Diethylene glycol ether-linked 3,4,5-trihydroxybenzamides as triply branched dendritic anchors to CdSe/ZnS core/shell type nanoparticles: Potential hydrophilic fluorescent probes

Article abstract of DOI:10.1039/b418806c

Functionalized N-2-mercaptoethyl-gallamides bearing three or five hydroxyl units that are tethered with diethylene glycol ether(s) allow for transferring hydrophobically pyridine-capped CdSe/ZnS core/shell nanoparticles from an organic to an aqueous layer

Full text of DOI:10.1039/b418806c

View Article Online / Journal Homepage / Table of Contents for this issue
COMMUNICATION
www.rsc.org/chemcomm | ChemComm
Diethylene glycol ether-linked 3,4,5-trihydroxybenzamides as triply
branched dendritic anchors to CdSe/ZnS core/shell type nanoparticles:
potential hydrophilic fluorescent probes{
Chien-Tien Chen,* Vijay D. Pawar, Yogesh S. Munot, Chia-Chun Chen* and Chih-Jung Hsu
Received (in Cambridge, UK) 15th December 2004, Accepted 14th March 2005
First published as an Advance Article on the web 29th March 2005
DOI: 10.1039/b418806c
Functionalized N-2-mercaptoethyl-gallamides bearing three or
five hydroxyl units that are tethered with diethylene glycol
ether(s) allow for transferring hydrophobically pyridine-capped
CdSe/ZnS core/shell nanoparticles from an organic to an
aqueous layer with intact fluorescent profiles.
During the past decade, semiconductor nanocrystals (quantum
dots) have attracted scientists’ attention in view of their unique size
dependent chemical and physical properties.1–3 These highly
fluorescent nanocrystals have shown great potential in light-
emitting4 and nonlinear optical5 devices, solar cells, and especially
as biological labels.6 For biological applications, robust, water
soluble functionalized nanohybrids are required. To achieve this
goal, synthetic strategies like surface modification with water
soluble ligands,6b silanization,7 and encapsulation with block-
copolymer micelles8 have been used.
Herein we report a new type of hydrophilic nanohybrid where
tripodal, dendritic gallamides-5 bearing a thiol anchoring group
Scheme 1 Synthesis of dendrons 5a and 5b.
with attached ethylene glycol unit(s) toward the periphery are
employed to overcoat CdSe/ZnS core/shell nanoparticles. The
unique feature of the nanohybrids is that they allow for further
functional group transformation of the terminal hydroxyl groups
to carboxylic acid, pyruvate, phosphate, carbohydrate, and bio-
active building blocks.9 In addition, they may serve as template
systems in extending single-site to tri- or penta-site multivalent
probes.10 Particularly in site-to-site carbohydrate–protein interac-
tions, moderate affinity has been identified. Wrapping such a type
of functionalized gallamides around nanocrystals may further
enhance polyvalent interactions with biomolecules.11
hydrolysis by using KOH in warm ethanol (60 uC) for 4 h to afford
the corresponding acids 3a and 3b in 75 and 95% yields,
respectively. Direct amidations were carried out (55 and 80%
yields, respectively) on both acids 3a,b by coupling with
2-tritylsulfanyl-ethylamine in the presence of Et3N, dicyclohexyl-
carbodiimide (DCC), and 1-hydroxybenzotriazole (HOBT) in
DMF. Finally, the trityl groups in 4a were unmasked by Et3SiH in
trifluoroacetic acid (TFA) at ambient temperature in 30 min to
furnish the ligand 5a in 95% yield. Dihydroxylation of the allyl
groups in 4b in aqueous acetone led to the corresponding tetraol-
4b9 (95% yield). Subsequent deprotection of both THP and trityl
groups in the tetraol-4b9 by Et3SiH in TFA led to 5b. Both readily
oxidized thiols were isolated in reasonably pure form by filtration
of the reaction mixture through a short plug of Celite.
The requisite dendritic gallamides, 5a and 5b, were prepared
from methyl 3,4,5-tris-[2-(2-hydroxy-ethoxy)-ethoxy]-benzoate (1a)
and
3,5-bis-allyloxy-4-[2-(2-hydroxy-ethoxy)-ethoxy]-benzoate
(1b), respectively. They are readily available from methyl gallate
by treatment with straight 2-chloroethoxyethanol (3 equiv) or
2-chloroethoxyethanol (1 equiv) followed by allyl bromide (2 equiv)
and K2CO3 in refluxed 2-butanone.{ The three terminal hydroxyl
groups in 1a were protected quantitatively as trityl ethers-2a
(3.5 mol% N,N-dimethylaminopyridine (DMAP), Ph3CCl, and
Et3N in CH2Cl2), Scheme 1. On the other hand, the single
hydroxyl unit in 1b was converted to tetrahydropyranyl (THP)
ether-2b in 95% yield. Both compounds were subjected to basic
Direct heating of TOPO-capped CdSe/ZnS core/shell nanopar-
ticles12 in warm pyridine (70 uC) for 12 h and then concentration
in vacuo allows one to fully replace TOPO on the particle surface
with intact size and photophysical attributes.13 Similar to TOPO,
pyridine is weakly bound14 to the surface of core/shell type
nanocrystals and therefore acts as an excellent passivating agent.
The pyridine-capped nanocrystals allow for more efficient access
to surface modification. Pyridine was replaced by ligands 5a,b
from the surface of CdSe/ZnS by partitioning in a biphasic system,
Scheme 2. The pyridine-capped nanocrystals were placed in
toluene and a solution of the ligand 5 in 10% aqueous MeOH
with 0.5 equiv of NaBH4 (to avoid oxidation of the thiols) was
{ Electronic supplementary information (ESI) available: experimental
1
1
procedures, spectral data, H and 13C NMR spectra for 1–5a,b, and H
NMR spectra and HR–TEM images for 6a,b. See http://www.rsc.org/
suppdata/cc/b4/b418806c/
*chefv043@scc.ntnu.edu.tw (Chien-Tien Chen)
This journal is ß The Royal Society of Chemistry 2005
Chem. Commun., 2005, 2483–2485 | 2483

View Article Online
concomitant coordination-to-bonding exchange action to bring
the nanocrystals in a nanohybrid form into the aqueous layer. The
organic phase, initially red in color, changed to colorless. And, the
originally colorless aqueous phase turned to red, indicative of
complete nanoparticle transfer.
This phase-transfer extraction process is irreversible in nature.
On the CdSe/ZnS nanocrystal surface, the coordinating pyridine
was supplanted by the thiolate dendrons (5a and 5b) in a covalent
bond fashion. In addition, the exchange process is further
facilitated at elevated temperature (i.e. 70–80 uC) in view of the
volatility15 of pyridine. Therefore, once the organic soluble,
pyridine-capped nanocrystals are phase-transferred to the resultant
aqueous soluble, dendron-capped nanocrystals, they cannot be
transferred back to the toluene layer.16 When the temperature of
the partitioning process is lowered, the rate of oxidation of thiol is
faster than the rate of ligand exchange. This will slow or even shut
down the exchange process. To avoid this, NaBH4 was thus
added and the biphasic ligand-exchange process was operated at
70–80 uC. After completion of surface modification, free pyridine
was removed by extensive extraction of the aqueous layer with
toluene. The aqueous layer was then separated and the
nanohybrids-6a,b were selectively precipitated by adding THF.
The pure dendron-capped nanohybrids can thus be collected by
centrifugation. The washing process with THF was repeated 3–4
times to remove all freely dissociated residual thiolate ligands.
For the characterization of the nanohybrids-6a and 6b, their
absorption and photoluminescence spectra (in deionised H2O)
were examined and compared with those (in toluene) of pyridine-
capped CdSe/ZnS core/shell nanoparticles, Fig. 1. Both absorption
spectra show first exciton absorption peaks at ca. 569 and 550 nm
with 50% and 25% decrease in intensity, respectively, relative to
those of the original pyridine-capped nanocrystals.17 On the other
hand, the emission maxima for 6a and 6b appear at ca. 587 and
Scheme 2 Anchoring of 5a and 5b to CdSe/ZnS nanoparticles.
added. The biphasic system was heated at 70–80 uC for 12–24 h to
provide the desired water soluble nanohybrids-6a and 6b. Heating
and vigorous stirring of the biphasic system are essential to effect
emulsion formation that facilitates the phase transfer with
Fig. 1 Absorption and photoluminescence spectra of (top) pyridine-capped CdSe/ZnS (toluene) and 6a (H2O); (bottom) pyridine-capped CdSe/ZnS
(toluene) and 6b (H2O).
2484 | Chem. Commun., 2005, 2483–2485
This journal is ß The Royal Society of Chemistry 2005

View Article Online
of the nanocrystals in these nanohybrids.{ The nanohybrids 6a
and 6b show excellent stability for at least 6 months.
In summary, we have documented the synthesis of a new type of
gallamide-based dendritic thiols possessing diethylene glycol ether
tether(s) with three or five diverted hydroxyl terminals. We have
also demonstrated a simple biphasic system for ligand exchange on
the surface of CdSe/ZnS nanocrystals. After covering the surfaces
of nanocrystals with these thiols, the resultant nanohybrids
become highly water soluble and retain the morphological and
photophysical properties of the original nanocrystals. Further
extension of this system to the synthesis of other metal- or metal
oxide-centered nanohybrids of biological interest is underway.
We thank the National Science Council of Taiwan for financial
support of this research.
Fig. 2 Partial 1H NMR spectra of 5a (top, CDCl3) and 6a (bottom,
Chien-Tien Chen,* Vijay D. Pawar, Yogesh S. Munot, Chia-Chun Chen*
and Chih-Jung Hsu
D2O).
Department of Chemistry, National Taiwan Normal University, #88,
Sec. 4, Ding-jou Road, Taipei, 11650, Taiwan.
E-mail: chefv043@scc.ntnu.edu.tw; Fax: +886 2 2932 4249;
Tel: +886 2 2930 9095
Notes and references
1 C. B. Murray, C. R. Kagan and M. G. Bawendi, Annu. Rev. Mater.,
2000, 30, 545.
2 A. P. Alivisatos, Science, 1996, 271, 933.
3 X. Peng, M. C. Schlamp, A. V. Kadavanich and A. P. Alivisatos, J. Am.
Chem. Soc., 1997, 119, 7019.
4 (a) A. P. Alivisatos, Nature, 1994, 370, 354; (b) A. A. Mamedov,
A. Belov, M. Giersig, N. N. Mamedova and N. A. Kotov, J. Am.
Chem. Soc., 2001, 123, 7738.
5 V. C. Sundar, H. J. Eisler and M. G. Bawendi, Adv. Mater., 2002, 14,
739.
6 (a) A. P. Alivisatos, Science, 1998, 281, 2013; (b) W. C. W. Chan and
S. Nie, Science, 1998, 281, 2016.
7 D. Gerion, F. Pinaud, S. C. Williams, W. J. Parak, D. Zanchet, S. Weiss
and A. P. Alivisatos, J. Phys. Chem. B, 2001, 105, 8861.
8 B. Dubertret, P. Skourides, D. J. Norris, V. Noireaux, A. H. Brivanlou
and A. Libchaber, Science, 2002, 298, 1759.
Fig. 3 Partial 1H NMR spectra of 5b (top, CDCl3) and 6b (bottom,
9 (a) C.-T. Chen, J.-H. Kuo, C.-H. Li, N. B. Barhate, S.-W. Hon,
T.-W. Li, S.-D. Chao, C.-C. Liu, Y.-C. Li, I.-H. Chang, J.-S. Lin,
C.-J. Liu and Y.-C. Chou, Org. Lett., 2001, 3, 3729; (b) C.-C. Lin,
Y.-C. Yeh, C.-Y. Yang, C.-L. Chen, G.-F. Chen, C.-C. Chen and
Y.-C. Wu, J. Am. Chem. Soc., 2002, 124, 3508; (c) C.-T. Chen, J.-S. Lin,
J.-H. Kuo, S.-S. Weng, T.-S. Cuo, Y.-W. Lin, C.-C. Cheng,
Y.-C. Huang, J.-K. Yu and P.-T. Chou, Org. Lett., 2004, 6, 4471; (d)
C.-T. Chen, J.-H. Kuo, C.-H. Ku, S.-S. Weng and C.-Y. Liu, J. Org.
Chem., 2005, 70, 1328; (e) C.-T. Chen, J.-H. Kuo, V. D. Pawar,
Y. S. Munot, S.-S. Weng, C.-H. Ku and C.-Y. Liu, J. Org. Chem., 2005,
70, 1188.
10 Y. A. Wang, J. J. Li, J. Chen and X. Peng, J. Am. Chem. Soc., 2002,
124, 2293.
11 M. Mammen, S. K. Choi and G. M. Whitesides, Angew. Chem., Int.
Ed., 1998, 37, 2754.
12 (a) J. E. B. Katari, V. L. Colvin and A. P. Alivisatos, J. Phys. Chem.,
1994, 98, 4109; (b) C. B. Murray, D. J. Norris and M. G. Bawendi,
J. Am. Chem. Soc., 1993, 115, 8706.
13 H. Skaff and T. Emrick, Chem. Commun., 2003, 52.
14 C. Zhang, S. O’Brien and L. Balogh, J. Phys. Chem. B, 2002, 106,
10316.
D2O).
564 nm, respectively. They are slightly red-shifted by 2 nm as
compared to those of pyridine-capped nanocrystals, presumably
due to slight increases in the overall size of the hybrids. The
evidence supporting the efficient attachment of thiols 5a and 5b to
the CdSe/ZnS surface comes from characteristic signal changes of
the –CH2CH2SH fragment in their (in CDCl3) and in the
nanohybrids’ (in D2O) 1H NMR spectra, Figs. 2 and 3. The
quartet at 2.78 and 2.72 ppm corresponds to –CH2CH2SH in 5a
and 5b, respectively. Peak broadening (usually observed after
attachment) and slight chemical shift changes (by 0.03 ppm) of the
methylene unit along with disappearance of the thiol proton
signals were observed for the corresponding nanohybrids.
The averaged extent of coverage was found to be greater than
82% with minor pyridine attachment as judged by the integration
values of the aromatic signals in their 1H NMR spectra in D2O.{
In addition, the nanoparticle size distributions for 6a and 6b
range from 4.0–4.8 and 3.1–3.8 nm, respectively, as evidenced by
high resolution transmission electron microscopy (HR–TEM)
measurements. The TEM images clearly indicate the crystallinity
15 B. S. Kim, L. Avila, L. E. Brus and I. P. Herman, Appl. Phys. Lett.,
2000, 76, 3715.
16 M. Green, N. Allsop, G. Wakefield, P. J. Dobson and J. L. Hutchison,
J. Mater. Chem., 2002, 12, 2671.
17 The differences in lmax are due to the use of two different batches of
pyridine-capped nanocrystals.
This journal is ß The Royal Society of Chemistry 2005
Chem. Commun., 2005, 2483–2485 | 2485