Supramolecular self-assembly of dendrimers containing orthogonal binding motifs

Article abstract of DOI:10.1039/b822043c

Two orthogonal non-covalent binding sites, namely metal-ligand complexation of Ru and bipyridine and intermolecular hydrogen bonding, facilitate the self-assembly of a new type of supramolecular dendrimers.

Full text of DOI:10.1039/b822043c

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Supramolecular self-assembly of dendrimers containing orthogonal
binding motifsw
Felix Grimm, Kristine Hartnagel, Florian Wessendorf and Andreas Hirsch*
Received (in Cambridge, UK) 9th December 2008, Accepted 26th January 2009
First published as an Advance Article on the web 11th February 2009
DOI: 10.1039/b822043c
Two orthogonal non-covalent binding sites, namely metal–ligand
complexation of Ru and bipyridine and intermolecular hydrogen
bonding, facilitate the self-assembly of a new type of supra-
molecular dendrimers.
For this purpose we first synthesized the AB2 building block
1, consisting of a focal 2,20-bipyridine moiety for metal com-
plexation and two Hamilton receptor units for the binding of
terminal cyanuric acid derivatives. The synthesis sequence
started with 2,20-bipyridinyl-4,40-dicarboxylic acid,8 which
was treated with N-hydroxysuccinimide (NHS) and dicyclo-
hexylcarbodiimide (DCC) to give the corresponding NHS-
ester 2 in 69% isolated yield (Scheme 2).
Self-assembly1 involves the spontaneous and thermodynamically
controlled formation of supramolecular architectures of suitable
tailor-made molecular building blocks. Recently, we reported
on the development of various self-assembled dendrimer
prototypes,2–4 which are based on the six-fold hydrogen bonding
of Hamilton receptor5 containing porphyrins or homotritopic
core molecules and branched cyanuric acid derivatives. In
another approach we used the complexation of depsipeptide
functionalized 2,20-bipyridine (bpy) ligands to ruthenium6 for
the assembly of a first type of chiral metallo dendrimers. These
two non-covalent interactions are highly specific and do not
interfere. A combination of two or more orthogonal binding
motifs opens up the opportunity to self-assemble high hierar-
chically ordered architectures such as the supramolecular
dendrimer schematically depicted in Scheme 1.
The subsequent coupling with 6-aminohexanoic acid pro-
moted by DCC in dry DMF afforded the bis-acid 3, which was
isolated in 62% yield. The final treatment of 3 with the amino
Hamilton receptor 49 under modified Steglich conditions
(DCC, DMAP, HOBt) and purification via column chromato-
graphy (silica, CH2Cl2–MeOH 99 : 1, gradient slope to
CH2Cl2–MeOH 95 : 5) afforded the desired AB2 building
block 1 in 53% yield as a colorless solid. The compound
1
was characterized by H-NMR, 13C-NMR, UV/Vis, and IR-
spectroscopy, by FAB mass spectrometry as well as by
elemental analysis (see ESIw).
In order to evaluate the suitability of 1 to act as a key
building block for the self-assembly of supramolecular
dendrimers we started with the investigation of the first part
of the overall process (Scheme 1), namely the formation of the
core structure 5 (Fig. 1).
So far there is only one precedent for the construction of a
supramolecular dendrimer involving orthogonal binding motifs,
which was recently published by Bohmer et al.7 On the other hand,
¨
triurea derivatives of triphenylmethanes and calix[4]arene derived
tetraaryl- and tetratosylureas are capable of forming hydrogen-
bonded homodimeric structures without mutual intervention.
Here, we report on the formation of a new type of supra-
For this purpose RuCl3ꢀxH2O was refluxed under nitrogen
atmosphere with 4 eq. of 1 in EtOH–CHCl3. The formation
of a ruthenium tris-bipyridine complex was attested by
UV/Vis-spectroscopy. The spectrum shows a ligand centered
band at 291 nm and a MLCT-band at 472 nm characteristic
for Ru(bpy)3 complexes,10 which proves the coordination of
3 AB2 ligands to the ruthenium core. Furthermore, the
targeted structure could be verified by MALDI-TOF mass
spectrometry, where the [Ru(AB2)3]+-ion could be detected at
m/z = 4761. As purification of the initially formed chloride of
5 by HPLC turned out to be very difficult due to aggregation
and complexation of solvents and by-products, the Clꢁ counter-
ion was exchanged against PF6ꢁ. After subsequent purifica-
tion by size-exclusion chromatography and recrystallization
from acetone–diethyl ether the hexafluorophosphate of metallo-
dendrimer 5 was obtained in 55% yield as red-orange micro-
crystals. It is readily soluble in aprotic polar solvents such as
chloroform (in contrast to the uncoordinated building block 1),
but shows a strong tendency towards aggregation, as reflected by
rather broad signals observed in the 1H-NMR spectrum recorded
in CDCl3. In DMSO, however, no intermolecular hydrogen
bonds take place and as a consequence further characterization
molecular dendrimers based on
a combination of the
orthogonal Hamilton receptor–cyanuric acid and Ru(bpy)3
metal–ligand interactions as outlined above.
Scheme 1 Self-assembly of a supramolecular dendrimer, consisting of
core, 3 AB2 branching units, and 6 end caps.
Department of Chemistry and Pharmacy & Interdisciplinary Center
for Molecular Materials (ICMM) Friedrich-Alexander Universitat
¨
Erlangen-Nurnberg, Henkestrasse 42, 91054 Erlangen, Germany.
¨
E-mail: andreas.hirsch@chemie.uni-erlangen.de;
Fax: +49 9131 85 26864; Tel: +49 9131 85 22537
w Electronic supplementary information (ESI) available: Detailed
experimental procedures. See DOI: 10.1039/b822043c
1
of 5 by H- and 13C-NMR spectroscopy was possible.
Small amounts (o10%) of a purple by-product could
be isolated via HPLC. The structure was determined as
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397 and 556 nm. The MALDI-TOF mass spectrum (dithranol)
displays the molecular ion peak at m/z = 3209).
The next step was the investigation of the binding of cyanuric
acid derivatives to Hamilton receptor termini of 5 leading to
self-assembled dendrimers 6a–c. The corresponding hydrogen-
binding as depicted in Scheme 3 was followed by NMR titration
experiments.3 For this purpose, three different end caps (Fig. 2)
were used. The cyanuric acid derivative 7 was chosen as first
generation dendritic ligand. The ligands 83 and 94 have already
been applied successfully in supramolecular architectures and
introduce either chirality (8) or the possibility for investigation
of electronic communication (9).
Scheme 2 Synthesis of the AB2 building block 1: (a) NHS, DCC,
DMF; (b) DCC, DMF; (c) DCC, DMAP, HOBt, CH2Cl2–DMF 1 : 1,
50 1C.
Scheme 3 Complete self-assembly of supramolecular structures 6a–c.
Fig. 1 Metallodendrimer [Ru(1)3](PF6)2 5.
cis-ruthenium bis-bipyridine [Ru(1)2Cl2](PF6)2 due to the
observation of characteristic MLCT absorption bands10 at
Fig. 2 End caps 7, 8, and 9.
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As our final aim was to achieve a complete self-assembly of
the multifunctional binding sites, the formation of supra-
molecular dendrimers 6 in a one-pot reaction was investigated
(Scheme 3). For this purpose RuCl3ꢀxH2O, three equivalents
of the AB2 1, and 6 equivalents of the end cap 7 were refluxed
in a one-pot procedure, yielding a vitreous, dark red solid
after removal of the solvent. The formation of a Ru(bpy)3
architecture was clearly demonstrated by the orange-red color
of the solution and the characteristic absorption profile in the
UV/Vis spectra. On the other hand the 1H-NMR spectrum of
6a is identical with the spectrum obtained after a stepwise
procedure, namely the treatment of the metallodendrimer 5
with a six-fold excess of end cap 7.
These findings attest the complexation of the ruthenium
core by the bpy functionalities of the building block as well as
hydrogen-bonding of latter to the end caps via the Hamilton
receptor moiety and therefore prove the formation of the
desired architecture in one single step.
Fig. 3 Chemical shifts of 1H-NMR titration (300 MHz, CDCl3) of
Ru(AB2)3(PF6)2 5 with various end caps.
In conclusion, we have introduced a new concept for
the self-assembly of supramolecular dendrimers involving
orthogonal Hamilton receptor–cyanuric acid and Ru(bpy)3
metal–ligand binding motifs. Both a successive divergent
reaction sequence as well as a one-pot reaction can be applied
for the synthesis of such supramolecular dendrimers. Further
extension of this concept by introducing three or more
orthogonal binding motifs will allow for the facile con-
struction of a supramolecular architecture with even higher
complexity and hierarchical order. Work along these lines is
currently under way in our laboratory.
Table 1 Stepwise formation constants K1–K6 [L molꢁ1
]
Complex
(5)ꢀ(7)
(5)ꢀ(8)
(5)ꢀ(9)
log K1
log K2
log K3
log K4
log K5
log K6
5.25
4.91
4.95
3.12
5.07
5.30
4.74
4.47
4.50
4.02
4.07
3.80
4.85
4.24
4.39
3.88
3.26
3.63
Upon complexation of the Hamilton receptor with cyanuric
acid derivatives, a complementary six-point hydrogen bonding
motif between host and guest is formed. This leads to a
significant downfield shift3 of the Hamilton receptor’s NH
Notes and references
1
protons, which can be observed in the H-NMR spectra. The
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[Ru(1)3](PF6)2 5 after the addition of the end caps 7, 8, and
9 are shown in Fig. 3. The graph depicts saturation after the
addition of about 6 equivalents of end cap, as all available
binding sites of the macromolecule are occupied.
The characteristic downfield shift of the NH protons of the
Hamilton receptor moiety was used to determine the stepwise
association constants K1–K6 with the help of the program
HypNMR,11and these are summarized in Table 1.
The calculated association constants are in good agreement
with those we reported earlier for other Hamilton receptor–
cyanuric acid complexes.3,4
V. Bohmer, J. Am. Chem. Soc., 2005, 127, 14168–14169.
¨
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Based on these calculations, the distribution of the various
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It shows that the 5ꢀL6 prevails over the other species after the
saturation is reached. After the addition of six equivalents of
end cap, the amount of the 5ꢀL6 complexes ranges between
98.4% for 8 and 99.9% for 6.
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A. Vacca, Anal. Biochem., 1995, 231, 374–382.
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Chem. Commun., 2009, 1331–1333 | 1333