THERAPEUTIC H2S DELIVERY:
Hydrogen sulfide (H2S) is known primarily as a foul-smelling, toxic pollutant. However, recent evidence shows that H2S is a vital biological signaling gas. Along with carbon monoxide and nitric oxide, H2S is the third member of the class of signaling gases known as gasotransmitters. As an endogenously produced signaling molecule, H2S is of interest as a therapeutic in a wide variety of disease and conditions. The majority of biological studies on H2S have been carried out with systemically administered small molecule H2S donors, which have little tissue specificity and the potential for off-target effects. As a result, delivering H2S to a desired site of action at therapeutic dosages remains difficult. To this end we focus on the development of new small molecules, polymers, and gels for targeted and localized H2S delivery.
PEPTIDE-BASED RESPONSIVE AND BIOACTIVE MATERIALS:
Peptides exhibit rich, well-defined secondary structures, which in many cases change in response to a shift in temperature, pH, or other stimuli. We aim to incorporate peptides into viscoelastic gels, with the goal of multiplying changes in peptide secondary structure across several orders of magnitude, from the molecular scale to the macroscale. We are also pursuing the development of self-assembling peptides for use as bioactive materials for drug delivery and regenerative medicine. Determining structure-property relationships in these peptide-based materials and measuring their effects on cell viability, proliferation, and differentiation are our major goals in this area of research.
The expansion of controlled polymerization techniques over the past two decades has enabled the construction of polymers with complex topologies. Bottlebrush polymers contain a polymer backbone with densely grafted polymer side chains, which force the backbone polymer into an extended conformation. These types of polymers may have applications as supersoft elastomers, vibration damping materials, and as nano-objects of controlled dimensions. We are pursuing new synthetic routes to bottlebrush polymers using a variety of polymerization techniques, including reversible addition-fragmentation transfer (RAFT) polymerization, atom transfer radical polymerization (ATRP), and ring-opening metathesis polymerization (ROMP).
RAFT transfer-to polymerization is a unique route toward the synthesis of bottlebrush polymers. During this process, the polymeric radical detatches from the bottlebrush backbone, propagates freely in solution, and returns to the backbone via a chain-transfer reaction. The transfer-to route is highly advantageous due to the fact that radical coupling between adjacent polymer side chains or between bottlebrush molecules does not occur. Therefore, very high molecular weight bottlebrush polymers can be synthesized using this method. We are interested in exploiting this advantage to prepare a variety of bottlebrush polymers with high molecular weights and narrow molecular weight distributions.