Date of Award

Spring 5-15-2022

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

Advisor(s)

Doyle, Robert P.

Second Advisor

Zubieta, Jon A.

Keywords

Magnesium, Micronutrient, Nutraceuticals

Subject Categories

Chemistry | Physical Sciences and Mathematics

Abstract

This thesis focuses on the treatment of micronutrient deficiency, specifically hypomagnesemia, through the synthesis and solution- and solid-state characterization of "pharma grade", biorelevant magnesium complexes (nutraceuticals) utilizing short-chain peptides (di- and tri-), pyrones, and amino acids. There is further emphasis placed on determining the in vitro uptake of all produced complexes. This work aims to mitigate the shortcomings of current magnesium supplements and better illustrate an understanding of the factors impacting magnesium uptake. Specifically, 1) There is a paucity of information regarding the coordination of biorelevant ligands to magnesium, most of which was investigated between the 1950s and 1980s, and that provided inconclusive structural determination of the resultant complexes and their impurities. 2) Current magnesium supplements suffer from a lack of proper characterization given an absence of strict regulations as are present in pharmaceuticals 3) The most ubiquitously used magnesium supplements often place emphasis on a high percentage magnesium composition, but exhibit poor water solubility and subsequently poor bioavailability thus resulting in less substantial magnesium uptake Q1. (Chapter 2) What is the expected ligand coordination of magnesium complexes and how does Mg2+ coordination manifest when probed utilizing 1D and 2D 1H/13C NMR? Goals: Synthesize and characterize a series of Mg2+ complexes utilizing pyrones and amino acids and employ 1D and 2D 1H/13C NMR to determine the mode of coordination assumed by the Mg2+ coordinate ligands. Furthermore, better outline how Mg2+ coordination is observed and manifested on NMR spectra (e.g., signal intensity reduction, resolution changes, shifting, etc.) Q2. (Chapter 3) Given the affinity for water of Mg2+, can solid-state methods be employed to determine the degree of complex hydration and elucidate the general composition of the Mg2+-complex core composition and provide additional insight as to the coordination mode of Mg2+ coordinate ligands? Goals: To utilize thermal analyses (TGA/DSC) and elemental analysis to determine the degree of hydration exhibited by the synthesized Mg2+ complexes and to determine the core structure of said synthesized complexes. Q3. (Chapter 4) How does Mg2+ complex solubility impact the overall cellular uptake of Mg2+ from synthesized complexes? Goals: To determine the solubility of synthesized Mg2+ complexes and determine if there is a relationship between the solubility of the complexes and the observed in vitro uptake of Mg2+ from the respective complexes. Q4. (Chapter 6) Can other complexes using similar biorelevant metals (e.g., Zn2+) be characterized in a similar way and does ligand coordination differ from that observed for Mg2+? Goals: To determine if analogous complexes utilizing different biorelevant divalent cations (e.g., Zn2+) can be synthesized and characterized in a similar fashion. Additionally, to determine if different metals exhibit different observables when characterized utilizing NMR, given difference in electron configuration, electropositivity/electronegativity.

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