Development of a novel highly anti-proliferative family of gold complexes: Au(i)-phosphonium-phosphines

Article abstract of DOI:10.1039/d0dt03708g

A family of gold(i)-phosphonium-phosphine complexes was synthesized thanks to an efficient 5-step strategy, which involves a phospha-Fries rearrangement. It enables the facile variation of the phosphonium moiety. All the complexes along with a synthetic intermediate were fully characterized (a crystal structure was obtained for two of them). The antiproliferative properties of the six novel complexes were evaluated on three human cancer cell lines (A549, MDA-MB-231, and SW480) and compared to those of three benchmark anticancer drugs used in clinics (oxaliplatin, 5-fluorouracil, andpaclitaxel) and to a phosphonium-free gold(i) complex [Au(PPh₃)Br]. All the gold(i) complexes, containing a phosphonium, displayed strong anti-proliferative properties. They were more efficient thanoxaliplatinand 5-fluorouracil, and one of the complexes was even more efficient thanpaclitaxel.

Full text of DOI:10.1039/d0dt03708g

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Development of a novel highly anti-proliferative
family of gold complexes: Au(I)-phosphonium-
phosphines†
Cite this: Dalton Trans., 2021, 50,
4880
a
b
a
a
Benjamin Rousselle, Florence Bouyer, Jérôme Bayardon,
Ma yriam Laly,
b
a
François Ghiringhelli,
Raluca Malacea-Kabbara
Yoann Rousselin,
Ewen Bodio * and
a
*
A family of gold(I)-phosphonium-phosphine complexes was synthesized thanks to an efficient 5-step
strategy, which involves a phospha-Fries rearrangement. It enables the facile variation of the phos-
phonium moiety. All the complexes along with a synthetic intermediate were fully characterized (a crystal
structure was obtained for two of them). The antiproliferative properties of the six novel complexes were
evaluated on three human cancer cell lines (A549, MDA-MB-231, and SW480) and compared to those of
three benchmark anticancer drugs used in clinics (oxaliplatin, 5-fluorouracil, and paclitaxel) and to a
Received 27th October 2020,
Accepted 23rd February 2021
3
phosphonium-free gold(I) complex [Au(PPh )Br]. All the gold(I) complexes, containing a phosphonium,
DOI: 10.1039/d0dt03708g
displayed strong anti-proliferative properties. They were more efficient than oxaliplatin and 5-fluorouracil,
and one of the complexes was even more efficient than paclitaxel.
rsc.li/dalton
1
1
cancer
agents. Concerning phosphonium-phosphine,
Introduction
Nakagawa and coll. reported an elegant study, in which they
Phosphonium-phosphines are a class of compounds, which developed an OFF/ON smart probe for detecting reactive
1
2
are not so common. They were mainly used as ligands – chiral oxygen species (ROS) in mitochondria. Bagherjeri and coll.
1
–5
or not – for catalysis or as Wittig intermediates.
They were chose to use the coordination properties of phosphine to
also used to give humidity-sensitive properties to polyelectro- develop a zwitterionic Hg(II)-based antibacterial complex,
6
lyte copolymers. However, in the present study, we are inter- where they took advantage of phosphonium to counterbalance
1
3
ested in their biological applications. Phosphonium is known the negative charge of the mercury complex.
to be a good vector to target mitochondria, especially in cancer In the present study, we decided to combine the vectoriza-
7
cells. Indeed, it was reported that phosphonium can accumu- tion properties of phosphonium with the ability of phosphine
late ten times more in cancer cells than in healthy ones, to coordinate gold(I) in order to develop novel anti-cancer
because the negative potential of cancer cell mitochondria is agents. Among the metal-based complexes, Au(I)-phosphine
8
higher than that of healthy ones (163 mV vs. 104). Moreover, complexes attract increasing interest since the repurposing of
the association of the water solubility brought by the positive auranofin – an anti-rheumatoid drug – for anticancer appli-
1
4
charge and the lipophilicity due to its delocalization facilitate cations. Gold(I) complexes were extensively studied by many
1
5–26
the crossing of the cell membrane of phosphonium deriva- researchers including our group.
In contrast to platinum
7
tives. These are some of the reasons why phosphoniums were derivatives, the main hypothesis concerning the mechanism of
9
10
used for vectorizing antioxidant, antibacterial,
or anti- action of gold(I)-based phosphine complexes is the inhibition
of thio and/or seleno-cysteine enzymes, such as thioredoxine
reductases (TrxRs), via the coordination of the gold center to
a
ICMUB UMR6302, CNRS, Univ. Bourgogne Franche-Comté, F-21000 Dijon, France.
E-mail: ewen.bodio@u-bourgogne.fr, raluca.malacea@u-bourgogne.fr;
Tel: +33(0)3 803 96 076, +33(0)3 803 937 73
thiols or selenols. TrxRs are in charge of the regulation of oxi-
dative stress and their inhibition leads to the increase of ROS
b
27–29
INSERM UMR 1231, Dijon, France
and to apoptosis.
Based on this observation, we wanted to
1
13
1
31
1
†
Electronic supplementary information (ESI) available: H, C{ H} and P{ H}
take advantage of the phosphonium to vectorise the Au(I)-
phosphine complex to the mitochondria, where TrxR2 is
located. Moreover, the presence of the phosphonium will
improve the solubility of the gold complexes in biological
media (Fig. 1).
NMR spectra of compounds 2, 3, 4, 5a-f, and Ia-g, stability study, water solubility
evaluation of the complexes, biological experimental data, crystal structure and
table of crystal data of compound Ie and If. CCDC 2036897 and 2036898. For ESI
and crystallographic data in CIF or other electronic format see DOI: 10.1039/
d0dt03708g
4880 | Dalton Trans., 2021, 50, 4880–4889
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Fig. 1 General structure of the targeted complexes.
Results and discussion
Synthesis of gold-phosphonium-phosphine complexes Ia-f
Scheme 2 Synthesis of ligand 5 by phosphine quaternization.
The synthesis of the phosphonium-phosphine ligands is based
on the quaternisation reaction of various phosphines with
[(2-bromo methyl)phenyl]diphenylphosphine borane 4. This
phosphonium-phosphine ligands 5 (Scheme 2). 2.5 equiva-
halogenated intermediate was prepared via a three-step syn-
thetic route starting from the commercially available 2-bromo-
benzyl alcohol (1) (Scheme 1). In the first step, the reaction of
lents of the phosphine PR R’ were necessary to enable the
2
nucleophilic substitution on the bromomethyl moiety and the
decoordination of the borane group in one single step. This
methodology avoids the homoleptic quaternisation of bromo
derivative 4 and gives the desired phosphonium phosphine
ligands 5 with yields up to 91%. Six different phosphines
1
with chlorodiphenylphosphine in the presence of ethyldiiso-
propylamine followed by BH ·DMS addition gave the 2-bromo-
benzyl phosphinite borane derivative 2 in 83% yield. Its
2
NMR spectrum presents a signal at 107.2 ppm in CD Cl the
3
3
1
P
2
bearing an alkyl or aryl group with electron withdrawing or
characteristic region for phosphinite borane derivatives. Metal-
halogen exchange takes place when tBuLi is added to 2 to
further give, by an elegant phospha-Fries rearrangement, the
31
electron donating groups were used for this study. The
P
NMR spectra of the ligands 5 present a signal ranging from
14 to −17 ppm for the phosphine moiety and a second one
ranging from 20 to 26 ppm for the phosphonium group
Table 1) except ligand 5d which gives a signal at +32.6 ppm
−
(2-hydroxymethylphenyl)phosphine borane derivative 3 in 77%
yield. This rearrangement is based on the reaction described
(
3
0
by Melvin in 1991 with aryl phosphates and further devel-
for the phosphonium group. This chemical shift is very
similar to that described in the literature for methyltributyl-
3
1
32
oped by Beak or Jugé with phosphinite borane derivatives.
3
1
A significant change is observed in the P NMR spectrum
with the appearance of a signal at 18.3 ppm. In the last step,
the Appel reaction allowed conversion of the alcohol 3 in the
corresponding alkyl halide 4 in 83% yield using triphenyl-
phosphine and tetrabromomethane at room temperature. A
33
phosphonium tetrafluoroborate at +32.8 ppm.
31
Table 1 Structures, P NMR data and yields for phosphonium-phos-
phines 5a-f
3
1
minor shift in the P NMR spectrum was observed for this
step (4: δ = 19.9 ppm). In the H NMR spectrum, the doublet No
1
31
Structure
P NMR (ppm)
Yield
87%
corresponding to the methylene of compound 3 (δ = 4.54 ppm,
J = 5.7 Hz) is transformed into a singlet for compound 4 due to
the loss of coupling with the hydroxyl proton.
The halogenated phosphine borane derivative 4 was further
reacted with various phosphines to give the corresponding
5
5
5
5
a
b
c
−15.12
+22.97
+22.08
+20.72
+32.60
−15.62
−17.24
−14.57
91%
82%
67%
d
5
5
e
f
−14.13
−15.53
+26.29
+21.75
90%
80%
Scheme 1 Synthesis of (o-bromomethylphenyl) phosphine borane 4.
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Gold complexes Ia-f were readily synthesized by reacting the
Dalton Transactions
phosphonium-phosphines 5a-f with the bromo(tetrahydrothio-
phene) gold(I) precursor in dichloromethane at room tempera-
3
1
ture (Scheme 2). The reaction was monitored by P NMR and
a significant shift for the phosphine moiety could be observed
from −15 ppm to 24–28 ppm (Table 2). After one hour at room
temperature, the reaction is completed, and the corresponding
gold complexes Ia-f were obtained with yields up to 94%. It is
worth noting that the use of [Au(tht)Br] instead of [Au(tht)Cl]
prevents the formation of a mixture of complexes. Indeed,
when using [Au(tht)Cl], the bromide counter anion of 5 can
exchange with the chlorido ligand of the gold complex leading
to the formation of “P–Au–Cl” and “P–Au–Br” complexes.
The stability of the complexes Ia-If was investigated thanks
to NMR studies. They were stable at least 72 h in DMSO and in
the presence of water (see the ESI† for details).
Single crystals suitable for DRX analysis were obtained for
Ie and If from a biphasic dichloromethane/cyclohexane
mixture. The structures determined by X-ray diffraction are
presented in Fig. 2 and 3. The structures of the two gold com-
plexes Ie (ferrocenyl substituent on phosphonium) and If
Fig. 2 ORTEP view of complex Ie Au1–Br1: 2.4026(4); Au1–P1: 2.2373
(9); P1–Au1–Br1: 172.73(2). Thermal ellipsoids are drawn at the 50%
probability plot. Hydrogen atoms and DCM solvent are omitted for
(methyl substituent on phosphonium) show similar data. The clarity.
geometry around the gold atom is almost linear, characteristic
3
4
of a phosphine-AuX complex. Nevertheless, the more bulky
ferrocenyl group leads to a different organization of the phos-
phonium moiety. The bond lengths around the gold atom in
complexes Ie and If are similar to those of the PPh
3
AuBr
complex (P–Au: 2.252(6); Au–Br: 2.407 (2)). In Ie, inter-
3
1
Table 2 Structures, P NMR data and yields for gold(I) complexes Ia-f
3
1
No
Structure
P NMR (ppm)
Yield
80%
Ia
+22.66
+25.98
Ib
Ic
Id
+21.76
+21.71
+26.91
+26.07
+26.03
+33.43
94%
64%
80%
Fig. 3 ORTEP view of complex If Au1–Br1: 2.371(5); Au1–P1: 2.250(5);
P1–Au1–Br1: 178.3(3). Thermal ellipsoids are drawn at the 30% prob-
ability plot. Hydrogen atoms and DCM solvent are omitted for clarity.
The complex was obtained with a mixture of Br/Cl, and the minor dis-
ordered part was omitted for clarity. See the ESI† for more details.
molecular interactions in the crystal lead to a P–Au–Br angle of
172.73°.
Ie
If
+26.43
+21.80
+27.88
+24.91
78%
87%
Anti-proliferative properties
The anti-proliferative properties of the different gold(I) com-
plexes Ia-f were evaluated on three human cancer cell lines:
A549 (lung carcinoma), MDA-MB-231 (breast adenocarcinoma),
and SW480 (colorectal adenocarcinoma) (Table 3). Their IC50
values were compared to those of three clinically used drugs:
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Table 3 Antiproliferative activity of our complexes Ia-g, oxaliplatin, 5- phonium on anti-proliferative properties of the compounds.
FU, and paclitaxel on three cancer cell lines (A549, MDA-MB-231, and
SW480)
+
They can be qualitatively ranked as follows: –P (p-Tol)
≫
3
+
+
+
+
+
2
–P (Ph) Fc ≈ –P (Ph)
3 3 2
> –P (Bu) > –P (Ph) Me > –P (p-fluoro-
phenyl)
3
. Thus, there is no obvious correlation between anti-
IC50 (µM)
proliferative properties of the complexes and either the electron
donating character of the substituents or their steric hindrance.
It seems that the best results were obtained, when the positive
Compound
A549
MDA-MB-231
SW480
Ia
Ib
Ic
Id
Ie
If
Ig
0.89 ± 0.03
0.34 ± 0.02
3.17 ± 0.50
0.86 ± 0.13
0.68 ± 0.20
2.44 ± 0.73
38.1 ± 7.79
7.5 ± 0.40
9.1 ± 0.90
0.33 ± 0.04
1.81 ± 1.20
0.47 ± 0.02
4.04 ± 0.55
3.18 ± 1.07
1.72 ± 0.20
4.28 ± 0.34
3.5 ± 1.26
14.4 ± 1.90
22.3 ± 0.60
0.39 ± 0.02
4.1 ± 1.30
0.44 ± 0.04 charge of phosphonium can be delocalized on several aromatic
9.36 ± 1.75
4.2 ± 0.30
5.08 ± 0.90
substituents and when these aromatic rings are substituted
with electron donating groups. The negative impact of p-fluoro-
4.46 ± 0.20 phenyl groups with respect to phenyl substituents on anti-prolif-
14.2 ± 2.20
9.2 ± 1.40
52.5 ± 8.40
2.0 ± 0.74
35
erative properties was also observed by Bricklebank and coll.
Oxaliplatin
5-FU
Paclitaxel
Conclusions
We reported an efficient strategy to synthesize phosphonium-
phosphine ligands and their corresponding gold(I) complexes.
This strategy enables the facile introduction of different types
of phosphoniums. The gold(I) complexes displayed IC50 in the
low micromolar to the submicromolar range, which is better
than that of 5-FU and oxaliplatin, and in the range of pacli-
taxel. These results are promising for future in vivo appli-
cations; even it would be interesting to synthesize analogues
with phosphonium bearing other electron donating substi-
tuted aromatic rings to improve again their anti-proliferative
properties. Moreover, it will be interesting to evaluate the
impact of tethering a vector on biological properties in order
to obtain selective therapeutic agents (i.e. it could be intro-
oxaliplatin used for the treatment of colorectal cancer, 5-fluor-
ouracil (5-FU) used for colorectal, breast, and ovarian cancers,
and paclitaxel used for lung, breast, and ovarian cancers, and
3
to a common Au(I)-phosphine complex [Au(PPh )Br] Ig. All the
tested complexes displayed strong anti-proliferative properties
on the three cell lines. Their activities are in the range of pacli-
taxel but significantly better than oxaliplatin (up to 30 times
more efficient) and 5-FU (up to 120 times more efficient)
(Fig. 4). It is worth noting that Ig displays an efficacy 10 to 100
times lower than the best complexes, which highlights the
positive impact of the presence of the phosphonium moiety on
anti-proliferative activity. This can be explained by the fact that
introducing a phosphonium greatly improves the water solubi-
lity of the complexes compared to the gold complexes not con-
taining phosphonium (by about a factor of 100 compared to
3
6
duced via substitution of the gold bromido ligand ).
3
[Au(PPh )Br], see the ESI† for details).
Their anti-proliferative properties were always better onto Experimental
A549 than onto the other cell lines and most of the time lower
onto SW480, except for complex Ib, which displays submicro-
molar IC50 for all the tested cancer cell lines. The results high-
light a significant impact of the substituents of the phos-
Materials and methods
All synthetic manipulations were carried out using standard
Schlenk techniques. All reagents were purchased either from
Acros Organics, Sigma-Aldrich, Fischer Scientific, Alfa Aesar,
TCI or ABCR and used without further purification. THF and
dichloromethane were dried over alumina cartridges using a
solvent purification system MB-SPS-800 model from
M. BRAUN. Column chromatography was conducted on silica
gel 60–200 μm or 40–63 μm purchased from Sigma-Aldrich.
1
13
13
19
31
NMR spectra ( H, C, C–Jmod
,
F, P) were recorded with
Bruker 300 MHz, 500 MHz or 600 MHz apparatus, using tetra-
1
13
methylsilane as the internal reference for H, C NMR, and
3
1
phosphoric acid (85%) as the external reference for P NMR.
Abbreviations used to describe the multiplicity of the signal
are: s (singlet), d (doublet), t (triplet), q (quartet), bs (broad
signal), and m (multiplet). Mass spectra were recorded under
electrospray ionization conditions (ESI) with a Thermo LTQ
Orbitrap XP.
Single crystal X-ray diffraction
Fig. 4 Comparison of the antiproliferative activity of our most active
complex Ib on three cancer cell lines with clinically used anticancer
agents.
All experimental data procedures and refinement are detailed
in the ESI.† Data CCDC 2036897 and 2036898† for compounds
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Ie and If contain the supplementary crystallographic data for δ 145.38 (d, J = 11.5 Hz, Caro), 134.22 (d, J = 6.2 Hz, Caro),
this paper.
133.33 (d, J = 9.0 Hz, Caro), 132.11 (d, J = 2.4 Hz, Caro), 131.66
d, J = 2.4 Hz, Caro), 131.22 (d, J = 8.8 Hz, Caro), 129.14 (d, J =
10.3 Hz, Caro), 129.08 (d, J = 58.5 Hz, Caro), 127.89 (d, J =
(
Synthesis of the ligand precursor 4
8
.8 Hz, C ), 127.33 (d, J = 53.9 Hz, Caro), 63.29 (d, J = 6.1 Hz,
aro
1
(2-Bromobenzyl)diphenylphosphinite borane (2).
3
1
2 2
CH ); P { H} NMR (202 MHz, methylene chloride-d ) δ 18.30
(
br.s).
(2-Bromomethyl)phenyl]diphenylphosphine borane (4).
[
To a solution of 2-bromobenzyl alcohol (1.6 g, 8.5 mmol) in
anhydrous THF (50 mL) was added ethyldiisopropylamine
To a solution of [(2-hydroxymethyl)phenyl]diphenylphosphine
borane 3 (1.44 g, 4.7 mmol) in DCM (5 mL), CBr (2.85 g,
.6 mmol) and PPh3 (2.47 g, 9.4 mmol) were successively
(5.0 mL, 28.7 mmol). The mixture was cooled at 0 °C, and then
4
chlorodiphenylphosphine (1.8 mL, 10.0 mmol) was added.
After 30 min of stirring at 0 °C, the precipitate was removed by
filtration using millipore and the solvent was evaporated. The
resulting white solid was dissolved in anhydrous THF (50 mL),
8
added under argon. After two hours of stirring at RT, the
solvent was removed and the residue was purified on silica gel
using DCM/PE 1 : 1 as the eluent.
3
and then BH ·DMS (2 mL, 21.0 mmol) was added at RT. After
1
Yield = 83%, m = 1.44 g, n = 3.9 mmol; white solid. H NMR
2
h of stirring, the resulting mixture was hydrolyzed by adding
(
500 MHz, methylene chloride-d
2
) δ 7.67 (ddd, J = 7.8, 4.2,
distilled water (50 mL). The aqueous phase was extracted with
ethyl acetate (3 × 50 mL). The organic phase was dried over
1.2 Hz, 1H, Haro), 7.63–7.44 (m, 11H, Haro), 7.28–7.22 (m, 1H,
H
H
aro), 7.00 (ddd, J = 11.6, 7.9, 1.3 Hz, 1H, Haro), 4.63 (s, 2H,
aro), 1.78–0.85 (m, 3H, BH ); C{ H} NMR (75 MHz, chloro-
3
MgSO . After removal of the solvent, the residue was purified
4
13
1
by recrystallization in methanol.
1
form-d) δ 138.71 (d, J = 10.4 Hz, Caro), 133.45 (d, J = 10.6 Hz,
aro), 133.28 (d, J = 9.7 Hz, Caro), 133.19 (d, J = 8.9 Hz, Caro),
32.13 (d, J = 2.5 Hz, Caro), 131.54 (d, J = 2.5 Hz, Caro), 130.26
d, J = 57.0 Hz, Caro), 129.38 (d, J = 10.2 Hz, Caro), 128.98 (d, J =
Yield = 83%, m = 2.72 g, n = 7.1 mmol; white crystals. H
C
1
NMR (300 MHz, chloroform-d) δ 7.81–7.72 (m, 4H, Haro),
7
(
1
.58–7.41 (m, 8H, Haro), 7.30 (td, J = 7.5, 1.3 Hz, 1H, Haro), 7.17
td, J = 7.7, 1.8 Hz, 1H, Haro), 5.09 (d, J = 6.7 Hz, 2H, CH ),
.50–0.15 (m, 3H, BH3); C{ H} NMR (75 MHz, chloroform-d)
(
2
3
1
1
1
3
1
2
10.3 Hz, Caro), 128.84 (d, J = 58.0 Hz, Caro), 32.58 (CH ); P{ H}
NMR (202 MHz, methylene chloride-d
(
9
2
) δ 19.90 (br.s); IR
cm ): 3059, 2389, 2354, 1478, 1434, 1214, 1102, 1058, 1027,
98, 761, 751, 691, 622, 604, 562, 511, 493, 483, 457, 427;
δ 136.22 (d, J = 8.3 Hz, Caro), 132.50 (d, J = 53.5 Hz, Caro),
32.26 (Caro), 132.11 (Caro), 131.49 (d, J = 11.4 Hz, Caro), 129.84
d, J = 1.5 Hz, Caro), 128.81 (d, J = 10.6 Hz, Caro), 127.65 (Caro),
23.06 (C ), 68.43 (CH ); one carbon signal is not seen.
−
1
1
(
+
HR-MS (ESI): m/z calcd for C19H19BBrPNa [M + Na] : 391.03930
1
aro
2
3
1
1
Da; found: 391.04037 Da.
P{ H} NMR (202 MHz, methylene chloride-d
2
) δ 107.20 (br.s).
[(2-Hydroxymethyl)phenyl]diphenylphosphine borane (3).
General synthesis of the phosphonium-phosphine ligands 5a–f
All the phosphonium phosphines are prepared using the fol-
lowing procedure: To a solution of [(2-bromomethyl)phenyl]
diphenyl phosphine borane 4 (0.5 mmol) in DCM (2 mL) was
added the tertiary phosphine (1.25 mmol, 2.5 equivalents).
The reaction mixture was stirred until completion (24–48 h).
To a solution of phosphinite 2 (2.37 g, 6.2 mmol) in THF
10 mL) was added dropwise t-BuLi (9.1 mL, 15.4 mmol, 1.7
M) at −78 °C under argon. After 2 h 30 of stirring, the tempera-
ture was allowed to reach 0 °C, and the resulting mixture was
hydrolyzed by adding distilled water (5 mL). The aqueous
phase was extracted with DCM (3 × 10 mL), and then the
After removing most of the solvent, Et O (5 mL) was added
2
(
and a precipitate appeared which was filtered and purified on
silica gel using MeOH/DCM 1 : 10 as the eluent.
[(2-Diphenylphosphanyl)phenyl]methyl-triphenylphospho-
nium bromide (5a).
organic phase was dried over MgSO
solvent, the residue was purified over silica gel using EA/PE
: 1 as the eluent.
Yield = 77%, m = 1.46 g, n = 4.8 mmol; white solid. H NMR
500 MHz, methylene chloride-d ) δ 7.64 (ddd, J = 7.7, 4.2,
4
. After removal of the
1
1
(
2
1
.4 Hz, 1H, Haro), 7.59–7.53 (m, 7H, Haro), 7.50–7.44 (m, 4H,
H
aro), 7.28–7.23 (m, 1H, Haro), 6.96 (ddd, J = 11.7, 7.8, 1.3 Hz, Stopped after 36 hours of reaction. Yield = 87%, m = 0.27 g, n =
1
1
H, Haro), 4.54 (d, J = 5.7 Hz, 2H, CH
2
), 2.32–2.24 (m, 1H, OH), 0.44 mmol; white solid, Mp >250 °C. H NMR (500 MHz,
1
3
1
1
.71–0.98 (m, 3H, BH3); C{ H} NMR (75 MHz, chloroform-d) methylene chloride-d ) δ 7.91–7.83 (m, 3H, Haro), 7.71–7.62 (m,
2
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6
H, Haro), 7.59–7.50 (m, 6H, Haro), 7.39–7.34 (m, 2H, Haro),
Caro), 133.5 (d, J = 19.9 Hz, Caro), 132.1 (dd, J = 27.1, 7.2 Hz,
7
.34–7.28 (m, 6H, Haro), 7.29–7.21 (m, 1H, Haro), 6.94–6.88 (m, Caro), 131.6 (t, J = 3.6 Hz, Caro), 130.2 (d, J = 3.6 Hz, Caro), 129.5
4
H, Haro), 6.87–6.81 (m, 1H, Haro), 5.09 (d, J = 13.9 Hz, 2H, (d, J = 3.6 Hz, Caro), 129.4 (Caro), 128.8 (d, J = 7.2 Hz, Caro),
1
3
1
2 2
CH ); C{ H} NMR (75 MHz, methylene chloride-d ) δ 138.6 118.0 (dd, J = 22.1, 13.6 Hz, Caro), 113.4 (dd, J = 90.1, 3.4 Hz,
3
1
1
(dd, J = 6.4, 12.8 Hz, Caro), 135.4 (d, J = 3.1 Hz, Caro), 134.8 (d, Caro), 30.0 (dd, J = 68.0, 23.4 Hz, CH ); P{ H} NMR (202 MHz,
2
) δ 20.72 (s), −17.24 (s); IR (cm− ): 3053,
1
J = 3.1 Hz, Caro), 134.5 (d, J = 9.7 Hz, Caro), 134.1 (d, J = 8.1 Hz, methylene chloride-d
2
Caro), 133.7 (d, J = 19.3 Hz, Caro), 132.0 (dd, J = 8.4, 25.2 Hz, 2973, 1589, 1498, 1434, 1399, 1310, 1239, 1164, 1108, 1010,
Caro), 131.1 (d, J = 4.6 Hz, Caro), 130.3 (d, J = 13.0 Hz, Caro), 828, 778, 746, 697; HR-MS (ESI): m/z calcd for C H F P
37
28
3
2
+
1
30.0 (d, J = 3.1 Hz, Caro), 129.5 (d, J = 3.8 Hz, Caro), 129.4 [M − Br] : 591.1613 Da; found: 591.1617 Da.
(
2
C
aro), 128.8 (d, J = 6.9 Hz, Caro), 117.4 (d, J = 92.2 Hz, Caro),
[(2-Diphenylphosphanyl)phenyl]methyltributyl-
3
1
1
9.9 (dd, J = 24.0, 48.0 Hz, CH2); P{ H} NMR (202 MHz, phosphonium bromide (5d).
) δ 22.97 (s), −15.12 (s); IR (cm− ): 3052,
006, 2818, 2758, 1476, 1433, 1343, 1184, 1107, 1027, 994, 823,
87, 748, 722, 690; HR-MS (ESI): m/z calcd for C H P
1
methylene chloride-d
3
7
2
3
7
31 2
+
[
M − Br] : 537.1896 Da; found: 537.1904 Da.
(2-Diphenylphosphanyl)phenyl]methyl-tri(p-tolyl)phos-
phonium bromide (5b).
[
Stopped after 24 hours of reaction. Yield = 67%, m = 0.19 g, n =
1
0
.33 mmol; yellow viscous solid. H NMR (500 MHz, methylene
chloride-d ) δ 7.80–7.75 (m, 1H, Haro), 7.47–7.34 (m, 7H, Haro),
.31–7.27 (m, 1H, Haro), 7.26–7.21 (m, 4H, Haro), 7.02–6.96 (m,
H, Haro), 4.30 (d, J = 15.4 Hz, 2H, CH ), 2.55–2.43 (m, 6H,
2
7
1
2
2 2 2
PCH ), 1.50–1.36 (m, 12H, CH CH ), 0.93 (t, J = 6.8 Hz, 9H,
1
3
1
CH3); C{ H} NMR (75 MHz, methylene chloride-d ) δ 136.8
2
Stopped after 24 hours of reaction. Yield = 91%, m = 0.30 g, n =
1
(dd, J = 13.3, 5.8 Hz, Caro), 134.8 (d, J = 2.5 Hz, Caro), 134.7 (d,
J = 7.5 Hz, Caro), 133.7 (d, J = 20.2 Hz, Caro), 133.7 (d, J = 35.8
Hz, Caro), 131.9 (d, J = 4.2 Hz, Caro), 130.1 (d, J = 3.1 Hz, Caro),
129.5 (Caro), 129.0 (d, J = 7.7 Hz, Caro), 128.8 (d, J = 3.5 Hz,
0
.45 mmol; white solid. H NMR (500 MHz, methylene chlor-
ide-d ) δ 7.47–7.41 (m, 6H, Haro), 7.38–7.19 (m, 14H, Haro),
2
7
1
.20–7.15 (m, 1H, Haro), 6.92–6.85 (m, 5H, Haro), 4.88 (dd, J =
3.8, 1.0 Hz, 2H, CH ), 2.52 (s, 9H, CH ); C{ H} NMR
2 3
1
3
1
Caro), 25.2 (dd, J = 45.0, 21.4 Hz; CH
2
), 24.0 (d, J = 14.6 Hz,
(75 MHz, methylene chloride-d ) δ 147.30 (d, J = 3.2 Hz, Caro),
2
CH ), 23.5 (d, J = 4.5 Hz, CH ), 19.3 (dd, J = 3.5, 45.5 Hz, CH ),
2
2
2
1
39.03–138.65 (m, Caro), 135.19 (d, J = 3.1 Hz, Caro), 134.73
aro), 134.63 (d, J = 10.3 Hz, Caro), 134.63 (m, Caro), 134.14
Caro), 133.98 (Caro), 132.79 (dd, J = 8.2, 25.8 Hz, Caro), 131.38
Caro), 131.33 (Caro), 131.28 (Caro), 130.41 (d, J = 3.5 Hz, Caro),
3
1
1
1
3.2 (CH3); P{ H} NMR (202 MHz, methylene chloride-d )
δ 32.60 (s), −14.57 (s); IR (cm ) 2959, 2931, 2871, 1621, 1586,
2
(
(
(
C
−1
1
7
4
464, 1434, 1403, 1381, 1344, 1234, 1186, 1093, 1000, 968, 909,
+
46, 697; HR-MS (ESI): m/z calcd for C H P [M − Br] :
3
1
43 2
1
29.83 (d, J = 3.7 Hz, Caro), 129.74 (Caro), 129.17 (d, J = 7.2 Hz,
77.2835 Da; found: 477.2812 Da.
Caro), 114.52 (d, J = 88.8 Hz, Caro), 30.59 (dd, J = 49.3, 24.7 Hz,
3
1
1
[(2-Diphenylphosphanyl)phenyl]methyldiphenylferrocenyl
phosphonium bromide (5e).
CH ), 22.01 (CH ); P{ H} NMR (202 MHz, methylene chlor-
2
3
ide-d
2
) δ 22.08 (s), −15.62 (s); IR (cm−1): 3403, 2867, 1594,
1
6
433, 1399, 11 312, 1190, 1158, 1107, 802, 773, 746, 721, 697,
56, 524, 498, 473, 448, 436; HR-MS (ESI): m/z calcd for
+
C
40
H
37
P
2
[M − Br] : 579.23650 Da; found: 579.23605 Da.
(2-Diphenylphosphanyl)phenyl]methyltri(p-fluorophenyl)
phosphonium bromide (5c).
[
Stopped after 48 hours of reaction. Yield = 90%, m = 0.33 g, n =
1
0
.45 mmol; orange solid, Mp: 130 °C (dec). H NMR (500 MHz,
methylene chloride-d
2
) δ 7.85–7.82 (m, 2H, Haro), 7.68–7.62 (m,
H, Haro), 7.49–7.24 (m, 9H, Haro), 7.02 (t, J = 7.5 Hz, 4H, Haro),
.78–6.76 (m, 1H, Haro), 5.07 (d, J = 13.8 Hz, 2H, CH ), 4.92 (s,
8
6
2
2
1
1
3
H, Cp), 4.55 (s, 2H, Cp), 4.39 (s, 5H, Cp); C{ H} NMR
) δ 137.8 (dd, J = 12.7, 6.1 Hz,
.41 mmol; white solid, Mp: 134 °C (dec). H NMR (500 MHz, Caro), 134.8 (d, J = 2.8 Hz, Caro), 134.3 (Caro), 134.2 (Caro), 134.1
Stopped after 48 hours of reaction. Yield = 82%, m = 0.27 g, n = (75 MHz, methylene chloride-d
2
1
0
2
methylene chloride-d ) δ 7.71 (ddd, J = 11.8, 8.6, 4.9 Hz, 6H, (d, J = 9.9 Hz, Caro), 133.7 (d, J = 19.9 Hz, Caro), 132.7 (dd, J =
H
aro), 7.57–7.52 (m, 1H, Haro), 7.36–7.23 (m, 14H, Haro), 24.8, 7.8 Hz, Caro), 131.5 (t, J = 4.4 Hz, Caro), 129.8 (d, J = 3.5
1
3
1
6
.92–6.82 (m, 5H, Haro), 5.63 (d, J = 14.2 Hz, 2H, CH2); C{ H} Hz, Caro), 129.7 (d, J = 12.6 Hz, Caro), 129.4 (Caro), 129.1 (d, J =
NMR (75 MHz, methylene chloride-d ) δ 167.0 (dd, J = 260.5, 3.8 Hz, Caro), 128.9 (d, J = 7.2 Hz, Caro), 119.3 (d, J = 87.7 Hz,
.9 Hz, Caro), 138.2 (dd, J = 12.7, 7.2 Hz, Caro), 137.5 (t, J = aro), 74.8 (Cp), 74.7 (Cp), 73.2 (d, J = 3.1 Hz, Cp), 73.1 (d, J =
0.9 Hz, Caro), 135.0 (d, J = 3.6 Hz, Caro), 134.2 (d, J = 7.2 Hz, 3.5 Hz, Cp), 70.9 (Cp), 60.8 (d, J = 100.9 Hz, Cp), 29.7 (dd, J =
2
3
1
C
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3
1
1
5
1.3, 22.3 Hz, CH
2
); P{ H} NMR (202 MHz, methylene chlor- 132.89 (m, Caro), 132.10 (d, J = 9.9 Hz, Caro), 130.95 (Caro),
−
1
ide-d ) δ 26.29 (s), −14.13 (s); IR (cm ): 3052, 2853, 1587, 130.87 (Caro), 130.54 (d, J = 12.6 Hz, Caro), 130.17 (d, J =
2
1
7
6
478, 1434, 1413, 1392, 1181, 1107, 1029, 998, 829, 781, 745, 11.7 Hz, Caro), 130.06–129.98 (m), 129.12 (d, J = 12.3 Hz, Caro),
+
26, 691; HR-MS (ESI): m/z calcd for C41
45.1557 Da; found: 645.1552 Da.
H
35FeP
2
[M − Br] : 117.50 (d, J = 86.3 Hz, Caro), 29.79 (dd, J = 48.9, 13.5 Hz, CH
2
).
3
1
1
P{ H} NMR (202 MHz, methylene chloride-d ) δ 25.98 (s),
2
1
[(2-Diphenylphosphanyl)phenyl]methyldiphenylmethyl
22.66 (bs); IR (cm− ): 3341, 3051, 1585, 1478, 1434, 1161, 1098,
995, 822, 780, 744, 687, 546, 494; m/z calcd for C37 31AuBrP
M − Br] : 813.0744 Da; found: 813.0739 Da. Elemental ana-
lysis calculated for C37 31AuBr : C% 49.69, H% 3.49;
obtained: C% 49.82, H% 3.51.
[(2-Diphenylphosphanyl)phenyl]methyltri(p-tolyl)phos-
phonium bromide} AuBr (Ib).
phosphonium bromide (5f).
H
2
+
[
H
2 2
P
{
Stopped after 24 hours of reaction. Yield = 80%, m = 0.22 g, n =
1
0
.4 mmol; white solid, Mp: 122 °C (dec). H NMR (500 MHz,
methylene chloride-d ) δ 7.86–7.78 (m, 6H, Haro), 7.68–7.62 (m,
H, Haro), 7.41–7.30 (m, 8H, Haro), 7.05–6.92 (m, 5H, Haro),
.10 (dd, J = 15.7, 1.2 Hz, 2H, CH ), 2.83 (d, J = 13.4 Hz, 3H,
); C{ H} NMR (126 MHz, methylene chloride-d ) δ 137.6
2
5
5
CH
2
1
3
1
3
2
(
(
1
1
1
dd, J = 13.8, 6.9 Hz, Caro), 135.0 (d, J = 2.6 Hz, Caro), 134.8
aro), 134.8 (d, J = 2.5 Hz, Caro), 133.6 (d, J = 20.2 Hz, Caro), Yield = 94%, m = 0.088 g, n = 0.094 mmol; white solid,
C
1
33.1 (d, J = 10.4 Hz, Caro), 132.6 (dd, J = 26.7, 8.5 Hz, Caro), Mp >250 °C. H NMR (500 MHz, methylene chloride-d
31.6 (t, J = 4.6 Hz, Caro), 130.0 (d, J = 3.7 Hz, Caro), 129.9 (d, J = (bs, 3H, Haro), 7.54–7.28 (m, 21H, Haro), 7.22–7.16 (m, 1H,
2.5 Hz, Caro), 129.2 (Caro), 129.0 (d, J = 3.6 Hz, Caro), 128.8 (d,
aro), 6.95–6.87 (m, 1H, Haro), 5.25–5.17 (m, 2H, CH ), 2.51 (s,
); C{ H} NMR (151 MHz, methylene chloride-d
3.4 Hz, CH ), 8.3 (dd, J = 56.1, 3.4 Hz, CH ). One carbon δ 147.51 (d, J = 2.9 Hz, Caro), 135.70 (d, J = 6.5 Hz, Caro), 134.86
) δ 7.57
2
H
2
1
3
1
J = 7.3 Hz, Caro), 118.9 (d, J = 84.3 Hz, Caro), 28.7 (dd, J = 47.8, 9H, CH
2
)
2
3
2
3
3
1
1
signal is not seen. P{ H} NMR (202 MHz, methylene chlor- (d, J = 10.5 Hz, Caro), 134.76 (d, J = 14.4 Hz, Caro), 132.95 (dd,
) δ 21.75 (s), −15.53 (s); IR (cm−1): 3053, 2882, 1618, J = 11.1, 6.8 Hz, Caro), 132.82–132.53 (m, Caro), 131.63 (Caro),
ide-d
588, 1476, 1434, 1186, 1161, 1116, 1027, 997, 900, 841, 743, 131.54 (Caro), 130.11 (d, J = 11.7 Hz, Caro), 129.95 (d, J = 3.2 Hz,
2
1
6
+
89; HR-MS (ESI): m/z calcd for C32
H
29
P
2
[M − Br] : 475.1739
C
aro), 129.90 (d, J = 3.2 Hz, Caro), 114.25 (d, J = 89.0 Hz, Caro),
3
1
1
Da; found: 475.1733 Da.
30.22 (dd, J = 50.5, 13.6 Hz, CH ), 22.10 (CH ); P{ H} NMR
2 3
(
(
8
202 MHz, methylene chloride-d ) δ 26.07 (s), 21.76 (s); IR
2
−
1
General synthesis of the phosphonium phosphine gold
complexes Ia-f
cm ): 3353, 2917, 1596, 1498, 1476, 1434, 1399, 1190, 1099,
01, 749, 692, 652, 541, 499; m/z calcd for C H AuBrP
2
4
0
37
+
[
M − Br] : 855.1214 Da; found: 855.1208 Da. Elemental ana-
lysis calculated for C40 37AuBr : C% 51.30, H% 3.98;
obtained: C% 51.04, H% 4.36.
[(2-Diphenylphosphanyl)phenyl]methyltri(p-fluorophenyl)
To a solution of phosphonium phosphine 5a-f (0.1 mmol) in
DCM (4 mL), bromo(tetrahydrothiophene)Au(I) (0.1 mmol) was
added under argon at RT. The reaction mixture was stirred
H
2 2
P
3
1
{
until completion, as determined by P NMR (one hour). Then
the resulting mixture was concentrated and the product was
precipitated using pentane and washed twice with a mixture of
pentane/DCM 10 : 1.
phosphonium bromide}AuBr (Ic).
{
[(2-Diphenylphosphanyl)phenyl]methyl-
triphenylphosphonium bromide} AuBr (Ia).
Yield = 64%, m = 0.061 g, n = 0.064 mmol; white solid,
1
Mp: 140 °C. H NMR (600 MHz, methylene chloride-d
2
)
δ 7.69–7.59 (m, 8H, Haro), 7.58–7.50 (m, 4H, Haro), 7.49 (t, J =
.6 Hz, 1H, Haro), 7.48–7.32 (m, 11H, Haro), 7.23 (t, J = 6.4 Hz,
Yield = 80%, m = 0.07 g, n = 0.08 mmol; white solid, 1H, Haro), 6.92 (dd, J = 12.4, 7.8 Hz, 1H, Haro), 5.52 (d, J =
7
1
13
1
Mp: 150 °C (dec). H NMR (500 MHz, methylene chloride-d ) 14.8 Hz, 2H, CH2). C{ H} NMR (151 MHz, methylene chlor-
2
δ 7.90–7.86 (m, 3H, Haro), 7.70–7.64 (m, 6H, Haro), 7.63–7.55 ide-d
2
) δ 167.63 (dd, J = 261.2, 3.0 Hz, Caro), 138.15 (d, J =
(m, 8H, Haro), 7.50 (bs, 4H, Haro), 7.41 (s, 3H, Haro), 7.33 (bs, 10.2 Hz, Caro), 138.07 (d, J = 10.2 Hz, Caro), 135.92 (d, J = 7.3
3
5
H, Haro), 7.28–7.23 (m, 1H, Haro), 6.93–6.86 (m, 1H, Haro), Hz, Caro), 134.86 (d, J = 14.3 Hz, Caro), 133.26 (m, Caro), 133.02
1
3
1
.55–5.43 (m, 2H, CH
) δ 135.94 (d, J = 3.0 Hz, Caro), 135.73 (d, J = 6.7 Hz, 127.33 (dd, J = 63.3, 3.5 Hz, Caro), 119.07 (d, J = 14.2 Hz, Caro),
Caro), 135.20 (Caro), 135.13 (Caro), 134.78 (d, J = 14.5 Hz, Caro), 118.96 (d, J = 14.3 Hz, Caro), 112.92 (d, J = 90.7 Hz, Caro), 30.29
2
). C{ H} NMR (151 MHz, methylene (Caro), 132.06 (d, J = 9.1 Hz, Caro), 130.36 (d, J = 12.2 Hz, Caro),
chloride-d
2
4886 | Dalton Trans., 2021, 50, 4880–4889
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Paper
3
1
1
(
dd, J = 50.4, 12.7 Hz, CH ), one carbon is not seen. P{ H} (dd, J = 57.9, 7.7 Hz, Caro), 127.75 (d, J = 63.0 Hz, Caro), 118.86
2
NMR (243 MHz, methylene chloride-d ) δ 26.07 (s), 21.71 (s); (d, J = 87.7 Hz, Caro), 75.09 (d, J = 10.7 Hz, Cp), 73.77 (d, J =
2
IR (cm− ): 3054, 1588, 1497, 1435, 1398, 1308, 1241, 1162, 13.0 Hz, Cp), 71.39 (Cp), 60.73 (d, J = 102.8 Hz, Cparo), 31.06
1
1
2
099, 1009, 828, 773, 747, 691, 661, 542, 515, 482, 443; m/z (dd, J = 53.9, 11.8 Hz, CH ); one quaternary carbon signal is
+
31
1
calcd for C H AuBrF P [M − Br] : 867.0462 Da; found: not seen. P{ H} NMR (243 MHz, methylene chloride-d )
3
7
28
3
2
2
δ 27.88 (s), 26.43 (s); IR (cm− ): 3388, 3054, 1586, 1478, 1434,
1
8
67.0464 Da. Elemental analysis calculated for C37
C% 46.86; H% 2.98; obtained: C% 47.09, H% 3.23.
[(2-Diphenylphosphany)lphenyl]methyltributyl-
phosphonium bromide}AuBr (Id).
2 3 2
H28AuBr F P :
1180, 1106, 1033, 996, 838, 781, 744, 726, 691, 598, 547, 469;
+
{
m/z calcd for C H AuBrFeP [M − Br] : 921.0409 Da; found:
4
1
35
2
921.0433
35AuBr
H% 3.52.
[(2-Diphenylphosphanyl)phenyl]methyldiphenylmethyl
phosphonium bromide}AuBr (If).
Da.
FeP
Elemental
analysis
calculated
for
C
41
H
2
2
: C% 49.13, H% 3.52; obtained: C% 48.92,
{
Yield = 80%, m = 0.067 g, n = 0.08 mmol, white solid, Mp:
1
1
6
2
6
2
6
2
52 °C. H NMR (500 MHz, methylene chloride-d ) δ 7.90 (t, J =
.6 Hz, 1H, Haro), 7.70 (t, J = 7.6 Hz, 1H, Haro), 7.67–7.61 (m,
H, Haro), 7.60–7.48 (m, 8H, Haro), 7.40 (t, J = 7.7 Hz, 1H, Haro),
.95 (ddd, J = 12.5, 7.8, 1.1 Hz, 1H, Haro), 4.58 (d, J = 15.5 Hz, The product was recrystallized by vapor diffusion of cyclo-
H, CH ), 2.62–2.51 (m, 6H), 1.52–1.27 (m, 12H), 0.93 (t, J = hexane in DCM. Yield = 87%, m = 0.072 g, n = 0.087 mmol;
2
1
3
1
1
.9 Hz, 9H); C{ H} NMR (151 MHz, methylene chloride-d
2
)
white solid, Mp: 158 °C. H NMR (500 MHz, methylene chlor-
δ 135.60 (d, J = 7.6 Hz, Caro), 134.85 (d, J = 14.0 Hz, Caro), ide-d ) δ 7.85–7.77 (m, 6H, Haro), 7.68–7.62 (m, 4H, Haro),
2
1
33.97–133.65 (m, Caro), 133.42 (t, J = 3.5 Hz, Caro), 133.30 (d, 7.61–7.56 (m, 2H, Haro), 7.54–7.45 (m, 6H, Haro), 7.39 (ddd, J =
J = 2.6 Hz, Caro), 132.14 (d, J = 10.0 Hz, Caro), 130.32 (d, J = 7.6, 6.1, 1.8 Hz, 1H, Haro), 7.33–7.25 (m, 4H, Haro), 6.93 (ddd,
1
5
4
2
2.2 Hz, Caro), 129.36 (dd, J = 9.5, 2.8 Hz, Caro), 127.94 (dd, J = J = 12.1, 7.8, 1.3 Hz, 1H, Haro), 5.50 (d, J = 15.6 Hz, 2H, CH ),
2
7.9, 6.6 Hz, Caro), 127.63 (d, J = 63.1 Hz, Caro), 26.33 (dd, J = 2.90 (d, J = 13.4 Hz, 3H, Me); C{ H} NMR (151 MHz, methyl-
1
3
1
5.5, 12.1 Hz, CH
0.49 (d, J = 45.5 Hz, CH
2
), 24.37 (CH
2
), 24.30 (d, J = 11.7 Hz, CH
2
), ene chloride-d ) δ 135.95 (d, J = 6.4 Hz, Caro), 135.47 (d, J =
2
3
1
1
2
3
), 13.66 (CH ). P{ H} NMR 3.1 Hz, Caro), 134.69 (d, J = 14.1 Hz, Caro), 134.09 (d, J = 10.0
(
(
5
202 MHz, methylene chloride-d ) δ 33.43 (s), 26.91 (s); IR Hz, Caro), 133.44–133.59 (m, Caro), 133.13 (Caro), 132.93–132.91
2
−
1
cm ): 2866, 1463, 1434, 1309, 1193, 1119, 911, 746, 691, 541, (m, Caro), 130.60 (d, J = 12.4 Hz, Caro), 130.11 (d, J = 12.1 Hz,
+
00, 474; m/z calcd for C H AuBrP [M − Br] : 753.16834 Da; Caro), 129.68 (dd, J = 9.1, 3.2 Hz, Caro), 127.83 (d, J = 61.8 Hz,
3
1
43
2
found: 753.16567 Da. Elemental analysis calculated for Caro), 118.70 (d, J = 84.5 Hz, Caro), 30.10 (dd, J = 48.7, 12.9 Hz,
3
1
1
31 2 2
2
C H43AuBr P : C% 44.62, H% 5.19; obtained: C% 44.98, H% CH ), 9.67 (d, J = 55.4 Hz, Me). P{ H} NMR (202 MHz,
−
1
5
.35.
methylene chloride-d ) δ 24.91 (s), 21.80 (s); IR (cm ): 3380,
2
{
[(2-Diphenylphosphanyl)phenyl]methyldiphenylferrocenyl
2824, 1586, 1435, 1307, 1189, 1099, 996, 902, 744, 689, 540,
+
phosphonium bromide}AuBr (Ie).
499, 473, 452; m/z calcd for C H AuBrP [M − Br] : 751.0588
3
2
29
2
Da; found: 751.0594 Da. Elemental analysis calculated for
C H AuBr P : C% 46.18, H% 3.51; obtained: C% 46.36, H%
3
2
29
2 2
3.88.
TriphenylphosphineAuBr (Ig).
The product was recrystallized by vapor diffusion of cyclo-
hexane in DCM. Yield = 78%, m = 0.078 g, n = 0.078 mmol;
1
orange solid, Mp: 190 °C. H NMR (600 MHz, methylene chlor-
ide-d
m, 15H, Haro), 7.49 (bs, 1H, Haro), 7.34 (bs, 1H, Haro), 6.77 (dd, DCM (2 mL), bromo(tetrahydrothiophene)Au(I) (36.5 mg,
J = 12.9, 7.0 Hz, 1H, Haro), 5.19 (d, J = 15.3 Hz, 2H, CH ), 4.82 0.1 mmol) was added under argon at RT. The reaction mixture
2
) δ 7.81 (bs, 2H, Haro), 7.75–7.67 (m, 4H, Haro), 7.66–7.50 To a solution of triphenylphosphine (26 mg, 0.1 mmol) in
(
2
1
3
1
31
(
(
1
(
2
(
s, 2H, Cp), 4.44 (s, 2H, Cp), 4.27 (s, 5H, Cp); C{ H} NMR was stirred until completion, as determined by P NMR (one
151 MHz, methylene chloride-d ) δ 135.47 (d, J = 3.0 Hz, Caro), hour). Then the resulting mixture was concentrated and the
35.23 (d, J = 6.4 Hz, Caro), 135.18 (d, J = 14.2 Hz, Caro), 134.81 product was precipitated using pentane and washed twice with
d, J = 10.2 Hz, Caro), 133.25 (d, J = 6.7 Hz, Caro), 133.17 (d, J = 5 mL of pentane to give Ig as a white powder.
.6 Hz, Caro), 132.72 (Caro), 130.60 (d, J = 12.7 Hz, Caro), 130.47 Yield = 69%, m = 0.037 g, n = 0.069 mmol. H NMR
d, J = 12.2 Hz, Caro), 129.59 (dd, J = 9.3, 2.6 Hz, Caro), 128.85 (500 MHz, methylene chloride-d ) δ 7.61–7.52 (m, 3H, Haro),
2
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.52–7.46 (m, 2H, Haro), P{ H} NMR (202 MHz, methylene National Agency (ANR) via project JCJC “SPID” ANR-16-CE07-
chloride-d ) δ 35.19 (s). Elemental analysis calculated for 0020 are gratefully acknowledged. This work is part of the pro-
2
C
18
H
15AuBrP: C% 40.10, H% 2.80; obtained: C% 39.92, H% jects “Pharmacoimagerie et agents théranostiques” et “Chimie
2
.68. durable, environnement et agroalimentaire” supported by the
Université de Bourgogne and the Conseil Régional de Bourgogne
Biological experimental procedures
through the Plan d’Actions Régional pour l’Innovation (PARI)
and the European Union through the PO FEDER-FSE Bourgogne
Cell lines and culture conditions. Human colon cancer (SW
80), human breast cancer (MDA-MB-231), and human lung
cancer (A-549) cell lines were obtained from the American
Type Culture Collections (Manassas, VA, United States). They
were cultured in RPMI 1640 medium (Biowhittaker, France)
supplemented with 10% fetal bovine serum (Biowhittaker,
2014/2020 programs. FrenchBIC and GDR AIM are acknowledged
4
for fruitful discussion. Ms M.-J. Penouilh and Mr Q. Bonnin are
gratefully acknowledged for HR-MS analysis.
France) at 37 °C under a humidified atmosphere containing Notes and references
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The Ministère de l’Enseignement Supérieur et de la Recherche,
the Centre National de la Recherche Scientifique (CNRS), the
Conseil Régional de Bourgogne, and the French Research
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