Thiol-Functionalized IGEPAL Surfactants as Novel Fluorescent Ligands for the Silica Coating of Gold Nanoparticles

Article abstract of DOI:10.1002/ijch.201500045

A synthesized thiol-functionalized non-ionic surfactant based on the IGEPAL (polyoxyethylene(5) nonyl phenyl ether) structure, has been used to replace citrate ions from the surface of gold nanoparticles with 13.5 nm diameters. Upon IGEPAL-type stabilizat

Full text of DOI:10.1002/ijch.201500045

Full Paper
DOI: 10.1002/ijch.201500045
ꢀ
Thiol-Functionalized IGEPAL Surfactants as Novel
Fluorescent Ligands for the Silica Coating of Gold
Nanoparticles
[
a]
[a]
[a]
[a]
Helena Gavilµn-Rubio, Jo¼o Paulo Coelho, Guillermo Gonzµlez-Rubio, Gloria Tardajos,
[
b]
[b]
[a]
JosØ Osío Barcina, Castor Salgado, and AndrØs Guerrero-Martínez*
Abstract: A synthesized thiol-functionalized non-ionic sur-
factant based on the IGEPAL (polyoxyethylene(5) nonyl
through the conventional Stçber approach. This method
allows fine control over the silica thickness, showing uni-
form and homogeneous core-shell nanoparticles. Additional-
ꢀ
phenyl ether) structure, has been used to replace citrate
ions from the surface of gold nanoparticles with 13.5 nm di-
ꢀ
ly, the luminescent properties of the IGEPAL surfactant
ꢀ
ameters. Upon IGEPAL -type stabilization in water, the
allow the versatile preparation of robust fluorescent nano-
particles with multiplexing potential as simultaneous plas-
monic and fluorescence probes.
nanoparticles were transferred to ethanol, where a layer of
silica was efficiently grown on the nanocrystal surface
Keywords: gold · nanomaterials · surfactants
1. Introduction
[
2]
The design of new chemical stabilizers is a driving force
in the broad field of colloid science. Such stabilizers could
be the answer to physicochemical challenges encountered
during the synthesis and use of colloidal particles, such as
colloids. These advantages render silica an ideal, low-
cost material to tailor surface properties. Additionally,
this coating should endow the cores with several benefi-
cial properties, such as the possibility of subsequent func-
[
1]
[1]
low stabilities and high tendencies to aggregate. The
synthesis of core-shell architectures is a methodology suc-
cessfully employed in a “bottom up” approach, which has
been efficiently used to overcome these limitations.
Within this context, the coating of colloidal nanoparticles
with inorganic silica has been frequently studied in mate-
tionalization and biocompatibility, which allow the use
of these nanomaterials to enhance both diagnostic and
therapeutic techniques.
the optical transparency of silica, this coating material is
used as a host matrix for highly luminescent dye mole-
cules that fit inside the porous structure. These organic
dyes are usually inserted after the silica coating by an ad-
ditional step of synthesis, leading to non-desired aggrega-
tion processes that significantly decrease the quantum
yields of the fluorophores. Therefore, the discovery of
new luminescent ligands that are present during the silica
coating process and whose photophysical properties do
[
12]
Within this context, owing to
[
2]
[
2]
rials science for the enhancement of colloidal stability.
Notable examples include the silica coating of colloidal
[
3]
[4]
systems for nanoscale metals, semiconductors, and
[5]
magnetic nanoparticles.
The use of silica as a coating material for colloids is
motivated mainly by its high stability – especially in
polar solvents – the easy regulation of the coating pro-
[6]
[7]
[8]
cess, the chemical inertness, and the characteristic op-
[
9]
tical transparency in the visible spectrum range. There
are mainly two factors favoring the remarkable stability
of silica-coated colloids: (i) the van der Waals interactions
among silica nanoparticles are much lower than those in-
volving other colloids, as a consequence of the low value
[
a] H. Gavilµn-Rubio, J. P. Coelho, G. Gonzµlez-Rubio, G. Tardajos,
A. Guerrero-Martínez
Departamento de Química Física I
Universidad Complutense de Madrid
Avda. Complutense s/n
28040 Madrid (Spain)
e-mail: aguerrero@quim.ucm.es
[10]
of the Hamaker constant; and (ii) cations and positively
charged molecules can be easily attached to the charac-
teristic polymeric silica layer at silica-water interfaces
[
b] J. O. Barcina, C. Salgado
Departamento de Química Orgµnica I
Universidad Complutense de Madrid
Avda. Complutense s/n
[11]
under basic conditions. Therefore, this silicate layer can
confer both steric and electrostatic protection on different
cores and act as a dispersing agent of many electrostatic
28040 Madrid (Spain)
Isr. J. Chem. 2016, 56, 249 – 256
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249

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not undergo significant modification is especially appeal-
ing.
A number of reports have been devoted to silica coat-
ing of colloidal metal nanoparticles (NPs) by aqueous
pentaoxyethylene nonyl phenyl ether structure, in which
the thiol group has been introduced on the alkyl chain on
the opposite side of the phenyl group to ensure coordina-
tion to the surface of previously synthesized gold nano-
particles (AuNPs). Using this surfactant, we present
a rapid, simple strategy that can be applied to coat
[
13]
classical methods, such as Stçber synthesis,
use of
[14]
silane coupling agents, and sodium silicate water-glass
[15]
methodology. This interest is based on the relevant op-
tical properties that noble metals, such as gold and silver,
exhibit at the nanoscale, due to the excitation of the lo-
calized surface plasmon resonance (LSPR). This optical
response can be tuned by changing different parameters
such as the size, shape, and composition of the NP. Ad-
ditionally, the LSPRs of NPs are extremely sensitive to
modifications of the local refractive index, a property
that is particularly attractive for sensing applications in
AuNPs with homogeneous silica shells (Au@SiO NPs)
2
and that allows control over shell thickness. The method-
ology involves the transfer of AuNPs to ethanol, where
silica can be directly condensed on the nanoparticle sur-
face by using the standard Stçber synthesis. Moreover,
[16]
[
17]
ꢀ
the luminescent properties of IGEPAL -type surfactants
offers a straightforward method to obtain robust fluores-
[18]
cent Au@SiO NPs, without the need for further incorpo-
2
[
12]
ration of fluorophores during the silica growth.
[19]
nanoplasmonics. The selection of a suitable silica coat-
ing method is mainly determined by the chemical affinity
of the metal colloid surface for silica, as well as by the
stability of the particles in the coating reaction medium.
Interestingly, surface modification with amphiphilic stabil-
izers greatly assists the transfer of nanoparticles from
2
. Results and Discussion
ꢀ
Synthesis of the thiol-functionalized IGEPAL -type sur-
factant. The synthesis of IgeSH (6) was carried out follow-
ing our optimization of a procedure described elsewhere
(Scheme 1), in which the yield was improved. In short,
for the preparation of the monotosylate 1, a modification
of the method reported by Bouzide et al. was em-
ployed. Thus, an improved yield of 1 (98% vs. 78%)
was obtained using a stoichiometric quantity of NaI in-
stead of catalytic KI. Under these reaction conditions, the
amount of the corresponding ditosylate formed as by-
product in the reaction was almost negligible.
reason for this behavior is the stability of the podand·ca-
tion complex formed as an intermediate in the reaction,
which is greater in the case of pentaethyleneglycol·Na
than with K . Selective monotosylation can be explained
[7,9]
water into various solvents,
such as alcohols, where
[
26]
silica coating can be achieved through controlled hydroly-
[13–15]
sis and condensation of silanes.
The most successful methods for silica coating of NPs
involve prior colloidal stabilization by polymers or surfac-
tants, due to the amphiphilic properties of these chemical
[
27]
[2]
species.
Among them, thiol-modified poly(ethylene
glycol) polymers have been efficiently used to replace
standard capping agents from the surface of NPs to con-
trol the direct growth of silica on the particle surfaces
[
28]
The
[9]
through the standard Stçber process. The combination
[
20]
+
of the high affinity of thiol groups for metal surfaces
+
and the non-charged hydrophilic environment that oxy-
ethylene groups offer in aqueous media renders this poly-
mer ideal for silica coating purposes. In relation to poly(-
by the different acidity of hydrogen atoms H and H in
the complex.
a
b
ꢀ
ethylene glycol) polymers, IGEPAL surfactants (poly-
Synthesis and stabilization of AuNPs. In a typical syn-
[21]
[29]
oxyethylene nonyl phenyl ethers),
have been used to
thesis of spherical AuNPs stabilized with citrate, a solu-
generate preferred sites for silica nucleation and growth,
due to the strong interaction that ether groups exhibit
tion of HAuCl was heated to boiling. Then, a solution of
4
sodium citrate was quickly injected into the above solu-
tion under vigorous stirring. The mixture was kept boiling
until the color changed to red. Then, at room tempera-
ture, the mixture was centrifuged to remove the excess of
sodium citrate and the precipitate was redispersed in the
same volume of water. The resulting citrate-stabilized
AuNPs presented a diameter of 13.5Æ1.5 nm as deter-
mined from TEM micrographs (Figure 1).
[22]
with silanes through hydrogen bonding.
Additionally,
these surfactants are very suitable because they present
well-differentiated structural patterns, which offer a way
to understand the effect of the chemical structure on
[23]
their amphiphilic properties. As a general rule, it has
been observed that the critical micelle concentration and
the cloud-point temperature of these molecules decrease
with shortening of the oxyethylene chain, which is ex-
plained in terms of a lower hydrophilic tail hydration,
Then, an aqueous solution of IgeSH was added to the
citrate AuNPs solution and stirred overnight. The citrate
[24]
À
which favors the formation of large aggregates. More-
ions were subsequently replaced by IgeS , a process
ꢀ
over, IGEPAL surfactants have shown interesting photo-
driven by the stronger interaction of thiol groups with the
[
20]
physical properties that strongly depend on the hydropho-
bic environment in which the phenyl moiety is immersed
gold surface (IgeS-AuNPs). The excess free IgeSH was
removed from the solution by centrifugation and redis-
persion in ethanol. By TEM, no significant differences in
the size of IgeS-AuNPs were observed with respect to the
initial citrate AuNPs. The replacement of citrate ions by
[25]
during aggregation processes.
With all this in mind, we report the synthesis of a new
ꢀ
thiolated IGEPAL -type surfactant (IgeSH) based on the
Isr. J. Chem. 2016, 56, 249 – 256
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Scheme 1. Chemical synthesis of the surfactant IgeSH (6).
Figure 1. (a) Representative TEM micrographs and (b) size distribution of citrate AuNPs.
3
À1
À1 [26]
the surfactant at the surface of the NPs was followed by
zeta potential measurements, which showed a decrease
from À30Æ2 mV to À15Æ2 mV, which is in good agree-
ment with the zeta potential values of AuNPs coated by
polyethylene glycol polymers with low molecular
3.1”10 Lmol cm ).
From this concentration and
2
considering an available surface of 573 nm for a AuNP
of 13.5 nm in diameter, the concentration of capping
agent around a nanocrystal has been estimated at ~4”
10 . From this geometric consideration, an area per sur-
factant molecule of 0.14 nm at the NP surface has been
3
[30]
2
weights.
À10
For a 2”10 M solution of IgeS-AuNPs, the final con-
centration of capping surfactant at the surface of the
nanocrystal was estimated at 1.2”10 M from the UV/
determined. Interestingly, this area is considerably lower
than that obtained with AuNPs coated with thiol-modi-
À6
2
fied poly(ethylene glycol) polymers (0.25 nm per mole-
[
9]
ꢀ
Vis spectrum of the supernatants, employing the calculat-
cule), indicating close-packing of IGEPAL -type mole-
cules at the surface of the nanocrystals.
ed molar absorptivity of IgeSH at 278 nm in water (e278
=
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The UV/Vis absorbance spectrum of the final IgeS-
AuNPs in ethanol shows two small maxima at 220 and
form silica shell (Figure 2b), the increase of r to 2.0 leads
to the formation of silica nanoparticles 180Æ20 nm in di-
ameter, which are decorated by a small fraction of the
available IgeS-AuNPs at their surfaces (Figure 2d). At in-
termediate ratios (r=1.0), uncontrolled aggregation of
IgeS-AuNPs within silica nanostructures is observed (Fig-
ure 2c). It is noteworthy that at low ratios r the coating
with a silica shell as thin as 8.0Æ1.1 nm (Figures 2a and
3a), which is close to the radius of the AuNPs, was suffi-
cient to render the metal colloids perfectly stable against
aggregation.
[26]
2
78 nm (Figure 2a), which correspond to the typical ab-
ꢀ
sorption bands of the IGEPAL unit, and the characteris-
tic LSPR band of AuNPs at 521 nm (Figure 2a). The max-
imum of the LSPR band is 5 nm red-shifted in compari-
son to the initial citrate AuNPs. This change in the LSPR
maximum is in good agreement with an increase in the
local refractive index of the AuNPs after IgeSH binding
[9]
and subsequent transfer to ethanol. The final structure
of the resulting IgeS-AuNPs resembles the morphology of
non-ionic micelles in water with two hydrophobic/hydro-
philic regions: the hydrocarbon and aromatic-like core di-
rectly attached to the nanocrystal surface and the external
hydrophilic oxyethylene layer in direct contact with sol-
An advantage of our method over previously reported
ones is that it readily provides fine control over the thick-
ness of the silica shells in the critical case of small
AuNPs, even for rather thin shells, by simply varying the
amount of TEOS added in the initial coating. This is
clearly demonstrated by the TEM micrographs in Fig-
ure 3a,b, in which r was slightly decreased from 0.4 to 0.2.
Thus, a uniform and homogeneous silica layer of 13.1Æ
2.0 nm was easily achieved by slight increase of the
TEOS concentration. This result demonstrates the versa-
[23]
vent molecules.
Silica coating of AuNPs stabilized with the thiol-func-
ꢀ
tionalized IGEPAL -type surfactant. The surface modifi-
cation of AuNPs by IgeSH molecules has assisted the
transfer of the nanocrystals from water into ethanol (Fig-
ure 2a), a prerequisite for the silica coating of AuNPs
[13]
ꢀ
based on the Stçber synthesis. After cleaning of IgeS-
AuNPs, a relatively concentrated aqueous solution of am-
monia was added under vigorous stirring, and finally a di-
luted solution of tetraethyl orthosilicate (TEOS) in etha-
nol was injected under gentle stirring. Under these condi-
tions, the IgeS-AuNPs can be directly coated with uni-
tility of thiolated IGEPAL -type surfactants as AuNP sta-
bilizers for fine control of thickness of the silica coating
in small AuNPs. This ability might be related to the
ꢀ
highly dense structure of IGEPAL -type molecules at the
surface of the nanocrystal.
Optical properties of silica-coated AuNPs. The effect of
the coating on the optical response of the core-shell
silica-based nanostructures is shown in Figure 2a. At low
ratios r, the LSPR band, initially at 522 nm, red-shifts
2 nm upon silica deposition because of an increase in the
local refractive index (from 1.36 in ethanol to 1.46 in
amorphous silica) around the AuNPs produced by the
form and homogenous silica shells (Au@SiO NPs) by
2
careful selection of the ammonia and TEOS concentra-
tions. Whereas at low ratios (r=[NH ]/[TEOS]=0.4)
3
every single IgeS-AuNP is individually coated with a uni-
Figure 2. (a) Normalized UV/Vis spectra of the colloids in ethanol,
obtained from the silica coating of AuNPs at different concentra-
tions of NH : initial IgeS-AuNPs (black); [NH ]=0.2 mM (red);
3
3
[
NH ]=2.0 mM (green); and [NH ]=4.0 mM (blue). The inset shows
3 3
the full UV/Vis spectrum of the initial IgeS-AuNPs, where the aster-
isks show the absorption bands of the ligand. TEM micrographs of
AuNPs coated with silica at [NH ]=0.2 mM (b), [NH ]=2.0 mM (c),
Figure 3. TEM micrographs Au@SiO NPs and their respective thick-
2
ness distributions of the silica layer, at [NH ]/[TEOS]=0.4 (a,b) and
3
3
3
and [NH ]=4.0 mM (d).
0.2 (c,d), respectively.
3
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silica shell. In contrast, the increase of r to 1.0 leads to
a larger shift of the LSPR band (5 nm) and increase of
the scattering background, due to the random aggregation
of NPs within a thick silica layer. Finally, large values of r
induce the formation of large silica NPs that strongly en-
hance the light scattering background of the UV/Vis spec-
parison of the fluorescence spectra, mainly due to the ab-
sence of overlapping between the emissive band of IgeSH
and the LSPR band of the metal core. Additionally, the
emission spectrum of the Au@SiO NPs (shell of 13.1 nm
2
À10
thickness) at a concentration of 1.6”10 M, shows
a slight broadness of the emission band with a red shift of
2 nm. These changes suggest a planarization of the aro-
matic rings at the surface of the AuNPs because of the
unfavorable incorporation of the nonpolar aromatic
moiety into the negatively charged silica shell, which is in
good agreement with the formation of excimers when
[2]
trum.
The effect of the silica shell thickness on the optical re-
sponse of these particles is displayed in Figure 4a. The in-
crease of such thickness from 8.0 to 13.1 nm shifts the
LSPR band 4 nm, which supports the idea that the restor-
ing force on the electron oscillation associated with the
plasmon mode decreases as the thickness of the silica
ꢀ
[25]
IGEPAL surfactants aggregate in polar media.
The
absence of significant changes in the emission intensity of
[31]
layer increases. Therefore, the observed optical effects
clearly confirm that there has been absolutely no aggrega-
tion during the silica coating at low values of r, unlike the
synthesis with high concentrations of ammonia (Fig-
ure 2c), pointing to the optimal conditions for the prepa-
the Au@SiO NPs hints at their multiplexing potential as
2
simultaneous plasmonic and fluorescence probes with
quantum yields of ~0.2. Moreover, no changes of the
emission intensity have been observed over time, which
ꢀ
indicates that the IGEPAL molecules are strongly at-
tached to the gold surface, preventing the release of fluo-
rophores.
3. Conclusions
In summary, we have synthesized a novel thiol functional-
ized non-ionic surfactant based on the chemical
ꢀ
IGEPAL structure to efficiently coat AuNPs with silica.
The methodology involves initial aqueous capping ligand
replacement, subsequent transfer to ethanol solution, and
finally TEOS condensation on the nanocrystal surface
through the standard Stçber process. The obtained silica
shells are uniform and homogenous, allowing a high
degree of control over shell thickness. The corresponding
core-shell structures were unambiguously characterized
through TEM and UV/Vis spectroscopy. Fluorescence
analysis showed that the silica coating of the NPs does
not significantly alter the luminescent properties of the
Figure 4. (a) Normalized UV/Vis spectra of the colloids in ethanol,
obtained from the silica coating of AuNPs at [NH ]/[TEOS]=0.4
3
(
red) and 0.2 (blue), in comparison to IgeS-AuNPs (black). (b) Emis-
sion spectra of equivalent IgeSH (black), IgeS-AuNPs (red), and
Au@SiO NPs (blue) solutions. The excitation wavelength was fixed
2
ꢀ
at 270 nm.
IGEPAL -type fluorophores. Thus, we have produced
robust plasmonic and fluorescence probes that, after func-
tionalization of the silica surface, may lead to desired bio-
compatibility; work in this direction is in progress.
ration of Au@SiO NPs. Additionally, no significant
2
changes in the UV/Vis spectra of Au@SiO NPs in ethanol
2
have been observed on the timescale of months, showing
the high stability and robustness of the coating material.
Finally, steady-state fluorescence measurements pro-
vide detailed information about the luminescent proper-
4. Experimental Section
4
.1 Synthesis and Characterization of the Thiol-Functonalized
ꢀ
IGEPAL -Type Surfactant
ties of the Au@SiO NPs. In their monomeric state, the
2
ꢀ
fluorescence spectrum of IGEPAL surfactants, under ex-
Materials and methods: All experiments were carried out
under argon atmosphere using standard Schlenk tech-
niques. Anhydrous solvents were distilled under argon
following standard procedures. Flash chromatography
was performed over silica gel 60 (230–400 mesh). All
commercially available compounds were purchased from
commercial suppliers and used without further purifica-
tion. The preparation of monotosylate 1 was carried out
citation at 270 nm, consists of a wide band with a maxi-
[
25]
mum at 299 nm with a typical quantum yield of 0.2.
Analogously, Figure 4b shows the fluorescence spectrum
À6
of IgeSH in ethanol at a concentration of 1.0”10 M,
which is the estimated concentration of ligands that is
present in a solution of IgeS-AuNPs of concentration
À10
1
.6”10 M. No significant quenching effects have been
[
1]
observed for the equivalent IgeS-AuNP system by com-
by modification of a reported procedure.
Isr. J. Chem. 2016, 56, 249 – 256
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Synthesis of monotosylate 1: To a stirred solution of
4H), 3.75–3.43 (m, 16H), 3.40 (t, J=6.8 Hz, 2H), 2.58–
2.44 (m, 2H), 1.90–1.11 (m, 20H) ppm; C NMR
13
1
.9 g (8 mmol) of pentaethyleneglycol in 50 mL of CH Cl2
2
at 08C C, 2.78 g (12 mmol) of Ag O, 1.27 g (8.8 mmol) of
(75 MHz, CDCl ) d: 156.9, 135.2, 129.3, 114.5, 99.0, 70.9,
2
3
NaI, and 1.6 g (8.4 mmol) of TsCl were added. The reac-
tion mixture was stirred at room temperature for 20 min,
70.72, 70.7, 70.6, 69.9, 67.5, 66.7, 62.3, 35.1, 34.1, 32.9,
31.7, 30.6, 29.5, 29.4, 29.2, 28.8, 28.2, 25.5, 19.5 ppm; MS
+
+
filtered, and washed with 10% NaHCO solution (1”
(70 eV): m/z (%): 604 (4) [(M+2) ], 602 (4) [M ], 518
(87), 474 (4), 440 (7), 386 (8), 342 (14), 324 (30), 298 (5),
177 (9), 151 (14), 133 (37), 107 (68), 85 (100), 73 (30).
Synthesis of compound 6: To a solution of 1.9 g
(3.15 mmol) of 5 in 40 mL of ethanol, 259 mg (3.39 mmol)
of thiourea were added. The reaction mixture was re-
fluxed for 3 h and cooled to room temperature. A 10%
solution of NaOH (2 mL) was added, and the reaction
mixture was refluxed for another 2 h. The flask was
cooled to 08C, acidified to pH 2 with concentrated HCl,
and stirred for 24 h at 258C. The reaction mixture was ex-
tracted with CH Cl (3”20 mL), and the organic layer
3
25 mL). Evaporation of the solvent, followed by flash
chromatography (silica gel, EtOAc) yielded 3.01 g (98%)
1
of 1. H NMR (300 MHz, DMSO-d ) d: 7.79–7.77 (d, 2H),
6
6
3
.49–6.46 (d, 2H), 4.59 (t, J=5.4 Hz, 1H); 4.11 (m, 2H),
.58–3.55 (m, 2 H), 3.49–3.32 (m, 16H) ppm.
Synthesis of compound 2: To a stirred solution of 2.34 g
(5.98 mmol) of monotosylate 1 and 1.14 g (6.58 mmol) of
p-bromophenol in 50 mL of CH CN, 909 mg (6.58 mmol)
3
of K CO were added. The reaction mixture was refluxed
2
3
for 48 h, filtered, and concentrated at reduced pressure.
The crude product was purified by flash chromatography
2
2
(
silica gel, EtOAc :EtOH=9 :1) to yield 2.21 g (94%) of
. H NMR (300 MHz, CDCl3) d: 7.38–7.29 (m, 2H),
was washed with H O (1”20 mL) and saturated NaCl so-
2
1
2
6
3
1
6
lution (1”25 mL) and dried over MgSO . After evapora-
4
.83–6.70 (m, 2H), 4.15–4.00 (m, 2H), 3.87–3.78 (m, 2H),
tion of the solvent, the residue was purified by flash chro-
1
3
.74–3.51 (m, 17H) ppm; C NMR (75 MHz, CDCl ) d:
matography (silica gel, EtOAc :MeOH=9 :1) to obtain
3
1
57.9, 132.3, 116.5, 113.1, 72.5, 70.8, 70.6, 70.5, 70.5, 70.3,
1.02 g (68%) of 6. H NMR (300 MHz, CDCl ) d: 7.08–
3
+
9.7, 67.7, 61.7 ppm; MS (70 eV): m/z (%): 392 (14) [M
7.05 (m, 2H), 6.84–6.81 (m, 2H), 4.12–4.09 (m, 2H), 3.86–
3.82 (2H, m), 3.74–3.58 (16H, m), 2.79 (1H, m), 2.50 (4H,
]
(
, 362 (2), 304 (3), 262 (8), 244 (9), 216 (11), 200 (60), 172
21), 133 (62), 120 (82), 89 (100), 87 (38).
13
m), 1.61–1.21 (15H, m) ppm; C NMR (75 MHz, CDCl3)
d: 156.9, 135.4, 129.3, 114.6, 72.7, 70.9, 70.7, 70.4, 69.9,
67.6, 61.8, 35.2, 32.3, 31.8, 29.85, 29.8, 29.6, 29.4,
Synthesis of compound 3: A solution of 500 mg
1.27 mmol) of 2, 214 mg (2.54 mmol) of dihydropyran,
(
+
and 64 mg (0.25 mmol) of PPTS in 20 mL of CH Cl was
29.1 ppm; MS (70 eV): m/z (%): 472 (2) [M ], 438 (2),
2
2
stirred for 4 h at 258C. The reaction mixture was extract-
394 (2), 340 (2), 311 (4), 283 (7), 246 (7), 220 (6), 177
(10), 135 (12), 133 (75), 107 (100), 89 (63).
ed with CH Cl (3”25 mL), and the organic layer was
2
2
washed with 10% NaHCO solution (1”25 mL) and H O
3
2
(
1”25 mL) and dried over MgSO . The solvent was
4
4
.2 Synthesis and Capping Agent Replacement of AuNPs
evaporated at reduced pressure, and the residue was puri-
fied by flash chromatography (silica gel, EtOAc) to
afford compound 3 (546 mg, 90%). H NMR (300 MHz,
CDCl ) d: 7.36–7.30 (m, 2H), 6.80–6.74 (m, 2H), 4.65–
4
Materials and methods: All the starting materials were
obtained from commercial suppliers and used without fur-
ther purification. Sodium citrate, ammonium hydroxide
(25% v/v), TEOS, and ethanol (96% v/v) were purchased
1
3
.59 (m, 1H), 4.08 (m, 2H), 3.92–3.80 (m, 4H), 3.74–3.55
1
3
(m, 16H), 1.91–1.44 (m, 6H) ppm; C NMR (75 MHz,
CDCl ) d: 157.9, 132.21, 116.5, 113.0, 98.9, 70.9, 70.6, 70.5,
from
Sigma-Aldrich.
Tetrachloroauric(III)
acid
(HAuCl ·3H O) was supplied by Alfa Aesar. Milli-Q
3
4
2
6
9.6, 67.7, 66.7, 62.2, 30.6, 25.4, 19.5 ppm; MS (70 eV): m/
water was used in all preparations (conductivity less than
16 mScm ).
+
+
À1
z (%): 478 (10) [(M+2) ], 476 (10) [M ], 392 (14), 362
(
(
6), 348 (9), 304 (11), 260 (19), 242 (21), 216 (15), 198
82), 120 (68), 85 (100).
Synthesis of compound 5: 3.8 mL of t-BuLi (1.7 M,
Synthesis of citrate-stabilized AuNPs: In this synthesis,
the reduction of chloroauric acid in the presence of
sodium citrate takes place, producing size-defined AuNPs.
Typically, 2 mL of a 25 mM HAuCl4 aqueous solution
were added to 125 mL of distilled water. The solution was
brought to its boiling point. Then, 5 mL of a 1% w/w
sodium citrate solution was added under vigorous stirring.
In approximately 10 min, a change of color from blackish
to red was observed. Once this point was reached, the so-
lution was allowed to cool to room temperature. In order
to remove the excess citrate ions, the as-synthesized solu-
tion was centrifuged for 90 min at 7500 rpm, and the pre-
cipitate was dispersed in distilled water.
6
.46 mmol) were slowly added under argon atmosphere
at À788C to a solution of 1.49 g (3.12 mmol) of 3 in
0 mL of THF. After 5 min, the resulting solution of 4
3
was added to 3.57 g (12.48 mmol) of 1,9-dibromononane
dissolved in 20 mL of THF at À148C and stirred at room
temperature for 12 h. After addition of 50 mL of water,
the reaction mixture was extracted with Et O (3”30 mL)
and dried over MgSO . Evaporation of the solvent and
2
4
purification of the residue by flash chromatography (silica
gel, hexane :EtOAc=9 :1) yielded 1.77 g (94%) of 5. H
1
NMR (300 MHz, CDCl ) d: 7.08–7.05 (m, 2H), 6.84–6.80
Capping agent replacement: Citrate-stabilized AuNPs
were transferred from aqueous media into ethanol via
3
(m, 2H), 4.63 (m, 1H), 4.19–4.03 (m, 2H), 3.92–3.79 (m,
Isr. J. Chem. 2016, 56, 249 – 256
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ꢀ
ligand exchange through the thiolated IGEPAL -type
surfactant. Thus, 40 mL of a 0.3 mM IgeSH aqueous solu-
tion were added to 10 mL of a 0.5 mM dispersion contain-
ing the AuNPs. The exchange reaction was allowed to
continue overnight under magnetic stirring. The sample
was washed with distilled water and centrifuged for
Acknowledgments
This work has been funded by the I Convocatoria de
Ayudas Fundación BBVA a Investigadores, Innovadores y
Creadores Culturales and the Madrid Regional Govern-
ment (S2013/MIT-2807). J. P. C. acknowledges receipt of
a CiÞncia sem Fronteiras fellowship from the CNPq of
Brazil. A. G.-M. acknowledges receipt of a Ramón y
Cajal Fellowship from the Spanish MINECO.
90 min at 7500 rpm, and the gold concentration was ad-
justed to 1.8 mM.
4.3 Silica Coating of AuNPs
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256