Determination of pKa in Non-Aqueous Solution using Chemical Shift Imaging

使用化学位移成像测定非水溶液中的 pKa

• 批准号: 1797785
• 金额: --
• 依托单位: University of Liverpool
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1797785
• 关键词: Determination; pKa; Non; Aqueous; Solution

pKa is a measure of the acidity of a molecule/ion (i.e. the ease with which it loses a proton). It is a widely used parameter in catalysis, pharmacology and chemical synthesis, allowing the prediction of chemical and physical behaviour of species in solution. Reactivity, solubility and the nature of chemical interaction are all governed by the protonation state of a molecule, and thereby its pKa. pKa is usually determined in aqueous solution, but frequently a compound is too insoluble or too reactive to do so. DMSO is commonly used as an alternative, as it is a relatively inert polar aprotic solvent supporting a wide pKa range (up to 35). Water solvates both cations and anions well while DMSO solvates cations well and anions poorly, making meaningful comparisons between pKaDMSO and pKa(aq) difficult. Experimental determination of pKa in DMSO is therefore necessary. Various methods are available to determine pKa, each with its advantages and drawbacks. Non-aqueous pKa measurements add another dimension of difficulty. In the example of potentiometric methods, equipment designed for aqueous measurements often must be adapted to the non-aqueous medium, risking equipment damage and inaccurate results.NMR titration methods are well known in the literature, with a range of NMR active nuclei available including 1H, 13C and 31P. Pure compounds are not necessary (as they must be for conductimetry) and no equipment modification is needed to measure in non-aqueous medium. The conventional NMR titration requires the acquisition of a large series of NMR spectra taken at incrementally changing pH. This is a labour intensive procedure requiring a large sample volume and long instrument times. As an alternative, we have developed a one-shot titration method for determining the pKa of compounds in DMSO solution. Using a set of NMR pH indicators and chemical shift imaging techniques, we can measure the pH of a sample as a function of position along a pH gradient within an NMR tube. From a single measurement we can determine the pKa of an acidic or basic analyte. The pKa of analytes determined using this method are in good agreement with literature values ( 0.1 units) and have been shown to be self-correcting for solution ionic strength.

pKa是分子/离子酸度的量度（即失去质子的容易程度）。它是催化、药理学和化学合成中广泛使用的参数，可以预测溶液中物质的化学和物理行为。反应性、溶解性和化学相互作用的性质都受分子的质子化状态以及其pKa的控制。pKa通常在水溶液中测定，但通常化合物太不溶或反应性太强而无法测定。DMSO通常用作替代品，因为它是一种相对惰性的极性非质子溶剂，支持较宽的pKa范围（高达35）。水能很好地溶剂化阳离子和阴离子，而DMSO能很好地溶剂化阳离子，而溶剂化阴离子很差，这使得pKaDMSO和pKa（aq）之间难以进行有意义的比较。因此，有必要通过实验测定DMSO中的pKa。有多种方法可用于确定pKa，每种方法都有其优点和缺点。非水pKa测量增加了另一个方面的困难。在电位滴定法的例子中，设计用于水性测量的设备通常必须适应非水性介质，这会带来设备损坏和结果不准确的风险。NMR滴定法在文献中是众所周知的，可获得一系列NMR活性核，包括1H、13 C和31 P。纯化合物是不必要的（因为它们必须用于电导测定），并且不需要对设备进行修改以在非水介质中进行测量。传统的NMR滴定法需要在pH值逐渐变化的情况下采集大量的NMR光谱。这是一个劳动密集型过程，需要大量的样品和较长的仪器时间。作为一种替代方法，我们已经开发了一种一次性滴定法用于测定化合物在DMSO溶液中的pKa。使用一组NMR pH指示剂和化学位移成像技术，我们可以测量样品的pH值作为NMR管内pH梯度沿着位置的函数。通过单次测量，我们可以确定酸性或碱性分析物的pKa。使用该方法测定的分析物的pKa值与文献值（0.1单位）一致，并且已被证明对溶液离子强度具有自校正作用。