Applying lithographic fabrication techniques from the computer industry, the DeSimone Group focuses on creating nanoscale particles using the PRINT®, Particle Replication in Non-wetting Templates, technology. Developed in DeSimone's lab, PRINT enables precise control over particle features such as size, shape, chemical composition, deformability, and surface functionality. Multidisciplinary in nature, the DeSimone Group's research shows significant promise for novel applications in both life and materials science, ranging from improved vaccines to new medicines and targeted drug delivery approaches, to particulate surfactants and colloids for emerging technologies in robotics and displays.
The Lawrence Group works at the interface between organic synthesis and cell biology. In fact, half the group resides in Chemistry's Kenan Labs and the other half can be found in the newly opened multidisciplinary Genetic Medicine Building in the medical school complex. The lab focuses on the design, synthesis, characterization, and application of probes of intracellular chemistry. Research interests include new diagnostic strategies for cancer, sensors of signaling pathways, mitochondrial proteomics, the molecular basis of memory and learning, and the control of gene expression in living animals.
Chancellor's Eminent Professor of Chemistry Joseph DeSimone has been elected into the National Academy of Sciences, one of the highest honors that a U.S. scientist or engineer can receive.
DeSimone is one of 84 new members and 21 foreign associates from 14 countries elected into the academy. He is the 12th UNC-Chapel Hill faculty member to be elected to the academy, a private organization of scientists and engineers dedicated to advancing science and technology and their use for the public good.
A critical need exists for effective delivery of RNA interference (RNAi) therapeutics to target tissues and cells. Self-assembled lipid- and polymer-based systems have been most extensively explored for transfection with small interfering RNA (siRNA) in liver and cancer therapies. Safety and compatibility of materials implemented in delivery systems must be ensured to maximize therapeutic indices. In a collaborative work published in JACS, scientists in the DeSimone Group explore hydrogel nanoparticles of defined dimensions and compositions, prepared via a particle molding process that is a unique off-shoot of soft lithography known as particle replication in nonwetting templates (PRINT), as delivery vectors.
Initially, siRNA was encapsulated in particles through electrostatic association and physical entrapment. Dose-dependent gene silencing was elicited by PEGylated hydrogels at low siRNA doses without cytotoxicity. To prevent disassociation of cargo from particles after systemic administration or during postfabrication processing for surface functionalization, a polymerizable siRNA pro-drug conjugate with a degradable, disulfide linkage was prepared. Triggered release of siRNA from the pro-drug hydrogels was observed under a reducing environment while cargo retention and integrity were maintained under physiological conditions.
Gene silencing efficiency and cytocompatibility were optimized by screening the amine content of the particles. When appropriate control siRNA cargos were loaded into hydrogels, gene knockdown was only encountered for hydrogels containing releasable, target-specific siRNAs, accompanied by minimal cell death. Further investigation into shape, size, and surface decoration of siRNA-conjugated hydrogels should enable efficacious targeted in vivo RNAi therapies.
Hydrogen production from water splitting provides a potential solution to storing harvested solar energy in chemical fuels, but this process requires active and robust catalysts that can oxidize water to provide a source of electrons for proton reduction. As reported in ACS Applied Materials and Interfaces, the Lin Group, in collaboration with Bruce Hinds's Group at the University of Kentucky, has developed a new way to study molecular water oxidation catalysts by grafting Ir complexes, directly and covalently, onto carbon electrodes.
Carbon-grafted Ir complexes electrochemically oxidize water with a turnover frequency of up to 3.3 s-1 and a turnover number of at least 644 during the first hour. Electrochemical water oxidation with grafted catalysts gave enhanced rates and stability compared to chemically driven water oxidation with the corresponding molecular catalysts. This strategy provides a way to systematically evaluate catalysts under tunable conditions, potentially providing new insights into electrochemical water oxidation processes and water oxidation catalyst design.
Congratulations to all students who were recognized at this year's Chemistry Commencement ceremony. Chemistry is considered one of the most demanding degrees offered at Carolina.
Professor and Department Chair Matthew Redindo delivered the welcome address, after which followed the doctoral hooding ceremony, presided over by Professor Mark Schoenfisch, Director of Graduate Studies. Miss Eva Archer then delivered the undergraduate student commencement address.
Dr. Marcey Waters, Professor and Director of Undergraduate Studies presented the undergraduate student awards. Congratulations to all winners.
Francis P. Venable Medal
Matthew Detter
Sophie Liu
Emmett Gladstone Rand Premedical Scholarship
Ryan Gardner
Kathryn Magee
Garrick Talmadge
David L. Stern Scholarships in Chemistry
Xiaoling Zang
Merck Index Award
Stephen Barilovits IV
Srikar Bongu
Carrie Ann Largent Award
Sean Doris
Teresa Long
Hypercube Scholar Award
Hannah Gavin
Nicholas Pinkin, Dennis Ashford, Sophie Liu, Travis LaJoie, Njamkou Noucti, Matt Smola, Mary Aiken and Robert Sharpe, from left to right below, are this year's recipients of grants from the The National Science Foundation's Graduate Research Fellowship Program, (GRFP).
GRFP helps ensure the vitality of the human resource base of science and engineering in the United States and reinforces its diversity. The program recognizes and supports outstanding graduate students in NSF-supported science, technology, engineering, and mathematics disciplines who are pursuing research-based master's and doctoral degrees at accredited US institutions.
α-Synuclein, an intrinsically-disordered protein associated with Parkinson's disease, interacts with mitochondria, but the details of this interaction are unknown. Researchers in the Pielak Group probed the interaction of α-synuclein and its A30P variant with lipid vesicles by using fluorescence anisotropy and 19F nuclear magnetic resonance. Both proteins interact strongly with large unilamellar vesicles whose composition is similar to that of the inner mitochondrial membrane, which contains cardiolipin. However, the proteins have no affinity for vesicles mimicking the outer mitochondrial membrane, which lacks cardiolipin. The 19F data show that the interaction involves α-synuclein's N-terminal region.
These data indicate that the middle of the N-terminal region, which contains the KAKEGVVAAAE repeats, is involved in binding, probably via electrostatic interactions between the lysines and cardiolipin. The group also found that the strength of α-synuclein binding depends on the nature of the cardiolipin acyl side chains. Eliminating one double bond increases affinity, while complete saturation dramatically decreases affinity. Increasing the temperature increases the binding of wild-type, but not the A30P variant. The data are interpreted in terms of the properties of the protein, cardiolipin demixing within the vesicles upon binding of α-synuclein, and packing density. The results advance our understanding of α-synuclein's interaction with mitochondrial membranes.