Browsing by Subject "Fluorine NMR"
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Item Combined Application of Density Functional Theory and Molecular Mechanics Sampling Techniques to study Chemical Systems, from Intramolecular Rearrangements to Polymerization Reactions(2023-05) Chiniforoush, SinaModern techniques in computational chemistry have allowed for the investigation of a diverse array of problems in chemistry and material sciences. However, one of the main challenges in the use of these techniques is the trade-off between computational cost and chemical accuracy. Methods like density-functional theory (DFT) are often accurate, but at the expense of higher computational resources. Methods like molecular mechanics (MM) are less computationally expensive, but fail to describe important features of chemical systems. While the study of chemical systems of relatively small size can often be carried out using methods like DFT, some of these systems have a high number of conformational degrees of freedom despite their relatively small size, and it’s often not possible to accurately describe important characteristics of these systems without capturing these all possible conformers. In this case, using MM-based sampling methods followed by DFT computations can allow for a relatively accurate description of these systems. This work contains three studies. In chapter 2, the mechanistic details of Newman-Kwart rearrangement under oxidative conditions is explored using DFT, and using theoretical predictions, modifications to the Newman-Kwart substrate are proposed to increase reactivity. In chapter 3, a combination of MM sampling methods and DFT are used to evaluate the temperature sensitivity of 19F chemical shifts in a library of organofluorine compounds screened for temperature sensing, and computations were used to successfully predict the chemical shift temperature sensitivity of these compounds, and finally used to guide the synthesis of more temperature sensitive compounds. In chapter 4, the same combination of DFT and MM techniques were used to describe two Aluminum-based ring-opening transesterification polymerization (ROTEP) catalysts, and a variety of the features of these catalysts, including the origin of their stereoselectivity, the mechanism of the inversion of catalyst chirality, and the relative stereoselectivity of the catalysts in the initiation stage, and the mechanism of stereoselectivity in the propagation stage, were described.Item Structural enzymology of soluble methane monooxygenase protein-protein interactions.(2021-05) Jones, JasonSoluble methane monooxygenase (sMMO) is a multicomponent metalloenzyme that activates molecular oxygen, breaks the 105 kcal/mol C-H bond of CH4, and inserts one atom of O to create methanol at ambient temperature and pressure. This feat of catalytic prowess requires all three protein components of sMMO for efficient multiple turnover catalysis: the hydroxylase (sMMOH), the reductase (MMOR), and the regulatory protein (MMOB). The structural mechanism of how these sMMO components interact to regulate the formation and decay of the chemical intermediates of the reaction cycle is not well understood. Our recent advances in sMMOH expression and purification have allowed us to obtain protein crystals of the sMMOH:MMOB complex. Using X-rays generated by either an X-ray free electron laser at room temperature or a synchrotron at 100 K, we obtained high resolution structures of the Methylosinus trichosporium OB3b sMMOH:MMOB complex for the first time. Analysis of the data shows in great detail how MMOB modulates the structure of sMMOH during the steps leading up to O2 binding. New insight is gained about the path O2 and methane take into the sMMOH active site, and how the selectivity and timing of this entry is controlled by MMOB in the sMMOH:MMOB complex. Additionally, biosynthetic incorporation of 5-fluorotryptophan into MMOB and MMOR, as well as post-translational modification of an MMOB variant with a trifluoroacetone probe, allowed us to use 1D-19F-NMR to investigate the complex series of sMMO protein interactions that regulate the beginning of the sMMO catalytic cycle. A new model emerges describing how sMMO protein component affinities and exchange from protein-protein complexes control the dynamics of reaction cycle intermediates to drive catalysis.