Students and researchers in the Pielak Group, use the formalisms of equilibrium thermodynamics and the tools of molecular biology and biophysics to understand protein structure, stability, and function.
Currently, our research focuses on In-cell NMR, a new method which allows us to obtain high resolution NMR data from proteins in living cells. Much of this work involves quantifying the effects of macromolecular crowding on protein chemistry. Additionally, we study the oxidative aggregation of the key protein involved in Parkinson's disease,
α-synuclein.
Associate professor Mark Schoenfisch in the analytical division, along with two of his senior graduate students, Susan Deupree and Evan Hetrick, recently returned from the Eighth World Biomaterials Congress, held this year in Amsterdam. The Congress featured posters and presentations from over 2800 papers, including three from the Schoenfisch group. Research presented by our lab showcased the efficacy of novel nitric oxide-releasing nanoparticles as anti-biofilm agents, the ability of these materials to aid in mediating the biocompatibility of implantable sensors, as well as an atomic force microscopy study of the mechanism of nitric oxide’s antimicrobial action.
Serotonin, also known as 5-HT is an important molecule in the brain that is implicated in mood and emotional processes. Although there is a heavy pharmaceutical emphasis on serotonin's involvement in many neurological disorders, in vivo, its dynamic release and uptake kinetics are poorly understood. This is due to a lack of analytical techniques for its rapid measurement. Whereas fast-scan cyclic voltammetry with carbon fiber microelectrodes is used frequently to monitor subsecond dopamine release in freely moving and anesthetized rats, the electrooxidation of serotonin forms products that quickly polymerize and irreversibly coat the carbon electrode surface.
In a paper published in Analytical Chemistry, the Wightman Group identifies the root of this fouling to not only be due to serotonin, but also to the negatively charged extracellular metabolites of serotonin, present in 200−1000 times the concentration of serotonin in vivo. To impede access of these negatively charged species, a thin layer of Nafion, a cation exchange polymer, was electrodeposited onto cylindrical carbon-fiber microelectrodes. The team visually confirmed the presence of the Nafion film using scanning electron microscopy and showed that the signals for negatively charged species were diminished. Interestingly, the properties of the Nafion also increased sensitivity to serotonin, providing an electrochemical signature of serotonin that could be verified in vitro. In vivo, the team used physiological, anatomical, and pharmacological evidence to validate the signal as serotonin. Using Nafion-modified microelectrodes, the Wightman Group presents the first endogenous recording of serotonin in the mammalian brain.
Joseph DeSimone, Chancellor's Eminent Professor of Chemistry at UNC, and William R. Kenan, Jr. Distinguished Professor of Chemical Engineering at NCSU, has been selected to receive this year's North Carolina Award in Science.
Considered one of the nation’s premier scientists, Joseph DeSimone was selected because of his cutting edge research with revolutionary results for cancer treatment, green chemistry and photovoltaics. His breakthroughs in nanotechnology applications and in the fields of polymer chemistry, pharmacology, and biomolecular engineering, have produced life-changing and world-saving inventions.
The North Carolina Award is the highest civilian award bestowed by the state of North Carolina, and is sometimes referred to as the "Nobel Prize of North Carolina." The awardees are chosen by the North Carolina Awards Committee, appointed by the governor of North Carolina and supervised by the state's Secretary of Cultural Resources.
Joseph DeSimone is the sixth Carolina chemist to be honored with this award. Previous Carolina recipients are Oscar Rice, 1966, Ernest Eliel, 1986, Robert Parr, 1999, Royce Murray, 2001, and Maurice Brookhart, 2008.
Carolina Chemist and John P. Barker Distinguished Professor Michael Rubinstein, has been awarded the 2010 Polymer Physics Prize from the American Physical Society. The prize recognizes outstanding contributions in polymer physics research, specifically professor Rubinstein's leadership in the field of structure and dynamics of polymer liquids, interfaces and gels.
Most of the materials around us, from plastics to tires, and inside us, DNA and proteins, are made of polymers - giant, chain-like molecules. The goal of Rubinstein’s research group is to understand how polymers move through a tangle formed by their molecule neighbors and how they are deformed if attached to each other in a network, then pulled apart, like stretching a rubber band. UNC researchers are modeling polymers in the lungs with the goal of developing treatments for diseases such as cystic fibrosis.
The unique properties of polymers that make them the materials of choice in many industries are their enormous size in comparison to ordinary molecules and their ability to change under the influence of surrounding molecules, according to Rubinstein.
Rubinstein received his bachelor’s degree from the California Institute of Technology and his master’s and doctorate degrees from Harvard University. He will be presented the award at a meeting of the American Physical Society in March 2010.
As reported in the October 23, 2009, issue of the journal Science, Carolina chemists in collaboration with colleagues at the University of Washington have taken an important step in converting methane gas to a liquid, potentially making it more useful as a fuel and as a source for making other chemicals.
The carbon-hydrogen bonds of alkanes are weak ligands and thus reports of isolation or spectroscopic observation of alkane complexes in solution are extremely rare. Nevertheless, such complexes are postulated as intermediates that form prior to C-H bond scission in most oxidative addition reactions of alkanes. The Shilov system for catalytic conversion of methane to methanol is thought to involve a Pt(II) methane complex as a key intermediate. While a postdoctoral fellow in the Brookhart Group, Wes Bernskoetter, now on the faculty at Brown, succeeded in preparing the first solution-stable, NMR-observable transition metal complex of the simplest alkane, methane (CH4).
The methane complex was obtained by low temperature protonation of a pincer rhodium methyl complex and fully characterized by 1H, 13C and 31P NMR spectroscopy. Cindy Schauer, co-author of the study, carried out DFT calculations that suggest one C-H bond interacts preferentially with the Rh center to form a three-center, two-electron bond, as per the above figure. The Brookhart Group hopes that investigation of the properties of this and other methane complexes may lead to more efficient catalysts for functionalization of alkanes.
This past summer 13 UNC students took their Chem 262 during the second summer session, not in Chapel Hill, but in Sevilla, Spain. They were the inaugural group of students who took advantage of a new study abroad initiative in which students can elect to take this important course, taught in English, by a UNC system professor in Spain.
In addition, the students took a 3 credit Spanish class, SPAN 104 or higher, taught by a Spanish professor from Sevilla. Students lived for the 5-6 weeks with Spanish families, where they ate all their meals. The organic courses was taught this year by Prof. Phil Brown of NCSU. Some of these students were so thrilled that they are opting to go back to Spain next year as exchange students, where they get to take their chemistry courses in Spanish.
Researchers in the Waters Group, as published in JACS, demonstrate how phosphorylated amino acids were incorporated into a designed β-hairpin peptide to study the effect on β-hairpin structure when the phosphate group is positioned to interact with a tryptophan residue on the neighboring strand. The three commonly phosphorylated residues in biological systems, serine, threonine, and tyrosine, were studied in the same β-hairpin system.
It was found that phosporylation destabilizes the hairpin structure by approximately 1.0 kcal/mol, regardless of the type of phosphorylated residue. In contrast, destabilization due to glutamic acid was about 0.3 kcal/mol. Double mutant cycles and pH studies are consistent with a repulsive interaction as the source of destabilization. These findings demonstrate a novel mechanism by which phosphorylation may influence protein structure and function.