Influence of surface protonation-deprotonation stimulion the chiroptica l responses of (R)-/(S)-mercaptosuccinic acid-protected gold nanoclusters

Article abstract of DOI:10.1246/cl.140953

Racemic mixtures of mercaptosuccinic acid (MSA) are opticall y resolved to obtain enantiopure (R)-/(S)-MSA, and the (R)-/(S)-MSA-protected gold nanoclusters are synthesized. Circular dichroism responses of the nanoclusters are strongly dependent on the pH of the solution. In particular, chiroptical enhancement is observed under highly acidic conditions, which can be due both to the electronic and conformational origins of the surface chiral MSA ligand.

Full text of DOI:10.1246/cl.140953

Received: October 16, 2014 | Accepted: November 9, 2014 | Web Released: November 22, 2014
CL-140953
Influence of Surface Protonation­Deprotonation Stimuli on the Chiroptical Responses
of (R)-/(S)-Mercaptosuccinic Acid-protected Gold Nanoclusters
Ryota Ueno and Hiroshi Yao*
Graduate School of Material Science, University of Hyogo, 3-2-1 Koto, Kamigori-cho, Ako-gun, Hyogo 678-1297
(
E-mail: yao@sci.u-hyogo.ac.jp)
Racemic mixtures of mercaptosuccinic acid (MSA) are
optically resolved to obtain enantiopure (R)-/(S)-MSA, and
the (R)-/(S)-MSA-protected gold nanoclusters are synthesized.
Circular dichroism responses of the nanoclusters are strongly
dependent on the pH of the solution. In particular, chiroptical
enhancement is observed under highly acidic conditions, which
can be due both to the electronic and conformational origins of the
surface chiral MSA ligand.
Gold nanoclusters with the diameter reduced to the order of
the metal’s Fermi wavelength are the most extensively studied due
to their relative ease of preparation and interesting photophysical
1
properties. In particular, thiolate-protected gold nanoclusters are
Figure 1. (a) Chemical structures of (S)-MSA and (R)-MSA. (b)
(Left) Absorption spectra of (R)-MSA in aqueous solution at pH 1.9,
3.2, and 10.3. Spectra are offset by a constant for clarity. (Right) CD
spectra of (R)-/(S)-/rac-MSA in aqueous solution at pH 1.9, 3.2, and
of importance and have attracted increasing interest both exper-
imentally and theoretically. Mercaptosuccinic acid (MSA, IUPAC
name: sulfanylsuccinic acid) is an intriguing thiol molecule to
protect Au nanoclusters for biological applications because of its
1
0.3.
2
high water solubility and/or biocompatibility. Indeed, the synthe-
sis, characterization, and self-assembling processes of MSA-
protected Au nanoclusters have been reported. On the other hand,
complex followed by the reduction of the metal ions with NaBH4
under a fixed MSA/Au molar ratio (= 2.0), which can be referred
to as Au­(R)-MSA and Au­(S)-MSA, respectively. The precip-
itate was completely washed with water/methanol and ethanol
repeatedly through a redispersion­centrifugation process to re-
move undesirable impurities. Finally, the precipitate dissolved in a
small amount of water was freeze-dried.
3
3
MSA molecules on the bulk gold surface have been studied by
4
surface-enhanced Raman spectroscopy (SERS), and it was found
that MSA chemisorbs via both sulfur atom and one carboxy group
(
closer to the sulfur atom) dissociated at natural (or slightly acidic)
4
pH. The influence of the solution pH on its monolayer structure
has also been examined. Meanwhile, MSA is a chiral compound,
4
MSA has three possibilities for acid dissociation, and the
corresponding pKa values reported are; pKa1 = 3.30, pKa2 = 4.94,
and pKa3 = 10.64, where pKa1 (pKa2) refers to the dissociation of
a carboxy group that is closer (more distant) to the sulfur atom,
although only the racemate is commercially available. If enantio-
pure MSA can be used to obtain optically active Au nanoclusters,
the ligand protonation­deprotonation stimuli would control their
chiroptical responses; thereby we can better understand the origin
of the optical activity of the chiral thiolate-protected Au nano-
clusters. In the present study, enantiopure (R)-/(S)-MSA is used to
synthesize monolayer-protected Au nanoclusters. Racemic MSA is
first optically resolved using a chiral amine molecule. Then the
pH-responsive circular dichroism (CD) is examined. We believe
this study will give an approach for finding strong optically active
nanomaterials.
4
and pKa3 to thiol group deprotonation. UV absorption and the
corresponding CD spectra of (R)-/(S)-MSA in aqueous solutions
of pH 1.9, 3.2, and 10.3 are shown in Figure 1b. At pH 1.9, MSA
has an absorption peak at ca. 235 nm, but the peak becomes blurred
and weakened at higher pH values. The intensity of the Cotton
effects at ca. 235 nm is also a function of pH (Figure 1b); the CD
response is increased with a decrease in the pH value. Note that
a red-tail absorption observed at ca. 260 nm at pH 10.3 is a
6
The optical resolution of racemic MSA (rac-MSA) was
conducted using (S)-1-phenylethylamine ((S)-PEA) according to
property of sulfide anions. In general, thiol groups (­SH) have
6
no absorption in the wavelength region longer than ca. 220 nm.
5
the literature. Briefly, rac-MSA and (S)-PEA were first dissolved
In addition, we confirmed that succinic acid did not show any
absorption at ²ca. 220 nm under the highly acidic condition.
Hence, to identify this peak of MSA, quantum chemical
calculations were conducted. We chose three forms of MSA on
the carboxy protonation­deprotonation; that is, neutral, singly, and
doubly deprotonated species. The calculation required several
steps: In the first step, a conformational optimization was
conducted for the chosen stereoisomer to obtain a local minimal
energy with the Gaussian 09 program at the density functional
theory (DFT) level using the B3PW91 functional and a 6-31+G*
basis set.7 Three typical, staggered conformations produced by
in 1-propanol. After keeping the solution at ¹10 °C overnight,
the precipitate (R)-MSA¢(S)-PEA was collected by filtration. The
precipitate was recrystallized, yielding pure (R)-MSA¢(S)-PEA.
To obtain diastereomeric (S)-MSA¢(S)-PEA, on the other hand,
the filtrate was evaporated. Next, an aqueous solution containing
(
R)-MSA¢(S)-PEA or (S)-MSA¢(S)-PEA was treated with an
+
Amberlite IR-120B ion-exchange resin in the H form. Con-
sequently, (R)-MSA or (S)-MSA was obtained after recrystalliza-
tion (Figure 1a). The synthesis of (R)-/(S)-MSA-protected Au
nanoclusters involves the preparation of an aqueous Au­thiolate
Chem. Lett. 2015, 44, 171–173 | doi:10.1246/cl.140953
© 2015 The Chemical Society of Japan | 171

Figure 2. Optimized conformations of neutral (left), singly (middle),
and doubly (right) deprotonated forms of (S)-MSA, along with the
corresponding absorption and CD spectra simulated, respectively.
(
b) HOMO and LUMO images of various forms of (S)-MSA.
Figure 3. (a) Typical STEM image and narrow size distribution of
MSA-protected Au nanoclusters. (b) Absorption spectra of Au­(R)-
MSA recorded at different pH solutions. Spectra are offset by a
constant for clarity. (c) Profiles of g-factor for the Au­(R)-MSA and
Au­(S)-MSA nanocluster samples recorded at different pH solutions.
rotation around the C2­C3 axis were considered. Next, for the
lowest-energy geometry, time-dependent DFT (TD-DFT) calcu-
lations were performed, obtaining the oscillator strength (¾) and
rotatory strength (¦¾). To include solvent (water) effects, the
conductor polarizable continuum model (C-PCM) present in
Figure 3b displays UV­vis absorption spectra of the Au­MSA
nanocluster compounds measured at various pHs. The pH of the
aqueous solution of the as-prepared nanocluster samples was 9.1,
so acidification was carried out by the addition of an appropriate
amount of HCl solution. In each spectrum, almost identical and
monotonically increasing absorbance toward shorter wavelengths
was observed. The result is in good agreement with the size of the
Au nanoclusters determined by STEM (<ca. 2 nm in diameter),
7
Gaussian 09 was used.
Results on the optimized geometry as well as the correspond-
ing absorption and CD spectra of neutral, singly or, doubly
deprotonated (S)-MSA are shown in Figure 2a. The lowest-
energy transition is dominated by the HOMO­LUMO transition
(
Figure 2b). In neutral MSA, the gauche conformation is stable,
and from the orbital pictures of the HOMO and LUMO, we can
determine that the absorption peak of ca. 235 nm observed at
pH 1.9 is due principally to the n­π* transition of C=O coupled
with the proximal sulfur atom. Upon deprotonation, both the
electronic structure and stable conformation of MSA were
significantly modulated; for example, the stable conformation of
singly or doubly deprotonated MSA was an anti form, and the
HOMO­LUMO transition, having a charge-transfer (CT) nature as
judged from Figures 2b and 2c, shifted to a higher energy. The
n­π* transitions of C=O were also shifted to more blue, in good
agreement with the observed data (Figure 1b). Note that the
calculations showed a difference from the experimental data on the
disappearance of the spectroscopic response at ca. 235 nm. This
may suggest that other conformers having different absorption and
CD responses (= electronic natures) should also be present in
high-pH solutions.8
Metal nanoclusters with chirality are attractive for their
stereochemistry.9 Hence, to examine how the modulation of
the electronic states of chiral MSA ligands upon protonation­
deprotonation stimuli influences the chiroptical responses of the
MSA-protected Au nanoclusters, we next evaluated Au­(R)-MSA
and Au­(S)-MSA samples. We first determined the mean core size
and typical size distribution of the Au­MSA samples by STEM
observations (Figure 3a). Both samples had similar size and
distribution, and according to the micrographs, we could determine
the mean diameters of 1.5 nm.
1
0
which scarcely supports the plasmon excitation characteristics.
In addition, these nanoclusters were stable in a wide range of pHs,
from ca. 2 to ca. 9, and absorption spectra were not influenced by
protonation­deprotonation stimuli for MSA ligands.
Figure 3c shows the chiroptical responses of the (R)-/(S)-
MSA-protected Au nanocluster samples at various pH values. The
typical ionization forms of MSA are also shown. The spectra are
shown as profiles of the anisotropy factor (g-factor) determined as
¦¾/¾, where ¦¾ and ¾ express the intensity of the molar dichroic
absorption and molar extinction coefficient, respectively. Impor-
tantly, the chiroptical activity of the chiral MSA-protected Au
nanoclusters is pH-responsive. It should be further emphasized
that nanoclusters protected by (S)-MSA show an almost complete
mirror image of the chiroptical response of that protected by (R)-
MSA. The mirror image relationship in metal-based electronic
transition regions suggests that these nanoclusters have a well-
11
defined stereostructure. Spectral shapes were, overall, similar
with each other; but with a close inspection, we found that (i) upon
acidification (pH 3.1 and 1.9), two new peaks (referred to as
bands b and c (Figure 3c) detected at ca. 280 and ca. 320 nm,
respectively) were resolved in addition to band a (extremum at ca.
235 nm) and band d (extremum at ca. 400 nm) that are also present
in the basic solution (pH 9.1); (ii) the response amplitudes for
bands a and d were successively enhanced with a decrease in
pH, but those for bands b and c were saturated at pH ¯3.1. The
172 | Chem. Lett. 2015, 44, 171–173 | doi:10.1246/cl.140953
© 2015 The Chemical Society of Japan

increase in the CD responses is strongly associated with that of
pure MSA. On the basis of the pKa values of MSA,4 two
protonation­deprotonation equilibria are present in aqueous
dispersion. At pH 1.9 (or 9.1), all protonated neutral (or doubly
transition frequency. In addition, Vij is the dipole­dipole inter-
action term, which couples the two electric transitions ®i and ®j,
and Im expresses the imaginary part of a dot product.16 According
to this relationship, the following conditions are required to obtain
large induced optical activity or rotatory strength; (i) ¯i is close to
¯j, (ii) Vij is large, (iii) ®i and mj are aligned, or (iv) ®i and/or mj is
large. On the basis of the quantum chemical calculations for MSA,
the electric dipole strengths (determined as the square of the
transition dipole moment) of the lowest transition for the neutral,
singly, or doubly deprotonated MSA were 0.124, 0.025, or 0.041
(au; {8.478 © 10 } C m ), and the magnetic dipole strengths
0.282, 0.268, or 0.392 (au), respectively. This means that only the
electric dipole moment of neutral MSA is significantly large, and
thus it can remarkably contribute to an enhancement of Vij via
dipole­dipole coupling. Meanwhile, when the solution pH value is
high, a blue shift of the perturber transition makes the frequency
difference (¯j ¹ ¯i) large, which contributes to the reduction in the
induced rotatory strength. Note that the geometrical factors of ®i
and mj might be averaged out if the conformational fluctuations of
the ligands (that is, perturber) are not sufficiently suppressed. In
summary, enhancement in the chiroptical response of chiral MSA-
protected Au nanoclusters was observed upon acidification of the
dispersion, which could be interpreted in terms of both the
electronic and conformational origins of the MSA ligands (that is,
CD stealing and restriction of the ligand mobility).
1
2
deprotonated) species are predominant. At pH 3.1, the existed
species are singly and doubly protonated forms of MSA. Hence,
the presence of ionized carboxylate (or non-ionized carboxy)
groups strongly modulates the chiroptical response (and overall
dissymmetric field) of the Au nanoclusters. In consideration with
the significant pH dependence of the electronic states and stable
geometries of MSA deduced from the quantum chemical calcu-
lations, the observed pH-responsive behaviors would reasonably
stem from both the electronic and conformational origins of the
MSA ligands.
¹30
2
2
2
It is now established that the Au­S interface in small Au
nanoclusters consists of staples or semi-rings of RS­(Au­SR)n,
so the thiolate-protected Au nanoclusters can be expressed in
the “divide and protect” notation; for example, Au25(SR)18 =
Au13[RS­(Au­SR)2].13 Moreover, in a molecule-like cluster
model, theoretical considerations have revealed that metal-based
electronic transitions with higher energy (than the HOMO­LUMO
1
4
transition) are imparted with ligand character. On this basis, it is
reasonable to assign that the characteristic chiroptical signals
observed at ca. 260­500 nm in the present Au nanoclusters should
arise from the electronic state mixing of the MSA ligands and
staple gold atoms, as has been discussed for chiral 2-phenyl-
1
4
propane-1-thiol-protected Au25 clusters. Therefore, an enhance-
ment of the chiroptical activity for the Au nanoclusters upon
acidification (or protonation) can be explained by (I) a decrease in
the conformational mobility of MSA ligands on the staples15 and/
or (II) an effective CD stealing from the chiral ligand response
The authors thank Ms. Risa Kakinoki (University of Hyogo)
for helping in the optical resolution of rac-MSA.
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1
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1
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1
6
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1
2
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1
4
1
Vij
R /
Imðꢀ ¢mjÞ
ð1Þ
i
2
2
ð¯j ꢀ ¯i Þ
5
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and magnetic transition moments, respectively, and ¯ is the
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Chem. Lett. 2015, 44, 171–173 | doi:10.1246/cl.140953
© 2015 The Chemical Society of Japan | 173