Synthesis and characterization of Au(I) and Au(III) complexes containing N-heterocyclic ligands derived from amino acids

Article abstract of DOI:10.1016/j.poly.2014.07.014

A series of [Au(NHC)₂] (1a–4a) complexes supported by NHC ligands derived from glycine, alanine, methionine and phenylalanine (1–4 respectively) were prepared via a direct transmetalation reaction of their respective silver complexes. The Au complexes were characterized by ESI-MS and NMR spectroscopy in solution. These compounds exhibit instability when the solvent is removed; they displayed a strong tendency to form colored solutions in the order 4a > 3a?> 2a > 1a, which is associated with gold nanoparticles. 1a and 2a undergo oxidative addition of elemental bromine, yielding [Au(NHC)₂Br₂] (1b) for 1a and a mixture of [Au(NHC)₂Br₂] (2b) and [Au(NHC)Br₃] (2c) for 2a. 2b and 2c were characterized by single crystal X-ray diffraction.

Full text of DOI:10.1016/j.poly.2014.07.014

Polyhedron 81 (2014) 564–571
Contents lists available at ScienceDirect
Polyhedron
journal homepage: www.elsevier.com/locate/poly
Synthesis and characterization of Au(I) and Au(III) complexes containing
N-heterocyclic ligands derived from amino acids
a
a
a
Mario A. Reynoso-Esparza , Irma I. Rangel-Salas , A. Aarón Peregrina-Lucano ,
b
c
c
José G. Alvarado-Rodríguez , Fernando A. López-Dellamary-Toral , Ricardo Manríquez-González ,
a
a,
⇑
María L. Espinosa-Macías , Sara A. Cortes-Llamas
a
Departamento de Química y Departamento de Farmacobiología, Centro Universitario de Ciencias Exactas e Ingenierías, Universidad de Guadalajara, Blvd. Marcelino García
Barragán #1421, esq. Olímpica, C.P. 44430 Guadalajara, Jalisco, Mexico
Universidad Autónoma del Estado de Hidalgo, Unidad Universitaria, km 4.5 Carretera Pachuca-Tulancingo, C.P. 42184 Mineral de la Reforma, Hidalgo, Mexico
b
c
Departamento de Madera, Celulosa y Papel, Centro Universitario de Ciencias Exactas e Ingenierías, Universidad de Guadalajara, Km 15.5 de la Carretera Guadalajara-Nogales,
C.P. 45220 Zapopan, Jalisco, Mexico
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of [Au(NHC) ] (1a–4a) complexes supported by NHC ligands derived from glycine, alanine,
methionine and phenylalanine (1–4 respectively) were prepared via a direct transmetalation reaction
of their respective silver complexes. The Au complexes were characterized by ESI-MS and NMR spectros-
copy in solution. These compounds exhibit instability when the solvent is removed; they displayed a
strong tendency to form colored solutions in the order 4a > 3a > 2a > 1a, which is associated with gold
2
Received 20 March 2014
Accepted 9 July 2014
Available online 16 July 2014
Keywords:
NHC ligand
Gold
Water solubility
Carbene
nanoparticles. 1a and 2a undergo oxidative addition of elemental bromine, yielding [Au(NHC)
1b) for 1a and a mixture of [Au(NHC) Br ] (2b) and [Au(NHC)Br ] (2c) for 2a. 2b and 2c were character-
ized by single crystal X-ray diffraction.
2 2
Br ]
(
2
2
3
Ó 2014 Elsevier Ltd. All rights reserved.
Amino acids
1
. Introduction
chiral centers, which open the possibility to obtain chiral ligands. For
example, Kühl et al. prepared imidazolium zwitterions from
amino acids; [18] these ligands possess wing-tip groups with car-
boxylate substituents in the -position of the wing-tip group, which
favors the water solubility. Despite the attractive features of these
ligands, there are few NHC-complexes with this sort of ligands
[19,20]. To obtain further information on the structure and stability
of water-soluble gold complexes, which have potential applications
in green chemistry and are compatible with physiological media, we
decided to explore the synthesis of Au(I) and Au(III) complexes sup-
ported by NHC ligands derived from amino acids.
a-
Water can be considered the ideal solvent for homogeneous
catalysis [1]. It is a non-toxic, economical and environmentally
friendly solvent. Consequently, there has been an intensive search
for water-soluble catalytic systems; [2] in this regard, ligands play
a critical role to stabilize metal centers in water. On the other hand,
a
N-heterocyclic carbene ligands (NHC) are excellent
r- donors that
are capable of stabilizing a large number of organometallic com-
pounds; [3–5] the metal–carbon bond in NHC complexes is suffi-
ciently strong that many of these compounds are not air or
moisture sensitive and can even be synthesized in an aqueous med-
ium [6]. In particular, Au-NHC complexes have emerged as excellent
catalysts [7,8], and efficient agents in medical applications such as
antitumor metallodrugs [9–12]. To fine-tune the lipophilic/hydro-
philic character of the complexes, substituents attached to the
imidazolium salt precursor, such as carboxylate [6], amide [13],
ester [14], and sulfonate [15,16] groups have been studied.
2. Results and discussion
Following the original procedure patented by Arduengo [21],
we attempted the synthesis of N, N´ -disubstituted symmetric imi-
dazolium zwitterions by a one-pot condensation between glyoxal,
L
2 equiv. of amino acid (glycine, L-alanine, L-methionine and -phen-
ylalanine for 1, 2, 3 and 4, respectively) and 1 equiv. of paraformal-
dehyde in the presence of hydrochloric acid [18]. This procedure
produced the desirable compounds in low yields with dark-brown
impurities. However, when acetic acid was used instead of hydro-
chloric acid, compounds 1–4 were obtained in good yields
(Scheme 1) [22].
A strategy for preparing water soluble imidazolium salts precur-
sors has been the use of
starting materials and water soluble; [17] furthermore they possess
a-amino acids which are inexpensive
⇑
Corresponding author.
E-mail address: sara.cortes@cucei.udg.mx (S.A. Cortes-Llamas).
http://dx.doi.org/10.1016/j.poly.2014.07.014
277-5387/Ó 2014 Elsevier Ltd. All rights reserved.
0

M.A. Reynoso-Esparza et al. / Polyhedron 81 (2014) 564–571
565
R
R
O
HO
O
R
CH
3
COOH
O
O
O
N
N
O
2
+
H
H
+
NH
2
50 °C
O
HO
R = H (1)
R = CH
R = CH
R = CH
3
2
2
(2)
CH
Ph (4)
1
2
2 2
) Ag O, NaOH/ H O
2
SCH
3
(3)
) (CH
3
)
2
SAuCl
OH
O
O
N
N
N
O
O
R
R
R
Au
R
O
N
OH
HO
1a - 4a
Scheme 1. Synthesis of 1–4.
chiral analogous compounds [18]. The equivalent N–C distances in
the heterocycle are significantly the same, indicating the expected
delocalization for an imidazolium ring. In the crystal structure, both
carboxylate groups participate in the formation of hydrogen bonds,
forming rows running along the c axis, with Oꢀ ꢀ ꢀO bond distances
O
H
N
H
N
O+
H O
2
RNH
2
H
3
R
R
N
N
+
R
R
O
O
H
H
Toluene
2
i
Scheme 2. One-pot synthesis for imidazolium salts.
of 2.476(8) Å (Fig. 1b). Based on the Oꢀ ꢀ ꢀO distance, the hydrogen
0
bonding can be categorized as very strong (<2.50 ÅA ), strong (2.50–
0
0
0
It is usually accepted that, in this protocol, the addition of two
equivalents of amine to paraformaldehyde in toluene leads to the
in situ formation of the N,N-disubstituted aminal (i); this interme-
diate condenses with one equiv. of glyoxal in the presence of HCl to
obtain the imidazolium chloride (Scheme 2) [23]. The condensa-
tion reactions are pH dependent; an acid is necessary to facilitate
the dehydration step, however if there is an excess of acid, the
amine is completely protonated and cannot act as a nucleophile
2.65 ÅA ), medium (2.65–2.80 ÅA ), or weak (>2.80 ÅA ) [25]. In 3, the
hydrogen bonds are very strong, as expected for intermolecular
ꢁ
´
O–Hꢀ ꢀ ꢀO interactions between two carboxylate groups.
For the synthesis of gold complexes (1a–4a) we use the classical
transmetalation reaction of the respective Ag(I)-NHC complexes in
the presence of [Au(SMe )Cl] in water solution at room tempera-
2
ture protected from the light (Scheme 1). Firstly, we tried to isolate
the silver complexes; spectroscopic analysis of the solutions indi-
cated the presence of several different species, including the start-
ing ligand. Therefore, we decided to prepare the gold complexes
[
24]. Therefore, every condensation has its own specific require-
ments; in our case, the use of acetic acid appears to afford the cor-
rect pH for these reactions.
without further isolation of the silver-NHC. After the excess Ag O
2
Compounds 1–4 were obtained as zwitterions (Scheme 1). Their
water solubility follows the order 4 < 3 < 2 < 1; however, all zwit-
terions are very soluble in water when one equiv. of NaOH is
added. The solubility of these compounds in methanol and DMSO
follows the reverse order, and they are insoluble in most other
was filtered off, the solutions exhibited different behaviors. Solu-
tions of 1a and 2a remained colorless for several weeks, as long
as the solvent is not removed. In contrast, solutions of 3a and 4a
presented a purplish-pink coloration with deposition of metallic
gold on the walls of the flask; this process was faster for complex
4a (approx. 3 days) in comparison with that for 3a (approx. one
week). In addition, 1a - 4a are also unstable in the solid state,
1
organic solvents. The characterization results for the compounds
prepared in this study are consistent with previously reported data
1
for 1, 2 and 4 (Figs. SI-1 and SI-2) [18]. For example, in the
H
showing
a
strong tendency to darken in the order
NMR spectrum, the imidazolium protons appear at approximately
ppm (d 8.85–9.33 ppm), which is consistent with the general
4a > 3a > 2a > 1a. We explore the synthesis of these compounds
under inert atmosphere in water, methanol and DMSO, however
when the final solutions were concentrated, they changed color.
9
C–H acidic proton shift of imidazolium salts (Fig. SI-1). The imidazo-
2
lium carbon C appears at approximately 136 ppm (d 135.53–
In addition, we use different imidazolium zwitterion:Ag O and
2
1
37.76 ppm) as the most notable feature in the 13C NMR spectrum.
imidazolium zwitterion:NaOH ratios, but unfortunately in all
Needle shaped single crystals suitable for X-ray diffraction analysis
were obtained for ligand 3 in water (Fig. 1a). Table 1 provides rele-
vant data for the crystal collection, and Table 2 lists selected bond
lengths and angles. 3 crystallizes in the monoclinic crystal system
cases, we observed the formation of pink, blue or black solutions,
which are associated with the formation of gold nanoparticles.
Thus, we decided to analyze the fresh filtered solutions by negative
ion mode electrospray ionization mass spectrometry (ESI-MS)
(Fig. SI-4). For 1a–4a, the mass spectrum showed fragmentation
patterns are consistent with the formation of such complexes; in
all cases, the molecular ion displaying the appropriate isotopic
ratio is also the base peak (m/z = 563.1, 619.2, 859.2 and 923.3
for 1a, 2a, 3a and 4a respectively). Peaks with m/z ratios greater
than the molecular ions are also observed. For example, 1a spec-
trum shows two additional peaks corresponding to the interaction
of two and four water molecules, which likely form hydrogen
bonds with the carboxylate groups of 1a. Furthermore, when an
1
in space group P2 . The molecular structure displays the two amino
acid residues on different sides of the imidazolium planar ring, with
0
both stereogenic carbon atoms in S,S configuration. This arrange-
ment can be associated to a pseudo two fold axis lying on the plane
of the imidazolium heterocycle, bisecting the N–C–N bond; the ideal
C axis is ‘‘avoided’’ due to the different environments of the carbox-
2
ylate groups. This structural behavior has been also observed in the
1
For example, 20 mg are dissolved in 1, 1.5, 10.5 and 17.5 mL of water for 1, 2, 3
2
excess of Ag O was used, in the case of 2a and 3a, the ESI-MS spec-
and 4 respectively at 25 °C. 1 and 2 are not soluble in methanol; 20 mg are dissolved
in 4 and 4.5 mL of methanol for 3 and 4 respectively at 25 °C.
trum exhibit peaks with higher m/z ratios, corresponding to

5
66
M.A. Reynoso-Esparza et al. / Polyhedron 81 (2014) 564–571
Fig. 1. (a) Perspective view of 3, showing thermal ellipsoids at the 50% probability level (hydrogen atoms have been omitted for clarity). (b) Crystal structure of 3.
+
additional Ag bound to the molecular ion, probably through the
carboxylate groups (for 2a) and sulfides (for 3a) (Fig. SI-5). In sev-
eral reports, bis-(carboxyl-alkyl)imidazolium ligands have been
used to stabilize metal centers through the coordination of carbox-
ylate groups, forming stable coordination polymers in the solid
state [26–30]. When an excess of NaCl is added to solutions of 2a
and 3a, we observed the precipitation of a white solid (AgCl), and
peaks with a higher m/z ratio than the molecular ion, are no longer
observed in the mass spectrum.
decomposition. In the NHC ligands, the carbene center is benefited
from the stabilization associated with the -electron-withdrawing
and -electron-donating character of the nitrogen atoms [23].
Contrary to the lower stabilization observed in the complexes 1a
– 4a in water and organic solvents, Hemmert et al. prepared stable
Au-NHC complexes with carboxylate groups in the b-position of
the wing-tip groups [6]. This fact could suggest that, in 1a–4a,
the electron-withdrawing character of carboxylate groups in the
r
p
a
-position of the wing-tip groups decreases the ability of the
nitrogen to stabilize the carbene center. In order to gain a greater
insight on the reactivity of [Au(NHC) ] complexes, we attempted
1
13
H and C NMR spectrum shows the expected signals for the
complex [Au(NHC)
1
13
2
] for 1a; H and C NMR spectrum for 2a, 3a
2
and 4a displayed two sets of signals, corresponding to the expected
complexes [Au(NHC) ] and the imidazolium zwitterions generated
the synthesis of gold(III) complexes by the addition of elemental
bromine to an aqueous solution of the corresponding gold(I)
1a–4a (Scheme 3). Thus, the reaction was successful for 1a and
2
2
from the decomposition of the respective complexes; the presence
of the goldꢁcarbene bond for compounds 1a–4a is unequivocally
confirmed by the characteristic resonance in the 13C NMR spec-
trum located at 185.88, 184.21, 182.43 and 183.80 ppm respec-
2a to afford 1b and 2b respectively; these complexes displayed a
similar behavior as the gold(I) complexes 1a–4a, if the solvent is
removed, they tend towards colloid formation and reduction of gold
2
+
tively (Fig. SI-3). This downfield shift for the C of the imidazole
(Au° and Au ). Unfortunately, for the reaction of either 3a or 4a with
is observed in most of the M-NHC complexes as a result of the
donation of electron density from the NHC ligand to the metal cen-
bromine, the formation of expected complexes of Au(III) was not
successful.
ter [31]. In general, due to their strong
r-electron-donating prop-
erties, NHC ligands form stronger bonds with metal centers than
most of the classical ligands, such as phosphines, thus yielding
transition metal complexes that are generally resistant to
2
For the synthesis of Au(III) complex, we use a batch of 2, prepared from R,S-
alanine.

M.A. Reynoso-Esparza et al. / Polyhedron 81 (2014) 564–571
567
Table 1
Summary of crystallographic data for 3, racemate-2cꢀH
2
O and R,S-2cꢀ2H
2
O.
Compound
3
racemate-2cꢀH
14AuBr
666.92
293(2)
0.71073
2
O
R,S-2cꢀ2H
2
O
Empirical formula
Formula weight (g/mol)
T (K)
Wavelength (Å)
Crystal system
Space group
Unit cell dimensions
a (Å)
C
13
H
20
N
2
O
S
4 2
C
9
H
3
N
2
O
5
C
9
H16AuBr N O
3 2 6
332.43
293(2)
0.71073
monoclinic
P 2
684.93
293(2)
0.71073
triclinic
P1ꢀ
triclinic
P1ꢀ
1
9.7275(5)
8.0390(5)
10.7507(8)
90
99.323(6)
90
829.59(9)
2
1.331
7.1101(2)
8.6458(4)
7.17534(16)
9.6223(2)
14.2249(3)
102.0417(19)
96.9045(18)
109.031(2)
889.01(4)
2
b (Å)
c (Å)
14.8314(5)
97.633(3)
90.716(3)
102.071(4)
882.90(6)
2
2.509
15.135
612
a
(°)
b (°)
(°)
c
3
V (Å )
Z
3
Density (calculated) (mg/m )
Absorption coefficient (mm 1)
F(000)
Crystal size (mm )
h Range for data collection (°)
2.559
15.039
632
ꢁ
0.336
352
3
0.600 ꢂ 0.100 ꢂ 0.010
0.20 ꢂ 0.01 ꢂ 0.01
0.75 ꢂ 0.25 ꢂ 0.08
3.084–25.681
2.932–26.367
2.991–26.370
Index ranges
ꢁ11 6 h 6 11, ꢁ9 6 k 6 9,
ꢁ8 6 h 6 8, ꢁ10 6 k 6 10,
ꢁ18 6 l 6 18
ꢁ8 6 h 6 8, ꢁ12 6 k 6 12,
ꢁ17 6 l 6 17
ꢁ
13 6 l 6 13
Reflections collected
19730
26278
50157
Independent reflections (Rint
)
3144 (0.1129)
3611 (0.0680)
3623 (0.1175)
Completeness to h = 25.242° (%)
Absorption correction
Refinement method
99.8
none
99.9
99.9
semi-empirical from equiv.s
full-matrix least-squares on F2
3611/9/195
semi-empirical from equiv.s
full-matrix least-squares on F2
3623/14/210
full-matrix least-squares on F2
Data/restraints/parameters
Goodness-of-fit (GOF) on F
3144/2/192
1.056
2
1.035
1.092
Final R indices [I > 2
R indices (all data)
r
(I)]
R
R
1
= 0.0725, wR
= 0.0964, wR
2
2
= 0.1967
= 0.2194
R
R
1
= 0.0391, wR
= 0.0543, wR
2
2
= 0.0863
= 0.0932
R
R
1
= 0.0519, wR
= 0.0585, wR
2
2
= 0.1695
= 0.1774
1
1
1
Extinction coefficient
n/a
n/a
1.492 and ꢁ1.456
n/a
Largest difference in peak and hole (e Åꢁ3) 0.400 and ꢁ0.334
2.767 and ꢁ2.981
Table 2
Selected bond lengths (Å) and angles (°) for compounds 3, racemate-2cꢀH
2
O and R,S-2cꢀ2H
2
O.
3
N(1)–C(1)
N(1)–C(2)
N(1)–C(4)
N(2)–C(1)
1.328(8)
1.386(9)
1.456(7)
1.324(8)
N(2)–C(1)–N(1)
C(1)–N(1)–C(4)
C(1)–N(2)–C(9)
109.6(5)
125.6(5)
125.6(5)
Racemate-2cꢀH
Au(1)–C(1)
Au(1)–Br(1)
Au(1)–Br(2)
Au(1)–Br(3)
2
O
2.046(7)
C(1)–Au(1)–Br(1)
C(1)–Au(1)–Br(3)
Br(3)–Au(1)–Br(1)
C(1)–Au(1)–Br(2)
88.10(17)
87.31(17)
175.38(3)
178.41(19)
2.4183(8)
2.4388(9)
2.4071(8)
R,S–2cꢀ2H
2
O
Au(1)–C(1)
Au(1)–Br(1)
Au(1)–Br(2)
Au(1)–Br(3)
2.028(10)
C(1)–Au(1)–Br(1)
C(1)–Au(1)–Br(3)
Br(1)–Au(1)–Br(3)
C(1)–Au(1)–Br(2)
86.3(3)
88.3(3)
174.45(5)
178.7(2)
2.4097(11)
2.4517(12)
2.4122(13)
OH
O
OH
R
O
OH
R
HO
R
O
O
N
N
N
N
O
O
O
O
N
N
O
O
Br
2
/ H
2
O
O
N
N
O
R
R
R
R
Au
+
R
Br Au Br
R
R
Br Au Br
Br
N
N
OH
HO
OH
HO
R = H (1a)
R = Me (2a)
R = H (1b)
R = Me (2b)
R = Me (2c)
Scheme 3. Synthesis of gold(II) complexes.
1
b was initially characterized by ESI-MS (Fig. SI-6); a base peak
2
with Br , the ESI-MS revealed the fragmentation pattern of two
was observed at m/z = 722.9 with the appropriate isotopic ratio cor-
responding to the molecular ion. In the case of the reaction of 2a
Au(III) complexes; the structures were elucidated as a monocarbe-
nic (2c) and a bis-carbenic (2b) (Fig. SI-6). All attempts to separate

5
68
M.A. Reynoso-Esparza et al. / Polyhedron 81 (2014) 564–571
Fig. 2. Perspective view of (a) racemate-2cꢀH
2
O and (b) R,S-2cꢀ2H
2
O showing thermal ellipsoids at the 50% probability level.
Fig. 3. Crystal structure of racemate-2cꢀH
2
O.
compounds 2b and 2c by means of column chromatography were
unsuccessful. We also attempted to avoid any excess of Br in the
distance that is trans to the NHC ligand is significantly longer than
the Au–Br distances in the Br(1)–Au–Br(3) moiety for S,S-2cꢀH O:
Au(1)–Br(2) = 2.4388(9), Au(1)–Br(1) = 2.4183(8) and Au(1)–
O: Au(1)–Br(2) = 2.4517(12),
Au(1)–Br(1) = 2.4097(11) and Au(1)–Br(3) = 2.4122(13) Å. This
observation reflects the trans influence, in which certain ligands lead
to a weakening of the metal–ligand bonds that are trans to them [35]
2
2
reaction to analyze whether the formation of 2b was favored; how-
ever, we always observed a mixture of both products. By means of
fractional crystallization by slow evaporation of a reaction mixture,
we isolated three crystals with different morphologies that were
analyzed by X-ray analysis. Crystals for 2b were found to be plates
and of very low quality; thus, only an isotropic model could be
obtained (Fig. SI-7). 2b crystallizes in the triclinic crystal system in
Br(3) = 2.4071(8) Å; for R,S-2cꢀ2H
2
Ligands with this capability are those that form strong bonds M–L (
r
or ); thus, in this case, the increase in the Au-Br bond length, local-
p
ꢀ
the space group P1 [a = 7.0919 (4), b = 10.1492 (20) and
ized trans to the NHC ligand, indicates that these are excellent r
c = 10.2025 (15) Å;
a
= 107.514 (14), b = 105.534 (8) and
donor ligands.
c
= 91,162 (9)°]. From the model can be seen that the gold atom
The molecular structure of both complexes display different
structural features; the monohydrate 2c displays the two alanine
residues on different sides of the imidazolic planar ring, with both
stereogenic carbon atoms in either S,S or R,R configuration, in a
similar way as the ligand 3. This arrangement can be associated
to a pseudo rotational symmetry. On the other hand, the diastereo-
has the expected square planar geometry with favorable trans
arrangements of the NHC ligands. The other two crystals correspond
to Au(III) tribromide complexes, 2c in the form of mono-hydrate
0
0
(
racemate-2cꢀH
2
O) and di-hydrate (R,S-2cꢀ2H
2
O) Au(III) tribromide
-ala-
complexes; the presence of diastereomers is due to the use of D L
,
nine used as starting material for the synthesis of 2. Table 1 gives rel-
evant data for the crystal collection, and Table 2 lists selected bond
lengths and angles. In both cases, the gold atom has a square planar
coordination geometry, and the Au–Br and Au–C bond distances are
consistent with those reported in the literature (Fig. 2) [32–34]. It is
interesting to note that, in both complexes, the Au–Br(2) bond
mer R,S-2cꢀ2H
2
O displays the arrangement of the two residues on
the same sides of the imidazolic ring; the presence of the enantio-
meric R,S pair in the same fragment now causes a pseudo-mirror
symmetry.
The mono- and dihydrate complexes crystallized in the
triclinic system in space group P1. In the crystal structure of
ꢀ

M.A. Reynoso-Esparza et al. / Polyhedron 81 (2014) 564–571
569
Fig. 4. Crystal structure of R,S-2cꢀ2H
2
O.
racemate-2cꢀH
2
O, the two carboxylic groups are involved in
of elemental bromine to 1a and 2a. In the case of 2a, a mixture of
biscarbene (2b) and monocarbene (2c) complexes was obtained;
2b and 2c were characterized by single crystal X–rays diffraction
studies. The crystal structures of the mono-and dihydrates of 2c
are based on extended hydrogen bond network. However, these
NHC-Au(III) complexes present poor stability in solution.
different intermolecular interactions (Fig. 3). In order to describe
the intermolecular interactions based on hydrogen bonding, we
used the graph analysis approach.[36] Thus, one carboxylic group
2
2
forms a centrosymmetric ring with a R (8) graph descriptor,
with Oꢀ ꢀ ꢀO bond distances of 2.602(8) Å. Concern the second
carboxylic group, this fragment now forms a bigger ring, where a
water molecule is linking the two –C(O)OH moieties, with
Oꢀ ꢀ ꢀO = 2.939(8) and Oꢀ ꢀ ꢀO = 2.597(7) Å intermolecular distances;
4
. Experimental
4
4
the arrangement can be described with the R (12) descriptor.
4.1. General information
These two hydrogen-bonded interactions form chains that are
joined by weak C–Hꢀ ꢀ ꢀO interactions.
Ag
2 3
O was prepared by the reaction of AgNO and NaOH. All
In R,S-2cꢀ2H
2
O, for each molecule of the complex, there are two
other reagents were obtained commercially and used as received.
H and C NMR spectrum were recorded on JEOL ECA 600 MHz
water molecules in the crystal structure (Fig. 4), displaying a more
complex network based on hydrogen bonding. The first water mol-
ecule is located in the central part of a complex (in the direction of
the imidazolic ring), bridging the two carboxylate groups of this
1
13
spectrometer. ESI mass spectrums were recorded on a 6410B triple
quadrupole LC/MS from Agilent Technologies. Compound 3 was
successfully recrystallized from a 1:3 water–methanol mixture,
whereas the mono and dihydrates of 2c from water. Single crystals
of suitable quality were glued on a glass fiber. The X-ray diffraction
data of 3, 2cꢀH
on an Oxford Diffraction Gemini CCD diffractometer with graphite-
monochromated MoK radiation (k = 0.71073 Å). Data were inte-
grated, scaled, sorted, and averaged using the CrysAlis software
package. An analytical numeric absorption correction using a mul-
tifaceted crystal model was applied using the CrysAlis software. The
structures were solved by direct methods, using SHELXTL NT Version
.10 and refined by full-matrix least squares against F . The dis-
complex by hydrogen bonding [Oꢀ ꢀ ꢀOH
2
= 2.858(13) Å; Oꢀ ꢀ ꢀOH
2
=
2
2
2
.827(12) Å]; the arrangement can be described by the R (12) graph
descriptor. Additionally, the same water molecule forms a hydrogen
bond with one of the –OH groups of another complex
2
O, and 2cꢀ2H
2
O were collected at room temperature
[
OHꢀ ꢀ ꢀOH
2
= 2.555(12) Å]. The arrangement can be described as
4
4
a
R (12). The second water molecule forms a hydrogen bond with a
carboxylate group (d: O (H)ꢀ ꢀ ꢀOH
2
= 2.592(13) Å) and with two
bromo ligands. These two rings can be described by the R (8) and
3
2
4
5
5
R (16) descriptors, where are also observed weak C–Hꢀ ꢀ ꢀO interac-
tions. These interactions allow the formation of an extended array
of molecules of the two complexes, as shown in Fig. 4.
2
4
5
placement parameters of non-hydrogen atoms were anisotropically
refined. The positions of the hydrogen atoms were kept fixed with
a common isotropic displacement parameter.
3
. Conclusions
We report the synthesis of gold(I) complexes 1a–4a with NHC
ligands derived from glycine, alanine, methionine and phenylala-
nine; 1a–4a were prepared via the direct transmetalation reaction
of the respective silver NHC complexes; they were characterized
by ESI-MS and NMR spectroscopy. 1a is stable in aqueous solution
for a prolonged time (weeks), while the other complexes are
degraded in water, with a strong tendency towards the formation
of nanoparticles. A study of the properties of these nanoparticles
is currently underway in our laboratory. On the other hand, the
synthesis of NHC-Au(III) was carried out by the oxidative addition
4.1.1. General procedure for the preparation of the zwitterions 1–4
Under nitrogen atmosphere, an amino acid (0.1 mol) and para-
formaldehyde (3.0 g, 0.1 mol) were heated in toluene (250 mL) at
50 °C for 30 min. Then, amino acid (0.1 mol), acetic acid 3 M
(40 mL, 0.12 mol), and glyoxal (5.8 g, 0.1 mol) were added
3
Oxford. Diffraction, CrysAlis Software System, Version 1.171.33.31, Oxford
Diffraction Ltd., Abingdon, UK, 2009.
4
SHELXTL 5.10 Bruker AXS, Inc., Madison, WI, USA, 1998.

5
70
M.A. Reynoso-Esparza et al. / Polyhedron 81 (2014) 564–571
⁄
separately with a difference of 15 min between additions. The mix-
ture was stirred for 12 h at 50 °C and then cooled to the freezing
point of water. The organic phase was decanted and water was
removed under vacuum. The resulting solid was washed with
methanol, filtered and dried.
ESI-MS for C14
bility: soluble in H
H
15AuN
4
O
8
negative ion (m/z): 563.1 (MꢁH ). Solu-
2
O, insoluble in organic solvents.
1
4.1.2.2. Gold(I) complex (2a). H NMR (D O, 600 MHz, d ppm): 7.30
2
4
5
13
(s, 4H, H /H ), 5.25 (m, 4H, CHCH ), 1.70 (d, 12H, CH ). C NMR
3
3
2
4
2
(D O, 150 MHz, d ppm): 184.21 (C ), 177.92 (C@O), 119.74 (C /
C ), 60.41 (CHCH ), 15.57 (CH ); ESI-MS for C18H23AuN O negative
3 3 4 8
ion (m/z): 619.2 (MꢁH ). Solubility: soluble in H O, insoluble in
5
4
.1.1.1. 1,3-Bis(carboxymethyl)imidazole (1). Yield: 90% of an off-
1
+
white powder. MP: 290 °C H NMR (D
2
O, 600 MHz, d ppm): 8.85
HH = 1.41, 2H, H /H ), 5.00 (m,
2
4
2
4
4
5
(
t,
J
HH = 1.41, 1H, H ), 7.51 (s,
J
organic solvents.
1
3
4
H, CH
2
); C NMR (D
2
O, 150 MHz, d ppm): 170.86 (C@O), 137.76
2
4
5
ꢁ1
1
(C ), 123.35 (C /C ), 51.07 (CH
2
); FTIR-ATR (cm ): 3433 (s) OH,
4.1.2.3. Gold(I) complex (3a). H NMR (D O, 600 MHz, d ppm): 7.30
(s, 4H, H /H ), 5.60 (m, 4H, CHCH ), 2.70 (m, 8H, CH ), 2.45 (m, 8H,
2 2
CH ), 2.05 (s, 12H, CH ). C NMR (D O, 150 MHz, d ppm): 182.43
2 3 2
(C ), 174.71 (C@O), 121.52 (C /C ), 63.05 (CHCH ), 34.02 (CH ),
2
4
5
1
731 (s) C@O, 1663 (s) C@O, 1604 (s) COO, 1572 (s) imidazole ring
+
13
vibration. ESI-MS (neg) for C
H
7 8
N
2
O
4
(m/z): 367.1 (MꢁH )
2
, 183.0
+
2
4
5
(
M–H ). Data correspond to those reported in the literature [18].
2
2
3
2.19 (CH
2
), 18.99 (CH
3
); ESI-MS for C26
H
39AuN
4
O
8
S
4
(m/z):
+
4
.1.1.2. 1,3-Bis(1-carboxyethyl)imidazole (2). Yield: 87% of an off-
859.2 (MꢁH ). Solubility: soluble in H O, partially soluble in DMF
2
1
white powder. MP: 218 °C. H NMR (D
2
O, 600 MHz, d ppm): 9.00
and DMSO, and insoluble in other conventional organic solvents.
4
2
4
4
5
(
t, JHH = 1.37, 1H, H ), 7.58 (d, JHH = 1.37, 2H, H /H ), 5.18 (m,
1
3
1
4
1
H, CHCH
3
) 1.81 (d, 6H, CH
3
); C NMR (D
2
O, 150 MHz, d ppm):
) 17.16
); FTIR-ATR (cm ): 3507 (s) OH, 1732 (s) C@O, 1701 (s)
C@O, 1665 (s) COO, 1560 (s) imidazole ring vibration. Elemental
Anal. Calc. for C : C, 50.95; H, 5.70; N, 13.20; O, 30.16.
4.1.2.4. Gold(I) complex (4a). H NMR (D O, 600 MHz, d ppm): 7.21
2
2
4
5
4
5
73.90 (C@O), 135.53 (C ), 121.72 (C /C ), 59.19 (CHCH
3
6 5 2
(s, 4H, H /H ), 7.01–6.86 (s, 20H, C H ), 4.99 (s, 4H, CHCH ), 3.57–
3.15 (m, 8H, CH2). C NMR (D O, 150 MHz d ppm): 183.80 (C ),
2
175.04 (C@O), 137.40 (C /C ), 128.64, 126.87, 122.62 (C H ),
ꢁ1
13
2
(CH
3
4
5
5
6
H
9 12
N
O
2 4
2 2 4
67.88 (CHCH ), 39.55 (CH ); ESI-MS for C42H39AuN O8 (m/z):
+
Found: C, 50.1962; H, 5.6513; N, 12.9457; O, 31.2068%. ESI-MS
923.3 (MꢁH ). Solubility: soluble in H O, alcohols, DMSO and DFM.
2
+
ꢁ
(
neg.) for C
9
H
12
N
2
O
4
(m/z): 423.2 (MꢁH )
2
, 211.1 (MꢁH ). Data
18
correspond to those reported in the literature.
4.1.3. General procedure for the preparation of the gold(III) complexes
2
Br (3.6 lL, 0.07 mmol) was added to a solution of the corre-
4
.1.1.3.
1,3-bis(1,carboxy-3-(methylthio)propylethyl)imidazole
sponding gold(I) complex (0.07 mmol in 4 mL of H O). The result-
2
1
(3). Yield: 80% of an off-white powder. MP: 240 °C. H NMR
ing solution was stirred for 8 h at room temperature. The solution
was filtered, and the solvent was removed by vacuum.
4
2
(
D
J
2
O, 600 MHz, d ppm): 9.18 (t,
J
HH = 1.38, 1H, H ), 7.68 (d,
4
4
5
HH = 1.38, 2H, H /H ), 5.30 (m, 2H, CHCH
.41 (m, 4H, CH
2
), 2.61 (m, 4H, CH
2
),
13
2
2
), 2.09 (s, 6H, CH
3
); C NMR (D
2
O, 150 MHz, d
4.1.3.1. Gold(III) complex (1b). ESI-MS for C14H15AuBr N O , nega-
2
4
8
2
4
5
+
ppm): 172.48 (C@O), 136.75 (C ), 122.13 (C /C ), 62.44 (CHCH
2
),
tive ion (m/z): 722.9 (MꢁH ).
ꢁ1
3
0.56 (CH
OH, 1727 (s) C@O, 1674 (s) C@O, 1611 (s) COO, 1557 (s) imidazole
ring vibration. Elemental Anal. Calc. for C13 : C, 46.97; H,
.06; N, 8.43; O, 19.25. Found: C, 46.4110; H, 5.9168; N, 8.3812; O,
7.1077. ESI-MS for C13 negative ion (m/z): 663.3 (M–
2 2 3
), 29.35 (CH ), 13.92 (CH ); FTIR-ATR (cm ): 3112 (s)
4
.1.3.2. Gold(III) complex (2b). ESI-MS for C18
tive ion (m/z): 779.1 (MꢁH ).
H
23AuBr
2
4
N O
8
, nega-
+
20 2 4 2
H N O S
6
2
20 2 4 2
H N O S
4
.1.3.3. Gold(III) complex (2c). ESI-MS for C
ion (m/z): 644.2 (MꢁH ).
9 3
H12AuBr N
2
O
4
positive
+
+
+
H )
2
, 331.1 (M–H ).
4
.1.1.4. 1,3-bis(1-carboxyphenylethyl)imidazole (4). Yield: 60% of an
Acknowledgments
1
6
off-white powder MP: 244 °C. H NMR (DMSO-D , 600 MHz, d
ppm): 9.33 (t,
7
CH
4
2
4
4
5
J
HH = 1.4, 1H, H ), 7.44 (d,
.16–6.06 (t, 10H, C ), 5.19 (s, 2H, CHCH
6
C NMR (DMSO-D , 150 MHz, d ppm): 169.34 (C@O),
J
HH = 1.4, 2H, H /H ),
This work was supported by the Consejo Nacional de Ciencia y
Tecnología (CONACYT) (Grant: 180717 and M.S. grant to M.A.R.-E).
6
H
5
2
), 3.47–3.16 (m, 4H,
1
3
2
);
2
4
5
1
36.89 (C ), 129.16, 128.95, 127.21 (C
6
H
1
5
), 121.98 (C /C ), 65.26
Appendix A. Supplementary data
ꢁ
(CHCH
2
), 38.81 (CH
2
); FTIR-ATR (cm ): 3442 (s) OH, 1727 (s)
C@O, 1674 (s) COO, 1562 (s) imidazole ring vibration. Elemental
Anal. Calc. for C21 : C, 69.22; H, 5.53; N, 7.69; O, 17.56.
CCDC 986007, 986008 and 986009 contains the supplementary
20 2 4
H N O
crystallographic data for 3, (racemate-2cꢀH
2
O) and di-hydrate (R,S-
cꢀ2H O). These data can be obtained free of charge via http://
Found: C, 68.9896; H, 5.6049; N, 7.7584; O, 17.6471%. ESI-MS for
2
2
+
+
C
21
20
H N
2
O
4
negative ion (m/z): 727.4 (MꢁH )
2
, 363.3 (MꢁH ). Data
www.ccdc.cam.ac.uk/conts/retrieving.html, or from the Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ,
UK; fax: (+44) 1223-336-033; or e-mail: deposit@ccdc.cam.ac.uk.
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.poly.2014.07.014.
correspond to those reported in the literature [18].
4.1.2. General procedure for the preparation of gold(I) complexes (1a–
4
a)
Under nitrogen atmosphere, a mixture of the zwitterionic
ligand (0.14 mmol), NaOH (11.2 mg, 0.28 mmol), Ag
2
O (16 mg,
O (4 mL) was stirred at room temperature for
4 h under protection from light. Then, (CH SAuCl (20 mg,
.07 mmol) was added, and the mixture was stirred for 24 h. The
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