Schenck, George, Baj, Krzysztof, Iggo, Jonathan A and Wallace, Matthew ORCID: 0000-0002-5751-1827
(2022)
Efficient p<i>K</i><sub>a</sub> Determination in a Nonaqueous Solvent Using Chemical Shift Imaging.
Analytical chemistry.
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Abstract
p<i>K</i><sub>a</sub> is an important property of a molecule which impacts many fields, such as drug design, catalysis, reactivity, and environmental toxicity. It is often necessary to measure p<i>K</i><sub>a</sub> in nonaqueous media due to the poor solubility of an analyte in water, for example, many compounds of pharmaceutical interest. Although NMR methods to measure p<i>K</i><sub>a</sub> in water are well established, determining p<i>K</i><sub>a</sub> in organic solvents is laborious and problematic. We present an efficient one-shot method to determine the p<i>K</i><sub>a</sub> of an analyte in an organic solvent in a single measurement. Diffusion of an acid into a basic solution of the analyte and a set of pH indicators establishes a pH gradient in the NMR tube. The chemical shift of a pH sensitive resonance of the analyte and the pH of the solution are then determined simultaneously as a function of position along the pH gradient by recording a chemical shift image of the NMR tube. The p<i>K</i><sub>a</sub> of the analyte is then determined using the Henderson-Hasselbalch equation. The method can be implemented in any laboratory with a gradient equipped NMR high-field spectrometer and is demonstrated for a range of pharmaceutical compounds and inorganic phosphazene bases.
Item Type: | Article |
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Divisions: | Faculty of Science and Engineering > School of Physical Sciences |
Depositing User: | Symplectic Admin |
Date Deposited: | 13 May 2022 14:18 |
Last Modified: | 18 Jan 2023 21:03 |
DOI: | 10.1021/acs.analchem.2c00200 |
URI: | https://livrepository.liverpool.ac.uk/id/eprint/3154734 |
Available Versions of this Item
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