbouring mo-
thesized (Scheme 4). Complex 13 was obtained by the reaction lecule (N(1)–H(1)···N(3) [–x + 1, –y, –z + 1] distance of 2.056 Å,
of [Au(C6F5)2(OEt2)2]ClO4, prepared in situ, with an equimolec- angle of 163.6°).
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Figure 3. Molecular crystal structures of 4, 6 and 10 (50 % thermal ellipsoids); H atoms are omitted for clarity. Selected bond lengths [Å] and angles [°]: 4:
Au(1)–C(1) 2.005(4); Au(1)–Cl(1) 2.307(1); C(1)–Au(1)–Cl(1) 179.2(1). 6: Au(1)–C(1) 2.019(6); Au(1)–Cl(1) 2.305(2); C(1)–Au(1)–Cl(1) 173.0(2). 10: Au(1)–C(38)
2.060(4); Au(1)–P(1) 2.288(1); C(38)–Au(1)–P(1) 177.3(1).
Figure 4. Examples of secondary bonds in 4 and 6: Chain polymer in 4 through aurophilic interactions and hydrogen bonding; formation of dimers in complex
6 through aurophilic contacts.
Complex 14 crystallizes in the triclinic P1 space group with displays a distorted square-planar geometry. The angles around
¯
one molecule by asymmetric unit (Figure 5). The gold(III) atom the gold(III) atom range from 87.2 to 93.2, the lowest corre-
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sponds to the C27–Au1–N1 angle of the chelating C,N ligand.
The mean deviation from the plane formed by the four donor
atoms (C1, C11, N1, and C27) of the gold center is 0.0641 Å.
The Au–Cpentafluorophenyl bond lengths are 2.057 and 2.015 Å.
The longest length is trans to the Au–Ccarbene, which is in agree-
ment with a higher trans influence of the carbene ligand than
the nitrogen one. A boat conformation is adopted by the six-
membered AuC4N chelate ring as have been observed in the
related gold(III) derivatives collected in reference 5a. There are
intra- and intermolecular NHamide···Oanion interactions that can
be considered as classical hydrogens bonds, the strongest be-
ing N(2)–H(3)··· O2 [x-1, y, z ] of 2.145 Å with an angle of 156.3°
and N3–H2···O1 of 2.264 Å with an angle of 155.8°.
Table 1. IC50 (μ
M
) (24 h) of complexes against Jurkat, MiaPaca2 and A549.
Compound
Jurkat
MiaPaca2
A549
Cisplatin[a]
(1)
(4)
(5)
(6)
(7)
(9)
(10)
(13)
10.8 1.2
0.61 0.2
>25
114.2 9.1
5.56 0.5
>25
76.5 7.4
22.22 1.1
>25
>25
>25
>25
>25
>25
>25
20.96 1.2
4.29 0.7
nt
>25
5.30 0.6
nt
9.85 0.8
13.63 1.3
13.81 0.4
>25
nt
nt
[a] Cisplatin was dissolved in H2O, see ref.[13] nt: not tested.
Table 2. IC50 (μM) (24 h) of complexes MDA-MB-231.
Compounds
MDA-MB-231
Cisplatin[a]
(10)
(13)
131.2 18
8.8 1.6
>25
(14)
16.0 5.4
[a] Cisplatin was dissolved in H2O, see ref.[13]
.
total of 24 h. Using the colorimetric MTT viability assay,[14]
(MTT 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium
=
bromide), the IC50 values (final concentration < 0.5 % DMSO)
were calculated from dose–response curves obtained by non-
linear regression analysis. IC50 values are concentrations of a
drug required to inhibit tumor cell proliferation by 50 %, com-
pared to the control cells treated with DMSO alone.
As can be seen in Table 1, the starting derivative 1 is very
active against the Jurkat and the MiaPaca cell lines but the
carbene chloride complexes 4, 5 and 6, with values of IC50 >25,
have not significant activity against the cell lines studied. Ber-
trand et al.[5b] have reported the low antiproliferative activity
against the A549 and MCF-7 cell lines of a series of neutral
chloride acyclic-carbene complexes. In our work, the substitu-
tion of chloride in 5 by 2-thiolpyridine (7) provided higher cyto-
toxicity against Jurkat and A-549 cell lines.
Figure 5. Molecular crystal structure of the cation of 14 (50 % thermal ellip-
soids); H atoms are omitted for clarity. Selected bond lengths [Å] and angles
[°]: Au(1)–C(1) 2.015(6); Au(1)–C(11) 2.057(6); Au(1)–C(27) 2.059(6); Au(1)–N(1)
2.089(5); C(11)–Au(1)–C(1) 88.9(3); C(1)–Au(1)–C(27) 90.5(2); C(11)–Au(1)–N(1)
93.2(2); C(27)–Au(1)–N(1) 87.2(2).
Cytotoxic Studies
The antiproliferative activity of the phosphane derivatives 9,
The in vitro cytotoxic activity of metal complexes 1, 4–7, 9, 10, against Jurkat, MiaPaca2, and A549, and 10, against A549 and
13, 14 has been studied. Compounds 1, 4–7 and 9 were tested MDA-MB-231, has also been measured (Table 2). Both are highly
against three different human tumor cell lines: Jurkat (T-cell effective against the cell lines tested (IC50 values range between
leukaemia), MiaPaca2 (pancreatic carcinoma) and A549 (lung 4.29 and 13.81 μ
M, notably lower than those found for cis-
carcinoma), 10 and 13 against A549 and the human breast can- platin). Complex 13 showed no significant activity against A549
cer cell line MDA-MB-231, and the gold(III) carbene 14 against and MDA-MB-231 while the carbene gold(III) derivative 14
the MDA-MB-231 cell line. Cytotoxicity values of cisplatin showed good activity against the MDA-MB-231 cell line with an
(chemotherapeutic platinum clinically employed) are used for IC50 value of 16.0 μ
M.
comparison purposes (Table 1 and Table 2).
In summary, while isocyanide gold(I) 1 showed high activity
The tested compounds are not soluble in water, but they are against Jurkat and MiaPaca cell lines and moderate against A-
soluble in DMSO and in the DMSO/water mixtures used in the 549, the chloride carbene derivatives 4, 5 and 6, with values of
tests, which contain a small amount of DMSO. We did not ob- IC50 >25, are not significantly actives against the cell lines stud-
serve any precipitation of the complexes or metallic gold while ied. Substitution of chloride by 2-thiolpyridine (7) provided
performing the test. Their colorless [D6]DMSO solutions are very higher cytotoxicity against Jurkat and A549 cell lines and the
1
stable at room temperature, as shown in the H NMR spectra phosphane derivatives 9 and 10 were highly effective against
in which the signals remain the same for weeks. Cells were the cell lines tested. The carbene gold(III) derivative 14 showed
exposed to different concentrations of each compound for a significant activity against the MDA-MB-231 cell line.
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General procedure of the synthesis of the complexes
[Au{C(NHR)(NHCH2py)}Cl] (R = Cy, (4), R = naphthyl (5), R = xylyl
(6))
Conclusions
A series of new gold(I) acyclic diamino gold(I) carbene com-
pounds with various ancillary ligands such as chloride
[Au{C(NHR)(NHCH2py)}Cl], thiolate [Au{C(NHR)(NHCH2py)}(Spy)]
or triphenylphosphane [Au{C(NHR)(NHCH2py}(PPh3)](OTf) have
been synthesized. Different conformational isomers, in solution
at room temperature, were observed for the gold(I) carbene
derivatives. Moreover, two gold(III) derivatives, cis-[Au(C6F5)2-
(2-picolylamine)]ClO4, and the bidentate N,C carbene species,
cis-[Au(C6F5)2{C(NHCy)(NHCH2py)}]ClO4, have been obtained.
IC50 values of the starting material [AuCl(CNCy)], and the com-
plexes in the tumor human cell lines Jurkat (T-cell leukaemia),
MiaPaca2 (pancreatic carcinoma), A549 (lung carcinoma) and
MDA-MB- 231 (breast carcinoma) were determined. The starting
material [AuCl(CNCy)] 1, the thiolate complex 7, the phosphane
derivatives 9 and 10 and the gold(III) carbene derivative 14
showed moderate to high activities against the cell lines tested.
A mixture of 2-picolylamine (0.0357 g, 0.33 mmol, ρ = 1.049 g mL–1)
and [AuCl(CNR)] (R = Cy: 0.1025 g, 0.3 mmol; naphthyl: 0.1157 g,
0.3 mmol; xylyl: 0.1091 g, 0.3 mmol) in dichloromethane (20 mL)
was stirred at room temperature for 24 h. The volume was reduced
to ca 5 mL and addition of n-hexane afforded 4–6 as white solids,
which were finally filtered.
Complex 4. Yield: 0.0516 g, 38 %. IR (cm–1): (NH) 3208, 3045; (C=N)
1566; (Au–Cl) 321. 1H NMR (400 MHz, CDCl3), three rotamers A, B,
C, relative ratio 1:0.6:0.2, δ: 8.46 (A, B and C) (m, 6H, 6-H, NHCy),
7.68 (A, B and C) (m, 3H, 4-H), 7.28 (A, B and C) (m, 9H, 3-H, 5-H,
NHpicolylamine), 4.96 (C) (m, 2H, CH2), 4.89 (B) (m, 2H, CH2), 4.37 (A)
(d, 2H, 3JH-H = 5.6 Hz, CH2), 4.00 and 3.44 (A, B and C) (m, 3H, CHCy),
1.91 (A, B and C) (m, 6H, Cy), 1.68 (A, B and C) (m, 9H, Cy), 1.30 (A,
B and C) (m, 15H, Cy) ppm. 13C{1H}-NMR (101 MHz, CDCl3) δ: 148.3
(s, C), 139.1 (s, C), 138.1 (s, C), 123.3 (s, C), 58.8 (s, CHCy), 49.3 (s,
CH2), 33.8 (s, CH2Cy), 25.2 (s, CH2Cy), 25.1 (s, CH2Cy), 24.5 (s, CH2Cy),
24.3 (s, CH2Cy) ppm. MS(ESI+): [M – Cl]+ m/z = 414 (100 %); [M +
H]+ m/z = 450 (42 %).
Complex 5. Yield: 0.1017 g, 69 %. IR (cm–1): (NH) 3211, 3046; (C=N)
1559, (Au–Cl) 324. 1H NMR (400 MHz, CDCl3), two rotamers A, B,
relative ratio 1:0.8, δ: 11.38 (A) (bs, 1H, NHnaphthyl), 8.63 (A) (m, 1H,
6-H), 8.53 (B) (bs, 1H, NHnaphthyl), 8.37 (B) (m, 1H, 6-H), 8.28 (B) (bs,
1H, NHpicolylamine), 8.11 (A) (bs, 1H, NHpicolylamine), 8.07 (m, 2H), 7.93–
7.28 (m, 17H), 7.18 (B) (m, 1H, 5-H), 5.01 (A) (m, 2H, CH2), 4.60 (B)
Experimental Section
Solvents were used as received without purification or drying. The
starting material [AuCltht] (tht = tetrahydrothiophene) was pre-
pared according to published procedures.[10] [Au(OTf)(PPh3)] was
obtained by reaction of [AuCl(PPh3)][15] with Ag(OTf) in dichloro-
methane and used “in situ”. The starting material
[Au(C6F5)2(OEt2)2]ClO4 was prepared by published procedures.[16] All
other reagents were commercially available and used without fur-
ther purification. 1H, 13C{1H}, 19F, and 31P{1H}, including 2D experi-
ments, were recorded at room temperature on a Bruker Avance 400
or a Bruker ARX 300 spectrometers. Chemical shifts (δ, ppm) were
reported relative to the solvent peaks in the 1H, 13C spectra or exter-
nal 85 % H3PO4 or CFCl3 in 31P or 19F spectra.
3
(d, 2H, JH-H = 5.7 Hz, CH2) ppm. 13C{1H} NMR (101 MHz, CDCl3) δ:
155.4 and 154.9 (2s, 2C), 149.2 (B) (s, 1C), 148.5 (A) (s, 1C), 138.5
and 137.2 (A and B) (2s, 2C), 138.3 and 137.6 (A and B) (2s, 2C),
133.8 and 132.6 (A and B) (2s, 2C), 133.5 and 131.9 (A and B) (2s,
2C), 130.7 (s), 129.3 (s); 129.2 (s), 128.0 (s), 127.9 (s); 127.4 (s), 127.1
(s), 126.8 (s), 126.0 (s, C), 125.8 (s), 124.3 (s), 123.7 (s), 123.2 (s), 123.0
(s), 122.1 (s), 121.8 (s), 120.0 (s), 119.4 (s), 53.9 (A) (s, 1C, CH2), 50.4
(B) (s, 1C, CH2) ppm. MS(ESI+): [M – Cl]+ m/z = 458 (100 %); [M +
H]+ m/z = 494 (9 %).
Caution: perchlorate salts with organic cations might be explosive.
Complex 6. Yield: 0.1085 g, 77 %. IR (cm–1): (NH) 3234, 3007; (C=N)
General procedure of the synthesis of the complexes
[AuCl(CNR)] (R = Cy (1), R = naphthyl (2), R = xylyl (3)).
1539; (Au–Cl) 308. In the explanation of the NMR spectra H and C
atoms of xylyl group that were identified have been noted as X′. 1H
A mixture of [AuCl(tht)] (0.6412 g, 2 mmol), and CNCy (0.2183 g,
2 mmol, ρ = 0.878 g mL–1) or CN-naphthyl (0.3064 g, 2 mmol) or
CN-xylyl (0.2624 g, 2 mmol) in dichloromethane (20 mL) was stirred
at room temperature for 2 h. The volume was reduced to ca 5 mL
and addition of n-hexane afforded 1–3 as white solids, which were
finally filtered.
3
NMR (400 MHz, CDCl3) δ: 8.38 (m, 1H, 6-H), 7.67 (td, 1H, JH-H
=
7.6 Hz, JH-H = 1.7 Hz, 4-H), 7.48 (bs, 1H, NHxylyl), 7.34 (d, 1H,
3JH-H = 7.8 Hz, 3-H), 7.26 (m, 1H, 4′-H), 7.16 (m, 4H, 5-H, 3′-H, 3′-H,
NHpicolylamine), 4.96 (d, 2H, 3JH-H =5.3 Hz, CH2), 2.22 (s, 6H, CH3) ppm.
13C{1H} NMR (101 MHz, CDCl3) δ: 190.6 (s, 1C, C=N), 155.4 (s, 1C),
149.3 (s, 1C, 6-C), 137.2 (s, 1C, 4-C), 136.2 (s, 1C), 132.6 (s, 1C), 129.6
(s, 1C), 129.4 (s, 2C, 3′-C, 3′-C), 128.7 (s, 1C, 4′-C), 123.0 (s, 1C, 5-C),
122.1 (s, 1C, 3-C), 53.9 (s, 1C, CH2), 18.4 (s, 2C, CH3) ppm. MS(ESI+):
[M – Cl]+ m/z = 436 (100 %); [M + H]+ m/z = 472 (16 %).
Complex 1. Yield: 0.5172 g, 76 %. IR (cm–1): (C≡ N) 2255; (Au–Cl) 354.
1H NMR (400 MHz, CDCl3) δ: 3.89 (m, 1H, CHCy), 2.00 (m, 2H, Cy),
1.78 (m, 4H, Cy), 1.47 (m, 4H, Cy) ppm. 13C{1H} NMR (101 MHz,
CDCl3) δ: 133.8 (t, 1C, 1JC,N = 24.7 Hz, C≡ N), 55.1 (m, 1C, CHCy), 31.7
(s, 2C, Cy), 24.7 (s, 1C, Cy), 22.7 (s, 2C, Cy) ppm.
Synthesis of [Au{C(NHR)(NHCH2py)}(Spy)] (R = naphthyl (7), R =
xylyl (8))
Complex 2. Yield: 0.7020 g, 91 %. IR (cm–1): (C≡ N) 2229; (Au–Cl)
To a suspension of K2CO3 (0.0456 g, 0.33 mmol) and 2-HSpy
(0.0334 g, 0.3 mmol) in 20 mL of dichloromethane were added
[Au{C(NHnaphthyl)(NHCH2py)}Cl] (5) (0.1481 g, 0.3 mmol) or
[Au{C(NHxylyl)(NHCH2py)}Cl] (6) (0.1415 g, 0.3 mmol) and the mix-
ture was stirred for 3 h. The suspension was filtered to remove the
KCl formed. Concentration of the solution to approximately 5 mL
and addition of hexane gave complexes 7 or 8 as white solids.
345. 1H NMR (400 MHz, CDCl3) δ: 8.10 (m, 1H), 7.97 (d, 1H, JH-H
8.8 Hz), 7.92 (m, 2H), 7.67 (m, 2H), 7.52 (dd, 1H, JH-H = 8.8 Hz, JH-H
=
=
2.1 Hz) ppm. 13C{1H} NMR (101 MHz, (CD3)2CO) δ: 164.1 (s, 1C, C≡ N),
131.3 (s, 1C), 129.9 (s, 1C), 129.3 (s, 1C), 129.1 (s, 1C), 128.9 (s, 1C),
123.8 (s, 1C) ppm. MS(ESI+): [M – Cl]+ m/z =351 (67 %).
Complex 3. Yield: 0.5208 g, 72 %. IR (cm–1): (C≡ N) 2213; (Au–Cl) 352.
3
1H NMR (400 MHz, CDCl3) δ: 7.35 (t, 1H, JH-H = 7.7 Hz, 4-H); 7.17 Complex 7. Yield: 0.0544 g, 32 %. IR (cm–1): (NH) 3195, 3008; (C=N)
3
1
(d, 2H, JH-H = 7.6 Hz, 3-H); 2.45 (s, 6H, CH3) ppm. 13C{1H} NMR
1572; (Au–S) 401. H NMR (400 MHz, (CD3)2CO), two rotamers A, B,
(101 MHz, CDCl3) δ: 131.2 (s, 1C, 4-C), 128.7 (s, 2C, 3-C, 3-C), 18.9 (s,
relative ratio 1:0.7, δ: 11.09 (B) (bs, 1H, NHnaphthyl), 10.37 (A) (bs,
1H,NHnaphthyl), 8.98 (A) (bs, 1H, NH), 8.51 (B) (bs, 1H, NH), 8.76 (m,
2C, CH3) ppm. MS(ESI+): [M – Cl]+ m/z = 329 (4 %).
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1H), 8.59 (m, 2H), 8.32 (m, 2H), 7.93 (m, 12H), 7.56 (m, 6H), 7.23 (m,
4H), 6.67 (m, 2H), 5.28 (A) (m, 2H, CH2), 4.85 (B) (m, 2H, CH2) ppm.
13C{1H} NMR (101 MHz, (CD3)2CO) δ: 170.7 (s, 1C, C=N), 150.0 (s),
138.9 (s), 129.7 (s), 128.6 (s), 127.5 (s), 126.4 (s), 124.0 (s), 123.5 (s),
Cmeta, PPh3), 124.9 (B) (s, 1C, 3-C), 123.2 (B) (s, 1C, 5-C), 122.6 (A) (s,
1C, 5-C), 121.9 (A) (s, 1C, 3-C), 59.7, 59.4 (A, B) (2s, 2C, CHCy), 54.2
(A) (s, 1C, CH2), 49.4 (B) (s, 1C, CH2), 34.1 (s, CH2Cy), 25.2 (m, CH2Cy),
25.0 (s, CH2Cy), 24.8 (s, CH2Cy) ppm. MS(ESI+): [M – OTf]+ m/z = 676
122.7 (s), 121.0 (s), 120.4 (s), 117.7 (s), 55.21 (A) (s, 1C, CH2), 49.9 (B) (100 %).
(s, 1C, CH2) ppm. MS(ESI+): [M + H]+ m/z = 569 (100 %).
Complex 11. Yield: 0.0623 g, 36 %. IR (cm–1): (NH) 3246, 3053; (C=
N) 1561; CF3SO3: 1276, 1240; 1222; 1151; 1027. H NMR (400 MHz,
CDCl3), two rotamers, relative ratio 1:0.6, δ: 11.83 (B) (m, 1H,
NHnaphthyl), 10.85 (A) (m, 1H, NHnaphthyl), 9.73 (A) (m, 1H, NH), 9.51
(B) (m, 1H, NH), 8.61 (B) (m, 1H, 6-H), 8.39 (A) (m, 1H, 6-H), 8.06 (m,
2H, naphthyl), 7.74, 7.62–7.15 (A, B) (2m, 48H, 3-H, 4-H, 5-H, naph-
Complex 8. Yield: 0.0738 g, 45 %. IR (cm–1): (NH) 3186; (C=N) 1572;
(Au–S) 402. H and C atoms of xylyl and 2-thiolpyridine groups have
been noted as X′ and X′′, respectively. 1H NMR (400 MHz, CDCl3),
three rotamers A, B, C, relative ratio 1:0.2:0.1, δ: 9.76 (B) (bs, 1H,
NHxylyl), 9.55 (C) (bs, 1H, NHxylyl), 9.32 (A) (bs, 1H, NHxylyl), 8.45 (B)
(m, 1H, 6-H), 8.45 (C) (m, 1H, 4-H), 8.42 (C) (m, 1H, 6-H), 8.40 (A) (m,
1H, 6-H), 8.10 (A, B and C) (m, 3H, 6′′-H), 7.68 (B) (m, 1H, 4-H), 7.63
1
thyl, PPh3), 5.04 (A) (d, 2H, JH-H = 6.0 Hz, CH2), 4.84 (B) (d, 2H, JH-H
=
5.7 Hz, CH2) ppm. 31P{1H} NMR (162 MHz, CDCl3) δ: 39.5, 39.0 (A, B)
(2s, 2P, PPh3) ppm. 19F NMR (376.5 MHz, CDCl3) δ: –78.2 (s, 3F,
CF3SO3) ppm. 13C{1H} NMR (75.5 MHz, CDCl3) δ: 157.2, 155.5 (A, B)
(2s, 2C, 2-C), 149.3 (A) (s, 1C, 6-C), 148.0 (B) (s, 1C, 6-C), 138.9 (s),
138.6, 137.4 (A, B) (2s, 2C, 4-C), 138.4 (s), 134.1 (m, Cortho, PPh3),
3
(A) (td, 1H, JH-H = 7.7 Hz, JH-H = 1.8 Hz, 4-H), 7.55 (B) (m, 1H, 3-H),
7.50 (B and C) (bs, 2H, NH), 7.41 (A) (m, 1H, 3-H), 7.37 (C) (m, 1H, 3-
H), 7.20–7.05 (A, B and C) (m, 18H, 5-H, 3′-H, 3′-H, 4′-H, 3′′-H, 4′′-H),
3
6.92 (A) (t, 1H, JH-H = 5.5 Hz, NH), 6.77 (A, B and C) (m, 3H, 5′′-H),
5.11 (C) (d, 2H, JH-H = 5.7 Hz, CH2), 4.97 (A) (d, 2H, JH-H = 5.7 Hz,
CH2), 4.58 (B) (d, 2H, JH-H = 6.1 Hz, CH2), 2.27 (C) (s, 6H, CH3), 2.18
(A) (s, 6H, CH3), 2.11 (B) (s, 6H, CH3) ppm. MS(ESI+): [M – py] m/z =
463 (100 %); [M + H]+ m/z = 547 (2 %).
133.5 (m), 132.1 (m, Cpara, PPh3), 131.9 (s, naphthyl), 129.5 (m, Cmeta
,
PPh3), 128.4 (s, naphthyl), 127.9 (s, naphthyl), 127.0 (s, naphthyl),
126.0 (s, naphthyl), 125.1, 122.0 (A, B) (2s, 2C, 3-C), 123.5, 122.7 (A,
B) (2s, 2C, 5-C), 123.0 (s, naphthyl), 122.8 (s, naphthyl), 120.6 (s,
naphthyl), 118.6 (s, naphthyl), 54.9 (A) (s, 1C, CH2), 49.9 (B) (s, 1C,
CH2) ppm. MS(ESI+): [M – OTf]+ m/z = 720 (100 %).
Synthesis de [Au(pyCH2NH2)(PPh3)](OTf) (9)
A solution of [Au(OTf)(PPh3)] (0.1277 g, 0.2 mmol) prepared in situ
and 2-picolylamine (0.0216 g, 0.2 mmol, ρ = 1.049 g mL–1) was
stirred in dichloromethane (20 mL) for 2 h at room temperature.
The volume was reduced to 5 mL, and addition of hexane afforded
compound 9 as a white solid.
Complex 12. Yield: 0.1299 g, 77 %. IR (cm–1): (NH) 3239, 3054; (C=
1
N) 1561; (CF3SO3) 1275, 1241, 1222, 1151, 1027. H NMR (400 MHz,
CDCl3), H and C atoms of xylyl group has been noted as X′, two
rotamers, A, B, relative ratio 1:0.9, δ: 10.40 (A) (bs, 1H, NHxylyl), 9.80
(A) (bs, 1H, NHxylyl), 9.66 (B) (m, 1H, NH), 9.31 (A) (m, 1H, NH), 8.40
(B) (m, 1H, 6-H), 8.46 (A) (m, 1H, 6-H), 7.80, 7.74 (A, B) (2m, 2H, 4-
H), 7.74, 7.52–7.02 (A, B) (2m, 39H, 3-H, 5-H, xylyl, PPh3), 4.93 (A) (d,
Complex 9. Yield: 0.1318 g, 92 %. IR (cm–1): (NH2) 3205; CF3SO3:
1279, 1251, 1223; 1148, 1027 cm–1
.
1H NMR (400 MHz, CDCl3), δ:
3
4
8.44 (m, 1H, 6-H), 7.71 (td, 1H, JH-H = 7.7 Hz, JH-H = 1.8 Hz, 4-H),
3
2H, JH-H = 5.8 Hz, CH2), 4.81 (B) (d, 2H, JH-H = 5.8 Hz, CH2), 2.30 (s,
3
7.49 (m, 15H, PPh3), 7.37 (d, 1H, JH-H = 7.7 Hz, 3-H), 7.23 (m, 1H, 5-
3H, CH3), 2.18 (s, 3H, CH3) ppm. 31P{1H} NMR (162 MHz, CDCl3) δ:
40.0 (s, 1P, PPh3) ppm. 19F NMR (282.4 MHz, CDCl3) δ: –78.3 (s, 3F,
CF3SO3) ppm. 13C{1H} NMR (75.5 MHz, CDCl3) δ: 158.3, 155.8 (A, B)
(2s, 2C, 2-C), 149.3 (A) (s, 1C, 6-C), 148.0 (B) (s, 1C, 6-C), 138.6, 138.2
(A, B) (2s), 138.5 (s), 137.3 (s), 137.1, 136.7 (A, B) (2s), 134.1 (bs),
132.1 (bs), 129.5 (bs), 128.5 (s), 128.2 (s), 128.2 (s), 125.1 (s), 123.4
(s), 122.9 (s), 122.7 (s), 121.7 (s), 118.7 (s), 54.1 (A) (s, 1C, CH2), 49.9
(B) (s, 1C, CH2), 19.0 (s, 1C, CH3), 19.0 (s, 1C, CH3) ppm. MS(ESI+):
[M – OTf]+ m/z = 698 (100 %).
H), 4.97 (m, 2H, NH2), 4.49 (m, 2H, CH2) ppm. 31P{1H} NMR (162 MHz,
CDCl3) δ: 30.9 (s, 1P, PPh3) ppm. 19F NMR (376.5 MHz, CDCl3) δ:
–78.1 (s, 3F, CF3SO3) ppm. 13C{1H} NMR (101 MHz, CDCl3) δ: 149.3
(s, 1C, 6-C), 139.0 (s, 1C, 4-C), 134.3 (d, 6C, 3Jc-p = 13.6 Hz, Cortho
,
PPh3), 132.4 (d, 3C, 5Jc-p = 2.5 Hz, Cpara, PPh3), 129.6 (d, 6C, 4Jc-p =
12.0 Hz, Cmeta, PPh3), 128.0 (d, 3C, 1Jc-p = 63.3 Hz, Cipso, PPh3), 123.3,
123.3 (2s, 2C, 3-C, 5-C), 49.23 (s, 1C, CH2) ppm. MS(ESI+): [M – OTf]+
m/z = 567 (100 %).
Synthesis of [Au{C(NHR)(NHCH2py}(PPh3)](OTf) (R = Cy (10), R =
naphthyl (11), R = xylyl (12))
Synthesis of cis-[Au(C6F5)2(pyCH2NH2)](ClO4) (13). Di-(2-pi-
colyl)amine (0.0598 g, 0.3 mmol, ρ = 1.107 g mL–1) was added to a
freshly prepared solution of [Au(C6F5)2(OEt2)2]ClO4 (0.2336 g,
0.3 mmol) in diethyl ether (20 mL), and the mixture was stirred for
1 h. Complex 13 precipitated as a white solid and was filtered off.
Yield: 0.124 g (56 %). IR: (NH2): 3219; (C6F5): 1508, 965; (cis-C6F5):
A mixture of [Au(pyCH2NH2)(PPh3)](OTf) (9) (0.1433 g, 0.2 mmol)
and CNCy (0.0249 g, 0.2 mmol, ρ = 0.878 g mL–1) or CN-naphthyl
(0.0306 g, 0.2 mmol) or CN-xylyl (0.0262 g, 0.2 mmol) in dichloro-
methane (20 mL) was stirred at room temperature for 48 h. The
volume was reduced to ca. 5 mL and addition of n-hexane afforded
10–12 as white solids, which were finally filtered.
1
818, 807; (ClO4): 1078, 621 cm–1. H NMR (400 MHz, (CD3)2SO): δ =
8.42 (td, JHH = 7.6 Hz, JHH = 1.2 Hz, 1H, 4-H), 8.25 (d, JHH = 5.6 Hz,
2H, 6-H), 8.07 (d, JHH = 8Hz, 1H, 3-H), 7.67 (t, JHH = 6.4 Hz, 1H, 5-H),
7.11 (s, 2H, NH2), 4.99 (s, 2H, CH2) ppm. 19F NMR (376.5 MHz,
(CD3)2SO): δ = –121.4 (m, “d”, 3Jo-F, m-F = 21.2 Hz, 2F, o-F), δ =
–122.9 (m, “d”, 3Jo-F, m-F = 21.2 Hz, 2F, o-F), –154.6 (m, “q”, 3Jp-F,
m-F = 22.4 Hz, 2F, p-F),–159.9 (m, 2F, m-F), –161.1 (m, 2F, m-F) ppm.
13C{1H} NMR (101 MHz, (CD3)2SO): δ = 165.7 (s, 1C, 2-C), 148.2 (s,
1C, 6-C), 143.3 (s, 1C, 4-C), 125.9 (s, 1C, 5-C), 123.6 (s, 2C, 3-C), 52.1
(s, 1C, CH2) ppm. MS(ESI+): [M – ClO4]+ m/z = 639 (100 %).
Complex 10. Yield: 0.0760 g, 46 %. IR (cm–1): (NH) 3265, 3055; (C=
1
N) 1570; CF3SO3: 1279, 1242, 1222, 1151, 1027. H NMR (400 MHz,
CDCl3), two rotamers A, B, relative ratio 1:0.7, δ: 9.04, 8.62 (A and B)
(2m, 2H, NHCy), 8.92 (A) (m, 1H, NH), 8.73 (B) (m, 1H, NH), 8.43 (B)
(m, 1H, 6-H), 8.36 (A) (m, 1H, 6-H), 7.72 (A, B) (m, 2H, 4-H), 7.65 (B)
(m, 1H, 3-H), 7.40 (A) (d, 1H, 3JH-H = 8.0 Hz, 3-H), 7.50 (A, B) (m, 30H,
PPh3), 7.22 (B) (m, 1H, 5-H), 7.13 (A) (m, 1H, 5-H), 4.84 (A) (d, 2H,
JH-H = 6.1 Hz, CH2), 4.55 (B) (d, 2H, JH-H = 5.5 Hz, CH2), 3.63 (A
and B) (m, 2H, CHCy), 2.00–0.88 (m, 20H, CH2Cy) ppm. 31P{1H} NMR
(162 MHz, CDCl3) δ: 40.5 (s, 1P, PPh3) ppm. 19F NMR (376.5 MHz,
CDCl3) δ: –78.3 (s, 3F, CF3SO3) ppm. 13C{1H} NMR (101 MHz, CDCl3)
δ: 158.5, 155.7 (A, B) (2s, 2C, 2-C), 149.1 (A) (s, 1C, 6-C), 147.8 (B) (s,
1C, 6-C), 138.2, 137.3 (A, B) (2s, 2C, 4-C), 134.2 (d, 6C, 3Jc-p = 13.2 Hz,
Synthesis of cis-[Au(C6F5)2{C(NHCy)(NHCH2py)}]ClO4 (14)
A mixture of CNCy (0.0218 g, 0.2 mmol) and complex 13 (0.0249 g,
0.2 mmol) in a mixture of dichloromethane/acetone (10 mL/5 mL),
was stirred at room temperature. After stirring for 48 h, the volume
was reduced to 5 mL and addition of n-hexane afforded complex
4
Cortho, PPh3), 132.3 (s, 3C, Cpara, PPh3), 129.7 (d, 6C, Jc-p = 10.8 Hz,
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14 as a white solid, which was finally filtered. Yield: 0.139 g (82 %).
IR(cm–1): (NH): 3264; (C=N): 1598; (C6F5): 1508, 961; (cis-C6F5): 815,
Acknowledgments
Authors thank the Ministerio de Economía y Competitividad
(MINECO-FEDER CTQ2016–75816-C2–1-P) and Gobierno de Ara-
gón-Fondo Social Europeo (E07_17R) for financial support. We
greatly acknowledged Dr. Isabel Marzo for her help in the cell
viability tests.
794; (ClO4): 1062, 620. 1H NMR (400 MHz, CDCl3): 8.38 (d, 1H, JH–H
5.2 Hz, 1H, 6-H), 8.24 (t, 1H, JH–H = 8 Hz, 4-H), 8.08 (d, 1H, JHH
=
=
8 Hz, 3-H), 7.64 (t, 1H, JHH = 7.2 Hz, 5-H), 6.14 (d, 1H, JHH = 8 Hz,
NHCy), 5.10 (bs, 2H, CH2), 3.69 (m, 1H, CHCy), 1.1 (m, 10H, Cy). 19F
3
NMR (376.5 MHz, CDCl3): δ = –122.9 (m, 2F, o-F), –151.9 (t, 2F, Jp-
F, m-F = 21.2 Hz, p-F), –152.6 (t, 2F, 3Jp-F, m-F = 20.8 Hz, p-F), –157.7
(m, 2F, m-F), –158.3 (m, 1F, m-F). 13C{1H} NMR (101 MHz, (CD3)2SO):
δ = 153.2 (s, 1C, 2-C), δ = 151.6 (s, 1C, 6-C), 143.8 (s, 1C, 4-C), 127.6
(s, 1C, 3-C), 126.7 (s, 1C, 5-C), 53.2 (s, 1C, CHCy), 51.1 (s, 1C, CH2),
32–22 (5s, 5C, Cy) ppm. [M – ClO4]+ m/z = 748 (100 %).
Keywords: Cancer · Carbene ligands · Cytotoxicity · Gold
[1] R. A. Michelin, A. J. L. Pombeiro, M. F. C. Guedes da Silva, Coord. Chem.
Rev. 2001, 218, 75–112.
Crystal Structure Determinations. Single crystals of complexes
were obtained by slow diffusion of hexane into a dichloromethane
solution (4, 6, 10) or chloroform (14). Data were registered on a
Bruker Smart 1000 CCD diffractometer. The crystals were mounted
in inert oil on glass fibers and transferred to the cold gas stream of
the diffractometer. Data were collected using monochromated
Mo-Kα radiation (λ = 0.71073) in ω-scans. Absorption corrections
based on multiple scans were applied with the program SADABS.
The structures were solved by direct methods and refined on F2
using the program SHELXL-2016.[17] All non-hydrogen atoms were
refined anisotropically. Hydrogen atoms were included using a rid-
ing model. CCDC numbers 1919426 (6), 1919427 (14), 1919428 (10)
and 1919429 (4) contains the supplementary crystallographic data.
These data can be obtained free of charge by The Cambridge Crys-
tallography Data Center.
[2] a) L. M. Slaughter, ACS Catal. 2012, 2, 1802–1816; b) V. P. Boyarskiya, K. V.
Luzyanina, V. Y. Kukushki, Coord. Chem. Rev. 2012, 256, 2029–2056; c) S.
Handa, L. M. Slaughter, Angew. Chem. Int. Ed. 2012, 51, 2912–2915;
Angew. Chem. 2012, 124, 2966; d) A. S. K. Hashmi, C. Lothschütz, C. Böhl-
ing, F. Rominger, Adv. Synth. Catal. 2010, 352, 3001–3012; e) V. Göker,
S. R. Kohl, F. Rominger, G. Meyer-Eppler, L. Volbach, G. Schnakenburg, A.
Lützen, A. S. K. Hashmi, J. Organomet. Chem. 2015, 795, 45–52; f) S.
Tšupova, M. Rudolph, F. Rominger, A. S. K. Hashmi, Adv. Synth. Catal.
2016, 358, 3999–4005; g) A. S. K. Hashmi, T. Hengst, C. Lothschtz, F.
Rominger, Adv. Synth. Catal. 2010, 352, 1315–1337; h) A. S. K. Hashmi,
T. Häffner, M. Rudolph, F. Rominger, Eur. J. Org. Chem. 2011, 667–671; i)
C. Bartolome, Z. Ramiro, D. García-Cuadrado, P. Pérez-Galán, M. Raducan,
C. Bour, A. M. Echavarren, P. Espinet, Organometallics 2010, 29, 951–956;
j) C. Bartolomé, D. García-Cuadrado, Z. Ramiro, P. Espinet, Organometallics
2010, 29, 3589–3592; k) Y. M. Wang, C. N. Kuzniewski, V. Rauniyar, C.
Hoong, F. D. Toste, J. Am. Chem. Soc. 2011, 133, 12972–12975; l) M. Ali-
aga-Lavrijsen, R. P. Herrera, M. D. Villacampa, M. C. Gimeno, ACS Omega
2018, 3, 9805–9813.
CCDC 1919426 (for 6), 1919427 (for 14), 1919428 (for 10), and
1919429 (for 4) contain the supplementary crystallographic data for
this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre.
[3] G. Ciancaleoni, L. Biasiolo, G. Bistoni, A. Macchioni, F. Tarantelli, D. Zuccac-
cia, L. Belpassi, Chem. Eur. J. 2015, 21, 2467–2473.
[4] a) O. Dada, D. Curran, C. O′Beirne, H. Müller-Bunz, X. Zhu, M. Tacke, J.
Organomet. Chem. 2017, 840, 30–37; b) W. Liu, R. Gust, Coord. Chem. Rev.
2016, 329, 191–213; c) I. Ott, Coord. Chem. Rev. 2009, 253, 1670–1681;
d) B. Bertrand, A. Citta, I. L. Franken, M. Picquet, A. Folda, V. Scalcon, M. P.
Rigobello, P. Le Gendre, A. Casini, E. Bodio, J. Biol. Inorg. Chem. 2015, 20,
1005–1020; e) A. M. Al-Majid, M. I. Choudhary, S. Yousuf, A. Jabeen, R.
Imad, K. Javeed, N. N. Shaikh, A. Collado, E. Sioriki, F. Nahra, S. P. Nolan,
ChemistrySelect 2017, 2, 5316–5320; f) J. Arcau, V. Andermark, M. Rod-
rigues, I. Giannicchi, L. Pérez-Garcia, I. Ott, L. Rodríguez, Eur. J. Inorg.
Chem. 2014, 6117–6125; g) C. Bazzicalupi, M. Ferraroni, F. Papi, L. Massai,
B. Bertrand, L. Messori, P. Gratteri, A. Casini, Angew. Chem. Int. Ed. 2016,
55, 4256–4259; Angew. Chem. 2016, 128, 4328; h) R. McCall, M. Miles, P.
Lascuna, B. Burney, Z. Patel, K. J. Sidoran, V. Sittaramane, J. Kocerha, D. A.
Grossie, J. L. Sessler, K. Arumugam, J. F. Arambula, Chem. Sci. 2017, 8,
5918–5929; i) C. Schmidt, B. Karge, R. Misgeld, A. Prokop, R. Franke, M.
Brönstrup, I. Ott, Chem. Eur. J. 2017, 23, 1869–1880; j) R. Visbal, V. Fernán-
dez-Moreira, I. Marzo, A. Laguna, M. C. Gimeno, Dalton Trans. 2016, 45,
15026–15033; k) T. Zou, C. N. Lok, P. K. Wan, Z. F. Zhang, S. Fung, C. M.
Che, Curr. Opin. Chem. Biol. 2018, 43, 30–36; l) M. Mora, M. C. Gimeno,
R. Visbal, Chem. Soc. Rev. 2019, 48, 447–462; m) C. Zhang, M.-L. Maddel-
ein, R. W.-Y. Sun, H. Gornitzka, O. Cuvillier, C. Hemmert, Eur. J. Med. Chem.
2018, 157, 320–332; n) N. Curado, N. Gimenez, K. Miachin, M. Aliaga-
Lavrijsen, M. A. Cornejo, A. A. Jarzecki, M. Contel, ChemMedChem 2019,
14, 1086–1095.
[5] a) S. Montanel-Pérez, R. P. Herrera, A. Laguna, M. D. Villacampa, M. C.
Gimeno, Dalton Trans. 2015, 44, 9052–9062; b) B. Bertrand, A. S. Roma-
nov, M. Brooks, J. Davis, C. Schmidt, I. Ott, M. O'Connell, M. Bochmann,
Dalton Trans. 2017, 46, 15875–15887; c) M. R. M. Williams, B. Bertrand, J.
Fernandez-Cestau, Z. A. E. Waller, M. A. O'Connell, M. Searcey, M. Boch-
mann, Dalton Trans. 2018, 47, 13523–13534; d) B. Bertrand, M. R. M.
Williams, M. Bochmann, Chem. Eur. J. 2018, 24, 11840–11851.
[6] R. Oun, Y. E. Moussa, N. J. Wheate, Dalton Trans. 2018, 47, 6645–6653.
[7] a) D. T. Felson, J. J. Anderson, R. F. Meenan, Arthritis Rheum. 1990, 33,
1449–1461; b) C. Fan, W. Zheng, X. Fu, X. Li, Y.-S. Wong, T. Chen, Cell
Death Dis. 2014, 5, 1191–1201; c) T. Zou, C. T. Lum, C.-N. Lok, J.-J. Zhanga,
C.-M. Che, Chem. Soc. Rev. 2015, 44, 8786–8801; d) B. K. Rana, A. Nandy,
Cell cultures
Jurkat (leukaemia) and MiaPaca2 (pancreatic carcinoma) cell lines
were maintained in RPMI 1640, while A549 (lung carcinoma) were
grown in DMEM (Dulbecco's modified Eagle's medium). Both media
were supplemented with 5 % fetal bovine serum (FBS), 200 U mL–1
penicillin, 100 μg mL–1 streptomycin and 2 mM L-glutamine. Me-
dium for A549 cells was also supplemented with 2.2 g L–1 Na2CO3,
100 μg mL–1 piruvate and 5 mL non-essential amino acids (Invitro-
gen). MDA-MB-231 cells are grown at 37 °C in Leibovitz's L-15 me-
dium supplemented with 2 m
M glutamine and 15 % fetal bovine
serum (FBS). Cultures were maintained in a humidified atmosphere
of 95 % air/ 5 % CO2 at 37 °C.
Cytotoxicity assays by MTT
The MTT assay was used to determine cell viability as an indicator
for cell sensitivity to the complexes. Exponentially growing cells
were seeded at a density of approximately 1 × 105 cells per mL
(A549, MiaPaca2) or 3 × 105 cells per mL (Jurkat, MDBA-MB-231) in
a 96-well flat-bottomed microplate and 24 h later they were incu-
bated for 24 h with the compounds. The complexes were dissolved
in DMSO and tested in concentrations ranging from 0.5 to 25 μ
M
and in quadruplicate. Cells were incubated with our compounds for
24 h at 37 °C. 10 μL of MTT (5 mg mL–1) was added and plates were
incubated for 1–3 h at 37 °C. Finally, 100 μL per well iPrOH (0.05
M
HCl) was added. The optical density was measured at 490 nm using
a 96-well multiscanner autoreader (ELISA). The IC50 was calculated
by nonlinear regression analysis using Origin software (Origin Soft-
ware, Electronic Arts, Redwood City, California, USA).
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V. Bertolasi, C. W. Bielawski, K. D. Saha, J. Dinda, Organometallics 2014,
33, 2544–2548; e) F. Cisnetti, A. Gautier, Angew. Chem. Int. Ed. 2013, 52,
11976–11978; Angew. Chem. 2013, 125, 12194; f) W. Liu, K. Bensdorf, M.
Proetto, U. Abram, A. Hagenbach, J. Med. Chem. 2012, 55, 3713–3724.
[8] a) E. Atrian-Blasco, S. Gascon, M. J. Rodíguez-Yoldi, M. Laguna, E. Cerrada,
Inorg. Chem. 2017, 56, 8562–8579; b) A. Gutiérrez, I. Marzo, C. Cativiela,
A. Laguna, M. C. Gimeno, Chem. Eur. J. 2015, 21, 11088–11095; c) E.
García-Moreno, S. Gascón, E. Atrián-Blasco, M. J. Rodriguez-Yoldi, E. Cer-
rada, M. Laguna, Eur. J. Med. Chem. 2014, 79, 164–172; d) A. Gutiérrez,
L. Gracia-Fleta, I. Marzo, C. Cativiela, A. Laguna, M. C. Gimeno, Dalton
Trans. 2014, 43, 17054–17066; e) H. Goitia, Y. Nieto, M. D. Villacampa, C.
Kasper, A. Laguna, M. C. Gimeno, Organometallics 2013, 32, 6069–6078;
f) J. C. Lima, L. Rodriguez, Anti-Cancer Agents Med. Chem. 2011, 11, 921–
928; g) L. Ortego, F. Cardoso, S. Martins, M. F. Fillat, A. Laguna, M. Meire-
les, M. D. Villacampa, M. C. Gimeno, J. Inorg. Biochem. 2014, 130, 32–37.
[9] a) R. L. White-Morris, M. M. Olmstead, A. L. Balch, O. Elbjeirami, M. A.
Omary, Inorg. Chem. 2003, 42, 6741–6748; b) . A. S. K. Hashmi, Y. Yu, F.
Rominger, Organometallics 2012, 31, 895–904; c) R. Heathcote, J. A. S.
Howell, N. Jennings, D. Cartlidge, L. Cobden, S. Coles, M. Hursthouse,
Dalton Trans. 2007, 1309–1315; d) V. P. Dyadchenko, N. M. Belov, V. P.
Dyadchenko, Y. L. Slovokhotov, A. M. Banaru, D. A. Lemenovskii, Russ.
Chem. Bukk. Int. Ed. 2010, 59, 539–543.
[10] R. Usón, A. Laguna, M. Laguna, Inorg. Synth. 1989, 26, 85–91.
[11] a) G. Banditelli, F. Bonati, S. Calogero, G. Valle, F. E. Wagner, R. Wordel,
Organometallics 1986, 5, 1346–1352; b) H. Seo, D. R. Snead, K. A. Abboud,
S. Hong, Organometallics 2011, 30, 5725–5730; c) C. Bartolomé, D. García-
Cuadrado, Z. Ramiro, P. Espinet, Organometallics 2010, 49, 9758–9764.
[12] C. Bartolomé, M. Carrasco-Rando, S. Coco, C. Cordovilla, J. M. Martín-
Álvarez, P. Espinet, Inorg. Chem. 2008, 47, 1616–1624.
[13] M. Frik, J. Fernández-Gallardo, O. Gonzalo, V. Mangas-Sanjuan, M. Gonzá-
lez-Alvarez, A. S. del Valle, C. Hu, I. González-Alvarez, M. Bermejo, I.
Marzo, M. Contel, J. Med. Chem. 2015, 58, 5825–5841.
[14] T. Mossman, J. Immunol. Methods 1983, 65, 55–63.
[15] R. Uson, A. Laguna, Organomet. Synth. 1986, 3, 322–342.
[16] R. Usón, A. Laguna, M. L. Arrese, Synth. React. Inorg. Met-Org. Chem. 1984,
14, 557–567.
[17] G. M. Sheldrick, Acta Crystallogr. Sect. C 2015, 71, 3–8.
Received: May 29, 2019
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Full Paper
Diamino Carbenes
A series of new gold(I) and gold(III)
acyclic diamino gold(I) carbene com-
pounds with various ancillary ligands
such as chloride, thiolate and phos-
phane have been synthesized and
their cytotoxic activity tested.
S. Montanel-Pérez, R. Elizalde,
A. Laguna, M. D. Villacampa,*
M. C. Gimeno* ................................. 1–10
Synthesis of Bioactive N-Acyclic
Gold(I) and Gold(III) Diamino Carb-
enes with Different Ancillary Li-
gands
DOI: 10.1002/ejic.201900606
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim