Synthesis, Structure and Properties of a Novel “Frustrated” Benzoxaborole and the Role of Boron in Bioconjugation

  • Author / Creator
    Bhangu, Jasmine
  • Chapter 2 describes an optimized 7-step successful synthesis of a first of its kind permanently open-form ortho-hydroxyalkyl arylboronic acid, otherwise known as a “frustrated benzoxaborole”, with a columnless purification and complete structure elucidation. This novel compound is completely water soluble due to its pKa of 7.5, which is unexpectedly low for a non-deactivated boronic acid. The rationale behind this low pKa is due to the ortho hydroxy involvement in stabilizing the trihydroxyboronate conjugate base by H-bonding to one of the boronate oxygens. Conjugation of this new compound with biological amino and thiol groups was comparable with current methods involving ortho formyl and acetyl phenylboronic acid.
    Chapter 3 summarizes collaborative work with the National Research Council in Halifax for the development of a boronic acid polymer gel column “catch-and-release” system of diol containing marine neurotoxins. Such a system would provide pre-purification of toxins to eliminate background noise for easier detection in analytical methods. A survey of 22 boronic acids was conducted for efficient boronate ester formation and acid hydrolysis utilizing tetrodotoxin as a model. 2-(Trifluoromethyl)phenylboronic acid proved to be the ideal compound and was redesigned and synthesized with a conjugatable carboxylic acid for installation on a polymer gel.
    Chapter 4 highlights work done in collaboration with Prof. Brudno at the University of North Carolina for the in vivo imaging of a boronate/thiosemicarbazone systems developed by the Hall Group. The previously published synthesis of the precursors was improved in terms of yield, purity and reproducibility, as well as derivatized for detection by fluorescence microscopy. The imaging in live mice was shown to be promising and future work will be planned to optimize the system.

  • Subjects / Keywords
  • Graduation date
    Spring 2020
  • Type of Item
  • Degree
    Master of Science
  • DOI
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