A ph switchable pseudorotaxane based on a metal cage and a bis-anionic thread

Article abstract of DOI:10.1002/chem.201002013

Please let me in! A new kind of (pseudo)rotaxane is formed quantitatively when a bis-anionic thread is added to a molecular cage comprised of two positively charged metal complexes. The rotaxanation mechanism follows two alternative ways depending on the metal (Pd vs. Pt) and the stopper size of the guest (see figure).

Full text of DOI:10.1002/chem.201002013

DOI: 10.1002/chem.201002013
A pH Switchable Pseudorotaxane Based on a Metal Cage and a Bis-anionic
Thread
Guido H. Clever[b] and Mitsuhiko Shionoya*[a]
Following the examples of nature, movable parts have
proven to be a key feature in the developing field of molec-
ular machinery.[1] In particular, rotaxanes are exquisite
building blocks to achieve control over molecular motions.
The state of the art in rotaxane chemistry is beautifully illus-
trated by the systems presented by the groups of Stoddart,[2]
Leigh,[3] Sauvage,[4] and others,[5] comprising shuttle-bus ro-
taxanes controlled by external stimuli, surface-bound archi-
tectures, and rotaxanes integrated into complicated frame-
works. The number of basic recognition systems underlying
rotaxane formation is, however, still limited, mainly com-
prising the interaction between two (charged) organic com-
pounds that are attracted by Coulomb forces, hydrogen
bonds, or held together by coordination of a metal ion be-
tween them.
Herein, we introduce a new kind of rotaxane based on
the attractive interaction between a bis-anionic organic
thread and positively charged but coordinatively saturated
metal complexes of a metal–organic coordination cage mol-
ecule.[6] Except for the recent report on a hybrid organic–in-
organic rotaxane,[7] we believe this is the first example of a
rotaxane in which the contained metal ions are not directly
bound by the thread, but only provide their positive charges
for attraction of the negatively charged thread.[8] Recently,
we reported the quantitative encapsulation of bis-anionic
guests inside PdII-mediated cage 1a comprising two spatially
preorganized, coordinatively saturated PdII centers serving
as electrostatic anchors (Scheme 1b).[9] The X-ray structure
showed that the assembly of the four concave-shaped lig-
AHCTUNGTRENNUNG
ands around the two PdII ions generates a hollow space ame-
nable to the incorporation of suitably sized guests such as
1,1’-ferrocene bis-sulfonate.[10]
Realizing that this binding principle could be utilized for
the construction of more complex molecular assemblies,
such as rotaxanes, we subsequently examined the encapsula-
tion of a variety of bis-sulfonates of suitable sizes.
Bis-sulfonate 2 was found to be readily incorporated into
1a, as shown by a characteristic upfield shift of the guest sig-
1
nals in a H NMR titration experiment and a diffusion ori-
ented spectroscopy (DOSY) NMR experiment showing the
increase of effective molecular size of the guest by the incor-
poration of 2 inside the cage. The peak at m/z 1825 observed
in the ESI mass spectrum can be assigned to the [2@1a]2+
ion (see the Supporting Information). Furthermore, com-
pound 2 is perfectly functionalized for our intended use,
since it contains the two necessary sulfonate groups in a
suitable distance and two azide functionalities amenable to
derivatization by click chemistry. Furthermore, it features a
photoswitchable stilbene double bond.[11] The CuI-catalyzed
cycloaddition with alkynes such as 3a or 3b smoothly yield-
ed rodlike molecules 4a and 4b as their tetrabutylammoni-
um salts (Scheme 1a).[12] Indeed, stepwise addition of 4a to
a solution of cage 1a in CD3CN resulted in immediate and
quantitative uptake of the rodlike molecule inside the
metal–organic cage molecule in the fashion of a pseudoro-
taxane (Figure 1a).
The NMR titration in Figure 2 shows that upon addition
of 0.5 equivalents of guest 4a, half of the PdII cage 1a has
taken up the guest without showing fast intermolecular ex-
change, as determined by the splitting of the cageꢀs NMR
signals into two subsets. After one equivalent of 4a had
been added, all of the cage molecules had taken up one
guest, which gave rise to one set of sharp NMR signals. The
NMR spectrum reveals which parts of the rodlike molecule
4a are located inside the shielding environment of the cage
and which are protruding through two of the cageꢀs four
portals: the signals of the guestꢀs central stilbene and tria-
[a] Prof. Dr. M. Shionoya
Department of Chemistry, Graduate School of Science
The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku
Tokyo 113-0033 (Japan)
Fax : (+81)3-5841-8061
E-mail: shionoya@chem.s.u-tokyo.ac.jp
[b] Prof. Dr. G. H. Clever
Institut fꢁr Anorganische Chemie
Georg-August-Universitꢂt Gçttingen
Tammannstrasse 4
37077 Gçttingen (Germany)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201002013.
11792
ꢃ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 11792 – 11796

COMMUNICATION
Scheme 1 and Figure 2) are
shifted downfield upon encap-
sulation of the negatively
charged guest, which is in ac-
cordance with our previous ob-
servations.[9] Most interesting,
however, is that the NMR spec-
tra even reveal the topology of
the pseudorotaxane, which is
not trivial, since the cage has
four portals and the guest could
in principle protrude through
two neighboring or two oppo-
site portals.[13] The NMR signals
of the cageꢀs hydrogen atoms
lining the sides of the portals
(Hd, dark blue in Scheme 1 and
Figure 2) show that guest 4a is
incorporated with both ends of
the rod protruding through op-
positely arranged portals of the
cage. In the NMR spectrum of
the “empty” cage, these protons
Scheme 1. a) Synthesis of guests 4a and 4b; b) formula of metal cages 1a and 1b.
give rise to only one singlet due
to the high D4h symmetry of the
cage in solution. In the rotax-
ane, however, the signal is split
into two singlets, indicating that these hydrogen atoms now
have fallen into two groups with one signal representing the
hydrogen atoms lining the two open portals and one signal
representing the two oppositely arranged portals filled by
the guest molecule.
Upon addition of a second equivalent of the guest 4a to
the host–guest complex 4a@1a, two sets of guest signals can
be distinguished: one for the encapsulated equivalent and
the other for the free excess guest molecules outside the
cage. In a comparison of the DOSY NMR spectra of the
free thread 4a and the pseudorotaxane 4a@1a, again an in-
crease in hydrodynamic radius was observed due to the for-
mation of the host–guest complex (see the Supporting Infor-
mation). In this case, the formed complex was even found to
be significantly bigger than the “empty” cage 1a alone;[9]
this is explained by the two tetraphenyl methane residues of
Figure 1. a) Proposed mechanism for the uptake of rodlike guests 4a with
a small stopper into cage 1a; b) uptake of guest 4b carrying a large stop-
4a protruding from the cageꢀs portals and thereby contrib
ACHTUNGTRENNUNGut-
per into cage 1a; c) top: guest 4a can be replaced by a stronger binder
such as guest 5; bottom: reversible switching of encapsulation by a
change in pH.
ACHTUNGTRENNUNG
NOESY NMR spectrum revealed two close contacts be-
tween the cage 1a and guest 4a (see the Supporting Infor-
mation). Additionally, the formation of the host–guest com-
plex 4a@1a gave rise to the observation of a single strong
signal in the ESI-TOF mass spectrum at m/z 2200, attributa-
ble to the ion [4a@1a]2+ (see the Supporting Information).
Free guest molecule 4a is highly fluorescent when excited
at 326 nm (emission maximum at 400 nm). Upon encapsula-
tion, we found that the fluorescence was quenched, presum-
ably by an energy transfer to 1a.[14] Furthermore, free guest
4a (a 18 mm solution in CHCl3/CH3CN (1:1), N2 purged) can
be isomerized into its cis isomer by irradiation at 365 nm
zole moieties (H11–H15) undergo a characteristic upfield
shift due to the interaction with the interior of the cage. In
contrast, the signals of the parts that lay within the portals
of the cage (H5 and H6) are shifted downfield due to their
position with respect to the aromatic rings of the cage. All
of the residual signals of the tetraphenyl methane groups
undergo no significant shifts. Second, the signals of the
cageꢀs inward pointing hydrogen atoms (Hi, light blue in
Chem. Eur. J. 2010, 16, 11792 – 11796
ꢃ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
11793

M. Shionoya and G. H. Clever
cage 1 led us to conclude that
the rodlike guest molecule 4a
can easily enter the cage
through its portals in contrast
to the bigger guest 4b, which
can only be encapsulated by an
alternative, slower mechanism
requiring a (partial) decomplex-
ation of the pyridine ligands
from the metal centers. This in-
terpretation is in good agree-
ment with the insights about
the relative sizes of the cageꢀs
portals and the guests 4a and
4b gained from molecular mod-
eling studies (Figure 3 and the
Supporting Information).
Next, we examined the re-
ACHUTNGRENNUvG ersACHTUNTGRNEiNUGN bility of the rotaxanation
process. 2,6-Naphthyl bis-sulfo-
nate 5 (Figure 4a) was envi-
sioned to be a perfectly fitting
guest for cage 1a from the re-
sults obtained by molecular
modeling. Indeed, this com-
pound is quantitatively incorpo-
rated inside the cage upon addi-
Figure 2. 1H NMR titration of 1a with 4a. (500 MHz, CD3CN, 293 K).
within 10 s, whereas encapsulated 4a is protected from the
photoisomerization within the cage 1a (see the Supporting
Information).[11]
Surprisingly, the uptake of 4a into 1a was finished within
seconds, and therefore, in light of considerably slow ligand
exchange with PdII ions, this occurs too quickly for a mecha-
nism that involves the decomplexation of the ligands from
the PdII centers of the cage. Furthermore, repeating the
uptake experiment with the corresponding PtII cage 1b,
which is expected to have a structure similar to that of cage
1a, indicated a similar quick encapsulation despite the fact
that the ligand exchange in PtII complexes is known to be
much slower than in PdII complexes (see the Supporting In-
formation).
Figure 3. MMFF[15] molecular models of a) 4a@1a and b) 4b@1a based
on the X-ray structure of 1a.[9] Numbers denote distances in ꢄ.[15]
To further elucidate the rotaxanation mechanism, we syn-
thesized guest 4b, which has much larger stopper groups at
both ends (Scheme 1 and Figure 1b). Interestingly, the en-
capsulation of 4b into 1a takes about 90 min at room tem-
perature as indicated by the NMR and ESI spectra (see the
Supporting Information). Inclusion of 4b into 1b was not
observed at room temperate, but several days of heating the
mixture of 1b and 4b to 808C in CD3CN also resulted in ro-
taxanation in this case (along with partial dissociation of the
cage).
Figure 4. a) Replacement of 4a from the inside of 1a by guest 5; b) re-
These observations and a comparison of the sizes of the
stopper groups of 4a and 4b with the big openings of the
A
ACHTUNGTRENiNUGN ble switching of encapsulation of 4a in 1a by a change in pH.
11794
www.chemeurj.org
ꢃ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 11792 – 11796

pH Switchable Pseudorotaxane
COMMUNICATION
see the Supporting Information). Unless otherwise noted, the NMR spec-
troscopy titrations were carried out by using 0.70 mm cage solutions in
CD3CN and 8.75 mm stock solutions of the respective guest compounds
(4a and 4b in CDCl3, 5 in CD3CN).
tion of one equivalent of its tetrabutylammonium salt to a
solution of cage 1a in CD3CN. Furthermore, guest 5 is able
to quantitatively replace guest 4a from the inside of cage 1a
as seen from the NMR spectroscopic data shown in Fig-
ure 4a.
Upon addition of 0.5 equivalents of bis-sulfonate 5 to the
4a@1a complex, in half of the cages the rodlike guest 4a is
replaced by 5 and after the addition of one equivalent of 5,
all of 4a is replaced by 5 inside the cages. The resulting
NMR spectrum is in accordance with the spectrum of the
pure 5@4 complex, especially regarding the shift of the
cageꢀs inward pointing hydrogen atom (light blue in
Figure 4). Furthermore, the 2-fold symmetry of the 4a@1a
complex is lost (dark blue in Figure 4) and again 4-fold sym-
metry is adapted, which can be explained by the ability of
the small guest 5 to freely rotate inside 1a.
Finally, we examined the effect of pH changes on the ro-
taxanation process. Upon addition of an acid such as HBF4
to pseudorotaxane 4a@1a, dethreading occurred, as deter-
mined from the signal changes observed in the NMR spec-
trum (Figure 4b). The process is reversible upon addition of
tributylamine and can be repeated several times in cycles
(see the Supporting Information). Going along with this pH
switching, however, is partial dissociation of the coordina-
tion compound releasing the free ligand, as indicated by the
emergence of characteristic NMR signals, most probably
due to a concomitant protonation of the ligandꢀs pyridine
rings and thus breaking of the coordinate bonds.
In conclusion, we have presented a new approach to the
synthesis of rotaxanes based on the combination of two
binding principles: metal coordination for assembly of the
cage and Coulomb interactions for guest binding. Rotaxana-
tion is thermodynamically highly favorable and kinetic con-
trol can be achieved by the choice of stopper size and metal
ion. In terms of topology, our system presented herein falls
into a small class of rotaxanes in which the thread is not sur-
rounded by a simple circular macrocycle, but by a molecular
cage that might be described as four hemicycles, the ends of
which are collectively joined by two nodes (the metal
ions).[13,16] Here, we only made use of two of the cageꢀs four
gates. We imagine that the fourfold symmetry of the cage
might allow the extension of rotaxane chemistry from the
first into the second dimension by the inclusion of an or-
thogonal pair of threads inside the cage.
Acknowledgements
G.C. thanks JSPS and the Alexander v. Humboldt Foundation for a post-
doctoral scholarship. This work was supported by Grants-in-Aid from
MEXT of Japan and the Global COE Program for Chemistry Innovation.
Keywords: anion recognition · cage compounds · host–guest
systems · rotaxanes · supramolecular chemistry
[1] a) E. R. Kay, D. A. Leigh, F. Zerbetto, Angew. Chem. 2007, 119, 72;
Angew. Chem. Int. Ed. 2007, 46, 72; b) W. R. Browne, B. L. Feringa,
Nat. Nanotechnol. 2006, 1, 25; c) K. Kinbara, T. Aida, Chem. Rev.
2005, 105, 1377; d) V. Balzani, A. Credi, F. M. Raymo, J. F. Stoddart,
Angew. Chem. 2000, 112, 3484; Angew. Chem. Int. Ed. 2000, 39,
3348; e) Molecular Catenanes, Rotaxanes and Knots (Eds.: J.-P. Sauv-
age, C. Dietrich-Buchecker), Wiley-VCH, Weinheim, 1999.
[2] a) A. Coskun, D. C. Friedman, H. Li, K. Patel, H. A. Khatib, J. F.
Stoddart, J. Am. Chem. Soc. 2009, 131, 2493; b) S. Angelos, Y.-W.
Yang, K. Patel, J. F. Stoddart, J. I. Zink, Angew. Chem. 2008, 120,
2254; Angew. Chem. Int. Ed. 2008, 47, 2222; c) V. Balzani, M. Clem-
ente-Leon, A. Credi, B. Ferrer, M. Venturi, A. H. Flood, J. F. Stod-
dart, Proc. Natl. Acad. Sci. USA 2006, 103, 1178.
[3] a) S. M. Goldup, D. Leigh, P. J. Lusby, R. T. McBurney, A. M. Z.
Slawin, Angew. Chem. 2008, 120, 3429; Angew. Chem. Int. Ed. 2008,
47, 3381; b) A. Fernandes, A. Viterisi, F. Coutrot, S. Potok, D. A.
Leigh, V. Aucagne, S. Papot, Angew. Chem. 2009, 121, 6565; Angew.
Chem. Int. Ed. 2009, 48, 6443.
[4] a) A. I. Prikhodko, J.-P. Sauvage, J. Am. Chem. Soc. 2009, 131, 6794;
b) J.-P. Collin, F. Durola, J. Lux, J.-P. Sauvage, Angew. Chem. 2009,
121, 8684; Angew. Chem. Int. Ed. 2009, 48, 8532.
[5] a) M. J. Chmielewski, L. Zhao, A. Brown, D. Curiel, M. R. Sam-
brook, A. L. Thompson, S. M. Santos, V. Felix, J. J. Davis, P. D. Beer,
Chem. Commun. 2008, 3154; b) W. Jiang, H. D. F. Winkler, C. A.
Schalley, J. Am. Chem. Soc. 2008, 130, 13852; c) T. Umehara, H.
Kawai, K. Fujiwara, T. Suzuki, J. Am. Chem. Soc. 2008, 130, 13981;
d) G. Wenz, B.-H. Han, A. Mꢁller, Chem. Rev. 2006, 106, 782;
e) S. J. Loeb, Chem. Commun. 2005, 1511; f) J. Terao, A. Tang, J. J.
Michels, A. Krivokapic, H. L. Anderson, Chem. Commun. 2004, 56;
g) O. Lukin, T. Kubota, Y. Okamoto, F. Schelhase, A. Yoneva,
W. M. Mꢁller, U. Mꢁller, F. Vçgtle, Angew. Chem. 2003, 115, 4681;
Angew. Chem. Int. Ed. 2003, 42, 4542; h) K. Kim, Chem. Soc. Rev.
2002, 31, 96; i) Y. Makita, N. Kihara, T. Takata, J. Org. Chem. 2008,
73, 9245.
[6] a) S. J. Dalgarno, N. P. Power, J. L. Atwood, Coord. Chem. Rev.
2008, 252, 825; b) J. W. Steed, J. L. Atwood, Supramolecular Chemis-
try: Second Edition, Wiley, Chichester, UK, 2009; c) M. Fukuda, R.
Sekiya, R. Kuroda, Angew. Chem. 2008, 120, 718; Angew. Chem. Int.
Ed. 2008, 47, 706.
Most gratifying, however, is that our experiments indicat-
ed two independent possibilities of switching the rotaxana-
tion process, which might prove useful for the use of our
system in information processing applications.
[7] C.-F. Lee, D. A. Leigh, R. G. Pritchard, D. Schultz, S. J. Teat, G. A.
Timco, R. E. P. Winpenny, Nature 2009, 458, 314.
[8] Anion Receptor Chemistry (Eds.: J. L. Sessler, P. A. Gale, W.-S.
Cho), RSC Publishing, Cambridge, 2006.
Experimental Section
[9] a) G. H. Clever, S. Tashiro, M. Shionoya, Angew. Chem. 2009, 121,
7144; Angew. Chem. Int. Ed. 2009, 48, 7010; b) G. H. Clever, S. Ta-
shiro, M. Shionoya, J. Am. Chem. Soc. 2010, 132, 9973.
Compounds 4a and 4b were synthesized by the CuI-catalyzed click reac-
tion from bis-azide 2 by using alkynes 3a or 3b (6 equiv), respectively,
[Cu
CH2Cl2. PtII cage 1b was prepared according to the procedure for synthe-
sizing PdII cage 1a[9] from the bis-pyridyl ligand and [Pt
(CH3CN)4]-
[BF4]2,[17] allowing a prolonged reaction time of 12 h at 808C (for details,
(CH3CN)4]
E
[10] We have recently reported coordination-based internal modification
of coordination capsules using bis-sulfonate ligands, see S. Hiraoka,
M. Kiyokawa, M. Shionoya, Angew. Chem. 2010, 122, 142; Angew.
Chem. Int. Ed. 2010, 49, 138.
ACHTUNGTRENNUNG
Chem. Eur. J. 2010, 16, 11792 – 11796
ꢃ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
11795

M. Shionoya and G. H. Clever
[11] O. Karthaus, M. Shimomura, M. Hioki, R. Tahara, H. Nakamura, J.
Am. Chem. Soc. 1996, 118, 9174.
[12] B. M. J. M. Suijkerbuijk, B. N. H. Aerts, H. P. Dijkstra, M. Lutz,
A. L. Spek, G. van Koten, R. J. M. Klein Gebbink, Dalton Trans.
2007, 1273.
[15] Molecular mechanics (MMFF) energy minimizations computed with
Spartan 08, Wavefunction Inc., Irvine USA (see also the Supporting
Information). Owing to the number and symmetry of the NMR sig-
nals of the host–guest complexes in solution, the guests are believed
to be able to quickly rock or tumble inside the cage.
[13] a) C.-F. Lin, Y.-H. Liu, C.-C. Lai, S.-M. Peng, S.-H. Chiu, Angew.
Chem. 2006, 118, 3248; Angew. Chem. Int. Ed. 2006, 45, 3176; b) C.-
F. Lin, C.-C. Lai, Y.-H. Liu, S.-M. Peng, S.-H. Chiu, Chem. Eur. J.
2007, 13, 4350.
[16] L. M. Klivansky, G. Koshkakaryan, D. Cao, Y. Liu, Angew. Chem.
2009, 121, 4249; Angew. Chem. Int. Ed. 2009, 48, 4185.
[17] A. de Renzi, A. Panunzi, A. Vitagliano, G. Paiaro, J. Chem. Soc.
Chem. Commun. 1976, 47.
[14] In our case fluorescence is totally quenched by encapsulation, for an
example of emissive host–guest complexes, see: J. K. Klosterman,
M. Iwamura, T. Tahara, M. Fujita, J. Am. Chem. Soc. 2009, 131,
9478.
Received: July 16, 2010
Published online: September 17, 2010
11796
www.chemeurj.org
ꢃ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 11792 – 11796