Chemistry & Biochemistry Theses and Dissertations
Permanent URI for this collectionhttp://hdl.handle.net/1903/2752
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Item Next-generation Mass Spectrometry With Multi-omics For Discoveries In Cell And Neurodevelopmental Biology(2022) Li, Jie; Nemes, Peter; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Understanding tissue formation advances our understanding of the causes of disease and the obtained knowledge can be potentially applied to develop personalized interventions. However, to explore the underlying mechanisms that govern tissue formation, there is a high and unmet need to develop new technologies to characterize different types of biomolecules from early-stage embryonic precursor cells and their descendent cells during development. This dissertation discusses new technological advancements to facilitate multi-omic (proteomic and metabolomic) analysis to explore cell-to-cell differences and uncover mechanisms underlying tissue formation. The work presented herein illustrates the development of in vivo microsampling and single-cell mass spectrometry (MS) to uncover cell heterogeneity among embryonic cells. Additionally, this dissertation work studies the biological role of metabolites in cell fate determination by exploring the mechanisms underlying metabolite-induced cell fate change. Moreover, this work introduces a novel technique called MagCar developed to track and isolate tissue-specific cells at later stages, which enables studying temporal molecular changes to gain new information about tissue formation.Item Correlating Chemical Activity and Structure in Mesoporous Metal Oxides for Nerve Agent Decomposition(2022) Li, Tianyu; Rodriguez,, Efrain E; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)GB (sarin), a chemical ware fare agent (CWA), due to its extreme fatal toxicity and its involvement in a few terrorist and battle attacks, has become an increasing concern for the national public and military safety. Developing filter materials that can strongly adsorb and effectively decompose GB thus attracts growing research interest. The great diversity of metaloxides and their abundant surface chemistry suggest an opportunity to realize their potential as filter materials. This dissertation outlines our effort to gain a fundamental understanding of the interaction between GB (also its simulant DMMP) and metal oxides. We aim to determine the structural factors that influence the performance of metal oxides on adsorbing and decomposing GB and to ultimately predict the behavior of a given metal oxide. We used two mesoporous metal oxides (TiO2 and CeO2) as two model systems and performed systematic studies on their interaction with GB and its simulant DMMP. We utilized multiple techniques to fully characterize the crystal and surface characters of the mesoporous metal oxides. The interactions between GB/DMMP and metal oxides were explored by different spectroscopic techniques (majorly infrared techniques). Combining the experimental observations and DFT calculations on two different metal oxides, we propose several governing parameters of the metal oxides to impact their reactivity for decomposing GB. We also derive a simplified and qualitative model to predict the reaction behavior and activity of metal oxides when interacting with GB.Item Defect Engineering of Supported Metal Catalysts for Selective Hydrogenation(2022) Zhang, Yuan; Liu, Dongxia; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Supported metal catalysts have been used extensively in industry. To construct supported metal catalysts with low cost and high catalytic performance, high dispersion of metal on the support material is greatly favored in recent years. With the downsizing of metal active phase, new challenges in catalyst synthesis and characterization have emerged. The highly dispersed metal active phase is prone to aggregate to decrease surface free energy, which requires innovative synthesis strategy to stabilize the metal species on support. High metal dispersion also created more interfacial sites and bonds between metal and support, therefore the metal-support interaction has more significant effects on the catalytic properties of high dispersion catalysts. Defect engineering has attracted much attention due to its ability to help stabilizing metal species and tune the metal-support interaction.This dissertation focuses on utilizing defect engineering to develop catalysts with high activity and selectivity in hydrogenation reaction. Harsh pH condition was applied in wetness impregnation process to generate cavity sites on TiO2 support surface, which resulted in stronger metal-support interaction between Pt and TiO2. The catalyst synthesized under harsh condition showed higher hydrogenation activity towards -NO2 group. Laser engraving was used as another defect engineering technique to create defects on TiO2 support. The laser engraved support showed distinct electronic and redox properties, which enhanced the electronic metal-support interaction of Pt and TiO2 support. The Pt/TiO2-LE catalyst showed superior activity and selectivity in the hydrogenation of 3-nitrostyrene and furfural alcohol. In addition, an effective method to probe the metal dispersion of Pt by styrene hydrogenation reaction kinetics was developed. This method has the potential to be applied to other catalysts systems and could be used to study the metal-support interaction in catalysts.Item Non Traditional Solvent Effect On Protein Behavior(2022) Lee, Pei-Yin; Matysiak, Silvina; Chemical Physics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Protein preservation has been a long lasting research topic due to its importance in many bio-pharmaceutical applications. A ”cold chain” is a commonplace solution to protein preservation, which stores biochemical products at a refrigerated temperature. A big advantage of cold chain is that the storing process is straightforward, without many further processes before the use of stored bio-products. However, it can also experience malfunction of the cooling system and results in economic lost and health care crisis. Ionic liquids (ILs), as a type of non traditional solvents, consist only of ions and are reported to be a potential candidate to replace the use of cold chain. The advantages of ILs include low flammability, high conductivity and less toxicity compared to some organic solvents. The most interesting feature of ILs is their extremely large number of cation-anion combinations, that can be tailored for specific use according to different needs. This thesis aims to investigate specific mechanism behind how ILs modulate protein behavior, specifically, how ILs affect protein stability, activity, and aggregation. We approach the research questions through the lens of molecular dynamics (MD) simulations and complement with experimental findings. In the first part of the thesis we first investigate the effects of two imidazolium based ILs (1-ethyl-3-methylimidazolium ethylsulfate, [EMIM]+[EtSO4]− and 1-ethyl-3-methylimidazolium diethylphosphate, [EMIM]+[Et2PO4]−) on lysozyme stability and activity. We collaborate with an experiment group at the University of Massachusetts (Bermudez lab) to complement our simulation results. Both ILs are found to destabilize lysozyme stability. In addition, both the cation and anions lower the stability of lysozyme, but in a different fashion. [EMIM]+ interacts with an Arg-Trp-Arg bridge that is critical in lysozyme stability through π–π and cation–π interactions, leading to a local induced destabilization. On the other hand, both anions interact with the whole protein surface through short-range electrostatic interactions, with [Et2PO4]− having a stronger effect than [EtSO4]−. Lysozyme activity is also reduced by the presence of the two ILs, but can be recovered after rehydration. It is found that the protein-ligand complex is less stable in the presence of ILs. In addition, a dense cloud of [EMIM]+ is found in the vicinity of the lysozyme active site residues, possibly leading to a competition with the sugar ligand. A fast leaving of these [EMIM]+ is observed after rehydration, which explains the reappearance of the active site and the recover of lysozyme activity. Although classical all-atom MD simulations can provide us with a great deal of microscopic information, they are often limited by the temporal-spatial scale of the simulated systems. For example, systems with high viscosity solvents or systems involving large number of atoms will be difficult to reach convergence for all-atom MD. In this case, coarse grained (CG) MD can come into play to achieve the desired time- and length- scales. The faster sampling obtained from CG MD is achieved by reducing the degree of freedom of the system and by removing local energetic barriers. In CG MD, similar atoms are grouped to functional groups and thus the free energy landscape is smoothen. We develop a novel CG MD named ”Protein Model with Polarizability and Transferability (ProMPT)”. The novelty of this model is the inclusion of the charged dummies that can result in change of dipoles. These dipoles can reflect the change of environments and thus allow the model to respond to different environmental stimulus. We validate ProMPT with several benchmark proteins: Trp-cage, Trpzip4, villin, ww-domain, and β-α-β. ProMPT is able to simulate folding-unfolding and secondary structure transformation with minimal constraints, which is not feasible with previous CG models. In addition, ProMPT can also reproduce the experimental results for the dimerization of glycophorin A (GpA) with different point mutations. Here we demonstrate the ability of the model to capture the change of conformational space caused by point mutation. In the last part of this thesis, we combine ProMPT and an in-house CG IL model to study the effects of [TEA]+[Ms]− on amyloid beta 16-22 (Aβ16−22) aggregation. Aβ16−22 is the hydrophobic core region and is the smallest fragment of Aβ that can fibrilize. Aβ has been extensively linked to the pathogenesis of the Alzheimer’s disease. [TEA]+[Ms]− is reported to suppress the formation of β-sheets and induce helices at high concentration. From our results, both β-sheet content and the aggregate size decrease with the increase of IL concentration, which are in agreement with experiments. Aggregates can form in both water and IL, but with different morphologies. In water, a nice hydrophobic core involving Phe-Phe interactions can form as well as intact β-sheet contacts. In addition, a cross β-sandwich structure is also observed, as seen from previous literature. However, the same hydrophobic core can not persist in the presence of IL. Aggregate structures in IL are not stable over time due to the [TEA]+-Phe interaction. Helicity is also computed for Aβ16−22 in water and in IL at different concentrations and a positive correlation is found. The increase in helicity at high [TEA]+[Ms]− concentration can be explained by the reduction of the inter-peptide contacts, which then increases the opportunity for the peptides to form helical structures. Single peptide studies also reveal that [TEA]+[Ms]− increases the helicity, possibly through cation-induced dipole enhancement. In this thesis, a series of detailed investigations on the effects of ILs on protein behavior is performed. Specific interactions between IL functional groups and protein local/global structures are examined. The mechanisms we studied here will help constructing a holistic view for the design of IL-protein pair applications. The construction of the new CG protein/IL model provides another tool for the scientific community to study secondary structure transformation, folding- unfolding, and other biochemical processes that are sensitive to the environment with CG MD.Item UNDERSTANDING AND TAILORING THE REACTIVE CHARACTERISTICS OF NANOENERGETIC COMPOSITES VIA STRUCTURAL AND CHEMICAL MODIFICATIONS(2022) XU, FEIYU; Zachariah, Michael R; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Nanoenergetic composites are nanostructured fuel and oxidizer mixtures that store a large amount of chemical energy and release it, typically in the form of heat, upon ignition. They are promising candidates for energy intensive applications such as propellants and pyrotechnics, due to their high energy density. The overall reaction kinetics of the heterogenous nanoenergetic system is controlled by mass transfer. The use of nanoparticles is to reduce diffusion length and thus increase energy release rate. The objective of the proposed research is to understand how intrinsic properties of fuel and oxidizer affect the reaction of nanoenergetic composites, and to develop novel, multifunctional nanoenergetic materials with tunable ignition threshold and energy release rate. Experiments were conducted utilizing primarily a time resolved Temperature-Jump time-of-flight mass spectrometer (T-Jump TOFMS) to analyze gas phase reaction intermediatespecies and products at a high heating rate (~105 K/s), along with a combustion cell for reactivity evaluation. New fuels including hydrogenated amorphous silicon, and oxidizers including oxygen deficient Co3O4-x and ferroelectric Bi2WO6 were investigated. The role of surface chemistry in the energetic characteristics of silicon nanoparticles was investigated, leading to the uncovering of a new reaction mechanism. Modulating the initiation temperature of aluminothermic reaction via defect engineered metal oxide was demonstrated. A study of piezoelectric oxidizers reveals the superior reactivity of a complex metal oxide. Moreover, tuning the energy release rate of I2O5 based biocidal nanoenergetic composites via a ternary system was studied. These results indicate that by modifying the chemistry or structure of fuels and oxidizers, the combustion characteristics of nanoenergetic composites can be tailored.Item Nanostructured Reactive Metals, Alloys, and Composites: Aerosol- and Laser-Assisted Synthesis, Assembly, and Characterization for Tunable Energy Release(2022) Ghildiyal, Pankaj; Zachariah, Michael R.; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Nanostructured heterogeneous energetic materials are a class of high-energy materials that utilize intimately mixed fuel and oxidizer particles to rapidly release a large amount of stored chemical energy in the form of heat, light, and intense pressures. Developing robust and scalable strategies to modify the structural features of these materials to tailor their energy release behavior is paramount to their success in large-scale propellant applications, which demand a consistent and predictable delivery of the stored material energy. This dissertation explores a multi-scale structure modification (nano-micro-macro) approach to achieve tunability in the functional energetic properties of reactive metal-based nanoscale fuels. Specifically, I have developed scalable aerosol- and laser-assisted techniques for the synthesis and assembly of nanostructured reactive metals, alloys, and their composites. This dissertation also identifies key fabrication, design, and assembly parameters that enable the tuning of material structural features such as particle size, composition, aggregate morphology, microstructure, and porosity. Additionally, the role of these structural modifications on their functional properties such as energy density, oxidation behavior, reaction pathways, ignition, and energy release characteristics has been extensively studied. Therefore, through these investigations, the dissertation establishes the critical process design-structure-property-function relationships in metal-based fuel systems. To achieve structural and reaction control on the nanoparticle scale, three strategies are explored. First, a vapor-phase route to surface-pure, core−shell nanoscale magnesium particles (Mg NPs) is employed, whereby controlled evaporation and growth are used to tune nanoparticle sizes and their size-dependent oxidation and energy release behavior are evaluated. Through direct observations from extensive in situ characterizations, I demonstrate that the remarkably high reactivity of Mg NPs (up to 10-fold higher than Al NPs) is a direct consequence of enhanced vaporization and Mg release from their high-energy surfaces that result in the accelerated energy release kinetics from their composites. Secondly, the synergistic role of Mg NP additives in inducing heterogeneous etching reactions on the surface of boron nanoparticles is studied. Specifically, I show that Mg NPs rapidly release vapor-phase Mg (~100 µs), which reacts exothermically (∆H_r= -420 kJ mol-1) with the molten B2O3 layer and assists in its removal during the reaction, causing ~6-fold reactivity enhancement and ~60% reduction in the burn times of boron. A third approach utilizes an in-flight surface modification of Mg NPs with a reactive element (Si) to form core-shell Mg-Si nanoparticles. Through mechanistic investigations of these systems, I find that the Si-coated Mg NPs themselves undergo an intraparticle condensed-phase alloying reaction between the Mg core and Si shell at relatively low-temperatures (400-500°C), resulting in highly accelerated reaction rates (~3-9-fold shorter reaction timescales) and lower ignition temperatures (~210°C lowering) than unfunctionalized Mg particles. Next, two aerosol-phase assembly techniques are explored to control the micron-scale structural and aggregation features of metal nanoparticle assemblies. First, an electrospray approach is used to incorporate plasma-synthesized ultrasmall Si particles to fill in the void structure of Al-based microparticles to augment their volumetric energy density and reactivity. This approach results in ~21% enhancement in energy density due to partial filling of structural voids and ~2-3-fold enhancement of reaction rates due to enhanced transport in ultrafine silicon particles. Another vapor-phase assembly approach employing external magnetic fields during synthesis is explored in directing the in-flight assembly of ferromagnetic metal nanoparticles into distinct aggregate morphologies with altered fractal dimensions. For control over the macroscale features of nanostructured composites, three robust and scalable techniques are employed. The first method utilizes spray drying as a highly scalable approach (production rates up to ~275 g h-1) to assemble metal and oxidizer nanoparticles into microparticle composites with ~2-7-fold higher reactivities than their physically mixed counterparts as a result of rapid gas generation and reduced nanoparticle sintering. I further demonstrate that these nanostructured microparticles can be further processed and additively manufactured into macroscale, hierarchical films (macro-micro-nano) without compromising their structural integrity. The third technique I have developed for macroscale structure modulation is by employing spatially and temporally resolved CO2 laser pulses to fabricate and write a high concentration of unaggregated, sub-10 nm metal nanoparticles directly in polymer films. Using this approach, I demonstrate that laser parameters – pulse duration, laser energy flux, and pulsed thermal loads – can be used for direct, in-situ modulation of particle size distributions of metal nanoclusters in polymer matrices. Rapid heating timescales employed in this approach allow for the scalable manufacturing and structural control of metal nanoclusters with production rates up to 1 g min-1. In conjunction with each other, all three techniques enable high-yield manufacturing of metal-based composites with a broad, nano- to macro-scale structural control. Finally, the structure and reaction modulation strategies are suggested for other fuel systems such as nanoscale reactive alloys (Al-Mg) to achieve controllable energy release behavior through further modifications of fuel composition and morphological features. The techniques developed in this dissertation will allow the strategic design of metal-based nanostructured energetic composites with tailored energy release rates and controllable structural features over a wide range of length scales.Item INVESTIGATION OF THE PRODUCTION AND DECAY PATHWAYS OF SUPEROXIDE BY CHROMOPHORIC DISSOLVED ORGANIC MATTER(2022) Le Roux, Danielle Marie; Blough, Neil; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Chromophoric dissolved organic matter (CDOM) in natural waters absorbs sunlight which leads to the production of a suite of reactive intermediates and reactive oxygen species (ROS) such as superoxide (O2⦁-) and hydrogen peroxide (H2O2). A significant amount of research over the years has investigated the sources and sinks of these two ROS. The currently accepted sequence of reactions for their production involves photochemically produced one-electron reductants (OER) within CDOM reacting with dissolved oxygen to form O2⦁-, which undergoes self-dismutation to produce H2O2. A previously used method to detect radical species with CDOM has been modified herein to be conducted simply using a fluorometer. Production rates of OER and H2O2 were measured for a variety of samples and correlations between the rates and optical/structural properties of the samples indicate that lower molecular weight species produce more OER and H2O2. Based on the stoichiometry of the mechanism above, the ratio of the production rate of OER to that of H2O2 should be two. However, ratios from five to sixteen were obtained, which suggests that O2⦁- undergoes oxidative reactions that compete with dismutation. The possibility of a light-dependent pathway for O2⦁- decay has been proposed but had yet to be explicitly demonstrated. Herein this sink is directly shown through O2⦁- spiking experiments. Rapid consumption of the O2⦁- spike occurs if injected into a sample during irradiation, as compared to a spike introduced into the sample in the dark, suggesting the presence of a light-dependent sink. Extensive data analysis and kinetic modeling of the O2⦁- decay data has allowed for approximations as to the extent of the sink and its decay rate constant. O2⦁- and H2O2 are environmentally important species, and a significant amount of work has been done on modeling their concentrations in natural waters. Based on the work here, O2⦁- is produced at higher concentrations than previously believed, which has implications on the modeling of O2⦁- and H2O2 in natural waters. Additionally, the light-dependent oxidative sink of O2⦁- could be with moieties within CDOM, providing further insight to the photochemical transformation of DOM during transit from terrestrial sources to marine waters.Item Mechanistic Study of Transition-Metal-Catalyzed Carbon-Carbon Bond Formation(2022) Song, Zhihui; Gutierrez, Osvaldo; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Transition-metal-catalyzed cross-coupling reactions (CCRs) have emerged as a powerful synthetic tool for the construction of carbon-carbon bonds, allowing a wide range of coupling partners to be combined efficiently. However, although some mechanistic experiments are performed, the detailed mechanisms of these transformations remain poorly understood. Quantum mechanical calculations were used to investigate the mechanism of transition-metal-catalyzed CCRs, leading to a deeper understanding of the molecular-level interactions in catalytic cycles to design new transformations. Specifically, DFT calculations were used to study in detail the mechanism of C-C bond formation in Ni diketonate-based catalytic systems (Chapter 1), showing the anionic ligand could be beneficial to the application of the steric radical in the CCRs to form quaternary center in the products. With this study in hand, the mechanism of fluorine-containing (vs nonfluorinated counterpart) decarboxylative C-C bond formation was explored, rationalizing the different reactivity for fluorinated system and nonfluorinated system (Chapter 2). With the molecular-level understanding of these reactions, optimized experiment conditions were used to promote the formation of the fluorinated products. Iron has been recognized as an economically and environmentally attractive transition metal catalyst. In particular, iron complexes have been demonstrated as powerful synthetic methods in the C-C bond formation. In Chapter 3, I used DFT and DLPNO-CCSD(T) calculations to investigate the nature of iron-catalyzed C-H allylations, unraveling the role of the ligand and the reaction pathways in this reaction. Computational studies revealed that the underlying allylation reaction pathway is consistent with an inner-sphere radical reaction mechanism, which involves the partial dissociation and rotation of the bisphosphine ligand. Finally, a dearomatization of Asmic isocyanides was studied computationally, implicating an electron transfer-initiated sequence that triggers an isocyanide rearrangement followed by radical-radical anion coupling to form the cyclohexadiene product (Chapter 4). This work shows the detailed mechanism of this dearomatization-dimerization-dislocation of Asmic isocyanides reaction, which provide a foundation for the synthesis of cyclohexadiene product.Item CHEMOENZYMATIC FC GLYCAN ENGINEERING FOR IMPROVING ANTIBODY IMMUNOTHERAPY(2022) Ou, Chong; Wang, Lai-Xi; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)IgG antibodies contain a conserved N-glycan on the Fc domain. The structures of the glycan play an important role in modulating an antibody’s effector functions. The Fc N-glycans also provide a suitable site for functionalization and conjugation of antibodies in a site-specific manner. The Wang lab have recently developed a general chemoenzymatic method for Fc glycan remodeling through endoglycosidase-based deglycosylation and reglycosylation. My thesis research focuses on three projects: Project 1, development of a site-selective conjugation method for synthesizing antibody-drug conjugates (ADCs); Project 2, application of the method for improving antibody’s complement-dependent cytotoxicity (CDC); Project 3, exploration of a dual functionalization method for enhancing internalization and lysosomal delivery of antibodies.Optimizing the synthesis for site-specific antibody conjugates using the glycan remodeling strategy is the first part of my thesis. We developed a facile synthetic strategy to functionalize glycan oxazolines from sialoglycan, which are the key donor substrates for enzymatic Fc glycan remodeling. An efficient chemoenzymatic method based on the EndoS2-D184M was also developed to functionalize therapeutical antibodies with different Clickable groups including azide-, cyclopropene-, and norbornene-tags. Homogenous antibody-drug conjugates (ADCs), with drug-antibody ratio of 4 were successfully obtained through three different Click reactions on the tags introduced. Comparison experiments indicated that the ADCs generated by these three Click reactions showed potent cancer cell killing activity and excellent serum stability. Complement-dependent cytotoxicity (CDC) is a major effector function for antibodies to deplete target cells. But for the IgG antibodies, which is the most widely used isotype for therapeutic antibodies, potent complement activation is restricted. With our optimized conjugation method, we constructed structurally well-defined antibody-αGal and antibody-rhamnose conjugates, which were designed to recruit natural anti-αGal and anti-rhamnose antibodies for enhancing CDC, using trastuzumab as a model antibody. Our preliminary in vitro study indicated that the antibody-rhamnose cluster conjugates could mediate potent CDC activity against targeted cancer cell with high selectivity. Since the rate of receptor internalization is a key factor for the selection of druggable antigen, enhancing the internalization efficiency could improve the efficacy of the ADC and possibly broaden the druggable antigens for ADCs. At the same time, the lysosomal delivery of ADCs could enhance their pharmaceutical efficacy. Therefore, we introduced a pair of orthogonal Click groups on the sialo-complex type glycan (SCT), and we used one of the clickable groups to ligate the drug, while using another one to carry an internalizing factor. This platform provided great flexibility to test out different combinations of antibodies, cytotoxic drugs, and internalizing factors. To date, preliminary cell-based studies have indicated that could improve the toxicity of a cetuximab based ADC with mannose-6-phosphate as an auxiliary internalization factor.Item Fluorescent Carbon Nanotubes as Molecular Sensors and Color-Center Hosts(2022) Qu, Haoran; Wang, YuHuang; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)This thesis demonstrates the application of single-walled carbon nanotubes (SWCNTs) as single-digit nanopores for molecular sieving and addresses a fundamental challenge pertaining to controlled synthesis of organic color-centers (OCCs) on the sp2 carbon lattice of SWCNTs. First, I describe a hyperspectral single-defect photoluminescence imager system that provides both hyperspectral imaging and super-resolution capabilities in the shortwave infrared. Second, I aim to understand the relationship between nanotube photoluminescence and encapsulated molecules. Using carbon nanotubes with sub-1 nm pores, I demonstrate molecular sieving of n-hexane from cyclohexane, which are nearly identical in size. Furthermore, I discovered a light irradiation method to drive structural transformation of OCCs which allow us to narrow the spectral distribution of defect emissions by 26%. Finally, I show that [2+2] cycloaddition can efficiently create OCCs. Remarkably, this novel defect chemistry reduces the number of OCC bonding configurations from six, which are commonly observed with monovalent defect chemistries, to just three. This work may have broad implications to the potential applications of SWCNTs and OCCs in chemical sensing, bioimaging, and quantum information science.