Honors Thesis Archive
| Author | Ethan M. Belknap |
|---|---|
| Title | Computational Model of the Nucleophilic Acyl Substitution Pathway |
| Department | Biochemistry/Molecular Biology |
| Advisor | Justin B. Houseknecht |
| Year | 2021 |
| Honors | University Honors |
| Full Text | View Thesis (281 KB) |
| Abstract | Nucleophilic acyl substitution (NAS), specifically as it proceeds through the associative pathway, is a fundamental chemical reaction that is found as a component in many biochemical pathways. A defining feature of nucleophilic acyl substitution is the formation of a tetrahedral intermediate, which functions to stabilize the reaction complex and lower the overall energy of reaction. This formation of an energetically favorable tetrahedral intermediate is a key aspect in the discussion of NAS as an important mechanistic component of biochemical and organic reactions. However, there is evidence to suggest that given the correct reaction conditions the dissociative pathway of nucleophilic acyl substitution, in which no tetrahedral intermediate is formed, is energetically favored over the associative pathway. The potential for the dissociative pathway’s favorability provides great incentive to explore this pathway by way of computational chemistry, and also grants the opportunity to model the energetics and geometry of the reaction and explore changes to them under varying conditions. In order to do so, ab initio calculations were utilized at every level of analysis within this research to determine the energy of the acyl system under different conditions modeled within the Wittenberg computing cluster (WARP2). By using these calculations, model systems were created for the NAS system in which correct transition state geometries and energetics were identified, and these data provide potential avenues for further development of the dissociative pathway model in the future. |
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