great advantage to many of the bistable systems created in the Stoddart
labs is that they are switchable only on demand. Despite the obvious
utility in molecular electronics, these systems can be anchored to
various surfaces and the same controlled switchability can be
replicated.1 By utilizing the well-understood complexation
between CBPQT4+ and BHEEN, a simple pseudorotaxane system has
be created2 at the surface of mesoporous silica nanoparticles
(MCM-41), which can act as a valve that opens and closes upon the
introduction of an appropriate stimulus such as electrochemical, redox
or even light (with the use of photosensitizers).
take this idea further, we have shown repeated release using a fully
reversible system based on a bistable rotaxane after a chemical redox
stimulus.3 We can therefore envision trapping guest molecules
(i.e. drugs) in the pores of the functionalized MCM-41 and releasing
them on demand and only on demand. By using different molecular systems
to functionalize the mesoporous silica nanoparticles, the release can
also be activated4 using pH control. All the work using
mesoporous silica is performed in collaboration with the group of
Professor Jeffrey Zink.
Multivalent Aggregation Inhibitor
Self-assembled pseudopolyrotaxanes consisting of lactoside-displaying
cyclodextrin (CD) "beads" threaded onto linear polyviologen "strings"
have been investigated5 for their ability to inhibit
galectin-1-mediated T-cell agglutination. The CDs of the
pseudopolyrotaxane are able to spin around the axis of the polymer chain
as well as to move back and forth along its backbone to alter the
presentation of its ligand. This supramolecular superstructure
incorporates all the advantages of polymeric structures, such as the
ability to span large distances, along with a distinctively dynamic
presentation of its lactoside ligands to afford a neoglycoconjugate that
can adjust to the relative stereochemistries of the lectin's binding
The pseudopolyrotaxane exhibited a valency-corrected 10-fold enhancement
over native lactose in the agglutination assay, which was greater than
the enhancements observed for traditional lactoside-bearing trivalent
glycoclusters and a lactoside-bearing chitosan polymer tested using the
same assay. The experimental results indicated that supramolecular
architectures, such as pseudopolyrotaxanes, provide tools for
investigating protein-carbohydrate interactions.
the course of this research, it was found6 that polyviologens
are responsive to the Bradford assay, which is traditionally highly
selective for proteins. The response of the pseudopolyrotaxanes to the
Bradford assay was dependant on, and thus indicative of, the degree of
threading of the CD rings onto the polyelectrolyte. The assay was then
used to report on the threading and dethreading of native and lactoside-bearing
a-CD rings onto and off of polyviologen chains, a phenomenon which
demonstrates the utility of biochemical assays to address problems
unique to supramolecular chemistry.
(a) Chia, S. Y.; Cao, J. G.; Stoddart,
J. F.; Zink, J. I., "Working Supramolecular Machines Trapped in
Glass and Mounted on a Film Surface," Angew. Chem. Int. Ed. 2001,
40, 2447. (b) Saha, S.; Johansson, L. E.; Flood, A. H.; Tseng,
H.-R.; Zink, J. I.; Stoddart, J. F. Small 2005, 1, 87-90. (c) Saha,
S.; Johansson, L. E.; Flood, A. H.; Tseng, H.-R.; Zink, J. I.;
Stoddart, J. F., Chem. Eur. J. 2005, 11, 6846-6858.
Hernandez, R.; Tseng, H.-R.; Wong, J.
W.; Stoddart, J. F.; Zink, J. I. J. Am. Chem. Soc. 2004, 126,
Nguyen, T. D.; Tseng, H.-R.; Celeste,
P. C.; Flood, A. H.; Liu, Y.; Stoddart, J. F.; Zink, J. I. Proc.
Natl. Acad. Sci. USA 2005, 102, 10029-10034.
(a) Nguyen, T. D.; Leung, K. C.-F.;
Liong, M.; Pentecost, C. D.; Stoddart, J. F.; Zink, J. I. Org. Lett.
2006, 8, 3363-3366. (b) Leung, K. C.-F.; Nguyen, T. D.; Stoddart, J.
F.; Zink, J. I. Chem. Mater. 2006, ASAP Article.
Nelson, A.; Belitsky, J. M.; Vidal, S.;
Joiner, C. S.; Baum, L. G.; Stoddart, J. F. "A Self- Assembled
Multivalent Pseudopolyrotaxane for Binding Galectin-1," J. Am. Chem.
Soc. 2004, 126, 11914-11922.
Belitsky, J. M.; Nelson, A.; Stoddart,
J. F., "Monitoring cyclodextrin-polyviologen pseudopolyrotaxanes
with the Bradford Assay," Org. Biomol. Chem. 2006, 4 , 250-256.