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Novel psychoactive substances (NPS) are synthetic drugs that pose serious public health and safety concerns as their ingestion by recreational drug users continues to cause adverse events and death. A multitude of NPS have been implicated in forensic investigations in the United States, but the identification of these emerging substances is challenging and complex, requiring advanced analytical capabilities and novel analysis workflows. The most common and effective manner for identifying NPS is by the use of mass spectrometry, while the true utility of this technology lies within non-targeted acquisition techniques. This research sought to utilize novel drug screening technologies and customized methodologies to characterize current NPS use in high risk populations through the analysis of biological sample extracts discarded from a partnering forensic toxicology reference laboratory. Specifically, NPS detection, identification, and characterization were the primary foci to produce increased awareness and education on a national level. To accomplish these goals, two novel workflows were developed: sample mining and data mining. A liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) assay was developed, validated, and implemented for forensic toxicology analytical testing. A SCIEX TripleTOF™ 5600+ QTOF-MS with SWATH® acquisition coupled to a Shimadzu Nexera XR UHPLC was used. Resulting data were compared against an extensive in-house library database containing more than 800 analytes. The LC-QTOF-MS assay was applied to the re-analysis of biological sample extracts to discover emergent NPS, their metabolites, and trends in use patterns. In total, 3,543 biological sample extracts were analyzed during this research and 21 emerging NPS were detected, some for the first time, through sample mining. Among these emerging substances were the NPS opioids: isopropyl-U-47700, 3,4-methylenedioxy-U-47700, and fluorofuranylfentanyl; the NPS opioid precursors: N-methyl norfentanyl and benzylfuranylfentanyl; the NPS hallucinogens: 2F-deschloroketamine, methoxy-PCP, and hydroxy-PCP; the NPS stimulants: 3,4-methylenedioxy-alpha-PHP, eutylone, and N-ethyl hexedrone; and the NPS benzodiazepine: flualprazolam. With respect to trends, NPS opioid positivity declined over time during this research; however, fentanyl positivity was persistent. Heroin and 3,4-methylenedioxymethamphetamine (MDMA) positivity appeared to decline slightly, but further temporal evaluation is necessary. NPS were less likely to be found in combination with other NPS; only one NPS substance was found in 82.5% of NPS-positive samples. Fentanyl poly-drug use was common, including concurrent or proximate use with traditional opioids (42.8%), NPS opioids (27.3%), cocaine (26.4%), methamphetamine (13.1%), NPS stimulants (4.2%), and other substances. The evaluation of in vitro metabolism for five emerging NPS detected for the first time during this research (3,4-methylenedioxy-U-47700, ortho-fluorofuranylfentanyl, 2F-deschloroketamine, eutylone, and N-ethyl hexedrone) resulted in the characterization of major metabolic pathways and the identification of metabolites presence in vivo by data mining of extract datafiles. These major metabolites provide utility for forensic laboratories to prolong detection windows for NPS. The primary metabolite identified for 3,4-methylenedioxy-U-47700 was N-demethyl-3,4-methylenedioxy-U-47700; the primary metabolite identified for ortho-fluorofuranylfentanyl was fluoro-4-ANPP; the primary metabolite identified for 2F-deschloroketamine was 2F-deschloro-norketamine; and the primary metabolites identified for eutylone and N-ethyl hexedrone were products of hydrogenation to the beta-ketone. As shown through this research, NPS continue to appear in forensic toxicology casework and novel assays for their detection and characterization are critical to remaining at the forefront of emerging drug trends and recreational drug use. LC-QTOF-MS was a vital piece of the analytical puzzle for discovering and characterizing emerging NPS and their metabolites. Analytical chemists must continue research involving NPS to broaden our understanding of synthetic drugs and their public health and safety impacts. / Chemistry

Successful methods for the separation of biomolecules like amino acids, proteins, peptides, and DNA have been developed previously using HPLC, GC, GC-MS, and CE. Recently CE has become a routine laboratory technique in the analysis of biological molecules. Even though high-resolution separations with small sample volumes is the main advantage, CE is limited by lower sensitivity detection of analytes when universal detectors like UV absorption or refractive index detectors are used. Therefore, sensitivity enhancement can be obtained by either using different detection schemes or electrophoretically based pre- or on-line concentration methods. These can be grouped into two categories. The first category includes IEF, CGF or TGF where sensitivity is achieved through equilibrium electrofocusing. In these methods, electrophoresis and bulk solution is combined in the capillary or separation column to form a null velocity point, a point at which the net velocity of the analyte is zero. Using these methods 10-10,000 fold sensitivity enhancement is achieved. The second category uses velocity gradients but not the nul velocity for the enrichment of samples. These methods include FASS, LVSS, NSM, etc., which are applied for the analysis of small molecules, and 10-10,000 fold sensitivity enhancement is reported by using these methods. In this work, first GEITP an on-line preconcentration technique is applied for the detection of amino acids (using Trp and Tyr as model analytes). This work also established the effects of different parameters on enrichment. The parameters studied include effect of current flow acceleration across capillary inner diameter, the effect of leading electrolyte (LE) concentration on current density, and the effect of applied electric fields on the current density. To explore the application of GEITP in biological fluids, optimized parameters were developed for the detection and separation of Trp and Tyr in artificial cerebrospinal fluid (aCSF). Next, GEITP was applied for enrichment and separation of physiologically relevant concentrations of chromophore-derivatized Asp and Glu in high conductivity samples like artificial cerebrospinal fluid (aCSF). It was concluded from this work that the major factors which influence the enrichment is the ratio of current density to sample conductivity. Finally, GEITP is applied as a prior step before CZE to increase the resolution between analytes without using ampholyte mixtures. In this method GEITP was combined to CZE to achieve resolution adjustment between amino acids mixture using low pressure hydrodynamic flow during CZE without changing the separation column, field strength, or electrolyte system. In this work, a rapid CE method for extraction and analysis of amino acids in planarians, labeled with 4-Fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F), was developed. This method was applied to detect the changes in the levels of amino acids when planarians were fed and starved. This method can be applied to study pharmacological effects in planaria, as it can monitor different amino acid levels with respect to feeding. Finally, ssDNA photoproducts of different lengths (11-mer and 63-mer) were separated using two different matrices, a traditional C18 and a PV/DBS (PLRP-S) matrix. A faster separation (within ~ 10 mins) was achieved for a 11-mer by the PLRP-S column. A separation was achieved in the PLRP-S column for the 63-mer while there was no separation in C18 column. Baseline resolution was not achieved. Therefore, C18 can best be used for small length DNA while PLRP-S can be applied for longer length DNA, as it is more hydrophobic than C18 column. Parameters can still be optimized for a baseline separation. / Chemistry

Molecular electronics based on bottom-up electronic circuit design is a potential solution to meet the continuous need to miniaturize electronic devices. The development of highly conductive molecular wires, especially for long distance charge transfer, is a major milestone in the molecular electronics roadmap. A challenge presented by single molecule conductance is to define the relative influence of the molecular "core" and the molecular "interconnects" on the observed currents. Much focus has been placed on designing conductive, conjugated molecules. However, the electrode-molecule contacts can dominate the responses of metal-molecule-metal devices. We have experimentally and theoretically probed charge transfer through single phenyleneethynylene molecules terminated with thiol and carbodithioate linkers, using STM break-junction and non-equilibrium Green's function methods. The STM break-junction method utilizes repeatedly formed circuits where one or a few molecules are trapped between two electrodes, at least one of which has nanoscale dimensions. The statistical analysis of thousands of measurements yields the conductance of single molecules. Experimental data demonstrate that the carbodithioate linker not only augments electronic coupling to the metal electrode relative to thiol, but reduces the barrier to charge injection into the phenyleneethynylene bridge. The theoretical analysis shows that sulfur hybridization provides the genesis for the order-of-magnitude increased conductance in carbodithioate-terminated systems relative to those that feature the thiol linker. Collectively, these data emphasize the promising role for carbodithioate-based connectivity in molecular electronics applications involving metallic and semi-conducting electrodes. One of the strategies for building molecular wires that can transfer charge over long distance is to incorporate metal ions into the conductive molecular core. Peptide nucleic acid (PNA) is a great candidate for this purpose. Studying the conductivity of PNA can not only contribute to a better understanding of charge transfer through biomolecules, but can also help develop better molecular wires and other building blocks of molecular electronics. We study the charge transfer of PNA molecules using the STM break-junction technique and compare with traditional macroscopic voltammetric measurements. By measuring the resistance of different PNA molecules, we hope to develop a deep understanding of how charge transport though PNA is affected by factors such as the number and type of natural and artificial bases, embedded metal ions, pH, etc. Self-assembled monolayers (SAMs) of porphyrins are of great interest due to their diverse applications, including molecular devices, nano-templates, electrocatalysis, solar cells, and photosynthesis. We combined a molecular level study of the redox reactions using electrochemical scanning tunneling microscopy (EC-STM) with a macroscopic electrochemical technique, cyclic voltammetry (CV), to study two redox active porphyrin molecules, TPyP (5,10,15,20-Tetra(4-Pyridyl)-21H,23H-Porphine) and 5, 10, 15, 20-tetrakis (4-carboxylphenyl)-21H, 23H-porphine (TCPP). We showed that the adsorbed oxidized TPyP molecules slowly change to brighter contrast, consistent with the appearance of the reduced form of TPyP, under reduction condition (0.0VSCE). The time scale of the slow reduction is in the order of tens of minutes at 0.0VSCE, but accelerates at more negative potentials. We propose that protonation and deprotonation processes play an important role in the surface redox reaction due to geometric restriction of the molecules adsorbed on the surface. EC-STM and CV experiments were performed at various pH values to investigate the mechanism of this anomalously slow redox reaction. Our results show that the increased concentration of H+ hinders the reduction of porphyrins, a feature that has not been reported preciously. This provides insight into the details of the surface redox reaction. / Chemistry

Biogenic monoamines such as dopamine play an important role as major neurotransmitters. Simultaneous determination of the concentration changes is thus crucial to understand brain function. Additionally, quantification of pharmaceutically active compounds (PhACs) and their metabolites in biological fluids is an important issue for forensic tests, clinical toxicology and pharmaceutical analysis. We have developed two postcolumn luminescence detection methods coupled to a 2-dimensional-solid phase extraction (2D-SPE) system. The postcolumn reaction methods used in this study are the redox-dependent photoluminescence-following electron-transfer (PFET) and Fenton-based chemiluminescence techniques, for the determination of certain neurotransmitter and nonsteroidal anti-inflammatory drugs (NSAIDs). A stable [Os(tmphen)3]3+ (tmphen = 3,4,7,8-tetramethyl-1,10-phenanthroline) reagent was prepared in neutral aqueous solution by oxidation of [Os(tmphen)3]2+ with lead(IV) oxide. [Os(tmphen)3]2+ and [Os(tmphen)3]3+ are characterized by absorption spectroscopy. [Os(tmphen)3]3+ stability is compared with [Ru(tmphen)3]3+ in the same pH 7 environment. The properties of Os(III) and Ru(III) complexes were investigated for use as the oxidant in a PFET system. Studies of photophysical and electrochemical properties, the stability of the Os(III) and Ru(III) complexes, and analytical application in PFET detection of oxidizable analytes are presented. The spectroscopic properties of the complexes were not very advantageous, but careful control of the detection system and reaction conditions enabled sensitive detection of the analytes. The method was fully validated and the optimized system was capable of detecting dopamine and acetaminophen at about 30.2 µg L-1 and 33.5 µg L-1, respectively. The limit of detection (LOD) was 1.5 µg L-1 for acetaminophen and 4.3 µg L-1 for dopamine. The accuracy and precision were within bioanalytical method validation limits (90.9 to 101.5 % and RSD < 12.0 %, respectively). Typical analysis time was less than 15 minutes. Two Fenton-based flow-injection chemiluminescence (CL) methods were developed and validated for the determination of naproxen. Under the optimal experimental conditions the proposed methods exhibited advantages in a larger linear range from 2,760 ng mL-1 to 207,000 ng mL-1 for the first CL method and 41.4 ng mL-1 to 700.0 ng mL-1 for the second CL method. The LOD was 13.8 ng mL-1 for naproxen. The CL mechanisms for the system, H2O2-FeIIEDTA-naproxen was further studied by batch experiments, chemiluminescence spectroscopy, fluorometry, high pressure liquid chromatography (HPLC) and Fourier transform infrared spectroscopy (FTIR). The effects of various interferences commonly found in biological and wastewater systems on the chemiluminescence intensity were also investigated. We used these methods to determine NSAIDs in commercial pharmaceutical formulations. Another application of these method was for detecting NSAIDs in biological samples. A 2x-1-Dimensional Solid Phase Extraction (2x-1D SPE) method was developed for determination of acetaminophen and naproxen in urine. This method uses both the methanol concentration and the pH advantageously to preferentially isolate analytes of interest from complex sample matrix. These methods were fully validated and had sufficient sensitivity (limit of quantification: acetaminophen; 40.41 mg L-1 - 360.0 mg L-1 and naproxen; 23.03 mg L-1 - 214.8 mg L-1) for biological matrices and applications. / Chemistry

This dissertation elucidates a greater understanding of the vaporization and electrospray post-ionization mechanisms when using femtosecond laser pulses for desorption of surface molecules and electrospray ionization for capture and mass analysis of the gas phase ions. The internal energy deposition from nonresonant vaporization with femtosecond laser pulses was measured using dried and liquid samples of p-substituted benzylpyridinium ions and peptides. In the comparison of the experiments of using 800 nm and 1042 nm laser pulses, it was found that there are different vaporization mechanisms for dried and liquid samples. It was established that LEMS is a "soft" mass analysis technique as it resulted in comparable internal energy distributions to ESI-MS with one caveat; multiphoton excitation of dried samples results in extensive fragmentation at higher pulse energies. The quantitative aspects of the laser electrospray mass spectrometry (LEMS) technique were established using various multicomponent mixtures of small biomolecules. Experiments with LEMS resulted in similar quantitative characteristics to ESI-MS except that ESI-MS demonstrated a greater degree of ion suppression when using higher concentrations, particularly in the four-component mixture. The lack of ion suppression in the LEMS measurements was due to the ~1% neutral capture efficiency and most likely not a result of nonequilibrium partitioning. This was supported by the excess charge limit not being surpassed in the LEMS experiments and the quantitative analysis requiring the use of response factors. This dissertation also expanded upon the use of multivariate analysis for the classification of samples that were directly mass analyzed without any sample preparation using LEMS. A novel electrospray complexation mixture using cationic pairing agents, a lipid, and sodium acetate enabled the simultaneous detection of positive, neutral and negative charged features of inorganic-based explosive residues in a single experiment. This complexation mixture also enabled the detection of new features from an RDX-based propellant mixture. Principal component analysis (PCA) proved reliable for accurate classifications of the explosive mixtures. PCA was also used for accurate classification of eight phenotypes of Impatiens plant flower petals after mass analysis with LEMS. The PCA loading values were used to identify the key biomarkers in the classification. These important mass spectral features were identified as the biologically-relevant anthocyanins, which are phytochemicals that are responsible for the color of the flower petals. / Chemistry

Carbon dioxide (CO2) is formed when fossil fuels such as oil, gas and coal are burned in power producing plants. CO2 is naturally found in the atmosphere as part of the carbon cycle, however it becomes a primary greenhouse gas when human activities disturb this natural balanced cycle by increasing levels in the atmosphere. In light of this fact, greenhouse gas mitigation strategies have garnered a lot of attention. Carbon capture, utilization and sequestration (CCUS) has emerged as a possible strategy to limit CO2 emissions into the atmosphere. The technology involves capturing CO2 at the point sources, using it for other markets or transporting to geological formations for safe storage. This thesis aims to understand and probe the chemistry of the reactions between CO2 and iron-bearing sediments to ensure secure storage for millennia. The dissertation work presented here focused on trapping CO2 as a carbonate mineral as a permanent and secure method of CO2 storage. The research also explored the use of iron-bearing minerals found in the geological subsurface as candidates for trapping CO2 and sulfide gas mixtures as siderite (FeCO3) and iron sulfides. Carbon dioxide sequestration via the use of sulfide reductants of the iron oxyhydroxide polymorphs lepidocrocite, goethite and akaganeite with supercritical CO2 (scCO2) was investigated using in situ attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), X-ray diffraction (XRD) and transmission electron microscopy (TEM). The exposure of the different iron oxyhydroxides to aqueous sulfide in contact with scCO2 at ~70-100 ˚C resulted in the partial transformation of the minerals to siderite (FeCO3). The order of mineral reactivity with regard to siderite formation in the scCO2/sulfide environment was goethite < lepidocrocite ≤ akaganéite. Overall, the results suggested that the carbonation of lepidocrocite and akaganéite with a CO2 waste stream containing ~1-5% H2S would sequester both the carbon and sulfide efficiently. Hence, it might be possible to develop a process that could be associated with large CO2 point sources in locations without suitable sedimentary strata for subsurface sequestration. This thesis also investigates the effect of salinity on the reactions between a ferric-bearing oxide phase, aqueous sulfide, and scCO2. ATR-FTIR was again used as an in situ probe to follow product formation in the reaction environment. X-ray diffraction along with Rietveld refinement was used to determine the relative proportion of solid product phases. ATR-FTIR results showed the evolution of siderite (FeCO3) in solutions containing NaCl(aq) concentrations that varied from 0.10 to 4.0 M. The yield of siderite was greatest under solution ionic strength conditions associated with NaCl(aq) concentrations of 0.1-1 M (siderite yield 40% of solid product) and lowest at the highest ionic strength achieved with 4 M NaCl(aq) (20% of solid product). Based partly on thermochemical calculations, it is suggested that a decrease in the concentration of aqueous HCO3- and a corresponding increase in co-ion formation, (i.e., NaHCO3) with increasing NaCl(aq) concentration resulted in the decreasing yield of siderite product. At all the ionic strength conditions used in this study, the most abundant solid phase product present after reaction was hematite (Fe2O3) and pyrite (FeS2). The former product likely formed via dissolution/reprecipitation reactions, whereas the reductive dissolution of ferric iron by the aqueous sulfide likely preceded the formation of pyrite. These in situ experiments allowed the ability to follow the reaction chemistry between the iron oxyhr(oxide), aqueous sulfide and CO2 under conditions relevant to subsurface conditions. Furthermore, very important results from these small-scale experiments show this process can be a potentially superior and operable method for mitigating CO2 emissions. / Chemistry

The localized surface plasmon resonance (LSPR), arising due to the collective oscillation of free electrons in metal nanoparticles, is a sensitive probe of the nanostructure and its surrounding dielectric medium. Synthetic strategies for developing surfactant free nanoparticles using ultrafast lasers providing direct access to the metallic surface that harvest the localized surface plasmons will be discussed first followed by the applications. It is well known that the hot carriers generated as a result of plasmonic excitation can participate and catalyze chemical reactions. One such reaction is the dissociation of hydrogen. By the virtue of plasmonic excitation, an inert metal like Au can become reactive enough to support the dissociation of hydrogen at room temperature, thereby making it possible to optically detect this explosive gas. The mechanism of sensing is still not well understood. However, a hypothesis is that the dissociation of hydrogen may lead to the formation of a metastable gold hydride with optical properties distinct from the initial Au nanostructures, causing a reversible increase in transmission and blue shift in LSPR. It will also be shown that by tracking the LSPR of bare Au nanoparticles grown on a substrate, the adsorption of halide ions on Au can be detected exclusively. The shift in LSPR frequency is attributed to changes in electron density rather than the morphology of the nanostructures, which is often the case. / Chemistry