Sumerlin Research Group

Research

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, with particular focus on those most closely related to biological applications.

  1. Functional polymer synthesis and efficient polymer modification via specific and orthogonal methodologies. 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.
     

  2. Stimuli-responsive water-soluble block copolymers. 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.
     

  3. Dynamic-covalent macromolecular materials. By constructing macromolecular assemblies with linkages that are reversibly covalent, we prepare new materials with 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. Materials constructed via covalent bonds that can be triggered to dissociate in response to specific chemical stimuli include smart nanoparticles, organogels, and self-healing coatings.
     

  4. Smart polymer-protein bioconjugates. 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, stability, or solubility of the protein can be tuned by capitalizing on the responsive nature of the immobilized synthetic polymer.  

General concepts of our work and details of selected publications are given below.

1. Functional polymer synthesis and 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.

2. Stimuli-responsive water-soluble block copolymers.
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 triggered by stimuli experienced in biological milieu. 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. For example, while the large majority of previous reports of stimuli-responsive block copolymers have involved well-known polymers with susceptibility to changes in temperature, pH, or ionic strength, we have helped expand the repertoire of applicable stimuli by preparing block copolymers that respond to changes in glucose concentration. These novel materials have potential therapeutic utility for the deliver of insulin during the treatment of diabetes.

3. Dynamic-covalent macromolecular materials
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 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.

4. Smart polymer-protein bioconjugates
Modification of biomacromolecules (e.g., proteins, nucleic acids, polysaccharides) with synthetic polymers is a viable means to increase efficacy for many in vivo and in vitro applications. In many cases, important characteristics (e.g., solubility, biocompatibility, stability, activity) of the biological component are conserved or enhanced due to the presence of the immobilized polymer. Typical conjugation methods primarily consist of grafting-from, which describes the polymerization of monomer from a biomolecule capable of initiation, and grafting-to, which involves immobilization of preformed polymer by reactive coupling. We have employed both methods, in combination with RAFT polymerization, to synthesize well-defined polymer-protein conjugates. While important, our research is not limited to the preparation of new biological materials with potential applications in drug delivery, enzymatic catalysis, etc. Rather, we also seek to elucidate and enhance the fundamental chemistry of the conjugation processes.