Analytical methods for evaluation of two classes of bioactive compounds

Abstract

Analytical chemistry and techniques are the underlying support of most kinds of chemical research, as well as biological and environmental research in general, and is a broad field with many different methodologies and modalities. The major subdivisions of analytical chemistry stated in this dissertation are characterization, separation, identification, and quantification, though these fields can overlap. This dissertation focuses on two different research projects involving analytical chemistry, a project focusing on the characterization of novel compounds versus a project consisting of the separation, identification and quantification of compounds in a complex mixture. However, these different research projects are linked through their use of analytical chemistry and the fact that both research projects involve the study of bioactive compounds. Chapter 1 is an introductory chapter consisting of a discussion of the types of analytical chemistry mentioned in later chapters, as well as an overview of the projects that comprise the bulk of the dissertation. Chapter 2 details the studies used to characterize Vanadium complexes for potential use as anti-cancer agents, specifically focusing on the electrochemical evaluation of the complexes' redox properties using non-aqueous cyclic voltammetry. In addition, the hydrolytic stability of the complexes in both saline solution and DMSO was evaluated using ultraviolet-visible light spectroscopy. The potential relationship of these experimentally determined properties was compared to computed properties of the complexes calculated using the Chemicalize website. Vanadium complexes have been studied for various biological properties, as vanadium is a relativity non-toxic metal with various oxidation states. These complexes have been synthesized with a Schiff-base backbone and non-innocent catecholate ligands, which can provide a variety of redox activity on both the metal centers and the ligand. Some compounds in this class of complexes are effective against cancer cells, particularly those of dangerous brain cancers like glioblastoma, while not being overly toxic with long-term use due to the compound degrading into less harmful byproducts upon exposure to water. However, changing the catecholate ligand on these complexes significantly changes the stability and redox properties of the complexes. The potential source of the changes in hydrolytic stability and redox potentials were evaluated. Chapter 3 details the research involving the attempt to separate, identify, and quantify all 24 neutral hexoses from complex samples at very low concentrations using Gas chromatography–Mass spectrometry. It describes issues with separating enantiomers and intermolecular condensation forming rings and anomers, which further complicates separation when one does not use a chiral column. It delves into the scientific literature for possible separation methods without derivatization and why they were not used for this project. It then describes two derivatization methods for hexose separation. Chapter 4 is a concluding chapter that speaks of what was learned from these projects and the potential future directions of those projects.