Molecular Studies in Mercury Toxicity Using X-ray Absorption Spectroscopy and High Energy Resolution Fluorescence Detection X-ray Absorption Spectroscopy

Abstract

Molecular understanding of mercury compounds is of considerable interest as the element is pervasive in the environment and certain chemical forms are highly toxic to humans at very low doses. Chalcogenides have high affinity for mercury and one in particular, selenium, may play a major role in the mechanisms involved with mercury toxicity in vivo. In this dissertation, conventional X-ray absorption spectroscopy (XAS) and high-energy resolution fluorescence detection X-ray absorption spectroscopy (HERFD XAS) have been employed to identify the chemical coordination of mercury with various ligand types relevant to mercury toxicity. XAS and density functional theory (DFT) calculations were used to identify the molecular structures responsible for the drastic changes in toxicity in zebrafish larvae exposed to a common hypopigment-inducer 1-phenyl-2-thiourea. Next, XAS and X-ray fluorescence imaging (XFI) were used to investigate the fate of mercury localization in zebrafish larvae following treatment with the dithiol 1,3-benzene-diamido-2-carboxylethanethiol. During the course of exploring the molecular structure of various mercury-ligand complexes, it was evident that current methods to probe the electronic structure of mercury compounds are met with challenges, and capabilities to observe richer spectroscopy would significantly benefit molecular studies of mercury toxicity. Hence, the quest to develop methods for enhanced chemical characterization using HERFD XAS was pursued to reveal the potential of increased chemical specificity and improved concentration sensitivity of this technique in natural relevant levels of a series of mercury and selenium compounds. The results present substantial improvements in chemical characterization of mercury and selenium compounds for applications in the study of mercury toxicity. HERFD XAS was thereupon employed as a complementary tool to conventional XAS in the investigations of species identification of mercury and selenium compounds in cases of biological organisms. XAS, HERFD XAS, and quantum-mechanical/molecular-mechanical (QM/MM) studies were employed to examine the interaction of Hg(II) with 1-methylthymine and a canonical DNA helix to understand this mode of biological coordination of Hg(II). Finally, mammalian tissue is examined to reveal unreported chemical species in a historical specimen showing signs of organomercury poisoning from Minamata Bay, Japan.