Date of Award
12-1-2023
Language
English
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
College/School/Department
Department of Chemistry
Dissertation/Thesis Chair
John Dr. Welch
Committee Members
Alan Dr. Chen, Mehmet Dr. Yigit, Omar Dr. Shehab
Keywords
Ab Initio Calculation, Aggregation, Fluorine Chemistry, GROMACS, Molecular Dynamics, Protein Folding
Subject Categories
Computational Chemistry
Abstract
Introduction of novel tetrafluoro(trifluoromethyl-λ6-sulfanyl) (CF3SF4) functional group has garnered substantial interest because of its increased hydrophobicity. This super fluorinated group attributed to increased lipophilicity, decreased heat of vaporization, and lowered dielectric constants. The highly electronegative nature of this group can profoundly influence the reactivity of compounds containing the CF3SF4 moiety. The hypervalency associated with this new group presents an exciting platform to explore the fundamental understanding of molecular interactions, reactivity patterns, and electronic behaviors. This dissertation investigates the molecular properties and behaviors of tetrafluoro(trifluoromethyl-λ6-sulfanyl) ethanes (CF3SF4-ethanes), with a specific emphasis on 2-tetrafluoro(trifluoromethyl)-λ6-sulfanylethan-1-ol (CF3SF4-ethanol) and 2-tetrafluoro(trifluoromethyl)-λ6-sulfanylethanamine (CF3SF4-ethanamine). Utilizing ab initio calculations combined with geometry optimization, force field parameterization, and molecular dynamics simulations, we sought to derive an in-depth understanding of electronic structures, bonding dynamics, and other inherent molecular properties of these hypervalent sulfur-containing compounds in chapter 1. In chapter 2, our study further investigates the aggregation mechanisms of these compounds in aqueous environments due to their hydrophobic interactions imparted by fluorine by molecular dynamic simulation and dynamic light scattering experiments. We validated our findings by comparing with well-known fluorinated alcohols such as 2,2,2-trifluoroethanol (TFE) and 1,1,1,3,3,3-hexafluoroisopropanol (HFIP). The higher propensity of aggregation by CF3SF4-ethanol at much lower concentration (8 % (v/v)) than TFE (40 % (v/v)) and HFIP (30 % (v/v) makes it a good substitute. We evaluated the aggregation phenomenon of CF3SF4-ethanamine to understand the potential of the compound as cosolvent. The CF3SF4-ethanamine being a green solvent emphasizing its utility as a biodegradable alternative unlike fluoroalcohols. Additionally, the utility of these compounds as cosolvents for enhancing protein folding stability was explored, further examination of the interactions with peptide backbones and their impact on peptide intramolecular hydrogen bonds. Our study was conducted on melittin which has stable helix in lipid membrane but becomes random coil in water. Our study demonstrated the stabilization of secondary structure of melittin in CF3SF4-ethanol and CF3SF4-ethanamine (8 % (v/v) for both), imparted by highly hydrophobic functional group CF3SF4 in comparison to TFE (40 % (v/v). The correlation of molecular dynamics simulations with experimental data from far UV circular dichroism measurements provides a comprehensive overview of the role of these fluorinated cosolvents in influencing peptide structures and interactions.
Recommended Citation
Biswas, Samadrita, "The Effects Of Aggregation Of Tetrafluoro(Trifluoromethyl-Λ6-Sulfanyl) Ethanes On The Secondary Structure Stabilization Of Melittin: A Molecular Dynamics Simulation Study" (2023). Legacy Theses & Dissertations (2009 - 2024). 3078.
https://scholarsarchive.library.albany.edu/legacy-etd/3078
