Advanced NMR Methods for Complex Mixture Analysis Driven by Industrial Challenges

  • Emma Gates

Student thesis: Phd

Abstract

NMR (nuclear magnetic resonance) spectroscopy is widely utilised across a diverse range of chemical and biological applications, offering a unique insight into the chemical environment of a nucleus. In solution-state NMR spectroscopy, studies typically revolve around the hydrogen (1H) nucleus, favoured for its relatively high sensitivity, and abundance in organic compounds. 1H NMR spectral analysis can be complicated in cases of complex samples or mixtures; the relatively narrow range of 1H chemical shifts and wide multiplet features leads to signals overlapping, increasing difficulties in signal identification, structure elucidation and molecular conformation analysis. This is a common challenge faced in industrial settings where complex mixtures with high dynamic ranges are common; for example, in the study of pharmaceutical formulations where impurities and excipients complicate analysis by conventional NMR methods. This thesis introduces new solution-state NMR experiments that aim to simplify 1H spectral analysis. The methods introduced build on recent developments from the NMR community, including pure shift NMR, where the effect of homonuclear scalar couplings are suppressed from spectra; ultraselective 1D methods, where single signals are observed despite signal overlap; and 1D heteronuclear spectral editing methods, where exploiting heteronuclear scalar couplings enables previously inaccessible 1H spin systems to be identified. These methods are shown to aid spectral analysis of a broad range of samples, including structurally complex oligosaccharides, alkaloid mixtures, hydrindane byproducts, phosphorous-containing metabolites, and pharmaceutical formulations. This thesis is comprised of journal-formatted research chapters:  Chapter 1 contains an overview of the thesis, highlighting the relevance of the research conducted.  Chapter 2 describes NMR theory and literature relevant to the thesis topics.  Chapters 3 – 7 contain five journal-formatted research chapters.  Chapter 8 reflects on the studies conducted and describes potential future work and applications.  Chapter 9 lists references used in the introductory chapters.  Appendices I and II contain two further journal articles (reported in Dr. Marshall J. Smith’s and Dr. Coral Mycroft’s theses, respectively, and which the author contributed to as a co-author).
Date of Award1 Aug 2025
Original languageEnglish
Awarding Institution
  • The University of Manchester
SupervisorGareth Morris (Supervisor), Ralph Adams (Supervisor) & Laura Castanar Acedo (Supervisor)

Keywords

  • Phosphorus
  • Proton
  • Pure shift
  • GEMSTONE
  • NMR
  • Complex mixtures

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