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The overall approach in the present investigation has been to explore applications of the Morita-Baylis-Hillman (MBH) reaction in asymmetric synthesis and in the continuation of systems with medicinal potential. To this end, a series of varied camphor-derived acrylate esters was prepared to serve as chiral substrates in asymmetric Morita-Baylis- Hillman reactions. Reduction of N-substituted camphor-10-sulfonamides afforded the 3- exo-hydroxy derivatives as the major products. Acylation of the corresponding sodium alkoxides gave the desired 3-exo-acrylate esters, isolation of which was complicated by concomitant formation of hydrochlorinated and diastereomeric competition products. Bulky camphorsulfonamides containing alkyl, dialkyl, aromatic and adamantyl groups were selected as N-substituents with the view of achieving stereoselective outcome in subsequent MBH reactions. The synthesis of novel camphor-derived Morita-Baylis-Hillman adducts using various pyridine-carboxaldehydes proceeded with exceptionally high yields with diastereoselectivities ranging from 7-33 % d.e. Both 1D and 2D NMR and HRMS techniques were employed to confirm the structures and an extensive study of the electropositive fragmentation patterns of a number of camphor-derived chiral acrylate esters was conducted. Attention has also been given to the application of MBH methodology in the construction of heterocyclic ‘cinnamate-like’ AZT conjugates which were designed to serve as dualaction HIV-1 integrase-reverse transcriptase (IN-RT) inhibitors. A number of pyridine carboxaldehyde-derived MBH adducts were synthesized using methyl, ethyl and t-butyl acrylates in the presence of 3-hydroxyquinuclidine (3-HQ) as catalyst. The yields for these reactions were excellent. The resulting MBH adducts were acetylated and subjected to aza-Michael addition using propargylamine. The resulting alkylamino compounds were then used in ‘Click reactions’ to form the targeted AZT-conjugates in moderate to excellent yield. In silico docking of computer modelled AZT-conjugates into the HIV-1 integrase and reverse transcriptase enzyme-active sites and potential hydrogen-bonding interaction with active-site amino acid residues were identified. The electrospray MS fragmentations of the AZT and the novel AZT-conjugates were also investigated and common fragmentation pathways were identified.

Indiana University-Purdue University Indianapolis (IUPUI) / Analyses of tobacco products and their usage are well-researched and have implications in analytical chemistry, forensic science, toxicology, and medicine. As such, analytical methods must be developed to extract compounds of interest from tobacco products and biological specimens in order to determine tobacco exposure. In 2009, R.J. Reynolds Tobacco Co. released a line of dissolvable tobacco products that are marketed as a smoking alternative. The dissolvables were extracted and prepared by ultrasonic extractions, derivatization, and headspace solid phase microextraction (SPME) with analysis by gas chromatography-mass spectrometry (GC-MS). The results show that the compounds present are nicotine, flavoring compounds, humectants and binders. Humectant concentrations vary among different tobacco types depending on the intended use. Humectants were quantified in various tobacco types by GC and “splitting” the column flow between a flame ionization detector (FID) and an MS using a microfluidic splitter in order to gain advantage from the MS’s selectivity. The results demonstrated excellent correlation between FID and MS and show that MS provides a higher level of selectivity and ensures peak purity. Chemometrics was also used to distinguish products by tobacco type. Hair is a common type of evidence in forensic investigations, and it is often subjected to mitochondrial DNA (mtDNA) analysis. Preliminary data was gathered on potential “lifestyle” markers for smoking status as well as any indications of subject age, gender, or race by investigating the organic “waste” produced during a mtDNA extraction procedure. The normally discarded organic fractions were analyzed by GC-MS and various lipids and fatty acids were detected. At this point, a total vaporization-SPME (TV-SPME) method was theorized, developed, and optimized for the specific determination of nicotine and its metabolite, cotinine. The theory of TV-SPME is to completely vaporize an organic extract which will eliminate the partitioning between the sample and the headspace, thereby simplifying the thermodynamic equilibrium. Parameters such as sample volume, incubation temperature, and extraction time were optimized to achieve the maximum analyte signal. Response surface methodology (RSM) is a statistical model that is very useful in predicting and determining optimum values for variables to ensure the ideal response. RSM was used to optimize the technique of TV-SPME for the analysis of nicotine and cotinine. Lastly, quantitation of nicotine and cotinine in human hair typically requires large sample sizes and extensive extraction procedures. Hence, a method using small sample sizes and a simple alkaline digestion followed by TV-SPME-GC-MS has been developed. Hair samples were collected from anonymous volunteers and nicotine and cotinine were identified and quantitated in the hair of tobacco users.

Indiana University-Purdue University Indianapolis (IUPUI) / Mercury (Hg) has proven to be a risk to the public, mainly through the consumption of fish. Because of this, many fish consumption advisories have been issued in Indiana. Although much is known about the global cycle of mercury, little is known about how local and regional emission sources of mercury impact local and regional mercury cycling. This study’s objective was to determine the scope of mercury concentration in central Indiana by using a broad grid of soil mercury measurements. Sampling was designed to capture the net retained mercury content in soils, and to determine whether spatial patterns in exist in soil mercury contents that could be related to emission sources of mercury and post-emission transport patterns from wind. Results from this study revealed significant differences in mercury concentrations for soils in central Indiana. The core of the study area, concentrated in the urban area of Indianapolis, exhibited soil mercury contents that were 20 times higher than values in the outskirts of the study area. The spatial pattern resembled a bulls-eye shape centered on Indianapolis, and with comparison to the reported Hg emission from local sources, including a coal-fired power plant, indicates a strong regional deposition signal linked to those emission sources but marked by wind-driven transport to the northeast. This effect of local emission sources resulting in local deposition indicates that limiting mercury emissions will have a net beneficial impact on local environmental quality and human health.

Indiana University-Purdue University Indianapolis (IUPUI) / Pipe bombs are a common form of improvised explosive device, due in part to their ease of construction. Despite their simplistic nature, the lethality of pipe bombs should not be dismissed. Due to the risk of harm and their commonality, research into the pipe bomb deflagration process and subsequent chemical analysis is necessary. The laboratory examination of pipe bomb fragments begins with a visual examination. While this is presumptive in nature, hypotheses formed here can lead to subsequent confirmatory exams. The purpose of this study was to measure the mass and velocity of pipe bomb fragments using high speed video. These values were used to discern any trends in container type (PVC or black/galvanized steel), energetic filler (Pyrodex or double base smokeless powder), and ambient temperature (13°C and -8°C). The results show patterns based on container type, energetic filler, and temperature. The second stage of a laboratory exam is chemical analysis to identify any explosive that may be present. Legality calls for identification only, not quantitation. The purpose of this study is to quantitate the amount of explosive residue on post-blast pipe bomb fragments. By doing so, the instrumental sensitivities required for this type of analysis will be known. Additionally, a distribution of the residue will be mapped to provide insight into the deflagration process of a device. This project used a novel sampling technique called total vaporization solid phase microextraction. The method was optimized for nitroglycerin, the main energetic in double base smokeless powder. Detection limits are in the part per billion range. Results show that the concentration of residue is not uniform, and the highest concentration is located on the endcaps regardless of container type. Total vaporization solid phase microextraction was also applied to automotive racing samples of interest to the National Hot Rod Association. The purpose of this project is two-fold; safety of the race teams in the form of dragstrip adhesive consistency and monitoring in the form of fuel testing for illegal adulteration. A suite of analyses, including gas chromatography mass spectrometry, infrared spectroscopy, and evaporation rate, were developed for the testing of dragstrip adhesives. Gas chromatography mass spectrometry methods were developed for both nitromethane based fuel as well as racing gasolines. Analyses of fuel from post-race cars were able to detect evidence of adulteration. Not only was a novel technique developed and optimized, but it was successfully implemented in the analysis of two different analytes, explosive residue and racing gasoline. TV-SPME shows tremendous promise for the future in its ability to analyze a broad spectrum of analytes.