Doctor of Philosophy (Ph.D.), Bowling Green State University, 2023, Photochemical Sciences

The lipid bilayer's integrity is essential for cell function as it acts as the primary barrier against external molecules like drugs and peptides, which can alter the bilayer's physical properties. This dissertation investigates how amphetamine (AMPH) and methamphetamine (METH), and the charged HIV1-TAT peptide impact the stability of lipid bilayers, using a home-built lipid bilayer apparatus that enables real-time monitoring through electrical and fluorescence measurements. Our findings indicate that AMPH and METH increase the lipid bilayer's ion permeability, with METH having a greater destabilizing effect. High concentrations of these stimulants, akin to levels in blood plasma of individuals with stimulant-related brain injuries, lead to pore formation in the bilayer. The extent of destabilization correlated with the drug concentration. We also studied the translocation dynamics of the charged HIV1-TAT peptide across the lipid bilayer. The analysis of current fluctuations showed that successful translocation of the TAT peptide is concentration-dependent, highlighting the significance of charge in inducing membrane deformation or pore formation. Additionally, molecular dynamic simulations were used to explore AMPH interactions with the lipid bilayer in greater detail. The results revealed AMPH's preferred orientation during interaction and its hydrophobic nature, as evidenced by the larger energy barrier encountered in the hydrophilic head group regions of the lipid bilayer. To complement these findings, we utilized surface-enhanced Raman spectroscopy (SERS) to estimate the concentrations of AMPH within lipid bilayers. The data showed a positive correlation between characteristic peak heights and AMPH concentrations. Moreover, whole-cell patch clamp measurements on neuronal cells were employed to examine AMPH's effects in a more intricate lipid environment. This research contributes to the understanding of how stimulants and charged peptides interact with lipid bi (open full item for complete abstract)

Committee: Hong Lu Ph.D. (Committee Chair); Dryw Dworsky Ph.D. (Other); Joseph Furgal Ph.D. (Committee Member); John Cable Ph.D. (Committee Member) Subjects: Chemistry

Doctor of Philosophy (PhD), Ohio University, 2020, Chemistry and Biochemistry (Arts and Sciences)

Investigating the specific local environment and molecular interactions at liquid surfaces is crucial in comprehending physical, chemical, and biological processes. Probing the interfacial molecular conformations will provide an insight into the relationship between surface structure and the governing interactions at the surface. Herein, this dissertation used the approach of the effect of substituents on the interfacial conformation of a methacrylate backbone, to observe such surface structure interaction relationships. The ethyl end of the methacrylate monomer was substituted with bulky groups and electron-withdrawing groups. These substituted monomers were synthesized via nucleophilic addition elimination reaction and characterized using sum frequency generation (SFG) spectroscopy at the air-liquid interface. The spectroscopic results were correlated with surface tension measurements and the overall dipole moment of the molecules. The presence of bulky substituents affected the orientation distribution of the interfacial molecules. On the other hand, in the presence of electron-withdrawing groups, the intensity of vibrational modes was affected, suggesting the changes in interfacial molecular conformations and existing intermolecular interactions. In another project, quaternary ammonium surfactants were utilized to assess their conformation and orientation at the air-water interface using SFG spectroscopy. Herein, the approach of solvent isotopic substitution was used to investigate the surfactant water interactions. The results showed the addition of deuterated water rearranges its head group parallel to the interface and straightens its chain with reduced gauche defects. The change in the conformation of the surfactant molecules at the air-liquid interface showcased the difference in intermolecular interactions for water and deuterated water. In summary, these studies revealed the importance of SFG spectroscopy as a tool to probe surface structures in gauging m (open full item for complete abstract)

Committee: Katherine Cimatu (Advisor) Subjects: Chemistry; Molecules; Optics; Physical Chemistry; Polymers

PhD, University of Cincinnati, 2019, Arts and Sciences: Chemistry

The physical properties of surfactant and amphiphile aggregate structures, for example folded globular proteins or surfactant solutions, are strongly modulated by changes in their aqueous environment such as solvated molecules, ions or solid substrates. The ability to study at a molecular level the structure and dynamics in these systems can aid in understanding the origin of many important properties and interactions ranging from medical implant biofouling to the activity of enzymatic scaffolds to the viscosity and stability of formulated soaps and detergents. To that end, I address two issues pertaining to these types of problems in this dissertation. In part I of this thesis, I use coarse-grained implicit solvent Langevin dynamics simulations to probe the unfolding of three protein fold motifs: an all-alpha four-helix bundle, a four strand beta barrel, and a mixed fold alpha/beta structure. These three protein folds are then placed near three hydrophobic surfaces: a planar hexagonal graphene-like structure and two curved hexagonal carbon nanotube-like surfaces. For the curved surfaces the radii of the tubes are created either with a relatively large or small radius and placed in a linear arrangement resulting in deep or shallow grooves. The proteins are initially oriented in several rotational states for each surface. My results indicate that binding and unfolding occur by different mechanisms depending on both the protein fold, its original orientation with respect to the surface and the topological character of the surface. Specifically, all-alpha four-helix bundle and the four strand beta barrel have competing stability profiles, where the four-helix bundle is more stable in the presence of curved surfaces and the beta barrel is stabilized in planar environments. This led to an interesting result with the alpha/beta fold, where the surface topology and initial orientation of the protein led to stable partially folded states following the trends found in th (open full item for complete abstract)

Committee: George Stan Ph.D. (Committee Chair); Thomas Beck Ph.D. (Committee Member); Charles Eads PhD (Committee Member); Anna Gudmundsdottir Ph.D. (Committee Member) Subjects: Physical Chemistry

MS, University of Cincinnati, 2015, Engineering and Applied Science: Chemical Engineering

Adsorption of polymers in solutions on surfaces depends on a variety of factors such as polymer-surface interaction strength, properties of the surface, temperature, length of polymer chains, and the quality of solvents. For adsorption to occur, the gain in energy by adsorbing onto a surface should be greater than the loss in conformation entropy of the polymer chain arising due to binding to the surface. Polymer adsorption on flat surfaces have been widely studied and well understood. However, polymer adsorption on rough surfaces is less understood due to the complexity involved in equilibration and sampling of such systems. The main goal of this study was to elucidate clearly the effect of surface roughness on adsorption of polymers. Molecular simulations techniques are employed to investigate the effect of surface roughness on polymer adsorption. Both Monte-Carlo simulations and molecular dynamics simulations are used to study the effects of irregular (self-affine) roughness and regular (uniform) roughness parameters, respectively. The Monte-Carlo simulations are carried out in the NVT ensemble. The adsorbed polymers are characterized by density and bond orientation profiles, adsorbed monomer fraction and chain topologies. The results of this study elucidate the extent to which adsorption or desorption can be controlled solely by tuning surface roughness parameters. In particular, the results from molecular dynamics study show that increasing surface roughness enhances polymer adsorption. However, the results from Monte-Carlo study are markedly different; the effect of surface roughness is to diminish the fraction of monomers adsorbed. This trend was observed as a result of using a wide range of chain population distribution in the study.

Committee: Vikram Kuppa Ph.D. (Committee Chair); Kelly Anderson Ph.D. (Committee Member); Sumanth Jamadagni Ph.D. (Committee Member); Vadim Guliants Ph.D. (Committee Member); Dale Schaefer Ph.D. (Committee Member) Subjects: Chemical Engineering