| dc.description.abstract | Chirality permeates through modern science, from the spin of elementary particles to mechanisms underlying biological life processes. The amino acids and sugars from which proteins and nucleic acids are built exhibit chirality. Chirality of molecules used for drugs can alter their bio-reactivity. The field of chiroptical spectroscopy has been established to probe and investigate chiral molecules. A theoretical framework has been derived using quantum mechanics. Modern computing power has allowed for the implementation of routine quantum chemical (QC) predictions of spectral properties. The goal of many parts of this project was to determine the absolute configuration (AC) of natural products and small synthetic molecules through direct QC prediction of chiroptical spectra. However, more often than not, more robust methods, techniques, or experimental planning were necessary to unequivocally determine the AC or other structural information for many compounds. These procedures and practices that have been employed include but are not limited to the following: (a) concerted investigation on chiroptical properties of a compound and a stereochemically unaltered derivative of that compound, excluding explicit hydrogen bonding solvent when the circumstances permit, (b) predicting Raman optical activity (ROA) on monomer conformers of dimer forming molecules, (c) using dissymmetry factor spectra as a tool for diastereomer discrimination, (d) utilizing systematic placement of explicit solvent molecules for QC predictions rather than extensive molecular dynamic simulations. These studies have demonstrated their value in teasing out structural details that may be missed or otherwise indiscernible. During these investigations I have also shown for the first time with QC predictions the importance of the electric-dipole--electric-quadrupole polarizability tensor contribution in ROA. | |
