Drug targeting is highly advantageous because the ability to deliver drugs exclusively to specific cells or organs reduces both the dosage and toxicity effects associated with nonspecific administration. However, targeted delivery of therapeutics is still challenging due to lack of an efficient drug carrier design. Carbohydrate complexes, such as glycolipids and glycoproteins, serve as cellular markers and receptors universally found on the outer membranes of mammalian cells. These glycoconjugates distinguish different types of cells from one another and enable cellular recognition and adhesion. Both the immune system and foreign pathogens rely on these glycoconjugates to bind and enter host cells. For viruses and bacteria, adhesion to host receptors is the first step towards infection. Because of this broad physiological usage, carbohydrates must be highly diverse, with each carbohydrate corresponding to a different receptor. By mimicking nature’s mechanism of cellular adhesion, chemists are using carbohydrates to target specific cells for drug delivery. The designed glycopolymer, as a potential drug carrier, is composed of two main components: carbohydrate for targeting cells in cell-specific manner and pyridal-disulfide (PDS) groups for bioconjugation and fluorescent labeling. In the first step of the synthesis of the glycopolymer, three different glycomonomers (mannose, galactose and N-acetyl-glucosamine) have been synthesized and characterized in order to construct structurally well-defined glycopolymers. Each glycomonomer can be utilized for the synthesis of reversible addition-fragmentation chain transfer (RAFT) glycopolymers. This carbohydrate-based polymer construct has promising potential in targeted drug delivery for its reduction in toxicity and increase in drug efficacy.

The acid-catalyzed dehydration of 4-methylcyclohexanol yields a mixture of several isomeric methylcyclohexene products. The major product of this elimination reaction, 4-methylcyclohexene, is produced through the E2 mechanism. However, mechanisms for the formation of the minor methylcyclohexene products are not predicted by the traditional textbook explanations of carbocation rearrangements. 1-methylcyclohexene is thought to be produced by means of an E1 mechanism in which rearrangement of a carbocation intermediate takes place. This experiment was designed to classify the hydride shifts by observing the products of this reaction using 1,2-²H-4-methylcyclohexanol. The deuterated starting materials for this reaction were prepared in our lab. Gas chromatography-mass spectroscopy and nuclear magnetic resonance analysis were used in the characterization of the products and for the classification of the pair of 1,2 hydryde shifts in tendem and of the single 1,3 di-axial hydride shift, leading to the formation of the 1-methylcyclohexene product. This is useful to know when trying to predict the products of reactions in which intermolecular rearrangements occur during carbocation intermediates.

Methylobacterium extorquens AM1 is a methylotroph that metabolizes reduced C₁ compounds. In particular, methanol metabolism by M. extorquens AM1 requires two cofactors: tetrahydromethanopterin (H₄MPT) and tetrahydrofolate (H₄F). MeOH is first oxidized to formaldehyde, a highly toxic compound. MtdB is involved in formaldehyde oxidation to formate using H₄MPT and both NAD+ and NADP+ as co-substrates. Formate is the branching point for either further oxidation to CO₂ or assimilation. MtdA is a NADP+-specific enzyme that uses H₄F to generate methylene-H₄F, the intermediate that enters the assimilatory serine cycle. Previous in vitro studies have shown that MtdA is capable of using both cofactors and more efficient using H₄MPT. This suggests that it may have a dual role in both the oxidation and assimilation steps of methanol metabolism. However, in vivo, MtdA is unable to fully substitute MtdB as an mtdB mutant is auxotrophic on methanol. Interestingly, when MtdA was over-expressed the same mutant was no longer methanol sensitive. This observation poses two questions: 1) What is the role of MtdA in the H₄MPT pathway? And 2) Why is MtdA activity unable to substitute for MtdB activity in vivo? To answer these questions, we identified that an mtdB mutant is able to grow on methylamine and that this growth is H₄MPT dependent. This suggests that MtdA under this condition is able to substitute for MtdB. Further, we identified that a higher defect on growth on methylamine correlated with increased MtdA expression. This strongly suggests the accumulation of a toxic compound. We have also shown that the different phenotypes of mtdB on methanol and methylamine are due to an alternative pathway for methylamine oxidation. Together, our results suggest that MtdA is a key factor for regulation of carbon flux from the oxidative pathway and the assimilation pathway on one carbon compound metabolism.

Single molecule microscopy techniques make it possible to observe the fluorescence of individual dye molecules. One observation previously obscured in ensemble measurements is fluorescence intermittency, where molecules undergo prolonged non-emissive periods, as well as other intermediate emissive states. We are trying to identify the photochemical processes that cause these fluctuations in intensity. The fluorescence of dye molecules can be affected by the environment in which they are immersed, specifically the substrate they are in. The polymer polyvinylidene fluoride (PVDF) is of special interest because of its ferroelectric properties, which allows polarization of domains in the polymer. I have been exploring procedures to make PVDF films with a high degree of domain polarization. Using infrared (IR) spectroscopy, I have characterized the percentage of domain polarization in these films. Future investigation is still needed though to understand how PVDF will act as a substrate and what influences it will have on fluorescent organic dyes. An expanded knowledge of organic materials is essential for the design of photochemically stable devices. Based on organic electronics, these new devices will be greener alternatives to semiconductor technologies.

It is well known that mammals contain several types of phospholipase A2. The cytosolic phospholipases A2 (cPLA₂s) are one type, and are composed of six enzymes: cPLA₂alpha, cPLA₂beta, cPLA₂gamma, cPLA₂delta, cPLA₂epsilon, and cPLA₂zeta. There has been significant interest in the cPLA₂alpha isoform because of the enzyme's 10 fold preference for the hydrolysis at the sn-2 position of the glycerol backbone in phospholipids, resulting in the liberation of arachidonic acid. Arachidonic acid serves as a precursor for several highly regulated inflammatory mediators that play an important role in asthma, atherosclerosis, and arthritis. To address these problems, inhibitors that target cPLA₂alpha have been developed to serve as anti-inflammatory therapeutics. Wyeth pharmaceuticals has released a class of indole inhibitors that inhibit cPLA₂zeta at <10 nM IC₅₀. However, a recent study has shown that in cPLA₂alpha^-/- stimulated lung fibroblasts arachidonic acid production is lessened but still pressent. cPLA₂zeta has been identified as the other enzyme involved in the release of arachidonic acid. Consequently, my research project is to develop a selective and potent inhibitor of the cPLA₂zeta isoform. Our synthetic strategy is to modify the scaffold of Wyeth's cPLA₂alpha inhibitor. Analysis of the structure-activity relationships and 3D molecular modeling has revealed 4 different places on the scaffold to introduce substitutions. To date, we have generated and assayed over 20 inhibitors, with many more in progress. These inhibitors display low nanomolar potency, but are not selective for cPLA₂zeta. Our main focus is to increase the selectivity of our inhibitors towards cPLA₂zeta in order to further regulate and understand cPLA₂zeta's role in arachidonic acid production. 

Surface plasmons of metal nanoparticles have been the source of much scientific study over the last decade due to their immediate and significant applications in biosensing, surface-enhanced Raman Specroscopy (SERS), and light absorption engineering in semiconductor nanodevices. Surface plasmons can be generated by high-energy electrons coupling with natural plasmonic resonances of a nanometal’s electron cloud. An abundant source of such relativistic electrons can be found in common electron energy-loss spectroscopy (EELS) experiment, in which surface plasmons generated by the experiment can further couple with plasmons of other nearby nanoparticles, giving rise to “hot spots” with very strong electric fields. Often these hot spots can magnify an incident electric field over 100-fold, giving rise to many of the applications mentioned previously. This work aims to produce a computational model that computes plasmon excitation due to a fast electron by using an existing Discrete Dipole Approximation (DDA) framework, and to compare theoretical results from metal nano-rods and metal nano-cubes with experimental data. Unlike experimental data, computational models are not limited by detector resolution; meaning that such a model will give significant insight into details of the EEL experiment. In this work we explore results that are higher-resolution than what is currently obtainable by modern techniques. The existence of such a model will allow researchers to obtain preliminary data before running time-consuming and expensive experiments, will allow enormous insight into the deeper physics of surface plasmons, and will give experimental results a theoretical foothold while also improving on their accuracy.