Interstaple dithiol cross-linking in Au25(SR)18 nanomolecules: A combined mass spectrometric and computational study

Article abstract of DOI:10.1021/ja206436x

A systematic study of cross-linking chemistry of the Au₂₅(SR) ₁₈ nanomolecule by dithiols of varying chain length, HS-(CH ₂)_n-SH where n = 2, 3, 4, 5, and 6, is presented here. Monothiolated Au₂₅ has six [RSAuSRAuSR] staple motifs on its surface, and MALDI mass spectrometry data of the ligand exchanged clusters show that propane (C3) and butane (C4) dithiols have ideal chain lengths for interstaple cross-linking and that up to six C3 or C4 dithiols can be facilely exchanged onto the cluster surface. Propanedithiol predominately exchanges with two monothiols at a time, making cross-linking bridges, while butanedithiol can exchange with either one or two monothiols at a time. The extent of cross-linking can be controlled by the Au₂₅(SR)₁₈ to dithiol ratio, the reaction time of ligand exchange, or the addition of a hydrophobic tail to the dithiol. MALDI MS suggests that during ethane (C2) dithiol exchange, two ethanedithiols become connected by a disulfide bond; this result is supported by density functional theory (DFT) prediction of the optimal chain length for the intrastaple coupling. Both optical absorption spectroscopy and DFT computations show that the electronic structure of the Au₂₅ nanomolecule retains its main features after exchange of up to eight monothiol ligands.

Full text of DOI:10.1021/ja206436x

ARTICLE
pubs.acs.org/JACS
Interstaple Dithiol Cross-Linking in Au25(SR)18 Nanomolecules:
A Combined Mass Spectrometric and Computational Study
Vijay Reddy Jupally,‡ Rajesh Kota,‡,§ Eric Van Dornshuld,‡,§ Daniell L. Mattern,‡ Gregory S. Tschumper,‡
De-en Jiang,† and Amala Dass*,‡
†Chemical Sciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, United States
‡Department of Chemistry and Biochemistry, University of Mississippi, University, Mississippi 38677, United States
S Supporting Information
b
ABSTRACT: A systematic study of cross-linking chemistry of the
Au25(SR)18 nanomolecule by dithiols of varying chain length, HSꢀ
(CH2)nꢀSH where n = 2, 3, 4, 5, and 6, is presented here.
Monothiolated Au25 has six [RSAuSRAuSR] staple motifs on its
surface, and MALDI mass spectrometry data of the ligand exchanged
clusters show that propane (C3) and butane (C4) dithiols have ideal
chain lengths for interstaple cross-linking and that up to six C3 or C4
dithiols can be facilely exchanged onto the cluster surface. Propane-
dithiol predominately exchanges with two monothiols at a time,
making cross-linking bridges, while butanedithiol can exchange with
either one or two monothiols at a time. The extent of cross-linking can be controlled by the Au25(SR)18 to dithiol ratio, the reaction
time of ligand exchange, or the addition of a hydrophobic tail to the dithiol. MALDI MS suggests that during ethane (C2) dithiol
exchange, two ethanedithiols become connected by a disulfide bond; this result is supported by density functional theory (DFT)
prediction of the optimal chain length for the intrastaple coupling. Both optical absorption spectroscopy and DFT computations
show that the electronic structure of the Au25 nanomolecule retains its main features after exchange of up to eight monothiol ligands.
’ INTRODUCTION
acidic or basic buffers. Surface passivation of Au nanoparticles by
multidentate thiol binding is shown to improve the colloidal
stability.30ꢀ39 Poly(ethylene glycol) (PEGylated) multidentate
ligands have been used to impart water solubility and minimize
nonspecific interactions.40
Previous reports have documented the synthesis of gold na-
noclusters protected by dithiols.35,41,42 Aromatic dithiol exchanges
on Au25 have been reported previously, and resultant nanoclusters
are shown to lose the distinct Au25 electronic transitions.43 The
exchange of a chiral aromatic dithiol, binapthyldithiol (BINAS), on
Au38 nanoclusters has been reported recently.44 Ligand exchange
has been used to introduce new functionality while the core size of
the nanocluster is preserved.45ꢀ48
Ultrasmall nanoclusters such as Au25(SR)18 are nanomolecules
that have precise number of core gold atoms and organic
passivating ligands. What is unique about Au25 is its high-symme-
try centered icosahedral core with six RSꢀAuꢀSRꢀAuꢀSR
motifs (also referred to as the semiring or long staple or staple
dimer motif; here we simply call it the staple motif). The
stereochemistry of these six motifs makes exchange of bidentate-
binding dithiols on Au25 very interesting, inviting many unansw-
ered questions. For example, what is the optimal carbon chain
length between the bidentate thiol groups to have the most ready
Metal and semiconducting nanoparticles1ꢀ3 have been widely
used in medicine,4 bioanalysis,5 drug delivery,6 catalysis,7,8 and other
applications.9 Thiolated gold nanoclusters,10 especially ultrasmall
gold nanomolecules11 (<2 nm), have garnered tremendous
interest12ꢀ14 due to their size-dependent electrochemical12,15,16
and optical properties.17,18 Among the various core sizes, Au25-
(SR)18 is shown to be extremely stable,19 and the R group has been
varied to produce both water-soluble19 and organic-solvent-soluble
clusters.20ꢀ25 Au25(SCH2CH2Ph)18 (simply referred to as Au25) is
the most-studied cluster due to its solubility in CH3CN20,26 and
relative ease of isolation from the nanocluster mixture.
Self-assembled monolayers (SAMs) are well-defined molecu-
lar assemblies that have reproducible properties.27,28 Thiolated
Au nanoclusters can be viewed as three-dimensional analogues of
SAMs or of surface layers on nanoparticles.27,29 In other words,
well-defined nanoclusters such as Au25(SR)18 can be used as a
model for studying Au surface chemistry. Au25, because of its
relative low mass of ∼7 kDa, is easily amenable to mass
measurements in commercially available mass spectrometers.
Thus, the highly stable, easily synthesized, and readily MS-
characterized Au25 nanoclusters can be used to study the surface
chemistry by mass measurements.
Gold nanoparticles are being used increasingly in biological
applications that require chemical stability, solubility in buffer
solutions, and stability under extreme conditions such as strongly
Received: July 11, 2011
Published: November 22, 2011
r
2011 American Chemical Society
20258
dx.doi.org/10.1021/ja206436x J. Am. Chem. Soc. 2011, 133, 20258–20266
|

Journal of the American Chemical Society
ARTICLE
Scheme 1. Synthesis of N-(1,3-Dimercaptopropan-2-yl)hexadecanamide (5)a
a Spectral data: 1H NMR (300 MHz) (MeOD) δ 0.91 (t, 3H), 1.30 (m, 26H), 1.62 (m, 2H), 2.2 (t, 2H), 3.6(d, 4H), 3.9 (q, 1H).13C NMR (300 MHz)
(MeOD) δ 14.6.0, 23.93, 26.9, 30.5, 30.6, 30.8, 30.9, 32.9, 37.3, 54.5, 61.9, 175.1.
exchange reaction? Are both of the thiol groups anchored on the
gold core? Do dithiols favor inter- or intrastaple binding? Does the
bidentate binding affect the electronic structure of the nanoclus-
ter? To answer these questions, we used a series of bidentate thiols
of increasing linker length from C2 to C6 to probe the ligand
exchange chemistry of Au25 by employing mass spectrometry,
UVꢀvis spectroscopy, and first-principles electronic structure
computation.
dithiol added per starting nanocluster. For example, 18:180 indicates
that for every 18 starting ligands, 180 dithiol molecules were added for
the ligand exchange.
Note that ligand exchange of sufficiently long and flexible dithiols (C4
and longer chains) may lead to cross-linking of multiple nanoclusters,
resulting in an insoluble material. The concentration of the Au25
nanoclusters and excess dithiols are optimized to minimize this cross-
linking.
Synthesis of N-(1,3-Dihydroxypropan-2-yl)hexadecanamide
(3). 2-Aminopropane-1,3-diol (2.00 g, 22.0 mmol) and triethylamine (2.26 g,
22.4 mmol) were dissolved in 250 mL of methanol, and the mixture was
cooled to ꢀ20 °C (Scheme 1). Then, 6.61 g (24.2 mmol) of palmitoyl
chloride in 20 mL of THF was slowly added with stirring. The reaction mixture
was stirred for another 3 h at ꢀ20 °C and then overnight at room temperature.
The C16-serinol compound 3 precipitated and was collected by filtration,
washed with methanol, and crystallized from 95% EtOH, giving 6.52 g
(90% yield) of white crystals, mp 124.5ꢀ125.5 °C (lit.49 125ꢀ125.5 °C).
Synthesis of S,S0-(2-Hexadecanamidopropane-1,3-diyl)
Diethanethioate (4). Diisopropyl azodicarboxylate (1.06 mL,
4.75 mmol) was added dropwise to a stirred solution of PPh3 (1.24 g,
4.74 mmol) in THF (2 mL) at 0 °C under nitrogen. After 5 h, a solution of
diol 3 (500 mg, 1.58 mmol) and thioacetic acid (603 mg, 7.92 mmol) in
THF (1 mL) was added. The reaction mixture was stirred at 0 °C for 1 h
and then at room temperature for 1 day. After dilution with AcOEt
(100 mL), the reaction mixture was washed with saturated NaHCO3
(aq), water, and saturated NaCl (aq), dried over MgSO4, and concentrated
in vacuum. The residue was purified by silica gel chromatography with
hexane:EtOAc (100:10ꢀ50) to give dithioacetate 4 (310 mg, 45%) as a
white crystalline solid, mp 85.5ꢀ86 (Rf = 0.50, hexane:ethyl acetate 1:1). 1H
NMR (500 MHz) (CDCl3) δ0.9 (t, 3H), 1.28 (m, 26H), 1.58 (m, 2H), 2.1
(t, 2H), 2.3 (s, 6H), 3.06ꢀ3.18 (d x d, 4H), 4.21 (m, 1H), 5.8 (d, 1H). 13C
NMR (500 MHz) (CDCl3) δ 14.11, 22.69, 25.61, 29.21, 29.35, 29.50,
29,63, 29.66, 29.69, 30.53, 31.92, 32.17, 36.74, 36.78, 50.09, 50.17, 173.14,
196.20.
Synthesis of N-(1,3-Dimercaptopropan-2-yl)hexadecanamide
(5). Deprotection of dithioacetate 4 was accomplished by dropwise
addition of 2 mL of acetyl chloride to a solution of 4 (100 mg,
0.232 mmol) in 10 mL of dry DCM and 2 mL of dry MeOH at 0 °C.
The reaction mixture was stirred at room temperature overnight. The
solvent was removed under reduced pressure, and the residue was
dissolved in DCM, washed twice with 20 mL of 5% NaHCO3, dried over
MgSO4, and concentrated in vacuum. The residue was purified by silica
gel chromatography with hexane: ethyl acetate (100:10ꢀ40) to yield 5
(20 mg, 30%) as a white solid (Rf = 0.50, hexane:ethyl acetate 1:1). This
compound was used for the ligand exchange reaction immediately. 1H
NMR (300 MHz) (CDCl3) δ 0.87 (t, 3H), 1.27 (m, 26H), 1.57ꢀ1.64
(m+s, 2H + H2O), 2.22 (t, 3H), 2.71 (m, 2 H), 2.94 (m, 2H), 4.20 (q,
1H), 5.7 (d, 1H). 13C NMR (300 MHz) (CDCl3) δ 14.15, 22.71, 25.74,
’ EXPERIMENTAL METHODS
Chemicals. The following chemicals were used:1,2-Ethanedithiol
(Pfaltz & Bauer, 95%), 1,3-propanedithiol (Aldrich, 99%), 1,4-butanedithiol
(Aldrich, 99%), 1,5-pentanedithiol (Aldrich, 96%), 1,6-hexanedithiol
(Aldrich, 96%), phenylethanemercaptan (SAFC, g99%), sodium borohy-
dride (Aldrich, g99%), tetraoctylammonium bromide (TOABr) (Acros,
98%), trans-2-[3-(4-tert-butylphenyl)-2-methyl-2-propenylidene]malo-
nonitrile (DCTB matrix) (Fluka, g99%). Solvents toluene, methanol,
dichloromethane, acetonitrile, and acetone were used from Fisher as received.
Equipment. UVꢀvisible absorption spectra were recorded in
toluene on a Shimadzu UV-1601 instrument. Matrix-assisted laser
desorption time-of-flight mass spectra were collected on a Bruker
Autoflex mass spectrometer in linear positive mode using a nitrogen
laser (337 nm) with DCTB as a matrix.
Synthesis of Au25(SCH2CH2Ph)18. HAuCl4 3H2O, dissolved in
3
water, was added to dichloromethane along with the phase transfer agent
TOABr. The mixture was stirred for 30 min at 500 rpm. The excess water
was removed from the reaction, and 2-phenylethanethiol (3 equiv with
respect to the Au salt) was added. The reaction was stirred for 30 min
until the solution turned colorless. Then a solution of sodium borohy-
dride (ca. 12 mol or 48 equiv with respect to the Au salt) in ice-cold
water was added to the reaction mixture. The whole reaction was
maintained at 0° for 1 h. Excess sodium borohydride was removed by
washing several times with water, and excess thiol was removed by
washing with methanol. Pure Au25(SCH2CH2Ph)18 was separated using
solvent fractionation.
Ligand Exchange Reaction. Au25(SCH2CH2Ph)18 (0.50 mg,
68 nmol) was dissolved in 0.5 mL of toluene. To this was added the
appropriate amount of dithiol corresponding to the specified ratio. The
stirring rate used was 500 rpm. Samples were collected at different time
intervals during the course ofthe reaction. The sampleswereconcentrated
by rotary evaporation and washed repeatedly with methanol until there
was no smell of thiol in the sample. After further rotary evaporation and
dissolution in toluene, MALDI spectra were recorded from a DCTB
matrix.
To avoid confusion in the nanocluster to dithiol ratio, here we use the
notation 18:x, where 18 represents the number of monothiol ligands
present in the starting nanocluster, and x represents the equivalents of
20259
dx.doi.org/10.1021/ja206436x |J. Am. Chem. Soc. 2011, 133, 20258–20266

Journal of the American Chemical Society
ARTICLE
26.75, 29.28, 29.35, 29.37, 29.50, 29.67, 29.70, 31.93, 36.87, 51.16,
172.85.
’ COMPUTATIONAL METHODS
Conformations of gas-phase dithiols HSꢀ(CH2)nꢀSH (n =
2ꢀ5) were explored at the B3LYP50ꢀ52/6-311+G**53,54 level of
theory as implemented in the Gaussian0955 quantum software
package. Initial structures were generated by systematically
sampling the torsional space of the C and S backbone. Full
geometry optimizations were performed for all unique permuta-
tions of τ(XꢀCꢀCꢀY) torsional angles (where X, Y = C or S)
corresponding to syn (0°), gauche ((60°), and anti (180°)
rotamers. An analysis of the intrastaple SꢀS distances in the Au25
XRD crystal structure as well as the interstaple first-, second-, and
third-nearest neighbor SꢀS distances revealed four target
R(SꢀS) range distances potentially suitable for dithiol bridges.
For dithiol conformations with an optimal SꢀS distance close
to or within the target ranges, a series of relaxed scans were
performed to examine how the electronic energy changed as
R(SꢀS) increased or decreased. In other words, all other
geometrical parameters were optimized for a series of fixed
SꢀS distances spanning the appropriate range.
Figure 1. MALDI MS of Au25(SCH2CH2Ph)18 ligand exchanged with
1,3-propanedithiol. The green peak corresponds to original Au25-
(SCH2CH2Ph)18 with no exchanges. The red peaks correspond to
one dithiol exchanging with two monothiols (1Df2). The numbers
denote the number of such exchanges. The remaining low intensity
peaks could not be assigned but are expected to arise from multiple
1Df1 exchanges. The ratio of original nanocluster ligand to incoming
thiol used is 18:1800.
The structure and energetics of Au25 after dithiol exchange
were computed using Turbomole V6.0 for parallel resolution-of-
identity density functional theory (RI-DFT) calculations.56 The
nonempirical TaoꢀPerdewꢀStaroverovꢀScuseria (TPSS)57
form of meta-generalized gradient approximation (meta-GGA)
was used for electron exchange and correlation, because it has
been shown58 that the TPSS functional can describe the auro-
philic interactions in gold clusters and gold complexes better
than the local density approximation (LDA), GGA, and hybrid
functionals. The def2-SV(P) orbital and auxiliary basis sets59
were used for all atoms for structural optimization. Effective core
potentials which have 19 valence electrons and include scalar
relativistic corrections were used for Au.60 The force conver-
gence criterion was set at 1.0 ꢁ 10ꢀ3 a.u.
by 1, 2, 3, 4, 5, and 6 appear at successive Δm’s of ꢀ168 and hence
correspond to a series of 1Df2 exchanges, where one dithiol
bridges the positions formerly occupied by two monothiols.
Exchange with 1,4-Butanedithiol. Ligand exchange data for
butanedithiol are shown in Figure 2. The mass, m, of the
SCH2CH2CH2CH2S and SCH2CH2Ph groups are 120 and
137 Da, respectively. The Δm's for 1Df1 and 1D f2 are
ꢀ16 and ꢀ154 Da, respectively. Red peaks denoted by 2, 3, 4, 5,
6, and 7 differ by multiples of ꢀ154 Da from the mass of the
original Au25, corresponding to 1Df2 exchanges. While the red
peaks are the most intense, a substantial fraction of blue peaks are
also present that correspond to multiple 1Df1 exchanges. This
is in contrast to propanedithiol, where only a very minor fraction
of smaller peaks appear and those only at higher exchanges.
Figure 2b shows that the maximum number of total exchanges
(including 1Df1 and 1Df2) proceeds up to 15 peaks, leaving
only 3 unexchanged phenylethyl thiolate ligands.
’ RESULTS AND DISCUSSION
The XRD crystal structure61,62 of the Au25(SCH2CH2Ph)18
nanomolecule shows the presence of 13 Au atoms in the core
protected by six [RSꢀAuꢀSRꢀAuꢀSR] staple entities. It is
easily synthesized, stable in air and most common laboratory
conditions, possesses distinct UVꢀvis features, and displays a
unique HOMOꢀLUMO gap and a molecular mass of ∼7400 Da,
making it amenable to characterization in commercially available
mass spectrometers. Here we have chosen Au25 as a model
system to probe the surface chemistry and interactions of dithiols
with the Au surface. Because the changes to Au25 can be
measured by a change in mass by mass spectroscopy, we can
obtain concrete information on the surface chemistry, which in
the past has had to rely on expensive and time-consuming
instrumentation such as Auger, XAFES, etc.
Exchange with 1,3-Propanedithiol. Figure 1 shows the
MALDI MS of the Au25(SCH2CH2Ph)18 nanomolecule after
ligand exchange with 1,3-propanedithiol. The masses m of the
SCH2CH2CH2S and SCH2CH2Ph groups are 106 and 137 Da,
respectively. If a single dithiol exchanges with one monothiol,
denoted as 1Df1, then the difference in mass, Δm, is ꢀ30 Da.
If a single dithiol exchanges with two monothiols, denoted as
1Df2, then Δm is ꢀ168 Da. The green peak marked by 0 is the
original nanoparticle with no exchanges. The red peaks marked
Exchange with 1,5-Pentanedithiol and 1,6-Hexanedithiol.
3 shows the ligand exchange data for Au25-
Figure
(SCH2CH2Ph)18 with 1,5-pentanedithiol and 1,6-hexanedithiol.
Both the C5 and C6 dithiols show clear 1Df2 exchanges, with
Δm of ꢀ140 and ꢀ126 Da, respectively. Possible 1Df1
exchanges with C5 and C6 would lead to Δm’s of ꢀ2 and +12 Da,
respectively, but these could not be observed because of limita-
tions in the instrumental resolution.
Effect of Dithiol Ratio. Next, we investigated the effect of the
nanomolecule to dithiol ratio on the extent of ligand exchange.
The ratio is denoted by the 18:x notation, where for every 18
starting ligand groups, x molecules of dithol are added. The mole
ratios of 18:18, 18:180, 18:1800, and 18:5000 were studied as
shown in Figure 4. The extent of exchange was proportional
to the ratio used, so that the number of exchanges and dis-
tribution of exchanges were controllable. Nanomolecules with
mainly one exchange were obtained with the 18:18 ratio.
Ratios of 18:180 and 18:1800 led to a broader distribution of
exchanges, and the 18:5000 ratio pushed the ligand exchanges to
mainly three, four, and five exchanges. Further exchanges are possible
but could not be observed in MALDI because of solubility issues.
20260
dx.doi.org/10.1021/ja206436x |J. Am. Chem. Soc. 2011, 133, 20258–20266

Journal of the American Chemical Society
ARTICLE
Figure 3. MALDI MS data for Au25(SCH2CH2Ph)18 exchanged with
(a) 1,5-pentanedithiol, or (b) 1,6-hexanedithiol. The green peak corre-
sponds to original unexchanged Au25(SCH2CH2Ph)18. The red peaks
correspond to one dithiol exchanging with two monothiols; the number
indicates the number of such dithiol exchanges. The ratio of original
nanocluster ligand to incoming thiol used is 18:1800.
Figure 2. (A) MALDI MS of Au25(SCH2CH2Ph)18 ligand exchanged
with 1,4-butanedithiol. The red peaks correspond to one dithiol ex-
changing with two monothiols; the number indicates the number of such
dithiol exchanges. The blue peaks correspond to one dithiol exchanging
with one monothiol. The ratio of original nanocluster ligand to incoming
thiol used is 18:1800. (B) Expanded view of 4 and 5 peaks that shows
number of 1Df2 and 1Df1 peaks in each set of peaks. The total
number of exchanges are also denoted and proceed up to 15.
Figure 4. Steady-state product of Au25(SCH2CH2Ph)18 ligand ex-
changed with 1,3-propanedithiol as a function of the ratio of starting
nanocluster to dithiol.
the linear SꢀAuꢀS bond, which is a thermodynamically favored
bonding mode.63 Therefore, an intrastaple coupling would be
likely if it could maintain the roughly linear SꢀAuꢀS bond. This
question can be addressed by examining the anion complex
between 1,n-dithiolate and Au(I) as shown in Scheme 2 and by
asking at what linker length n a linear SꢀAuꢀS bond is best
achieved; Figure 6 plots the SꢀAuꢀS angles in the optimized
geometries of the anion complexes. One can see that once the
linker length reaches six (i.e., for 1,6-dithiolate), the SꢀAuꢀS
angle is roughly linear (171°), and a nearly linear angle (179°)
can be achieved for 1,8-dithiolate. The angle for 1,7-dithiolate is
in between (176°). For 1,2-dithiolate the SꢀAuꢀS bond is
substantially strained. In fact, intrastaple coupling is unlikely for
1,2-dithiol to 1,5-dithiol; these dithiols may prefer interstaple
coupling. Moreover, 1,6-, 1,7-, and 1,8-dithiols are good candi-
dates for intrastaple coupling.
Time Evolution of Exchange. The extent and number of
ligand exchanges were also studied as a function of reaction time.
Figure 5 shows the progression of ligand exchange with 1,4-
butanedithiol with time. As noted earlier in Figure 2, the C4 data
showed many 1Df1 peaks in addition to the more-prominent
1Df2 peaks. Figure 5 shows that the number of 1Df1 peaks
increases with time.
Intrastaple versus Interstaple Dithiol Binding. The experi-
mental results of dithiol exchange above prompts the question of
how exactly a dithiol(ate) replaces two monothiolates of the
RSꢀAuꢀSRꢀAuꢀSR staple motifs on the surface of the Au25
cluster. Because we know the structure of the Au25 cluster already,
this question can be addressed through electronic-structure com-
putational techniques. One unique feature of the staple motif is
We have performed a direct computational comparison of
intrastaple versus interstaple coupling for 1,4-dithiols and 1,5-dithiols.
20261
dx.doi.org/10.1021/ja206436x |J. Am. Chem. Soc. 2011, 133, 20258–20266

Journal of the American Chemical Society
ARTICLE
Figure 8. Proposed mode of interstaple coupling by a dithiol: (a)
middle-terminal coupling (upper dashed line) and long-range middle-
terminal couping (lower dashed line); (b) terminalꢀterminal coupling
(2nd nearest neighbor). (Au, green; S, blue; C and H, not shown).
Figure 5. MALDI data of Au25(SCH2CH2Ph)18 ligand exchanged with
1,4-butanedithiol as a function of time.
Scheme 2. Au(I) Binds to a Dithiolate Ligand: What Linker
Length (n) Best Maintains the Linear SꢀAuꢀS Bond?
ꢀ
Figure 9. DFT-optimized structure Au25(1,3-propanedithiolate)9
.
The three dithiolates with the terminalꢀterminal coupling mode
(T-T) are highlighted; the rest are with the middle-terminal mode.
Au, green; S, blue; C, red; H, black.
(Figure 7a) than in the intrastaple mode (Figure 7b). For
1,4-dithiol exchange, the interstaple mode is even more stable, by 18
kcal/mol. This computational comparison clearly shows that the
interstaple coupling is favored compared to intrastaple coupling
for 1,5- or shorter dithiols.
Interstaple coupling for short dithiols can explain why six
exchanges are easily achieved in the case of 1,3-dithiol or 1,4-
dithiol. The reason is that the 18 monothiolates on Au25 can be
divided into two groups: six in the middle of each staple that are
farther from the Au13 core, and 12 at the terminals of the six
RSꢀAuꢀSRꢀAuꢀSR motifs. We propose that the preferred
exchange for small dithiolates happens between the middle
thiolate of one staple and one terminal thiolate of a neighboring
staple (shown by the upper dashed line in Figure 8a). We call this
interstaple coupling the “middle-terminal” mode. The middle-
terminal mode is analogous to the first nearest neighbor defini-
tion introduced earlier for SꢀS distances and discussed further
below. There is another long-range variant of this mode that
corresponds to third nearest neighbor in the crystal structure
(shown by the lower dashed line in Figure 8a). The six middle
thiolates should yield six facile middle-terminal couplings, as
observed in the case of 1,3- and 1,4-dithiols. After six middle-
terminal exchanges, then terminalꢀterminal coupling (shown by
the dashed line in Figure 8b) can happen, which is analogous to
the second nearest neighbor.
Figure 6. SꢀAuꢀS angle in the optimized structure of the anion
complex between Au(I) and 1,n-dithiolate (see Scheme 2 for the
structure).
Figure 7. Au25(SCH3)16(1,5-pentanedithiolate): (a) interstaple cou-
pling versus (b) intrastaple coupling. Interstaple coupling is 9 kcal/mol
more stable than intrastaple coupling. Au, green; S, blue; C, red; H,
not shown.
Is a Complete Dithiol Exchange (9 dithiols exchanging 18
monothiols) Possible in Au25? In principle, one can achieve the
full nine exchanges, i.e., six middle-terminal couplings and three
terminal-terminal couplings. Figure 9 shows a DFT-optimized
ꢀ
Using Au25(SCH3)18 as the parent cluster, we found that
the exchange product Au25(SCH3)16(1,5-pentanedithiolate)ꢀ
is 9 kcal/mol more stable in the interstaple mode
20262
dx.doi.org/10.1021/ja206436x |J. Am. Chem. Soc. 2011, 133, 20258–20266

Journal of the American Chemical Society
ARTICLE
Figure 10. MALDI MS data of Au25(SCH2CH2Ph)18 ligand exchanged
with 5, a propanedithiol attached to a C15 chain through an amide
group. The green peak corresponds to original unexchanged Au25-
(SCH2CH2Ph)18. The red peaks correspond to one dithiol exchanging
with two monothiols; the number indicates the number of such dithiol
exchanges. The blue peaks correspond to one dithiol exchanging with
one monothiol.
Figure 11. MALDI MS data of Au25(SCH2CH2Ph)18 ligand
exchanged with 1,2-ethanedithiol. The green peak corresponds to
original Au25(SCH2CH2Ph)18 with no exchanges. In solution, two
molecules of 1,2-ethanedithiol combine to form a disulfide (HSꢀCH2ꢀ
CH2ꢀSꢀSꢀCH2ꢀCH2ꢀSH). Peak 1* corresponds to one such
disulfide replacing two monothiols. The numbers on the peaks
correspond to the number of disulfides replacing two monothiols
each. Please refer to Scheme 3. The peaks that are heavier than original
Au25 are unidentified.
structure of a fully exchanged Au25 cluster with nine 1,3-
ditholates. The overall geometry of the Au25 cluster is well
maintained; the electronic structure (frontier orbitals and
HOMOꢀLUMO gap) is also almost unchanged from the Au25-
(SCH3)18ꢀ (data not shown). Of course, under the experimental
conditions, the probability of exchange will decrease significantly
after six changes, as some terminal thiolates may be left too far
apart to be coupled after six middle-terminal exchanges. How-
ever, if the exchange process is reversible and dynamic, we
assume that the cluster will try to lower its energy by achieving
the most stable configuration and degree of exchange. In the case
of 1,4-dithiol, seven exchanges occur (Figure 2a) but not in the
case of 1,3-dithiol (Figure 1). Figure 9 indicates that, in principle,
more than six exchanges can be achieved for 1,3-dithiol.
Scheme 3. 1,2-Ethanedithiol Forming Disulfide before Un-
dergoing Ligand Exchange with Au25(SCH2CH2Ph)18
In an earlier work on chiral and rigid aromatic dithiol
(binapthyldithiol, BINAS) exchange on Au38 and Au40 nanoclus-
ters, we suggest an intrastaple binding.44 It is important to note the
differences between the two systems: (a) The current work utilizes
Au25, which has six identical long [SRꢀAuꢀSRꢀAuꢀSR] staples,
while the earlier work with Au38 has a mixture of short
[SRꢀAuꢀSR] and long staples, (b) the current work employs
flexible aliphatic ligands of variable chain length while the earlier
work utilizes rigid aromatic ligands. In the previous work, we
proposed that the BINAS ligand exchanges with the sulfurs in the
short staple only.
To achieve more than six exchanges for 1,3-dithiol, we
employed the “like dissolves like” principle to increase the
likeness between the monothiolate and the dithiol(ate), to
facilitate the exchange. We synthesized 5, an analogue of the
C3 dithiol with a C15 chain tethered by an amide group
(Scheme 1). When a 1,3-propanedithiol replaces two phenyl-
ethanethiols, 16 carbon atoms are replaced by 3. When five or six
such exchanges occur, solubility is dramatically lowered. When
5 replaces two phenylethanethiols, 16 carbon atoms are replaced
by 19, leaving the solubility of the nanocluster product relatively
unaffected. Figure 10 shows the MALDI data of Au25-
(SCH2CH2Ph)18 exchanged with 5. The intense peaks in the
spectra correspond to 1Df2 exchange with a Δm of +222 Da. This
pattern, with a series of 1Df2 predominant peaks, agrees well with
that of the 1,3-propanedithiol data (Figure 1). More importantly, we
see a significant increase in six and seven exchanges and a minor
peak for eight exchanges using the C15 analogue.
Ligand Exchange of Au25(SCH2CH2Ph)18 with 1,2-Ethane-
dithiol. The MS (Figure 11) does not show peaks that corre-
spond to either 1Df1 (Δm ꢀ44) or 1Df2 (Δm ꢀ182).
However, the peaks match with exchange of the disulfide dimer
of ethanedithiol as shown in Scheme 3 (Δm ꢀ90). We propose
an intrastaple coupling mode because this agrees well with our
prediction that 1,6-dithiol or longer can have intrastaple coupling
(Figure 6), and the disulfide bond makes this ligand resemble a
1,6-dithiol. Although we show the disulfide forming before
exchange in Scheme 3, it is also conceivable that two 1Df1
exchanges occur first, followed by oxidative coupling of the
dangling thiolates to make the disufide bridge.
SulfurꢀSulfur Distances. The ranges of first-, second-, and
third-nearest neighbor interstaple SꢀS distances in the crystal
structure of Au25 are denoted in Figure 12 by arrows at
20263
dx.doi.org/10.1021/ja206436x |J. Am. Chem. Soc. 2011, 133, 20258–20266

Journal of the American Chemical Society
ARTICLE
Figure 12. Relative energies (ΔE) and interstaple SꢀS distances, R(SꢀS), of the low energy conformers of C2, C3, C4, and C5, where the 1st, 2nd, and
3rd nearest neighbor (NN) ranges are indicated by the arrows.
3.69ꢀ4.50 Å, 4.64ꢀ5.49 Å, and 7.08ꢀ8.46 Å, respectively. The
intrastaple target range is located at 4.61ꢀ4.65 Å. These target
ranges allow the prediction of which dithiols are candidates to
make dithiol bridges on Au25 staples. The length of dithiols
needed to bridge third-nearest neighbors is likely underestimated
because of steric interactions from nearby atoms spatially prohi-
biting a direct dithiol bridge linkage.
The effect of the SꢀS distance on the gas-phase dithiol
conformer energy shows which conformers are candidates for
forming interstaple and intrastaple bridges in Au25. The target
energy for a likely bridge candidate is within 2 kcal molꢀ1 of its
global minimum.
well with the target range for interstaple bridging between third
nearest neighbors. These computational results are consistent
with the lack of experimental evidence for dithiol bridging in C2.
Effect of Dithiol Exchange on the Electronic Structure of
Au25. We investigated if the cross-linking of two staple moieties by
dithiols affects the electronic structure of the Au25 nanomolecules.
To this end, aliquots of samples were obtained over time and
purified to remove dithiols. The optical spectra of these processed
dithiol exchanged aliquots were recorded, and then mass spectra
were obtained, as shown in Figure 13. First, we note that the optical
density of the processed Au25 nanoclusters decreased with time,
suggesting loss of soluble material. The decrease in concentration
of soluble Au25 is likely due to multiple reasons: (a) internanoclus-
ter cross-linking may lead to insoluble oligo/polymers, (b) Au25
nanoclusters stirred for longer durations (several hours) in the
presence of excess thiol may convert to Au(I) thiolate species, (c)
purification of sample aliquots to remove excess thiol before optical
measurements will lead to some loss of Au25.
Second, and more importantly, we note that the fine spectral
features of Au25 are not affected significantly even after one, two,
and three exchanges have occurred with 1,4-butanedithiol. In
other words, despite the decrease in optical density, the electronic
features of Au25 are preserved even after dithiol exchange. This
contradicts an earlier report where the ligand exchange of Au25
with toluene-3,4-dithiol results in a complete loss of electronic
features.43 The aromatic dithiol employed in the earlier work is
much more rigid compared to the series of aliphatic dithiols,
specifically the 1,4-butanedithiol used in Figure 13 here. It would
appear that the rigidity of the dithiol may play a role in how the
electronic structure is affected by ligand exchange. However, it is
more likely that the Au25 ligand exchange with aromatic thiols
(unpublished results) leads to decomposition of the Au25
nanoclusters, as suggested in the earlier report.43
One C2 conformer (Figure 12) has a minimum within the first
nearest neighbor target range of 3.69ꢀ4.50 Å, suggesting candi-
dacy for nearest-neighbor SꢀS bridging. However, this particular
conformer has a torsional angle τ(SꢀCꢀCꢀS) of approximately
180°, which means the two carbons would encroach on the
intervening Au atom even though the SꢀS separation is favor-
able. Another low-energy conformation can be found near
R(SꢀS) = 3.41 Å. This structure has a more favorable
τ(SꢀCꢀCꢀS) of 65° for interstaple alignment, but placing
the S atoms at the closest target distance of 3.69 Å increases the
energy by about 2 kcal molꢀ1
.
Several low-energy C3 conformers (Figure 12) have multiple
SꢀS separations that fall within the first- and second-nearest
neighbor ranges of 3.69ꢀ4.50 Å and 4.64ꢀ5.49 Å as well as the
intrastaple target range of 4.61ꢀ4.65 Å. The energies of all
sampled conformations rapidly increase for larger values of
R(SꢀS), and it appears that propanedithiol is too short to bridge
the third-nearest neighbor sulfurs. Several low-energy C4 con-
formers (Figure 12) have SꢀS separations that fall within the
second nearest neighbor range of 4.64ꢀ5.49 Å [not shown in
Figure 12] as well as the intrastaple target range of 4.61ꢀ4.65 Å.
The energies of the C4 conformers rapidly increase for smaller
and larger values of R(SꢀS) suggesting that they are not good
candidates for first or third nearest neighbor bridging. Several
low-energy C5 conformers have multiple SꢀSseparations thatalign
To corroborate our UVꢀvis results, we calculated the electro-
nic-structure change as the number of exchanges of 1,4-butane-
dithiol onꢀthe Au25 cluster increased. The unexchanged Au25-
(SCH3)18 cluster has a HOMOꢀLUMO gap of 1.36 eV,
20264
dx.doi.org/10.1021/ja206436x |J. Am. Chem. Soc. 2011, 133, 20258–20266

Journal of the American Chemical Society
ARTICLE
and LUMO levels. However, the basic features of the electronic
structure of the Au25 cluster remain unchanged, in clear agree-
ment with the experimental UVꢀvis results from Figure 13.
’ CONCLUSIONS
In summary, several homologues of the alkanedithiol series
were used foꢀr the ligand exchange experiments with the Au25-
(SCH2Ph)18 nanocluster. The extent of exchange reactions,
monitored via mass spectrometry, depends on chain length,
concentration of the dithiol, and reaction time. A direct energy
comparison of the interstaple versus intrastaple binding is made
in support of the interstaple binding. Behavior of individual
dithiols in such reactions is also verified computationally and
presented in parallel to the experimental data. Propanedithiol
(C3) and butanedithiol (C4) have optimal chain lengths for
interstaple binding onto the nanoparticle surface, achieving more
than six interstaple bindings. Pentanedithiol (C5) and hexane-
dithiol (C6) also participate in these reactions to a lesser extent,
while ethanedithiol (C2) does not have optimal chain length for
bidentate binding. Moreover, analysis of the SꢀAuꢀS angle for
the dithiols and formation of the disulfide bond from C2 during
exchange indicate that intrastaple binding is likely for C6 or
longer dithiols. Further, probing the electronic properties of the
postexchange clusters through UVꢀvis measurements shows the
conservation of electronic properties. Efforts will be made in the
direction of controlled and complete exchange of such multi-
dentate ligands onto the nanocluster surface.
’ ASSOCIATED CONTENT
S
Supporting Information. Additional MALDI-MS and
b
NMR data. Complete ref 55. This material is available free of
charge via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
amal@olemiss.edu
Figure 13. Changes in (a) UVꢀvis electronic transitions of Au25-
(SCH2CH2Ph)18 in toluene as a function of ligand exchange with 1,4-
butanedithiol, as shown by (b) MALDI MS data. The starting ligand to
dithiol ratio was 18:1800. Aliquots of the reaction mixture were purified to
remove excess thiol before UVꢀvis and MALDI measurements were made.
Author Contributions
§These authors contributed equally.
’ ACKNOWLEDGMENT
A.D. gratefully acknowledges support from the National
Science Foundation (0903787), University of Mississippi Startup
Fund, and CLA summer research grant. G.T. acknowledges NSF
(CHE-0957317 and EPS-0903787) and the Mississippi Center
for Supercomputing Research. D.L.M. gratefully acknowledges
support from the National Science Foundation CHE 0848206.
D-E.J was supported by the Division of Chemical Sciences,
Geosciences, and Biosciences, Office of Basic Energy Sciences,
U.S. Department of Energy. We thank Charles Hussey, Glen
Hopkins, and College of Liberal Arts for Bruker Autoflex I MALDI
TOF instrumentation support. This research used resources of
the National Energy Research Scientific Computing Center,
which is supported by the Office of Science of the U.S. Depart-
ment of Energy under Contract No. DE-AC02-05CH11231.
Table 1. HOMOꢀLUMO Gap for 1,4-Butanedithiol-(BDT)-
Exchanged Au25(SCH3)18ꢀ and Energy Levels of Frontier
Orbitals-(all in eV)
HOMOꢀ
LUMO gap
cluster
HOMO levels
LUMO levels
ꢀ
Au25(SCH3)18
1.36
1.35
1.31
1.31
1.30
ꢀ2.12, ꢀ2.10, ꢀ2.08 ꢀ0.72, ꢀ0.69
ꢀ2.12, ꢀ2.09, ꢀ2.09 ꢀ0.73, ꢀ0.70
ꢀ2.12, ꢀ2.09, ꢀ2.07 ꢀ0.76, ꢀ0.70
ꢀ2.11, ꢀ2.10, ꢀ2.06 ꢀ0.75, ꢀ0.72
ꢀ2.12, ꢀ2.10, ꢀ2.07 ꢀ0.77, ꢀ0.73
ꢀ
ꢀ
ꢀ
ꢀ
Au25(SCH3)16 (BDT)1
Au25(SCH3)14 (BDT)2
Au25(SCH3)12 (BDT)3
Au25(SCH3)10 (BDT)4
together with roughly triply degenerate HOMOs and doubly
degenerate LUMOs. With an increasing number of 1,4-butane-
dithiol exchanges for SCH3, there is a slow narrowing of the
HOMOꢀLUMO gap and slight perturbations of the HOMO
’ REFERENCES
(1) Daniel, M.-C.; Astruc, D. Chem. Rev. 2003, 104, 293–346.
(2) Alivisatos, A. P. Science 1996, 271, 933–937.
20265
dx.doi.org/10.1021/ja206436x |J. Am. Chem. Soc. 2011, 133, 20258–20266

Journal of the American Chemical Society
ARTICLE
(3) Medintz, I. L.; Uyeda, H. T.; Goldman, E. R.; Mattoussi, H. Nat.
Mater. 2005, 4, 435–446.
(4) Bowman, M. C.; Ballard, T. E.; Ackerson, C. J.; Feldheim, D. L.;
Margolis, D. M.; Melander, C. J. Am. Chem. Soc. 2008, 130, 6896–+.
(5) Penn, S. G.; He, L.; Natan, M. J. Curr. Opin. Chem. Biol. 2003,
7, 609–615.
(6) Han, G.; Ghosh, P.; Rotello, V. M. Nanomedicine 2007, 2,
113–123.
(7) Aiken, J. D.; Finke, R. G. J. Mol. Catal. A: Chem. 1999, 145, 1–44.
(8) Zhu, Y.; Qian, H. F.; Jin, R. C. Chem.—Eur. J. 2010,
16, 11455–11462.
(38) Abad, J. M.; Mertens, S. F. L.; Pita, M.; Fernꢀandez, V. M.;
Schiffrin, D. J. J. Am. Chem. Soc. 2005, 127, 5689–5694.
(39) Volkert, A. A.; Subramaniam, V.; Ivanov, M. R.; Goodman,
A. M.; Haes, A. J. ACS Nano 2011, 5, 4570–4580.
(40) Stewart, M. H.; Susumu, K.; Mei, B. C.; Medintz, I. L.;
Delehanty, J. B.; Blanco-Canosa, J. B.; Dawson, P. E.; Mattoussi, H.
J. Am. Chem. Soc. 2010, 132, 9804–9813.
(41) Tang, Z.; Xu, B.; Wu, B.; Germann, M. W.; Wang, G. J. Am.
Chem. Soc. 2010, 132, 3367–3374.
(42) Tang, Z.; Xu, B.; Wu, B.; Robinson, D. A.; Bokossa, N.; Wang,
G. Langmuir 2011, 27, 2989–2996.
(43) Fields-Zinna, C. A.; Parker, J. F.; Murray, R. W. J. Am. Chem.
Soc. 2010, 132, 17193–17198.
(44) Knoppe, S.; Dharmaratne, A. C.; Schreiner, E.; Dass, A.; B€urgi,
T. J. Am. Chem. Soc. 2010, 132, 16783–16789.
(9) Schmid, G.; Baumle, M.; Geerkens, M.; Helm, I.; Osemann, C.;
Sawitowski, T. Chem. Soc. Rev. 1999, 28, 179–185.
(10) Brust, M.; Walker, M.; Bethell, D.; Schiffrin, D. J.; Whyman, R.
J. Chem. Soc., Chem. Commun. 1994, 801–802.
(45) Templeton, A. C.; Hostetler, M. J.; Warmoth, E. K.; Chen,
S. W.; Hartshorn, C. M.; Krishnamurthy, V. M.; Forbes, M. D. E.;
Murray, R. W. J. Am. Chem. Soc. 1998, 120, 4845–4849.
(46) Hostetler, M. J.; Templeton, A. C.; Murray, R. W. Langmuir
1999, 15, 3782–3789.
(47) Dass, A.; Holt, K.; Parker, J. F.; Feldberg, S. W.; Murray, R. W.
J. Phys. Chem. C 2008, 112, 20276–20283.
(48) Shichibu, Y.; Negishi, Y.; Tsukuda, T.; Teranishi, T. J. Am.
Chem. Soc. 2005, 127, 13464–13465.
(49) Chalfant, C. E.; Szulc, Z.; Roddy, P.; Bielawska, A.; Hannun,
Y. A. J. Lipid Res. 2004, 45, 496–506.
(50) Becke, A. D. Phys. Rev. A 1988, 38, 3098–3100.
(51) Lee, C. T.; Yang, W. T.; Parr, R. G. Phys. Rev. B 1988,
37, 785–789.
(52) Becke, A. D. J. Chem. Phys. 1993, 98, 5648–5652.
(53) Clark, T.; Chandrasekhar, J.; Spitznagel, G. W.; Schleyer, P. V.
J. Comput. Chem. 1983, 4, 294–301.
(54) Krishnan, R.; Binkley, J. S.; Seeger, R.; Pople, J. A. J. Chem. Phys.
1980, 72, 650–654.
(55) Frisch, M. J.; et al. Gaussian 09.
(56) Ahlrichs, R.; Bar, M.; Haser, M.; Horn, H.; Kolmel, C. Chem.
Phys. Lett. 1989, 162, 165–169.
(57) Tao, J. M.; Perdew, J. P.; Staroverov, V. N.; Scuseria, G. E. Phys.
Rev. Lett. 2003, 91, 146401.
(58) Johansson, M. P.; Lechtken, A.; Schooss, D.; Kappes, M. M.;
Furche, F. Phys. Rev. A 2008, 77, 053202.
(59) Weigend, F.; Haser, M.; Patzelt, H.; Ahlrichs, R. Chem. Phys.
Lett. 1998, 294, 143–152.
(60) Andrae, D.; Haussermann, U.; Dolg, M.; Stoll, H.; Preuss, H.
Theor. Chim. Acta 1990, 77, 123–141.
(61) Heaven, M. W.; Dass, A.; White, P. S.; Holt, K. M.; Murray,
R. W. J. Am. Chem. Soc. 2008, 130, 3754–3755.
(11) Whetten, R. L.; Khoury, J. T.; Alvarez, M. M.; Murthy, S.;
Vezmar, I.; Wang, Z. L.; Stephens, P. W.; Cleveland, C. L.; Luedtke,
W. D.; Landman, U. Adv. Mater. 1996, 8, 428–433.
(12) Murray, R. W. Chem. Rev. 2008, 108, 2688–2720.
(13) Jin, R. Nanoscale 2010, 2, 343–362.
(14) Sardar, R.; Funston, A. M.; Mulvaney, P.; Murray, R. W.
Langmuir 2009, 25, 13840–13851.
(15) Chen, S. W.; Ingram, R. S.; Hostetler, M. J.; Pietron, J. J.;
Murray, R. W.; Schaaff, T. G.; Khoury, J. T.; Alvarez, M. M.; Whetten,
R. L. Science 1998, 280, 2098–2101.
(16) Quinn, B. M.; Liljeroth, P.; Ruiz, V.; Laaksonen, T.; Kontturi, K.
J. Am. Chem. Soc. 2003, 125, 6644–6645.
(17) Wyrwas, R. B.; Alvarez, M. M.; Khoury, J. T.; Price, R. C.;
Schaaff, T. G.; Whetten, R. L. Eur. Phys. J. D 2007, 43, 91–95.
(18) Alvarez, M. M.; Khoury, J. T.; Schaaff, T. G.; Shafigullin, M. N.;
Vezmar, I.; Whetten, R. L. J. Phys. Chem. B 1997, 101, 3706–3712.
(19) Shichibu, Y.; Negishi, Y.; Tsunoyama, H.; Kanehara, M.;
Teranishi, T.; Tsukuda, T. Small 2007, 3, 835–839.
(20) Donkers, R. L.; Lee, D.; Murray, R. W. Langmuir 2004,
20, 1945–1952.
(21) Jimenez, V. L.; Georganopoulou, D. G.; White, R. J.; Harper,
A. S.; Mills, A. J.; Lee, D. I.; Murray, R. W. Langmuir 2004,
20, 6864–6870.
(22) Negishi, Y.; Nobusada, K.; Tsukuda, T. J. Am. Chem. Soc. 2005,
127, 5261–5270.
(23) Negishi, Y.; Chaki, N. K.; Shichibu, Y.; Whetten, R. L.; Tsukuda,
T. J. Am. Chem. Soc. 2007, 129, 11322–11323.
(24) Wu, Z.; Suhan, J.; Jin, R. J. Mater. Chem. 2009, 19, 622–626.
(25) Dharmaratne, A. C.; Krick, T.; Dass, A. J. Am. Chem. Soc. 2009,
131, 13604–13605.
(26) Donkers, R. L.; Lee, D.; Murray, R. W. Langmuir 2008,
24, 5976–5976.
(27) Love, J. C.; Estroff, L. A.; Kriebel, J. K.; Nuzzo, R. G.; Whitesides,
G. M. Chem. Rev. 2005, 105, 1103–1169.
(62) Zhu, M.; Aikens, C. M.; Hollander, F. J.; Schatz, G. C.; Jin, R.
J. Am. Chem. Soc. 2008, 130, 5883–5885.
(63) Jiang, D. E.; Tiago, M. L.; Luo, W. D.; Dai, S. J. Am. Chem. Soc.
2008, 130, 2777–2779.
(28) Ulman, A. Chem. Rev. 1996, 96, 1533–1554.
(29) Templeton, A. C.; Wuelfing, M. P.; Murray, R. W. Acc. Chem.
Res. 2000, 33, 27–36.
(30) Chinwangso, P.; Jamison, A. C.; Lee, T. R. Acc. Chem. Res. 2011,
44, 511–519.
(31) Park, J.-S.; Vo, A. N.; Barriet, D.; Shon, Y.-S.; Lee, T. R.
Langmuir 2005, 21, 2902–2911.
(32) Srisombat, L.-o.; Park, J.-S.; Zhang, S.; Lee, T. R. Langmuir
2008, 24, 7750–7754.
(33) Zhang, S.; Leem, G.; Srisombat, L.-o.; Lee, T. R. J. Am. Chem.
Soc. 2007, 130, 113–120.
’ NOTE ADDED AFTER ASAP PUBLICATION
The Supporting Information published ASAP November 22,
2011, did not include the MALDI spectra. The complete Supporting
Information was reposted November 29, 2011.
(34) Mei, B. C.; Susumu, K.; Medintz, I. L.; Mattoussi, H. Nat.
Protocols 2009, 4, 412–423.
(35) Roux, S.; Garcia, B.; Bridot, J.-L.; Salomꢀe, M.; Marquette, C.;
Lemelle, L.; Gillet, P.; Blum, L.; Perriat, P.; Tillement, O. Langmuir
2005, 21, 2526–2536.
(36) Hou, W.; Dasog, M.; Scott, R. W. J. Langmuir 2009,
25, 12954–12961.
(37) Zheng, F.; et al. Nanotechnology 2008, 19, 235603.
20266
dx.doi.org/10.1021/ja206436x |J. Am. Chem. Soc. 2011, 133, 20258–20266