Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, U.K.
School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, U. K.
Anal Chem. 2022 Jun 14;94(23):8115-8119. doi: 10.1021/acs.analchem.2c00200. Epub 2022 May 27.
p 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 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 in water are well established, determining p in organic solvents is laborious and problematic. We present an efficient one-shot method to determine the p 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 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.
p 是分子的一个重要性质，它影响许多领域，如药物设计、催化、反应性和环境毒性。由于分析物在水中的溶解度较差，例如许多具有药物应用前景的化合物，因此通常需要在非水介质中测量 p。虽然已经建立了用于在水中测量 p 的 NMR 方法，但在有机溶剂中确定 p 是繁琐且有问题的。我们提出了一种高效的单次测量方法，可在单个测量中确定有机溶剂中分析物的 p。酸扩散到分析物的碱性溶液中和一组 pH 指示剂在 NMR 管中建立 pH 梯度。然后，通过记录 NMR 管的化学位移图像，同时确定分析物的 pH 敏感共振的化学位移和溶液的 pH 值作为沿 pH 梯度位置的函数。然后使用 Henderson-Hasselbalch 方程确定分析物的 p 值。该方法可以在配备梯度的 NMR 高场光谱仪的任何实验室中实施，并针对一系列药物化合物和无机膦氮烯碱进行了演示。
