Metal-Containing Dendritic Polymers
Fiona J. Stoddart and Thomas Welton*
Department of Chemistry, Imperial College of Science, Technology and Medicine, South
Kensington, London SW7 2AY, UK.
Abstract
Metal-containing dendrimers (metallodendrimers) have attracted a great deal of attention
recently and their study is becoming a growing field. Many workers have entered the field
and it is rapidly developing. In this review, the preparation, characterisation and applications
of metal-containing denrimers are discussed. The principal methodologies for the preparation
of dendrimers are first demonstrated and then the derivatisation of organic dendrimers to
form suitable potential ligands is presented. Finally the formation of transition-metal
complexes of the dendrimers is discussed. The manuscript is organised such that the
metallodendrimers are discussed by donor element in the dendrimer. As one might expect,
phoshine and nitrogen-donor complexes have dominated this initial phase of synthesis.
However, there are reports of metallodendrimers with a wide variety of donor atoms. In the
few years since the first metallodendrimers were prepared the field has moved rapidly
towards potential applications, and this has been noted.
1
Introduction
Over the last twenty years, a new class of polymers known as dendrimers has fascinated many
chemists. This review concentrates on those dendrimers that contain metals. However, a
brief introduction to dendrimers in general and the major approaches to their syntheses is
given. More detailed reviews on this subject have been given elsewhere.1
The term dendrimer is derived from the Greek word dendra meaning tree. These
highly branched macromolecules have compelling molecular structures that are reminiscent
of patterns often observed in nature and particularly those found in trees and in coral.
Dendrimers – also called arborols2 or cascade3 molecules – exhibit controlled patterns of
branching and ideally are monodisperse, i.e.; all the molecules should have exactly the same
molecular masses, constitutions and average dimensions. The larger dendrimers, which have
globular structures, carry many close-packed surface end groups and contain internal cavities.
The interest in dendritic polymers stems from the possibility that their architectures, which
differ from those of traditional linear step-growth polymers, offer exciting prospects of new
applications.4
Before 1940, branched molecular structures had been considered to be responsible for
the insoluble and intractable materials formed during polymerisations.1b These materials
were largely ignored since it was invariably impossible to isolate discrete molecular
compounds and assign them definite structures.
In 1978 Vögtle and co-workers published a synthetic strategy which involved the
“cascade-like” synthesis of acyclic, branched polyamines.5 The synthesis, which is illustrated
in Scheme 1, began with an exhaustive Michael addition of the monoamine 1 to acrylonitrile,
leading to the annexation of two branches per amino group, thus affording the bisnitrile 2.
The nitrile groups were then reduced to amine functions, using cobalt(II)/sodium borohydride
2
to give the bisamine 3. Repetition of these two steps afforded the hexa-branched tetraamine
5, via the tetranitrile 4. Although this synthesis was not continued beyond this point because
of problems encountered in the reduction step, the principle that repeated cycles of reactions
could lead to controlled polymer growth had been demonstrated.
R
R
R
CN
NH2
N
Co(III)/NaBH 4
N
AcOH
MeOH
CN
NC
1
H2N
2
3
NH2
R
R
N
N
CN
Co(III)/NaBH 4
AcOH
N
N
CN CN
NC NC
4
Scheme 1.
N
N
MeOH
H2N
H2N
NH2
NH2
5
“Cascade-like” synthesis of acyclic, branched polyamines
In 1981, Denkewalter et al.6 patented the synthesis of highly branched polylysine derivatives.
Each member of this series of compounds was monodisperse, consisting of branching units of
differing lengths. From 1985 onwards, two research groups, one headed by Tomalia7 and the
other by Newkome,2,8 simultaneously developed families of dendrimers synthesised using this
divergent method (see below). In 1990, Fréchet and Hawker9 employed a different method,
the convergent approach (see below), to prepare poly(aryl ether) dendrimers.
3
Dendritic Structure
Figure 1 depicts the structure of a typical dendrimer.
The following points must be
considered and, where appropriate, adapted when describing the structures of dendrimers:-
(i)
There is a central point known as the initiator core: in the dendrimer shown in Figure
1, four branches emanate from a core and so the core multiplicity (Nc) is four.
(ii)
Each branch contains further branching sites: in the example illustrated in Figure 1,
the degree of branching (Nb) is two.
(iii)
Each new layer of branches that are constructed upon old branch points is called a
generation (G): generations are numbered at 0, 1, 2, 3 ... and so on.
(iv)
The branch cell unit lengths (l) are determined by the choice of branched monomers.
G=2
l
4
G=1
Figure 1.
Schematic representation of a dendrimer
The number of monomer units in a dendrimer increases exponentially as a function of the
generation. As the dendrimer grows in size, the end groups reside closer and closer to one
another. Eventually, this branch-growing process results in surface congestion, a feature that
prevents further growth from all branch points with the consequence that the dendrimer can
no longer be monodisperse. The highest generation at which the dendrimer is still potentially
monodisperse is described as its “starburst limit”.
5
Dendrimer Synthesis
Dendrimers are constructed in stages using repetitive synthetic strategies. Both the divergent
and convergent approaches to dendrimer synthesis have advantages and disadvantages.
The Divergent Approach
The synthetic approach to dendrimer formation, which has become known as the divergent
method, emerged during the period 1978-1987 with many of the seminal contributions
coming from Newkome 2,8 and Tomalia.7 The basic concept, which is that of starting at the
core and working outwards in a divergent fashion to create a highly branched structure, has
subsequently been developed and exploited by many research groups world-wide.10 An
illustration of the divergent approach to the synthesis of a dendrimer is shown in Scheme 2.
8x
4x
Core
molecule
Scheme 2.
6
First-generation
dendrimer
Second-generation
molecule
Schematic representation of the divergent synthesis of dendrimers
A multifunctional core molecule – in this case, one with four functional groups – is reacted
with four monomer molecules to give the first generation dendrimer. Repetitive addition of
similar building blocks – usually achieved by a protection-deprotection procedure – affords
successive generations. It is important to ensure that each set of reactions leading to these
new generations has been completed before the next cycle of reactions is commenced, if
defects in the dendritic structure are to be avoided.
Using the divergent approach, it is possible to prepare up to tenth generation
dendrimers with molecular weights of the order of 700,000 and with more than 3,000 end
groups per molecule.11 The advantage of the divergent method is that the production of
several grams of dendrimer is easily attainable since, with each subsequent generation, the
molar mass of the dendrimer is greatly increased.
This method is not without its drawbacks. As the dendrimer grows in size, the
number of end groups involved in the reaction increases and the likelihood of incomplete
growth steps leading to defects in the structure becomes greater. It is often difficult to detect
the precise extent of conversion from one generation to the next.
As a consequence,
imperfect samples of dendrimers, which are virtually impossible to purify and characterise,
since they may differ only slightly from the desired monodisperse samples, are obtained.
Therefore, if the divergent method is to be employed successfully, extremely efficient and
high-yielding reactions are required in order to ensure the production of dendrimers with low
polydispersities. This often poses a great synthetic challenge.
The Convergent Approach
Fréchet and Hawker first proposed an alternative approach to dendrimer syntheses, known as
the convergent method.9,12
7
Here, the reverse of the divergent method is applied; the
synthesis starts at what will eventually become the periphery of the dendrimer and progresses
inwards. Surface units are linked together increasingly with more monomers until a wedgeshaped molecule is generated, carrying a reactive group at its apex. The final step of the
synthesis involves attaching the desired number of wedges to a multifunctional core. This
approach is illustrated in Scheme 3.
The attraction of the convergent method lies in the fact that only a small number of
molecules are involved in the reaction steps that form each successive generation.
In
contrast, increasing numbers of molecules are involved in the reactions in the later stages of a
synthesis using the divergent approach. Large excesses of reagents and slight impurities can
also be avoided, without sacrificing high yields and, because of easier purification, reactions
no longer need to be as efficient, meaning that a much larger choice of reaction types are
available.
Two of I
+
II
I
Two of II
+
Three wedges
Repeat
n times
+
Wedge
Dendrimer
8
Scheme 3.
Schematic representation of the convergent synthesis of dendrimers
The main disadvantage of the convergent approach is that it is not accompanied, after
each reaction cycle, by the marked increase in molar mass, which is observed in the case of
the divergent method.
The total number of steps involved in the construction of the
dendrimer using the convergent method is not actually reduced compared with that needed in
the divergent approach, yet significantly more starting material is required. Also the higher
generation dendritic wedges can experience severe steric problems when reactions to attach
their reactive apex groups to core molecules are attempted. Thus, the convergent approach
has been found to be less useful than the divergent one for the synthesis of dendrimers
approaching their starburst limit.
Metallodendrimers
During the last decade, those working with dendrimers have switched their focus from the
initial synthetic directions explored mainly by organic chemists to a more applied emphasis.
Thus, metallodendrimers are becoming of interest from a materials science perspective
because of their unique physical properties, leading to potential photophysical and catalytic
applications. Metallodendrimers show substantial structural diversity and their properties and
applications are wide-ranging. Metallodendrimers may be classified by where the metal
appears in the dendrimer, at the centre, as connectors, as branching units, or as peripheral
units of the dendrimer.13 However, here the metallodendrimers are classified by ligand type,
i.e., the particular ligand which complexes the metal centre to/within the dendrimer – thus
viewing them from the perspective of the inorganic chemist. In many of the following
illustrations, only one section of the dendrimer has been portrayed and a “W” within a wedge9
shaped motif represents other dendritic arms identical to the one which has been drawn out in
full.
Dendrimers as Counter ions
Perhaps the simplest way in which to include metals in a dendritic structure is to use the
dendrimer as a counterion for a well-defined metal or metal complex. The metal may bind to
a surface site on the dendrimer (exo-receptor) or to a site within the internal cavaties of the
dendrimer (endo-receptor).
Hydrolysis of ester-terminated PAMAM dendrimers with Group 1 metal (Na+, K+,
Cs+ and Rb+) hydroxides resulted in the formation of salts as white hygroscopic powders.7d
Direct observation of these single dendrimer molecules by Channel Tunelling Electron
Microscopy has been achieved. Further studies were conducted using carboxylate-terminated
PAMAMs and their complexes with Fe3+, Gd3+, Mn2+, Pr3+ and Y3+ ions.1g
In another investigation,14 which sought to support the molecular mechanics
simulations with experimental evidence, the properties of the carboxylate salts of the halfgeneration PAMAM dendrimers were likened to those of anionic micelles. The ability of
these anionic dendrimers to effect the kinetics of the electron-transfer quenching of
photoexcited Ru(phen)32+ has been examined.15 The emission decay of the metal-to-ligand
charge transfer (MLCT) excited state of the probe – Ru(phen)32+ bound to half-generation
PAMAMs was analysed in the presence and absence of the quencher – Co(phen)33+. The
studies showed that the probe lifetimes were enhanced when the complexes were bound to
dendrimers as compared with unbound complexes. It was concluded that the quenching of
dendrimer-bound Ru(phen)32+ by Co(phen)32+ occurs at the surface of the dendrimer. These
results indicate that the cationic Ru(phen)32+ binds strongly to the negative surface of the
10
dendrimer. This has been confirmed by another study study of Ru(phen)32+ labeled with a
nitroxide radical, via –NHC(O)OCH2- or –O(CH2)8O- units, as an EPR probe.16
More
recently, similar results using protonated amino-terminated PAMAMs and Ru(4,7(SO3C6H5)2-phen)34- as the probe have been reported.17
Hence, these systems provide
examples of a dendrimer acting as an exo-receptor.
Phosphorus-Donor Metallodendrimers
Phosphorus-containing dendrimers, in which the core and subsequent branch points are
pentavalent phosphorus atoms and which possess peripheral aldehyde groups have been
prepared by Majoral et al.10d
The dendrimers – up to the tenth generation – were
functionalised with phosphino groups and then reacted with AuCl(tetrahydrothiophene) to
give dendrimers with AuCl moieties as the peripheral units.18 The authors note that the
reactivity of all generations towards gold complexation is similar, and therefore, independent
of the size of dendrimer used. Most recently, Majoral et al.19 have reported the incorporation
of gold into different generational layers of dendritic molecules. Complexation occurs both at
the sulfur-donor P=N-P=N-P=S fragments and the terminal CH2PPh2 moieties. The dendritic
fragment, shown in Figure 2, has been modified at the generation 1 level to introduce
ligands, which are able to coordinate gold. The metallodendrimer has eighteen internal AuCl
units – six at the P=N-P=N-P=S linkages and twelve at the phosphino groups.
complexes formed can be characterised unambiguously by
31
The
P NMR spectroscopy. Studies
are currently underway to extend this methodology to incorporate a variety of different metals
within the cascade structure of dendrimers.
11
Me
N
H N
C
S
Me
W
W
N
H
C
N
P
W
W
P
N
N
P
N
P
OAr
OAr
P
S
O
O
Me
H
C N
Me
O
C
H
N
W
N
C P
H2
Cl-Au
N
P
N
S
O
N
C N
H
Me
C
H
O
N
N
Ph
N
N
Me
Me
Me
N
N
P
S
OAr
OAr
Ph
P
Au-C l
Ph
Ph
Figure 2.
HC
N
P
OAr
O
H
C
Cl-Au
OAr
P
O
P
S
N
S
Me
O
CH
OAr
S
P
O
OAr
N P
Gold complexation within the cascade structure of a dendrimer
Majoral et al.20 have also prepared diphosphino-terminated dendrimers complexed to
rhodium, palladium, platinum and ruthenium.
Addition of hydrazine to dendrimers –
generations 1-3 – with terminal aldehyde groups produced CH=NNH2 end groups and
subsequent reaction with Ph2PCH2OH (2 equivalents per NH2 group) led to the formation of
the desired diphosphine ligands.
Reaction of these ligands with RuH2(PPh3)4 gave the
metallodendrimers shown in Scheme 4. The reactivity of these dendritic complexes was
found to be very limited, compared with the reactivity of the monomeric starting material
complex.
However, the metallodendrimers reacted slowly with CO to give dihydrido
carbonyl derivatives, where the CO ligand is located trans to one of the hydrides. In order to
produce a more reactive ruthenium site, the diphosphino-terminated dendrimers were reacted
with RuH2(H2)2(PCy3)2 to give the isomeric dihydride dihydrogen derivatives shown in
Scheme 4. The isomer produced is dependent on the reaction conditions employed, but all of
the isomers reacted with CO to give one unique dihydrido carbonyl complex. Majoral et al.20
12
are currently investigating the extent of the chemical reactivity displayed by these complexes
and their application as catalysts for ketone hydrogenation.
PPh2
RuH 2(PPh3)4
N
PPh2
PPh3
PPh3
Ru
Ph2P
H
H
CO
Ph2P
N
n
CO
Ph2P
PPh3
Ru
N
Ph2P
H
H
n
n
RuH 2(H 2)2(PCy 3)2
H
H
H
Ph2P
Ph2P
PCy3
N
Ru
N
Ph2P
H
H
H
Ru
Ph2P
n
N
PCy3
H
H
PCy3
H
Ru
Ph2P
H
H H
Ph2P
n
n
CO
CO
CO
CO
Ph2P
N
PCy3
Ru
Ph2P
H
H
= Dendrimer
Scheme 4.
n
G = 1, n = 6; G = 2, n = 12; G = 3, n = 24
Reactivity of diphosphine-terminated dendrimers
Schmidbaur et al.21 have used “spacers”, e.g., -(diphenylphosphino)propionic acid, to
functionalise third and fourth generation poly(propylene)imine dendrimers with terminal
diphenylphosphino groups. Subsequent addition of (dimethyl sulfide)gold chloride gave the
metallodendrimers as stable colourless solids (Scheme 5). Monomeric model compounds
were also synthesised from methylamine and ethylenediamine in order to ascertain suitable
coupling conditions for the synthesis of the dendritic N-alkylamides. Schmidbaur et al.21
envisage applications for these metallodendrimers in biochemical diagnostics and imaging
and as antiflammatory and antitumour drugs.
13
HOOC-C 2H4-PPh2
NH2
H
O
N C
H
N
n
n EDC, NEt 3
= Dendrimer
Scheme 5.
Me2SAuCl
PPh2
O
C
PPh2 AuCl
n
G = 3, n = 16; G = 4, n = 32
Synthesis of chlorogold(I)diphenylphosphino-terminated dendrimers
Second and third generation polypropylene(imine)22 dendrimers have also been surface
functionalised by Reetz et al.23 In this case, a double phosphinomethylation – similar to that
of Majoral et al.20 described above – of each of the peripheral primary amine functions was
achieved. A variety of palladium, iridium, nickel and rhodium complexes were reacted with
the diphosphino-terminated
dendrimers.
The palladium-containing dendrimers were
employed as catalysts in the Heck reaction. A significantly higher catalytic activity was
observed for the dendritic catalysts compared with the activities of the monomeric analogues.
The authors attributed this enhancement of activity to the thermal stability of the dendrimers
which prevents the undesired formation of elemental palladium from occurring – a major
problem for the monomeric complexes. By contrast, the rhodium-containing dendrimers
display comparable catalytic activities in hydroformylations to that of the monomeric
complex.
14
O
P(OR)2
P(OR)2 LAH
Ph P
PhPH2
O
PH 2
P(OR)2
P
LAH
Ph P
PH 2
Ph P
PH 2
P(OR)2
7
6
PH 2
O
O
PH 2
P
8
PH 2
9
NCMe
Pd
R 2P
R 2P
PR 2
P
PR 2
PR 2
P
P
[Pd(MeCN) 4](BF4) 2
P
Ph
Ph P
P
P
R 2P
Pd
Me CN
PR 2
P
PR 2
PR 2
P
P
PR 2
P
PR 2
P
PR 2
P
PR 2 R2
P
NCMe
Pd
Pd
P
R 2P
Pd
P
PR 2 R2
NCMe
NCMe
10a,b
R = Ph, Et
Scheme 6.
11a,b
Synthesis of palladium-containing dendrimers
Palladium complexes of several small organophosphine dendrimers synthesised by
DuBois et al.10c exhibit catalytic activity for the electrochemical reduction of CO2 to CO.
The synthesis of one example of these metallodendrimers is shown in Scheme 6. Addition of
diethyl vinylphosphonate to the primary phosphine 6 gave the phosphonate 7 and subsequent
reduction with lithium aluminium hydride resulted in the phosphine 8. Repetition of these
two steps afforded the phosphine 9 which undergoes reaction with vinyldiphenylphosphine or
vinyldiethylphosphine to give dendrimers 10a and 10b, respectively. The reaction of 10a,b
with [Pd(MeCN)4][BF4]2 formed the metallodendrimers 11a,b containing five square planar
metal centres. These dendritic acetonitrile complexes catalyse electrochemical CO2 reduction
with rates and selectivities which are similar to analogous monomeric catalysts.
15
16
Nitrogen-Donor Metallodendrimers
The majority of the metallodendrimers described in the literature belong to this category, with
many examples involving polypyridine-type ligands.
Balzani et al.24 have developed a synthetic procedure in which a complex is used as a
ligand and another is used as a metal (“complexes as ligands/complexes as metals”) to
prepare luminescent and redox-active metallodendrimers.
Dendrimers that incorporate
specific “pieces of information” in their building blocks, such as the abilities to absorb and
emit visible light and to undergo reversible multielectron redox processes, have potential
applications in molecular electronics and photochemical molecular devices.
Both the divergent and convergent approaches to the synthesis of nitrogen-containing
metallodendrimers have been employed and are illustrated in Scheme 7. Using the divergent
method, the first step is the construction of the core, [Ru(2,3-dpp)3]2+ (12), which has three
chelate sites available and is, therefore, a “complex as ligand.” The building block, [Ru(2,3Medpp)2Cl2]2+ (13) has two labile chlorides – therefore representing a “complex as metal” –
and two bridging ligands, which have been protected to prevent further metal coordination.
The reaction of 12 with 13 gives the first generation metallodendrimer 14 and deprotection of
the six peripheral chelating sites yields compound 15. The second generation dendrimer 17,
which has ten ruthenium centres, is formed by the reaction of 15 with the capping unit,
[Ru(bpy)2Cl2] 16. In the convergent approach, the dendritic wedge 18 – “complex as metal”
is reacted with the core compound 12 to give the metallodendrimer 17.
17
4+
20 +
N N
N N
N Ru N
N N
N Ru N
N N
Cl
N
Cl Ru N
N N
N N
2+
N
N
N Ru N
N N
N
18
N
N
N N
N N
N Ru N
N N
N Ru N
N N
N Ru N
N N
N Ru N
N N
N
N N
N N
N N
N Ru N
N N
N N
N N
N Ru N
N N
N Ru N
N N
N N
N N
N Ru N
N N
N Ru N
N N
12
N N
N Ru N
N N
2+
Me
N N
N
Me
17
N N
N Ru N
Cl
Cl
N
N N
N Ru N
Cl
Cl
13
16
Me
N N
N
Me
14 +
N
N N
N
N Ru N
N
N
N Ru N
N N
N
N
N
N Ru N
N
N
N
N
Me
N Me
14
N
N N
N Ru N
N N
N Ru N
N N
N N
N Ru N
N
N
Deprotection
N N
8+
N
N N
N
Me
N N
N N
Me
N
N
N
N N
Ru
N
N
N
N N
N
N
N
N Ru N
N
N
N
N
N
15
Scheme 7. Convergent and divergent synthesis of the Balzani dendrimers
The absorption spectrum and redox patterns of the dendrimer resemble the sum of those
of its mononuclear component units and each of these units brings its own redox properties
18
into the macromolecular structure. By varying the metals and/or ligands of the building
blocks employed, it is possible to design dendrimers with predetermined redox patterns.
Thus, synthetic control of the number of electrons exchanged at a certain given potential is
achieved and their application as multielectron-transfer catalysts is of potential interest.
Constable and co-workers25 have prepared a variety of metallodendrimers employing
terpyridine-based ligands using both divergent and convergent methodologies. Their latest
development, using convergent assembly, is shown in Scheme 8. A ruthenium complex 19 is
reacted with an electrophile – bis(bromomethyl)benzene – to give complex 20 possessing an
electrophilic site remote from the metal centre.
Reaction with a nucleophile – 4,4-
dihydroxy-2,2-bipyridine – yields the binuclear dendritic wedge 21 which has a bipyridine
ligand at its focal point. Thus, rapid coordination with either iron(II) or cobalt(II) leads to the
formation of the heptanuclear metallodendrimer 22.
Vögtle and Balzani26 have employed a similar strategy to that described above in the
synthesis of ruthenium complexes of dendritic bipyridine ligands. The ligands have been
prepared by the attachment of branches at the 4 and 4 positions of bipyridine using a
procedure reported by Newkome et al.8 The dendritic bipyridines – generations 1-3 – were
reacted with Ru(III) chloride to produce a metallodendrimer where the metal is only present
in the core. These complexes exhibit similar absorption and emission properties to those of
an unsubstituted Ru(II) bipyridine complex. However, a longer excited-state lifetime was
observed for the higher generation dendrimers because of the shielding effect of the dendritic
branches on the metal core, which limits the quenching effect of molecular oxygen.
19
N
N
N
OH
Br
N
Ru
N
N
O
N
O
N
N
N
Ru
N
N
N
N
Br
N
N
OH
Ru
N
N
N
N
N
N
OH
O
O
O
N
N
N
Ru
19
20
N
21
Br
N
N
N
Ru
N
N
N
O
N
N
Ru
N
N
N
N
N
N
N
O
O
O
N
Ru
N
N
O
O
N
N
N
M
N
O
N
N
N
N
O
O
O
O
N
N
N
N
Ru
Ru
N
N
N
N
N
N
O
M = Fe, Co
N
N
N
Ru
22
Scheme 8.
20
N
N
N
N
N
Convergent synthesis of a Constable dendrimer
Recently, more attention has been focused on the ability to incorporate predetermined
subunits into the dendritic structure, thus possessing the synthetic control necessary to create
series of “dendritic assemblies.” With this aim in view, Newkome et al.27 investigated the
connection of two different sized dendritic fragments to a ruthenium centre, thus forming a
bis-dendrimer. A recent publication by Newkome et al.28 describes the connection of two
different dendritic fragments to two separate dendritic core molecules to give the snowflakelike metallodendrimers shown in Figure 3.
This shift in focus from the synthesis of
traditional dendrimers, where the repeat/branching units are identical, to the preparation of
macromolecular dendritic assemblies is becoming more apparent in recent research.
Chemists are interested in tailor-made dendritic molecules that allow a greater control of the
properties exhibited by the macromolecular array.
A convergent synthesis of organoplatinum dendrimers developed by Puddephatt et
al.29 is illustrated in Scheme 9. An oxidative addition reaction of the bromomethyl groups on
bipyridine 24 to two square planar dimethylplatinum centres on 23 gave the dendritic unit 25.
The diimine group at the centre of the molecule was then complexed to a different
dimethylplatinum centre 26 to yield the trinuclear complex 27.
These two steps were
repeated to give the dendritic wedge 28 and subsequent reaction with the core compound 29 –
1,2,4,5-tetrakis(bromomethyl)benzene – yielded metallodendrimer 30 containing 28 platinum
centres.
Dendrimers that possess a metal porphyrin unit as the core have the potential to mimic
the biological functions of haemoproteins and act as sterically hindered oxidation catalysts.
Dendrimers (generations 1-3) with a zinc-porphyrin core and Newkome-type8 polyether
amide branches synthesised by Diederich et al.30 can be viewed as encapsulated redox-active
centres. The influence of the close-packed dendritic branches on the redox properties of the
21
central zinc porphyrin unit was studied by cyclic voltametry. A decrease in the first reduction
potential of the zinc-porphyrins with increasing dendrimer generation was observed. Thus,
the dendritic fragments serve to shield the porphyrin centre and hinder the addition of
electrons to it. More recently, Diederich et al.31 have modified the peripheral groups on the
dendrimer to prepare water-soluble dendritic iron-porphyrins and similar electrochemical
behaviour was observed.
Fréchet et al.32 have also investigated the effects of the dendrimer generation on the
properties of a porphyrin core. They discovered that although higher generation dendrimers
can bury the core site and hinder electron-transfer to it, small molecules such as
benzylviologen are able to penetrate the dendritic shell. Photophysical studies revealed that
the dendritic shell does not interfere with the ability of benzylviologen to quench the
fluorescence of the metalloporphyrin.
This result suggests that dendrimers with
metalloporphyrin cores could be employed as catalysts. Modification at the periphery of the
dendrimer, or incorporation of rate enhancing ligands into the dendritic structure, would
allow their fine-tuning for specific catalytic applications.
These, apparently contradictory, results can be explained by the methods used to study
the electron transfer (cyclic voltametry) and excited state quenching (fluorescence
spectroscopy). The former is an interfacial experiment where the metal centre is required to
come into close contact with a large solid electrode. The dendritic structure around the metal
porphyrin prevents this close contact and hence inhibits electron transfer. The latter is a
solution experiment where the flexibility of the dendritic arms allows the probe molecule to
approach the metal centre.
Suslick et al.33 have studied the role of dendritic porphyrins as regioselective catalysts
in the epoxidation of olefins.
22
The metallodendrimer shown in Figure 4 and its first
generation equivalent were prepared using a convergent synthesis. The peripheral tert-butyl
groups served to increase steric hinderance and enhance solubility.
Epoxidation of
nonconjugated dienes and mixtures of linear and cyclo-alkenes were carried out using
iodosylbenzene as the oxygen donor.
Using 1:1 alkene mixtures, the dendrimer-
metalloporphyrins showed greater selectivity for epoxidation of 1-alkenes over cyclooctene.
This selectivity was higher for the second generation metallodendrimer than for the first
generation one. The reason for this increase in selectivity shown by the dendritic catalyst was
attributed to the steric influence of the bulky second generation dendrimer which led to
preferential penetration of the linear alkenes.
The synthesis and properties of dendrimer porphyrins have also been reported by Aida
et al.34
Most recently, they have used negatively and positively charged dendrimer-
metalloporphyrins to construct electrostatic assemblies.35 Studies on these systems showed
that the spatial arrangement of these two communicating functionalities could be controlled
with nanometric precision. Thus, their potential application in nanomaterials science can be
anticipated.
23
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
N
MnCl
N
N
N
O
W
O
W
W
Figure 4.
A dendrimer-metalloporphyrin
Porphyrin-functionalised dendrimers have also been investigated for their
potential biological/therapeutic uses. The use of antibodies, modified with radioisotopes or
cytotoxic drugs in cancer imaging and therapy, is of great interest on account of the inherent
specificity of the antibody-antigen interaction. However, these modifications often diminish
or eliminate the biological activity of the macromolecule, therefore destroying its targeting
potential. In order to prevent these problems, intermediate linker molecules, which can be
highly modified with a drug, but which will only modify a single site on the surface of the
antibody, would be of great advantage. Roberts et al.36 have used PAMAM dendrimers to
covalently couple synthetic copper-chelated porphyrins to antibody molecules. The antibodydendrimer-porphyrin conjugate is illustrated in Figure 5.
24
Gansow
et
al.37
have
attached
the
nitrogen-donor
macrocycle
1,4,7,10-
tetraazacyclododecanetetraacetic acid to PAMAM dendrimers and then formed antibody
conjugates. The chelator-dendrimer-antibody constructs were easily labeled with
and
212
90
Y,
111
In
Bi, suggesting that these types of complexes could be used in radiotherapy and
imaging. In a more detailed study, dendritic magnetic resonance imaging contrast agents,
consisting of Gd(III) complexes of the chelator 2-(4-isothiocyanatobenzyl)-6-methyldiethylenetriaminepentaacetic acid anchored to amino-terminated PAMAMs, were developed
by Tomalia et al.38 These complexes enhanced magnetic resonance images and were found to
be more effective contrast agents than other commercially available macromolecule-chelate
complexes, such as those formed using albumin, polylysine and dextran.
Antibody
O
CH
Dendrimer
CH2
NH
NH2
H 2N
NO2
NH2
H 2N
O
HN
CH2
C
SO3 –
N
H
N
Porphyrin
H
N
–
25
N
O3S
SO3 –
Figure 5. Representation of an antibody-dendrimer-porphyrin conjugate
Nickel-containing dendritic catalysts have been designed and tested for their catalytic
activity in the Kharasch addition by van Koten et al.39 The catalysts – a second generation
example of which is shown in Figure 6 – are carbosilane dendrimers, which have been
surface-functionalised with nickel complexes.
Although the catalytic activities of the
dendrimers were found to be lower than that of the monomeric analogue, the catalysts could
be easily precipitated from solution and therefore recycled. More recently, van Koten et al.40
have reported the preparation of platinum-containing dendrimers which possess the same
surface functionalities as those of the dendrimer shown in Figure 6, yet contain aryl-ester
branching units instead of carbosilane backbones. The complexes reversibly bind SO2 both
in the solid state and in solution and can therefore be used as molecular sensors for this toxic
gas. Desorption of SO2 is achieved using mild conditions, thus regenerating the “detector”
compounds.
26
Me 2N
Br
Ni
NMe2
O
O
Me
W
W
Si
Si
W
O
Si Me
Me
O
Si
Me
Me
Si O
N
H
O
O
NMe2
N
H
Ni Br
NMe2
Me
O
O
HN
NMe2
Ni
Br
NMe2
Figure 6. Second generation silane dendrimer functionalised with nickel complexes
Chow and Mak41 have prepared dendritic bis(oxazoline) copper complexes (generations 0-3)
which catalyse the Diels-Alder reaction. The catalytic centre is at the focal point of a
dendritic wedge constructed of Fréchet-type9 polyaryl ether dendrons. The catalysis of the
Diels-Alder reaction between cyclopentadiene and crotonyl imide (Scheme 10) was studied.
Lower rates of reaction were observed using generation 3 dendrimer catalysts than when
generations 0-2 were used.
This observation is thought to be a consequence of the
morphological change shown by the dendrimer as the generation increases. The catalytic core
is essentially open to the surroundings at lower generations but is partially buried in the
interior of the dendritic branches at generation 3. These and other studies discussed above
27
indicate that a variety of types of dendritic catalyst can be synthesised but further work on the
dendritic structure is needed before superior catalysts can be prepared.
W
W
O
O
N
O
O
N
Scheme 10.
N
Cu
(OTf)2
O
O
N
O
O
Diels-Alder reaction catalysed by bis(oxazoline)copper(II) dendrimers
Organometallic Dendrimers
Astruc et al.42 reported the synthesis of ferrocenyl star polymers using the Fe(-C5H5)+
induced perfuctionalisation of polymethylaromatics.
Very recently,43 they have reacted
amino-terminated dendrimers with ferrocenylcarbonylchlorides to give amidoferrocenes such
as the example illustrated in Figure 7. A dendritic effect in molecular recognition has been
demonstrated using these metallodendrimers. The binding of several inorganic anions to the
ferrocenyl units was investigated by examining the shift in the position of the cyclic
voltammetric wave. The apparent association constants were found to increase in the order
NO3- < Cl- < HSO4- < H2PO4-. In addition, the magnitude of the interaction of higher
generation dendrimers with the anions was greater than that of the lower generation
analogues.
28
Fe
CO
N
H
Fe
O
C
N
NH
W
CO
O
Fe
NH
O
CO
N
NH
Fe
O
W
N
NH
H
N
CO
Figure 7.
Fe
O
C
Fe
An amidoferrocene dendrimer
Organosilicon dendrimers with ferrocenyl peripheral units have been prepared by Cuadrado et
al.44 and their electrochemical properties studied. Cyclic voltammograms of the first and
second generation dendrimers show a unique wave corresponding to the oxidation of all of
the redox centres. Therefore, the ferrocenyl moieties are electrochemically equivalent noninteracting redox centres. Cuadrado et al.45 have also surface-functionalised poly(propylene
imine) dendrimers with ferrocenyl units. In order to prepare inclusion complexes where the
dendritic terminal groups act as the guests, the binding of cyclodextrin – a well known
molecular host – to the ferrocene moieties in these dendrimers was studied. The authors
discovered that although the aqueous solubility of the dendrimers was enhanced by the
29
presence of cyclodextrin, it decreased with increasing dendrimer generation. In addition to
this, they also observed two different voltammetric waves for the highest generation
dendrimer, indicating that complexed and uncomplexed ferrocene units were present and
thus, complete complexation of all surface moieties was not possible.
Both these
observations were attributed to the steric congestion present at the surface of the larger
dendrimer, which limits the number of ferrocene residues that can be included by the bulky
cyclodextrin hosts.
Pugin et al.46 have attached chiral diphosphine ferrocenyl complexes to dendritic
ligands in order to examine their catalytic activity in hydrogenation reactions. The rhodiumcatalysed asymmetric hydrogenation of dimethyl itaconate was studied using different sizes of
dendritic complexes. The enantioselectivities shown by the dendritic catalysts were found to
be slightly lower than that of the corresponding mononuclear catalyst. Pugin et al.46 are
currently investigating the use of larger dendrimers in other catalytic reactions in order to
ascertain the influence of the dendrimer backbone on the selectivities of reactions.
30
O
O
O O
O
O
O
O
O
N
H
N
H
O
O
O
NH
O
O
O
O
Figure 8.
O
O
O
Fe
O
NH
O
O
Asymmetric redox-active dendrimer with ferrocene subunit
Another recent report by Kaifer et al.47 describes the synthesis of asymmetric redoxactive dendrimers. A single ferrocene unit is appended to a dendritic branch of variable size
to form compounds such as the one illustrated in Figure 8. The electrochemical behaviour of
these dendrimers is similar to that described by Diederich and co-workers30 for their
porphyrin-based systems. Again, the redox-active centre is partially shielded by the higher
generation dendritic branches, thus hindering electron transfer to the ferrocene unit.
31
N
O
CN
O
PhS
O
SPh
Pd
Cl
Pd
S
Ph
Cl
S
Ph
31
O
PhS
Cl
NH
O
Pd
Pd
S
Ph
AgBF 4
SPh
Cl
S
Ph
32
CN
O
PhS
Ph
S
Cl
Pd
N
Pd
PhS
O
O
Pd
S
Ph
S
Ph
Cl
Scheme 11.
N
Pd
NH
O
Cl
SPh
O
O
PhS Pd
Ph
S
O
NH
O
SPh
PhS Pd
SPh
SPh
Cl
33
Convergent synthesis of palladium-containing dendritic wedge
Reinhoudt et al.48, 49 have utilised palladium-containing building blocks to construct
metallodendrimers using both convergent and divergent approaches. Dendritic growth was
achieved by the substitution of an N-donor ligand for a chloride in a two-step process.
Scheme 11 shows the convergent synthesis of a second generation dendritic wedge. Firstly,
the palladium complex 31 was activated by removing the chloride ion using Ag[BF4].
Subsequent addition of two equivalents of pyridine-based building block 32 gave a second
generation dendritic wedge 33 with a cyano group at its focal point. Repetition of these two
steps afforded a third generation wedge. In the final stage of the synthesis, the dendritic
32
wedges were coupled to a trifunctional palladium-containing core molecule. In one report,
the dendrimers were synthesised using a combination of both coordinative and hydrogen
bonds.50
Another type of organopalladium dendrimer has been prepared by van Koten et al.51
via the insertion of palladium into peripheral carbon-iodine bonds of carbosilane dendrimers.
The organopalladium moieties were attached to the periphery of the dendrimer exclusively
via palladium-carbon bonds. Reactions of these complexes with transmetalation reagents
LiMe and SnMe4 were attempted but were unsuccessful.
Ph
Bu3P
Pt
PBu3
PBu3
Ph
Pt
Ph
PBu3
Pt
Bu3P
PBu3
Bu3P
Pt PBu
3
PBu3
Pt
PBu3
Bu3P
Pt
PBu3
Pt
Bu3P
PBu3
Ph
Ph
Pt
PBu3
Pt
PBu3
Bu3P
Ph
Figure 9.
33
PBu3
Organoplatinum dendrimer
Stang et al.52 and Takahashi et al.53 have also employed metal-carbon bonds to
construct their organoplatinum dendrimers. In these examples, the metals are present in every
generational layer of the dendrimer. Stang et al.52 used a stepwise divergent approach to
synthesise first and second generation metallodendrimers with a backbone of -bonded triand tetra-ethynylbenzene units.
A similar strategy devised by Takahashi et al.53 used
triethynyl-trimethylbenzene as a building block to form metallodendrimers such as the one
illustrated in Figure 9.
A final example of the use of metal-carbon -bonds in the construction of
organotransition metal dendrimer synthesis has been reported by Liao and Moss.54 They have
prepared dendrimers with the functional group (CpM(CO)2CH2CH2CH2-) – where M = Fe,
Ru –
located exclusively at the periphery.
Using the convergent approach, the metal
complexes were attached to a Fréchet-type9 poly(aryl ether) dendritic wedge. The largest
dendrimer synthesised – generation 4 – contained 48 ruthenium atoms and has an estimated
diameter of about 5 nm.
Sulfur-Donor Dendrimers
Majoral et al.19 have prepared gold chloride containing dendrimers with the gold atom
coordinated to sulfur in the internal cavaties of the dendrimer and to phosphorus at the
surface (see Figure 2). The palladacycle dendrimers of Reinhouldt et. al.48,49,50 also use
sulfur donors in S-C-S double pincer ligands.
Welton et al. have prepared PAMAM dendrimers with a terminal secondary amine
rather than the normal primary amine.55 They have then used these to prepare sodium
dithiocarbamate dendrimers that they then coordinated to a variety of ruthenium complexes
(Scheme 12).
34
35
Conclusions
These aesthetically pleasing macromolecules known as dendrimers are attracting an
increasingly large amount of attention from chemists and biochemists in all research areas.
Over 600 papers in this field were published during 1998 alone. Metallodendrimers are
beginning to show real promise in catalysis, with catalytic activities per metal centre being
equivalent to those of monomeric analogues. The possibility of using dendrimers to prevent
catalyst losses from reaction mixtures could soon lead to commercialisation of these
materials.
Future progress will undoubtedly include the formation of tailor-made dendritic
assemblies where predetermined properties can be introduced into specific sites in the
dendritic structure. The synthetic control and fine-tuning of the dendrimer needed to produce
molecules with specific properties should lead to the proposed applications of these
molecules becoming a reality.
36
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