Decoration of gold nanoparticles by a double-armed calix[4]pyrrole: A receptor-decorated nanoensemble for anion sensing and extraction

Article abstract of DOI:10.1002/chem.201300472

Gold nanoparticles decorated with a double-armed, deep-cavity calix[4]pyrrole were prepared and fully characterized. Transmission electron microscopy imaging revealed that the average diameter of the particles was approximately 4 nm both before and after attachment of the receptor to the surface. The calix[4]pyrrole-functionalized nanoparticles exhibited highly elevated sensing behavior (approximately 1000 times in dichloromethane) relative to its monomeric congener while maintaining its guest selectivity. The receptor-nanoparticle conjugate (nanoreceptor) showed significant aggregation upon addition of the biphenolate anion, an effect ascribed to anion-mediated interparticle linking. The receptor-nanoparticle conjugate is also capable of extracting the fluoride anion (as its tetrabutylammonium salt) from an aqueous layer to an organic medium. Control experiments revealed that this extraction is not possible when using the analogous monomeric receptor. Copyright

Full text of DOI:10.1002/chem.201300472

FULL PAPER
DOI: 10.1002/chem.201300472
Decoration of Gold Nanoparticles by a Double-Armed Calix[4]pyrrole: A
Receptor-Decorated Nanoensemble for Anion Sensing and Extraction
Punidha Sokkalingam,[a] Seong-Jin Hong,[a] Abdullah Aydogan,[b]
Jonathan L. Sessler,*[b] and Chang-Hee Lee*[a]
Chem. Eur. J. 2013, 00, 0 – 0
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Abstract: Gold nanoparticles decorated
with a double-armed, deep-cavity calix-
ACHTUNGTRENNUNG[4]pyrrole were prepared and fully
1000 times in dichloromethane) rela-
tive to its monomeric congener while
maintaining its guest selectivity. The re-
ceptor–nanoparticle conjugate (nanore-
ceptor) showed significant aggregation
upon addition of the biphenolate
anion, an effect ascribed to anion-
mediated interparticle linking. The re-
ceptor–nanoparticle conjugate is also
capable of extracting the fluoride anion
(as its tetrabutylammonium salt) from
an aqueous layer to an organic
medium. Control experiments revealed
that this extraction is not possible
when using the analogous monomeric
receptor.
characterized. Transmission electron
microscopy imaging revealed that the
average diameter of the particles was
approximately 4 nm both before and
after attachment of the receptor to the
surface. The calix[4]pyrrole-functional-
ized nanoparticles exhibited highly ele-
vated sensing behavior (approximately
Keywords: aggregation · anions ·
nanoparticles · nanosensors · recep-
tors
Introduction
binding affinity and selectivity of calix[4]pyrroles. These ef-
forts have mostly focused on polymeric scaffolds, wherein
the calix[4]pyrrole receptor is tethered to a polymer back-
bone, either during polymerization or on a preformed poly-
meric support.[2a,7] However, attractive as these systems are
for extraction of certain anions, they generally fail to pro-
duce an appreciable change in optical signature when ex-
posed to various anions. One potential way to overcome this
limitation would be to attach the calixpyrrole subunit to a
gold nanoparticle (AuNP). Because of the known toxicity of
fluoride ions,[8] we remain interested in developing so-called
chemosensors for this Lewis basic species.[9–12] We recently
demonstrated that a calix[4]pyrrole that bore cis-bis(4-
The importance and ubiquity of anions in a wide range of
chemical and biological processes, including sensing, extrac-
tion, and catalysis, have encouraged intensive research in
the area of anion recognition chemistry.[1] As a subset of this
effort, the covalent attachment of anion receptors to solid
substrates has gained significant attention in recent years be-
cause of the enhanced binding affinity towards anionic
guests that can be achieved using this approach as compared
to the use of analogous monomeric entities.[2] Gold nanopar-
ticles (AuNPs) are of special interest as supports because of
their large, highly exposed surface area, and the fact that
they can be modified both in terms of surface functionality
and particle size.[3,4] The high molar absorptivity of AuNPs
in the visible region also makes them attractive as potential
optical nanoprobes for anionic species. These considerations
provide an incentive to prepare anion-receptor-functional-
ized AuNPs.
fluoroACHTNUTRGNEpNUG henyl) pickets (compound 4) displayed a remarkable
Among the better studied anion-binding receptors are
calixACHTUNGTRENNUNG[4]pyrroles, a class of tetrapyrrolic nonaromatic macro-
cycles that are characterized by their simple molecular
design and extremely convenient synthesis.[5] Whereas the
use of calix[4]pyrroles for the selective recognition of anions
in organic media is well developed,[6] their utility in polar
competitive media, such as water, remains limited. Recently,
significant progress has been made in improving the anion-
[a] Dr. P. Sokkalingam, S.-J. Hong, Prof. C.-H. Lee
Department of Chemistry
binding affinity for fluoride anion salts and selectivity over
other anions in organic media.[5] However, the receptor ex-
hibited an almost negligible binding affinity for the fluoride
anion in aqueous media. We envisioned that by attaching
the same receptor to the surface of AuNPs, not only would
the affinity towards the fluoride anion be enhanced, a viable
optical sensing system might also be achieved. The change
in overall system polarity that would likewise accrue from
this attachment led to the further consideration that calix[4]-
pyrrole-functionalized AuNPs might have a role to play as
anion extractants.
Kangwon National University
Chun Cheon 200-701 (Korea)
Fax : (+82)33-253-7582
E-mail: chhlee@kangwon.ac.kr
Homepage: http://www.cc.kangwon.ac.kr/~chhlee
[b] A. Aydogan, Prof. J. L. Sessler
Department of Chemistry and Biochemistry
University of Texas at Austin
Austin, TX 78712-0165 (USA)
E-mail: sessler@mail.utexas.edu
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201300472.
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Decoration of Gold Nanoparticles
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Results and Discussion
solvents). Finally, the basic substitution pattern on the cal-
ix[4]pyrrole subunit previously demonstrated to enhance flu-
oride anion recognition was retained.
As detailed below, we have now proof-of-concept support
for these postulates. Specifically, we have prepared and char-
acterized calix[4]pyrrole-functionalized AuNPs based on 5
(i.e., Au·[1]n) and show their use in colorimetric/fluores-
cence-based fluoride anion binding and sensing. These sys-
tems bind the fluoride anion effectively and with high selec-
tivity. Moreover, and in marked contrast to the correspond-
ing monomeric receptor, organic solutions of the nanorecep-
tor Au·[1]n are capable of extracting fluoride anions from
aqueous solution (Scheme 1). To the best of our knowledge,
this is the first example of calix[4]pyrrole receptor-coated
AuNPs and the first supported calixpyrrole system that can
carry out both dual-mode sensing (i.e., both colorimetric-
Preparation of the thiol group, double-armed calix[4]pyr-
role scaffold 1 began with the synthesis of a functionalized
calix[4]pyrrole monomer 10 that featured cis-bis(p-fluoro-
phenyl) groups and hydroxy linkers, which can be directly
coupled to carboxyl-terminated thiol-protected moiety 14
(Scheme 2). The initial precursor that led to 10 (i.e., the di-
pyrromethane ethyl ester 8) was synthesized by means of
the acid-catalyzed condensation of ethyl-3-(4-fluoroben-
zoyl)propionate with pyrrole. The calix[4]pyrrole intermedi-
ate 9 was then obtained by condensing 8 with acetone in the
presence of a catalytic amount of BF3. The desired hydrox-
yl-terminated calix[4]pyrrole 10 was prepared in 70% yield
from 9 through NaBH4 reduction. To obtain the other key
precursor, 14, the thiol group present in compound 12 (pre-
pared through a literature procedure)[14] was subject to pro-
tection using the pyridine disulfide to afford 13. Saponifica-
tion in aqueous lithium hydroxide then gave the carboxyl-
terminated thiol-protected moiety 14. Compound 11 was
then obtained by coupling a slight excess amount of 14
(2.5 equiv) with 10 in the presence of appropriate coupling
agents, namely, 1,3-diisopropyl carbodiimide (DIPC) and
4-(N,N’-dimethylamino)pyridinium-4-toluenesulfonate
(DPTS).[15] Finally, dithiothreitol (DTT) was employed to
remove the pyridine-containing protecting group. This gave
the target receptor system 1. All new compounds were char-
Scheme 1. Schematic representation of probe-bound receptor attached to
AuNPs. Also shown is the monitoring of guest recognition through fluor-
ACHTUNGTRENNUNGescence dye displacement.
and fluorescence-based) and
function as a carrier for aque-
ous-organic fluoride anion ex-
traction.
With a view to attaching the
calix[4]pyrrole subunit to an
AuNP center [AuACTHNUGTRNEG(UN SC12H25)n,
core diameterꢀ4 nm] effective-
ly, an effort was made to incor-
porate three design considera-
tions. First,
a calix[4]pyrrole
with two thiol-bearing alkyl
chains was used; this was ex-
pected to provide for a stable
but flexible double anchoring
of the anion recognition subunit
to the nanocore. Second, the
AuNPs were further decorated
with a corona of polyethylene
glycol so as to increase the solu-
bility of the nanoparticles[13]
(since initial attempts to pro-
duce functionalized AuNPs
using only alkyl-chain substitu-
tion yielded nanoparticles that
were not dispersible in organic Scheme 2. Synthesis of target compounds.
Chem. Eur. J. 2013, 00, 0 – 0
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J. L. Sessler, C.-H. Lee et al.
acterized by standard spectroscopic methods and were
found to give data consistent with the proposed structures
(see the Supporting Information).
present on the AuACTHUNGTERN(NUG SC12H25)n surface. Based on the integra-
tion of protons in the methylene directly adjacent to the ter-
minal sulfur atom in the alkyl chains present in
With receptor 1 in hand, the synthesis of the receptor-
functionalized AuNPs, Au·[1]n could be completed. It was
found that the key attachment chemistry could be carried
out using an exchange reaction. Specifically, an excess
amount of 1 was mixed with dodecanethiol-functionalized
AuACTHUNGRETNN(UG SC12H25)n, as well as those for the b-pyrrolic protons, it
proved possible to estimate the molar ratio of the dodecane
thiol subunits to calix[4]pyrrole-appended thiols as 2:1:1
(see the Supporting Information).
As recorded in CH2Cl2, solutions of Au·[1]n gave rise to
UV/Vis spectra that were characterized by a highly intense
absorption band at 228 nm that is considered diagnostic of
the calix[4]pyrrole moiety.[5] In addition, a weaker plasmon
resonance band at 518 nm, which corresponds to the
AuNPs,[3] was observed. The combined observation of both
these spectral features is taken as further support for the
conclusion that Au·[1]n was formed as per the synthetic
design.
AuNPs, AuACHTUNGTRENNUNG(SC12H25)n, in CH2Cl2. The nanoparticles pre-
pared in this way were subject to analysis using TEM, SEM,
1H NMR spectroscopy, and UV/Vis spectroscopy. Figure 1a
To estimate the number of calix[4]pyrrole molecules pres-
ent on the Au·[1]n surface, thermogravimetric analysis
(TGA) was performed.[15] As a control, Au
ACTHNUTRGNEGN(U SC12H25)n was
analyzed to measure the amount of organic material (thiol
ligands) present before the exchange that leads to Au·[1]n
was carried out. Previously it was reported, on the basis of
TGA analyses, that 4 nm gold clusters contain approximate-
ly 1977 atoms (MAu =390 kDa)[4a,e] and that roughly 342
thiol ligands serve to cover their surface. In the case of
decane thiol-based systems, this accounts for around
14.99% of the mass of the AuNPs. Using this same analysis,
the composition of Au·[1]n was determined to be 38.26%
organic and 61.74% metallic (i.e., Au). Since the molecular
weight of the gold core is unchanged (i.e., 390 kDa), the
total molecular weight of the organic shell is calculated to
be 631 kDa. Assuming that approximately half of the dodec-
Figure 1. TEM images (and average sizes) of a) AuNPs ((3.97Æ
0.33) nm), b) Au·[1]n ((3.90Æ0.11) nm), c) Au·[1]n after addition of TBAF
((3.90Æ0.10) nm), and d) Au·[1]n after addition of the 4,4’-biphenolate
anion (as its TBA salt) 3 ((3.90Æ0.10) nm). Scale bars are 20 nm.
1
shows a low-resolution TEM image of Au(SC12H25)n. On the
G
ane thiol ligands (calculated from the H NMR spectroscop-
basis of this analysis, it was concluded that the average size
of the particles was roughly 4 nm ((3.97Æ0.33) nm). Impor-
tantly, TEM imaging of the final product, Au·[1]n, revealed
the presence of spherical particles of almost the same aver-
age size ((3.90Æ0.11) nm; Figure 1b).[3,15] The slight de-
crease in average size observed after functionalization is
within the limits of experimental error. However, to the
extent any such decrease occurs, it could reflect attachment
of the bulky calix[4]pyrrole moieties to the AuNP core and
the production of a less well-ordered surface structure. SEM
images of Au·[1]n are in agreement with the TEM results
and reveal little gross change in structure and morphology
(see the Supporting Information).
ic analysis discussed above) have undergone exchange with
the thiols present in calix[4]pyrrole 1, the molecular weight
of the calix[4]pyrrole moieties is 207 kDa. This corresponds
to approximately 137 ligand sites. Therefore, we infer that
there are approximately 69 receptor molecules per particle
(see the Supporting Information for details of the analysis
and calculations).
The anion-binding properties Au·[1]n were analyzed using
UV/Vis and fluorescence spectroscopic titrations. The addi-
tion of the fluoride anion (as its tetrabutylammonium
(TBA) salt) to a solution of Au·[1]n in CH2Cl2 resulted in
dramatic changes in both absorption bands. Upon this addi-
tion, the absorption band at 228 nm underwent a 20–25%
enhancement with a slight redshift. Based on previous stud-
ies, such a finding is consistent with the complexation of an
anion by the calix[4]pyrrole receptors.[5] The intensity of the
plasmon band at 518 nm was also found to decrease by 7–
A comparison of the 1H NMR spectra of the AuNPs
before and after functionalization with receptor 1 showed
the appearance of characteristic resonances for the pyrrole
and aromatic protons. This latter finding provided initial
support for the conclusion that the thiol-functionalized
calix[4]pyrrole 1 was successfully attached to the surface of
the AuNP (see the Supporting Information). More detailed
analysis of the 1H NMR spectrum allowed the degree of
functionalization to be approximated. Since 1 has two free
thiols and one calix[4]pyrrole functionality, each molecule of
1 would displace two of the original thiol-bound ligand sites
12%. The solution of AuACHTNUTRGEN(UNG SC12H25)n alone did not show any
significant spectral change in the plasmon band upon expo-
sure to anions including TBAF (see the Supporting Informa-
tion). Thus, the changes in the absorption spectra associated
with the addition of TBAF are ascribed to salt–receptor in-
teractions, presumably anion binding to the calix[4]pyrrole
subunits.
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Anion binding to calix[4]pyrroles typically leads conver-
sion from the less organized 1,3-alternate to the correspond-
ing cone conformation. The decrease in molar absorptivity
of the plasmon band is thus consistent with the proposed
anion binding event; it would lead to an increase in local
order and to a blocking of the nanoparticle interior. On the
other hand, no appreciable change in the color of the nano-
particles (reflective of the plasmon band) was expected
since the nanoreceptor–fluoride complex resides relatively
far from the gold nanoparticle surface.
Taken in concert, these observations are fully consistent
with the changes expected for anion binding to a calix[4]pyr-
role subunit.
An effort was made to exploit the strong, selective bind-
ing of the fluoride anion to nanoreceptor Au·[1]n for the
purposes of sensing. Towards this end, the fluorescence dye
displacement assay (FDDA) method, wherein a signaling
fluorophore is released upon interaction with the targeted
analytes, was explored. Fluorescence “turn-on” chemosen-
sors based on the FDDA approach are often more sensitive
than sensors based on other optical sensing techniques.
Moreover, the use of a Au·[1]n core for this purpose ap-
peared particularly attractive given that the nanoparticle
would be expected to quench the fluorescence of a fluoro-
phore prior to analyte-induced displacement. This could
make this system ideal for the detection of anions.[5,17] To
test this hypothesis, tetrabutylammonium-2-oxo-4-(trifluoro-
methyl)-2H-chromen-7-olate (2) was used as the fluoro-
phore signaling agent. This dye is highly fluorescent in solu-
tion but, in accord with design expectations, became com-
pletely nonfluorescent upon binding to Au·[1]n. However, in
the presence of the more strongly binding fluoride anion,
displacement occurs, and 2 is released in its native, highly
fluorescent form. Quantitative titrations of nanoreceptor
Au·[1]n with 2 in CH2Cl2 resulted in concentration-depend-
ent quenching of the fluorescence centered at 500 nm. At
4.76 nm Au·[1]n, nearly complete quenching (99%) was ob-
served (see the Supporting Information). A significant en-
hancement in the absorption intensity at 228 nm and a de-
crease in that of the plasmon band at 518 nm were also ob-
served. These optical changes were taken as evidence that
fluorophore 2 binds to the nanoreceptor Au·[1]n (see the
Supporting Information).
The beneficial competitiveness of this assay was demon-
strated by testing the efficiency of the FDDA with fluoride
anions. The sequential addition of the fluoride anion (as the
TBA salt) in CH2Cl2 resulted in a dramatic enhancement in
the fluorescence intensity (Figure 2). The original fluores-
cence intensity of 2 was fully recovered at 51 nm fluoride
(approximately 1000-fold enhancement relative to the
quenched form, complex 2·Au·[1]n); this permitted the
direct visual detection of fluoride anions through the expect-
ed “turn-on” fluorescence produced as the result of anion
displacement (Figure 3c). Gratifyingly, the fluorescence en-
hancement upon addition of fluoride anions was found to be
linear at low concentrations (0–41ꢁ10À11 m; see the Support-
ing Information). The detection limit for 2·Au·[1]n was thus
taken to be subnanomolar in concentration (Figure 4). This
represents an approximately 500-fold increase in the effec-
tive limit of detection relative to receptor 4 (using the same
fluorophore 2 and a similar FDDA assay) and an extremely
low limit in absolute terms.
UV/Vis titrations of Au·[1]n with various anions (as their
corresponding TBA salts) in CH2Cl2 revealed that the addi-
tion of TBAF produced the largest enhancement of the
228 nm absorption feature. For instance, addition of chloride
or bromide (as the corresponding TBA salts) resulted in
comparatively small enhancements in this band (see the
Supporting Information). Only negligible changes were ob-
served upon the addition of other anions (CNÀ, AcOÀ,
À
À
À
NO3 , HSO4 , H2PO4 , and HP2O73À, all as their TBA salts).
These anions do not bind appreciably to monomer 4 and
presumably the lack of spectroscopic changes seen with
Au·[1]n reflects the weak (or negligible) interaction between
the anion and the receptor in these instances.
On the basis of the above comparisons and analysis, we
suggest that the current nanohybrid receptor Au·[1]n is se-
lective for the fluoride anion. The calculated association
constants,[16] K, for the calix[4]pyrrole functionality present
in Au·[1]n (effective concentration of 1 per nanoparticle=
1.01ꢁ10À8 m per molecule) and receptor 4 (1.01ꢁ10À5 m) for
fluoride-anion binding in CH2Cl2 were (1.43Æ0.16)ꢁ108 and
(9.84Æ0.25)ꢁ106 mÀ1, respectively. These results provide
support for the notion that attachment of the calix[4]pyrrole
to the nanoparticles serves to enhanced the binding affinity
increase the sensitivity in such a way that Au·[1]n is capable
of sensing fluoride anions at much lower effective concen-
trations (ꢀ10À8 m) than receptor 4 (ꢀ10À5 m). It is consid-
ered to be a manifestation of multivalency, and is thought to
reflect the cooperative action of the individual subunits of
receptor 1 assembled on the nanoparticle at a relatively high
local concentration. Association constants for the other
anions tested follow a similar trend. However, the binding
interactions involved are substantially weaker even to the
point of being below the limits of detection.
Further support for the strong interactions between
1
Au·[1]n and the fluoride anion came from H NMR spectro-
scopic studies. Specifically, significant chemical-shift changes
À
were seen for the pyrrole NH proton signals (i.e., from d=
7.2 to 12.6 ppm) upon the addition of TBAF. The final
signal was also found to be split with a J=40.1 Hz coupling
constant. Such changes (i.e., shifts and signal splitting) are
À
À
typical of those associated with NH F hydrogen bond seen
for other calix[4]pyrrole systems (see the Supporting Infor-
mation). The two signals that correspond to the b-pyrrolic
protons, which initially appeared at d=5.81 and 5.92 ppm,
were shifted to d=5.65 and 5.75 ppm, respectively. Two sets
of phenyl protons also underwent upfield shifts from d=
6.95 and 7.18 ppm to d=6.61 and 6.80 ppm, respectively.
In an effort to establish whether the interactions that un-
derlie the fluoride recognition and selectivity observed in
chloroform would be retained in a more polar environment,
Au·[1]n was tested as a fluoride anion extractant. Towards
this end, a D2O solution of TBAF (14 mm) was mixed with a
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J. L. Sessler, C.-H. Lee et al.
solution of Au·[1]n (1.42 mm) in
CDCl3 and subjected to vigo-
rous shaking. The organic phase
was then analyzed by using
1H NMR spectroscopy. Gratify-
ingly, this analysis revealed that
both the anion (FÀ) and the
counter cation (TBA+) were
extracted into the organic
phase as evidenced by the ob-
servation of a substantial down-
À
field shift for the pyrrole NH
resonance (Ddꢀ2.73 ppm) and
the appearance of new signals
that correspond to the methyl-
ene in the TBA counter cation
(at d=3.15 ppm) that were not
present in the original solution
of Au·[1]n in CDCl3. These re-
sults stand in sharp contrast to
the lack of spectral changes
seen when a solution of the
monomeric molecular receptor
4 (4.61 mm in CDCl3) was con-
tacted with an aqueous solution
of TBAF in D2O. These dispa-
rate findings (nanoreceptor
versus free receptor) are taken
as further evidence that attach-
ment of the receptor to the NPs
served to enhance the recogni-
tion efficacy of the calix[4]pyr-
role subunits, even to the point
Figure 2. a) Changes in the fluorescence intensity of 2 (2.1 mm) observed upon titration with receptor Au·[1]n
(4.76ꢁ10À9 m) in CH2Cl2 at 258C (lex =410 nm). The inset shows the corresponding Stern–Volmer plot of the
associated fluorophore (2)-dependent fluorescence quenching (KSV =2.36ꢁ107). b) Recovery of fluorescence
seen upon titration of complex 2·Au·[1]n with fluoride anion (as the TBA salt, 0–5.13ꢁ10À8 m) in CH2Cl2 (lex
=
410 nm). Inset shows a plot of I/I0 versus fluoride anion concentration. c) Photos of the solutions indicated in where different operational re-
these figures under (top) ambient light and (bottom) upon irradiation with a UV lamp (lex =365 nm).
sults were obtained (i.e., effec-
tive TBAF extraction with
Au·[1]n but not 4). As above,
these improvements in application-related function are as-
cribed to multivalency, namely, the presence of multiple re-
ceptors within a localized environment.
As a final test of the features of Au·[1]n, it was treated
with the 4,4’-biphenolate dianion, 3 (as the TBA salt). This
study was undertaken because it was envisioned that the
nanoreceptor 1 would react with appropriately chosen bis-
anionic guests to create a linked dimeric nanoparticle en-
semble.[18] In fact, adding 3 to a solution of Au·[1]n in di-
chloromethane gave rise to a higher level of aggregation as
inferred from TEM measurements (see Figure 1).
The nanoreceptor Au·[1]n was also exposed to the fluoride
anion under identical conditions. However, no evidence of
aggregation was seen, even at high fluoride anion concentra-
tions (Figure 1c,d). These results provide support for the
Figure 3. UV/Vis spectroscopic titration curves corresponding to the
notion that polyanions, such as 3, can be used to crosslink
calixpyrrole-functionalized gold nanoparticles. In due
course, this feature could be exploited to create even more
selective receptors and sensors.
interaction of Au·[1]n with various anions (as the corresponding TBA
salts) in CH2Cl2 at 258C. The absorption changes were measured at
228 nm.
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Decoration of Gold Nanoparticles
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ed nanoparticles. The potential for recognition, sensing, and
extraction leads us to suggest that receptor-substituted nano-
particles, such as Au·[1]n, could have a role to play in vari-
ous practical applications in which the effective and selec-
tive binding of the fluoride anion is required.
Experimental Section
Compound 1: Dithiothreitol (DTT; 59 mg, 0.38 mmol) was added to a
solution of 11 (0.3 g, 0.17 mmol) in 3:1 anhydrous DMF/CH2Cl2 (16 mL).
The reaction mixture was then stirred at room temperature for 3 h. The
absence of starting material as inferred from TLC analysis was taken to
indicate complete removal of the pyridine moiety. The reaction was
quenched by subjecting the reaction mixture to a threefold dilution with
dichloromethane followed by two water extractions to remove DMF. The
crude product was purified by column chromatography over silica gel
using a mixture of CH2Cl2/CH3OH=9.9:0.1 as eluent to afford pure
product 1 as a colorless viscous liquid. Yield: 0.14 g (52%); 1H NMR
(600 MHz, CDCl3, 258C, TMS): d=7.13 (brs, 4H; pyrrole-NH), 7.08–
7.06 (m, 4H; aryl-H), 6.95–6.92 (m, 4H; aryl-H), 5.90–5.89 (m, 4H; pyr-
À
À
role-H), 5.80–5.79 (m, 4H; pyrrole-H), 4.11 (s, 4H; COCH2O ), 4.05 (t,
À
À
J=6.52 Hz, 4H; OCH2), 3.72–3.70 (m, 4H; OCH2), 3.68–3.67 (m, 4H;
À
À
À
OCH2), 3.65–3.61 (m, 20H; OCH2), 3.58–3.56 (m, 4H; OCH2), 3.44
À
À
(t, J=6.80 Hz, 4H; OCH2), 2.54–2.50 (m, 4H; SCH2), 2.27–2.24 (m,
À
À
À
À
4H; CH2), 1.61–1.56 (m, 18H; CH2 + CH3), 1.44 (s, 6H; CH3), 1.38–
1.36 (m, 4H; CH2), 1.34–1.27 ppm (m, 24H; CH2); 13C NMR
(150 MHz, CDCl3, 258C, TMS): d=170.39, 162.23, 160.69, 140.01, 138.69,
134.93, 129.78, 129.74, 114.60, 114.46, 106.43, 103.01, 71.55, 70.95, 70.63,
70.58, 70.51, 70.06, 68.58, 64.84, 48.12, 36.91, 35.04, 34.05, 29.65, 29.57,
29.50, 29.07, 28.38, 28.18, 26.10, 24.88, 24.66 ppm; MALDI-MS: m/z (%)
calcd for C84H126F2N4O14S2: 1516.87; found: 1539.83 (100) [M+Na].
À
À
5,15-(4-Fluorophenyl)-5,15-(ethylpropionate)-10,10,20,20-
tetramethylcalixACHTNUGTRNEUNG[4]pyrrole (9): BF3·OEt2 (0.73 mL, 5.88 mmol) was added
to a solution of compound 8 (1.0 g, 2.94 mmol) in acetone (60 mL), and
the mixture was stirred for 12 h at room temperature. The reaction mix-
ture was quenched through the addition of triethylamine (1.76 mL,
12.6 mmol). Excess amounts of acetone were removed under reduced
pressure, and the mixture was combined with water and extracted with
CH2Cl2 (100 mLꢁ2). The organic layer was dried over anhydrous
Na2SO4, and the solvent was removed under vacuum. Column chroma-
tography on silica gel afforded a clear separation of the two isomers. The
first fraction that contained the trans isomer (0.18 g, 8%) was collected
using a mixture of 9.6:0.4 CH2Cl2/EtOAc as an eluent. The second frac-
tion that contained the required cis isomer 9 was collected by using a
mixture of 9.4:0.6 CH2Cl2/EtOAc as the eluent; it was obtained in the
form of a light yellow solid. Yield: 0.20 g (9%); 1H NMR (400 MHz,
CDCl3, 258C, TMS): d=7.14–7.11 (m, 8H; aryl-H+pyrrole-NH), 6.97–
6.92 (m, 4H; aryl-H), 5.91–5.89 (m, 4H; pyrrole-H), 5.83–5.82 (m, 4H;
Figure 4. Estimation of the detection limit of complex 2·Au·[1]n for FÀ.
a) Fluorescence spectral change (lex=410 nm) of the solution of Au·[1]n
(effective concentration of calix[4]pyrrole functionality per nanoparti-
cle=4.76ꢁ10À9 m upon addition of 2 (2.1 mm)) upon addition of TBAF
(0–41ꢁ10À11 m) in CH2Cl2. b) Plot of the emission intensity (lem=500 nm)
versus TBAF concentration. Error bars represent standard deviations of
three experiments. Note that (for this experiment only) an emission slit
width of 15 nm was used for more sensitive detection.
À
À
pyrrole-H), 4.05 (q, J=7.10 Hz, 4H; OCH2), 2.59–2.55 (m, 4H; CH2),
Conclusion
À
À
À
2.26–2.22 (m, 4H; CH2), 1.56 (s, 6H; CH3), 1.44 (s, 6H; CH3),
1.20 ppm (t, J=7.10 Hz, 6H; CH3); 13C NMR (100 MHz, CDCl3, 258C,
À
We have synthesized calix[4]pyrrole-functionalized AuNPs
that permit the sensitive recognition of fluoride anions in or-
ganic media. The system shows both a chromogenic and a
“turn-on” fluorogenic response upon exposure to TBAF.
Moreover, it does so with a level of sensitivity that is greatly
enhanced relative to the corresponding monomeric receptor.
Under biphasic aqueous-organic conditions, Au·[1]n acts as
an effective extractant for TBAF, something that is not ob-
served (within applicable error limits) for the corresponding
control system, 4. Aggregation of the functionalized nano-
particles of this report was seen upon exposure to the biphe-
nolate anion, thus demonstrating the potential for control-
ling the size, and perhaps the properties, of receptor-mediat-
TMS): d=173.95, 173.83, 163.19, 160.74, 139.99, 139.96, 139.19, 134.86,
134.38, 130.17, 130.09, 129.91, 115.58, 115.37, 115.16, 114.95, 107.95,
106.90, 106.28, 103.41, 60.90, 48.50, 48.38, 35.75, 35.59, 35.45, 34.91, 31.26,
31.15, 30.06, 29.67, 28.71, 14.57 ppm; MALDI-MS: m/z (%) calcd for
C46H50F2N4O4: 760.38; found: 761.47 (100) [M+1].
Nanoreceptor Au·[1]n: Dodecanethiol-functionalized gold nanoparticles
AuACTHNUGTRNEUN(G SC12H25)n (10 mg) were taken from a stock solution in toluene and
dried on a rotary evaporator at 458C. The dried particles were then dis-
solved in dichloromethane (1 mL). Compound 1 (50 mg, 33 mol) was dis-
solved in dichloromethane (2 mL). After purging both solution with ni-
trogen for 30 min, they were mixed together and stirred for approximate-
ly 3 d at room temperature. The solvent was removed under vacuum, and
the crude product was then dissolved in DMF and placed in a 10 kDa re-
generated cellulose membrane filter. The sample was purified by ultra-
centrifugation at 3000 rpm for 15 min. The solution was then concentrat-
Chem. Eur. J. 2013, 00, 0 – 0
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J. L. Sessler, C.-H. Lee et al.
ed under vacuum and precipitated from hexane to give Au·[1]n (30 mg).
1H NMR (600 MHz, CDCl3, 258C, TMS): d=7.10–7.06 (m; pyrrole-NH+
aryl-H), 6.95–6.92 (m, 4H; aryl-H), 5.91–5.90 (m, 4H; pyrrole-H), 5.80–
netti, V. Bartocci, F. Pucciarelli, L. Petetta, Polyhedron 2008, 27,
1047–1053.
[5] C.-H. Lee, H. Miyaji, D. W. Yoon, J. L. Sessler, Chem. Commun.
2008, 24–35.
À
À
5.79 (m, 4H; pyrrole-H), 4.11 (s, 4H; COCH2O ), 4.06 (t, J=6.42 Hz,
À
À
À
4H; OCH2), 3.72–3.70 (m, 4H; OCH2), 3.69–3.67 (m, 4H; OCH2),
[6] a) P. Sokkalingam, J. Yoo, H. Hwang, P. H. Lee, Y. M. Jung, C.-H.
Lee, Eur. J. Org. Chem. 2011, 2911–2915; b) P. Sokkalingam, D. S.
Kim, H. Hwang, J. L. Sessler, C.-H. Lee, Chem. Sci. 2012, 3, 1819–
1824; c) J. Yoo, M.-S. Kim, S.-J. Hong, J. L. sessler, C.-H. Lee, J.
Org. Chem. 2009, 74, 1065–1069; d) S.-J. Hong, C.-H. Lee, Tetrahe-
dron Lett. 2012, 53, 3119–3122; e) J. L. Sessler, D. An, W. S. Cho,
V. M. Lynch, M. Marquez, Chem. Commun. 2005, 540–542; f) M. P.
Wintergerst, T. G. Levitskaia, B. A. Moyer, J. L. Sessler, L. H.
Deimau, J. Am. Chem. Soc. 2008, 130, 4129–4139; g) D. W. Yoon,
H. Hwang, C.-H. Lee, Angew. Chem. 2002, 114, 1835–1837; Angew.
Chem. Int. Ed. 2002, 41, 1757–1759; h) C.-H. Lee, H. K. Na, D. W.
Yoon, D. H. Won, W. S. Cho, V. M. Lynch, S. V. Shevchuk, J. L. Sess-
ler, J. Am. Chem. Soc. 2003, 125, 7301–7306; i) J. L. Sessler, V. Kral,
T. V. Shishkanova, P. A. Gale, Proc. Natl. Acad. Sci. USA 2002, 99,
4848–4853; j) E. A. Katayev, Y. A. Ustynyuk, J. L. Sessler, Coord.
Chem. Rev. 2006, 250, 3004–3037; k) S. H. Kim, S. J. Hong, J. Yoo,
S. K. Kim, J. L. Sessler, C.-H. Lee, Org. Lett. 2009, 11, 3626–3629;
l) S.-J. Hong, J. Yoo, S.-H. Kim, J.-S. Kim, J. Yoon, C.-H. Lee, Chem.
Commun. 2009, 189–191; m) D.-W. Yoon, D. E. Gross, V. M. Lynch,
J. L. Sessler, B. P. Hay, C.-H. Lee, Angew. Chem. 2008, 120, 5116–
5120; Angew. Chem. Int. Ed. 2008, 47, 5038–5042; n) S.-D. Jeong, J.
Yoo, H.-K. Na, D. Y. Chi, C.-H. Lee, Supramol. Chem. 2007, 19,
271–275.
À
À
3.65–3.61 (m, 20H; OCH2), 3.58–3.56 (m, 4H; OCH2), 3.44 (t, J=
6.80 Hz, 4H; OCH2), 2.54–2.50 (m, 4H; SCH2 of 1), 2.27–2.24 (m, 4H;
CH2), 2.04–2.01 (m, 2H; SCH2 of AuACHTUNGTRNEG(UN SC12H25)n), 1.62–1.55 (m, 44H;
À
À
À
À
À
À
À
CH2 of AuACHTUNGTRENNUNG(SC12H25)n), 1.45 (s, 6H; CH3), 1.38–1.36 (m, 6H; CH2),
1.34–1.26 ppm (m, 43H; CH2 + CH3); 13C NMR (150 MHz, CDCl3,
258C, TMS): d=170.39, 160.69, 140.00, 138.66, 134.90, 129.78, 129.74,
114.60, 114.46, 106.44, 103.01, 71.55, 70.95, 70.63, 70.58, 70.50, 70.05,
68.58, 64.84, 48.12, 36.89, 35.04, 34.05, 31.93, 29.65, 29.57, 29.51, 29.25,
29.07, 28.55, 28.38, 28.16, 26.10, 24.87, 24.66, 22.69, 14.12 ppm.
À
À
Acknowledgements
We are grateful for support from the Korean Basic Science Research
Program provided through the NRF (MEST 2009-0087013 to C.-H.L.)
and the CRI (2012-0001245 to C.-H.L.). The work in Austin was support-
ed by the Office of Basic Energy Sciences, U.S. Department of Energy
(DOE) (grant no. DE-FG02-01ER15186 to J.L.S.). Fellowship support
(to A.A.) by the TUBITAK is also gratefully acknowledged.
[7] a) J. L. Sessler, P. A. Gale, J. W. Genge, Chem. Eur. J. 1998, 4, 1095–
1099; b) A. Aydogan, D. J. Coady, S. K. Kim, A. Akar, C. W. Bielaw-
ski, M. Marquez, J. L. Sessler, Angew. Chem. 2008, 120, 9794–9798;
Angew. Chem. Int. Ed. 2008, 47, 9648–9652.
[8] a) I. A. Guralꢃskiy, P. V. Solntsev, H. Krautscheid, K. V. Domase-
vitch, Chem. Commun. 2006, 4808–4810; b) R. Custelcean, B. A.
Moyer, Eur. J. Inorg. Chem. 2007, 1321–1340; c) S. R. Halper, L.
Do, J. R. Stork, S. M. Cohen, J. Am. Chem. Soc. 2006, 128, 15255–
15268; d) R. T. Custelcean, J. B. Haverlock, A. Moyer, Inorg. Chem.
2006, 45, 6446–6452; e) C. R. Wade, A. J. Broomsgrove, S. Aldridge,
F. P. Gabbai, Chem. Rev. 2010, 110, 3958–3984; f) M. Cametti, K.
Rissanen, Chem. Commun. 2009, 2809–2829; g) M. Cametti, K. Ris-
sanen, Chem. Soc. Rev. 2013, 42, 2016–2038.
[9] a) P. Sokkalingam, C.-H. Lee, J. Org. Chem. 2011, 76, 3820–3828;
b) J. L. Sessler, S. K. Kim, D. E. Gross, C.-H. Lee, J.-S. Kim, V. M.
Lynch, J. Am. Chem. Soc. 2008, 130, 13162–13166; c) I.-W. Park, J.
Yoo, B. Kim, S. Adhikari, S. K. Kim, Y. Yeon, C. J. E. Haynes, J. L.
Sutton, C. C. Tong, V. M. Lynch, J. J. Sessler, P. A. Gale, C.-H. Lee,
Chem. Eur. J. 2012, 18, 2514–2523.
[1] a) J. L. Sessler, P. A. Gale, W. S. Cho, Anion Receptor Chemistry
(Monographs in Supramolecular Chemistry); J. F. Stoddart, Eds.;
RSC: Cambridge, U. K. 2006; b) P. A. Gale, S. E. Garcia-Garrido, J.
Garric, Chem. Soc. Rev. 2008, 37, 151–190; c) P. A. Gale, Chem.
Soc. Rev. 2010, 39, 3746–3771; d) K. M. Mullen, P. D. Beer, Chem.
Soc. Rev. 2009, 38, 1701–1713; e) J. W. Steed, Chem. Soc. Rev. 2009,
38, 506–519; f) C. J. E. Haynes, P. A. Gale, Chem. Commun. 2011,
47, 8203–8209.
[2] a) A. Aydogan, D. J. Coady, V. M. Lynch, A. Akar, M. Marquez,
C. W. Bielawski, J. L. Sessler, Chem. Commun. 2008, 1455–1457;
b) A. Herland, O. Inganꢂs, Macromol. Rapid Commun. 2007, 28,
1703–1713; c) S. W. Thomas III, G. D. Joly, T. M. Swager, Chem.
Rev. 2007, 107, 1339–1386; d) H. N. Kim, Z. Guo, W. Zhu, J. Yoon,
H. Tian, Chem. Soc. Rev. 2011, 40, 79–93; e) A. Rostami, M. S.
Taylor, Macromol. Rapid Commun. 2012, 33, 21–34.
[3] a) H. Itoh, K. Naka, Y. Chujo, J. Am. Chem. Soc. 2004, 126, 3026–
3027; b) S. Y. Lin, C.-H. Chen, M.-C. Lin, H.-F. Hsu, Anal. Chem.
2005, 77, 4821–4828; c) C. A. Mirkin, R. L. Letsinger, R. C. Mucic,
J. J. Storhoff, Nature 1996, 382, 607–609; d) J. R. Aranzaes, C. Belin,
D. Astruc, Chem. Commun. 2007, 3456–3458; e) P. D. Beer, D. P.
Cormode, J. Davis, Chem. Commun. 2004, 414–415; f) S. Kado, A.
Furui, Y. Akiyama, Y. Nakahara, K. Kimura, Anal. Sci. 2009, 25,
261–265.
[10] P. A. Gale, Chem. Commun. 2008, 4525–4540 and references are
therein.
[11] M. G. Fisher, P. A. Gale, J. R. Hiscock, M. B. Hursthouse, M. E.
Light, F. P. Schmidtchen, C. C. Tong, Chem. Commun. 2009, 3017–
3019.
[4] a) M. J. Hostetler, J. E. Wingate, C. J. Zhong, J. E. Harris, R. W.
Vachet, M. R. Clark, J. D. Londono, S. J. Green, J. J. Stokes, G. D.
Wignall, G. L. Glish, M. D. Porter, N. D. Evans, R. W. Murray, Lang-
muir 1998, 14, 17–30; b) M. J. Hostetler, A. C. Templeton, R. W.
Murray, Langmuir 1999, 15, 3782–3789; c) Y.-S. Shon, C. Mazzitelli,
R. W. Murray, Langmuir 2001, 17, 7735–7741; d) X. Liu, M. Atwa-
ter, J. Wang, Q. Huo, Colloids Surf. B Colloids and Surfaces B: Bio-
interfaces. 2007, 58, 3–7; e) M.-C. Daniel, D. Astruc, Chem. Rev.
2004, 104, 293–346; f) C. Burda, X. Chen, R. Narayanan, M. A. El-
Sayed, Chem. Rev. 2005, 105, 1025–1102; g) E. Katz, I. Willner,
Angew. Chem. 2004, 116, 6166–6235; Angew. Chem. Int. Ed. 2004,
43, 6042–6108; h) M. J. Kogan, N. G. Bastus, R. Amigo, D. Grillo-
Bosch, E. Araya, Nano Lett. 2006, 6, 110–115; i) D. V. Leff, L.
Brandt, J. R. Heath, Langmuir 1996, 12, 4723–4730; j) W. Haiss,
N. T. K. Thanh, J. Aveyard, D. G. Fernig, Anal. Chem. 2007, 79,
4215–4221; k) S. Roux, B. Garcia, J.-L. Bridot, M. salome, C. mar-
quette, L. Lemelle, P. Gillet, L. Blum, P. Perriat, O. Tillement, Lang-
muir 2005, 21, 2526–2536; l) G. H. Woehrle, L. O. Brown, J. E.
Hutchison, J. Am. Chem. Soc. 2005, 127, 2172–2183; m) R. Giovan-
[12] C.-H. Lee, Bull. Korean Chem. Soc. 2011, 32, 768–778.
[13] C. B. Murray, C. R. Kagan, M. G. Bawendi, Science 1995, 270, 1335–
1338.
[14] B. T. Houseman, M. Mrksich, J. Org. Chem. 1998, 63, 7552–7555.
[15] J. D. Gibson, B. P. Khanal, E. R. Zubarev, J. Am. Chem. Soc. 2007,
129, 11653–11661.
[16] J. Bourson, J. Pouget, B. Valeur, J. Phys. Chem. 1993, 97, 4552–4557.
[17] a) S. L. Wiskur, H. Ait-Haddou, J. L. Lavigne, E. V. Anslyn, Acc.
Chem. Res. 2001, 34, 963–972; and references are therein b) B. T.
Nguyen, E. V. Anslyn, Coord. Chem. Rev. 2006, 250, 3118–3127;
c) T. Zhang, E. V. Anslyn, Org. Lett. 2007, 9, 1627–1629.
[18] a) G. Cafeo, F. H. Kohnke, L. Valenti, A. J. P. White, Chem. Eur. J.
2008, 14, 11593–11600; b) P. Ballester, Isr. J. Chem. 2011, 51, 710–
724; c) G. Cafeo, F. H. Kohnke, L. Valenti, Tetrahedron Lett. 2009,
50, 4138–4140.
Received: February 26, 2013
Published online: && &&, 0000
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Decoration of Gold Nanoparticles
FULL PAPER
Nanoparticles
P. Sokkalingam, S.-J. Hong,
A. Aydogan, J. L. Sessler,*
C.-H. Lee* ..................... &&&& — &&&&
Decoration of Gold Nanoparticles by a
Double-Armed Calix[4]pyrrole: A
Receptor-Decorated Nanoensemble
for Anion Sensing and Extraction
Decorate and ye shall receive: Gold
nanoparticles decorated with a double-
armed, deep-cavity calix[4]pyrrole pro-
duced so-called nanoreceptors with an
average diameter of approximately
4 nm (see figure). These constructs
could be used to sense the fluoride
anion with high selectivity and efficacy
in organic media.
Gold Nanoparticles
Calix[4]pyrroles, a class of tetrapyrrolic nonaromatic
macrocycle, are known to selectively bind anions in
organic media. In their Full Paper on page && ff, J. L.
Sessler, C.-H, Lee et al, have shown that when gold nano-
particles are decorated with these macrocycles, the
resulting conjugate exhibits enhanced sensing ability with
similar selectivity compared to the monomeric macrocycle.
Furthermore, in biphasic media, the conjugates are able to
extract fluoride anion from the aqueous phase into the
organic phase.
Chem. Eur. J. 2013, 00, 0 – 0
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www.chemeurj.org
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