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

• Applicant: Privatdozent Dr. Alexander Schiller
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation ; Analytical Chemistry ; Biological and Biomimetic Chemistry
• Term: from 2015 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 266495512

• Final Report Year: 2019

Final Report Abstract

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. We have combined fluorine moieties on arene boronic acids to create a new generation of supramolecular receptors for diol-containing analytes at physiological conditions. In addition, anions, such as fluoride, cyanide and phosphates have been included as they proved already to bind to boronic acids. Our main target was the discrimination of biological substrates in aqueous solution via 19F NMR, such as sugars, phosphosugars, nucleotides, oligo-RNAs, and catechol compounds. The overall objective of this project was the synthesis and characterization of novel fluorinated boronic acids to detect and discriminate diol-containing analytes and anions via 19F NMR at physiological conditions. We learnt which aspects, such as water solubility, pKa and analyte selectivity, can be already addressed by commercially available and literature-known fluorinated boronic acids. Density functional theory (DFT) methods provided theoretical 19F NMR shifts. Boronic acid appended pyridinium and imidazolium salts with improved properties in water solubility and analyte selectivity have been developed; replacing the fluorine moiety by CF3-groups helped to vary sensitivity. With DFT calculations we were able to predict 19F NMR shifts in combination with specific diol-containing analytes. 19F NMR signals of a group of analytes from several fluorinated receptors have been processed by multivariate analysis to discriminate challenging substrates. Easy-to-read barcodes (1D and 2D) have been generated from 19F NMR spectra and the new concept of acousto-visual discrimination has been established. Fluorinated boronic acids have been used to follow carbohydrate-active enzyme reactions. The transformation produces diols with high binding affinities to the fluorinated boronic acids. Enzyme kinetics were followed by 19F NMR. The interaction of sialic-acid coated nanoparticle(s) with the surface of influenza virus was probed with the fluorinated boronic acid receptors via displacement assay. It was not successful.

Publications

• Fluorinated Boronic Acid-Appended Bipyridinium Salts for Diol Recognition & Discrimination via 19F NMR Barcodes. J. Am. Chem. Soc. 137, 15402-15405 (2015)
  Axthelm, J.; Görls, H.; Schubert, U. S. & Schiller, A.
  
• Fluorinated Boronic Acid-Appended Pyridinium Salts and 19F NMR Spectroscopy for Diol Sensing. J. Am. Chem. Soc. 139, 11413–11420 (2017)
  Axthelm, J.; Elstner, M.; Reddy, G. U.; Görls, H.; Bellstedt, P.; Schiller, A.