cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.7274/25571514
title: Reverse Non-Equilibrium Molecular Dynamics Simulations of Thermal Transport through Functionalized Gold Interfaces

description: In this dissertation, I present work in performing reverse non-equilibrium molecular dynamics simulations of heat transfer through complex metal/ligand/solvent interfaces. More specifically, I characterize heat transfer through gold interfaces that are functionalized with anti-aggregation agents. The effects of gold facet, curvature, size, polarizability, and ligand identity and density on the interfacial thermal conductance are examined. I also explore the effects of ligand choice on the solvent thermal conductivity.

Simulations of solvated gold functionalized with sodium citrate are explored in Chapter 2. The binding preferences of citrate were found to depend on gold curvature more than polarizability. The solvent conductivity was determined to be water-dominated, as the conductivity in citrate-containing systems was nearly identical to those of pristine gold solvated in water. Interestingly, the dependence of conductance on polarizability was found to vary depending on the morphology of the particle.

In Chapter 3, the ligand of interest was a low molecular weight thiolated polyethylene glycol (PEG). There was a significant increase in conductance compared to the citrate-capped interfaces, indicating that strong metal-to-ligand and ligand-to-solvent coupling are likely responsible.

Chapter 4 examines thermal transport through interfaces functionalized with cetyl trimethylammonium bromide (CTAB) or (16-mercaptohexadecyl) trimethylammonium bromide (MTAB). The link between increased conductance and strong ligand-involved coupling was further observed, as the CTAB-capped systems had lower conductance values than any other system. With only strong metal-to-ligand coupling available in the MTAB systems, the conductance here was higher than in CTAB systems.

Finally, Chapter 5 details simulation studies for a different project in collaboration with experimental researchers. The binding behaviors of different PFAS molecules on a graphene surface were investigated. The five molecules (Tf, PFES, PFBS, PFHxS, and PFOS) were found to bind to graphene in different fractions via their oxygen and fluorine atoms, as well as their centers of mass.
DOI: 10.7274/25571514.v1
title: Reverse Non-Equilibrium Molecular Dynamics Simulations of Thermal Transport through Functionalized Gold Interfaces

description: In this dissertation, I present work in performing reverse non-equilibrium molecular dynamics simulations of heat transfer through complex metal/ligand/solvent interfaces. More specifically, I characterize heat transfer through gold interfaces that are functionalized with anti-aggregation agents. The effects of gold facet, curvature, size, polarizability, and ligand identity and density on the interfacial thermal conductance are examined. I also explore the effects of ligand choice on the solvent thermal conductivity.

Simulations of solvated gold functionalized with sodium citrate are explored in Chapter 2. The binding preferences of citrate were found to depend on gold curvature more than polarizability. The solvent conductivity was determined to be water-dominated, as the conductivity in citrate-containing systems was nearly identical to those of pristine gold solvated in water. Interestingly, the dependence of conductance on polarizability was found to vary depending on the morphology of the particle.

In Chapter 3, the ligand of interest was a low molecular weight thiolated polyethylene glycol (PEG). There was a significant increase in conductance compared to the citrate-capped interfaces, indicating that strong metal-to-ligand and ligand-to-solvent coupling are likely responsible.

Chapter 4 examines thermal transport through interfaces functionalized with cetyl trimethylammonium bromide (CTAB) or (16-mercaptohexadecyl) trimethylammonium bromide (MTAB). The link between increased conductance and strong ligand-involved coupling was further observed, as the CTAB-capped systems had lower conductance values than any other system. With only strong metal-to-ligand coupling available in the MTAB systems, the conductance here was higher than in CTAB systems.

Finally, Chapter 5 details simulation studies for a different project in collaboration with experimental researchers. The binding behaviors of different PFAS molecules on a graphene surface were investigated. The five molecules (Tf, PFES, PFBS, PFHxS, and PFOS) were found to bind to graphene in different fractions via their oxygen and fluorine atoms, as well as their centers of mass.
DOI: 10.7274/25571526
title: Synthesis of Molecular Tools and Evaluation of Dirhodium Catalyst Conformations

description: In this thesis, topics ranging from synthetic organic chemistry to computational DFT studies have been explored. For the first project, photocaged enzyme substrates were synthesized to be used in crystallographic studies of the enzyme PmHMGR. This includes a novel asymmetric synthesis of mevalonic acid stereoisomers. The photophysical properties of caged substrates were explored from both an experimental and computational approach. Preliminary crystallographic experiments have been carried out which indicate possible stability issues of the caged compounds within the crystal environment. A control compound was synthesized and crystallographic efforts are ongoing. 

For the second project, a novel cholesterol mimic was synthesized to be used for studying cholesterol cellular trafficking. This compound has been made available to the broader research community. An additional project involves the scale up of potential NPC drug CP2. The compound was synthesized and efforts to scale up the drug candidate are discussed.

The final two projects involve DFT studies. Conformation energetics of dirhodium paddle wheel complexes were evaluated computationally. For a system involving a psuedoarmoatic ligand scaffold, known as Rh2(Pro-SqEB)4, the C4 conformation was found to be the lowest energy conformer. Additionally, a heteroleptic system, known as Rh2(S-PTTL)2(1S,2R-DPPhTCB)2, was studied with a thioether coordinating group. Cis/trans configurations were evaluated along with a conformational study and the nature of the thioether was assessed. An ether variation was proposed as a synthetic target for future direction and the energetics of this complex were assessed. 

For the second DFT study, oxazolidinone was evaluated as a directing group for palladium catalyzed concerted metalation deprotonation on an aromatic ring. Results indicated that each heteroatomic site of oxazolidinone was a poor director for the system studied. Oxazolidinthione was evaluated in place of oxazolidinone and was found to be a better directing group but did not outcompete undirected concerted metalation deprotonation.
DOI: 10.7274/25571526.v1
title: Synthesis of Molecular Tools and Evaluation of Dirhodium Catalyst Conformations

description: In this thesis, topics ranging from synthetic organic chemistry to computational DFT studies have been explored. For the first project, photocaged enzyme substrates were synthesized to be used in crystallographic studies of the enzyme PmHMGR. This includes a novel asymmetric synthesis of mevalonic acid stereoisomers. The photophysical properties of caged substrates were explored from both an experimental and computational approach. Preliminary crystallographic experiments have been carried out which indicate possible stability issues of the caged compounds within the crystal environment. A control compound was synthesized and crystallographic efforts are ongoing. 

For the second project, a novel cholesterol mimic was synthesized to be used for studying cholesterol cellular trafficking. This compound has been made available to the broader research community. An additional project involves the scale up of potential NPC drug CP2. The compound was synthesized and efforts to scale up the drug candidate are discussed.

The final two projects involve DFT studies. Conformation energetics of dirhodium paddle wheel complexes were evaluated computationally. For a system involving a psuedoarmoatic ligand scaffold, known as Rh2(Pro-SqEB)4, the C4 conformation was found to be the lowest energy conformer. Additionally, a heteroleptic system, known as Rh2(S-PTTL)2(1S,2R-DPPhTCB)2, was studied with a thioether coordinating group. Cis/trans configurations were evaluated along with a conformational study and the nature of the thioether was assessed. An ether variation was proposed as a synthetic target for future direction and the energetics of this complex were assessed. 

For the second DFT study, oxazolidinone was evaluated as a directing group for palladium catalyzed concerted metalation deprotonation on an aromatic ring. Results indicated that each heteroatomic site of oxazolidinone was a poor director for the system studied. Oxazolidinthione was evaluated in place of oxazolidinone and was found to be a better directing group but did not outcompete undirected concerted metalation deprotonation.
DOI: 10.7274/25582110
title: Sulfur Reduction by 1,2-Aminothiols and Spectroscopic Tools for Studying Nanocrystal Surfaces

description: This dissertation reports three separate projects during my time at the University of Notre Dame. Chapter 1 reviews the research conducted on the reduction, oxidation, and electrostatics of nanocrystals (NCs) surfaces, highlighting their impact on electronic properties. The emphasis is placed on reviewing the spectroscopic, electrochemical, and computational techniques employed to investigate the redox-active surface sites and trap states.
Chapter 2 describes research with nucleophilic 1,2-aminothiol compounds that reduce elemental sulfur to form polysulfides in both aqueous and nonpolar organic solvents. By monitoring the formation of these polysulfides, we show the hydrogen-bonding group of the amine with the closest proximity results in the most rapid reduction of elemental sulfur. We then apply the knowledge gained from studying these interactions between aminothiols, and elemental sulfur to facilitate the transfer elemental sulfur to alkenes with the aid of these aminothiol compounds.
Chapter 3 describes the study of the surfaces of cesium lead halide perovskite nanocrystals (CsPbX3 NCs) through the utilization of trimethylsilyl trifluoromethanesulfonate (Me3SiOTf) for the quantitative and irreversible silylation of anionic ligands in OA-- and oleylamine-capped CsPbBr3 and CsPbCl3 NCs. Employing 
NMR and FTIR spectroscopies alongside elemental analysis, the study demonstrates the distinct reactivity of Me3SiOTf with CsPbBr3 and CsPbCl3 NCs. In the case of CsPbBr3 NCs, Me3SiOTf reacts by removing a weakly bound ligand population from the surface while revealing an inert, strongly bound ligand population. This treatment induces surface anion exchange for trifluoromethanesulfonate resulting in enhanced photoluminescence quantum yields. For CsPbCl3 NCs, Me3SiOTf abstracts chlorides resulting in the destabilization of the NC lattice. We account this difference in reactivity by the Si–Cl bond being stronger than the Si–Br bond which results in Me3SiOTf abstracting all the chlorides from the NC. 
Chapter 4 describes efforts to probe CdSe NCs surface dipole and facets. We show the development of a [CdFe(CO)4] probe that is sensitive to changes in the surface dipole. We show evidence that [CdFe(CO)4] probe preferentially binds to the (111) facet. These results demonstrate the probe can be utilized to track changes to the (111) facet.
DOI: 10.7274/25582110.v1
title: Sulfur Reduction by 1,2-Aminothiols and Spectroscopic Tools for Studying Nanocrystal Surfaces

description: This dissertation reports three separate projects during my time at the University of Notre Dame. Chapter 1 reviews the research conducted on the reduction, oxidation, and electrostatics of nanocrystals (NCs) surfaces, highlighting their impact on electronic properties. The emphasis is placed on reviewing the spectroscopic, electrochemical, and computational techniques employed to investigate the redox-active surface sites and trap states.
Chapter 2 describes research with nucleophilic 1,2-aminothiol compounds that reduce elemental sulfur to form polysulfides in both aqueous and nonpolar organic solvents. By monitoring the formation of these polysulfides, we show the hydrogen-bonding group of the amine with the closest proximity results in the most rapid reduction of elemental sulfur. We then apply the knowledge gained from studying these interactions between aminothiols, and elemental sulfur to facilitate the transfer elemental sulfur to alkenes with the aid of these aminothiol compounds.
Chapter 3 describes the study of the surfaces of cesium lead halide perovskite nanocrystals (CsPbX3 NCs) through the utilization of trimethylsilyl trifluoromethanesulfonate (Me3SiOTf) for the quantitative and irreversible silylation of anionic ligands in OA-- and oleylamine-capped CsPbBr3 and CsPbCl3 NCs. Employing 
NMR and FTIR spectroscopies alongside elemental analysis, the study demonstrates the distinct reactivity of Me3SiOTf with CsPbBr3 and CsPbCl3 NCs. In the case of CsPbBr3 NCs, Me3SiOTf reacts by removing a weakly bound ligand population from the surface while revealing an inert, strongly bound ligand population. This treatment induces surface anion exchange for trifluoromethanesulfonate resulting in enhanced photoluminescence quantum yields. For CsPbCl3 NCs, Me3SiOTf abstracts chlorides resulting in the destabilization of the NC lattice. We account this difference in reactivity by the Si–Cl bond being stronger than the Si–Br bond which results in Me3SiOTf abstracting all the chlorides from the NC. 
Chapter 4 describes efforts to probe CdSe NCs surface dipole and facets. We show the development of a [CdFe(CO)4] probe that is sensitive to changes in the surface dipole. We show evidence that [CdFe(CO)4] probe preferentially binds to the (111) facet. These results demonstrate the probe can be utilized to track changes to the (111) facet.
DOI: 10.7274/25586250
title: Dianiline Squaraine Dyes: Synthetic and Non-Synthetic Applications

description: Dianiline squaraine dyes, vibrantly colored compounds, are renowned for their physical and analytical chemistry applications. These dyes have a core structure consisting of a cyclobutenedione ring with two aniline derivatives attached in a 1,3 configuration, creating a stabilizing electron transfer effect between donor and acceptor groups. This unique electronic profile enables dianiline squaraine dyes to absorb and emit light in the near-infrared spectrum. Traditionally, these compounds are extensively employed in biological imaging, photodynamic therapy, non-linear optics, photovoltaics, and ion-sensing. Despite possessing multiple sites of potential reactivity, few reported studies examine the use of squaraine dyes as synthetic building blocks. This thesis explores the development of squaraine scaffolds with versatile, functional groups as readily available starting materials for building more complex small molecules and leveraging their inherent reactivity to design chemically-driven analytical protocols. To date, the applications of squaraine dyes have been successfully extended towards: (1) the development of squaraine dyes as colorimetric chemodosimeters for trace transition metals, (2) accessing highly functionalized NHC-Squaraines via an NHC-mediated dearomative skeletal rearrangement of squaraine dyes, (3) the development of proline bound 1,3-semisquaraine as a catalyst in Brønsted acid catalysis, (4) the design of proline bound 1,3-squaramide as chiral transition metal-ligand in enantioselective catalysis.
DOI: 10.7274/25586250.v1
title: Dianiline Squaraine Dyes: Synthetic and Non-Synthetic Applications

description: Dianiline squaraine dyes, vibrantly colored compounds, are renowned for their physical and analytical chemistry applications. These dyes have a core structure consisting of a cyclobutenedione ring with two aniline derivatives attached in a 1,3 configuration, creating a stabilizing electron transfer effect between donor and acceptor groups. This unique electronic profile enables dianiline squaraine dyes to absorb and emit light in the near-infrared spectrum. Traditionally, these compounds are extensively employed in biological imaging, photodynamic therapy, non-linear optics, photovoltaics, and ion-sensing. Despite possessing multiple sites of potential reactivity, few reported studies examine the use of squaraine dyes as synthetic building blocks. This thesis explores the development of squaraine scaffolds with versatile, functional groups as readily available starting materials for building more complex small molecules and leveraging their inherent reactivity to design chemically-driven analytical protocols. To date, the applications of squaraine dyes have been successfully extended towards: (1) the development of squaraine dyes as colorimetric chemodosimeters for trace transition metals, (2) accessing highly functionalized NHC-Squaraines via an NHC-mediated dearomative skeletal rearrangement of squaraine dyes, (3) the development of proline bound 1,3-semisquaraine as a catalyst in Brønsted acid catalysis, (4) the design of proline bound 1,3-squaramide as chiral transition metal-ligand in enantioselective catalysis.
DOI: 10.7274/25586727
title: Investigating the Mechanisms of pH-dependent Protein Regulation

description: Transient changes in intracellular pH (pHi) regulate normal cell behaviors such as migration, differentiation, proliferation, and apoptosis. While pHi dynamics regulate normal cell biology, dysregulated pHi is associated with cancer and neurological disorders. There are a few characterized pHi-associated cell behaviors that have identified pH sensitive proteins (pH sensors) with known mechanisms of pH sensing; however, for many pHi-associated processes the essential pH sensing proteins are unknown. In recent years, the first pH sensor with pH-dependent abundance was identified (ß-catenin). In conjunction with established roles for protein abundance in regulating biological processes and disease phenotypes, it is crucial to understand how pHi dynamics drive broad proteomic changes. Additionally, neither global gene expression profiles nor the cellular proteome have ever been explored in the context of pHi. The use of global transcriptomic and proteomic approaches can identify gene expression and protein abundance differences that are regulated by pHi, providing a holistic view of pH-sensitive pathways and proteins that regulate pH-dependent cell phenotypes. By identifying the pathways and proteins that are regulated by changes in pHi, we will more rapidly characterize novel pH sensors and determine the mechanisms by which pHi regulates cell phenotype. Identification of new pH-sensitive proteins and pathways could reveal new therapeutic targets associated with diseases where pHi is dysregulated, including cancer (increased pHi) and neurodegeneration (decreased pHi).
DOI: 10.7274/25586727.v1
title: Investigating the Mechanisms of pH-dependent Protein Regulation

description: Transient changes in intracellular pH (pHi) regulate normal cell behaviors such as migration, differentiation, proliferation, and apoptosis. While pHi dynamics regulate normal cell biology, dysregulated pHi is associated with cancer and neurological disorders. There are a few characterized pHi-associated cell behaviors that have identified pH sensitive proteins (pH sensors) with known mechanisms of pH sensing; however, for many pHi-associated processes the essential pH sensing proteins are unknown. In recent years, the first pH sensor with pH-dependent abundance was identified (ß-catenin). In conjunction with established roles for protein abundance in regulating biological processes and disease phenotypes, it is crucial to understand how pHi dynamics drive broad proteomic changes. Additionally, neither global gene expression profiles nor the cellular proteome have ever been explored in the context of pHi. The use of global transcriptomic and proteomic approaches can identify gene expression and protein abundance differences that are regulated by pHi, providing a holistic view of pH-sensitive pathways and proteins that regulate pH-dependent cell phenotypes. By identifying the pathways and proteins that are regulated by changes in pHi, we will more rapidly characterize novel pH sensors and determine the mechanisms by which pHi regulates cell phenotype. Identification of new pH-sensitive proteins and pathways could reveal new therapeutic targets associated with diseases where pHi is dysregulated, including cancer (increased pHi) and neurodegeneration (decreased pHi).
DOI: 10.7274/25588119
title: Scalable Fabrication of Paper Analytical Devices for Chemical Education and Pharmaceutical Screening

description: Microfluidic paper analytical devices (µPADs) promise to provide an ideal platform for point-of-use tests because of their low cost, user-friendliness, rapidity, and portability. Few µPADs, however, successfully move beyond the proof-of-concept stage to become viable commercial or clinical products, largely due to the lack of scalable fabrication methods. Wax printing was once hailed as the method of choice for µPAD fabrication, but with the growing scarcity of wax printers, alternative methods are needed.

 Here, I present the air-gap PAD, a low-cost paper device that can be produced with roll-to-roll manufacturing. I successfully adapted two devices previously made with wax printing—a paper-based titration device used for chemical education and a multi-lane PAD used for pharmaceutical quality control and illicit drug checking—to an air-gap format, and partnered with a commercial manufacturer to produce these devices at scale. I developed a reproducible, semi-automated method for depositing colorimetric reagents on the PADs, designed devices to apply both liquid and solid drug samples to the PAD with no need for sample preparation, and collaborated to test a mobile application to read, interpret, and catalog the PAD’s colorimetric pharmaceutical screening results. These advances in µPAD manufacturability, quantitative usefulness, and user-friendliness will make µPADs a more viable platform for point-of-use testing in low-resource settings.
DOI: 10.7274/25588119.v1
title: Scalable Fabrication of Paper Analytical Devices for Chemical Education and Pharmaceutical Screening

description: Microfluidic paper analytical devices (µPADs) promise to provide an ideal platform for point-of-use tests because of their low cost, user-friendliness, rapidity, and portability. Few µPADs, however, successfully move beyond the proof-of-concept stage to become viable commercial or clinical products, largely due to the lack of scalable fabrication methods. Wax printing was once hailed as the method of choice for µPAD fabrication, but with the growing scarcity of wax printers, alternative methods are needed.

 Here, I present the air-gap PAD, a low-cost paper device that can be produced with roll-to-roll manufacturing. I successfully adapted two devices previously made with wax printing—a paper-based titration device used for chemical education and a multi-lane PAD used for pharmaceutical quality control and illicit drug checking—to an air-gap format, and partnered with a commercial manufacturer to produce these devices at scale. I developed a reproducible, semi-automated method for depositing colorimetric reagents on the PADs, designed devices to apply both liquid and solid drug samples to the PAD with no need for sample preparation, and collaborated to test a mobile application to read, interpret, and catalog the PAD’s colorimetric pharmaceutical screening results. These advances in µPAD manufacturability, quantitative usefulness, and user-friendliness will make µPADs a more viable platform for point-of-use testing in low-resource settings.