Accepted Manuscript

Title: Coordination chemistry with phosphorus dendrimers.

Applications as catalysts, for materials, and in biology

Author: Anne-Marie Caminade Armelle Ouali Régis Laurent

Cédric-Olivier Turrin Jean-Pierre Majoral

PII: S0010-8545(15)00211-8
DOI: http://dx.doi.org/doi:10.1016/j.ccr.2015.06.007
Reference: CCR 112093

To appear in: Coordination Chemistry Reviews

Received date: 27-2-2015

Revised date: 16-6-2015
Accepted date: 17-6-2015

Please cite this article as: A.-M. Caminade, A. Ouali, R. Laurent, C.-O. Turrin,
J.-P. Majoral, Coordination chemistry with phosphorus dendrimers. Applications as
catalysts, for materials, and in biology, Coordination Chemistry Reviews (2015),
http://dx.doi.org/10.1016/j.ccr.2015.06.007

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Edited June 17

Coordination chemistry with phosphorus dendrimers. Applications as catalysts, for

materials, and in biology.

Anne-Marie Caminade,a,b* Armelle Ouali,a,b Régis Laurent,a,b Cédric-Olivier Turrin,a,b Jean-

Pierre Majoral a,b
a
CNRS, LCC (Laboratoire de Chimie de Coordination), 205 route de Narbonne, BP 44099,
F-31077 Toulouse Cedex 4, France
b
Université de Toulouse, UPS, INPT, F-31077 Toulouse Cedex 4, France

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e-mail addresses: anne-marie.caminade@lcc-toulouse.fr (A.M. Caminade, corresponding

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author); armelle.ouali@lcc-toulouse.fr (A. Ouali); regis.laurent@lcc-toulouse.fr (R. Laurent);
cedric-olivier.turrin@lcc-toulouse.fr (C.O. Turrin); jean-pierre.majoral@lcc-toulouse.fr (J.P.

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Majoral).

Dedicated to the memory of our friend Dr Guy Lavigne (deceased April 23th 2015)

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Abstract:
Dendrimers are hyperbranched macromolecules having a perfectly defined and
multifunctionalized structure, constituted of branches emanating radially from a central core.
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The structure of dendrimers is particularly modular, and can incorporate in different parts
coordination complexes. In this review, we will present the interplay between dendrimers and
coordination chemistry in three main field: catalysis, materials, and biology. Most of the
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examples will be taken from the work done with phosphorus-containing dendrimers, but the
pioneering work carried out with other dendrimers will be also presented. One of the major
improvements that metallodendrimers have afforded concerning catalysis is their easy
recovery and reuse, bridging the gap between homogeneous and heterogeneous catalysis.
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Another major improvement concerns the “dendritic effect” which can afford impressive
outcomes concerning the increase of yield and of enantioselectivity, together with a decrease
of the leaching of metals, and consequently of waste. Dendrimers can be used also for the
synthesis and stabilization of metallic nanoparticles, for the modification of metallic surfaces
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at the nanometric scale, and for the synthesis of mesoscopically ordered hybrid materials.
Finally metallodendrimers have high potency against cancerous cell lines, and they appear to
operate via a different mechanism of action compared with native metallodrug, opening new
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avenues for the search of improved anti-cancer agents.

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Highlights:
* metallodendrimers are efficient, reusable catalysts that may induce dendritic effects
* the dendritic effect improves the yield, enantioselectivity, decreases metal leaching
* dendrimers can produce and stabilize metallic nanoparticles
* dendrimers can produce mesoscopically ordered hybrid materials
* metallodendrimers can be used as drugs, in particular against cancerous cells

Keywords: dendrimer; metallodendrimer; catalysis; nanoparticle; hybrid material;

metallodrug

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Content

1. Introduction

2. Catalysis with complexes of dendrimers

2.1 Recovery and reuse of dendrimers
2.1.1 Recovery by precipitation
2.1.2. Magnetic recovery
2.2. The dendritic effect in catalysis

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2.2.1. Influence on the yield

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2.2.2. Influence on the metal leaching
2.2.3. Influence on the enantioselectivity

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2.2.4. Redox-switchable catalysis

3. Interactions of dendrimers with metals in the solid state

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3.1 Dendrimers for the synthesis and stabilization of inorganic nanoparticles
3.2. Modification of metallic surfaces by dendrimers
3.3. Elaboration of hybrid organic/inorganic materials with dendrimers
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4. Biological applications of complexes of dendrimers

5. Conclusions
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6. References
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1. Introduction

Dendrimers are hyperbranched macromolecules having a perfectly defined and

multifunctionalized structure, reminiscent of tree branches. Because of the repeated use of
identical building blocks in their structure, dendrimers are part of the large family of
polymers. However, as they are never synthesized by polymerization reaction, but step-by-
step for the building of branches emanating radially from a central core, they are also part of
molecular chemistry. The size and molecular mass of dendrimers can be very-well controlled
thus improving significantly the physical characteristics such as polydispersity, structural
control, architecture, and the chemical characteristics compared with classical polymers.

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Scheme 1 displays the principle of the divergent synthesis of dendrimers. Each time a new

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layer is added, a new generation is obtained, denoted as Gn, with n being the number of layers
of branching points. Dendrimers have a 3-dimensional structure, which is not reflected in the

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classical drawings shown in Scheme 1, and in all the other Schemes and Figures of this
review.

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Scheme 1 here

The very first example of dendrimers was proposed by F. Vögtle et al. in 1978 (called
“cascade structure”) [1], then R.G. Denkewalter et al. patented (but not published) the
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synthesis of polylysine dendrimers in 1981 [2]. The name “dendrimer” was created later, from
the Greek word δένδρον (déndros, meaning tree) by D.A. Tomalia in 1983, when he patented,
then published in 1985, the first synthesis of Polyamidoamine (PAMAM) dendrimers [3],
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which are the most widely used types of dendrimers. Since that time, dendrimers have gained
an increasing popularity, with more than 22,000 publications and more than 5,500 patents in
the field to date [4]. The interest in dendrimers is nowadays mainly driven by their
applications in numerous fields, which pertain to three main domains: catalysis, materials, and
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biology/medicine [5].
Coordination chemistry accompanied the field of dendrimers very early, since the very
beginning of the nineties. J.C. Roberts et al. proposed in 1990 the use of PAMAM dendrimers
as linkers to couple synthetic porphyrins complexing radioactive 67CuCl2 with antibodies.
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Only a small fraction of the terminal groups of the dendrimers reacted in these experiments
(stochastic functionalization) [6]. V. Balzani et al. synthesized in 1991 dendrimers containing
chelating moieties inside the structure; bridging bipyridyl ligands complexing ruthenium
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constitute all the branching points [7]. Phosphonium dendrimers bearing a phosphine as core
were proposed in 1993 for the complexation of gold by R. Engel et al. [8]. In 1994, two
papers reported the very first uses of dendrimer complexes for catalysis. The first one,
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proposed by D.L. DuBois et al., concerned the palladium complexes of small phosphine
dendrimers, which were used for catalyzing the electrochemical reduction of CO2 to CO [9].
The second example of catalysis was proposed by J.W.J. Knapen, P. Wijkens, G. van Koten et
al. It consisted in a silane dendrimer ended by nickel complexes, which was used for
catalyzing the Kharasch addition of polyhalogenoalkane to an olefinic double bond, in
homogeneous conditions [10]. Figure 1 displays these five early examples of dendrimers
incorporating somewhere in their structure one or several coordination complexes. These
examples illustrate both the diversity of the dendrimers structure, and the diversity of the
location and type of ligands and metals. Several early reviews covered the first attempts in
the field of coordination chemistry of dendrimers [11, 12, 13]. Metallodendrimers continue to
attract interest, as shown by recent papers [14-16].

Figure 1 here

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These early examples spawned a multitude of publications connecting coordination chemistry

and dendrimers. Many early examples concerned the synthetic aspects, but most of the work
for much time has concerned their use for catalysis, and to a lesser extent for materials and
biology. The topic of coordination chemistry with dendrimers is so large nowadays (several
thousands of publications) that it is impossible to produce an exhaustive review. Thus, this
review will focus on the coordination chemistry carried out with one special type of
dendrimer: phosphorus-containing dendrimers, i.e. dendrimers having phosphorus atoms at all
the branching points. The very first examples of such type of dendrimers, proposed by R.
Engel et al. in 1990 [17], possess phosphonium groups at each branching point, as already

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illustrated in Figure 1c. Another type of phosphorus-containing dendrimers, based on

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thiophosphate branching points, was proposed by G.M. Salamonczyk et al. in 2000 [18].
However, the most widely used type of phosphorus-containing dendrimers (more than 350

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references) is the phosphorhydrazone dendrimers that we have proposed in 1994 [19]. Their
iterative synthesis is based on two quantitative reactions: the nucleophilic substitution of Cl
on P(X)Cl2 groups (X = O, most generally S), and a condensation reaction between aldehydes

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and hydrazides. The process has been carried out up to the eighth generation starting from a
hexafunctional core [20], as illustrated in Scheme 2, and up to the twelfth generation starting
from the trifunctional core P(S)Cl3 [21].
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Scheme 2 here

These dendrimers can accommodate many types of functional groups, at all levels of the
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structure, of course as terminal groups, but also in the branches, at the branching points, and
at the core. These functional groups concern in particular coordination chemistry. The very
first example is the complexation of gold on phosphine terminal groups, up to the tenth
generation [22]. In most cases the complexation is carried out on all the terminal groups [23],
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but in a few cases only half of the terminal groups are used for the complexation [24]. In most
cases the ligands are phosphines, but some particular cases concern the complexation of Na
by a crown ether [25], the presence of zirconocenes [26,27] or ferrocenes [28] as terminal
groups, or the complexation of gadolinium by bisphosphonate groups [29]. Two reviews have
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gathered the early examples concerning the complexation of terminal groups of phosphorus-
containing dendrimers [30,31], and selected examples are shown in Figure 2.
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Figure 2 here

Various types of complexes can be found in very different locations of the dendrimers. The
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presence of complexes as branches of phosphorus dendrimers is generally due to ferrocene

derivatives at one [32] or several layers [33], whereas the presence of a complex at the core is
mainly due to macrocycles (phthalocyanine [34] or triazatriolefine [35]). The branching
points (P=S groups) can be used also for new reactivity when they are included in P=N-P=S
linkages [36]. A selective complexation of gold on sulfur is observed with such linkages [37],
and has recently been used in “onion peel” structures [38]. Recent DFT calculations and
Natural Bond Order analyses have shown that P=N-P=S linkages have a high electron density
on sulfur which allows for the regiospecific complexation of gold, whereas the other P=S
groups do not react this way [39]. Two reviews have gathered the early examples of
coordination chemistry inside phosphorus dendrimers [40,41]. Selected examples of the 3
types of internal coordination complexes are shown in Figure 3.

Figure 3 here

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As emphasis is mainly put nowadays on the uses of dendrimers, and not on their synthesis or
reactivity, the main part of this review will deal with the applications of coordination
chemistry to phosphorus-containing dendrimers, to generate catalysts, nano-materials, and
even drugs.

2. Catalysis with complexes of dendrimers

Catalysis is undoubtedly the most important topic for coordination chemistry of dendrimers.

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This topic has been reviewed many times; the most important and/or recent reviews can be

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found in the following references [42-51]. Phosphines are certainly the most versatile type of
ligands [52], thus they have been used in many cases of catalysis, and with all types of

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dendrimers; this is true also in the case of phosphorus-containing dendrimers. Grafting
catalytic entities to dendrimers can deeply modify the properties of these catalytic entities.
Two types of properties are expected: i) the dendritic catalysts are soluble, but they should be

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easily recovered due to their large size (larger than that of the reagents and products), and thus
reused; ii) the presence of a large number of catalytic sites in close proximity on the surface
may modify the catalytic efficiency, whatever the meaning that can be given to this word
(differences in rate, yield, purity, selectivity, etc.). The following paragraphs will display
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these properties, which in some cases are specific for dendrimers (the “dendritic effect”), with
illustrations of catalyzed reactions carried out in homogeneous conditions with phosphorus-
containing dendrimers.
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2.1 Recovery and reuse of dendrimers

In one of the first examples of dendritic catalysts, it was anticipated that the dendrimer could
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be recovered by filtration methods in a membrane reactor [10, 53-57], in a “tea bag” [58], and
in biphasic systems [59, 60], including in ionic liquids [61, 62]. However, there is a much
simpler way to recover soluble dendritic catalysts, as most of them can be easily precipitated
by adding a non-solvent (a solvent in which the dendrimer is not soluble).
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2.1.1 Recovery by precipitation

One of the very early examples of recovery of a dendritic catalyst used in homogeneous
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conditions concerned a G3 phosphorus dendrimers ended by diphosphine ligands, suitable for

the complexation of palladium [63] or ruthenium [64], and used for catalyzing Stille
couplings (cases A and B in Figure 4), or Knoevenagel condensations (cases C and D in
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Figure 4) and Michael additions (case E in Figure 4), respectively [65]. In all these cases, the
recovery is performed by adding diethylether to the reaction mixture in DMF or THF at the
end of the catalysis. The products remain in solution, whereas the dendritic catalysts are
precipitated, and recovered by filtration. The precipitate is solubilized again in DMF or THF,
and used for catalyzing a new run after new addition of the substrates to the mixture.
Generally the percentage of conversion is identical for the first and second runs, and a slight
decrease is observed in several cases for the third run, probably due to a partial loss of the
catalytic dendrimer in the work-up. In the case of the diastereoselective Michael additions, the
efficiency of the catalyst ended by 24 Ru complexes is compared with the efficiency of 24
equivalents of the dendrimer having a single Ru complex at the core. The diastereoisomeric
ratios, the % of conversion in the initial run and after reuse are identical (case E in Figure 4),
and also identical to what was previously reported when using the monomeric RuH2(PPh3)4
[66]. In several cases, encapsulation of a catalyst in a dendrimer has a deleterious effect on the

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catalytic rate and thus efficiency [67], but in other cases an enhancement of the catalysts
stability upon encapsulation has been observed [68,69]. In our case, the encapsulation of the
catalytic site is presumably not sufficient to induce any effect.

Figure 4 here

Another example of recovery and re-use is afforded by a G3 dendritic palladium complex of

chiral P,N ligands used for catalyzing asymmetric allylic alkylations, in various conditions. In
all cases the dendritic catalysts can be recovered by precipitation and re-used two times after
the first run with almost the same efficiency concerning both the yield and the enantiomeric

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excess (ee) (Figure 5) [70].

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Figure 5 here

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A larger number of recovery/re-use cycles has been carried out with dendrimers ended by
triazatriolefinic macrocyclic derivatives. Such macrocycles are able to afford either discrete

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complexes when adding a stoichiometric amount of Pd(0), or Pd nanoparticles if a larger
amount of Pd is used. Both discrete complexes and Pd nanoparticles were used for catalyzing
Heck couplings, and for re-using the catalysts 4 times. In the case of the complex of the small
dendrimer G0, the recovery and re-use have no influence on the yield. On the contrary, in the
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case of the nanoparticles produced by the dendrimer G0, an increase of the efficiency is
observed when the number of recycling experiments increases. This surprising effect is due to
a decrease of the size of the nanoparticles as shown by electron microscopy. The same effect
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is observed, but to a lesser extent, with the nanoparticles obtained with the generation 4
dendrimer, in which the nanoparticles are probably more protected, inside the structure of the
dendrimers (Figure 6) [71]. Nanoparticles entrapped in dendrimers have been used very early
for catalysis, in particular by the group of R.M. Crooks [72,73], and the field has been
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reviewed [74,75].

Figure 6 here
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Another original experiment for recovering and re-using dendritic catalysts concerns a G4
dendrimer ended by terpyridine-scandium triflate complexes. These complexes efficiently
catalyze the Friedel-Crafts acylations of a wide range of aromatic and heteroaromatic
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electrophiles under microwave irradiation with high yields and short reaction times (15
minutes to 2 h). The catalytic system could be successfully used in 12 consecutive runs, with
recovery and re-use of the catalyst by precipitation, using different substrates for each cycle.
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A slight loss of activity is observed from the fifth run, as shown by the increased time needed
to obtain an identical yield in experiments carried out with the same substrates (see runs 4 and
12 in Figure 7, necessitating 30 min. and 2 h., respectively) [76].

Figure 7 here

In our experience, the dendritic catalysts can be always recovered by precipitation and re-
used. The only exception that we have encountered to date concerns dendritic β-diketones
suitable for the complexation of copper, and used for catalyzing the formation of a
diarylether. In this case it was impossible to re-use the catalyst. Analyzing carefully the
different components after the catalysis experiments revealed that the dendrimer was broken,
especially the diketone moieties were released from the surface of the dendrimer [77]. Thus

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every time a dendritic catalyst cannot be re-used, a cleavage of the structure should be
envisaged, and verified.

2.1.2. Magnetic recovery

Another type of recovery, which has been recently reviewed [78,79], concerns the use of
magnetic nanoparticles coated with polymeric or dendritic catalysts [80]. An original example
concerns a small dendrimer having a pyrene linked to the core, and phosphines suitable for
the complexation of palladium as terminal groups. The pyrene interacts by π-stacking with the
graphene layers covering the magnetic cobalt nanoparticles, thus at room temperature, the

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dendrimers are stacked on the nanoparticles. This assembly has been assayed for catalyzing

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Suzuki couplings, in particular for the synthesis of the anti-inflammatory drug Felbinac.
Desorption of the dendrimers from the surface of the nanoparticles was observed when

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heating the suspension to 60°C, thus the catalysis occurs in homogeneous conditions. When
cooling to room temperature, this desorption is reversible, the dendrimers are again
completely absorbed onto the nanoparticles, which is very easily separated from the media,

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using a magnet. The recovery and re-use are extremely efficient, as illustrated by the
quantitative yields in Felbinac obtained from run 1 to run 12 (Figure 8) [81].

Figure 8 here
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2.2. The dendritic effect in catalysis
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The dendritic effect (or dendrimer effect) is observed when a functional group behaves
differently when it is alone or linked to a dendrimer; its property can even vary depending on
the generation of the dendrimers. Of course the number of functional groups has to remain
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constant in all comparative experiments, as shown in Figure 9 [82]. The dendritic effect,
which is reminiscent to the multivalency effect [83], can be observed for any type of
dendrimer and for any of their properties, including in biology [84], even if it has been most
generally tracked in the field of catalysis [85,86]. The dendrimer effect is not always positive,
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but a bias is introduced in the literature, as many cases of negative dendritic effects are never
published. However, one of the very first example of a dendritic catalyst reported a negative
dendritic effect. Indeed, the dendrimer shown in Figure 1e, used for catalyzing Kharasch
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addition was less efficient than the corresponding monomer for this reaction [10].

Figure 9 here
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The dendritic effect can influence many different aspects of the catalytic experiments, as will
be illustrated in the following paragraphs. It has been related in some cases to a cooperative
interaction between multiple catalysts entities [87]. The most spectacular example is certainly
the ester hydrolysis catalyzed by peptide-dendrimers composed of histidine-serine in the
whole structure, as enzyme models, proposed by J.L Reymond et al. In the best case, the
dendrimer of generation 4 was 140,000-fold more efficient than the reference catalyst for
ester hydrolysis [88].

2.2.1. Influence on the yield

In several cases, no effect or only a very slight effect on the yield (related to the rate) of the
catalyzed reactions is observed when varying the generations of the dendrimers, and

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compared with the monomer. The absence of dendritic effect has been observed for instance
for catalytic Stille coupling reactions carried out with iminophosphine-palladium complexes
as catalysts [89], and for the palladium-catalyzed asymmetric allylic alkylation reaction
carried out with dendrimers bearing chiral ferrocenyl phosphine-thioether ligands [90]. A very
slightly positive dendritic effect has been observed for catalytic C-C cross-coupling reactions
catalyzed with monomers or dendrimers bearing as terminal groups palladium complexes of
diphosphino tyramine derivatives [91]. The structure of the three dendrimers and of the
corresponding monomers is shown in Figure 10.

Figure 10 here

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However, in some cases a dramatic effect of the dendrimer on the yield can be observed. An
exaltation of the catalytic properties for N-arylations has been obtained with a series of

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dendrimers ended by pyridine-imine ligands complexing copper (I), using the same number of
catalytic sites in all cases, as for all the experiments that will be reported bellow. When using
iodobenzene as arylation agent, the monomeric complex has practically no activity, whereas

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all dendrimers from generations 1 to 3 have a very high activity. When using bromobenzene,
the monomer is still non active, but the dendrimers have an increased efficiency when the
generation increases, demonstrating a true dendritic effect (Figure 11) [92]. Of course the
number of catalytic entities (the quantity of copper) is kept constant for all experiments, in
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this case, as for all the cases of dendritic catalysts shown in this review.

Figure 11 here
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Another example of dendritic effect has been observed in a biphasic media (water/hexane),
using ruthenium complexes of PTA (phosphatriaza adamantane) [93] for catalyzing the
isomerization of an allylic alcohol (1-octen-3-ol) into ketone (3-octanone), under strong
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stirring. The presence of positive charges on the surface of the dendrimers induces solubility
in water [94,95], whereas the reactants and products are soluble in the organic phase. The
strong stirring enhances the surface of the interface, allowing the catalysis to occur. The
monomer is very soluble in water, whereas the dendrimers become less soluble in water when
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the generation increases, due to an increase of their hydrophobic content (the internal
structure). When the generation increases, the dendrimers are more located at the interface,
facilitating the catalysis, and thus inducing a clear dendrimer effect, as illustrated in Figure 12
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[96]. It has been shown also with dendrimers ended by PTA complexes that an increase in the
density of terminal groups may have a positive effect on the yield [97].
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Figure 12 here

2.2.2. Influence on the metal leaching

The loss of metal (leaching) is a major problem of catalysis with metal derivatives, as it
induces a pollution of the products, and an increased cost due to difficulties of purification of
the products, increase of wastes, and loss of (costly) precious metal. Classical answers to this
problem consist in using heterogeneous catalysts [98], or organocatalysts (no metal) [99].
Dendrimer might be an alternative to solve these problems. In an experiment analogous to the
one shown in Figure 8, using the same Suzuki process, but applied to the synthesis of
biphenyl, the Pd leaching was measured to be decreasing with the number of re-uses of the
catalyst. Indeed, the Pd leaching measured by ICP-MS was 274 ppm (ca. 14% of introduced

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Pd) after the 1st run, 110 ppm (ca. 6%) after the 2nd, 35 ppm (ca. 2%) after the 5th run and 9
ppm (ca. 0.5%) after the 10th run. These results point to a non-specific binding of Pd outside
the ligand; this Pd being mainly removed in the extraction procedures of the first two runs.
[81].
In another example of Suzuki coupling, different monomeric and dendritic catalysts have been
used, with the aim of measuring the influence of both the type of ligand (triphenylphosphine
or thiazolyldiphenyl phosphine) and the monomer versus dendrimers on the leaching of Pd.
The results are shown in Figure 13. For both monomers the leaching is very important,
whereas it is reduced with both G1 dendrimers. In the case of the dendrimeric thiazolyl
phosphine (b-G1 in Figure 13), the leaching is undetectable, whereas it is 173 ppm in the case

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of the dendritic triphenyl phosphine (a-G1). This metal leaching might contribute to explain

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the neat decrease of efficiency observed with a-G1 after 3 runs, whereas the efficiency
remains identical after 5 runs with b-G1 (Figure 13) [100].

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Figure 13 here

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2.2.3. Influence on the enantioselectivity

Asymmetric catalysis has dramatically changed the procedures of chemical synthesis, which
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approximate, or even sometimes exceeds that of natural biological processes [101]. In the
field of dendrimers, the use of chiral catalysts as terminal groups [45] has first produced either
negative or neutral effects, compared with the efficiency of a chiral monomer [102], but also
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highly positive dendrimer effects, as shown by L.H. Gade et al. with an increase in selectivity
from 9% ee for a monomer to 69% ee for a G4 PAMAM dendrimer bearing Pyrphos-Pd as
terminal groups, and used for catalyzed allylic amination of 1,3-diphenyl-1-acetoxypropene
[103]. Phosphorus-containing dendrimers (up to G3) bearing azabis(oxazolines) as terminal
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groups for complexing copper (II) were used for catalyzing asymmetric benzoylations. A
slight increase of ee is observed on going from the first to the second generation, but a large
detrimental effect is observed with the third generation. All generations can be recovered and
reused with an excellent efficiency (Figure 14) [104].
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Figure 14 here
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A dramatic influence of the dendrimers compared with the monomer has been observed with
dendritic phosphoramidite ligands used for Rh-catalyzed [2+2+2] cycloaddition reactions. As
shown in Figure 15, the monomer induces no enantiomeric excess, whereas all the generations
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of the dendrimers, from G1 to G3 afford very high ee, even after recovery and reuse (95 to 98
% ee), leading to axially chiral biaryl compounds [105]. One may presume that the
dendrimers afford a chiral surface, highly beneficial for the outcome of the reaction; the
importance of chiral surfaces for asymmetric catalysis is well known in the case of
heterogeneous catalysts [106].

Figure 15 here

2.2.4. Redox-switchable catalysis

Redox-switchable catalysis (RSC) is a field of growing importance for which oxidation and
reduction influence the electron-donating ability of a ligand and thus result in altered activity

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or selectivity of the catalyst [107]. Despite recent papers in the field of RSC [108,109], this
concept has never been applied to dendrimers before our work. A first generation phosphorus
dendrimer ended by ferrocenyl phosphane ligands for complexing Ru(p-cym)Cl2 (cym =
cymene) and the corresponding monomer were used for catalyzing the isomerization of allylic
alcohol (1-octen-3-ol) (see Figure 12 for the reaction). The dendrimer is more efficient (turn
over frequency, TOF = 600 h-1) than the monomer for such reaction (TOF = 400 h-1). Both
complexes were used for RSC. In the oxidation step, addition of 1 equiv. of [Fe{η5-
C5H4C(O)Me}Cp][BF4] per catalytic function induces a markedly reduced rate. Part of the
catalysts precipitates at this step; this should contribute to the loss of activity. After reduction
with [FeCp*2] (Cp* = C5Me5), all the catalysts become again soluble, and full conversion is

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observed with a degree of activity similar to that of the original catalyst before oxidation, as

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shown in Figure 16 [110]. This is the first example of a reversible switch off and on of a
dendritic catalyst. The use of other dendritic ferrocenyl phosphane complexes as catalysts is

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currently under development [111].

Figure 16 here

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3. Interactions of dendrimers with metals in the solid state
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Materials science, when it concerns metal derivatives, can be considered as a subset of
coordination chemistry, in the sense that the metals are surrounded by ligands. In the
following paragraphs we will display examples in three main fields: dendrimers for the
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elaboration of inorganic nanoparticles, dendrimers for the modification of the surface of
metallic materials at the nanometric scale [112], and dendrimers for the synthesis of hybrid
organic-inorganic nanomaterials [113,114].
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3.1. Dendrimers for the synthesis and stabilization of inorganic nanoparticles

As already indicated just before Figure 6, there is a number of work concerning the
interaction of dendrimers with nanoparticles, mainly in the field of catalysis [115], but not
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only, as recently reviewed [116]. In some cases, the dendrimers do not interact directly with
the nanoparticles, which are synthesized and functionalized before. This is for example the
case of quantum dots [117,118], and of gold nanoparticles [119-121]. As such examples are
ce

not relevant to coordination chemistry of the dendrimers, they will not be discussed in this
paper, which will be limited to the cases in which the nanoparticles are produced thanks to the
dendrimers. Dendrimers can even mediate formation ofnanoparticles that were unknown
Ac

before; this is in particular the case for phosphorus dendrimers of different generations ended
by thiol derivatives. Their reaction with the gold cluster Au55(PPh3)12Cl6 induce the formation
of Au55 nanocrystals, in which the gold clusters are naked (Scheme 3). The role of the
dendrimers ended by thiols is not only to remove the ligands of gold (phosphine and chlorine)
owing to the known affinity of thiols for gold, but also to act as an ideal matrix for growing
the crystals of Au55 and protecting them by a thin amorphous external layer around the
nanocrystals [122]. All previous attempts to grow crystals of Au55 resulted in crystals of Au
(metal, not cluster). Analogous experiments were carried out in two dimensions, with a layer
of the same dendrimer deposited by spin coating on a silicon wafer, and used with
Au55(PPh3)12Cl6. Images of the surface by scanning electron microscopy (SEM), demonstrate
first the appearance of Au55 nanoparticles, which merge into Au55 nanocrystals entrapped in
the layer of dendrimers [123].

Page 10 of 57
Edited June 17

Scheme 3 here

Another example of organization of metals was provided by dendrimers ended by 15-

membered triolefinic azamacrocycles [124]. These dendrimers are suitable for engineering
nanoparticles, which can be used as catalysts, as already shown in Figure 6 in the case of
palladium [71]. An unexpected behavior has been observed in the case of platinum. These
dendrimers induce the formation of self-assembled Pt nanoparticle networks (Scheme 4). The
Pt network has a dendritic structure, for which the length of the “branches” is directly related
to the generation (size) of the dendrimers, affording for the first time a very unique
organization of organic dendritic structures interweaved with inorganic dendritic structures

t
[125].

ip
Scheme 4 here

cr
In another approach for the synthesis of metallic nanoparticles, aminosilanized silica
nanoparticles (mean diameter 12 nm) were first reacted with the first generation dendrimer

us
ended by aldehydes. On the remaining unreacted aldehydes, an amine-functionalized
poly(ethyleneglycol) (PEG, approximately 11 units) was condensed, then
hydrophosphorylation of the resulting Schiff bases was carried out with dialkyl phosphite.
Further addition of silver acetate resulted in the formation of various silver oxide (AgO,
an
Ag2O, Ag3O…) nanoparticles, only on the modified silica (Figure 17). These silver-loaded
silica nanoparticles present interesting anti-bacterial activities [126]
M
Figure 17 here

A recent example of a molecular asterisk [127] (the only branching point is the core, to which
long linear arms are linked) constituted of viologen units linked to the cyclotriphosphazene
ed

core and ended by phosphonate groups was used for obtaining gold nanoparticles from
HAuCl4 as precursor (Scheme 5). These asterisks efficiently stabilize the gold nanoparticles
for more than eight months [128].
pt

Scheme 5 here

Nanoparticles are most generally composed of metals (or their oxides), but there exist also
ce

organic nanoparticles [129]. Nanolatexes of diameter 15 nm, having the 1,4,8,11-

tetraazacyclotetradecane (cyclam) ligand on the surface [130], were then functionalized with a
phosphorus dendritic compound having an activated vinyl group at the core, and bearing
Ac

Girard-T reagents as terminal groups, for inducing solubility in water. This functionalization
provides a remarkable improvement of the colloidal stability of the nanolatexes, since the
suspensions in water remain stable with no change in the particle size in the absence of
surfactant, while the starting nanolatexes are stable only in the presence of DTAB
(dodecyltrimethyl ammonium bromide) and aggregate in the absence of surfactant. The
dendronized nanoparticles retain their metal-complexing ability for Cu(II), thus demonstrating
the permeability of the dendritic shell (Figure 17) [131]. They also produce rigid and
translucent hydrogels on standing one week. Hydrogels were also obtained with phosphorus
dendrimers having the same type of terminal groups (Girard T or Girard P); gelation is
accelerated if a metal ion (Ni(OAc)2, Y(OAc)3, or Er(OAc)3) is added to the water solution
containing these dendrimers (7 hours instead of 13 days for a G4 dendrimer at 1.8 % in weight
in water) [132]. The gelation properties have been expanded for obtaining macroscopic fibers,
using a flow process. A dendrimer in aqueous solution is continuously injected through a

Page 11 of 57
Edited June 17

syringe, moving horizontally and at a controlled velocity into a flocculating La(NO3)3 solution
in water. As the filaments of the dendrimer solution emerge from the needle, they precipitate
and solidify, forming the fiber composed of the dendrimers interacting with La(NO3)3 [133].

Figure 18 here

3.2. Modification of metallic surfaces by dendrimers

Dendrimers are considered as ideal molecular building blocks for a wide range of interfacial

t
materials involving self-assembled monolayers, Langmuir films, multilayers, and other

ip
surface-confined assemblies [134]. However, only a part of these utilizations of dendrimers
on surfaces concerns their direct interaction with metals that may be considered as relevant to

cr
coordination chemistry. The first examples in the field concerned the immobilization on the
surface of metallic electrodes of redox active dendrimers, for which early [135] and recent
[136] reviews have been published. All the ferrocenyl dendrimers have in particular such

us
properties [28,32,33,90,110,111]. However, other types of redox active dendrimers can be
used for the functionalization of metallic electrodes, such as dendrimers having bithiophene
derivatives as terminal groups (Figure 19), which polymerize irreversibly onto a Pt electrode
[137]. Another example of an organic redox group concerns a semi-crown ether incorporating
an
a TTF (tetrathiafulvalene) derivative in the structure. The functionalized dendrimer deposits
onto a Pt electrode upon cycling. The macrocycle is suitable for the complexation of Ba2+
(Figure 19). Such complexation induces a modification of the electrochemical response of the
M
modified Pt electrode. This dendrimer constitutes one of the very early example of sensing
with organic redox active dendrimers [138], but the field of electrochemical sensing with
dendrimers was first disclosed using ferrocenyl dendrimers [139,140], and has been reviewed
[136].
ed

Figure 19 here

Another example of sensor is provided by a small dissymmetrical dendrimers having on one

pt

side two phosphonate groups suitable for the grafting onto a nanocrystalline mesoporous
titania thin film, and on the other side 5 maleimide fluorophores (Figure 20). The film
functionalized by this dendrimer displays a bright fluorescence. This new hybrid sensor
ce

exhibits high sensitivity to phenolic OH moieties (especially those from resorcinol and 2-
nitroresorcinol), which induces the quenching of fluorescence, more efficiently in the solid
state than in solution [141]. The use of dendrimers as sensors in the solid state is known since
Ac

a long time [142], and has been reviewed [143,144].

Figure 20 here

3.3. Elaboration of hybrid organic/inorganic materials with dendrimers

Hybrid materials (organic/inorganic) are mainly based on silica as the inorganic component,
generally obtained by a sol-gel process of silicon alkoxide precursors. This is true when using
small molecules as the organic part, but also in the case of dendrimers [145,146], including
for phosphorus dendrimers [112,147], but this topic is not relevant for this review. However,
the same process can be applied to metal alkoxides, in particular to titanium alkoxides, even if
the organic-inorganic interfaces built from non-silicate precursors are often more difficult to

Page 12 of 57
Edited June 17

control. The first example concerned small dendrimers (G1) ended by alcohol or carboxylic
acid functions, reacted with the titanium oxo cluster [Ti16O16(OEt)32]. In both cases
mesoscopically ordered hybrid materials are obtained (Scheme 6). The nature of the interface
depends on the type of dendrimers; with alcohol end groups, a transalcoholysis is observed,
whereas with the carboxylic acid functions the interaction occurs via bridging carboxylates
[148]. The same process was applied to larger dendrimers (G5 and G7, both ended by
carboxylic acids) and Ti(OR)4 (R = Et, iPr, Bu) or Ce(OiPr)4 as the inorganic precursors. The
resulting materials have sponge-like mesostructures with macroporosities [149].

Scheme 6 here

t
ip
A series of phosphorus dendrimers having various types of terminal functions were also
reacted with Ti(OiPr)4. With phosphonic acid derivatives as terminal groups, the reaction

cr
induces the formation of titanium nanoparticles of anatase structure, entrapped in the dendritic
network. A remarkable increase of stability of the anatase form is observed up to 800°C, and
no transformation to the brookite or rutile phase, commonly observed at this temperature

us
range, has been detected [150]. The same phenomenon is observed also with dendrimers
ended by ammonium or diketone groups (Scheme 7). Further studies have demonstrated that
the cyclotriphosphazene core opens at about 500°C to form a polyphosphazene skeleton,
while preserving the structure of the anatase nanoparticles [151].
an
Scheme 7 here
M
4. Biological applications of complexes of dendrimers

Cis-platin [152] and its derivatives [153] are undoubtedly the most famous coordination
ed

compounds used in anti-cancer chemotherapies. However, the use of metallodrugs is not

limited to anti-cancer therapies, but have also very interesting biological activities as
antimalarial, antibacterial, or neuro-protector agents, against arthritis, etc. As dendrimers
nowadays play a crucial role in biology [84,154], metallodrug-dendrimer conjugates and
pt

encapsulation of metallodrugs in dendrimers constitute a field of current interest [155], in

particular with the aim of reducing the toxicity, enhancing the bioavailability, and overcoming
resistances.
ce

Recently, a series of phosphorus dendrimers complexing copper (II) has demonstrated anti-
tumor activities. Dendrimers having either N-(pyridin-2-ylmethylene)ethanamine, or N-
(di(pyridin-2-yl)methylene)ethanamine, or 2-(2-methylenehydrazinyl)pyridine terminal
Ac

groups were synthesized from generation 1 to generation 3, as well as the corresponding

monomers. The corresponding copper complexes were also synthesized (Figure 21). All the
compounds ended by the complexes, but also all the compounds ended by the free ligands
were tested towards cancer cells. Generations 3 are the most efficient. Surprisingly, both the
free ligands and the complexes display anti-proliferative activities, even at low concentration
(1 µM); however, the copper complexes are generally more potent. The efficiency also
depends on the type of ligands: the series with N-(pyridin-2-ylmethylene)ethanamine (series
A) (free ligands and complexes) is the most potent, as illustrated by the percentage of
cancerous HL60 cell growth inhibition (graph in Figure 21) [156]. In order to clarify the
interaction mode of the Cu(II) ions in a biological medium, comparative electron
paramagnetic resonance (EPR) studies of both Cu(II)-conjugated dendrimers and the
corresponding Cu(II)-monomers bearing different ligand moieties were carried out, in water
solution, and also in the presence of HCT-116 cancer cells, and MRC-5 normal cells. It

Page 13 of 57
Edited June 17

appears that the copper complexes of the A series are the most stable and have the highest
affinity for the HCT-116 cancer cells [157], in excellent correlation with their higher anti-
tumor activity.

Figure 21 here

5. Conclusions

We have shown that phosphorus dendrimers display a large palette of properties when

t
associated with metallic derivatives. Many other types of dendrimers have been used also for

ip
such associations, but phosphorus dendrimers appear as particularly suitable for inducing
positive dendritic effects, even if there is no direct comparison with the same type of ligand

cr
and metals, but linked to different dendrimers. However, a very recent study has been carried
out with a series of dendrimers having phosphonic acids as terminal groups, linked to various
internal structures (various phosphorus dendrimers, carbosilane dendrimers, PAMAM

us
dendrimers, PPI dendrimers, polyLysine dendrimers) and used for the activation of human
monocytes. Such study demonstrates for the first time the crucial role played by the internal
structure. In this direct comparison, the phosphorus dendrimers are the most biologically
active, with the carbosilane dendrimers to a lesser extent, whereas PAMAM, PPI, and
an
PolyLysine dendrimers display no activity [158]. Even if it does not involve coordination
complexes of dendrimers, such study demonstrates that phosphorus dendrimers are indeed
special among all types of dendrimers.
M
Association of coordination chemistry with dendritic structures has been mainly used for
creating new catalysts. One of the major improvements that all types of dendrimers have
afforded in this field concerns their easy recovery and reuse, bridging the gap between
homogeneous and heterogeneous catalysis. Indeed dendritic catalysts are soluble in the
ed

reaction media, but their large size and slightly lower solubility than that of products allow in
many cases for their recovery, in particular by precipitation. As dendrimers are relatively
costly to synthesize, and many metals are also costly, the possibility to recover and reuse
dendritic catalysts is particularly relevant. The other major improvement afforded by dendritic
pt

catalysts concerns the so-called dendritic effect, which can afford impressive outcomes
somehow related to the multivalency effect, but which is often non-predictable. This fact is
illustrated by 3 examples gathered in Table 1, all carried out with phosphorus dendrimers
ce

decorated with various ligands. In two cases, there is no difference between monomers and
dendrimers on the percentage of conversion and enantiomeric excess (ee), whereas in a third
case there is a dramatic difference. The dendritic effect can improve the yield (related also to
Ac

the rate), decrease the leaching of metals and consequently the quantity of wastes, and
increase the enantioselectivity, sometimes in a dramatic proportion, compared with
monomeric catalysts (Table 1). Taking altogether these properties, the use of dendrimers as
catalysts holds great promises that are currently realized in laboratories, but have not yet made
the leap to industry, probably due to the lack of understanding and predictability of the effects
observed.
In an extended sense of the concept, since the type of coordination is not always well defined,
coordination chemistry with dendrimers in the field of materials is related to three main areas.
The most important concerns the use of dendrimers for creating and/or stabilizing metallic
nanoparticles, which can be used in particular as catalysts. The second one concerns the
modification of metallic surfaces by arrays of dendrimers at the nanometric scale, for instance
to produce sensitive sensors. The third area concerns the synthesis of hybrid materials

Page 14 of 57
Edited June 17

obtained by reaction of dendrimers with organometallic precursors. Different types of original

mesoscopically ordered hybrid materials have been obtained in this way.

The last field relating coordination chemistry and dendrimers concerns biology, and more
precisely metallodrugs. The number of metallodrugs currently used is not large compared
with purely organic drugs, but well-known examples can be found in particular as anti-cancer
agents. The architecture of dendrimers induces a large proportion of functional group
exposition at their surfaces that may increase the cellular uptake level of the drugs. Thus,
dendrimers functionalized with metallodrugs have high potency against sensitive and resistant
metallodrug cell lines. Preliminary results indicate that metallodendrimers appear to operate

t
via a different mechanism of action compared with native metallodrugs, opening new avenues

ip
in the search of novel candidates as antitumor agents. Even if the number of examples of
metallodendrimers used in biology is limited, this area is certainly a very promising one for

cr
the future.

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6. References

[1] E. Buhleier, F. Wehner, F. Vögtle, Synthesis, 78 (1978) 155-158.

an
[2] R.G. Denkewalter, J. Kolc, W.J. Lukasavage, US 4289872 (published 1981, filed 1979).

[3] D.A. Tomalia, H. Baker, J. Dewald, M. Hall, G. Kallos, S. Martin, J. Roeck, J. Ryder, P.
M
Smith, Polymer J., 17 (1985) 117-132.

[4] Source CAPLUS accessed on January 27th 2015 at https://scifinder.cas.org/scifinder/

ed

[5] A.M. Caminade, C.O. Turrin, R. Laurent, A. Ouali, B. Delavaux-Nicot, Editors,

Dendrimers: Towards Catalytic, Material and Biomedical Uses, John Wiley & Sons Ltd.,
Chichester, UK, 2011.
pt

[6] J.C. Roberts, Y.E. Adams, D. Tomalia, J.A. Mercer-Smith, D.K. Lavallee, Bioconjugate
Chem., 1 (1990) 305-308.
ce

[7] S. Serroni, G. Denti, S. Campagna, M. Ciano, V. Balzani, J. Chem. Soc.-Chem. Commun.,

(1991) 944-945.
Ac

[8] R. Engel, K. Rengan, C.S. Chan, Heteroat. Chem., 4 (1993) 181-184.

[9] A. Miedaner, C.J. Curtis, R.M. Barkley, D.L. DuBois, Inorg. Chem., 33 (1994) 5482-
5490.

[10] J.W.J. Knapen, A.W. van der Made, J.C. de Wilde, P. van Leeuwen, P. Wijkens, D.M.
Grove, G. van Koten, Nature, 372 (1994) 659-663.

[11] V. Balzani, S. Campagna, G. Denti, A. Juris, S. Serroni, M. Venturi, Acc. Chem. Res., 31
(1998) 26-34.

[12] I. Cuadrado, M. Moran, C.M. Casado, B. Alonso, J. Losada, Coord. Chem. Rev., 193-
195 (1999) 395-445.

Page 15 of 57
Edited June 17

[13] G.R. Newkome, E.F. He, C.N. Moorefield, Chem. Rev., 99 (1999) 1689-1746.

[14] L. Xu, L.J. Chen, H.B. Yang, Chem. Commun., 50 (2014) 5156-5170.

[15] L.J. Chen, G.Z. Zhao, B. Jiang, B. Sun, M. Wang, L. Xu, J.M. He, Z. Abliz, H.W. Tan,
X.P. Li, H.B. Yang, J. Am. Chem. Soc., 136 (2014) 5993-6001.

[16] A.M. Caminade, R. Laurent, A. Ouali, J.P. Majoral, Inorg. Chim. Acta, 409 (2014) 68-
88.

t
ip
[17] K. Rengan, R. Engel, J. Chem. Soc.-Chem. Commun., (1990) 1084-1085.

cr
[18] G.M. Salamonczyk, M. Kuznikowski, A. Skowronska, Tetrahedron Lett., 41 (2000)
1643-1645.

us
[19] N. Launay, A.M. Caminade, R. Lahana, J.P. Majoral, Angew. Chem.-Int. Edit. Engl., 33
(1994) 1589-1592.

[20] N. Launay, A.M. Caminade, J.P. Majoral, J. Organomet. Chem., 529 (1997) 51-58.
an
[21] M.L. Lartigue, B. Donnadieu, C. Galliot, A.M. Caminade, J.P. Majoral, J.P. Fayet,
Macromolecules, 30 (1997) 7335-7337.
M
[22] M. Slany, M. Bardaji, M.J. Casanove, A.M. Caminade, J.P. Majoral, B. Chaudret, J. Am.
Chem. Soc., 117 (1995) 9764-9765.
ed

[23] M. Slany, M. Bardaji, A.M. Caminade, B. Chaudret, J.P. Majoral, Inorg. Chem., 36
(1997) 1939-1945.

[24] M. Slany, A.M. Caminade, J.P. Majoral, Tetrahedron Lett., 37 (1996) 9053-9056.
pt

[25] N. Launay, M. Slany, A.M. Caminade, J.P. Majoral, J. Org. Chem., 61 (1996) 3799-
3805.
ce

[26] V. Cadierno, A. Igau, B. Donnadieu, A.M. Caminade, J.P. Majoral, Organometallics, 18

(1999) 1580-1582.
Ac

[27] J.P. Majoral, M. Zablocka, New J. Chem., 29 (2005) 32-41.

[28] C.O. Turrin, J. Chiffre, J.C. Daran, D. de Montauzon, A.M. Caminade, E. Manoury, G.
Balavoine, J.P. Majoral, Tetrahedron, 57 (2001) 2521-2536.

[29] G. Franc, C.O. Turrin, E. Cavero, J.P. Costes, C. Duhayon, A.M. Caminade, J.P.
Majoral, Eur. J. Org. Chem., (2009) 4290-4299.

[30] A.M. Caminade, R. Laurent, B. Chaudret, J.P. Majoral, Coord. Chem. Rev., 178 (1998)
793-821.

Page 16 of 57
Edited June 17

[31] J.P. Majoral, A.M. Caminade, R. Laurent, Metallo groups linked to the surface of
phosphorus-containing dendrimers, in: U.S. Schubert, G.R. Newkome, I. Manners (Eds.)
Metal-Containing and Metallosupramolecular Polymers and Materials, Amer Chem. Soc,
Washington, 2006, pp. 230-243.

[32] C.O. Turrin, J. Chiffre, D. de Montauzon, G. Balavoine, E. Manoury, A.M. Caminade,

J.P. Majoral, Organometallics, 21 (2002) 1891-1897.

[33] C.O. Turrin, J. Chiffre, D. de Montauzon, J.C. Daran, A.M. Caminade, E. Manoury, G.
Balavoine, J.P. Majoral, Macromolecules, 33 (2000) 7328-7336.

t
ip
[34] J. Leclaire, R. Dagiral, A. Pla-Quintana, A.M. Caminade, J.P. Majoral, Eur. J. Inorg.
Chem., (2007) 2890-2896.

cr
[35] E. Badetti, G. Franc, J.P. Majoral, A.M. Caminade, R.M. Sebastian, M. Moreno-Manas,
Eur. J. Org. Chem., (2011) 1256-1265.

us
[36] C. Galliot, C. Larré, A.M. Caminade, J.P. Majoral, Science, 277 (1997) 1981-1984.

[37] C. Larré, B. Donnadieu, A.M. Caminade, J.P. Majoral, Chem.-Eur. J., 4 (1998) 2031-
2036. an
[38] N. Katir, N. El Brahmi, A. El Kadib, S. Mignani, A.M. Caminade, M. Bousmina, J.P.
M
Majoral, Chem.-Eur. J., 21 (2015) 6400-6408.

[39] V. Furer, A.E. Vandyukov, J.P. Majoral, A.M. Caminade, S. Gottis, R. Laurent, V.I.
Kovalenko, J. Mol. Struct., 1084 (2015) 103-113.
ed

[40] J.P. Majoral, C. Larré, R. Laurent, A.M. Caminade, Coord. Chem. Rev., 192 (1999) 3-18.

[41] A.M. Caminade, J.P. Majoral, Coord. Chem. Rev., 249 (2005) 1917-1926.
pt

[42] Y.M. He, Y. Feng, Q.H. Fan, Acc. Chem. Res., 47 (2014) 2894-2906.
ce

[43] N. El Brahmi, S. El Kazzouli, S. Mignani, M. Bousmina, J.P. Majoral, Tetrahedron, 69

(2013) 3103-3133.
Ac

[44] D. Wang, D. Astruc, Coord. Chem. Rev., 257 (2013) 2317-2334.

[45] A.M. Caminade, P. Servin, R. Laurent, J.P. Majoral, Chem. Soc. Rev., 37 (2008) 56-67.

[46] D. Mery, D. Astruc, Coord. Chem. Rev., 250 (2006) 1965-1979.

[47] L.J. Twyman, A.S.H. King, I.K. Martin, Chem. Soc. Rev., 31 (2002) 69-82.

[48] R. van Heerbeek, P.C.J. Kamer, P. van Leeuwen, J.N.H. Reek, Chem. Rev., 102 (2002)
3717-3756.

[49] G.E. Oosterom, J.N.H. Reek, P.C.J. Kamer, P. van Leeuwen, Angew. Chem. Int. Ed., 40
(2001) 1828-1849.

Page 17 of 57
Edited June 17

[50] D. Astruc, F. Chardac, Chem. Rev., 101 (2001) 2991-3023.

[51] L.H. Gade, Editor, Dendrimer Catalysis, Topics in Organometallic Chemistry, vol 20,
Springer, 2006.

[52] A.M. Caminade, J.P. Majoral, R. Mathieu, Chem. Rev., 91 (1991) 575-612.

[53] N. Brinkmann, D. Giebel, G. Lohmer, M.T. Reetz, U. Kragl, J. Catal., 183 (1999) 163-
168.

t
ip
[54] N.J. Hovestad, E.B. Eggeling, H.J. Heidbuchel, J. Jastrzebski, U. Kragl, W. Keim, D.
Vogt, G. van Koten, Angew. Chem. Int. Ed., 38 (1999) 1655-1658.

cr
[55] D. de Groot, E.B. Eggeling, J.C. de Wilde, H. Kooijman, R.J. van Haaren, A.W. van der
Made, A.L. Spek, D. Vogt, J.N.H. Reek, P.C.J. Kamer, P. van Leeuwen, Chem.Commun.,

us
(1999) 1623-1624.

[56] D. de Groot, B.F.M. de Waal, J.N.H. Reek, A. Schenning, P.C.J. Kramer, E.W. Meijer,
P. van Leeuwen, J. Am. Chem. Soc., 123 (2001) 8453-8458.
an
[57] N.J.M. Pijnenburg, H.P. Dijkstra, G. van Koten, R. Gebbink, Dalton Trans., 40 (2011)
8896-8905.
M
[58] M. Gaab, S. Bellemin-Laponnaz, L.H. Gade, Chem.-Eur. J., 15 (2009) 5450-5462.

[56] V. Chechik, R.M. Crooks, J. Am. Chem. Soc., 122 (2000) 1243-1244.
ed

[60] A. Garcia-Bernabe, M. Kramer, B. Olah, R. Haag, Chem.-Eur. J., 10 (2004) 2822-2830.

[61] G.N. Ou, L. Xu, B.Y. He, Y.Z. Yuan, Chem.Commun., (2008) 4210-4212.
pt

[62] J.K. Kassube, L.H. Gade, Adv. Synth. Catal., 351 (2009) 739-749.
ce

[63] M. Bardaji, M. Kustos, A.M. Caminade, J.P. Majoral, B. Chaudret, Organometallics, 16

(1997) 403-410.
Ac

[64] M. Bardaji, A.M. Caminade, J.P. Majoral, B. Chaudret, Organometallics, 16 (1997)

3489-3497.

[65] V. Maraval, R. Laurent, A.M. Caminade, J.P. Majoral, Organometallics, 19 (2000) 4025-
4029.

[66] S.I. Murahashi, T. Naota, H. Taki, M. Mizonu, H. Takaya, S. Komiya, Y. Mizuho, N.

Oyasato, M. Hiraoka, M. Hirano, A. Fukuoka, J. Am. Chem. Soc., 117 (1995) 12436-12451.

[67] A. Zubia, F.P. Cossio, I. Morao, M. Rieumont, X. Lopez, J. Am. Chem. Soc., 126 (2004)
5243-5252.

[68] S. Hecht, J. M. J. Fréchet, Angew. Chem. Int. Ed., 40 (2001) 74-91.

Page 18 of 57
Edited June 17

[69] C. Müller, L.J. Ackerman, J.N.H. Reek, P.C.J. Kamer, P.W.N.M. van Leeuwen, J. Am.
Chem. Soc., 126 (2004) 14960-14963.

[70] R. Laurent, A.M. Caminade, J.P. Majoral, Tetrahedron Lett., 46 (2005) 6503-6506.

[71] E. Badetti, A.M. Caminade, J.P. Majoral, M. Moreno-Manas, R.M. Sebastian, Langmuir,
24 (2008) 2090-2101

[72] M.Q. Zhao, R.M. Crooks, Angew. Chem. Int. Ed., 38 (1999) 364-366.

t
ip
[73] M.Q. Zhao, R.M. Crooks, Adv. Mater., 11 (1999) 217-220.

cr
[74] R.M. Crooks, M. Zhao, L. Sun, V. Chechik, L.K. Yeung, Acc. Chem. Res., 34 (2001)
181-190.

us
[75] V.S. Myers, M.G. Weir, E.V. Carino, D.F. Yancey, S. Pande, R.M. Crooks, Chemical
Science, 2 (2011) 1632-1646.

[76] A. Perrier, M. Keller, A.M. Caminade, J.P. Majoral, A. Ouali, Green Chem., 15 (2013)
2075-2080. an
[77] M. Keller, M. Ianchuk, S. Ladeira, M. Taillefer, A.M. Caminade, J.P. Majoral, A. Ouali,
M
Eur. J. Org. Chem., (2012) 1056-1062.

[78] Q.M. Kainz, O. Reiser, Acc. Chem. Res., 47 (2014) 667-677.

ed

[79] R.B. Nasir Baig, M.N. Nadagouda, R.S. Varma, Coord. Chem. Rev., 287 (2015) 137-
156.

[80] M. Keller, A. Perrier, R. Linhardt, L. Travers, S. Wittmann, A.M. Caminade, J.P.

pt

Majoral, O. Reiser, A. Ouali, Adv. Synth. Catal., 355 (2013) 1748-1754.

[81] M. Keller, V. Collière, O. Reiser, A.M. Caminade, J.P. Majoral, A. Ouali, Angew. Chem.
ce

Int. Ed., 52 (2013) 3626-3629.

[82] A.M. Caminade, A. Ouali, R. Laurent, C.O. Turrin, J.P. Majoral, Chem. Soc. Rev., 44
Ac

(2015) 3890-3899.

[83] J.D. Badjic, A. Nelson, S.J. Cantrill, W.B. Turnbull, J.F. Stoddart, Acc. Chem. Res., 38
(2005) 723-732.

[84] O. Rolland, C.O. Turrin, A.M. Caminade, J.P. Majoral, New. J. Chem., 33 (2009) 1809-
1824.

[85] B. Helms, J.M.J. Fréchet, Adv. Synth. Catal., 348 (2006) 1125-1148.

[86] J.K. Kassube, H. Wadepohl, L.H. Gade, Adv. Synth. Catal., 351 (2009) 607-616.

[87] R. Breinbauer, E. N. Jacobsen, Angew. Chem. Int. Ed., 39 (2000) 3604-3607.

Page 19 of 57
Edited June 17

[88] E. Delort, T. Darbre, J.L. Reymond, J. Am. Chem. Soc., 126 (2004) 15642-15643.

[89] M. Koprowski, R.M. Sebastian, V. Maraval, M. Zablocka, V. Cadierno-Menendez, B.

Donnadieu, A. Igau, A.M. Caminade, J.P. Majoral, Organometallics, 21 (2002) 4680-4687.

[90] L. Routaboul, S. Vincendeau, C.O. Turrin, A.M. Caminade, J.P. Majoral, J.C. Daran, E.
Manoury, J. Organomet. Chem., 692 (2007) 1064-1073.

[91] P. Servin, R. Laurent, A. Romerosa, M. Peruzzini, J.P. Majoral, A.M. Caminade,

t
Organometallics, 27 (2008) 2066-2073.

ip
[92] A. Ouali, R. Laurent, A.M. Caminade, J.P. Majoral, M. Taillefer, J. Am. Chem. Soc., 128

cr
(2006) 15990-15991.

[93] M. Zablocka, A. Hameau, A.M. Caminade, J.P. Majoral, Adv. Synth. Catal., 352 (2010)

us
2341-2358.

[94] A.M. Caminade, J.P. Majoral, Prog. Polym. Sci., 30 (2005) 491-505.
an
[95] A.M. Caminade, A. Hameau, J.P. Majoral, Chem. Eur. J., 15 (2009) 9270-9285.

[96] P. Servin, R. Laurent, L. Gonsalvi, M. Tristany, M. Peruzzini, J.P. Majoral, A.M.

M
Caminade, Dalton Trans., (2009) 4432-4434.

[97] P. Servin, R. Laurent, H. Dib, L. Gonsalvi, M. Peruzzini, J.P. Majoral, A.M. Caminade,
Tetrahedron Lett., 53 (2012) 3876-3879.
ed

[98] R.A. Sheldon, M. Wallau, I.W.C.E. Arends, U. Schuchardt, Acc. Chem. Res., 31 (1998)
485-493.
pt

[99] P.I. Dalko, L. Moisan, Angew. Chem. Int. Ed., 43 (2004) 5138-5175.

[100] M. Keller, A. Hameau, G. Spataro, S. Ladeira, A.M. Caminade, J.P. Majoral, A. Ouali,
ce

Green Chem., 14 (2012) 2807-2815.

[101] R. Noyori, Angew. Chem. Int. Ed., 41 (2002) 2008-2022.

Ac

[102] C. Koellner, B. Pugin, A. Togni, J. Am. Chem. Soc., 120 (1998) 10274-10275.

[103] Y. Ribourdouille, G.D. Engel, M. Richard-Plouet, L.H. Gade, Chem. Commun., (2003)
1228-1229.

[104] A. Gissibl, C. Padié, M. Hager, F. Jaroschick, R. Rasappan, E. Cuevas-Yanez, C.O.

Turrin, A.M. Caminade, J.P. Majoral, O. Reiser, Org. Lett., 9 (2007) 2895-2898.

[105] L. Garcia, A. Roglans, R. Laurent, J.P. Majoral, A. Pla-Quintana, A.M. Caminade,

Chem. Commun., 48 (2012) 9248-9250.

[106] T. Mallat, E. Orglmeister, A. Baiker, Chem. Rev., 107 (2007) 4863-4890.

Page 20 of 57
Edited June 17

[107] A. M. Allgeier, C. A. Mirkin, Angew. Chem. Int. Ed., 37 (1998) 894-908.

[108] E. M. Broderick, N. Guo, C.S. Vogel, C. Xu, J. Sutter, J.T. Miller, K. Meyer, P.
Mehrkhodavandi, P.L. Diaconescu, J. Am. Chem. Soc., 133 (2011) 9278-9281.

[109] K. Arumugam, C.D. Varnado Jr., S. Sproules, V.M. Lynch, C.W. Bielawski, Chem.
Eur. J., 19 (2013) 10866-10875.

[110] P. Neumann, H. Dib, A.M. Caminade, E. Hey-Hawkins, Angew. Chem. Int. Ed., 54

t
(2015) 311-314.

ip
[111] P. Neumann, H. Dib, A. Sournia-Saquet, T. Grell, M. Handke, A.M. Caminade, E. Hey-

cr
Hawkins, Chem. Eur. J., 21 (2015) 6590-6604.

[112] A.M. Caminade, J.P. Majoral, Acc. Chem. Res., 37 (2004) 341-348.

us
[113] A.M. Caminade, J.P. Majoral, J. Mat. Chem., 15 (2005) 3643-3649.

[114] D.K. Smith, Chem. Commun., (2006) 34-44.

an
[115] R.W.J. Scott, O.M. Wilson, R.M. Crooks, J. Phys. Chem. B, 109 (2005) 692-704.
M
[116] L.M. Bronstein, Z.B. Shifrina, Chem. Rev., 111 (2011) 5301-5344.

[117] C.L. Feng, X.H. Zhong, M. Steinhart, A.M. Caminade, J.P. Majoral, W. Knoll, Adv.
Mater., 19 (2007) 1933-1936.
ed

[118] C.L. Feng, X.H. Zhong, M. Steinhart, A.M. Caminade, J.P. Majoral, W. Knoll, Small, 4
(2008) 566-571.
pt

[119] L. Nicu, M. Guirardel, F. Chambosse, P. Rougerie, S. Hinh, E. Trevisiol, J.M. Francois,

J.P. Majoral, A.M. Caminade, E. Cattan, C. Bergaud, Sens. Actuator B-Chem., 110 (2005)
125-136.
ce

[120] J.L. Hernandez-Lopez, H.L. Khor, A.M. Caminade, J.P. Majoral, S. Mittler, W. Knoll,
D.H. Kim, Thin Solid Films, 516 (2008) 1256-1264.
Ac

[121] W.B. Zhao, J. Park, A.M. Caminade, S.J. Jeong, Y.H. Jang, S.O. Kim, J.P. Majoral, J.
Cho, D.H. Kim, J. Mater. Chem., 19 (2009) 2006-2012.

[122] G. Schmid, W. Meyer-Zaika, R. Pugin, T. Sawitowski, J.P. Majoral, A.M. Caminade,

C.O. Turrin, Chem. Eur. J., 6 (2000) 1693-1697.

[123] G. Schmid, E. Emmrich, J.P. Majoral, A.M. Caminade, Small, 1 (2005) 73-75.

[124] G. Franc, E. Badetti, C. Duhayon, Y. Coppel, C.O. Turrin, J.P. Majoral, R.M.
Sebastian, A.M. Caminade, New. J. Chem., 34 (2010) 547-555.

Page 21 of 57
Edited June 17

[125] G. Franc, E. Badetti, V. Collière, J.P. Majoral, R.M. Sebastian, A.M. Caminade,
Nanoscale, 1 (2009) 233-237.

[126] A. Hameau, V. Colliere, J. Grimoud, P. Fau, C. Roques, A.M. Caminade, C.O. Turrin,
RSC Advances, 3 (2013) 19015-19026.

[127] M. Gingras, A. Pinchart, C. Dallaire, Angew. Chem. Int. Ed., 37 (1998) 3149-3151.

[128] N. Katir, A. El Kadib, V. Collière, J.P. Majoral, M. Bousmina, Chem. Commun., 50

(2014) 6981-6983.

t
ip
[129] D. Horn, J. Rieger, Angew. Chem. Int. Ed., 40 (2001) 4330-4361.

cr
[130] C. Larpent, S. Amigoni-Gerbier, Macromolecules, 33 (1999) 9071-9073.

[131] C. Larpent, C. Geniès, A.P. De Sousa Delgado, A.M. Caminade, J.P. Majoral, J.F.

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Sassi, F. Leising, Chem. Commun., (2004) 1816-1817.

[132] C. Marmillon, F. Gauffre, T. Gulik-Krzywicki, C. Loup, A.M. Caminade, J.P. Majoral

J.P. Vors, E. Rump, Angew. Chem. Int. Ed., 40 (2001) 2626-2629.
an
[133] A. El Ghzaoui, F. Gauffre, A.M. Caminade, J.P. Majoral, H. Lannibois-Drean,
Langmuir, 20 (2004) 9348-9353.
M
[134] D.C. Tully, J.M.J. Fréchet, Chem. Commun., (2001) 1229-1239.

[135] C.M. Casado, I. Cuadrado, M. Moran, B. Alonso, B. Garcia, B. Gonzalez, J Losada,

ed

Coord. Chem. Rev., 185-186 (1999) 53-79.

[136] D. Astruc, C. Ornelas, J. Ruiz, Acc. Chem. Res., 41 (2008) 841-856.

pt

[137] R.M. Sebastian, A.M. Caminade, J.P. Majoral, E. Levillain, L. Huchet, J. Roncali,
Chem. Commun., (2000) 507-508.
ce

[138] F. Le Derf, E. Levillain, A. Gorgues, M. Sallé, R.M. Sebastian, A.M. Caminade, J.P.
Majoral, Angew. Chem. Int. Ed., 40 (2001) 224-227.
Ac

[139] J. Losada, I. Cuadrado, M. Moran, C.M. Casado, B. Alonso, M. Barranco, Anal. Chim.
Acta, 338 (1997) 191-198.

[140] C. Valerio, J.L. Fillaut, J. Ruiz, J. Guittard, J.C. Blais, D. Astruc, J. Am. Chem. Soc.,
119 (1997) 2588-2589.

[141] E. Martinez-Ferrero, G. Franc, S. Mazères, C.O. Turrin, A.M. Caminade, J.P. Majoral,
C. Sanchez, Chem. Eur. J., 14 (2008) 7658-7669.

[142] M. Wells, R.M. Crooks, J. Am. Chem. Soc., 118 (1996) 3988-3989.

[143] A.M. Caminade, C. Padié, R. Laurent, A. Maraval, J.P. Majoral, Sensors, 6 (2006) 901-
914.

Page 22 of 57
Edited June 17

[144] J. Satija, V.V.R. Sai, S. Mukherji, J. Mater. Chem., 21 (2011) 14367-14386.

[145] B. Boury, R.J.P. Corriu, R. Nunez, Chem. Mater., 10 (1998) 1795-1804.

[146] B.K. Cho, A. Jain, S. Mahajan, H. Ow, S.M. Gruner, U. Wiesner, J. Amer. Chem. Soc.,
126 (2004) 4070-4071.

[147] C.O. Turrin, V. Maraval, A.M. Caminade, J.P. Majoral, A. Mehdi, C. Reyé, Chem.
Mater., 12 (2000) 3848-3856.

t
ip
[148] M.K. Boggiano, G.J.A.A. Soler-Illia, L. Rozes, C. Sanchez, C.O. Turrin, A.M.
Caminade, J.P. Majoral, Angew. Chem. Int. Ed., 39 (2000) 4249-4254.

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[149] A. Bouchara, L. Rozes, G.J.A.A. Soler-Illia, C. Sanchez, C.O. Turrin, A.M. Caminade,
J.P. Majoral, J. Sol-Gel Sci. Tech., 26 (2003) 629-633.

us
[150] Y. Brahmi, N. Katir, A. Hameau, A. Essoumhi, E.M. Essassi, A.M. Caminade, M.
Bousmina, J.P. Majoral, A. El Kadib, Chem. Commun., 47 (2011) 8626-8629.
an
[151] Y. Brahmi, N. Katir, M. Ianchuk, V. Collière, E.M. Essassi, A. Ouali, A.M. Caminade,
M. Bousmina, J.P. Majoral, A. El Kadib, Nanoscale, 5 (2013) 2850-2856.
M
[152] B. Rosenberg, L. VanCamp, J.E. Trosko, V.H. Mansour, Nature, 222 (1969) 385-386.

[153] L. Kelland, Nature Rev. Cancer, 7 (2007) 573-584.

ed

[154] A.M. Caminade, C.O. Turrin, J. Mat. Chem. B, 2 (2014) 4055-4066.

[155] S. El Kazzouli, N. El Brahmi, S. Mignani, M. Bousmina, M. Zablocka, J.P. Majoral,

Current Med. Chem., 19 (2012) 4995-5010.
pt

[156] N. El Brahmi, S. El Kazzouli, S.M. Mignani, E.M. Essassi, G. Aubert, R. Laurent, A.M.
Caminade, M.M., Bousmina, T. Cresteil, J.P. Majoral, Mol. Pharm., 10 (2013) 1459-1464.
ce

[157] M.F. Ottaviani, N. El Brahmi, M. Cangiotti, C. Coppola, F. Buccella, T. Cresteil, S.

Mignani, A.M. Caminade, J.P. Costes, J.P. Majoral, RSC Advances, 4 (2014) 36573-36583.
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[158] A.M. Caminade, S. Fruchon, C.O. Turrin, M. Poupot, A. Ouali, A. Maraval, M.

Garzoni, M. Maly, V. Furer, V. Kovalenko, J.P. Majoral, G.M. Pavan, R. Poupot, Nature
Comm. (accepted).

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Graphical Abstract (for review)

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*Highlights (for review)

Highlights:
* metallodendrimers are efficient, reusable catalysts that may induce dendritic effects
* the dendritic effect improves the yield, enantioselectivity, decreases metal leaching
* dendrimers can produce and stabilize metallic nanoparticles
* dendrimers can produce mesoscopically ordered hybrid materials
* metallodendrimers can be used as drugs, in particular against cancerous cells

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Figure(s)

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Figure(s)

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Figure(s)

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Figure(s)

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Figure(s)

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Figure(s)

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Figure(s)

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Figure(s)

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Figure(s)

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Figure(s)

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Figure(s)

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Figure(s)

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Figure(s)

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Figure(s)

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Figure(s)

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Figure(s)

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Figure(s)

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Figure(s)

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Figure(s)

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Figure(s)

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Figure(s)

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Scheme 1

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Scheme 2

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Scheme 3

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Scheme 4

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Scheme 5

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Scheme 6

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Scheme 7

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Page 53 of 57
Table(s)

Table 1. Comparison of the efficiency of dendrimers versus monomers for asymmetric

catalyzed reactions.
Type of Ligand Metal % ee Ref.
reaction conversion %
Asymmetric PdCl(allyl)2 [89]
allylic
substitution as
in Figure 5
Monomer 100 93
G1 100 93

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G2 100 92

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G3 100 90
G4 100 91

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Asymmetric CuCl2 [103]
benzoylation
of diols as in

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Figure 14

Monomer 35 80
G1
G2
G3
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41
40
78
80
73
Asymmetric [Rh(C2H4)2Cl]2 [104]
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[2+2+2]
cycloadditions
as in Figure 15
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Monomer 49 2
Branch (2 monomers) 32 3
G1 99 98
G2 97 96
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G3 98 97
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Page 54 of 57
caption to Figures and schemes

Caption to Figures and Schemes

Figure 1. a) G3 PAMAM dendrimer showing the stochastic grafting of one porphyrin

complex [6]; b) Complexes of ruthenium constituting all the branching points of a G2
dendrimer [7]; c) Phosphonium G2 dendrimer complexing gold at the core [8]; d) The first
example of dendritic catalyst, based on the Pd complexes of G2 phosphine dendrimers [9]; e)
Silane G1 dendrimer ended by nickel complexes, and used as catalyst [10].

Figure 2. Selected examples of complexes as terminal groups of phosphorus-containing

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dendrimers. a) complexes of phosphines as all terminal groups [22,23] cod = cyclooctadiene;

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acac = acetylacetonate; b) complexes of phosphines for half of the terminal groups [24]; c)
crown-ethers for the complexation of sodium [25]; d) Zwitter-ionic zirconocene derivatives as

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terminal groups [26]; e) ferrocenes as terminal groups [28]; f) gadolinium complexes of
bisphosphonate terminal groups [29].

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Figure 3. Selected examples of complexes inside the structure of phosphorus-containing
dendrimers. a) ferrocene at a single layer [32]; b) ferrocene at all layers [33]; c)
phthalocyanine as core [34]; d) triazatriolefinic macrocycle as core [35]; e) selective
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complexation of P=N-P=S linkages [36]; f) complexation of phosphine and of P=N-P=N-P=S
linkages inside the structure [37] g) “onion peel” structure [38].

Figure 4. Dendrimers ended by diphosphine groups or having one diphosphine group at the
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core. Pd complexes used for catalyzing Stille couplings (cases A and B); Ru complexes used
for catalyzing Knoevenagel condensations (cases C and D); Comparison between the
efficiency of the dendrimer ended by Ru complexes and that of the dendrimer having a single
complex at the core for catalyzing diastereoselective Michael additions (case E) [65]. In all
ed

cases, the first runs are represented in black, the re-uses after recovery by precipitation in
grey.
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Figure 5. Asymmetric allylic alkylations catalyzed by Pd complexes of (2S)-2-amino-1-

(diphenylphosphinyl)-3-methylbutane used as terminal groups of a G3 dendrimer. Influence of
two recovery and re-use of the dendritic catalyst on the yield and ee, with different bases and
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substituents [70].

Figure 6. Comparison of the efficiency of recycling of Pd complexes and Pd nanoparticles,

for catalyzing Heck couplings. Black bars for the first runs, grey bars for the re-use [71].
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Figure 7. Recycling experiments (in grey) carried out by changing the substrates at each step.
The arrows for runs 4 and 12 indicate that both experiments were carried out with the same
substrates, and afforded the product with the same yield, after 3 and 11 re-uses, respectively
but with a longer time of reaction (2 hours (run 12) versus 30 minutes (run 4)) [76].

Figure 8. Non-covalent grafting of a dendritic catalyst onto magnetic cobalt nanoparticles

protected by graphene layers, and their use for Suzuki couplings. Eleven recycling
experiments carried out using a magnet for the synthesis of the anti-inflammatory drug
felbinac [81].

Figure 9. Illustration of the dendritic (or dendrimer) effect. Same number of functions, but
different generations, and different efficiency.

Page 55 of 57
Figure 10. Three types of monomeric and dendritic complexes for which no or very slight
dendritic effects have been observed when catalyzing a) Stille couplings [89], b) asymmetric
allylic alkylations [90], and c) C-C cross-coupling reactions [91].

Figure 11. Copper catalyzed arylations. Comparison of the efficiency of a monomer and
generations 1 to 3 of the dendrimer, using the same quantity of copper in all cases [92].

Figure 12. Increased catalytic efficiency of positively charged dendrimers for 1-octen-3-ol
isomerization when the generation of the dendrimer increases [96].

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Figure 13. Suzuki couplings carried out with two monomers and two dendrimers,

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emphasizing the efficiency of dendrimers for decreasing metal leaching. Influence of Pd
leaching on the percentage of reaction when re-using the dendritic catalysts [100].

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Figure 14. Azabis(oxazolines) as terminal groups complexing Cu, for catalyzing asymmetric
benzoylations. Influence of the generation and the recycling on the yield and ee. The

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maximum theoretical yield is 50% [104].

Figure 15. Comparison of the efficiency of a monomeric catalyst and of 3 dendritic catalysts
for increasing the ee in an asymmetric [2+2+2] cycloaddition reaction [105].
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Figure 16. Switch ON/OFF/ON experiments carried out with a monomer and a first
generation dendrimer for the isomerization of 1-octen-3-ol into 3-octanone (the graph on the
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left corresponds to the percentage of isomerization with time induced by the dendrimer in the
switch process) [110].

Figure 17. Illustration of the synthesis of AgxO nanoparticles with dendrimers grafted to
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silica nanoparticles and functionalized by PEG and phosphonate functions [126].

Figure 18. A water-soluble dendritic structure linked to a nanolatex through a

tetraazamacrocycle suitable for the complexation of Cu2+ [131].
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Figure 19. Organic redox active functions as terminal groups of dendrimers, used for the
surface modification of Pt electrodes [137]. The electrochemical response of the TTF crown
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ether is modified by the complexation of Ba2+ [138].

Figure 20. Optic sensor based on a dissymmetrical fluorescent dendrimer grafted to a titania
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thin film, and used for the detection of phenols which quench the fluorescence (quencher =
functionalized phenols, in particular nitrophenols) [141].

Figure 21. Dendrimers with different diaza ligands as terminal groups and the corresponding
copper (II) complexes. A: N-(pyridin-2-ylmethylene)ethanamine series; B: N-(di(pyridin-2-
yl)methylene)ethanamine series; C: 2-(2-methylenehydrazinyl)pyridine series. Graph:
Antiproliferative activity of couples of G3 dendrimers (free ligands and complexes) towards
HL60 cells after a 72 h exposure, expressed as the percentage of cell growth inhibition at 1
μM concentration of dendrimers [156].

Page 56 of 57
Scheme 1. The principle of the step-by-step divergent synthesis of dendrimers. The activation
step can be any type of modification of the terminal groups.

Scheme 2. Synthesis of phosphorhydrazone dendrimers, starting from a hexafunctional core

[20]. Two types of drawings are shown: the full structure, and the linear representation with
parentheses for each generation, which will be used in many of the following Schemes and
Figures.

Scheme 3. Dendrimers ended by thiols for the synthesis of nanocrystals of naked Au55
clusters [122].

t
ip
Scheme 4. Reaction of dendrimers ended by 15-membered triolefinic azamacrocycles with
Pt2(dba)3 (dba = dibenzylidene acetone), resulting in Pt nanoparticles organized in dendritic

cr
networks, i.e. organic dendritic structures interweaved with inorganic dendritic structures
[125].

us
Scheme 5. Molecular asterisks composed of viologen linear arms, for the synthesis and
stabilization of gold nanoparticles [128].

Scheme 6. Hybrid nanomaterials based on the cluster [Ti16O16(OEt)32] and first generation
an
dendrimers ended by alcohol or carboxylic acid groups [148].

Scheme 7. G4 dendrimers variously functionalized (phosphonic salts [150], ammoniums or

M
diketones [151]), and used for obtaining networks of anatase nanoparticles by reaction with
Ti(OiPr)4.
ed
pt
ce
Ac

Page 57 of 57