My research focuses on the study of protein and nucleic acid structure with site-specificity utilizing a variety of spectroscopic methods including NMR and FTIR spectroscopy coupled with isotopic and/or chemical labels.
We use organic synthesis to build molecules for practical purposes, including the study of other molecules. Research projects involve:
1) The synthesis of nucleotides and proteins with an azide (R-N3) probe to monitor electrostatic environments and solvent dynamics by vibrational (IR) spectroscopy. In addition to azides we also explore other vibrational probes such as nitriles and thiocyanates.
2) The design and synthesis of air-stable hydrocarbon radicals for an NMR technique known as dynamic nuclear polarization (DNP). The radicals are stabilized by resonance and steric protection.
3) The history of organic chemistry in the United States.
4) Collaborative work to synthesize ganglioside GM3 to help Amish children.
5) Molecular knots.
Elucidating the fundamental processes of glow discharge plasmas that lead to their analytical utility and expanding their applications in trace element analysis in diverse fields ranging from environmental monitoring to materials science.
My research centers on elucidating the molecular-scale mechanisms that govern the incorporation of impurities into naturally occurring inorganic solids during crystal growth. Impurities can alter the chemical and physical properties of solid materials by disrupting the crystal lattice structure and symmetry, resulting in bulk and interfacial properties different from those of the pure (i.e., impurity-free) phase. Research in my group centers on the experimental synthesis of geologically and environmentally important minerals.
The Leber Research Group has been studying the vinylcyclobutane-to-cyclohexene rearrangement of bicyclo[3.2.0]hept-2-enes and bicyclo[4.2.0]oct-2-enes. Based on our experimental work as well as that of others coupled with dynamic modeling studies, current thinking is that the rearrangement occurs via a short-lived diradical intermediate. We are currently attempting to utilize the cyclopropylcarbinyl (CPC)-homoallylic radical rearrangement as an indirect probe of the purported diradical intermediate.
My research focuses on better understanding trace metal cycling in the marine environment. Since metals do not degrade, metal accumulation can be used to understand changes in the amount of metals being added to the marine environment and/or changes in conditions that affect metal accumulation over time. To improve our understanding of metal cycling, we study sediments obtained from marine waters. Because of the complexity of environmental samples, my research group also studies single mineral phases in conjunction with simple organic molecules in the laboratory to discern individual controls on metal adsorption that might be occurring in the environment. Both approaches provide us with information regarding metal sequestration in sediments under various conditions.
I am interested in the relationships between surface and solid-state properties of materials and their technologically important behavior. The size and composition of semiconductor particles affects how they absorb light and conduct electrical charge, and we use this to design particles effective in solar energy conversion devices. We also explore how the self-assembly of organic molecules into ordered monolayers at the liquid/solid interface influences solution and surface phenomena.
My research is aimed at synthesizing many new heterocyclic compounds, mostly derivatives of folate and other pterins, for the purposes of developing small molecule therapeutic agents. New chemistry will be explored to rapidly generate structurally diverse compounds. Specifically, these new molecules are aimed at inhibiting B12-independent Methionine Synthase, for the purposes of broad spectrum anti-fungal drugs.
Solvent effects on solution photophysics.
Work in my lab will utilize a variety of biochemical techniques and will focus on understanding protein function through structure using X-ray crystallography. An overarching theme of the projects I am interested in is how cells sense and respond to their environment. One project uses in vitro techniques to study how the pathogenic bacteria Vibrio cholerae utilizes exogenous heme as an iron source for the cell while preventing the toxic side effects that heme could cause. Another project begins to investigate the protein interactions involved in a new nitric oxide (NO) signaling pathway in eukaryotes involving S-nitrosothiols. The third project aims to study the mechanism by which a bacterium involved in bioremediation of the environment, Dehalococcoides ethenogenes, senses and degrades the pollutant tetrachloroethene which is produced by dry cleaners and chemical industries.
Nucleophilic and electrophilic substitution reactions in ionic liquids. Photo-acid catalyzed organic reactions.
We are interested in the design, synthesis, and study of molecular devices that incorporate the elements of molecular recognition and host/guest chemistry. One category of such devices that we have focused on for the past few years is conformationally flexible host molecules that can be organized by an analyte to subsequently bind solvatochromic fluorescent indicators. This cooperative association can be used to signal the analyte binding event. Our novel design for fluorescent chemosensing may be applicable to the detection of low concentrations of so-called quenching heavy metal or transition metal ions in aqueous solution. The last few years we have turned some attention to organic oxidations and reductions. Most recently we have begun studying Hantzsch dihydropyridines as transfer hydrogenation agents modeling NADH activity.
The seemingly simple inorganic component of bone and teeth--hydroxylapatite, Ca5(PO4)3OH--has occupied our attention for the last decade. We are intrigued by the fact that a great variety of ions can replace, in part, those of apatite, which leads to applications such as remediation of heavy metals, ion-exchange, nuclear waste encapsulation, phosphors, and so on. We have prepared apatites containing different divalent cations of elements such as Sr, Ba, Pb, and Cd and have explored the structure of these using solid state NMR and infrared spectroscopy, as well as X-ray diffraction. Our most recent focus has been on the substitution of the carbonate ion for phosphate or hydroxide and the presence of water in the structural channels that are important to the flexibility of the these compounds. Currently we are attempting to identify the location of the carbonate ion in the structure of various apatite types, with the hope of understanding how composition and structure may affect its location.