Bioorganic, Biophysical, & Chemical Biology. Peptides and their mimetics can target protein surfaces in ways small molecules rarely do, making peptide libraries attractive for screening for nontraditional modes of action. The Kritzer research group takes advantage of peptide and peptidomimetic libraries to bypass many of the disadvantages of small molecule screening. They also explore how modifications such as substitution of peptide bonds with isosteres, amide N-methylation, and head-to-tail cyclization affect the activities, specificities, and bioavailabilities of functional peptides. By combining powerful techniques from organic synthesis, biophysical chemistry, molecular biology and genetics, they are developing new molecules and new strategies to attack cancer, inflammation, and autoimmune diseases.
Organic Synthesis, Carbohydrate Chemistry, Synthetic Methodology, Bioorganic Chemistry. Complex carbohydrates play critical roles in a number of biological processes including, protein folding, cellular adhesion and signaling. Despite their importance, very little is understood about the molecular basis of their activity. This is largely due to the fact that the only source of pure oligosaccharides is tedious multi-step synthesis, which can take months or even years to compete. Our research is focused on developing methodologies, based on asymmetric catalysis, to streamline complex oligosaccharide synthesis. Ultimately such methods will aid in the rapid and routine preparation of oligosaccharides for biophysical studies and drug discovery.
Analytical Chemistry, Separations, Mass Spectrometry, RNA Modifications, Neuro-analytical Chemistry. Our group is interested in the characterization of RNA modifications in the central nervous system and single cells. These naturally occurring modifications to RNA biopolymers play important roles in regulating protein translation, but little is known about their functions in the brain. We are focused on developing new approaches for chromatographic separations and mass spectrometry measurements of in small-volume samples such that they can be applied for the simultaneous profiling of multiple RNA modifications in single neurons. The Clark Lab is particularly interested in ionic liquid solvents and ion-tagged oligonucleotides as customizable materials for nucleic acid sample preparation that can be leveraged to improve the performance of downstream analysis methods. We combine our analytical methodologies with a powerful neurobiological model, the marine mollusk Aplysia californica, to investigate relationships between the dynamic landscape of RNA modifications and animal behavior, learning and memory, and function of the central nervous system in health and disease.
I am interested in synthesis and characterization in inorganic and materials chemistry. I am especially interested in fundamental chemistry that has important societal implications.
My research laboratory currently works in several areas:
Earth-abundant molecular light absorbers and emitters.
Molecular light absorbers and emitters are used in photoredox catalysis, dye-sensitized solar cells, and organic light-emitting diodes (OLEDs). We are exploring high-spin complexes of iron and manganese to prepare new molecules that absorb and emit light.
Volatile molecules carrying metal-atom equivalents for superconducting wires.
Cryogenic superconducting wires enable quantum bits based on Josephson junctions. We are developing new molecules and methods to deposit the electropositive metals that make up these wires from chemical vapors.
Thin-film photovoltaics with earth-abundant, sulfide-based absorber layers.
Thin-film photovoltaics (solar cells) provide electricity from sunlight with just a few hundred nm of light-absorbing material. We are exploring binary and ternary sulfides as new sources of earth-abundant photovoltaics.
I am developing new research programs in several areas:
The synthesis of iron metal from iron ore contributes ca. 4% of global carbon dioxide emissions. I am interested in alternative thermochemical methods of making iron from iron oxides.
New superconducting materials.
Near-room-temperature superconductors have recently been realized in compressed hydrides. I am interested in new hydride compounds that are stable at ambient pressure and might serve as ambient-pressure, ambient-temperature superconductors.
Planetary Chemical Analysis & Astrobiology -
In the search for life in our solar system over the past several decades, it has become increasingly clear that there may be multiple worlds besides Earth that either once had or may still have environments capable of supporting microbial life as we know it. Our current research is focused on two aspects of this search:
(1) In the search for life on Mars, one key question is; how are biologically-produced molecules (biomarkers) altered when exposed to solar ultraviolet radiation in the presence of oxychlorines and their intermediate formation products? To help answer this question we are investigating the "fragmentation" patterns of such altered biogenic compounds which could then be used to identify the original biomarker and thus provide evidence for life on Mars.
(2) We are developing in-situ analytical instrumentation that is designed to unambiguously detect microbial life and determine the habitability of planetary environments that may be present at the surface or subsurface of Mars, and the oceans of icy-worlds such as Saturn's moon Enceladus or Jupiter's moon Europa.
Robinson Professor of Chemistry
Bioorganic Chemistry and Chemical Biology
The research interests of the Kumar laboratory are centered on the (1) use of chemistry to design molecules to interrogate and illuminate fundamental mechanisms in biology, or be used as therapeutics; and (2) use of biology to "evolve" and "select" molecules that can perform chemistry in non-biological and medicinal settings.
These are some questions we are trying to answer: (i) Is it possible to design and mimic natural proteins and other biological macromolecules by use of building blocks that nature does not use – and whether such constructs can be endowed with properties that are not found in biology?; (ii) How did the first enzymes arise in the imagined Darwin's pond – is there a way to recreate this scenario and in the process develop a fundamentally new method to create enzymes?; (iii) Biology uses phase separation, that is, clustering of different compounds in confined locations – a process that is key in orchestrating the daily activities of a cell – can we find methods that can predictably dictate where molecules are located in a given environment and thereby direct the phenotype that is generated?; (iv) Can we rationally design small molecules and peptides that can function against antibiotic resistant bacteria that are threatening the most basic tenet of modern medicine?
Theoretical and Computational Biophysical Chemistry. The YSL Group aims to elucidate the structures and functions of biomolecules by integrating the power of advanced computations with the elegance of chemical theory. Our focus is to develop and apply computational methodology to significant biological problems that are difficult to address experimentally. Two major research projects in the YSL Group are (1) to understand and design cyclic peptides with desired conformations to modulate protein–protein interactions and (2) to elucidate the structural and functional roles of post-translational modifications and non-natural amino acids on protein folding.
Bioanalytical and Materials Chemistry. The Mace group applies a multidisciplinary approach—combining aspects of chemistry, materials science, biophysics, and engineering—to study the properties of interfaces, develop new materials, and solve outstanding problems in global health. Immiscible Systems. When mixed, many solutions of polymers, surfactants, and salts form immiscible phases. We are interested in characterizing the properties of the interfaces between immiscible liquid phases and applying immiscible systems to the study of complex mixtures. We are particularly interested in those immiscible systems that share water as a common solvent. Paper Diagnostics. Successful implementation of point-of-care diagnostics has the potential to affect the global management of diseases. Paper is an attractive platform with which to develop assays designed specifically for the developing world because the infrastructure required to develop them is minimal and the materials needed to manufacture them are inexpensive. We will develop new materials that can enable biochemical assays that are not currently possible using paper alone.
Bioorganic Chemistry and Chemical Biology. A significant frontier in chemical biology lies in the ability to develop new, selective chemical transformations that transpire at mild temperatures amidst many other reactive species and in parallel with the countless transformations that occur inside of a living cell. Research in the Scheck laboratory focuses on the invention and application of encodable, bioorthogonal chemical strategies. These tools will be used to report on inducible changes in protein function in living cells. Current efforts in the lab fall into two broad categories: 1) The development of new chemical methods that are used to study complex posttranslational modification networks and 2) The study of native and unnatural posttranslational modifications to provide valuable chemical and synthetic biology tools.
Physical Chemistry and Surface Science. The Shultz group applies physics and chemistry to understand the inner workings of hydrogen bonding. Hydrogen bonding plays key roles in environmental, biological, and atmospheric chemistry. Our program has research thrusts in all three directions. We specialize both in devising environments that clearly reveal key interactions and in developing new instrumentation. The most recent focus is on icy surfaces and on clathrate formation. Probing the ice surface begins with a well-prepared single-crystal surface. We have unique capabilities for growing single-crystal ice from the melt and for and preparing any desired ice face. Our clean water efforts are aimed at developing new materials to fill the significant need for safe drinking water. According to the World Health Organization, over one billion people lack safe drinking water. Our program is based on using photo catalysts to capture readily available sunlight to turn pollutants into benign CO2 and water. We developed methods to grow ultra-nano (~2 nm) particles that have well-controlled surface structures and chemistry.
Physical Chemistry, Surface Science, and Nanoscience. The Sykes group utilizes state of the art scanning probes and surface science instrumentation to study technologically important systems. For example, scanning tunneling microscopy enables visualization of geometric and electronic properties of catalytically relevant metal alloy surfaces at the nanoscale. Using temperature programmed reaction studies of well defined model catalyst surfaces structure-property-activity relationships are drawn. Of particular interest is the addition of individual atoms of a reactive metal to a relatively inert host. In this way reactivity can be tuned, and provided the energetic landscapes are understood, novel bifunctional catalytic systems can be designed with unique properties that include low temperature activation and highly selective chemistry. Newly developed curved single crystal surface are also being used to open up previously inaccessible areas of structure sensitive surface chemistry and chiral surface geometries. In a different thrust, the group has developed various molecular motor systems that are enabling us to study many important fundamental aspects of molecular rotation and translation with unprecedented resolution.
Professor and Dean of Academic Affairs
Organic Materials Chemistry
Our group applies the philosophy of physical organic chemistry to organic materials, in the forms of polymers, crystals and surfaces. Specifically, we investigate new materials that show macroscopic changes in properties upon exposure to external stimuli. Our main focus has been new materials that respond to light, which has a unique combination of characteristics: i) easy control over where light goes and when it goes there (spatiotemporal control), ii) easy control over intensity and energy, and iii) the ability to pass through many solid materials that traditional chemical reagents cannot. Our research has focused in three separate areas.
1. Photochemical control of charge. As interactions between charges dictate much of molecular behavior, controlling charge can yield control over matter. We have developed a series of materials in which light switches the charge-based interactions between polymer chains from attractive. By combining this top-down fabrication approach of with the bottom-up fabrication method of layer-by-layer assembly, we have developed thin films in which photochemical lability is confined to individual nanoscale compartments, yielding photo-delaminated free-standing films and multi-height photolithography.
2. Using functional side chains to control conjugated materials. Conjugated materials hold great promise for applications including solar cells and displays. We have focused on expanding the role of the side-chains of these materials, which occupy up to half of their mass but are typically reserved only for solubility. Early work in our group focused on integrating photolabile side chains for negative conjugated photoresists. This has evolved to using the non-covalent interactions of aromatic side-chains for controlling interactions between molecules, and therefore their material properties, including the use of mechanical force to control luminescence—mechanofluorochromism.
3. Singlet-oxygen responsive materials. Singlet oxygen (1O2) is a critical reactive oxygen species in photodynamic therapy for cancer as well as in damage to plants upon overexposure to light. Its photochemical production is also chemically amplified through a photochemical reaction, which is the lynchpin of several commercial bioanalytical technologies. Through a combination of fundamental physical organic chemistry and materials chemistry, we have luminescent conjugated polymer nanoparticles as probes for 1O2 in water that shows improved limit of detection over the commercially available luminescent probe for 1O2.
Professor and Department Chair of Chemistry
Physical and Surface Chemistry. The Utz group studies how molecules react on surfaces. Reactions at the gas-surface interface are highly dynamical events. Large-scale atomic and vibrational motions transform reactants into products on sub-ps and Å scales. The experiments probe ultrafast nuclear motion and energy flow dynamics that underlie heterogeneous catalysis and chemical vapor deposition. The goal is to to better model existing processes and direct the rational design of new catalytic materials and deposition techniques. The experiments use vibrational- and rotational-state selective laser excitation of molecules in a supersonic molecular beam to provide precise control over the energetics and orientation of the gas-phase reagent as it approaches the surface. Reaction probability and product identity is then quantified as a function of the reagent's energetic configuration. These experiments have shown that the vibrational state of the incident molecule can have a profound effect on reaction probability, and suggest that energy redisribution within the reaction complex is not complete prior to reaction and that the competing kinetics of energy redistribution and reaction might be manipulated to control the outcome of a reaction. This has been subsequently confirmed by exerting bond-elective control over a heterogeneously catalyzed reaction.