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作为化学传感器用于识别含二醇的分析物，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氟化硼酸，以在生理条件下通过19 F NMR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对硼部分的结合环境极其敏感的NMR探针。当在生理介质中将糖添加到受体时，硼酸转化为硼酸酯，诱导19 F NMR光谱中的化学位移。首先，我们研究了二醇与市售的氟化芳烃硼酸。我们将了解哪些方面，如水溶性，pKa和分析物的选择性，可以已经解决了商业和文献已知的氟化硼酸。密度泛函理论（DFT）方法将提供理论19 F NMR位移。随后，将合成在水溶性和分析物选择性方面具有改进性质的新型受体。硼酸附加吡啶和咪唑盐将是理想的候选人在水溶性和分析物的选择性。用CF 3-基团取代氟部分将有助于提高灵敏度。通过DFT计算，我们将能够预测19 F NMR位移与特定的含二醇的分析物的组合。然后，传感器阵列和模式分析将建立与氟化硼酸受体。来自几种氟化受体的一组分析物的19 F NMR信号将通过多变量分析进行处理，以区分挑战性底物。将从19 F NMR光谱生成易于读取的条形码和声光辨别。将创建19 F NMR酶测定，以跟踪碳水化合物活性酶与氟化硼酸的反应。最后，将开发一种病毒检测方法，使用硅酸涂层纳米颗粒和竞争性氟化硼酸受体，以19 F NMR光谱法检测流感病毒。

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.