Our research concerns
the identification, synthesis, and characterization of
polymers with selected functionality, composition, and
molecular architecture. Several areas of polymer chemistry
are being investigated.
A significant effort is dedicated to devising new
synthetic routes to functional macromolecules. In addition to
relying on living/controlled radical polymerization techniques to
prepare polymers of controlled molecular weight and retained end
group functionality, highly efficient postpolymerization
modification is required to incorporate functionality not easily
included in monomer, initiator, or chain transfer agents. Many
chemical transformations employed in organic synthesis do not
demonstrate the same degree of efficiency and orthogonality when
used for functionalization of high molecular weight
macromolecules. Therefore, a significant effort in our group has
involved the extension of "click chemistry" methodologies for
functional polymer synthesis.
The solution
behavior of polymers that exhibit "smart" behavior in
aqueous media is being investigated. Responsive block copolymers can be induced to form micelles, vesicles, or gels, and
may ultimately lead to new applications in controlled drug delivery,
tissue engineering, and surface biocompatibilization.
Modifying
biological molecules with "smart" polymers provides a means to
externally control the solubility and activity of proteins,
peptides, and nucleic acids. Examples of such hybrid materials
include polymer-protein conjugates in which the activity of the
protein can be tuned by capitalizing on the responsive nature of the
immobilized synthetic polymer.
Polymers that demonstrate responsive behavior in organic media or in
the bulk phase are also considered.
In these cases, the responsive behavior arises from the reversible
nature of dynamic covalent chemistry. Materials prepared by this
approach include smart nanoparticles, organogels, and self-healing materials.
General concepts of our work and details of selected publications are given
below.
Efficient
polymer modification via specific and orthogonal methodologies
Responsive polymeric materials can be
prepared by a wide variety of synthetic techniques, though not all of
these methods are widely applicable. We seek to develop routes to
complex polymers by using only simple and straightforward chemical
transformations. For instance, copper-catalyzed azide-alkyne coupling and other efficient
synthetic strategies (Diels-Alder reactions, Michael addition, etc.)
can be used to prepare, for example, functional telechelics, molecular
bottle-brush copolymers, and thermoresponsive hyperbranches. We have
developed new azido-functionalized chain transfer agents that allow
end-functional polymers to be prepared by reversible
addition-fragmentation chain transfer (RAFT) polymerization. In addition
to have controlled molecular weights, the resulting polymers contain
azido groups capable of quantitatively reacting with small molecule or
polymeric alkynes under non-demanding conditions. We also
investigate end group transformations that exploit the telechelic sulfur functionality
inherent to polymers prepared by RAFT. We have demonstrated that
dithioester or trithiocarbonate end groups can be readily reduced to
thiols capable of efficiently reacting with electron deficient alkenes
to yield a range of materials, including modular block copolymers,
functionalized surfaces, or polymer-protein conjugates. Many of the synthetic methods
we consider fall
within the realm of “click chemistry,” and have proven to be excellent
candidates for materials derivatization.
Stimuli-responsive and dynamic covalent polymer assemblies
By constructing macromolecular
assemblies with linkages that are reversibly covalent, we prepare new
materials that have the ability to adapt their structure, constitution,
and reactivity depending on the nature of the surrounding environment.
Reversibility being a key attribute, these systems offer versatility
typically associated with supramolecular materials (dynamic
rearrangement, self-assembly, self-repair, etc.), while maintaining the
integrity and robust nature of covalently formed polymers. Reversible covalent
assemblies
are constitutionally dynamic, having the ability to modify their
constitution by incorporating or exchanging
their components. Thus, after macromolecular dissociation,
reconstruction in the presence of a competing
equilibrium results in exchange of polymer building blocks to yield an
entirely new material. The ability to reshuffle constituents through
assembly-disassembly is also being employed to induce dramatic
topological rearrangements in solution. This research exploits
reversible covalent chemistries to prepare adaptive
materials and to increase understanding of telechelic polymer
self-assembly into dynamic covalent macromolecular systems.
Polymers with
biological relevance
The ability to prepare
controlled-architecture, functional polymers is a significant advantage
when trying to design new materials for applications in drug delivery,
biological imaging, tissue engineering, etc. We explore routes to
macromolecules that can be used in such applications because of the
ability to self-assemble/dissociate in response to an applied stimulus.
For instance, we prepare block copolymers that form micelles or vesicles
when appropriately triggered. In some cases, these nanoassemblies are
decorated
with biological ligands that facilitate targeted delivery to tumors in
order to localize the delivery of anticancer drugs. Systems with
potential for delivery of other drugs have also been prepared by
appropriately designing new responsive polymeric micelles and vesicles.
Additionally,
covalent modification of proteins with synthetic polymers allows tuning
of enzymatic activity and bioavailability for protein therapy and
catalysis applications. We seek to expand the synthetic repertoire by
which such materials can be prepared.
