Detection and differentiation of diols by 19F NMR with fluorinated benzene boronic acids

含硼酸的分子探针已被开发为识别含二醇分析物的化学传感器，如碳水化合物、核苷酸、儿茶酚和羟基羧酸。本项目的目标是合成和表征新型含氟硼酸，以便在生理条件下通过~(19)F核磁共振检测和区分含二醇的分析物和阴离子。例如，氟苯硼酸中氟核的存在提供了一种对硼部分的结合环境极其敏感的核磁共振探针。当在生理介质中将糖添加到受体上时，硼酸被转化为硼酸酯，从而导致19F核磁共振谱中的化学位移。首先，我们研究商业上可以买到的含氟芳烃硼酸的二元醇。我们将学习哪些方面，如水的溶解度，pKA和分析物的选择性，已经可以通过商业和文献已知的氟化硼酸来解决。密度泛函理论(DFT)方法将提供~(19)F核磁共振理论位移。随后，将合成具有更好的水溶性和分析物选择性的新型受体。在水溶性和分析物选择性方面，添加了吡啶盐和咪唑盐的硼酸将是理想的候选物。用CF3-基团取代氟部分将有助于提高灵敏度。通过密度泛函计算，我们将能够结合特定的含有二元醇的分析物来预测19F核磁共振位移。然后，将建立含氟硼酸受体的传感器阵列和模式分析。来自几个氟化受体的一组分析物的19F核磁共振信号将被多变量分析处理以识别具有挑战性的底物。19F核磁共振波谱将产生易于阅读的条形码和声光识别。将创建19F核磁共振酶分析来跟踪碳水化合物活性酶与氟化硼酸的反应。最后，用唾液酸包被的纳米粒子和竞争的氟化硼酸受体建立病毒检测方法，用19F核磁共振波谱检测流感病毒。

Boronic acid-containing molecular probes have been developed as chemosensors for the recognition of diol-containing analytes, such as carbohydrates, nucleotides, catechols, and hydroxyl carboxylic acids. The objective of this project is the synthesis and characterization of novel fluorinated boronic acids to detect and discriminate diol-containing analytes and anions via 19F NMR at physiological conditions. The presence of a fluorine nucleus in the fluoro-benzene boronic acid, for example, provides an NMR probe which is extremely sensitive to the binding environment of the boron moiety. When a saccharide is added to the receptor in a physiological medium, the boronic acids are converted into boronate esters inducing a chemical shift in the 19F NMR spectrum. First, we investigate diols with commercially available fluorinated arene boronic acids. We will learn which aspects, such as water solubility, pKa and analyte selectivity, can be already addressed by commercial and literature-known fluorinated boronic acids. Density functional theory (DFT) methods will provide theoretical 19F NMR shifts. Subsequently, novel receptors with improved properties in water solubility and analyte selectivity will be synthesized. Boronic acid appended pyridinium and imidazolium salts will be ideal candidates in terms of water solubility and analyte selectivity. Replacing the fluorine moiety by CF3-groups will help to improve sensitivity. With DFT calculations we will be able to predict 19F NMR shifts in combination with specific diol-containing analytes. Then sensor arrays and pattern analysis will be established with fluorinated boronic acid receptors. 19F NMR signals of a group of analytes from several fluorinated receptors will be processed by multivariate analysis to discriminate challenging substrates. Easy-to-read barcodes and acousto-visual discrimination will be generated from 19F NMR spectra. 19F NMR enzyme assays will be created to follow carbohydrate-active enzyme reactions with fluorinated boronic acids. Finally, a virus assay will be developed with sialic-acid coated nanoparticles and competing fluorinated boronic acid receptors to detect influenza virus with 19F NMR spectroscopy.