Temperature Controls Guest Uptake and Release from Zn4L4 Tetrahedra

Article abstract of DOI:10.1021/jacs.9b07307

We report the preparation of triazatruxene-faced tetrahedral cage 1, which exhibits two diastereomeric configurations (T1 and T2) that differ in the handedness of the ligand faces relative to that of the octahedrally coordinated metal centers. At lower temperatures, T1 is favored, whereas T2 predominates at higher temperatures. Host-guest studies show that T1 binds small aliphatic guests, whereas T2 binds larger aromatic molecules, with these changes in binding preference resulting from differences in cavity size and degree of enclosure. Thus, by a change in temperature the cage system can be triggered to eject one bound guest and take up another.

Full text of DOI:10.1021/jacs.9b07307

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Communication
Temperature Controls Guest Uptake and Release from Zn4L4 Tetrahedra
Dawei Zhang, Tanya K Ronson, Songül Güryel, John Thoburn, David J. Wales, and Jonathan R. Nitschke
J. Am. Chem. Soc., Just Accepted Manuscript • Publication Date (Web): 03 Sep 2019
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Temperature Controls Guest Uptake and Release from Zn4L4
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Dawei Zhang, Tanya K. Ronson, Songül Güryel, John Thoburn, David J. Wales, and Jonathan R.
Nitschke*
Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, United Kingdom.
Supporting Information Placeholder
we demonstrate the functioning of such a system for the first
time. Our system consists of a mixture of two thermally
interconverting Zn4L4 tetrahedral diastereomers (Figure 1).
ABSTRACT: We report the preparation of triazatruxene-
faced tetrahedral cage 1, which exhibits two diastereomeric
configurations (T1 and T2), differing in the handedness of the
ligand faces relative to that of the octahedrally coordinated
metal centers. At lower temperatures, T1 is favored, whereas
T2 predominates at higher temperatures. Host-guest studies
show that T1 binds small aliphatic guests, whereas T2 binds
larger aromatic molecules, with these changes in binding
preference resulting from differences in cavity size and
degree of enclosure. By changing the temperature, the cage
system can thus be triggered to eject one bound guest and
take up another.
(a)
Stimuli-responsive molecules1 and molecular hosts2 that
are capable of adapting to changes in their environments
have attracted substantial attention.3 The ability of these
species to switch between distinct states can enable them to
be built into artificial molecular systems with useful
functions.4 One such function is the stimulus-controlled
uptake and release of guests by molecular containers.5 Such
behavior has the potential to direct the outcome of chemical
processes,4h,6 control the transport and storage of chemicals,7
and enable new means of drug delivery.8
(b)
(b)
H5+H7+H10
H2
H8
H10+H9
H1
H2
H3
H4
H8
H9+H4
H7
H1
H5
H3
Subcomponent self-assembled capsules are attractive
candidates to achieve guest uptake and release, as the
reversible formation of the dynamic covalent and
coordinative bonds that hold the structures together provide
different potential modes of opening.9 Systems have thus
been designed containing two or three capsules, where the
application of chemical signals led to selective disassembly of
individual cages and the release of their guests.10 An
alternative route for achieving guest uptake and release is the
interconversion between supramolecular hosts with different
guest preferences. However, these host transformations have
been irreversible to date, in many cases resulting from the
addition of new ligands11 or templates12. Reversibility can be
achieved in some cases by noninvasive stimuli, such as
light,5c,13 or a change in solvent14 or concentration,15 enabling
uptake and release of a single guest.
Et2O
H12
25 oC, T1 : T2 = 66% : 34%
H6
H6
H11
H12
H11
80 oC, T1 : T2 = 17% : 83%
ppm
Figure 1. Subcomponent self-assembly of
A with 2-
formylpyridine and ZnII produced (a) two diastereomeric
pairs of enantiomers, as illustrated by the structures of C4Δ4-1
and A4Δ4-1, (b) the H NMR spectra (CD3CN, 500 MHz) of
which are shown at 25 and 80 °C. Spectra of (C4Δ4/A4Λ4)-1
(T1) and (A4∆4/C4Λ4)-1 (T2) have been assigned and are
indicated by green and blue labels, respectively.
1
We hypothesized that stimuli-induced reconfiguration
between two metal-organic hosts16 with different guest
preferences could lead to a system exhibiting switchable and
reversible uptake and release of different guests. In this work
Triazatruxene subcomponent A (4 equiv) reacted with 2-
formylpyridine
(12
equiv)
and
zinc(II)
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bis(trifluoromethanesulfonyl)imide (triflimide, Tf2N−, 4 equiv)
enthalpically favorable (ΔH = -8.51 kcal mol−1), whereas T2
was entropically favored (ΔS = 2.73 × 10−2 kcal K−1 mol−1)
(Figure S16). Computation of the vibrational frequencies of
the two structures also indicated enhancement of the relative
stability of T2 versus T1 with increased temperature (see
Section 4 in the Supporting Information), consistent with the
experimental trend.
1
2
3
4
5
6
7
8
in acetonitrile to give tetrahedron 1 (Figure 1a). The Zn4L4
stoichiometry of the assembly was confirmed by ESI-MS
(Figure S10). The triazatruxene moieties can be oriented
either clockwise (C) or anticlockwise (A) within the faces of 1
(Figure 1a), and each tris-chelated octahedral vertex of the
tetrahedron may adopt either Λ or Δ handedness. The
combination of these two stereochemical elements can thus
Cage 1 was first investigated as a host for smaller aliphatic
guests. All of the guests shown in Figure 3a were observed to
encapsulate within T1 in slow exchange on the NMR time
scale at room temperature (Figure 4a and Figure S22-S41).
Titration of a guest into the host solution resulted in the
appearance and increase in intensity of characteristically
upfield-shifted signals for the bound guests in the range
between -2.7 and -0.6 ppm, corresponding to 1:1 guest⊂T1
produce diastereomers.17 The 1H NMR spectrum of
1
exhibited two sets of ligand signals with the same DOSY
diffusion coefficients (Figure 1b and Figure S8), consistent
with the presence of two distinct diastereomeric pairs of
9
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enanatiomers, each belonging to the
T point group,
(C4Δ4/A4Λ4)-1 (T1) and (A4∆4/C4Λ4)-1 (T2). In contrast, when
iron(II) triflimide had been used to produce an analogous
tetrahedron from the same subcomponent precursors, only
one of the two diastereomeric pairs was observed, exclusively
(A4∆4/C4Λ4)-FeII4L4.18 Comparison between the 1H NMR
spectral features of Zn4L4 1 and the previous Fe4L4 structure,
along with observations of their guest binding properties,
1
complexes by H NMR integration. NOESY cross-peaks were
observed between the bound guest signals and the aromatic
and methyl peaks of occupied T1 (see Section 6.1 in the
Supporting Information); no correlations were observed with
those of T2. Slight shifts in the phenyl and methyl signals of
T2 (H6 and H12) were also observed in the presence of these
guests, suggesting interactions that were rapid on the NMR
time scale at room temperature. The presence of multiple
equilibria in solution (Figure S21) prevented quantification of
the binding strengths of these small guests.
1
allowed us to assign each of the two sets of signals in the H
NMR spectrum of 1 to the corresponding isomer (see Section
2.2 in the Supporting Information).
Density functional theory (DFT) calculations provided
insight into the structural properties of the two
diastereomers of 1. The optimized structures showed that T2
has larger pores between pairs of triazatruxene faces,
rendering the tetrahedral framework more open than that of
T1, as illustrated in Figure 2, and greatly increasing the void
cavity size. Moreover, the orientation of the ethyl groups on
the triazatruxene faces of the tetrahedron, either towards or
away from the center, has also been found to affect the
degree of enclosure, cavity volume, and cage stability (see
Section 4 in the Supporting Information).
T1
T2
Figure 2. VOIDOO-calculated void space (green mesh)
within the DFT-optimized models of C4Δ4-1 (T1, volume: 423
Å 3) and A4∆4-1 (T2, volume: 902 Å 3) with all ethyl groups
pointing outside of the cavities, viewed down a pore between
two faces. Distances are shown between the closest protons
across adjacent faces, highlighting the different degrees of
cavity enclosure.
Figure 3. Guests investigated for 1. (a) Smaller aliphatic
guests and (b) larger aromatic guests were bound
respectively by T1 and T2 in slow exchange on the NMR time
scale at room temperature.
Cage 1 was then investigated as a receptor for the larger
guests bearing aromatic rings listed in Figure 3b. These
guests were found to interact only with T2, in slow exchange
on the NMR time scale at room temperature (Figure 4b and
Figures S43-S61). Upon titration with each guest, new
The two cage isomers, T1 and T2, were observed to
interconvert in a temperature-dependent equilibrium (Figure
1 and Figure S15). At 25 °C, a 66 : 34 ratio of T1 : T2 was
observed with T1 predominating. The proportion of T2
increased with temperature, leading to a 17 : 83 of T1 : T2
ratio at 80 °C. Re-equilibration back to the original
proportions was observed after the mixture had been cooled
back to 25 °C for 12 h. A van't Hoff analysis revealed T1 to be
1
guest⊂T2 H NMR signals were observed between 4.0 and 6.5
ppm, increasing in intensity as the guest was added. NOESY
spectra exhibited cross-peaks between the signals of the
bound guests and the aromatic protons of occupied T2 (see
Section 6.2 in the Supporting Information); no such
correlations were observed between signals from the guests
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of Figure 3b and those of T1. Integration of the host-guest
T2 (see Section 6.2 in the Supporting Information). Our
results showed that the progressive addition of each guest
gradually switched the sign of ΔG′ from positive to negative
(Tables S7-S12), thus favoring species T2 to a progressively
greater degree by the end of the titrations.
1
2
3
4
5
6
7
8
signals indicated a 1:1 binding stoichiometry in all cases.
1
Based on H NMR titrations, the binding constants of T2 for
these larger guests were determined, showing a binding
hierarchy of bianthracene
>
di(p-tolyl)fluorine
>
tetraphenylmethane > other guests (Table 1). We infer that
both the abundance of aromatic rings and the three-
dimensional structures of the guests play important roles in
the favorable binding interactions.
We infer that the different binding preferences of T1 and
T2 derive from their differences in cavity size and degree of
cavity enclosure. The smaller and more enclosed cavity of T1
is more suitable for encapsulation of small aliphatic guests,
in contrast to the larger and more open cavity of T2 (Figure
2), which is better adapted to larger aromatic molecules.
(a)
H1
G⊂T1
9
H6
H1
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We then explored the use of temperature to trigger the
uptake and release of the different guests. Heating a mixture
of 1 with one of the aliphatic guests listed in Figure 3a from
25 to 80 °C led to a significant decrease in the peak
intensities of T1 with a concomitant increase of those of T2
(Figures S62-S69). The peaks of the bound guests within T1
became nearly undetectable at 80 °C, indicating the release
of these guests from T1. Cooling the mixture back to 25 °C for
two days regenerated the initial ratio of T1 and T2, leading to
re-uptake of the released guests by T1. For instance, the
equilibrium mixture of 1 and dibromoadamantane contained
50% and 9% guest⊂T1 at 25 and 80 °C, respectively (Table
S13). Switching the temperature thus enabled the reversible
uptake and release of dibromoadamantane from T1 due to
the 41% change in the population of guest⊂T1.
Zn4L4
1
7
ppm
ppm
7.5
8.5
8.0
6.0
-1.5
9.0
(b)
G⊂T2
H1
H1
H6
H11
In contrast, heating a mixture of 1 and one of the aromatic
guests listed in Figure 3b increased the population of
guest⊂T2 (Figures S70-S73) due to the greater
thermodynamic stability of T2 at higher temperatures, which
drove the uptake of the guest. Re-equilibration of the
mixture at 25 °C for two days led to a decrease in the T2
population and the release of the T2-bound guest. This
process can be illustrated by the case of calix[4]arene, which
showed a 15% change in the population of guest⊂T2,
switching between 24% and 39% by changing the
temperature between 25 and 80 °C, leading to the reversible
uptake and release of calix[4]arene from T2 (Table S14).It
should be noted that the temperature dependent capture and
release by T2 is impracticable in the presence of a large
excess of the aromatic guest in Figure 3b due to the complete
formation of guest⊂T2 even at 25 °C (Figure S43), as
discussed above.
Zn4L4 1
2
ppm
4.5
5.0
6.0
5.5
6.5
ppm
7.0
7.5
8.5
8.0
9.0
1
Figure 4. H NMR spectra (CD3CN, 500 MHz, 25 °C) of 1 in
the presence of excess representative aliphatic (a) and
aromatic (b) guests. Peak assignments are given in Figure 1; ●
and ▲ indicate the peaks of the guests bound in T1 and T2,
respectively. The peaks of the free aromatic guests in (b) are
marked by .
Table 1. Binding Constants of T2 for Large Aromatic
Guests in CD3CN at 25 °C.
Guest
Ka (M−1)
Bianthracene
Di(p-tolyl)fluorene
Calix[4]arene
Tetraphenylmethane
4-Tritylphenol
4-Tritylanisole
(2.3±0.1)×105
(4.6±0.4)×104
(2.6±0.1)×103
(1.2±0.1)×104
(1.7±0.2)×103
(7.7±0.1)×103
Figure 5. Schematic representation of reversible uptake and
release of dibromoadamantane (G1) and calix[4]arene (G2)
guests respectively by T1 and T2 via thermoswitching.
We noted that the addition of these guests also drove the
equilibrium from T1 to T2, and the presence of a large excess
of guests resulted in the guest⊂T2 complexes exclusively
(Figure S43). The effect of guest binding on the equilibrium
between T1 and T2 was investigated by considering the
guest-induced change in the apparent Gibbs free energy
difference (ΔG′) between the total concentrations of T1 and
We then investigated the simultaneous uptake and release of
a pair of different guests, dibromoadamantane (G1) and
calix[4]arene (G2), within a single system (Figure 5). The
initial equilibrium mixture at 25 °C contained G1⊂T1 as the
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J.; Gordon, M. R.; Ventura, J.; Li, L.; Thayumanavan, S. Multi-stimuli
major species (52%), relative to the populations of G2⊂T2
(16%) and empty T1 and T2 (32% in total) (Figure S74 and
Table S18). This hierarchy inverted at 80 °C, showing only 3%
G1⊂T1 and 50% G2⊂T2. The temperature increase thus
resulted in the release of G1 from T1 and the uptake of G2 by
T2. Conversely, the release of G2 from T2 and the uptake of
G1 by T1 occurred as the initial equilibrium population was
re-established when the mixture re-equilibrated at 25 °C over
two days.
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The Supporting Information is available free of charge on the
ACS Publications website.
Complete experimental details (PDF)
AUTHOR INFORMATION
Corresponding Authors
*J.N. jrn34@cam.ac.uk
ORCID
Dawei Zhang: 0000-0002-0898-9795
Tanya K. Ronson: 0000-0002-6917-3685
Songül Güryel: 0000-0003-3055-4963
John Thoburn: 0000-0002-2422-8478
David J. Wales: 0000-0002-3555-6645
Jonathan R. Nitschke: 0000-0002-4060-5122
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
This work was supported by the European Research Council
(695009) and the UK Engineering and Physical Sciences
Research Council (EPSRC EP/M008258/1). The authors thank
the Department of Chemistry NMR facility, University of
Cambridge for performing some NMR experiments, and the
EPSRC UK National Mass Spectrometry Facility at Swansea
University for carrying out high resolution mass
spectrometry. D. Z. acknowledges a Herchel Smith Research
Fellowship from the University of Cambridge.
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