Integrative self-sorting: Construction of a cascade-stoppered hetero[3]rotaxane

Article abstract of DOI:10.1021/ja806009d

In this Communication, a competing self-sorting system containing benzo-21-crown-7, dibenzo-24-crown-8 and two secondary ammonium salts is constructed, which is then modified to achieve a hetero[3]pseudorotaxane with a specific sequence of wheels. With these two systems, we successfully demonstrate the concept of integrative self-sorting, and their relation. Furthermore, based on this self-sorting scheme, a hetero[3]rotaxane with an efficient stopper cascade has been synthesized. Copyright

Full text of DOI:10.1021/ja806009d

Published on Web 09/26/2008
Integrative Self-Sorting: Construction of a Cascade-Stoppered
Hetero[3]rotaxane
Wei Jiang, Henrik D. F. Winkler, and Christoph A. Schalley*
Institut fu¨r Chemie und Biochemie, Freie UniVersita¨t Berlin, Takustrasse 3, 14195 Berlin, Germany
Received July 31, 2008; E-mail: schalley@chemie.fu-berlin.de
Nature efficiently uses the principles of noncovalent self-
assembly1 together with self-sorting phenomena to generate com-
plex, functional architectures from many different building blocks.
Self-sorting thus integrates different subunits into the architecture
with precise positional control. In contrast, most synthetic self-
assembled architectures repetitively use ever the same building
blocks thus severely restricting the implementation of function. Self-
sorting will certainly contribute to solving this problem.2
The more similar the building blocks become, the more difficult
self-sorting is to achieve. Here, we report two self-sorting systems
based on two very similar crown ethers. When two binding sites
are integrated in one axle component, self-sorting almost quanti-
tatively generates a hetero[3]pseudorotaxane with a defined se-
quence of two different wheels. Stoppering gives rise to the
corresponding “cascade-stoppered” hetero[3]rotaxane.
Figure 1. Electrospray-ionization Fourier-transform ion-cyclotron-reso-
nance (ESI-FTICR) mass spectrum of an equimolar mixture of 1-H·PF6,
2-H·PF6, C7, and C8 in DCM and their chemical structures (inset).
Recently, Huang et al.3 reported secondary dialkyl ammonium
ions to thread through the cavity of benzo-21-crown-7 (C7) to form
pseudorotaxanes. Phenyl groups suffice as stoppers to trap C7 on
the axle. In contrast, dibenzo-24-crown-8 (C8) forms pseudoro-
taxanes even with secondary dibenzyl ammonium ions showing the
phenyl groups not to be efficient stoppers for C8.4
On the basis of this literature knowledge, we have designed a
four-component self-sorting system consisting of 1-H·PF6, 2-H·PF6,
C7, and C8 (Figure 1, inset). The corresponding association
constants5 indicate [1-H@C8]·PF6 and [2-H@C7]·PF6 to be more
stable than [2-H@C8]·PF6. Thermodynamic properties thus control
the preference of C8 for 1-H·PF6. Because of two stoppers
anthracenyl and phenyl groups attached to 1-H · PF6, a too high
barrier exists for C7 to slip onto axle 1-H·PF6. The ESI mass
spectrum (Figure 1) of an equimolar mixture of all four components
in dichloromethane (DCM) shows the result of both effects: Only
two intense peaks are observed, one for [2-H@C7]+ (m/z 550) and
one for [1-H@C8]+ (m/z 746). A signal for [2-H@C8]+ is hardly
visible at m/z 642, while no complex ion of 1-H+ and C7 is detected
at all (m/z 654). This high-fidelity self-sorting is clearly confirmed
by 1H NMR experiments (Supporting Information, Figures S12-S18).
The above self-sorting system is nonintegratiVe because it merely
leads to a smaller than possible set of discrete complexes from
subunits each equipped with just one binding site. In contrast, an
integratiVe self-sorting system is characterized by the formation
of one complex, in which more than two different subunits are
bound in two or more recognition events with positional control.6
As a prerequisite, more than one binding site must be integrated in
at least one of the components. This strategy ensures program-
mability and correct positioning of all distinct subunits in the final
complex.
Figure 2. Sequence-specific formation of hetero[3]pseudorotaxane 4-2H·
2PF6 based on an integrative self-sorting process and the synthesis of
“cascade-stoppered” hetero[3]rotaxane 5-2H·2PF6.
In noncompetitive solvents, the sequence-specific hetero[3]-
pseudorotaxane 4-2H·2PF6 is expected to prevail in an equimolar
solution of 3-2H ·2PF6, C7, and C8. The 1H NMR spectrum (Figure
3a) of a 1:1 mixture of 3-2H·2PF6 and C7 confirmed C7 to bind
exclusively at site B. While the signals for Hc, Hd, and He experience
significant complexation-induced shifts, Ha and Hb remain almost
unaffected with respect to the free axle (Figure 3b). Adding 1 equiv
of C8 to 3-2H·2PF6 (Figure 3c) caused changes for all protons on
both sites A and B, but the changes for the protons on site A are
more obvious, indicating C8 to equilibrate between A and B with
a clear preference for A in agreement with the binding constants
discussed above. In the equimolar mixture of 3-2H·2PF6, C7, and
C8, site B is occupied by C7 as most clearly seen from the shift of
He to the same position observed in Figure 3a. Site A is bound to
C8 as characterized by downfield shifts of Ha and Hb almost
identical to those observed in Figures 3c (also see Figures S21 and
S22). In line with expectation, C8 and C7 are thus bound almost
quantitatively to A and B, respectively. Furthermore, irrespective
of the mixing order of the three components, the 1H NMR spectrum
is always the same. This implies the equilibrium of all accessible
complexes to be reached with 4-2H·2PF6 being the only major
component.
An integrative self-sorting system can conceptually be derived
from the one above by combining the two axles 1-H·PF6 and
2-H·PF6 into divalent counterpart 3-2H ·2PF6 (Figures 2 and S19).
Axle 3-2H·2PF6 is equipped with two binding sites A and B, of
which site A is inherited from 1-H·PF6, and site B from 2-H·PF6.
An ESI mass spectrum of the equimolar mixture of 3-2H·2PF6,
C7, and C8 in DCM confirmed the integrative self-sorting: In the
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10.1021/ja806009d CCC: $40.75
2008 American Chemical Society

C O M M U N I C A T I O N S
of excess Et3N (Figure S27). Afterward, no free components or
deprotonated products have been detected by 1H NMR experiments
providing evidence for the rotaxane structure and quite a high
stability of the [3]rotaxane against dethreading of one of the wheels.
In an IRMPD experiment conducted with mass-selected
[5-2H·PF6]+ (Figure S28 and S29), a complex fragmentation
pattern was observed. In contrast to the pseudorotaxane, the rotaxane
first loses HPF6 indicating the dethreading of C7 now to be more
energy-demanding than the HPF6 loss because of the phenyl
stopper’s presence. When the resulting [5-H]+ fragment is reisolated
in an MS3 experiment and again irradiated with the IR laser, C7
first slips over the phenyl group.9 Only after C7, C8 can dissociate.
Finally, an IRMPD experiment conducted with the mass-selected
dication [5-2H]2+ at m/z 661 (Figure S30) displays the cleavage
of the anthracenyl methyl-nitrogen bond which is driven by charge
repulsion and leads to the simultaneous loss of the anthracenyl
methyl cation (m/z 191) and neutral C8. The second fragment (m/z
683) is a rotaxane with C7 still trapped on the remainder of the
axle. All these experiments confirm the rotaxane structure as well
as the sequence of wheels.
In conclusion, we have successfully demonstrated the concept
of integrative self-sorting with a hetero[3]pseudorotaxane as a model
system. Conceptually, it is derived from a self-sorting system with
four discrete components. We applied this concept to the synthesis
of a hetero[3]rotaxane with an efficient cascade-stoppering system.
We believe integrative self-sorting, as an important “programming
language” in nature, will be highly useful in constructing complex
supramolecular assemblies and various artificial smart materials with
well-organized structure, distinct topology, and function.
Figure 3. Partial 1H NMR spectra (500 MHz, 298 K, CDCl3:CD3CN )
2:1, 10.0 mM) of (b) 3-2H·2PF6 alone and equimolar mixtures of (a)
3-2H·2PF6 and C7; (c) 3-2H·2PF6 and C8; (d) 3-2H·2PF6, C7, and C8.
Complexed and uncomplexed species are denoted by “c” and “uc” in the
parentheses, respectively.
Acknowledgment. We thank Dr. Andreas Springer for help with
the ESI-FTICR experiments. This work was supported by Deutsche
Forschungsgemeinschaft (SFB 765 “multivalency”). CAS acknowl-
edges the Fonds der Chemischen Industrie for a Dozentenstipendium
and the DFG and FCI for financial support.
Supporting Information Available: Synthesis and characterization
of 3-2H·2PF6 and 5-2H·2PF6; 1H NMR spectra, 1H-1H-COSY spectra;
ESI-FTICR mass spectra of 5-2H·2PF6; Figures S1-S30. This material
is available free of charge via the Internet at http://pubs.acs.org.
Figure 4. (Top) ESI-FTICR mass spectrum of a 1:1:1 DCM solution of
3-2H · 2PF6, C7, and C8; (bottom) infrared-multiphoton dissociation
(IRMPD) experiments (MS/MS) of mass-selected [4-2H·PF6]+.
References
(1) (a) Whitesides, G. M.; Mathias, J. P.; Seto, C. T. Science 1991, 254, 1312–
1319. (b) Lehn, J.-M. Science 2002, 295, 2400–2403.
(2) (a) Wu, A.; Isaacs, L. J. Am. Chem. Soc. 2003, 125, 4831–4835. (b)
Mukhopadhyay, P.; Wu, A.; Isaacs, L. J. Org. Chem. 2004, 69, 6157–6164.
(3) Zhang, C.-J.; Li, S.-J.; Zhang, J.-Q.; Zhu, K.-L.; Li, N.; Huang, F.-H. Org.
Lett. 2007, 9, 5553–5556.
clean spectrum (Figure 4), only one intense peak appears at m/z
1364 which corresponds to [4-2H·PF6]+. Moreover, the fragmenta-
tion reactions of mass-selected pseudorotaxane ions confirm the
sequence of wheels: Infrared-multiphoton dissociation (IRMPD)
experiments7 with [4-2H·PF6]+ reveal the loss of C8 to occur only
at higher laser intensities as a consecutive fragment after losing
C7 and HPF6. This fragmentation pattern is only in agreement with
C8 occupying site A and C7 site B. Thus, NMR and MS
experiments agree that an integrative self-sorting system with a well-
organized structure has successfully been constructed from the
equimolar mixture of 3-2H·2PF6, C7, and C8.
(4) (a) Ashton, P. R.; Campbell, P. J.; Chrystal, E. J. T.; Glink, P.; Menzer, S.;
Philp, D.; Spencer, N.; Stoddart, J. F.; Tasker, P. A.; Williams, D. J. Angew.
Chem., Int. Ed. 1995, 34, 1865–1869. (b) Ashton, P. R.; Ballardini, R.;
Balzani, V.; Go´mez-Lo´pez, M.; Lawrence, S. E.; Mart´ınez-D´ıaz, M. V.;
Montalti, M.; Piersanti, A.; Prodi, L.; Stoddart, J. F.; Williams, D. J. J. Am.
Chem. Soc. 1997, 119, 10641–10651. (c) Clifford, T.; Abushamleh, A.;
Busch, D. H. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 4830–4836.
(5) Association constants (acetone-d6): [1-H@C8] · PF6, 496 ( 18 M-1 (Figure
S11); [2-H@C7] · PF6, 615 ( 36 M-1; and [2-H@C8] · PF6, 155 ( 8 M-1
(ref 3).
(6) For three examples of integrated self-sorting, see: (a) Miyauchi, M.; Harada,
A. J. Am. Chem. Soc. 2004, 126, 11418–11419. (b) Rudzevich, Y.;
Rudzevich, V.; Moon, C.; Schnell, I.; Fischer, K.; Bo¨hmer, V. J. Am. Chem.
Soc. 2005, 127, 14168–14169. (c) Wang, F.; Han, C.-Y.; He, C.-L.; Zhou,
Q.-Z.; Zhang, J.-Q.; Wang, C.; Li, N.; Huang, F.-H. J. Am. Chem. Soc. 2008,
130, 11254–11255.
(7) Reviews on the MS analysis of supramolecules: (a) Schalley, C. A. Mass
Spectrom. ReV. 2001, 20, 253–309. (b) Baytekin, B.; Baytekin, H. T.;
Schalley, C. A. Org. Biomol. Chem. 2006, 4, 2825–2841.
(8) Tachibana, Y.; Kawasaki, H.; Kihara, N.; Takata, T. J. Org. Chem. 2006,
71, 5093–5104.
(9) A similar situation between C8 and p-tert-butylphenyl group: Tachibana,
Y.; Kihara, N.; Furusho, Y.; Takata, T. Org. Lett. 2004, 6, 4507–4509.
A phenyl group is an efficient stopper for C7.3 Thus, the
hetero[3]rotaxane 5-2H·2PF6 (Figure 2) can be synthesized by
treating the hetero[3]pseudorotaxane 4-2H·2PF6 with benzoic
anhydride in the presence of tributyl phosphine as the catalyst8 in
70% yield. In this rotaxane, the phenyl groups at the end and middle
of the axle trap C7. C8 can still slip over the central phenyl group,
but certainly not over C7 so that it is also trapped by what could
be considered as a “stopper cascade”.
The cascade-stoppering strategy in 5-2H·2PF6 has been tested
by heating its DMSO-d6 solution at 80 °C for 2 days in the presence
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