Encapsulation and stabilization of gold nanoparticles with "click" polyethyleneglycol dendrimers

Article abstract of DOI:10.1021/ja909133f

Water-soluble arene-cored "clicked" and non-"clicked" dendrimers terminated by 27, 81, and 243 triethyleneglycol (TEG) tethers (respectively generations G0, G1, and G2) have been synthesized and shown to form dendrimer-encapsulated gold nanoparticles (DEA

Full text of DOI:10.1021/ja909133f

Published on Web 02/04/2010
Encapsulation and Stabilization of Gold Nanoparticles with
“Click” Polyethyleneglycol Dendrimers
Elodie Boisselier,† Abdou K. Diallo,† Lionel Salmon,‡ Ca´tia Ornelas,† Jaime Ruiz,†
and Didier Astruc*,†
Institut des Sciences Mole´culaires, UMR CNRS No 5255, UniVersite´ Bordeaux 1, 33405 Talence
Cedex, France, and Laboratoire de Chimie de Coordination, UPR CNRS No 8241,
205 Route de Narbonne, 31077 Toulouse Cedex 04, France
Received October 27, 2009; E-mail: d.astruc@ism.u-bordeaux1.fr
Abstract: Water-soluble arene-cored “clicked” and non-“clicked” dendrimers terminated by 27, 81, and
243 triethyleneglycol (TEG) tethers (respectively generations G0, G1, and G2) have been synthesized and
shown to form dendrimer-encapsulated gold nanoparticles (DEAuNPs) and dendrimer-stabilized gold
nanoparticles (DSAuNPs). The dendrimers have been characterized by IR, 1H NMR, 13C NMR, size-exclusion
chromatography, elemental analysis, MALDI-TOF mass spectroscopy, DOSY NMR, and dynamic light
scattering. The AuNPs have been generated and stabilized by these PEGylated dendrimers using a variety
of reduction modes, including NaBH4 in methanol, various single-electron metallocene-type reductants,
and even in the absence of additional reductants. The active role of the “clicked” triazole rings, dendrimer
generation, stoichiometry of Au precursor, and nature of the reductant and of the solvent are delineated,
leading to DSAuNPs with the G0 dendrimer and smaller DEAuNPs with the G1 and G2 dendrimers.
Altogether, AuNPs in the size range from 1.8 to 42 nm were formed and characterized by transmission
electron microscopy (TEM), high resolution TEM (HRTEM) and UV-vis spectroscopy. Both 1,2,3-triazole
and PEGylated Percec-type dendrons are required in the dendrimer structure for the stabilization of AuNPs
upon NaBH4 reduction of HAuCl4 in methanol. On the other hand, in the absence of other reductant in
water, only PEGylated Percec-type dendrons in dendrimers were found to be indispensable, because of
their semicavitand shape, for the spontaneous reduction of HAuCl4 and stabilization of DSAuNPs.
Introduction
“green” conditions and have shown that the dendrimer plays
the role of a nanoreactor and nanofilter.8 In particular, NP
Substrate encapsulation by dendrimers1 is a major property
of dendrimer chemistry that has potential applications in
catalysis,2 photophysics,3 materials science4 and nanomedicine.5
One of the most remarkable examples of dendritic encapsulation
is that of transition-metal nanoparticles (NPs) that was disclosed
more than a decade ago using polyamidoamine (PAMAM)
dendrimers,6 then polypropyleneimine (PPI) dendrimers.7 Crooks
and his group,8 among others,7–9 have demonstrated the
enormous potential of this concept in catalysis under various
encapsulation has been applied to many transition metals
including the use of a redox reaction between a NP and other
metal cations.2 However, the studies of dendrimer-encapsulated
NPs (DENs) have essentially concerned the PAMAM and PPI
dendrimer families that are commercial, with the main exception
(4) (a) Newkome, G. R.; Yao, Z.; Baker, G. R.; Gupta, V. K. J. Org.
Chem. 1985, 50, 2003–2004. (b) Jansen, J. F. G. A.; de Brabander-
van den Berg, E. M. M.; Meijer, E. W. Science 1994, 266, 1226–
1229. (c) Moorefield, C. N.; Newkome, G. R. C. R. Chimie 2003, 6,
715–724. (d) Schenning, A. P. H.; Meijer, E. W. Chem. Commun.
2005, 3245–3258. (e) Hahn, U.; Cardinali, F.; Nierengarten, J.-F. New
J. Chem. 2007, 31, 1128–1138. (f) Hwang, S.-H.; Shreiner, C. D.;
Moorefield, C. N.; Newkome, C. N. New J. Chem. 2007, 31, 1192–
1217. (g) Knecht, M. R.; Crooks, R. M. New J. Chem. 2007, 31, 1349–
1353.
† Institut des Sciences Mole´culaires.
‡ Laboratoire de Chimie de Coordination.
(1) (a) Newkome, G. R.; Moorefield, C. N.; Vo¨gtle, F. Dendrimers and
Dendrons. Concepts, Syntheses, Applications; Wiley-VCH: Weinheim,
2001. (b) Dendrimers and Other Dendritic Polymers; Tomalia, D. A.,
Fre´chet, J. M. J., Eds.; Wiley: Amsterdam, 2003. (c) Dendrimers and
Nanosciences; Astruc, D., Chimie, C. R., Eds.; Elsevier: Paris, 2003;
Vol. 6. (d) Vo¨gtle, F.; Richardt, G.; Werner, N. Dendrimer Chemistry:
Concepts, Syntheses, Properties, Applications; Wiley: Weinheim, 2009.
(2) (a) Crooks, R. M.; Zhao, M.; Sun, L.; Chechik, V.; Yeung, L. K. Acc.
Chem. Res. 2001, 34, 181–190. (b) Scott, R. W. J.; Wilson, O. M.;
Crooks, R. M. J. Phys. Chem. B 2005, 109, 692–704. (c) Helms, B.;
Fre´chet, J. M. J. AdV. Syn. Catal. 2006, 348, 1125–1148. (d) Chandler,
B. D.; Gilbertson, J. D. Top. Organomet. 2006, 20, 97–120.
(3) (a) Juris, A.; Balzani, V.; Barrigelletti, F.; Campagna, S.; Denti, G.;
Juris, A.; Serroni, S.; Venturi, M. Acc. Chem. Res. 1998, 31, 26–34.
(b) Andronov, A.; Fre´chet, J. M. J. Chem. Commun. 2000, 1701–
1710. (c) Hecht, S.; Fre´chet, J. M. J. Angew. Chem., Int. Ed. 2001,
40, 74–91. (d) Ceroni, P.; Bergamini, G.; Marchioni, F.; Balzani, V.
Prog. Polym. Sci. 2005, 30, 453–473.
(5) (a) Liu, M.; Kono, K.; Fre´chet, J. M. J. Controlled Release 2000, 85,
85–90. (b) Boas, U.; Heegaard, P. M. H. Chem. Soc. ReV. 2004, 33,
43–63. (c) Svenson, S.; Tomalia, D. A. AdV. Drug DeliVery ReV. 2005,
57, 2106–2129. (d) Patri, A. K.; Kukowska-Latallo, J. F.; Baker, J. R.,
Jr. AdV. Drug. DeliV. ReV. 2005, 57, 2203–2214. (e) Duncan, R.; Izzo,
L. AdV. Drug. DeliV. ReV. 2005, 57, 2215–2237. (f) D’Emanuele, A.;
Attwood, D. AdV. Drug DeliVery ReV. 2005, 57, 2147–2162. (g)
Grinstaff, J. J. Polym. Sci., Part A: Polym. Chem. 2008, 46, 383–400.
(h) Dendrimer based nanomedicine; Majoros, I. J., Baker, J. R., Jr.
Eds.; Pan Stanford Publishing: Stanford, 2008. (i) Fox, M. E.; Szoka,
F. C.; Tekade, R.; Kumar, P. V.; Jain, N. K. Chem. ReV. 2009, 109,
49–87. (j) Fre´chet, J. M. J. Acc. Chem. Res. 2009, 42, 1141–1151.
(6) (a) Zhao, M.; Sun, L.; Crooks, R. M. J. Am. Chem. Soc. 1998, 120,
4877–4878. (b) Balogh, L.; Tomalia, D. A. J. Am. Chem. Soc. 1998,
120, 7355–7356.
9
10.1021/ja909133f © 2010 American Chemical Society
J. AM. CHEM. SOC. 2010, 132, 2729–2742 2729

A R T I C L E S
Boisselier et al.
of Yamamoto’s phenylazomethine dendrimers whose rigidity
brings about new specific features for properties of phenyla-
zomethine-DENs in materials science.9
AuNPs using polyethyleneglycol-terminated dendrimers,17 be-
cause of their biocompatibility17 and the applications of AuNPs
in nanomedicine.18
It has recently been shown that dendrimers assembled by click
chemistry10 can coordinate and electrochemically recognize
various transition-metal cations,11 and that such palladodendritic
complexes can be reduced to DEPdNPs that have remarkable
catalytic properties.12 Such a strategy does not work in the same
way for an approach to arene-cored DEAuNPs,13 and the
investigation toward a rationalization of the syntheses toward
this goal is presented and generalized here. Besides encapsula-
tion, exodendrimer stabilization is also well-known,14 and this
alternative has also been searched with arene-cored dendrimers15
constructed using a Newkome-type 1 f 3 connectivity.16
Moreover, our goal was to stabilize and inter alia encapsulate
A major finding in this work is that Percec-type triethyleneg-
lycol (TEG) tethers19 are not only tolerated for the synthesis of
DEAuNPs and DSAuNPs but they are even required for this
purpose in this new arene-cored dendrimer series, and under
certain circumstances they allow the AuNP formation. The key
additional role of the intradendritic 1,2,3-triazole rings, formed
by “click” reaction, on the AuNP formation and stabilization is
also shown.
Results
The synthesis of two series of arene-cored, PEG terminated
dendrimers of three generations has been carried out. For both
series, the dendrimer syntheses start by CpFe+-induced nona-
allylation of mesitylene15 followed by photolytic decomplex-
ation20 and Newkome-type 1 f 3 connectivity.16 The first series
of dendrimers was synthesized using “click” chemistry (den-
drimers 4, 5 and 6, Scheme 1), and the other one using the
Williamson reaction (dendrimers 9, 10 and 11, Scheme 2) in
order to graft PEG dendrons at the periphery of the dendrimers.
The AuNPs are stabilized by these PEGylated dendrimers,
synthesized by “click” chemistry (4, 5 and 6), in methanol using
NaBH4 as the reductant. The PEG-terminated (dendronized)
dendrimers (4-6 and 9-11) also allowed the reduction of AuIII
to Au0 in water without the presence of an additional reductant.
The shape and the size of the AuNPs have been studied by
UV-vis spectroscopy and transmission electron microscopy
(TEM) and the kinetics of formation and size variations of the
(7) (a) Yeung, L. K.; Crooks, R. M. Nano Lett. 2001, 1, 14–17. (b) Rahim,
E. H.; Kamounah, F. S.; Frederiksen, J.; Christensen, J. B. Nano Lett.
2001, 1, 499–503. (c) Li, Y.; El Sayed, M. A. J. Chem. Phys. B 2001,
105, 8938–8946. (d) Oee, M.; Murata, M.; Mizugaki, T.; Ebitani, K.;
Kaneda, K. Nano Lett. 2002, 2, 999–1002. (e) Pittelkow, M.; Moth-
Poulsen, K.; Boas, U.; Christensen, J. B. Langmuir 2003, 19, 7682.
(f) Chung, Y.; Rhee, H. K. J. Mol. Catal. A 2003, 206, 291–298. (g)
Ooe, M.; Murata, M.; Mizugaki, T.; Ebitani, K. J. Am. Chem. Soc.
2004, 126, 1604–1608. (h) Lemo, J.; Heuze, K.; Astruc, D. Inorg.
Chim. Acta 2006, 359, 4909–4911.
(8) (a) Zhao, M.; Crooks, R. M. Angew. Chem., Int. Ed. 1999, 38, 364–
366. Sun, L.; Crooks, R. M. Langmuir 2002, 18, 8231–8236. (b) Scottt,
R. W. J.; Datye, A. K.; Crooks, R. M. J. Am. Chem. Soc. 2003, 125,
3708–3709. (c) Scott, R. W.; Wilson, O. M.; Oh, S.-K.; Kenik, E. A.;
Crooks, R. M. J. Am. Chem. Soc. 2004, 126, 15583–15591. (d) Wilson,
O. M.; Scott, R. W. J.; Garcia-Martinez, J. C.; Crooks, R. M. J. Am.
Chem. Soc. 2005, 127, 1015–1024. (e) Scott, R. W. J.; Sivadirana-
rayana, C.; Wilson, O. M.; Yan, Z.; Goodman, D. W.; Crooks, R. M.
J. Am. Chem. Soc. 2005, 127, 1380–1381. (f) Gomez, M. V.; Guerra,
J.; Velders, A. H.; Crooks, R. M. J. Am. Chem. Soc. 2008, 131, 341–
350. (g) Feng, Z. V.; Lyon, J. L.; Croley, J. S.; Crooks, R. M.; Vanden
Bout, D. A.; Stevenson, K. J. J. Chem. Educ. 2009, 86, 368–372.
(9) (a) Higushi, M.; Shiki, S.; Ariga, S.; Yamamoto, K. J. Am. Chem.
Soc. 2001, 123, 4414–4420. (b) Yamamoto, K.; Higushi, M.; Shiki,
S.; Tsuruta, M.; Chiba, H. Nature 2002, 415, 509–511. (c) Satoh, N.;
Cho, J. S.; Higushi, M.; Yamamoto, K. J. Am. Chem. Soc. 2003, 125,
8104–8105. (d) Higushi, M.; Shiki, S.; Yamamoto, K. Org. Lett. 2000,
2, 3079–3082. (e) Cho, J.-S.; Takanashi, K.; Higushi, M.; Yamamoto,
M. Syn. Metals 2005, 150, 79–82. (f) Nakashjima, T.; Satoh, N.;
Albrecht, K.; Yamamoto, K. Chem. Mater. 2008, 20, 2538–2543. (g)
Satoh, N.; Nakashima, T.; Kamikura, K.; Yamamoto, K. Nat.
Nanotechnol. 2008, 3, 106–111. (h) Yamamoto, K.; Takanashi, K.
Polymer 2008, 49, 4033–4041. (i) Nakamula, I.; Yamanoi, T.;
Yonezawa, T.; Imaoka, K.; Nishihara, H. Chem. Commun. 2008, 5716–
5718. (j) Vassilieff, T.; Sutton, A.; Kakkar, A. K. J. Mater. Chem.
2008, 18, 4031–4033. (k) Sutton, A.; Franc, G.; Kakkar, A. K. J.
Polym. Sci., Part A: Polym. Chem. 2009, 47, 4482–4493.
(14) (a) Esumi, K.; Suzuki, A.; Aihara, N.; Usui, K.; Torigoe, K. Langmuir
1998, 14, 3157–3159. (b) Yoshimura, T.; Fukai, J.; Mizutani, H.;
Esumi, K. J. Colloid Interf. Sci. 2002, 255, 428–431. (c) Esumi, K.;
Akiyama, S.; Yoshimura, T. Langmuir 2003, 19, 7679–7681.
(15) (a) Sartor, V.; Djakovitch, L.; Fillaut, J.-L.; Moulines, F.; Neveu, F.;
Marvaud, V.; Guittard, J.; Blais, J.-C.; Astruc, D. J. Am. Chem. Soc.
1999, 121, 2929–2930. (b) Ruiz, J.; Lafuente, G.; Marcen, S.; Ornelas,
C.; Lazare, S.; Blais, J.-C.; Cloutet, E.; Astruc, D. J. Am. Chem. Soc.
2003, 125, 7250–7257. (c) Ornelas, C.; Ruiz, J.; Belin, C.; Astruc, D.
J. Am. Chem. Soc. 2009, 131, 590–601.
(16) (a) Newkome, G. R.; Moorefield, C. N. Aldrichimica Acta 1992, 25,
31–38. (b) Newkome, G. R. Pure Appl. Chem. 1998, 70, 2337–2343.
(c) Moulines, F.; Djakovitch, L.; Boese, R.; Gloaguen, B.; Thiel, W.;
Fillaut, J.-L.; Delville, M.-H.; Astruc, D. Angew. Chem., Int. Ed. Engl.
1993, 32, 1075–1077. (d) Nlate, S.; Ruiz, J.; Blais, J.-C.; Astruc, D.
Chem. Commun. 2000, 417–418.
(17) (a) Liu, M.; Kono, K.; Fre´chet, J. M. J. Polym. Sci. A 1999, 37, 3492–
3503. (b) Liu, M.; Kono, K.; Fre´chet, J. M. J. Controlled Release
2000, 65, 121–131. (c) Duncan, R. Nat. ReV. Drug. DiscoVery 2003,
2, 347–360.
(10) (a) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B.
Angew. Chem., Int. Ed. 2002, 41, 2596–2599. (b) Tornoe, C. X. W.;
Christensen, C.; Meldal, M. J. Org. Chem. 2002, 67, 3057–3064. (c)
Feldman, A. K.; Nugent, A. K.; Hawker, C. J.; Scheel, A.; Voit, B.;
Pyun, J.; Fre´chet, J. M. J.; Sharpless, K. B. Angew. Chem., Int. Ed.
2004, 43, 3928–3932Reviews: (d) Kolb, H. C.; Finn, M. G.; Sharpless,
K. B. Angew. Chem., Int. Ed. 2001, 40, 2004–2021. (e) Bock, V. D.;
Hiemstra, H.; van Maarseveen, J. H. Eur. J. Org. Chem. 2006, 51–
68. (f) Wu, P.; Meldal, M.; Tornoe, C. W. Chem. ReV. 2008, 10, 2952–
3015.
(18) (a) Katz, E.; Willner, I. Angew. Chem., Int. Ed. 2004, 43, 6042–6108.
(b) Dreshler, U.; Erdogan, B.; Rotello, V. M. Chem.sEur. J. 2004,
10, 5570–5579. (c) Paciotti, G. F.; Myer, L.; Weinreich, D. Drug DeliV.
2004, 11, 169–183. (d) Daniel, M.-C.; Astruc, D. Chem. ReV. 2004,
104, 293–346. (e) Jain, P.; El-Sayed, I.-H.; El-Sayed, M. A. Nanotoday
2007, 2, 18–29. (f) Murphy, C. J.; Gole, A. M.; Hunyadi, S. E.; Stone,
J. W.; Sisco, P. N.; Alkilany, A.; Kinard, B. E.; Hankins, P. Chem.
Commun. 2008, 544–557. (g) Lal, S. L.; Clare, S. E.; Halas, N. J.
Acc. Chem. Res. 2008, 41, 1842–1851. (h) Boisselier, E.; Astruc, D.
Chem. Soc. ReV. 2009, 38, 1759–1782.
(11) (a) Ornelas, C.; Ruiz, J.; Cloutet, E.; Alves, S.; Astruc, D. Angew.
Chem., Int. Ed. 2007, 46, 872–877. (b) Camponovo, J.; Ruiz, J.;
Cloutet, E.; Astruc, D. Chem., Eur. J. 2009, 15, 2990–3002. (c) Astruc,
D.; Daniel, M.-C.; Ruiz, J. Chem. Commun. 2004, 2637–2649. (d)
Bade`che, S.; Daran, J.-C.; Ruiz, J.; Astruc, D. Inorg. Chem. 2008,
47, 4903–4908.
(19) (a) Percec, V.; Johansson, G.; Ungar, G.; Zhou, J. J. Am. Chem. Soc.
1996, 118, 9855–9866. (b) Balagurusamy, V. S. K.; Ungar, G.; Percec,
V.; Johansson, G. J. Am. Chem. Soc. 1997, 119, 1539–1555. (c) Percec,
V.; Smidrkal, J.; Peterca, M.; Mitchell, C. M.; Nummelin, S.; Dulcey,
A. E.; Sienkowska, M. J.; Heiney, P. A. Chemistry 2007, 13, 3989–
4007. (d) Percec, V.; Peterca, M.; Dulcey, A. E.; Imam, M. R.; Hudson,
S. D.; Nummelin, S.; Adelman, P.; Heiney, P. A. J. Am. Chem. Soc.
2008, 130, 13079–13094.
(12) (a) Ornelas, C.; Salmon, L.; Ruiz, J.; Astruc, D. Chem.sEur. J. 2008,
14, 50–64. (b) Ornelas, C.; Salmon, L.; Ruiz, J.; Astruc, D. Chem.
Commun. 2007, 4946–4948. (c) Diallo, A. K.; Ornelas, C.; Salmon,
L.; Ruiz, J.; Astruc, D. Angew. Chem., Int. Ed. 2007, 46, 8644–8648.
(d) Ornelas, C.; Ruiz, J.; Salmon, L.; Astruc, D. AdV. Syn. Catal. 2008,
350, 837–845.
(20) (a) Catheline, D.; Astruc, D. J. Organomet. Chem. 1983, 248, C9–
C12. (b) Catheline, D.; Astruc, D. J. Organomet. Chem. 1984, 272,
417–426.
(13) Boisselier, E.; Diallo, A. K.; Salmon, L.; Ruiz, J.; Astruc, D. Chem.
Commun. 2008, 4819–4821.
9
2730 J. AM. CHEM. SOC. VOL. 132, NO. 8, 2010

“Click” Polyethyleneglycol Dendrimers
A R T I C L E S
Scheme 1. Synthesis of the Three Generations of “Click” Dendrimers 4, 5 and 6
AuNPs have been examined when the number of equivalents
of HAuCl4 added per dendrimer was increased. The influence
of the nature of the reductant used in methanol, that is, NaBH4
or an electron-reservoir organometallic sandwich complex, was
also studied, and the role of the standard redox potential of the
reductant on the AuNP formation was finally scrutinized.
Overall, the synthesis of AuNPs stabilized or encapsulated by
PEGylated dendrimers is detailed.
1. Synthesis and Characterizations of Dendrimers 4, 5
and 6 Synthesized by “Click” Chemistry. The synthesis of three
generations of arene-cored dendrimers with 1f 3 connectivity
(4, 5 and 6) terminated with 27, 81 and 243 PEG tethers (G0 to
G2) is shown in Scheme 1. The dendritic precursors with 9
chloromethyl and azido groups were reported earlier.15 The
Newkome-type 1 f 3 connectivity16 was continued by the
Williamson reaction between the nonachloromethyl core and a
Percec-type dendron.19 This dendron was synthesized from a
modified gallic acid core functionalized at the focal point by a
tetraethyleneglycol (TAEG) linker, then by a propargyl group,
and on the peripheral tethers by triethylene glycol (TEG) termini
(3). Finally, the dendrons were linked to the core using the CuI-
catalyzed “click” reaction between the terminal alkyne tail and
the azido-terminated dendritic core.11 A stoichiometric amount
of CuI, generated using CuSO4 and sodium ascorbate, has been
9
J. AM. CHEM. SOC. VOL. 132, NO. 8, 2010 2731

A R T I C L E S
Boisselier et al.
Figure 1. Size Exclusion Chromatography of the three generations of the
“click” dendrimers 4-6 containing polyethyleneglycol tethers (PDI ) 1.02
( 0.01).
Figure 3. DOSY NMR spectrum of the dendrimer 4. D ) 1.16 ((0.1) ×
10-10 m2/s, Rh ) 4.9 ((0.1) nm. D, diffusion coefficient; Rh, hydrodynamic
radius.
at M+: calcd 7311.54; found: 7334.47 (MNa+). DOSY NMR
and dynamic light scattering provide consistent data for the
dendrimers 10 and 11, both methods giving a diameter values
of 13 ( 1.2 nm for 10 and 15 ( 1.5 nm for 11. For the
dendrimer 9, DOSY NMR yielded a diameter value of 8 ( 0.6
nm (ESI).
3. AuNPs Synthesized using NaBH4 and Stabilization in
Methanol by the “Click” Dendrimers 4, 5 and 6. The AuNPs
were synthesized by reaction between the “click” dendrimers
4, 5 and 6, and a stoichiometric amount of HAuCl4 vs. the
dendrimer triazole groups, followed by NaBH4 reduction in
methanol. This stoichiometry was selected, because we believed
that the AuNPs formed would contain a number of atoms equal
to the number of triazole rings in the dendrimer, as with PdNPs.
It also allows comparisons between the various procedures used
throughout this study. Later, the amount of HAuCl4 was also
increased, in order to examine its influence on the AuNP size.
The UV-vis spectrum shows a plasmon band at 540 nm for
the dendrimer 4-stabilized AuNPs, but this band is absent
in the spectrum of the AuNPs stabilized by the higher-generation
dendrimers 5 and 6 (Figure 4). The transmission electron
microscopy (TEM) data confirm this trend (Figure 5) showing
that the dendrimer 4-stabilized AuNPs are larger than the
dendrimer (4.1 ( 0.5 nm) and cannot be encapsulated in such
a small dendrimer that contains only 27 tethers. Thus, several
dendrimers 4 are surrounding each AuNP (Figure 6). On the
other hand, the larger dendrimers 5 and 6 containing respectively
81 and 243 TEG tethers encapsulate AuNPs of small size (1.9
( 0.4 nm). Dendrimer 4 has an open structure, and any AuNPs
formed therein will start to come out and aggregate into larger
AuNPs, while dendrimers 5 and 6 will engulf any forming
AuNPs.
Figure 2. MALDI-TOF mass spectrum of the dendrimer 4. Calcd for
C414H741O153N27Si9: 8798; found: 8821.25 (MNa).
used, because dendritic metal encapsulation considerably slows
down the click reaction or inhibits it,11,21 especially with large
dendrimers. The dendrimers of generation 0 (4, 27 TEG termini)
to 2 (6, 243 TEG termini) were synthesized in this way in nearly
quantitative yields (92-95%), and characterized by IR, 1H and
13C NMR, size exclusion chromatography (4, 5 and 6, Figure
1), correct elemental analysis (4), and MALDI TOF (4, major
peak at MNa+: calcd 8820.91; found: 8821.24, Figure 2). DOSY
NMR and dynamic light scattering give consistent data for
dendrimers 4 and 5, both methods giving a diameter values of
9 ( 1 nm for 4 and 18 ( 2 nm for 5. For the dendrimer 6, light
scattering provides a diameter value of 20 ( 2 nm (Figure 3,
see also the Supporting Information, ESI).
2. Synthesis and Characterizations of Dendrimers 9, 10
and 11 by the Williamson Reaction. The syntheses of three
generations of the arene-cored, TEG-terminated dendrimers 9,
10 and 11 with 27, 81 and 243 TEG dendrimers (G0 to G2) are
shown in Scheme 2. They start with the same steps as for the
syntheses of dendrimers 4, 5 and 6 (see Scheme 1) until the
hydrosilylation step. Then, reaction of the dendrimer core
terminated by chloromethylsilyl groups with NaI yields the
nonaiodomethylsilyl core (7). The Percec-type dendron is
functionalized at the focal point by a hydroquinone linker in
order to introduce a phenol terminus (8). Finally, the dendrons
are linked to the core using a Williamson reaction between the
terminal phenol tail and the iodomethylsilyl-terminated dendritic
core. The dendrimers 9, 10 and 11 of generation 0 (9, 27 TEG
termini) to 2 (11, 243 TEG termini) were synthesized in this
way and characterized by IR, 1H and 13C NMR, size exclusion
chromatography (9, 10 and 11), MALDI TOF (9, major peak
4. Attempts to Stabilize AuNPs in Methanol by Other
Dendrimers. The syntheses and stabilization of AuNPs using a
stoichiometric amount of HAuCl4 per triazole or Percec-type
dendron and NaBH4 reduction in methanol was attempted using
six others dendrimers. Three of them, that were reported
earlier,12a only contain triazole groups and do not contain any
PEG (12, 13 and 14), and the three others only contain PEG
but no triazole groups (9, 10 and 11).15b “Click” dendrimers
with 27 and 81 allyl tethers (13 and 14) and a “click” dendrimer
with 27 phenyl tethers (12) were used (Chart 1).
(21) Candelon, N.; Laste´coue`res, D.; Diallo, A. K.; Ruiz, J.; Astruc, D.;
Vincent, J.-M. Chem. Commun. 2008, 741–743.
(22) (a) Komeda, S.; Lutz, M.; Speck, A. L.; Yamanaka, Y.; Sato, T.;
Chikuma, M.; Reedijk, J. J. Am. Chem. Soc. 1997, 119, 2588. (b)
Barz, M.; Herdtweck, E.; Thiel, W. R. Angew. Chem., Int. Ed. 1998,
37, 2262–2265. (c) Chan, T. R.; Holgraf, R.; Sharpless, K. B.; Fokin,
V. V. Org. Lett. 2004, 6, 2853–2856.
The procedure used for the addition and reduction of HAuCl4
in these dendrimers was the same one as that previously
described using a stoichiometric amount of HAuCl4 vs the
dendrimer triazole groups. When NaBH4 in methanol was added,
9
2732 J. AM. CHEM. SOC. VOL. 132, NO. 8, 2010

“Click” Polyethyleneglycol Dendrimers
A R T I C L E S
Scheme 2. Syntheses of the Three Generations of Dendrimers 9, 10 and 11 by the Williamson Reactions
the AuNPs were formed, but they precipitated after a few
minutes, and AuNPs could never be stabilized (although PdNP
could be stabilized19).
immediately precipitated when NaBH4 in methanol was added,
and no AuNP could be obtained.
These six experiments support the fact that the presence of
both the PEG and triazole groups in the dendrimers 4, 5 and 6
are essential for the stabilization of AuNPs in methanol, when
NaBH4 is used as the reductant.
5. AuNP Size Variation upon Change of HAuCl4
Stoichiometry in Methanol. The size variation of the AuNPs
synthesized using NaBH4 in methanol was observed in the case
of AuNP stabilization with the dendrimer 5 upon change of
The dendrimers 9, 10 and 11 containing respectively 27, 81
and 243 PEG tethers but no triazole ligand were used for
comparison (Scheme 2). The procedure used for the addition
and reduction of HAuCl4 in this dendrimer was the same as
previously described with 27, 81 and 243 equiv of Au per
dendrimer. The result was similar to that obtained with the above
dendrimers containing only triazole groups, that is, AuNPs
9
J. AM. CHEM. SOC. VOL. 132, NO. 8, 2010 2733

A R T I C L E S
Boisselier et al.
linearly with the number of HAuCl4 equiv added before reaching
a plateau at approximately 11 nm (Figure 7). This maximum
size is expected, because the AuNPs are stabilized with the
dendrimer 5 in an intradendritic way (see section 2), and the
diameter of this dendrimer is confirmed by both DOSY NMR
and light scattering (18 ( 2 nm). When the number of
equivalents of HAuCl4 per triazole is larger than 10, excess Au0
immediately precipitates.
6. AuNP Synthesis in Water and Stabilization by
Dendrimers Terminated by Percec-Type PEG Dendrons in
the Absence of External Reductant. AuNPs were synthesized
according to a new protocol, without external reductant and in
aqueous dendrimer solution at room temperature. The AuNP
were formed by reaction between the TEGylated dendrimers
and a stoichiometric amount of HAuCl4 per PEG dendron in
water in the dark (i.e., 9 equiv of HAuCl4 per dendrimers 4
and 9, 27 per dendrimers 5 and 10 and 81 per dendrimers 6
and 11). The solution became red after a few minutes of stirring.
The synthesis of the AuNPs in the presence of dendrimers 9,
10 and 11 was faster than for the AuNPs obtained with “click”
dendrimers 4, 5 and 6. This reduction was followed by the
evolution of the AuNP plasmon band in UV-vis spectroscopy.
For example, the synthesis of the AuNPs with the dendrimer 9
Figure 4. UV-Vis spectra of AuNPs stabilized by several dendrimers 4
and encapsulated by dendrimers 5 and 6.
stoichiometry of the HAuCl4 precursor. TEM images were
recorded (Figure 6) for an increase of the equiv. number of
added HAuCl4 from 1 to 20 AuIII per intradendritic triazole
ligand. All the AuNPs obtained are spherical, and their size is
very homogeneous. Moreover, a high resolution TEM was
recorded for 7 equiv of AuIII per triazole, in order to observe
the crystalline structure of the AuNP (Figure 6, G). The increase
of the number of equiv. HAuCl4 per triazole leads to a variation
of the diameter of the AuNPs from 1.9 ( 0.2 nm (1 equiv of
AuIII per triazole) to 11.3 ( 1 nm (20 equiv of AuIII per triazole).
From 1 to 10 equiv of AuIII per triazole, the AuNP size varies
Figure 5. (a) Dendrimer 4/AuNPs: TEM image and size distribution. (b) Dendrimer 5/AuNPs: TEM image and size distribution. (c) Dendrimer 6/AuNPs:
TEM image and size distribution.
9
2734 J. AM. CHEM. SOC. VOL. 132, NO. 8, 2010

“Click” Polyethyleneglycol Dendrimers
A R T I C L E S
Figure 6. (A) Dendrimer 5 + 1 equiv of HAuCl4 per triazole, diameter ) 1.9 ((0.2) nm; (B) dendrimer 5 + 3 equiv of HAuCl4 per triazole, diameter )
3.8 ((0.4) nm; (C) dendrimer 5 + 5 equiv of HAuCl4 per triazole, diameter ) 5.3 ((0.5) nm; (D) dendrimer 5 + 7 equiv of HAuCl4 per triazole, diameter
) 6.8 ((0.7) nm; (E) dendrimer 5 + 10 equiv of HAuCl4 per triazole, diameter ) 11.0 ((1) nm; (F) dendrimer 2 + 20 equiv of HAuCl4 per triazole,
diameter ) 11.3 ((1) nm; (G) HRTEM of dendrimer 5 + 7 equiv of HAuCl4 per triazole.
was completed in 3.5 h, whereas that with the dendrimer 5 was
completed in one day in order to achieve complete reduction
(Figure 8).
The sizes of these AuNPs are much larger than those observed
with the first protocol with NaBH4 in methanol. The presence
of Percec-type PEG tethers in these dendrimers is required for
the reduction and the stabilization of AuNPs in water.
For all the experiments, the UV-vis spectrum shows a
plasmon band between 530 and 570 nm depending on the cases
(see the examples with the dendrimers 9, 10 and 11 in Figure
9). This means that all the observed AuNPs have a diameter
larger than 3 nm. The transmission electron microscopy (TEM)
data confirm this trend (see ESI), showing that the dendrimer
9-stabilized AuNPs have a diameter of 23 ( 0.5 nm, the
dendrimer 10-stabilized AuNPs have a diameter of 34 ( 1 nm
and the dendrimer 11-stabilized AuNPs have a diameter of 36
( 0.5 nm.
The various generations of “click” dendrimers 4, 5 and 6 give
the same AuNP diameters as dendrimers 9, 10 and 11. Indeed,
the dendrimer 4-stabilized AuNPs have a diameter of 22 ( 0.5
nm, the dendrimer 5-stabilized AuNPs have a diameter of 33
( 0.5 nm, and the dendrimer 3-stabilized AuNPs have a
diameter of 36 ( 1 nm (see ESI). This leads to a characteristic
size for each generation of dendrimers containing or not triazole
groups, and in these syntheses only the reaction time changes.
Several tests were performed with the two PEGylated Percec-
type dendrons 3 and 8 (used to synthesize the PEGylated
dendrimers), and the PEG polymer 15 (mass molar: 5000 g
mol-1) (Chart 2). Mixing 3, 8 or 15 with HAuCl4 in water did
not result in any color change of the yellow aqueous solution
after several days nor any change in the UV-vis spectrum.
Thus, reduction of AuNPs did not proceed in these cases, in
sharp contrast to what was observed with the PEGylated
dendrimers under the same conditions. This shows that a
PEGylated dendron or PEG polymer is not sufficient to reduce
HAuCl4 in water, but that the PEGylated dendron must be
embedded within the dendritic structure to become efficient for
this process.
To further examine the frontier of the feasibility of HAuCl4
reduction and AuNP stabilization in water in the absence of
external reductant, we synthesized the dendrimer 16 by “click”
reaction between the 27-azido dendrimer precursor of 5 and
9
J. AM. CHEM. SOC. VOL. 132, NO. 8, 2010 2735

A R T I C L E S
Boisselier et al.
Chart 1. Structure of the Known Dendrimers 12-14 that Do Not Contain PEG Termini and Stabilize PdNPs12a but Not AuNPs.
Chart 2. PEG Dendrons and Polymer that Do Not Undergo AuNP Formation from HAuCl4 in Water in the Absence of External Reductant,
Unlike the PEGylated Dendrimers 4-6 and 9-11
propargyltetraethylene glycol (instead of the dendron 3 used
for the synthesis of 6; compare Chart 3 with Scheme 2). The
structure of 16 is thus intermediate between those of the
PEGylated dendrimers 4 and 5, but with 27 linear (nonden-
dronic) tetraethyleneglycol tethers instead of PEGylated Percec-
type dendrons (Chart 3). In 16, the branching point of the 1 f
3 connectivity is remote from the tetraethyleneglycol groups,
unlike in 4 and 5.
with the similar experiments carried with all the dendrimers
terminated by Percec-type PEG dendrons that produced red
AuNPs (Scheme 3).
Many transition-metal-1,2,3-triazole complexes are known
with a variety of coordination modes.11d,21 With ferrocenyl
“click” dendrons and ferrocenyl-terminated “click” dendrimers
related to 12-14, such intradendritic triazole complexation by
late transition-metal cations has also been shown by
electrochemistry11a and X-ray crystal structures.11d In the present
case, complexation of the triazole group of the dendrimer 4 has
been monitored by UV-vis spectroscopy before NaBH4 reduc-
tion to AuNPs (ESI), although the complexation mode is still
unknown, the possibilities being multifold in the literature.11d,21
It can be concluded that the driving force provided by the
linear TEG termini in 16 or by the open PEG structures 3, 8
and 15 of Chart 1 is insufficient to reduce AuIII. This shows
that it is the semicavitand-shaped Percec-type PEG, when it is
sterically constrained within the dendrimer frame, that is
Mixing this white crystalline dendrimer 16 with the yellow
aqueous solution of HAuCl4 resulted in a clear yellow solution
from which a pale yellow precipitate formed after 15 min,
whereas the solution became colorless. Addition of dichlo-
romethane and shaking the two phases recovered the clear
yellow aqueous solution of AuIII and the colorless organic phase
from which the dendrimer 16 was recovered quantitatively and
1
identified by H NMR. Extraction with dichloromethane ap-
parently breaks the weak triazole-AuIII bond, but no AuNPs
were formed in this process. This experiment is in sharp contrast
9
2736 J. AM. CHEM. SOC. VOL. 132, NO. 8, 2010

“Click” Polyethyleneglycol Dendrimers
A R T I C L E S
the dendrimers presumably occurs, before oxidative C-O
cleavage concomitant with AuIII reduction.
7. AuNPs Size Variation in Water upon Change of the
AuCl4 Stoichiometry. The AuNP size variation when HAuCl4
is reduced and the AuNPs stabilized by dendrimers 9, 10 and
11 in water is observed when the number of equivalents of added
HAuCl4 is multiplied by two and by five (i.e., 18 and 45 equiv
of Au for 9, 54 and 135 equiv of Au for 10, and 162 and 405
equiv of Au for 11). The TEM images were recorded (see ESI),
and the diameters of the AuNPs obtained were estimated (Table
1). The diameter of dendrimer 9-stabilized AuNPs varies from
23 ( 0.5 nm to 32 ( 1 nm, from 34 ( 1 nm to 38 ( 1 nm for
dendrimer 10-stabilized AuNPs and from 36 ( 0.5 nm to 42 (
1 nm for dendrimer 11-stabilized AuNPs.
8. AuNP Formation in Methanol upon HAuCl4 Reduction
by Organometallic “Electron-Reservoir” Complexes. The AuNP
precursor HAuCl4 was also reduced in methanol to AuNPs by
the organometallic electron-reservoir sandwich complexes,
[FeICp(η6-C6Me6)],24 ferrocene, ethynylferrocene and decam-
ethylferrocene that are single-electron reductants with various
redox potentials. In these cases, the AuNPs were synthesized
by reaction between the “click” dendrimer 5 and a stoichiometric
amount of HAuCl4 per dendrimer triazole group, followed by
reduction in methanol using the organometallic compound. The
TEM data (see ESI) show that the dendrimer 5-stabilized AuNPs
obtained using the organometallic compounds are much larger
than the AuNPs obtained by reduction using NaBH4 (1.9 ( 0.4
nm). Indeed, the AuNP diameter synthesized using ferrocene
is 38 ( 3 nm, with ethynylferrocene it is 30 ( 3 nm, with
decamethylferrocene it is 23 ( 2 nm, and with [FeICp(η6-
C6Me6)] it is 7 ( 1 nm. The high resolution TEM (Figure 10B)
shows the cubic crystalline structure of the AuNPs obtained
AuNP under these conditions using [FeICp(η6-C6Me6)] as the
reductant.
Figure 7. Size variation of AuNPs stabilized by the “click” dendrimer 6
G1-81-PEG in methanol upon reduction using NaBH4 in methanol.
Discussion
Dendrimers that contain both triazole rings and TEGylated
Percec-type dendrons are able to stabilize AuNPs in methanol,
but related dendrimers lacking one of these structural features
cannot stabilize AuNPs upon NaBH4 reduction of HAuCl4 in
this solvent. We already know from previous electrochemical11a
and X-ray structural studies11d that various late transition-metal
ions are coordinated by the intradendritic triazole ligands of
“click” dendrimers. Thus, in the present case, the triazole ligands
analogously serve to trap the AuIII ions inside the “click”
dendrimers, then stabilization of the reduced Au atoms in AuNPs
is provided by the nearby semicavitand formed by the TEGy-
Figure 8. UV-Vis spectra of AuNPs formed and stabilized by the
dendrimers 5 and 9 at different times.
responsible for reduction of HAuCl4 and stabilization of AuNPs.
The experiment with the nonclick PEGylated dendrimers 9-11
that also reduce HAuCl4 shows that the triazole ring is not
involved in the reduction, as also confirmed by the negative
result obtained with the dendrimer 16. When both the triazole
and dendronic Percec-type PEG are present in the dendrimer
structure, reduction of HAuCl4 still occurs, but more slowly than
in the absence of triazole, because of triazole complexation.
Some PEGs are known to complex and reduce AuIII to AuNPs,23
the mechanism involving oxidative cleavage of ether C-O
bonds by the strong oxidant AuIII.23f It appears here that the
dendronic nature of the Percec-type TEGs strongly favors this
process compared to linear tetraethylene glycol termini. Chelat-
ing or encapsulating oxygen atoms of crown ethers are much
more easily protonated than linear PEG,23c and ion pair
(23) (a) Liu, K. J. Macromolecules 1968, 1, 308–311. (b) Yanagida, S.;
Takahashi, K.; Okahara, M. Bull. Chem. Soc. Jpn. 1977, 50, 1386–
1390. (c) Warshawsky, A.; Kalir, R.; Deshe, A.; Berkovitz, H.;
Patchornik, A. J. Am. Chem. Soc. 1979, 101, 4249–4256. (d) Yokota,
K.; Matsumura, M.; Yamaguchi, K.; Takada, Y. Makromol. Chem.
Rapid Commun. 1983, 4, 721–724. (e) Adams, M. D.; Wade, P. W.;
Hancock, R. D. Talanta 1990, 37, 875–883. (f) Longenberger, L.;
Mills, G. J. Phys. Chem. 1995, 99, 475–478. Mathur, A. M.; Scranton,
A. B. Sep. Sci. Technol. 1995, 30, 1071–1086. (g) Sanai, Y.; Ono,
K.; Hidaka, T.; Takagi, M.; Cattrall, R. W. Bull. Chem. Soc. Jpn. 2000,
73, 1165–1169. (h) Elliott, B. J.; Scranton, A. B.; Cameron, J. H.;
Bowman, C. N. Chem. Mater. 2000, 12, 633–642. (i) Sakai, T.;
Alexandridis, P. J. Phys. Chem. B 2005, 109, 7766–7777.
-
formation den-PEGH+, AuCl4 or den-PEGH+, [AuCl3(OH]-
(24) (a) Hamon, J.-R.; Astruc, D.; Michaud, P. J. Am. Chem. Soc. 1981,
103, 758–766. (b) Green, J. C.; Kelly, M. R.; Payne, M. P.; Seddon,
E. A.; Astruc, D.; Hamon, J.-R.; Michaud, P. Organometallics 1983,
2, 211–218. (c) Desbois, M.-H.; Astruc, D.; Guillin, J.; Varret, F.;
Trautwein, A. X.; Villeneuve, G. J. Am. Chem. Soc. 1989, 111, 5800–
5809.
becomes possible,23c which accounts for intradendritic extraction
of HAuCl4 by the dendritic Percec-type PEG from the peripheral
aqueous medium. Finally, coordination/chelation of AuIII by
PEG oxygen atoms of the Percec-type dendron constrained in
9
J. AM. CHEM. SOC. VOL. 132, NO. 8, 2010 2737

A R T I C L E S
Boisselier et al.
Figure 9. UV-Vis spectra of AuNPs formed and stabilized by the dendrimers 9, 10 and 11.
Scheme 3. Dramatic Influence of the Dendronic Percec-type PEG in 4-6 on AuIII Reduction and AuNP Formation in Water without
Additional Reductant, Compared to a Linear TEG in 16
lated Percec-type dendrons. “Click” TEG-terminated dendrimer
stabilized AuNPs formed upon NaBH4 reduction in methanol,
but the generation dependence influenced the AuNP size and
mode of stabilization. DSAuNPs are formed with G0-27TEG,
and they are larger (4.1 nm) than the dendrimer and thus
surrounded by several dendrimers (Figure 11). On the other
hand, DEAuNPs are formed from the large G1-81TEG and G2-
243 TEG dendrimers. These findings were obtained using a 1:1
HAuCl4/triazole stoichiometry, but the AuNP size was steadily
increased when this stoichiometry was increased until a plateau
was reached at a 10:1 stoichiometry with G1-81TEG, indicating
that the AuNPs have become so large that they could no longer
be encapsulated. This shows the progressive transition between
DEAuNPs and DSAuNPs as well as the maximum size of
AuNPs that can be reached by this method.
Whereas AuNPs were easily formed from PAMAM and PIP
dendrimers by the pioneers in the area,6 it is surprising that
AuNPs could not be formed here by NaBH4 reduction in
methanol of AuIII complexes of arene-cored “clicked” dendrim-
ers in the absence of TEG termini. This is all the more striking
as our previous studies had shown that, using these same
dendrimers, PdNPs were formed and were shown to be very
active in the catalysis of alkene hydrogenation and C-C forming
reactions. This contrast might be due to the difference of
aggregation mechanism and rate between these two metals.
Also remarkable is the success to form these AuNPs when
the TEG termini were introduced as structural complement for
all the dendrimers studied here. It is thus likely that this
outstanding property of Percec-type TEG termini could be
extended to many other dendrimers. Another interesting distinc-
tion is the impossibility to form the dendrimer-stabilized AuNPs
by NaBH4 reduction of HAuCl4 in methanol when the arene-
cored TEG-terminated dendrimers do not contain the 1,2,3-
triazole ring whatever the generation (nonclick dendrimer series
9, 10 and 11). NaBH4 is currently believed to be a convenient
reductant of AuIII to form AuNPs (despite the undesired
formation of borides at the AuNP surface),24b but this study
demonstrates that it does not always work, probably because
in this precise case the reduction is too fast to be compatible
with stabilization of the AuNPs.
Even if NaBH4 fails to lead to the formation of AuNPs with
TEG-terminated dendrimers that do not contain a triazole ring,
however, the presence of Percec-type TEG termini is sufficient
to allow the formation of the AuNPs in water in this case in
the absence of reductant. The dendritic effect is required for
this property, as it is shown that nondendritic linear PEGs,
tripodal dendronic PEGs that are not incorporated in dendrimers,
and even a “click” dendrimer terminated by 27 linear (non
dendronic) TEG tethers does not have this property. AuIII is a
rather strong oxidant,25 but oxidation of nondendritic PEG is
endergonic and not sufficiently entropy-driven. On the other
hand, AuIII encapsulation achieved upon multiple proton coor-
dination by the oxygen atoms of the TEG semicavitands is
facilitated by the dendritic constraint, which brings about ion
pairing to trap AuIII with favorable entropy conditions for AuIII
reduction. Yet, the AuNP formation is slow in “click” den-
drimers terminated by Percec-type PEG dendrons, due to the
AuIII-triazole coordination that is distal from the dendronic PEG
reduction site. Either the requirement of a distal electron transfer
slows it down or the reversible AuIII-triazole coordination
renders AuIII less available at the dendronic PEG reduction site.
(25) Cotton, F. A.; Wilkinson, G.; Murillo, C. A.; Bochmann, M. AdVanced
Inorganic Chemistry, 6th ed.; John Wiley: New York,;
pp 1084-1086.
9
2738 J. AM. CHEM. SOC. VOL. 132, NO. 8, 2010

“Click” Polyethyleneglycol Dendrimers
A R T I C L E S
Chart 3. Structure of the Dendrimer 16 that Contain Linear (non-Percec-type) TEG Termini and Does Not Undergo AuNP Formation from
HAuCl4 in Water in the Absence of External Reductant
Table 1. Size Evolution of AuNPs Stabilized by Dendrimers 9, 10
or 11 in Water
dendrimer + number of equiv of Au per dendron
AuNP diameter (nm)
Dendrimer 9 + 1 equiv
Dendrimer 9 + 2 equiv
Dendrimer 9 + 5 equiv
Dendrimer 10 + 1 equiv
Dendrimer 10 + 2 equiv
Dendrimer 10 + 5 equiv
Dendrimer 11 + 1 equiv
Dendrimer 11 + 2 equiv
Dendrimer 11 + 5 equiv
23 ( 0.5
26 ( 1.0
32 ( 1.0
34 ( 1.0
36 ( 0.5
38 ( 1.0
36 ( 0.5
38 ( 1.0
42 ( 1.0
Figure 10. (A) TEM of the dendrimer 5 + 1 equiv of HAuCl4 reduced by
[FeICp(η6-C6Me6)]. (B) HRTEM of the dendrimer 5 + 1 equiv of HAuCl4
reduced by [FeICp(η6-C6Me6)].
The large size of the AuNPs formed by this process is due to
this very slow kinetics. This means that the AuNPs start growing
inside the dendrimers, and that these germs continue growing
outside the dendrimers owing to their large size by trapping
the Au atoms formed in the TEG semicavitands near the
dendrimer periphery. It is likely that, once the large AuNPs
grow, the native Au atoms do not form small stable DEAuNPs
inside the dendrimer, because the latter are not observed by
TEM.
Note that the AuNPs obtained by this method have the same
size whether or not they contain triazole ligands, confirming
that it is the TEG oxygen pseudocavities that play the main
role in the AuNP formation in this case rather that the triazole
ring. The DSAuNPs formed in this way are much larger than
those formed by NaBH4 reduction, because the driving force is
considerably larger with NaBH4 than with the TEG semicavitand
dendrimer termini.
It is surprising that, owing to the undesired boride impurities
formed at the AuNP surface of AuNPs synthesized using
NaBH4,18d no monoelectronic reductant has been probed to form
clean AuNPs. For biomedical applications, the AuNPs are
usually synthesized with the Turkevich method,26 because most
(although not all) of the temporary citrate stabilizers can be
removed to introduce the biomedical probe or target, and the
large AuNPs formed by this method allow monitoring an intense
9
J. AM. CHEM. SOC. VOL. 132, NO. 8, 2010 2739

A R T I C L E S
Boisselier et al.
PdNPs are all the larger as the driving force is weaker.29 This
is also what is found here with the series of monoelectronic
reductants, as the DSAuNPs formed are all the larger as the
standard oxidation potential of the reductant is more positive
(or less negative). Since the reactions of electron-reservoir
complexes are clean because, by definition, both the oxidized
and reduced forms are stable,24 it is possible to define the size
of the DSAuNPs between 7 nm (strong FeI monoelectronic
reductant) and 38 nm (weakest FeII monoelectronic reductant).
The standard potentials of these electron-reservoir complexes
are perfectly defined and can be easily tuned even with small
variations by change of the nature and number of ring substit-
uents of the transition-metal sandwich complex.30 This flexibility
allows to also finely tune the AuNPs size without inhibiting
the AuNP surface upon ligand coordination.
Concluding Remarks
This study shows the critical structural conditions for the
dendrimer-induced formation of DEAuNPs and DSAuNPs of
various sizes ranging from 1.8 to 42 nm. A variety of new
dendrimers synthesized using 1 f 3 connectivity with Percec-
type TEG termini provide ideal conditions for AuNP formations
from HAuCl4 either using NaBH4 as the reductant or without
external reductant. With NaBH4, it is also indispensable to use
“click” dendrimers terminated by Percec-type TEG dendrons
in order to introduce AuIII inside the dendrimer by coordination
to the triazole rings, which adequately modulates the nucleation.
On the other hand, in the absence of external reductant, AuIII-
triazole coordination slows down AuIII reduction, because the
distal Percec-type dendron itself is the reductant. The semicav-
itand effect is then crucial, as shown by the failure of AuIII
reduction using a “click” dendrimer terminated by a linear
tertraethylene glycol instead of a Percec-type TEG dendron.
DSAuNPs are formed with all the dendrimers from HAuCl4 in
this way in the absence of additional reductant (23 to 42 nm-
size depending on the generation but not on presence of triazole
in the dendrimer structure). Finally, choosing the AuCl4/
dendrimer stoichiometry can orient the size of the AuNPs
formed in these processes. Monoelectronic reductants have also
been used for the first time for the reduction of HAuCl4 to
AuNPs. Their outer-sphere reduction mechanism implies a much
slower reduction than with the inner-sphere reductant NaBH4,
and the size of the DSAuNP formed (between 7 and 38 nm) is
directly related to the standard oxidation potentials of the FeI
and FeII reductants. This provides the possibility to finely tune
the DSAuNP size.
Figure 11. (a) AuNPs stabilized by several dendrimers 4; (b) dendrimer
5-encapsulated AuNPs.
plasmon absorption. Also, whereas small AuNPs (< 5 nm) are
of great interest for efficient catalysis,27 large AuNPs are
important in nanomedicine, because the plasmon band (AuNP
> 3 nm) is an indispensable tool in this later area.18
(26) (a) Turkevitch, J.; Stevenson, P. C.; Hillier, J. Disc. Faraday Soc.
1951, 11, 55–75. (b) Turkevitch, J.; Kim, G. Science 1970, 169, 873–
879. (c) Watson, K. J.; Ngyuen, S. B. T.; Mirkin, C. A. J. Am. Chem.
Soc. 1999, 121, 462–463.
In the present study, the use of single-electron reductants
successfully leads to the formation of AuNPs that are much
larger than those formed using NaBH4 reduction. This is due
to the fact that the mechanism of NaBH4 reduction follows inner-
sphere electron transfer involving chloride elimination from
AuCl4-, whereas the mechanism of the single-electron reductants
involves outer-sphere electron transfer. As shown by the seminal
work of Henry Taube, inner-sphere mechanisms are consider-
ably superior to outer-sphere electron-transfer mechanisms in
terms of reaction kinetics.28 Again, slow reduction is well-known
to result in a prolonged aggregation process leading to large
NPs.26 Reetz has shown a linear correlation between the driving
force of carboxylate reductants and the PdNP size, that is, the
(27) (a) Haruta, M.; Kobayashi, T.; Sano, H.; Yamada, N. Chem. Lett. 1987,
405–410. (b) Haruta, M.; Tsuboda, S.; Kobayashi, T.; Kagehiama,
H.; Genet, M. J.; Demon, B. J. Catal. 1993, 144, 175–180. (c) Haruta,
M. CATTECH 2002, 6, 102–107. (d) Nanoparticles and Catalysis;
Astruc, D., Ed. Wiley-VCH: Weinheim, 2007.
(28) (a) Taube, H.; Myers, H.; Rich, R. L. J. Am. Chem. Soc. 1953, 75,
4118–4123. (b) Taube, H. Angew. Chem., Int. Ed. 1984, 23, 329–
340. (c) Taube, H. Electron-Transfer Reactions of Complex Ions in
Solution; Academic Press: New York, 1970.
(29) (a) Reetz, M. T.; Maase, M. AdV. Mater. 1999, 11, 773–777. (b) For
an insightful discussion, see Reetz, M. T. in ref 24, Chapter 8.
(30) (a) Connelly, N. G.; Geiger, W. E. Chem. ReV. 1996, 96, 877–910.
(b) Geiger, W. E. Organometallics 2007, 26, 5738–5765. (c) Astruc,
D. Bull. Soc. Chim. Jpn. 2007, 80, 1658–1671. (d) Astruc, D. New
J. Chem. 2009, 33, 1191–1206.
9
2740 J. AM. CHEM. SOC. VOL. 132, NO. 8, 2010

“Click” Polyethyleneglycol Dendrimers
A R T I C L E S
into a Schlenk flask, and dry DMF (30 mL) was added. K2CO3
(315 mg, 2.28 mmol) was added to the solution. The mixture was
stirred for 18 h at 80 °C under reflux. At the end of the reaction,
DMF was removed. The product was extracted with CH2Cl2,
washed with water, and purified by chromatography (CH2Cl2/
MeOH, (97:3). 205 mg of a yellow oil was obtained (65% yield).
1H RMN (CDCl3, 250 MHz): 3.35 (CH3O); 3.63 (CH2O); 4.11
(CH2O arom.); 4.83 (OCH2arom.); 6.59 (CH arom.); 6.87 (CH
arom.-OH); 13C NMR (CDCl3, 62 MHz): 152.82 (Cq-O-CH2),
152.19 ((Cq-OH),150.56 (Cq extern.-CH2-O), 137.87 (Cq middle-
CH2-O), 132.83 (CH2-Cq), 116.17 (CH arom.-Cq-O), 107.19 (CH
arom.-Cq-CH2), 71.93 (O-CH2-arom), 70.71 (O-CH2), 59.06 (O-
CH3). MALDI TOF: Calcd for C34H54O14: 686.35; found: 709.34
(MNa+). Anal. Calcd for C54H54O14: C 59.46, H 7.92; found: C
59.21, H 8.18.
4. General Procedure for the Synthesis of the Dendrimers
9, 10, and 11 by the Williamson Reaction. The iodo-terminated
dendrimer20d 7 (5.46 × 10-6 mol) and the phenol dendron 8 (10
equiv for G0, 30 equiv for G1 and 90 equiv for G2) were introduced
into a Schlenk flask, and dry DMF (30 mL) was added, then K2CO3
(2 equiv per dendron) was added to the solution. The mixture was
stirred for 2 days at 80 °C under reflux. At the end of the reaction,
DMF was removed. The product was extracted with CH2Cl2 and
washed with water. G0 and G1 were purified by chromatography
(CH2Cl2:MeOH, (97:3) to remove the excess dendron and then (90:
10) to extract the dendrimer). G2dHQ was precipitated with MeOH/
ether in order to remove the excess dendron. The yields were 80%
for 9 (G0), 78% for 10 (G1) and 85% for 11 (G2).
All these water-soluble dendrimer-stabilized PEGylated AuNPs
are only weakly stabilized and thus should be very useful for
catalytic (small size) and biomedical applications (large size).
Experimental Section
1. Synthesis and Characterization of the Alkyne Dendron
3 (see ESI). A Percec-type dendron19 containing a tris-(triethylene
glycol) group (1 g, 1.57 mmol) and tetraethylene glycol (2.95 g,
15.7 mmol) were introduced into a Schlenk flask, and dry THF
(50 mL) was added. NaH (108 mg, 2.7 mmol) was added to the
solution. The mixture was stirred for 12 h at 50 °C. At the end of
the reaction, water was added, and then THF was removed under
vacuum. The product was extracted with CH2Cl2 and purified by
chromatography (MeOH) giving 1 g of yellow oil (83% yield).
The tris-(triethylene glycol) tetraethylene glycol dendron (600
mg, 0.65 mmol) and dry THF (50 mL) were introduced into a
Schlenk flask, and NaH (47 mg, 1.95 mmol) was added at 0 °C.
Propargyl bromide (155 mg, 1.3 mmol) was added to the solution,
and the mixture was stirred for 2 h at 0 °C, then 2 h at 25 °C. At
the end of the reaction, water was added, then THF and excess
propargyl bromide were removed under vacuum. The product was
extracted with CH2Cl2, yielding 600 mg of yellow oil (95% yield).
1H NMR (CDCl3, 250 MHz): 6.39 (2H, CH-arom. extern), 4.26
(2H, O-CH2-arom. extern), 3.98 (4H, CH2O-arom. extern and CH2-
alkyne), 3.46 (30H, OCH2CH2O), 3.17 (9H, CH3O), 2.36 (1H,
C-CH alkyne); 13C NMR (CDCl3, 62 MHz): 152.41 (Cq-O arom.),
137.50 (Cq-CH2 arom.), 133.63 (Cq-CH2-O), 106.87 (CH arom.),
79.54 (Cq alkyne), 74.75 (CH alkyne), 70.46 (O-CH2), 58.74(O-
CH3), 58.13 (CH2-alkyne). Infrared υalkyne: 2100 cm-1; MALDI
TOF: Calcd for C39H68O17: 808; found: 831 (MNa+)
Characterization of the dendrimer 9: 1H NMR (CDCl3, 250
MHz): 6.92 (CH-arom. core), 6.87 (CH-arom. intern), 6.65 (CH-
arom. extern), 4.85 (0- CH2-arom. extern), 4.16 (CH2O-arom.
extern), 3.65 (OCH2CH2O and Si-CH2O), 3.38 (CH3O), 1.69
(CH2CH2CH2Si), 1.12 (CH2CH2CH2Si), 0.62 (CH2CH2CH2Si), 0.06
(Si(CH3)2); 13C NMR (CDCl3, 62 MHz): 156.09 (O-Cq intern),
152.61 (Cq intern), 144.71 (Cq arom. Core), 137.97 (Cq-Cq intern),
130.95 (CH arom. extern), 118.55 (CH arom. core), 115.61 (CH-
arom intern), 114.79 (CH arom extern), 107.07 (CH arom intern),
72.3 (OCH2CH2), 70.80 (OCH2 arom extern), 68.85 (SiCH2O),
59.05 (CH3O), 43.77 (CH2CH2CH2Si), 17.82 (CH2CH2CH2Si),
14.49 (CH2CH2CH2Si), -4.58 (Si(CH3)2). MALDI TOF: Calc. for
2. General Procedure for the Synthesis of the “Clicked”
PEG Dendrimers 4, 5 and 6. The azido-terminated dendrimer (2
for the synthesis of the dendrimer 5, 1 equiv.) and the alkyne
dendron 3 (1.5 equiv. per branch) were dissolved in THF. At 0 °C,
CuSO4 was added (2 equiv per branch, 1 M water solution),
followed by the dropwise addition of a freshly prepared solution
of sodium ascorbate (4 equiv per branch, 1 M water solution) in
order to set a 1:1 (THF/water) ratio. The solution was allowed to
stir for 12 h at 25 °C under N2. After removing THF under vacuum,
CH2Cl2 and an aqueous ammonia solution were added. The mixture
was allowed to stir for 10 min to remove all the CuII trapped inside
the dendrimer as [Cu(NH3)6]2+. The organic phase was washed
twice with water, dried with sodium sulfate, and the solvent was
removed under vacuum. The product was precipitated with MeOH/
ether in order to remove the excess dendron.19 Yields: 96% (4);
95% (5) and 92% (6). (See details in the ESI.)
C
369H606O126Si9: 7311.54; found: 7334.47 (MNa+); DOSY: D )
1.47 ((0.1) × 10-10 m2/s, Rh ) 3.9 ((0.3) nm (D: diffusion
coefficient; Rh: hydrodynamic radius); SEC: polydispersity ) 1.05.
Anal. Calcd for C369H606O126Si9: C 60.62, H 8.35; found: C 59.64,
H 8.57.
5. Synthesis and Characterization of the Dendrimer 16. The
27 azido-terminated dendrimer precursor of 5 and 16 (see structure
in ESI)11a,12a (0.2 g, 0.032 mmol) and tetraethylene glycol methyl
propargyl ether (0.319 g, 1.296 mmol, 1.5 equiv per branch) were
dissolved in 50 mL of THF. At 0 °C, CuSO4 was added (0.431 g,
1.728 mmol, 2 equiv per branch, 1 M water solution), followed by
dropwise addition of a freshly prepared solution of sodium ascorbate
(0.685 g, 3.456 mmol, 4 equiv. per branch, 1 M water solution) in
order to set a 1:1 (THF/water) ratio. The solution was allowed to
stir for 12 h at 25 °C under N2. After removing THF under vacuum,
CH2Cl2 and an aqueous ammonia solution (28% w/w) were added.
The mixture was allowed to stir for 10 min in order to remove all
the CuII trapped inside the dendrimer as [Cu(NH3)6]2+. The organic
phase was washed twice with water, dried with sodium sulfate,
and the solvent was removed under vacuum. The product was
precipitated with MeOH/ether to remove the excess of tetraethylene
glycol methyl propargyl ether; 0.336 g of 16 was obtained (81%
yield). 1H NMR (CDCl3, 250 MHz): 7.40 (27H, CH-tiazole), 7.08
(18H, CH-arom. extern.), 7.02 (3H, CH-arom. intern.), 4.61 (54H,
triazole-CH2-O), 3.81 (18H, CH2O-arom.), 3.49-3.62 (432H,
OCH2CH2O), 3.33 (81H, CH3O), 1.55 (72H, CH2CH2CH2Si), 1.04
(72H, CH2CH2CH2Si), 0.55 (72H, CH2CH2CH2Si), 0.06 (54H,
O-CH2Si(CH3)2), 0.007 (162H, trazole-CH2Si(CH3)2). 13C NMR
(CDCl3, 62 MHz): 158.96 (Cq of O-arom.), 144.53 (Cq of triazole),
1
Characterization of 4: H NMR (CDCl3, 250 MHz): 7.45 (9H,
CH-triazole), 6.93 (36H, CH-arom. intern), 6.56 (18H, CH-arom.
extern), 4.62 (18H, triazole-CH2-0), 4.43 (18H, O-CH2-arom.
extern), 4.11 (72H, CH2O-arom. extern and Si-CH2-triazole), 3.64
(414H, OCH2CH2O), 3.37 (27H, CH3O), 1.59 (18H, CH2-
CH2CH2Si), 1.07 (18H, CH2CH2CH2Si), 0.60 (18H, CH2CH2-
CH2Si), 0.006 (54H, Si(CH3)2); 13C NMR (CDCl3, 62 MHz): 151.62
(CH, extern arom.), 144.48 (Cq of triazole), 136.83 (Cq, arom. core),
132.75 (Cq, arom. extern), 123.52 (CH of triazole and arom. core),
106.23 (CqCH2O), 69.54 (OCH2CH2O), 63.53 (triazole-CH2-O),
58.00 (CH3O), 53.38 (OCH2-arom. extern), 43.77 (CH2CH2CH2Si),
42.7 (SiCH2-triazole), 40.93 (Cq-arom. intern), 17.82
(CH2CH2CH2Si), 14.90 (CH2CH2CH2Si), -4.84 (Si(CH3)2); DOSY:
D ) 1.16 ((0.1) × 10-10 m2/s, Rh ) 4.9 ((0.1) nm (D: diffusion
coefficient; Rh: hydrodynamic radius); IR: no alkyne and azide
bands; MALDI-TOF mass spectrum: Calcd for C414H741O153N27Si9:
8798; found: 8824 (MNa+). Anal. Calcd for C414H741O153N27Si9: C
56.52, H 8.49; found: C 56.31, H 8.49; light scattering: diameter
) 9 ( 0.8 nm.
3. Synthesis and Characterization of the Phenol Dendron
8 (see ESI). The tris-(triethylene glycol) dendron (300 mg, 0.46
mmol) and hydroquinone (251 mg, 2.28 mmol) were introduced
9
J. AM. CHEM. SOC. VOL. 132, NO. 8, 2010 2741

A R T I C L E S
Boisselier et al.
138.61 (Cq, arom. core) 126.94 (CH-arom.) 123.26 (CH of triazole
and arom. core), 113.36 (CH-arom.), 70.33 (OCH2CH2O), 69.39
(Si-CH2-O), 64.51 (triazole-CH2-O), 58.87 (CH3O), 42.28
(CH2CH2CH2Si), 41.7 (SiCH2-triazole), 40.7 (Cq-arom. inter.),
17.26 (CH2CH2CH2Si), 14.64 (CH2CH2CH2Si), -4.09 (Si(CH3)2).
IR: no alkyne and azide bands. MALDI TOF: Calcd for C612H1187
O144N81Si36: 12946.297; found: 12971, major peak (calcd: 12969:
MNa+). Anal. Calcd for C612H1187 O144N81Si36: C 56.78, H 8.85;
found: C 55.68, H 8.46.
6. General Procedure for AuNPs Reduction in Methanol
with Dendrimers 4, 5 and 6. The following procedure is described
using the preparation of the dendrimer 4: 1 mL of a 1.14 × 10-4
M solution of dendrimer (1 mg, 1.14 × 10-4 mmol) in MeOH was
introduced into a Schlenk flask under nitrogen, then 0.349 mL of
a 2.94 × 10-3 M solution of HAuCl4 (0.349 mg, 1.03 × 10-3 mmol,
1 equiv per triazole) and 4.65 mL of MeOH was added in order to
obtain a solution 2.21 × 10-4 M (in Au). The solution was stirred
for 1 h, the reductant NaBH4 (0.39 mg), [FeICp(η6-C6Me6)] (4.4
mg), ferrocene (1.92 mg), ethynylferrocene (2.16 mg) or decam-
ethylferrocene (3.36 mg)] was added (1.03 × 10-2 mmol, 10 equiv
per Au), and the yellow solution turned to golden brown indicating
the formation of the AuNPs.
8. Transmission Electron Microscopy (TEM and HRTEM). The
samples were prepared by placing a drop of 1.6 × 10-4 M solution
of AuNPs (concentration in mol Au) on a holey-carbon-coated Cu
TEM grid and they were then analyzed with a JEOL JEM 1011
machine.
Acknowledgment. We are grateful to Dr. Eric Cloutet (LCPO,
Bordeaux) for helpful assistance and discussion concerning the SEC
and DLS data. Financial support from the Institut Universitaire de
France (IUF, D.A.), the Universite´ Bordeaux 1, the Centre National
de la Recherche Scientique (CNRS), the Agence Nationale de la
Recherche (ANR, Ph. D. grants to E.B. and A.K.D.), the Fundac¸a˜o
para a Cieˆncia e a Tecnologia (FTC, Portugal, Ph. D. grant to C.O.)
is gratefully acknowledged.
Note Added after ASAP Publication. The version published
ASAP on February 4, 2010, had incorrect labeling of Figures 10
and 11. The corrected version will publish with the issue on March
3, 2010.
Supporting Information Available: Details of the syntheses,
1
characterizations, H and 13C spectra for all the new dendrons
7. General Procedure for the Preparation of AuNPs in
Water without Reductant. The following procedure is described
and dendrimers, size-exclusion chromatograms of the dendrimers
9-11, determination of the diffusion coefficient of the den-
drimers by DOSY NMR, transmission electron microscopy of
the DEAuNPs and DSAuNPs, and UV-vis spectra of HAuCl4,
complexation by dendrimer 4, and reduction to AuNPs by
NaBH4. This material is available free of charge via the Internet
at http://pubs.acs.org.
using the preparation of the dendrimer 9:1 mL of a 1.37 × 10-4
M
solution of dendrimer (1 mg, 1.37 × 10-4 mmol) in H2O was placed
into a Schlenk flask under ambient condition, then 0.416 mL of a
1.23 × 10-3 M solution of HAuCl4 (0.416 mg, 1.23 × 10-3 mmol,
1 equiv per tether). 1.584 mL of H2O was added in order to obtain
a final volume of 3 mL. The solution was stirred, and the yellow
solution turned to pink then red, indicating the formation of the
AuNPs.
JA909133F
9
2742 J. AM. CHEM. SOC. VOL. 132, NO. 8, 2010