Browsing by Author "McNally, Andrew, committee member"
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Item Open Access Assay development for pathogen detection at the point-of-need(Colorado State University. Libraries, 2020) Carrell, Cody S., author; Henry, Charles S., advisor; Farmer, Delphine K., committee member; McNally, Andrew, committee member; Reardon, Kenneth F., committee memberInfectious diseases are responsible for roughly one third of worldwide deaths, which disproportionately occur in low- and middle-income countries. Government health agencies recognize high quality diagnostics as a key tool to slow the spread and reduce the burden of disease in these countries. The same diagnostics that have minimized deaths from infectious disease in developed nations, however, cannot simply be implemented in all locations. Low- and middle-income countries lack the financial resources and infrastructure required to use the sophisticated instruments found in modern hospital laboratories. Instead of relying on current diagnostic technologies to reduce the burden of infectious disease, there is an urgent need to develop new technologies suited for the resource-limited settings they will be used in. The work described in this thesis aims to advance the capabilities of diagnostic sensors for use at the point-of-need. Microfluidic devices have been used for decades to perform complex analysis using compact devices with small sample and reagent volumes. Their portability and low-cost make them ideal candidates for analysis in resource limited settings, but their fabrication is tedious and expensive. To improve the fabrication process, Chapter Two of this thesis describes two methods for simplified 3D-printing of microfluidic devices. The 3D printer and resin used are inexpensive and commercially available and the fabrication process is not limited by the need to remove uncured resin from enclosed channels. Instead, open-faced channels in 3D-printed pieces were silanized and sealed to a secondary substrate. Common microfluidic devices including a droplet generator and herringbone mixer were created with the new fabrication method to demonstrate the strength of the seal and ability for the printer to create microfluidic channels. We envision this method being used for rapid prototyping and increased innovation in the field of microfluidic sensors. Traditional polymer microfluidics are limited in their usefulness in point-of-need situations because they require a pump to drive flow. Paper-based microfluidics use capillary action to drive flow instead of a pump and have emerged as an easy-to-use and inexpensive alternative to traditional microfluidics in situations where a power source is not available. However, paper-based microfluidics often suffer from poor analytical performance, and efforts to improve result in increased complexity. Chapter Three of this thesis describes a paper-based device that increases the sensitivity of a Salmonella assay while retaining ease-of-use. The device combines paper-pads for reagent storage with a 3D-printed rotational manifold to perform an enzyme-linked immunosorbent assay (ELISA). Typically, this assay requires dozens of complex pipetting steps, but the rotary device simplifies this process into four semi-automated steps. A detection limit of 440 colony forming units/mL was found using the paper-based device. As demonstrated in Chapter Three, common issues with paper-based microfluidics can be solved by integrating paper with other inexpensive components like 3D-printed polymer. In the final study in Chapter Four, we created a device to further simplify the steps of an ELISA using a combination of paper, polyester transparency film, and double-sided adhesive. The device, termed a disposable ELISA (dELISA), automatically performed the sequential reagent delivery and washing steps required for a traditional ELISA and require only two end user steps. The dELISA was then used to perform a serology assay for SARS-CoV-2 antibodies from whole-blood. The detection limit of the assay was 2.8 ng/mL for the dELISA, which was nearly identical to the detection limit found using a tradition well-plate assay (1.2 ng/mL).Item Embargo Charge carrier dynamics of 2-dimensional photoelectrodes probed via ultrafast spectroelectrochemistry(Colorado State University. Libraries, 2024) Austin, Rachelle, author; Sambur, Justin, advisor; Krummel, Amber, advisor; Rappe, Anthony, committee member; Prieto, Amy, committee member; McNally, Andrew, committee member; Brewer, Samuel, committee memberThe integration of hot charge carrier-based energy conversion systems with two-dimensional (2D) semiconductors holds immense promise for enhancing the efficiency of solar energy technologies and enabling novel photochemical reactions. Current approaches, however, often rely on costly multijunction architectures. In this dissertation, I present research that combines spectroelectrochemical and in-operando transient absorption spectroscopy measurements to unveil ultrafast (<50 fs) hot exciton and free charge carrier extraction in a proof-of-concept photoelectrochemical solar cell constructed from earth-abundant monolayer (ML) MoS2. Theoretical analyses of exciton states reveal enhanced electronic coupling between hot exciton states and neighboring contacts, facilitating rapid charge transfer. Additionally, I discuss insights into the physical interpretation of transient absorption (TA) spectroscopy data in 2D semiconductors, comparing historical perspectives from physical chemistry and solid-state physics literature. My perspective encompasses various physical explanations for spectral features and experimental trends, particularly focusing on the contribution of trions to TA spectra. Furthermore, I examine how different physical interpretations and data analysis procedures can yield distinct timescales and mechanisms from the same experimental results, providing a comprehensive framework for understanding charge carrier dynamics in 2D semiconductor-based optoelectronic devices.Item Open Access Combining mechanistic and statistical models for predicting reaction outcomes in organic synthesis(Colorado State University. Libraries, 2023) Gallegos, Liliana Cabrera, author; Paton, Robert S., advisor; McNally, Andrew, committee member; Rappé, Anthony, committee member; Hess, Ann, committee memberComputational modeling and machine learning tools have assisted in the fundamental challenge of predicting the "over-the-arrow" optimal reaction conditions to maximize the output (e.g., yield and selectivity). The work presented here explores multiple challenging synthetic reactions for reaction optimization ranging from: (i) precise photocatalytic transformations in chemical biology, (ii) new reactivity using organobismuth(V) reagents, (iii) challenging reversible nucleophilic alcohol addition reactions influence at equilibrium, and (iv) a late-stage key reaction step in a total synthesis project. Overall, this dissertation aims to assist in predicting optimal reaction outcomes by understanding and formulating reaction mechanisms from quantum mechanics and statistical methods while using open-source automated workflows to improve transparency and reproducibility within data-chemistry fields. Chapter 1 provides the necessary background to introduce the methods behind computational and statistical models that assist in addressing the challenges faced within the optimization process and the limitations of each strategy. First, there will be a brief overview of the computational protocols to generate and understand reaction mechanisms using quantum mechanical methods. Then, a summary of the data-driven approach introduces the statistical methods and metrics that build relationships to chemical reactivity using computer-readable mechanistically derived molecular descriptions. Chapter 2 tackles the challenge of studying the chemical reactivity in large biological systems (e.g., peptides and proteins) with quantum mechanical methods. First, the precise photocatalytic functionalization at selenocysteine reaction developed by the Payne lab is simulated using a simplified model substrate followed by a more realistic model that generates the final energy profile. Based on the resulting computational analysis, the utility of this late-stage functionalization reaction is later demonstrated on large polypeptide chains. Chapters 3 and 4 embark on a journey into new bismuth chemistry developed by the Ball group. The bismuth arylation reaction published in Nature transformed the following collaborative work discussed here, ranging from the computational protocols implemented in selectivity problems to the versatile chemical reactivity originating from bismuth(V) reagents. From the previously reported but otherwise unexplored DFT integration grid effects, the computed free energies on organobismuth reactions explored here would have led to significant errors and incorrectly predicting selectivities. With the optimal computational protocols, new reactivity using organobismuth reagents is investigated in Chapter 3 to propose a reaction mechanism for the selective arylation of 2- and 4-pyridiones. Chapter 4 describes the mechanistic investigation of the developed palladium-catalyzed cross-coupling reaction to achieve challenging C-C couplings in mild reaction conditions with the amino-bridged bismacycle reagent. A statistical modeling approach using automated workflows discussed in Chapter 7 is applied here to predict an optimal reaction design and capture the origin of the reactivity for various coupling substrates and modified organobismuth(V)-reagents for the developed Bisma-Stille cross-coupling reaction. Chapter 5 describes a mechanistic investigation to optimize a challenging key reaction in the total synthesis of the natural product of allopupukeanane developed by the Sarpong group. The reaction success in late-stage synthetic plans becomes detrimental as the availability of reactants in a multiple-step natural product synthesis becomes limiting. The elementary step influencing the reactivity is identified in the palladium-mediated cascade reaction. Then, a data-driven approach is implemented to screen various ligands and collect mechanistically derived molecular DFT features to incorporate into a Bayesian optimization tool developed by the Doyle lab. Automated workflows discussed in Chapter 7 were utilized to collect the features. This approach successfully identified more suitable and efficient reaction conditions for racemic mixture, byproduct formation, and catalyst decomposition challenges. The overall synthesis plan to access multiple natural products via the bridged bicycle scaffold highlighted in this chapter is an ongoing project by the Sarpong group. Chapter 6 pivots into data-driven approaches to formulate statistical relationships sampled over small and large datasets. First, the collaborative research in section 6.2 dives into building a multivariate linear regression model with a small dataset to explain the reaction performance in various solvents on the challenging reversible nucleophilic alcohol addition reaction developed by the Bandar group. The statistical conclusions provide the bases for modeling the solvent effects via DFT methods. Next, in section 6.3, a machine learning model is trained on a large diverse molecule dataset to predict NMR chemical shifts with high accuracy to DFT-derived NMR values at only a fraction of the cost of DFT methods. Here are two examples where a successful prediction is evaluated based on the research goal to obtain model accuracy or interpretability. Chapter 7 focuses on facilitating the transparency and reproducibility for collecting and generating meaningful statistical models for the data chemist in low- and high-throughput studies. The open-source, automated workflows, DISCO and REGGAE, allowed for the execution of projects mentioned in Chapters 4 to 6 at different stages of the research process (e.g., chemical data collection, feature selection, and then statistical modeling).Item Open Access Development of an asymmetric NHC-catalyzed cascade reaction and studies towards the asymmetric aminomethylation of enals(Colorado State University. Libraries, 2015) Ozboya, Kerem, author; Rovis, Tomislav, advisor; Henry, Charles, committee member; McNally, Andrew, committee member; Kennan, Alan, committee member; Inamine, Julia, committee memberA cascade reaction is developed to form complex cyclopentanones using an asymmetric Michael/Benzoin sequence. This reaction employs simple aliphatic aldehydes and ketoesters in conjunction with a chiral amine catalyst and a chiral NHC catalyst. Further investigation reveals a surprising interplay between these two catalysts. This relationship is manifested in a pseudo-dynamic kinetic resolution, which is responsible for the high diastereoselectivity observed. Subsequent work details the discovery of the aminomethylation of enals using NHC catalysis. This reaction utilizes an iminium source as well as cinnamaldehyde derivatives to form gamma-amino butyrate derivatives. Rendering this reaction asymmetric has proven a challenge, despite extensive effort to resolve these issues. In the course of these studies, an unexpected NHC-catalyzed Morita-Baylis-Hillman reaction was observed. Optimal conditions for this reaction were established, proving access to useful amino-enals. In an effort to design suitable catalysts for the asymmetric aminomethylation reaction, a strategy for the late-stage manipulation of NHC catalysts was developed. Key to this strategy is the `protection' of the triazolium salt by reduction to the triazoline. An aryl C-Br bond is then exploited for cross-coupling reactions, building a small library of new catalysts. The triazolium salt is then recovered by oxidation with a trityl salt.Item Open Access Engineering and evolving helical proteins that improve in vivo stability and inhibit entry of Enfuvirtide-resistant HIV-1(Colorado State University. Libraries, 2019) Walker, Susanne N., author; Kennan, Alan, advisor; Yao, Tingting, committee member; McNally, Andrew, committee member; Paton, Robert, committee memberMethods for the stabilization of well-defined helical peptide drugs and basic research tools have received considerable attention in the last decade. Enfuvirtide is a 36-residue chemically synthesized helical peptide that targets the viral gp41 protein and inhibits viral membrane fusion. Enfuvirtide-resistant HIV, however, has been prolific, and this peptide therapy requires daily injection due to proteolytic degradation. In this dissertation I have developed a method for stabilizing helical peptide therapeutics termed helix-grafted display proteins. These consist of the HIV-1 gp41 C-peptide helix grafted onto Pleckstrin Homology domains. Some of these earlier protein biologics inhibit HIV-1 entry with modest and variable potencies (IC50 190 nM - >1 μM). After optimization of the scaffold and the helix, our designer peptide therapeutic potently inhibited HIV-1 entry in a live-virus assay (IC50 1.9-12.4 nM). Sequence optimization of solvent-exposed helical residues using yeast display as a screening method led to improved biologics with enhanced protein expression in Escherichia coli (E. coli, a common bio-expression host), with no appreciable change in viral membrane fusion suppression. Optimized proteins suppress the viral entry of a clinically-relevant double mutant of HIV-1 that is gp41 C-peptide sensitive and Enfuvirtide-resistant. Protein fusions engineered for serum-stability also potently inhibit HIV-1 entry.Item Open Access Fluoroalkyl and fluoroaryl fullerenes, polycyclic aromatic hydrocarbons, and copper(I) complexes: synthesis, structure, electrochemical, photophysical, and device properties(Colorado State University. Libraries, 2020) Reeves, Brian J., author; Strauss, Steven H., advisor; Shores, Matthew P., committee member; Rappé, Anthony K., committee member; McNally, Andrew, committee member; Ridley, John, committee memberIn many fields of research, ranging from materials chemistry to medicinal chemistry, understanding the structural, electrochemical, and photophysical properties of materials is essential to establishing trends and predicting usefulness and future performance. This work has focused on the impact of strongly electron withdrawing perfluoroaryl and perfluoroalkyl substituents on the properties of fullerenes, polycyclic aromatic hydrocarbons (PAHs), hetero-PAHs, and copper(I) complexes with the goal of establishing and understanding the fundamental reasons for any observed trends. In Chapter 1, the first successful example of vacuum-deposited organic photovoltaic cells (OPVs) based on a fullerene derivative and a small-molecule donor is reported. A series of thermally robust fluorous fullerene acceptors with experimental gas-phase electron affinities ranging from 2.8 to 3.3 eV are paired with new dicyanovinyl thiophene-based molecular donors to enable direct comparison of their performance in planar and bulk heterojunction architectures in cells fabricated by vacuum deposition. Unprecedented insights into the role of the acceptor intrinsic molecular and electronic structures are obtained, which are not obscured by solvent and additive effects as in the typical solution-processed fullerene-based OPVs. Additionally, the fullerene derivative, C60CF2, was utilized in vacuum-deposited organic field effect transistors (OFETs), and it was shown to have superior device lifetime compared to C60 based OFETs. In Chapter 2, a new synthesis of 9,10-bis(perfluorobenzyl)anthracene, a promising blue organic light emitting diode (OLED) material is reported. The yield was improved from 7% to 17%, while the separations conditions were improved to only require one stage of HPLC. In Chapters 3 and 4, the trifluoromethylation of two hetero-PAHs, phenanthroline and phenanthridine, is discussed. The structure, solid-state packing, and electronic properties of the products are examined. Previously unknown structure-property relationships were established between the electronic properties and the position of CF3 groups. Additionally, the synthesis and excited-state dynamics for a series of homoleptic copper(I) phenanthroline complexes with 2, 3, and 4 trifluoromethyl groups are reported. Surprisingly, the observed time-resolved dynamics and emission trend is that addition of trifluoromethyl groups past two decreases the excited state lifetime and increases excited-state distortion.Item Open Access Fundamental and applied studies of polymeric photonic crystals: the role of polymer architecture and 3D printing(Colorado State University. Libraries, 2020) Boyle, Bret Michael, author; Miyake, Garret, advisor; McNally, Andrew, committee member; Menoni, Carmen, committee member; Prawel, David, committee memberBlock copolymers (BCP) provide a bottom-up, economical approach to synthesizing polymeric photonic crystals (PC) through the process of self-assembly. Photonic crystals (PC) are defined as periodic, dielectric nanostructures able to reflect certain wavelengths of light within a photonic band gap. The ability to directly tailor the synthesis, conformation, and self- assembly of a BCP to affect the properties of the resulting PC material creates a modular platform for PC materials design. Even though this platform exists for polymeric PC materials, the direct result of modulating the polymer architecture on the dynamics, self-assembly, and application of PC materials remains relatively unexplored. To help close this gap, this dissertation presents the polymer synthesis, characterization, and self-assembly of macromolecules within two unique classes of polymer architecture, dendritic block copolymers (DBCP) and bottlebrush block copolymers (BBCP). DBCPs were shown to possess many characteristics similar to those of bottlebrush polymers such as a rod-like conformation, a reduced capability for chain entanglement, and lower glassy moduli compared to non-rigid, linear polymers. Further, DBCPs possess high free energy parameters, as well as glass transition temperatures below melt extrusion 3D printing operating conditions, and were shown to self- assemble into PCs during the process of 3D printing. DBCP PCs represented the first example of 3D printing structural color. For BBCPs, the backbone composition's effect on the global BBCP conformation and in modulating self-assembly processes was examined. The backbone composition was shown to dramatically shift the wavelength of reflection of the PC material at similar molecular weights as well as improve the fidelity of the nanostructure morphology as the molecular weight increases from 50,000 g/mol to 2 million g/mol. The structure-property relationships illuminated herein have laid the groundwork for new research efforts into engineering BCPs for novel PC applications.Item Open Access Investigations into photocatalysis and electronic structure for transition metal and actinide complexes(Colorado State University. Libraries, 2018) Higgins, Robert F., author; Shores, Matthew P., advisor; Rappé, Anthony K., committee member; Neilson, James R., committee member; McNally, Andrew, committee member; Wu, Mingzhong, committee memberPresented herein are investigations into the electronic structure of various metal complexes and how they effect reactivity. The first chapters are centered on how [Cr(Ph2phen)3]3+ reacts as a photooxidant. The latter part of this work concerns magnetic properties of various first row transition metal and actinide complexes. In Chapter 1, I provide a background on how understanding electronic structure of transition metal complexes has motivated later work in reactivity. This Chapter also includes a detailed background in photoredox catalysis and different electronic structures of Ru-, Ir- and Cr-containing photosensitizers. It ends with a lead-in to our initial hypotheses and motivations for using Cr as a paramagnetic, Earth-abundant congener to Ru photosensitizers in photoredox manifolds. Chapters 2-4 illustrate our mechanistic studies into transformations using Cr as a photooxidant to perform [4+2] cycloaddition reactions between (trans and cis)-anethole and dienes. Chapter 2 focuses on the interactions of oxygen (O2) in the reaction of trans-anethole and isoprene mediated by [Cr(Ph2phen)3]3+. We determined three separate, yet invaluable roles that oxygen performs in this reaction, which include: (1) protection of the catalyst through excited-state energy-transfer giving 1O2, (2) 1O2 oxidation of the reduced form of the catalyst, regenerating the ground state species and giving 2O2•- as well as (3) 2O2•- reduction of the radical cation of the [4+2] product, completing the catalytic cycle. In Chapter 3, I discuss the association that trans-anethole and similar dienophiles show with [Cr(Ph2phen)3]3+ and how this affects the overall reactivity. Interestingly, diamagnetic analogues do not show the same association. Finally, in Chapter 4, trans-anethole is replaced with cis-anethole to determine how the overall reactivity changes. These data are supported by reactivity, kinetic and quenching studies to probe the reactivity. Chapters 5-7 concern similar mechanistic details involving [Cr(Ph2phen)3]3+ in photocatlytic cycloaddition reactions, except that trans-anethole, which is electron-rich, is replaced by 4-methoxychlacone, which is electron-poor. Chapter 5 discusses the synthetic utility of this reaction manifold and initial mechanistic details of the transformation, which reveal an orthogonal mechanism which proceeds through energy transfer when compared to the reactivity of trans-anethole with [Cr(Ph2phen)3]3+. In Chapter 6, the observation of enhanced regioselectivity that is observed when [Cr(Ph2phen)3]3+ is used is investigated, specifically in comparison to all other Cr- and Ru-photooxidants attempted. This regioselectivity is manifested in the stabilization of a one-bond intermediate, as well as an association between 4-methoxychalcone and [Cr(Ph2phen)3]3+. To conclude this section, Chapter 7 focuses on the interesting solution-phase equilibria of 4-methoxychalcone and how the association of 4-methoxychlacone with itself and [Cr(Ph2phen)3]3+ impacts the overall reaction mechanism. Chapter 8 provides an interesting method of using ferrocenium as an inexpensive and abundant electron-transfer reagent in reactions similar to common photoredox reactions. This uncommon reaction pathway provides an interesting reactivity compared to traditional pericyclic reactions. The remaining Chapters (9-13) explore the magnetic properties and electronic structures of a variety of first-row and actinide complexes and clusters. Chapter 9 focuses on spin-state switching through oxidation chemistry of both iron and nitrogen atoms in organometallic complexes. The ground states of these complexes can be controllably tuned through sequential oxidation reactions. In Chapter 10, I present the synthesis and magnetic properties of mono- and bis-terpyridine Co(II) complexes. These Co complexes display a variety of coordination geometries which affect their dynamic magnetic properties. Chapter 11 focuses on the reactivity and magnetic properties of a family of U-acetylide species, where interesting redox chemistry is noted upon addition of redox-inactive crown ether molecules. In Chapter 12, I discuss the magnetic properties of 3 different families of uranium complexes measured in collaboration with Prof. Suzanne Bart's group at Purdue University. Finally, in Chapter 13, I give some broad conclusions about what was learned in the mechanistic studies of Cr-photocatalysis and possible interesting avenues for future work.Item Open Access Reaction development and mechanistic investigation of rhodium-catalyzed pyridine synthesis via C-H activation(Colorado State University. Libraries, 2014) Neely, Jamie M., author; Rovis, Tomislav, advisor; McNally, Andrew, committee member; Fisk, John D., committee member; Neilson, James R., committee member; Inamine, Julia M., committee memberDescribed herein are two complementary rhodium-catalyzed methods for the synthesis of substituted pyridines from unsaturated oxime derivatives and alkenes. In the first, formal [4+2] cycloaddition of O-pivaloyl α, β-unsaturated oxime esters and activated terminal alkenes was discovered to proceed in high yields and with excellent selectivity for 6-substituted pyridine products. Mechanistic experiments were found to be consistent with a reversible C-H activation step and a C-N bond forming, N-O bond cleaving process en route to pyridine formation. Rhodium-catalyzed coupling using unactivated alkene substrates was shown to present important information regarding the influence of the alkene component on product distribution. In a second method, access to 5-substituted pyridine derivatives was achieved by decarboxylative annulation of α, β-unsaturated oxime esters and β-substituted acrylic acid derivatives. In this case, carboxylic acids were found to serve as traceless activating groups for selective alkene incorporation. A wealth of mechanistic insight was gained by identification of and decomposition studies regarding catalytically relevant rhodium complexes.Item Open Access The development and applications of light-gated cobalt catalysis(Colorado State University. Libraries, 2017) Ruhl, Kyle E., author; Rovis, Tomislav, advisor; McNally, Andrew, committee member; Neilson, James R., committee member; Kipper, Matthew J., committee memberTransition metals are an important natural resource and an essential component of many industrial processes and applications. Examples of these include air-quality control, electronics manufacture, agriculture, pharmaceuticals, and petro-chemistry. Within the field of synthetic chemistry, transition metal catalysts minimize waste, decrease expense, and enable rapid construction of small molecules. Over the past decade, transition-metal-based polypyridyl complexes have been the cornerstone of photo-redox catalysis which facilitate electron transfer and allow synthetic chemists to functionalize inert functionalities using visible-light energy. The first chapter of this work introduces rhodium- and cobalt-catalyzed [2+2+2] cycloadditions as well as photo-redox catalysis. The following chapter covers our group's progress toward the merger of photo-redox and cobalt catalysis as well as the multi-disciplinary approach we have used to understand mechanism. The third chapter explores light-gated catalysis and its importance for spatially and temporally resolved methods. Finally, the fourth chapter focuses on the applications of light-gated cobalt catalysis. We have found a light-gated cobalt catalyst to temporally control the [2+2+2] cycloaddition, and when combined with photolithography, enable a spatially resolved method for arene formation.