From left to right: Brown, Ruttinger, Vaidya, Alabi and Clancy
Introducing the researchers:
Joseph S Brown is currently a Postdoctoral Associate at the Massachusetts Institute of Technology in Professor Bradley Pentelute’s Lab in Chemistry. He received his B.Sc. in Chemical and Biomolecular Engineering from North Carolina State University in 2013 with Valedictorian Honors. At Cornell University, he earned his Ph.D. in Chemical and Biomolecular Engineering working with Professor Christopher Alabi on the structural and biophysical characterization of sequence-defined oligothioetheramides as a National Science Foundation (NSF) Graduate Research Fellow. He plans to apply his skills in synthetic chemistry, biophysical characterization, and biochemistry to aid the drug discovery of biologics focusing on the therapeutic disruption and modulation of protein-protein interactions.
Andrew W Ruttinger is currently a Ph.D. candidate in Chemical and Biomolecular Engineering at Cornell University, with Professor Paulette Clancy on the development of low-carbon and renewable energy technology. He earned his Bachelor of Engineering in Chemical Engineering from the University of Western Ontario, Canada. Upon graduation, Andrew plans to work in science policy, using his experience in developing green technology towards protecting Canada’s environment and climate.
Akash Vaidya received his B.S. in Chemical Engineering from Cornell University, where he was an undergraduate researcher for Professor Christopher Alabi. He spent two summers as a undergraduate research fellow with the Lyssiotis Research Group at the University of Michigan Medical School. Akash is currently pursuing his Ph.D. in Chemical and Biomolecular Engineering at the University of Delaware, where he plans to design (bio)polymeric materials for medical applications and lead outreach programs to promote diversity and inclusion in engineering.
Christopher Alabi is the Nancy and Peter Meinig Family Investigator in the Life Sciences at the Robert Frederick Smith School of Chemical and Biomolecular Engineering at Cornell University. Research in the Alabi lab seeks to utilize synthetic and analytical tools to understand how the composition and sequence of a macromolecular chain affects its chemical, structural and biological properties with an eye towards engineering sustainable materials and biomolecular therapeutics.
Paulette Clancy is a Professor and inaugural Head of the Department of Chemical and Biomolecular Engineering at the Johns Hopkins University. She is also the Samuel and Diane Bodman Professor Emerita of Chemical Engineering at Cornell. Her group develops new algorithms to advance our ability to make accurate models of materials, especially electronic materials and sustainable energy systems. More recently, her group is developing new machine learning techniques to accelerate the search for optimal materials processing protocols and new materials.
What inspired your research in this area?
We were inspired to pursue this work because it promised to unlock new and exciting chemical reaction schemes including automated, robotic, and/or combinatorial syntheses using the thiol-Michael addition. While we chose to study oligothioetheramides (oligoTEAs) in this work, we expect that the new mechanistic understanding of the thiol-Michael addition reaction that we have uncovered will be broadly applicable, allowing us to create designer monomers for other types of materials and polymer science applications.
What do you personally feel is the most interesting outcome of your study?
While surprising at first, our most interesting finding was that physical associations could be strong enough to dictate rate-limiting steps within the reaction mechanism. Other groups have observed this for acrylates (Desmet et al., Polymer Chemistry (2017)), but the addition of this work has clarified our understanding of the exact mechanism, including product decomplexation. It was also exciting to see the nearly quantitative agreement between experiments and accurate DFT calculations coupled to a method of finding energy barriers (Nudged Elastic Band) that give exquisitely detailed insight into the mechanism that underlies this popular Michael addition reaction.
What are you going to be working on next?
We believe that sequence-defined materials like oligoTEAs could offer a promising new approach to controlling the design of new biomaterials. Precision biomaterials are still finding their niche, but are well-positioned to contribute as therapeutics, diagnostics, catalysts, and others. Many of these applications rely on selective and high-affinity molecular recognition events, which is our focus at this time. Computationally, we are working on a new approach that deploys machine learning to accelerate discovery of sequence-controlled oligoTEAs to match a given objective. Even with just 12-15 “beads” on the oligoTEA backbone, the size of the combinatorial problem precludes a trial-and-error search, whether computationally or experimentally. Machine learning can help us tame this otherwise overwhelming design space.
Read the full article: Decomplexation as a rate limitation in the thiol-Michael addition of N- acrylamides
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