Advancing benchtop nuclear magnetic resonance (NMR) spectroscopy as a tool for pharmaceutical development
department or school: Science, Faculty of
department or school: Chemistry, Department of
data provider: DSpace
degree campus: UBCV
creator: Maschmeyer-Tombs, Tristan
issued: 2023-12-18T21:58:28Z
issued: 2023
related degree: Doctor of Philosophy - PhD
degree grantor: University of British Columbia
description: The ability to quantitatively monitor chemical species through a reaction allows for insight to enhance process efficiency and/or safety. Nuclear magnetic resonance (NMR) spectroscopy is a powerful analytical technique, known for the ability to provide structural and quantitative data in a non-destructive manner. There has been significant growth in the development and availability of benchtop NMR spectrometers in the last decade. The use of permanent magnets result in smaller applied magnetic fields, a decrease in sensitivity and signal dispersion, but a more compact size and affordable cost. Particularly, benchtop NMR can allow for the powerful analytical capabilities associated with NMR spectroscopy to enter non-traditional settings, such as a synthetic laboratory. Therefore, this thesis focuses on leveraging these systems for reaction monitoring. First, an on-line continuous-flow benchtop NMR system is explored. Particular attention is given to the impact of flow on the mixing behaviour of analyte within the flow cell, mixing/emptying behaviour, the spin-lattice relaxation time, and sensitivity of data measurement with two sets of acquisition parameters. The complex nature of continuous-flow analyses prompted the development and application of an on-line stopped-flow benchtop NMR system, with all hardware centrally controlled with a Python script. The utility of this system was showcased using difficult to monitor model reaction systems. These reactions include activation of a carboxylic acid with sulfuryl fluoride (SO₂F₂) and carbamate formation as a result of an alcohol reacting with an isocyanate resultant from a modified Curtius rearrangement. An external calibration quantitative NMR (qNMR) method is further highlighted, allowing for robust qNMR analyses without an internal standard or special hardware. The utility of the qNMR method is demonstrated by monitoring all synthetic steps of a highly relevant chemical transformation to the pharmaceutical industry:…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/86975
note: ADVANCING BENCHTOP NUCLEAR MAGNETIC RESONANCE (NMR) SPECTROSCOPY AS A TOOL FOR PHARMACEUTICAL DEVELOPMENT by Tristan Maschmeyer-Tombs B.Sc. with Honors, University of California, Santa Cruz, 2018 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Chemistry) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) December 2023 © Tristan Maschmeyer-Tombs, 2023 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the dissertation entitled: Advancing Benchtop Nuclear Magnetic Resonance (NMR) Spectroscopy as a Tool for Pharmaceutical Development submitted by Tristan Maschmeyer-Tombs in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Chemistry Examining Committee: Jason E. Hein, Associate Professor, Chemistry, UBC Supervisor Parisa Mehrkhodavandi, Professor, Chemistry, UBC Supervisory Committee Member Glenn M. Sammis, Professor, Chemistry, UBC University Examiner Dan Bizzotto, Professor, Chemistry, UBC University Examiner Additional Supervisory Committee Members: Martin E. Tanner, Professor, Chemistry, UBC Supervisory Committee Member Raymond J. Andersen, Professor, Chemistry, UBC Supervisory Committee Member iii Abstract The ability to quantitatively monitor chemical species through a reaction allows for insight to enhance process efficiency and/or safety. Nuclear magnetic resonance (NMR) spectroscopy is a powerful analytical technique, known for the ability to provide structural and quantitative data in a non-destructive manner. There has been significant growth in the development and availability of benchtop NMR spectrometers in the last decade. The use of permanent magnets result in smaller applied magnetic fields, a decrease in sensitivity and signal dispersion, but a more compact size and affordable cost. Particularly, benchtop NMR can allow for the powerf…
has type: Thesis/Dissertation
date issued: 2024-05
is shown at: 10.14288/1.0438307
language: eng
degree discipline: Chemistry
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
contributor: Hein, Jason
type: Text
identifier URI: http://hdl.handle.net/2429/86975