Self-assembled squares and triangles by simultaneous hydrogen bonding and metal coordination

Article abstract of DOI:10.1021/ol400326r

Through the combination of hydrogen bonding and metal-templated self-assembly, molecular squares and molecular triangles are observed in chloroform solution upon the complexation of hydrogen-bonded dimers of para-pyridyl-substituted 2-ureido-4-[1H]-pyrimi

Full text of DOI:10.1021/ol400326r

ORGANIC
LETTERS
2013
Vol. 15, No. 7
1548–1551
Self-Assembled Squares and Triangles by
Simultaneous Hydrogen Bonding and
Metal Coordination
Laura J. Marshall and Javier de Mendoza*
Institute of Chemical Research of Catalonia (ICIQ), 43007-Tarragona, Spain
jmendoza@iciq.es
Received February 4, 2013
ABSTRACT
Through the combination of hydrogen bonding and metal-templated self-assembly, molecular squares and molecular triangles are observed in
chloroform solution upon the complexation of hydrogen-bonded dimers of para-pyridyl-substituted 2-ureido-4-[1H]-pyrimidinone (UPy) and an
appropriate cis-substituted palladium complex. Molecular modeling studies and NMR analysis confirmed the presence of two distinct structures
in solution: the tubular structure of the molecular square and propeller-bowl structure of the molecular triangle.
Hydrogen bonding has been widely employed to
build up rosette-like supramolecular structures.1,2 Use of
cyanuric acidꢀmelamine combinations,3 hydrogen bond
scaffolds inspired by GꢀC pairs,4 or G-quartet mimics,5
among others,6 have been reported. Also, 2-ureido-4-[1H]-
pyrimidinone (UPy) has been efficiently employed to build
up self-assembled architectures,7 due to the remarkable
strength of the dimers arising from its DDAA hydrogen
bonding array [Ka(chloroform)>107 Mꢀ1].8 We recently
reported a 16 hydrogen bonded self-assembly of tubular
(1) (a) Lindoy, L. F.; Atkinson, I. M. Self-assembly in Supramole-
cular Systems; Royal Society of Chemistry: Cambridge, 2000. (b) Lehn,
J.-M. Science 2002, 295, 2400. (c) Whitesides, G. M.; Grzybowski, B.
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(2) For a discussion on the factors that favor rosettes over open-
chain oligomers, see: Ballester,P. and de Mendoza, J. In Modern
Supramolecular Chemistry: Strategies for Macrocycle Synthesis;
Diederich, F., Stang, P. J., Tykwinski, R. R., WileyꢀVCH: Weinheim,
2008; pp 69.
(3) For reviews on cyanuric acidꢀmelamine rosettes, see: (a) Whitesides,
G.M.;Simanek,E.E.;Mathias,J.P.;Seto,C.T.;Chin,D.N.;Mammen,M.;
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2004, 33, 363.
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Ed. 2004, 43, 668. (b) Davis, J. T.; Spada, G. P. Chem. Soc. Rev. 2007,
36, 296.
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Zimmerman, S. C. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 5099. (b)
Todd, E. M.; Zimmerman, S. C. Tetrahedron 2008, 64, 8558.
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(7) (a) Gonzalez, J. J.; Prados, P.; de Mendoza, J. Angew. Chem., Int.
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Ed. 1999, 38, 525. (b) Keizer, H. M.; Gonzalez, J. J.; Segura, M.; Prados,
P.; Sijbesma, R. P.; Meijer, E. W.; de Mendoza, J. Chem.;Eur. J. 2005,
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11, 4602. (c) Hahn, U.; Gonzalez, J. J.; Huerta, E.; Segura, M.; Eckert,
J.-F.; Cardinali, F.; de Mendoza, J.; Nierengarten, J.-F. Chem.;Eur. J.
2005, 11, 6666. (d) Huerta, E.; Metselaar, G. A.; Fragoso, A.; Santos, E.;
Bo, C.; de Mendoza, J. Angew. Chem., Int. Engl. 2007, 46, 202.
(e) Huerta, E.; Cequier, E.; de Mendoza, J. Chem. Commun. 2007, 5016.
(8) (a) Sijbesma, R. P.; Beijer, F. H.; Brunsveld, L.; Folmer, B. J. B.;
Hirschberg, J. H. K. K.; Lange, R. F. M.; Lowe, J. K. L; Meijer, E. W.
(4) (a) Marsh, A.; Silvestri, M.; Lehn, J.-M. Chem. Commun. 1996,
1527. (b) Mascal, M.; Hext, N. M.; Warmuth, R.; Moore, M. H.;
Turkenburg, J. P. Angew. Chem., Int. Ed. Engl. 1996, 35, 2204. (c)
Kolotuchin, S. V.; Zimmerman, S. C. J. Am. Chem. Soc. 1998, 120, 9092.
(d) Ma, Y.; Kolotuchin, S. V.; Zimmerman, S. C. J. Am. Chem. Soc.
2002, 124, 13757. (e) Fenniri, H.; Deng, B. L.; Ribbe, A. E. J. Am. Chem.
Soc. 2002, 124, 11064. (f) Johnson, R. S.; Yamazaki, T.; Kovalenko, A.;
Fenniri, H. J. Am. Chem. Soc. 2007, 129, 5735.
€
Science 1997, 278, 1601. (b) Sontjens, S. H. M.; Sijbesma, R. P.; van
Genderen, M. H. P.; Meijer, E. W. J. Am. Chem. Soc. 2000, 122, 7487.
r
10.1021/ol400326r
Published on Web 03/18/2013
2013 American Chemical Society

cyclic tetramers based on UPy subunits attached to a 3,6-
carbazolyl core, in which substituents are oriented to both
edges of theringtoimprovethesolubility ofthe aggregate.9
Alternatively, self-assembly into helices, macrocycles,
and cages can be achieved through metal coordination.
Independent work pioneered by Fujita and Stang, utilizing
square planar Pd(II) or Pt(II) metal centers coordinated to
4,40-bypyridine ligands, generates charged, cyclic frame-
works.10ꢀ12 The combination of the 90° angle of the cis-
coordinated metal centers with the 180° angle of the linear
ligand provides the basis for the square framework. Fujita
also reportedmolecular triangles in solution, depending on
the length and flexibility of the ligands, with short inflex-
ible ligands more likely to form squares than longer,
flexible ones, which often result in a square-triangle
equilibrium.
Initially, we prepared compound 1 with no methylene
spacer between the UPy and pyridyl moieties (see Support-
ing Information (SI)). However, this compound was not
soluble in CDCl3, except in the presence of a trace of
trifluoroacetic acid (TFA), and no dimers were observed
1
by H NMR spectroscopy under these conditions. The
formation of dimers was also unsuccessful in tetrahydro-
furan (THF). In contrast, dimer 22 bearing the methylene
spacer for increased flexibility showed the well-defined,
1
typical signature for a UPy dimer in H NMR (CDCl3,
sharp peaks at 12.97, 12.17, and 11.04 ppm).7,9,15 The
addition of traces of TFA allowed characterization of the
monomeric species 2.
We reasoned that the substitution of our carbazolyl
moiety9 for a square planar cis-coordinated Pd(II) species
would favor the formation of neutral tetrameric cyclic
arrangements, each UPy dimer constituting an edge and
each metal center a corner (Figure 1). To the best of our
knowledge, the combination of both hydrogen bonding
and metal-templated self-assembly, without interference,
for the formation of discrete cyclic molecular squares and
triangles has never been reported.13,14 As we previously
observed,9 the presence of a methylene spacer between the
carbazole and the UPy moieties was essential for the
formation of cyclic aggregates.
Figure 2. DOSY spectra of aggregates Pd3-26 and Pd4-28 (CDCl3)
at 1 mM (light blue), 20 mM (pink), and 40 mM (dark blue).
From the variety of cis-protected square planar palladium(II)
complexes tested for complexation to the dimer (solubility,
1H and 19F NMR analysis), only (1,5-cyclooctadiene)bis-
(3,5-dichloro-2,4,6-trifluorobenzene) palladium(II) 3 was
found to be successful. Upon mixing equimolecular
amounts of 22 and 3, shifts were observed in the hydrogen-
1
bonding and pyridyl regions of the H NMR spectra,
(12) For other recent examples, see: (a) Hess, J. L.; Hseih,
C.-H.; Brothers, S. M.; Hall, M. B.; Darensbourg, M. Y. J. Am.
Chem. Soc. 2011, 133, 20426. (b) Karthikeyan, S.; Velavan, K.;
Sathishkumar, R.; Varghese, B.; Manimaran, B. Organometallics
2012, 31, 1952.
(13) For further examples of orthogonality in supramolecular
chemistry, see: (a) Huck, W. T. S.; Hulst, R.; Timmerman, P.; van
Veggel, F. C. J. M.; Reinhoudt, D. N. Angew. Chem., Int. Ed. Engl. 1997,
36, 1006. (b) Wong, C.-H.; Zimmerman, S. C. Chem. Commun. 2013, 49,
1679.
Figure 1. Para-substituted UPy dimer 22 (edge), two monomers
of 2 coordinated to the Pd(II) species Pd-22, and schematic
representation of conformations around the UPy subunits.
(14) For a combination of metals and hydrogen bonds in dimeric
capsules, see: (a) Yamanaka, M.; Toyoda, N.; Kobayashi, K. J. Am.
Chem. Soc. 2009, 131, 9880–9881. (b) Yamanaka, M.; Kawaharada, M.;
Nito, Y.; Takaya, H.; Kobayashi, K. J. Am. Chem. Soc. 2011, 133,
16650.
(9) Yang, Y.; Xue, M.; Marshall, L. J.; de Mendoza, J. Org. Lett.
2011, 13, 3186.
(10) (a) Fujita, M.; Sasaki, P. O.; Mitsuhashi, T.; Fujita, J.; Yazaki,
K.; Yamaguchi, K.; Ogura, K. Chem. Commun. 1996, 1535. (b) Fujita,
M.; Yazaki, J.; Ogura, K. J. Am. Chem. Soc. 1990, 112, 5645. (c) Stang,
P. J.; Cao, D. H. J. Am. Chem. Soc. 1994, 116, 4981.
(11) Recent reviews: (a) Yoshizawa, M.; Klosterman, J. K.; Fujita,
M. Angew. Chem., Int. Ed. 2009, 48, 3418. (b) Cook, T. R.; Zheng, Y.-R.;
Stang, P. J. Chem. Rev. 2013, 113, 734.
(15) (a) Sijbesma, R. P.; Beijer, F. H.; Brunsveld, L.; Folmer, B. J. B.;
Hirschberg, J. H. K. K.; Lange, R. F. M.; Lowe, J. K. L; Meijer, E. W.
Science 1997, 278, 1601. (b) Beijer, F. H.; Kooijman, H.; Spek, A. L.;
Sijbesma, R. P.; Meijer, E. W. Angew. Chem., Int. Ed. 1998, 110, 79. (c)
€
Sontjens, S. H. M.; Sijbesma, R. P.; van Genderen, M. H. P.; Meijer,
E. W. J. Am. Chem. Soc. 2000, 122, 7487.
Org. Lett., Vol. 15, No. 7, 2013
1549

as well in the 19F NMR spectra, corresponding to the
fluorine atoms on the Pd ligands.
Two species displaying a high level of symmetry at room
1
temperature were observed. Variable concentration H
DOSY diffusion experiments in CDCl3 (Figure 2) con-
firmed the presence of two discrete species of different sizes
(observation of two well-definedsignalson theD axis). The
spectra show the slight change of D with the concentration
increase, which favors cyclic oligomers.2 Using the Stokesꢀ
Einstein equation, the experimentally found diffusion
coefficients of the two species were converted to approx-
Figure 4. Optimized CPK models of molecular triangle Pd3-26
showing the bowl-shaped aggregate. (a) Bottom view omitting
undecyl chains (colored by atom type). (b) Top view showing
undecyl chains (colored by unit Pd-22). (c) Side view showing
orientation of undecyl chains.
imate hydrodynamic radii.16 Thus, values of 8.9 and 6.4 A
˚
at 20 mM for the large and small species respectively were
calculated, translating into “spherical” volumes of 3070
3
and 1148 A . The average theoretically estimated radii/
˚
3
volumes for a square (9.9 A/4064 A ) and triangle (6.7 A/
˚
˚
˚
3
1260 A ) strongly point toward these two species being
˚
3
present in solution (pentamer >5000 A ).
17ꢀ19
Further spectroscopic studies were in full agreement
with our predictions of the presence of a molecular square
and a molecular triangle (see SI for spectra). For instance,
at lower concentrations (∼1 mM) the triangle was present
in greater abundance, with the amount of the square
increasing linearly as concentration was increased, as
expected (DOSY).
˚
Figure 3. Schematic representation of cyclic aggregates from 22
and 3. (a) Propeller-shaped triangle. (b) Propeller-shaped
square. (c) Tubular-shaped tetramer.
The assembly of flat, rosette-like structures (schemati-
cally shown in Figure 3) is unlikely, as it would result in
significant torsional strain, and subsequent unfavorable
hydrogen-bonding angles, due to the presence of the
undecyl chains at the inner region of the rosette, as clearly
revealed by model inspection. In contrast, folded struc-
tures can easily be arranged. Indeed, model optimiza-
tions18 for the triangle are fully compatible with a propel-
ler-like shape (at 25 °C) or a bowl-shaped aggregate (at low
temperature) where both UPy subunits in each monomer
are pointing to opposite sides (Figures 3a and 4). In the
case of the square, although a propeller-like structure is
also possible (Figure 3b), model optimizations suggest that
a very favorable, sterically unhindered tubular (belt-like)
shape can be generated (Figures 3c and 5), as with our
carbazole tetramer.9 In this case both UPy subunits are
mirror images pointing to the same side of the spacer and
all alkyl chains orient away from the assembly, and intothe
bulk solvent.
Figure 5. Optimized CPK models of molecular square Pd4-28
showing the tubular-shaped aggregate. (a) Top view omitting
undecyl chains (colored by atom type). (b) Top view showing
undecyl chains (colored by unit Pd-22). (c) Side view.
1
Variable temperature H and 19F NMR studies con-
firmed that the aggregates were destroyed at high tem-
peratures (>378 K). Upon increasing the temperature,
formation of the entropically more stable, but enthalpi-
cally less stable, triangle was favored. Upon lowering the
temperature the enthalpically more stable square was
observed. It is also likely that, at low temperatures, where
both species are less flexible, the bowl shaped triangle is
more sterically hindered than the tubular square species
and is, therefore, less favorable.10,11
NOESY spectra at 298 K (CDCl3) give little information
regarding the conformation of the two species, as all
aggregates are dynamic at room temperature. However,
one NH proton of each species (10.96 and 11.12 ppm for
the triangle and square respectively) does not show con-
tacts with the first CH2 of the undecyl chain. However at
213 K, where the structures are “frozen”, the NH proton at
10.96 ppm shows contacts with both the first methylene
group of the undecyl chain and the UPy CH proton (5.80
ppm) of its dimeric partner. Generally the NH protons of
(16) rh = kbT/(6πηD), in which the solute is a spherical species.
(17) Theoretical values can be approximately calculated by taking the
average of the length, width, and height of the dissolved species, as
measured on the optimized models for the different cyclic oligomers.
(18) Structures were minimized in vacuo by molecular mechanics
using Augmented MM3 parameters (OG_MM-MM3 protocol) within
the SCIGRESS 7.7.0.47 software (Fujitsu Ltd.).
(19) Timmerman, P.; Weidmann, J.-L.; Jollife, J. A.; Prins, L. J.;
Reindhoudt, D. N.; Shinkai, S.; Frish, L.; Cohen, Y. J. Chem. Soc.,
Perkin Trans. 2 2000, 2077.
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Org. Lett., Vol. 15, No. 7, 2013

1
resulted in the destruction of the aggregates. In the H
the triangular species show greater interactions with the
protons of the undecyl chain than the square due to their
closer proximity at lower temperatures. These interactions
are not observed in the square, thus confirming that at
lower temperatures the triangular species is likely to adopt
the bowl conformation, whereas in the square the tubular
arrangement (Figure 5) prevails, as in our carbazole
tetramer,9 with both hydrogen bonded edges oriented in
a similar way as the 4,40-bypyridine ligands of Fujita’s
squares.10,11 As our “edges” are longer and more flexible
than 4,40-bipyridine, this also accounts for the observation
of both squares and triangles in solution.
NMR spectrum at low temperatures a small splitting was
observed in the NH signal at 11.11 ppm and the CH2 signal
at 4.38 ppm (corresponding to the methylene spacer). This
suggests not only that these two protons are coupling to
one another but also that the environments of the two
protons on the methylene spacer are nonequivalent at low
temperatures.
DOSY diffusion experiments (1ꢀ40 mM, CDCl3) and
use of the StokesꢀEinstein equation yielded an approx-
˚
imate hydrodynamic radius of only 5.3 A, giving a “spher-
3
ical” volume of 670 A . This value is too small to represent
˚
In order to examine the effect of the angle between the
two pyridyl-UPy substituents on the metal center, dimer 42
was prepared, where a meta-substituted pyridine center is
utilized. Thisislikely toincrease theangle between the UPy
substituents (Figure 6a), as the other conformations
(Figures 6bꢀc) are not likely to be observed due to steric
reasons.
any discrete cyclic aggregate. For the monomeric species
(after addition of TFA) an approximate hydrodynamic
3
˚
˚
radius of 3.7 A (212 A ) was calculated. This suggests a
dynamic mixture of small hydrogen-bonded and metal-
coordinated species in solution, which are equivalent on
the NMR time scale at room temperature. The 19F NMR
spectrum shows the presence of more than one signal for
boththe ortho- and para-fluorine atoms, further suggesting
that more than one species is present. Also, low tempera-
ture NMR studies confirm the lower symmetry of these
species compared to the discrete cyclic aggregates.
An attempt to reduce the length of the chains (butyl
instead of undecyl) of the meta-substituted species to favor
cyclic aggregates (see SI for compounds 5, Pd4-58, and
Pd3-56) resulted in poor solubility. Finally, complexation
of dimeric species 22 with a platinum complex instead of a
palladium one was attempted but this was unsuccessful.
In summary, we have demonstrated that through
hydrogen bonding (UPy dimers) and metal coordination
(Pd-pyridine), self-assembly occurs in chloroform solution
to form neutral molecular squares and triangles, without
interference of both supramolecular interactions. As ex-
pected, the process is sensitive to slight structural changes
relating to internal angles, steric factors, and solubility
issues, highlighting the need for careful design in these
types of systems.9 These results pave the way for the design
of more complex molecular architectures by the combina-
tion of hydrogen bonding and metal complexation.
Figure 6. Meta-substituted UPy dimer 42, two monomers of 4
coordinated to the Pd(II) species (Pd-42), and schematic repre-
sentation of conformations around the UPy subunits.
Acknowledgment. The Ministry of Economy and Com-
petitivity (MINECO, Spain) (Projects CTQ2008-00183
and CTQ2011-28677), the ICIQ Foundation, and Con-
solider Ingenio (Grant 2010 CSD 2006-0003) are kindly
acknowledged.
Since the angle is closer to 180° than in the para-
substituted compounds (∼90°), it is possible that oligo-
meric or polymeric species may form. Indeed dimers were
observed in solution (CDCl3) for 42, and a discrete species
formed upon addition of the palladium species 3, as sharp
signals were observed in the 1H NMR spectrum. At lower
concentrations (1 mM) two species were present in equal
amounts, but at a higher concentration (<40 mM) the
intensity of the signals of only one species increased. As
expected, variable temperature 1H and 19F NMR studies
showed that increasing the temperature above 378 K
Supporting Information Available. Experimental de-
tails, characterization, and spectral data. This material is
available free of charge via the Internet at http://pubs.acs.
org.
The authors declare no competing financial interest.
Org. Lett., Vol. 15, No. 7, 2013
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