Two-component control of guest binding in a self-assembled cage molecule

Article abstract of DOI:10.1039/c0cc00234h

A self-assembled M₂L₄ palladium-pyridyl cluster with a paddle-wheel structure shows binding affinity in competitive organic solvents for neutral organic guests that possess both the correct size and electrostatic complementarity.

Full text of DOI:10.1039/c0cc00234h

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Two-component control of guest binding in a self-assembled cage
moleculew
Puhong Liao, Brian W. Langloss, Amber M. Johnson, Eric R. Knudsen, Fook S. Tham,
Ryan R. Julian and Richard J. Hooley*
Received 5th March 2010, Accepted 13th May 2010
First published as an Advance Article on the web 4th June 2010
DOI: 10.1039/c0cc00234h
2 4
A self-assembled M L palladium–pyridyl cluster with a
‘
‘paddle-wheel’’ structure shows binding affinity in competitive
organic solvents for neutral organic guests that possess both the
correct size and electrostatic complementarity.
Metal–ligand interactions have been used to create a number
1
of self-assembled host molecules. For example, one of the
II
most common structural linkages uses pyridine–Pd contacts,
taking advantage of the square-planar geometry of the
2
coordinatively saturated metal center. These systems can
form host : guest inclusion complexes that have been exploited
for a variety of purposes. Examples include controlling reaction
3
rates, isolating reactive intermediates and unstable species,
4
5
6
2 4
Fig. 1 Synthesis of M L ‘‘paddle-wheel’’ cluster 4; its minimized
or altering reaction pathways. The guest binding is most often
controlled by interactions between guest and the aromatic
ligands used to form the cluster walls. Water-soluble clusters
have been shown to be highly effective hosts for aromatic
structure indicating the resultant cavity (SPARTAN; AM1 forcefield)
and a minimized structure of the 4Áterephthalonitrile complex.
unreactive, and treatment with Pd(OAc) gave an intractable
2
7
hydrocarbon species due to the hydrophobic effect, whereas
solid. The solubility properties of the complex were highly
negatively charged clusters with electron rich walls often favor
8
the binding of organic cations. The binding of desired guests
dependent on counterion—4Á(NO ) was only soluble in
3
4
DMSO, although mixtures of DMSO and small amounts of
water, acetone and chloroform were tolerated. Complexes 4Á
(BPh ) and 4Á(OTf) also showed some solubility in acetone,
in organic solvents is rarer, as the solvent often outcompetes
the binding of other added species. Above all, fully enclosed
clusters are shape-selective, and only bind species that fit in the
cavity. The metals used to form the clusters are coordinatively
saturated, and generally seen as structural vertices, not used to
aid guest binding. Here we report a paddle-wheel shaped
metal–ligand cluster that uses weak electrostatic interactions
between metal and guest as well as steric effects to control
binding selectivity.
4
4
4
methanol and acetonitrile.
X-Ray quality crystals of 4Á(OTf) were obtained from slow
4
evaporation from acetonitrile solution, and show that the
cluster forms
10,11
(Fig. 2).
a
symmetrical ‘‘paddle-wheel’’ structure
The structure shows the presence of one disordered
triflate group in the interior cavity of the cluster. There is a
The ligand 3 was synthesized via Sonogashira coupling of
9
,3-diethynylbenzene and 3-bromopyridine. Upon addition
1
1
of Pd(NO ) to a solution of ligand 3 in DMSO-d , H NMR
3
2
6
analysis showed the formation of a new complex 4 (see
Fig. 1and 4c). This complex is kinetically stable, and symmetric;
the integrals for each of the protons on the ligand remain
unchanged, and each peak remains sharp, indicating the
formation of only one complex. Cluster formation was only
observed with a weakly ligated palladium source. Three
counterions proved suitable for the synthesis of the complex;
nitrate, triflate and tetraphenylborate. Palladium chloride was
Department of Chemistry, University of California, Riverside,
CA 92521, USA. E-mail: richard.hooley@ucr.edu;
Fax: +1 951-827-4713; Tel: +1 951-827-4924
w Electronic supplementary information (ESI) available: Synthetic
procedures and selected NMR data, X-ray diffraction data, and
exchange NMR analysis. CCDC 768969. For ESI and crystallographic
data in CIF or other electronic format see DOI: 10.1039/c0cc00234h
Fig. 2 ORTEP representation of the X-ray diffraction structure of
cluster 4. One disordered triflate molecule is present in the cavity, and
has been removed for clarity.
4
932 | Chem. Commun., 2010, 46, 4932–4934
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significant amount of open space in the unit cell between
clusters, with the interstitial space between cluster subunits
filled with disordered acetonitrile solvent and triflate ions
(
see ESIw).
Electrospray mass spectrometric analysis was also possible
if performed under gentle ionization source conditions (see
ESIw). Analysis of 4Á(NO showed the presence of two
3 4
)
2
+
+
species, [M
M = Pd
. The triflate salt 4Á(OTf)
and an ESI-MS spectrum (Fig. 3) could be obtained of the
+
2NO
3
]
and [M
3
+ 3NO ] , where
2
L
4
4
proved far more stable,
+
3
] ).
cluster alone, with the loss of one triflate ion (i.e. [4Á(OTf)
Both of these peaks displayed the correct isotope pattern for
the cluster containing two Pd atoms. Interestingly, even
though the m-pyridine group can freely rotate and could be
expected to adopt a number of orientations, formation of
1
2
polymers or other oligomers has not been observed, indicating
the favorability of the paddle-wheel structure. Most self-
assembled metal–ligand clusters are designed so that the ligand
has as few degrees of freedom as possible to prevent the
1c
formation of different aggregates. This is not necessary here,
as the self-assembly process forms only one species.
1
Fig. 4 Downfield regions of H NMR spectra (400 MHz, DMSO-d
98 K) of (a) ligand 3; (b) Pt cluster 5; (c) Pd cluster 4; (d) 1.7 mM
cluster 4 + 1.7 mM terephthalonitrile, (e) 1.7 mM cluster 4 + 14 mM
6
,
2
The cluster is stable in air at room temperature in both the
solid state and DMSO solution for months, and no special
handling precautions are necessary. It is stable at elevated
temperatures for hours, although prolonged heating over
terephthalonitrile, and (f) 1.7 mM cluster
terephthalonitrile.
4
+
28 mM
1
3
7
0 1C caused decomposition. Exchange NMR spectroscopy
of a 1 : 1 mixture of cluster 4 and ligand 3 in DMSO-d (see
cavity. The protons on the periphery of the cluster were only
slightly affected.
6
ESI w) showed no evidence of ligand exchange on the NMR
timescale, so it is reasonable to suggest that the cluster stays
To explore this behavior further, we exposed the cluster to a
series of neutral guests; the results are displayed in Table 1. A
‘‘two-component’’ pattern in guest binding was observed.
Only species of the correct size and shape displayed binding,
and then only if there was a suitable lone-pair containing
donor group present. Two donor groups are not necessary for
binding, as 4-tolunitrile and benzonitrile showed similar binding
affinities to terephthalonitrile. 1,4-Difluorobenzene also showed
binding, indicating that a nitrile is not the only coordinating
group tolerated. Interestingly, dichlorobenzene showed no
binding affinity, although 4-chlorobenzonitrile did. Strong
ligands such as pyridine, N,N-dimethylaminopyridine, aniline
or aliphatic amines destroyed the cluster, forming an unidentified
insoluble Pd complex and leaving free ligand to be observed in
1
4
intact for a period of at least minutes at room temperature.
The presence of highly disordered anion in the cavity interior
led us to study the solution-phase host : guest properties of the
˚
cluster. The cluster has a cavity approximately 6 A wide and
˚
0 A deep, suggesting that molecules such as p-xylene would fit
1
in the cavity. Unfortunately, the cluster displayed no affinity
towards suitably sized hydrocarbons such as naphthalene,
p-xylene or toluene. On the other hand, addition of 1,4-
dicyanobenzene caused an upfield shift in the NMR spectrum
of the nitrate salt of host. Guest exchange was rapid on the
NMR timescale (the cluster retains an averaged D4h symmetry
by NMR), and only changes in host chemical shift could be
1
5
observed. Benesi–Hildebrand analysis gave a binding affinity
À1
1
of 11.1 M . The most shifted peak (colored red in Fig. 4d–f)
the H NMR spectrum. The cluster was tolerant to excess
was assigned to the proton H
1
, pointing into the center of the
nitrile. Addition of a 50-fold excess of the nitriles in Table 1
did not show appreciable dissociation of cluster, and 4Á(OTf)4
a
Table 1 Binding affinities for guests in cluster 4Á(NO
3 4
)
À1
Guest
a
K /M
Terephthalonitrile
4-Chlorobenzonitrile
Benzonitrile
11.1
12.4
10.2
9.9
7.8
0
4
1
1
-Tolunitrile
,4-Difluorobenzene
,4-Dichlorobenzene
p-Xylene
0
1
1
,4-Dicyanobutane
,6-Dicyanohexane
0
0
Acetonitrile
0
Fig. 3 ESI-MS spectrum of 4Á(OTf)
4
. (a) observed and (b) calculated
a
2
6
98 K, [4] = 2 mM, DMSO-d .
+
isotope pattern for [4Á(OTf)
3
] .
This journal is ꢀc The Royal Society of Chemistry 2010
Chem. Commun., 2010, 46, 4932–4934 | 4933

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was suitably tolerant to acetonitrile solvent to allow crystal
growth.
We are grateful to UC Riverside for funding. RRJ acknowl-
edges funding from the National Institute of General Medical
Sciences (R01GM084106).
The presence of an electron pair donor group was not all that
was required for binding. Small nitriles such as acetonitrile gave
no binding (even in the solid state), nor did flexible dinitriles such
as 1,4-dicyanobutane or 1,6-dicyanohexane. These species are
too long to fit in the pocket without unfavorable alkyl chain
Notes and references
1
(a) P. Baxter, J.-M. Lehn and A. DeCian, Angew. Chem., Int. Ed.
Engl., 1993, 32, 69; (b) R. W. Saalfrank, H. Maid and A. Scheurer,
Angew. Chem., Int. Ed., 2008, 47, 8794; (c) M. Fujita,
K. Umemoto, M. Yoshizawa, N. Fujita, T. Kusukawa and
K. Biradha, Chem. Commun., 2001, 509; (d) D. L. Caulder and
K. N. Raymond, Acc. Chem. Res., 1999, 32, 975; (e) P. Mal,
D. Schultz, K. Beyeh, K. Rissanen and J. R. Nitschke, Angew.
Chem., Int. Ed., 2008, 47, 8297.
1
6
compression. Molecular modeling of the 4ÁNC–C
6 4
H –CN
complex shows that the guest causes slight deformation of the
cluster to allow binding. This is consistent with the observation
that species with extra ‘‘width’’ such as 1,2,4,5-tetracyanobenzene
and 1,8-dicyanoanthracene show no binding affinity, even
though they are of the correct ‘‘height’’.
2 (a) S. Sato, J. Iida, K. Suzuki, M. Kawano, T. Ozeki and
M. Fujita, Science, 2006, 313, 1273; (b) K. Suzuki, J. Iida,
S. Sato, M. Kawano and M. Fujita, Angew. Chem., Int. Ed.,
The binding affinity of neutral guests is moderate, mainly
due to the competitive interaction between host and the
solvent and counterion. Both 4Á(NO ) and 4Á(OTf) have
2
008, 47, 5780; (c) K. Suzuki, M. Kawano, S. Sato and
M. Fujita, J. Am. Chem. Soc., 2007, 129, 10652.
(a) D. Fiedler, R. G. Bergman and K. N. Raymond, Angew.
Chem., Int. Ed., 2004, 43, 6748; (b) D. Fiedler, H. van Halbeek,
R. G. Bergman and K. N. Raymond, J. Am. Chem. Soc., 2006, 128,
10240.
3
4
4
3
limited solubility in solvents other than DMSO, which can
also occupy the host cavity and is present in far greater
concentration than the guests in Table 1. Nitrate cluster 4Á
(
NO
3
)
4
was the most effective host. The use of host 4Á(OTf)
4
4 (a) V. M. Dong, D. Fiedler, B. Carl, R. G. Bergman and
K. N. Raymond, J. Am. Chem. Soc., 2006, 128, 14464;
lowered the binding affinities further, presumably due to
additional competition from the counterion, as seen in the
solid-state structure. The smaller nitrate ion can only partially
fill the cavity, allowing other species to bind more effectively.
In order to study the effect of guest : metal interaction
further, we studied the other group 8 metals as cluster termini.
No discrete cluster formation was observed upon treatment
with Ni(II) salts, however Pt cluster 5 (Fig. 4b) was successfully
(
2
b) M. D. Pluth, R. G. Bergman and K. N. Raymond, Science,
007, 316, 85; (c) M. Ziegler, J. L. Brumaghim and
K. N. Raymond, Angew. Chem., Int. Ed., 2000, 39, 4119.
5
(a) P. Mal, B. Breiner, K. Rissanen and J. R. Nitschke, Science,
2
M. Fujita, J. Am. Chem. Soc., 2006, 128, 6558.
M. Yoshizawa, M. Tamura and M. Fujita, Science, 2006, 312,
251.
(a) M. Yoshizawa, T. Kusukawa, M. Fujita, S. Sakamoto and
K. Yamaguchi, J. Am. Chem. Soc., 2001, 123, 10454;
(
009, 324, 1697; (b) M. Kawano, Y. Kobayashi, T. Ozeki and
6
7
2 3 6
synthesized (by treatment of 3 with PtCl /AgNO in DMSO-d
b) S. M. Biros, R. G. Bergman and K. N. Raymond, J. Am.
followed by filtration) and exposed to the guests in Table 1.
This cluster has the same properties (although slightly smaller
changes in chemical shift upon addition of metal salt to ligand
Chem. Soc., 2007, 129, 12094; (c) M. Yoshizawa, M. Tamura and
M. Fujita, J. Am. Chem. Soc., 2004, 126, 6846.
(a) D. Fiedler, D. H. Leung, R. G. Bergman and K. N. Raymond,
Acc. Chem. Res., 2005, 38, 351; (b) A. V. Davis, D. Fiedler,
G. Seeber, A. Zahl, R. van Eldik and K. N. Raymond, J. Am.
Chem. Soc., 2006, 128, 1324.
´
R. Chinchilla and C. Najera, Chem. Rev., 2007, 107, 874.
0 N. L. S. Yue, D. J. Eisler, M. C. Jennings and R. J. Puddephatt,
Inorg. Chem., 2004, 43, 7671.
8
9
II
II
3
) as Pd cluster 4. Pt , however, is less Lewis acidic than Pd ,
and so the affinity of 5 for donor guests would be expected to
be much smaller than that of 4. Indeed, addition of both
terephthalonitrile and difluorobenzene showed no change in
1
1
4
+
4À
the H NMR spectra with over 100-fold excess of guest (no
1
1 Crystal data: [C80
H
48
N
8
Pd
2
]
[CF
3
SO
3
]
768969, M = 2399.95, monoclinic, space group Cm (no. 8), a =
(4Á(OTf)
4
), CCDC
decomposition was observed). This lowered affinity for Lewis
donor guests removes one component of the ‘‘two-component’’
recognition, and so no host : guest behavior is observed. This
behavior is unusual; most host : guest binding in metal–ligand
systems comes from size and shape complementarity of the
hydrophobic effect. Structures such as covalently linked
˚
˚
˚
2
1
7.6097(22) A, b = 15.0085(12)A, c = 14.2322(11) A, b =
07.6573(11)1, V = 5619.7(8) A , Z = 2, calculated density
3
˚
À3
D
c
= 1.418 g cm , colorless prism fragment (0.40 Â 0.38 Â
0.35 mm) coated with paratone oil, T = 100(2) K, 44 210 reflections
˚
measured (0.71 A resolution), 16 961 unique (Rint = 0.0236,
completeness = 99.7%), final R
intensity I > 2s (I).
2 H.-J. Kim, E. Lee, M. G. Kim, M.-C. Kim, M. Lee and E. Sim,
1 2
= 0.0326, wR = 0.0877 with
1
7
metal–bisporphyrins can complex strong ligands such as
pyridines or DABCO, but binding weak donors such as
organofluorides is unprecedented, especially in competitive
solvents such as DMSO.
1
Chem.–Eur. J., 2008, 14, 3883.
3 C. L. Perrin and T. J. Dwyer, Chem. Rev., 1990, 90, 935.
4 (a) S. Sato, Y. Ishido and M. Fujita, J. Am. Chem. Soc., 2009, 131,
1
1
6
064; (b) Y.-R. Zheng and P. J. Stang, J. Am. Chem. Soc., 2009,
131, 3487.
15 L. Fielding, Tetrahedron, 2000, 56, 6151.
In summary, we have created a new self-assembled M L
2
4
palladium–pyridyl cluster with a ‘‘paddle-wheel’’ motif, and
showed its affinity for guests with both the correct size and
electronic complementarity. Further studies of these systems
are underway in our laboratory.
1
6 R. J. Hooley, S. M. Biros and J. Rebek, Jr., Chem. Commun., 2006,
09.
5
1
7 C. J. Walter, H. L. Anderson and J. K. M. Sanders, J. Chem. Soc.,
Chem. Commun., 1993, 458.
4
934 | Chem. Commun., 2010, 46, 4932–4934
This journal is ꢀc The Royal Society of Chemistry 2010