Designed enclosure enables guest binding within the 4200 ?3 cavity of a self-assembled cube

Article abstract of DOI:10.1002/anie.201501892

Metal-organic self-assembly has proven to be of great use in constructing structures of increasing size and intricacy, but the largest assemblies lack the functions associated with the ability to bind guests. Here we demonstrate the self-assembly of two s

Full text of DOI:10.1002/anie.201501892

Angewandte
Chemie
International Edition: DOI: 10.1002/anie.201501892
German Edition: DOI: 10.1002/ange.201501892
Host–Guest Chemistry
3
Designed Enclosure Enables Guest Binding Within the 4200 ꢀ Cavity
of a Self-Assembled Cube**
William J. Ramsay, Filip T. Szczypi n´ ski, Haim Weissman, Tanya K. Ronson,
Maarten M. J. Smulders, Boris Rybtchinski, and Jonathan R. Nitschke*
[
6]
[7]
Abstract: Metal–organic self-assembly has proven to be of
great use in constructing structures of increasing size and
intricacy, but the largest assemblies lack the functions associ-
ated with the ability to bind guests. Here we demonstrate the
recognition, sensing, and reaction modulation. However,
the size and functionality of supramolecular assemblies often
run counter to one another: tight, selective binding is
[
8]
achieved by minimizing size, whereas the largest self-
assembled structures show no binding properties. Feats
such as the encapsulation of ubiquitin
II
[9]
self-assembly of two simple organic molecules with Cd and
II
[10]
Pt into a giant heterometallic supramolecular cube which is
require covalent
capable of binding a variety of mono- and dianionic guests
within an enclosed cavity greater than 4200 ꢀ . Its structure
tethering of the guest to the host framework. The develop-
ment of a method that allows for increasing the size of self-
assembled structures whilst maintaining a functional cavity
will allow encapsulation chemistry to begin to approach the
complexity of biological systems, as larger collections of
guests, or larger, more complex discrete guests, may be bound.
The present study builds upon the demonstration that
integrative self-sorting is an effective method for assembling
3
was established by X-ray crystallography and cryogenic trans-
mission electron microscopy. This cube is the largest discrete
abiological assembly that has been observed to bind guests in
solution; cavity enclosure and coulombic effects appear to be
crucial drivers of host–guest chemistry at this scale. The degree
of cavity occupancy, however, appears less important: the
largest guest studied, bound the most weakly, occupying only
[
11]
[
9a]
subcomponents into a large and complex structure
(1a;
II
II
1
1% of the host cavity.
Figure 1), whereby two different metal ions, Fe and Pt , act
in concert to define the threefold and fourfold symmetry axes
of a cube, respectively. Here we show that by substituting Pd
II
T
he spontaneous and precise self-assembly of multiple
II
protein subunits into well-defined, functional superstructures,
for Pt in the self-assembly procedure, a new cube 1b may be
[
1]
[2]
such as spherical virus capsids and ferritin, inspires the
generated, which formed single crystals suitable for X-ray
diffraction (see Section 1.2 in the Supporting Information).
However, cubes 1a and 1b have a porous framework, within
[
3]
preparation of synthetic analogues. The construction of
these nanoscale structures harnesses the self-assembly of rigid
organic ligands and metal ions with well-defined coordination
spheres, in which the host cavity created by the ligand
arrangement allows for diverse applications, such as guest
[
9a]
which none of a collection of prospective guests
were
[4]
observed to bind. We thus designed subcomponent A (see
[
5]
[12]
Section 1.3 in the Supporting Information) to panel
the
faces of the cubic structure, thereby both enclosing and
expanding the cavity (Figure 1).
[
*] W. J. Ramsay, F. T. Szczypi n´ ski, Dr. T. K. Ronson, Prof. J. R. Nitschke
University of Cambridge, Department of Chemistry
Lensfield Road, Cambridge, CB2 1EW (UK)
E-mail: jrn34@cam.ac.uk
The reaction between 2-formylpyridine (24 equiv), A
(24 equiv), cadmium(II) trifluoromethanesulfonate (triflate,
8 equiv), cis-bis(benzonitrile)dichloroplatinum(II) (6 equiv),
and silver triflate (12 equiv) in acetonitrile produced cage 2 as
the uniquely observed product after heating to 508C for 8 h
Homepage: http://www-jrn.ch.cam.ac.uk/
Dr. H. Weissman, Prof. B. Rybtchinski
Weizmann Institute of Science, Department of Organic Chemistry
Rehovot, 76100 (Israel)
(
Figure 1; see Section 1.4 in the Supporting Information).
II
II
II
When Pd was used in place of Pt , or Fe was used instead of
Cd in the self-assembly procedure, only multiple broad
signals were observed in the H NMR spectra after 8 h at
Dr. M. M. J. Smulders
Wageningen University, Laboratory of Organic Chemistry
P.O. Box 8026, 6700EG Wageningen (The Netherlands)
II
1
5
08C, thus suggesting that a discrete species had not formed.
[
**] This work was supported by the Marie Curie Academic-Industrial
II
We infer the larger radius of the Cd ion (109 pm) in
comparison to Fe (75 pm) to be necessary to accommodate
the steric demands of the ligand,
coordinative pyridine–Pt bonds
Initial Training Network on Dynamic Molecular Nanostructures
II
(
DYNAMOL; W.J.R.) and the Engineering and Physical Sciences
[
13]
Research Council (EPSRC). B.R. and H.W. acknowledge support
from the Gerhardt M. J. Schmidt Minerva Centre of Supramolecular
Architectures and the Helen and Martin Kimmel Centre for
Molecular Design. The TEM studies were conducted at the Irving
and Cherna Moskowitz Centre for Nano and Bio-Nano Imaging
and that the stronger
may be important in
II
[14]
holding the structure together despite minor steric clashes
and geometric misalignments. NMR spectroscopic analysis of
2
gave results consistent with the formation of a symmetrical
(
Weizmann Institute). M.M.J.S. acknowledges support from The
face-capped cubic architecture (Figures S4–S7 in the Support-
Netherlands Organization for Scientific Research. We thank Dia-
mond Light Source (UK) for synchrotron beamtime on I19 (MT7569
and MT8464).
1
13
ing Information). The H and C NMR spectra displayed
a single set of signals for the pyridine, anthracene, and phenyl
protons of the ligand, which suggests the ligands were rapidly
rotating along their axes on the NMR time scale. A single
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201501892.
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1
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.
Angewandte
Communications
centers opposite, thus
giving the cube approxi-
mate Cs point symmetry,
which has not previously
been observed for M L
8
6
[
17]
structures
(Figure 2b,d).
As the observed NMR
spectra of 2 in solution
indicated higher symmetry,
we posit that the solid-state
arrangement of 2 resulted
from maximization of CÀ
H···p interactions between
neighboring anthracenes
around
the
corners,
thereby rendering the Cs
diastereomer the most
energetically
favorable
conformation in the solid
state.
In both 1b and 2, the
cube faces consist of six
II
II
square-planar Pd and Pt
metal ions, respectively,
coordinated by the pyri-
dine moieties. The four
pyridyl rings around the
central
square-planar
metal ion are sterically
constrained to lie orthogo-
nally to the cube face. In
the case of 2, the anthra-
cenyl group of A is in turn
constrained to orthogonal-
ity with the pyridyl ring,
thus leading it to lie
roughly parallel to its cube
face. This parallel orienta-
tion provides enclosure;
Figure 1. The one-pot synthetic procedure for cubes 1a and b starting from free subcomponents and metal
ions (top) was adapted to prepare cube 2 from subcomponent A; only one cube face is shown in each case for
clarity.
diffusion coefficient (log(D)) of À9.48 was observed for 2 in
the DOSY spectrum (Figure S8). High-resolution electro-
spray ionization mass spectrometry (HRMS-ESI) produced
results consistent with fragments of the proposed structure of
longer analogues of A could be similarly designed to provide
access to yet larger enclosed architectures.
The diagonal distance across the cube from the outermost
hydrogen atoms of the farthest-spaced ligands is 3.5 nm in 1b,
and 5.0 nm in 2, which rivals the size of the largest structurally
2
(Figure S9), but no signals were observed at the m/z value of
[
3a,18]
the parent ion; we infer that the high charge and large size of
characterized synthetic metal–organic structures.
Impor-
[15]
3
the structure resulted in its fragmentation in the gas phase.
Single-crystal X-ray diffraction at Diamond Light
tantly, 2 encloses a cavity of 4225 ꢀ (see Section 1.4.1 in the
Supporting Information), which dynamic motion in solution
[
16]
3
Source
The approximately O-symmetric solid-state structure of 1b
Figure 2a,c) is consistent with the high-symmetry NMR
revealed the solid-state structures of 1b and 2.
might further increase to up to 7000 ꢀ : the cavity size for 2 in
which the anthracenyl groups are modeled to lie strictly
parallel to the cube faces. In the crystal, some of these groups
protrude slightly into the cavity, as a result of crystal-packing
effects, thus reducing the volume available for guest binding.
Cube 2 has large faces that can come together in aqueous
(
spectra recorded in solution. Although X-ray analysis iden-
À
tified eight BF4 ions occupying the cavity of 1b (Figure 2a),
no evidence of encapsulation was observed in solution by
1
9
[19]
F NMR spectroscopy. The eight tris(pyridylimine)iron(II)
media, thereby leading to the formation of superstructures.
vertices in 1b all have the same D or L stereochemistry; both
enantiomers are present in the crystal lattice. Although the
eight tris(pyridylimine)cadmium(II) vertices in 2 also have
facial stereochemistry, X-ray analysis identified four metal
centers on one face to have L handedness, with four D metal
We employed cryogenic transmission electron microscopy
(cryo-TEM) imaging to visualize directly the structure of 2 in
À6
a 1:1 water/acetonitrile solution (3 ꢁ 10 m; Figure 3). The
cryo-TEM images displayed lamellar structures consistent
with the formation of aggregates of 2. When these structures
2
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Chemie
Figure 2. Framework representation of the X-ray crystal structure of
Figure 3. Cryo-TEM images of 2 in a 1:1 water/acetonitrile solution
À
a) [1b][BF ] , where the 8 BF anions occupying the cavity are shown
À6
4
28
4
(3ꢀ10 m) a) Higher magnification of the stick-like structures in (b)
II
in space-filling representation, and b) 2, where Cd centers of D
handedness are shown in green, and Cd centers of opposite L
reveals segmented features. b) Monomolecular lamellar structures are
observed in different orientations relative to the optical axis. The stick-
like structures (the lamella) as viewed from the side (lamella cross-
sections that are parallel to optical axis); round features are due to ice
contamination.
II
handedness are shown in light yellow. The space-filling representation
of c) [1b][BF4]28 shows the pores at the edges of the cube, which are
effectively closed off by the anthracene paneling in 2 (d). Color
scheme: C gray, N blue, Fe purple, H white, Pt light orange, Pd dark
orange, F light blue, B pink. Disordered, non-encapsulated anions and
solvent molecules are omitted for clarity. The edges of both cubic
frameworks are highlighted by lines. All structures are depicted at the
same scale.
2À
À
rate (B F ), tetraphenylborate (BPh ), carborane
1
À
2
12
4
(
CB H ),
and
tetrakis(pentafluorophenyl)borate
1
1
12
À
(
B(C F ) ; see Sections 3.1–3.5, respectively, in the Support-
6
5 4
are perpendicular to the optical axis, lower contrast platelets
are observed due to a thinner optical pathway; when parallel
to the optical axis, the lamellae exhibit high-contrast cross-
sections (20 to 200 nm long, Figure 3b and Figure S11). The
thickness of the lamellae cross-sections is 3.1 Æ 0.2 nm, and
their straightness is indicative of rigidity. The segmented
nature of the cross-sections is revealed at high magnification
ing Information). In all the studies, the binding processes were
1
followed by H NMR titrations in [D ]acetonitrile, whereby
3
II
the pyridine protons closest to the Pt centers on the faces of 2
1
(H ) were observed to shift upfield upon saturation of the
solution with a guest, thus indicating fast exchange on the
NMR time scale; the imine peak of 2 also underwent spectral
shifts consistent with guest binding. Such shifts were not
observed during host–guest investigations with 1a or 1b, and
we infer they were caused by binding of the guest to the cavity
(
1
Figure 3a and Figure S12). The periodicity of the segments is
.9 nm, which corresponds to a cube–cube spacing of 3.8 nm;
1
9
it is consistent with the cubes (3.4 nm in length) stacking
through their parallel faces. Hierarchical organization of
individual 2 units into the ordered rigid monolayer, as
observed by cryo-TEM, appears to result from an energetic
balance between ionic and hydrophobic interactions.
Although robust, covalently linked 2D structures on this
of 2. Downfield chemical shifts in the F NMR spectra of the
2
À
À
4
fluorinated species B F
and B(C F ) were observed
1
2
12
6 5
(Figures S18 and S27, respectively) in the presence of 2,
consistent with their binding. NOESY correlations between
À
II
1
2
BPh4 and the Pt -bound pyridine protons from 2 (H and H )
were observed (Figure S21), which suggested a Coulombic
attraction of the negatively charged guest to the center of the
[20]
length scale have been imaged on surfaces,
we are not
aware of other cases where hierarchical, noncovalently linked
assemblies having porous structures have been directly
observed without the need for a surface support.
faces of the host; the DOSY spectrum of the host–guest
À
complex also revealed a slower diffusion coefficient for BPh
4
[
21]
À
when compared to free BPh4 in solution (Figure S22). Job’s
The guest-binding properties of 2 were investigated by
plots by UV/Vis spectroscopy identified the stoichiometry of
binding to be 1:1 in all cases, and the titration data were,
therefore, fitted to 1:1 binding isotherms (see Section 3 in the
Supporting Information); the low solubility of the host–guest
complexes required the stoichiometry experiments to be
screening the same neutral and anionic guests explored
[
9a]
previously with 1a and 1b. Although no neutral guests were
found to undergo complexation, several large, anionic species
were observed to bind inside the cavity of 2, including
2
À
hexamolybdate (Mo O ), dodecafluoro-closo-dodecabo-
6
19
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3
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Angewandte
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À1
Table 1: Binding constants (K , M ) of selected guests with cubic host 2
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TBA Mo O
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2.2Æ0.1ꢀ10
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8.8
5.2
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K B F
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TBABPh4
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2.05Æ0.08ꢀ10
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À
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The observation that the dianions (Mo O
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6
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À
À
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Angewandte
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200; b) S. Pasquale, S. Sattin, E. C. Escudero-Adꢆn, M.
Received: February 27, 2015
Published online: && &&, &&&&
Martꢃnez-Belmonte, J. de Mendoza, Nat. Commun. 2012, 3, 785.
Angew. Chem. Int. Ed. 2015, 54, 1 – 6
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!

.
Angewandte
Communications
Communications
Host–Guest Chemistry
Brobdingnagian: A giant, heterometallic
cube with host–guest properties was
prepared by successful application of
a rational strategy to increase the
dimensions whilst maintaining an
enclosed cavity (see X-ray crystal struc-
ture). A variety of mono- and dianionic
guests was bound in the cavity in solu-
tion. Hierarchical aggregation of the
cubes into a rigid monolayer was visual-
ized by cryogenic transmission electron
microscopy.
W. J. Ramsay, F. T. Szczypi n´ ski,
H. Weissman, T. K. Ronson,
M. M. J. Smulders, B. Rybtchinski,
J. R. Nitschke*
&&&& — &&&&
Designed Enclosure Enables Guest
Binding Within the 4200 ꢁ Cavity of
a Self-Assembled Cube
3
6
www.angewandte.org
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2015, 54, 1 – 6
These are not the final page numbers!