Combined Application of Density Functional Theory and Molecular Mechanics Sampling Techniques to study Chemical Systems, from Intramolecular Rearrangements to Polymerization Reactions

Abstract

Modern 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.