Computational Chemistry Commons^™

Discovery Of The Multi-Ion Bridge Intermediate: A Computational Exploration Of The Mechanism For Azomethine Ylide Formation From N-Oxides, Martin J. Neal

Electronic Theses and Dissertations

Density functional theory (DFT) provides a method for calculating the ground-state energies of complex molecular systems through evaluating the electron density instead of the full wave function. When results match either experimental outcomes, calculations with DFT offer a computationally efficient method to help explain chemical phenomena. The transformation of tertiary amine N-oxides to azomethine ylides, a simple route to the precursor for 1,3-dipolar cycloadditions that result in the pyrrolidine scaffolds found in natural products, has received only minimal attention due to concerns that its mechanism includes a highly electrophilic intermediate. Utilizing DFT to model the mechanism of the conversion …

Symmetry, Stability, And Robust Optimization Strategies For Nonorthogonal Multiconfiguration Self-Consistent Field Wavefunctions., Zihui Song

Electronic Theses and Dissertations

The "different orbital different configuration" (DODC) framework is a general formulation of multireference wavefunctions that allows each configuration (determinant) to possess its own set of optimized molecular orbitals, rather than sharing a common orbital basis as in conventional orthogonal configuration interaction (CI) or Complete Active Space Self-Consistent Field (CASSCF) methods. One prominent example of the DODC framework is the Nonorthogonal Configuration Interaction (NOCI) method, which relaxes the orthogonality constraint between the orbitals of different configurations. This relaxation enables a compact yet flexible description of systems exhibiting strong correlation. By employing multiple nonorthogonal reference determinants, NOCI naturally incorporates orbital relaxation and …

Divergent Responses Of Branched-Chain And Straight-Chain Lipid Membranes To Butanol Stress Revealed By All-Atom Molecular Dynamics Simulations, Joshua Olaf Aggrey

Electronic Theses and Dissertations

Membrane integrity under chemical stress is critical to cellular survival and industrial microbial bioproduction, yet the molecular basis of bilayer resilience remains poorly understood. Using all-atom molecular dynamics simulation, we compare the effect of increasing concentrations of 1‑butanol on membranes composed of straight-chain (1,2-dipalmitoyl-sn-glycero-3-phosphocholine, DPPC) and branched-chain (1-anteiso-palmitoyl-2-palmitoyl-sn-glycero-3-phosphocholine, APPC) lipids, which differ in the point of attachment of a single methyl group. In the absence of butanol, both membranes exhibit well-ordered architectures consistent with experimental benchmarks; however, under increasing solvent stress, their behaviors diverge markedly. DPPC membranes display gradual thinning, modest area per lipid …

Intrinsic Gas-Phase Behavior Of Uranium Species: A Comprehensive Reactivity Study Of [O=U≡Ch]+ And [Uh]+, Justin Terhorst

Electronic Theses and Dissertations

The intrinsic chemistry of actinide elements, particularly uranium, remains a key challenge in understanding f-block reactivity due to the complexity introduced by solvent interactions, counter-ions, and complex equilibria in the condensed phase. In this dissertation, a systematic gas-phase study utilizing preparative tandem ion-trap mass spectrometry (PTMSⁿ) is presented, focusing on the reactivity of uranium-centered species, specifically [OUCH]⁺, an oxy uranium methylidyne species, and [UH]⁺ ions. By stripping away solvent effects and isolating the ions, PTMSⁿ provides a powerful platform to probe the fundamental chemical behavior of uranium species in their intrinsic state.

The …

Rna Structural-Dynamical Hierarchy: Sars-Cov, Sars-Cov-2, And Delta/Omicron Variant S2m Monomers, Kissing Complexes, And Extended Duplexes, Adam Kensinger

Electronic Theses and Dissertations

The power and promise of ribonucleic acid (RNA) molecules are only beginning to be realized in living organisms and pharmaceutical intervention. Specifically, defining the chemical physics of RNA’s heterogenous structural ensemble and dynamics, which has experienced expansive growth over the last few years, is central to a complete understanding, yet continues to be a significant challenge. A 41-nucleotide hairpin called the stem-loop II motif (s2m), present in the viral genomes of severe acute respiratory syndrome (SARS), SARS-coronavirus-2 (SARS-CoV-2), and the Delta and Omicron variants responsible for the COVID-19 pandemic, is a potential antiviral target due to its high sequence conservation …

Structure-Function Relationships In Neurodegenerative And Infectious Diseases: Biophysical Characterization Of Rna Secondary Structures By Computational Techniques, Kendy Guarinoni

Electronic Theses and Dissertations

The research described in this dissertation focuses on the investigation of the structure and dynamics of regions of RNA implicated in two diseases: COVID-19 and amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD). Both studies sought to create experimentally corroborated models that were used to characterize the structure and dynamics of the C9orf72 repeat expansion and the s2m region in coronaviruses, respectively and provided the foundation for future work. In our work involving the s2m region of SARS-CoV-2, the virus responsible for COVID-19, we determined that the homology modeling approach commonly used to derive atomistic structures when no coordinates are available yields a …

Use Of Computational Methods To Determine The Relative Thermodynamic Stability Of Myricetin, Quercetin And 4-Methylesculetin For Use As Spin Traps, Cole Walker

Electronic Theses and Dissertations

The research conducted focused on the oxidative intermediates of antioxidants known as Myricetin, Quercetin, and 4-Methylesutin by calculating the reaction mechanism. During this research, computational quantum chemistry on selected parts for the 3 antioxidants previously mentioned were performed to find the most stable intermediate to act as a spin trap. The hypothesis is that the intermediates found can act as spin traps which will allow longer preservation of a free radical to be identified using Electron Paramagnetic Resonance (EPR) spectroscopy. This may be because the buildup of excess free radicals in a system leads them to cause damage down to …

Computational Investigations Of Bond Breaking Processes Using Dft And Td-Dft Approaches., Saurav Parmar

Electronic Theses and Dissertations

The efficient application of DFT and TD-DFT has been harnessed to study bond-breaking processes in some molecules which play a prominent role in enzymatic reactions. The first application includes Radical S-adenosyl methionine (SAM) enzymes which are fundamentally important sources of organic radicals to initiate diverse radical reactions. Recently a bio-organometallic intermediate (Ω) that contains an Fe‒C bond has been characterized and shown to be a common feature of radical SAM enzymes. The strength of Fe‒C bond in Ω has been computed using broken-symmetry density functional theory (BS‒DFT). Additionally, Fe‒C bond dissociation energy (BDE) in Ω has been compared to that …

Computational Quantum Chemistry Studies Of The Stabilities Of Radical Adducts Formed During The Oxidation Of Melatonin Derivatives, James Horne

Electronic Theses and Dissertations

Melatonin is a natural antioxidant that has been investigated for properties as a potential spin trap to identify short-lived free radicals. Computational quantum chemistry studies have been performed for the oxidation of melatonin to N¹-acetyl-N²-formyl-5-methoxykynuramine. This research focused on modification of melatonin into derivatives and analyzing the change in total molecular energy from melatonin to its oxidation product, as well as the corresponding derivatives. Each of the molecular geometries were optimized at the DFT/B3LYP/6-31G(d), DFT/B3LYP/cc-pVXZ (X = D, T), HF/6-31G(d), HF/cc-PVXZ (X = D, T), MP2/6-31G(d), and MP2/cc-PVXZ (X = D, T) levels of theory. …

Development Of Nonorthogonal Wavefunction Theories And Application To Multistate Reaction Processes., Emily Kempfer

Electronic Theses and Dissertations

Many prominent areas of technological development rely on exploiting the photochemical response of molecules. An application of particular interest is the control of molecular switches through a combination of different external stimuli. However, despite significant advances in theoretical approaches and numerous cases of successful application of theory, simulating photochemical reactions remains a computational challenge. Theoretical methods for describing excited states can be broadly divided into single-reference response methods and multireference methods. Single reference methods provide reliable semiquantitative results for single excitations. However, these methods cannot describe double-excited states, systems with strongly correlated ground states, or regions of degeneracy on the …

Quantum Computations And Molecular Dynamics Simulations: From The Fundamentals Of Antimicrobial Resistance To Neurological Diseases, Angel Tamez

Electronic Theses and Dissertations

Biophysical phenomena are modeled using a combination of quantum and classical methods to interpret and supplement three distinct and diverse problems in this dissertation. In the first project, decarboxylation reactions are ubiquitous across chemical and biological disciplines, yet the origin of non-catalytic solvent effects remains elusive. Specific solvent structure and energetics have not been well described for the monoanion of malonate, nor corrected from the gas-phase charge-assisted intramolecular hydrogen bond model known as “pseudochair”. In the aqueous phase, a low-lying energy conformer known as the “orthogonal conformation” is computed to be preferred by a three-water cluster of hydrogen bonding over …

Turning Ligands On Their Side: Computational Investigation Into The Binding Of N2o And N2 In Transition Metal Complexes, Cole Donald

Electronic Theses and Dissertations

Common greenhouse gas nitrous oxide (N₂O) is a thermodynamically potent and environmentally benign oxidant, making it a desirable target for metal center activation. Unfortunately, N₂O is a poor ligand for transition metals due to its weak sigma-donating and pi-accepting properties; as a result, few transition metal complexes capable of interacting with N₂O have been found. As the primary source of all nitrogen in organisms, abundant gas dinitrogen (N₂) is a crucially important tiny molecule and an essential part of daily existence. However, due to its inertness, it has limited practical uses in …

Theory Of Aqueous Solvation: Uninterrupted, Cyclic Hydrogen-Bonding Essential For Accurate Keto-Enol Energies And Grotthuss Tautomerism Of Acetone, Mark Recznik

Electronic Theses and Dissertations

Keto-enol tautomerization (KET) is a fundamental process impacting a range of molecular phenomena in organic and biochemistry. However, the accurate computation of solution-phase KET energies remains a challenge, even for prototypical acetone.

In Part I, keto-enol tautomers of acetone were incorporated into solvent clusters that interact via uninterrupted, cyclic hydrogen-bonding (UCHB) networks. An empirical model was created to predict accurate KET energies, E_taut, of simple carbonyl compounds. Based on the availability of experimental data and structural simplicity, acetone was selected as a prototype. A discrete-continuum strategy was employed – accounting simultaneously for local noncovalent interactions and bulk-phase effects …