Student-faculty collaborative research is one of our programmatic strengths. Including analytical, physical, organic, inorganic and biochemistry projects, our faculty engage students in diverse and interdisciplinary research topics.
Students pursuing the American Chemical Society-approved major complete one year of undergraduate research.
Secondary metabolites are molecules produced by organisms that are not essential for survival. However, these molecules provide an evolutionary advantage to the producing organism in a complex biological environment where nutrients are limiting. Organisms produce secondary metabolites as a defense mechanism to promote their survival by inhibiting the growth of or killing competing species. This secret “chemical warfare” is continuously evolving in nature.
Scientific discovery of this microbial “arms-race” has led directly to the treatment of bacterial and fungal infections as well as cancer. These compounds produced in the “chemical warfare” between species in nature have been employed therapeutically as antibiotics and chemotherapeutics. A few of the commonly known antibiotic and chemotherapeutic compounds include doxorubicin, erythromycin, vancomycin, and penicillin. In fact, antibiotic compounds like penicillin were discovered and have been used in treating diseases since the 1940s.
Since the 1970s, discovery of new antibiotic and chemotherapeutic molecules has slowed. Concurrently, there has been a drastic rise in the number of antibiotic–resistant strains of bacteria. To combat these new strains of bacteria, new compounds with enhanced therapeutic activities need to be discovered. One class of compounds, known as the pyrrolopyrimidine containing metabolites (PYPOL), are interesting from the drug discovery perspective. My research focuses on the discovery and characterization of enzymes that catalyze steps in the synthesis of the PYPOL containing compounds in various bacterial organisms. The biosynthesis of the PYPOL containing molecule toyocamycin (TOY, Figure 1) is proposed to require 9 enzymes. However, the function of 5 of the 9 enzymes have yet to be experimentally determined. Current research focuses on functional characterization of the 5 enzymes in order to better understand how bacteria produces TOY. Future investigations will focus on understanding the substrate specificity of these enzymes with a goal of trying to create novel derivatives of TOY. Students that work in my lab will learn a variety of biochemistry and molecular biology techniques including polymerase chain reaction, cloning, Escherichia coli cell culture, protein expression, protein purification, and enzyme kinetics.
My research interests are based on the practical application of fluorescence and luminescence techniques for the detection and quantification of select species in mixtures. This can take on either a theoretical or experimental application. On the theoretical side, our goal is to develop simple, matrix-based algorithms that can model the spectroscopic response from the components of a mixture. The results are compared with experimental results to determine the validity of the model. On the experimental side, we use pulsed (laser based) and non-pulsed (traditional lamp) techniques to generate fluorescence lifetimes (pulsed mode) or fluorescence signatures (lamp) from species on surfaces, species separated via chromatographic techniques, or species intrinsic to a mixture.
Other projects include establishing a Resonance Enhanced Multiphoton Ionization (REMPI) workstation for ultratrace detection of aromatic species in the gas phase. I am also involved in understanding the nature of dative bonding via several techniques including IR grazing angle and possibly Surface Enhanced Raman Spectroscopy (SERS) on self assembled monolayers, gas phase IR in a supersonic slit expansion (in collaboration with the U of MN), and fluorescence signatures of select B-N species in solution phase.
My work requires a “hands-on” aptitude to work with chemical instrumentation and to trouble-shoot experimental methodology. Although programming skills are not necessary, students desiring to develop programming skills are especially welcome. I believe that students ultimately interested in graduate or post- SCSU activities in a physical/analytical laboratory are a good fit for my lab.
We are investigating simple microextraction techniques capable of performing trace analysis on environmental or biological samples. In particular, we are developing and applying a technique called solvent microextraction in which a microliter of extracting solvent is suspended from the tip of a syringe needle in the headspace above (or directly immersed in) an aqueous sample. Volatile or semi-volatile organic compounds (pollutants such as chloroform and benzene) are preconcentrated in the microdrop, which is then analyzed by gas chromatography-mass spectrometry or other techniques. Current and future research in this area includes: application of the technique to new analytical problems of interest, and investigation of the mass transfer kinetics of the headspace (3-phase) system.
One strategy in cancer treatment is the development of drugs that will selectively induce apoptosis in tumor cells. The ability of cancer cells to avoid apoptosis and continue to proliferate is one of the key steps in cancer development. One potential source for new chemotherapeutic agents is natural products. Natural products and synthetic derivatives of natural products make up over 60 percent of all cancer drugs used today.
For example, we are working on the natural product goniothalamin, which comes from the dried stem bark of trees and shrubs from the goniothalamus genus. In preliminary studies, goniothalamin has exhibited low micromolar IC50 values against a variety of different cancer cell lines. These IC50 values illustrate that goniothalamin’s structure could potentially be used as a template for chemotherapeutic drug design. A better understanding of goniothalamin’s mechanism of action might lead to the synthesis of derivatives that demonstrate even more potent cytotoxicity.
The research in my laboratory is directed toward the design and synthesis of novel natural product analogues that will exhibit lower IC50 values against cancer cell lines than the natural product itself. By making hypotheses on the natural products’ mechanism of action, we design analogues by altering the steric and/or electronic properties of the natural product to make it more biologically active. The ultimate goal in this research is to design compounds that are more effective in inducing apoptosis in cancer cells and therefore more potent chemotherapeutic agents.
Physical surface chemistry of metal oxides, with interdisciplinary research with physics and materials science, focusing primarily the composition and speciation of aquatic systems influenced by chemical processes occurring at the solid-solution interface to develop a detailed understanding of the influence of bulk composition and structure, surface orientation, and interaction of water and other surface modifying solutes on the structure and reactivity at the mineral-fluid interface
What makes a chemical reaction work? In undergraduate chemistry we discuss the reaction mechanism – a series of molecular-scale processes or elementary steps that convert a reactant molecule to a product. Many reaction mechanisms involve reactive intermediates: short-lived species that are created and destroyed in the course of the reaction mechanism. Despite their fleeting existence (some have lifetimes less than a billionth of a second), the structure and energetics of reactive intermediates can have profound effects on the outcomes of chemical reactions. If we want to understand, and use, chemical reactions, we need to understand the nature of critical reactive intermediates. The Poole research group studies the structure, thermodynamics and kinetics of reactive intermediates using a range of chemical tools, from organic synthesis to spectroscopic and chromatographic analysis, through to computational chemistry. Some recent studies include investigations of:
(1) The hydroxyl radical (HO·). This apparently simple compound undergoes a vast array of reactions that are important for chemical processes ranging from the scale of a single cell to planetary scale. We have developed analytical methods that determine where on a complex molecule and hydroxyl radical might react, and how fast the rate of reaction is. These data can be used to improve models for hydroxyl radical reactions used in biological and environmental chemistry.
(2) Nitrenes are unusual compounds that contain a nitrogen atom with only six electrons in its valence shell, rather than the preferred eight. They are generated by heating or exposing organic azides to UV radiation. Nitrenes exhibit a rich and varied chemistry that is controlled largely by the arrangement of the valence electrons on nitrogen. We are interested in the room-temperature chemistry of triplet aryl nitrenes, where two of the electrons in the valence shell of nitrogen are unpaired and have parallel spin. In the future, we are also interested in utilizing the high reactivity of nitrenes to construct large fused ring structures containing nitrogen atoms, which are anticipated to have unusual and potentially useful redox and optoelectronic properties.