Construction of Lewis Pairs for Optimal Enantioresolution via Recognition-Enabled "Chromatographic" 19F NMR Spectroscopy.

Chirality is a ubiquitous phenomenon in nature, serving as a foundation for a variety of life activities on earth. Separation-free methods that rapidly and accurately distinguish chiral analytes in complex systems are highly demanded in fields ranging from drug quality control to the screening of privileged chiral catalysts. However, in situ enantidifferentiation methods possessing resolution and tunability that are comparable to those achieved by chiral high-performance liquid chromatography are rare. Herein, we report a Lewis pair-based system for enantioanalysis via recognition-enabled "chromatographic" 19F NMR spectroscopy. The construction of Lewis pairs renders the detecting system not only enhanced affinity to chiral analytes but also superior and tunable resolving capability. Using this strategy, as many as 16 chiral analytes are simultaneously resolved without need for separation, thus opening new avenues for the development of precise and real-time detection methods that are robust enough for dealing with complex real-world samples.

[1]  Zhenchuang Xu,et al.  Tailoring Sensors and Solvents for Optimal Analysis of Complex Mixtures Via Discriminative 19F NMR Chemosensing. , 2021, Analytical chemistry.

[2]  Sumin Jang,et al.  Direct Chiral 19F NMR Analysis of Fluorine-Containing Analytes and Its Application to Simultaneous Chiral Analysis. , 2020, Organic letters.

[3]  Yanchuan Zhao,et al.  Separation-free Enantiodifferentiation with Chromatogram-like Output , 2020 .

[4]  Si‐Yong Qin,et al.  Measurement of Residual Dipolar Couplings of Organic Molecules in Multiple Solvent Systems using a Liquid Crystalline based Medium. , 2020, Angewandte Chemie.

[5]  Wen‐Xiong Zhang,et al.  Frustrated Lewis Pairs: Discovery and Overviews in Catalysis , 2020, Chinese Journal of Chemistry.

[6]  K. Engel.  Chirality- an important phenomenon regarding biosynthesis, perception and authenticity of flavour compounds. , 2020, Journal of agricultural and food chemistry.

[7]  A. Meddour,et al.  Multinuclear NMR in polypeptide liquid crystals: Three fertile decades of methodological developments and analytical challenges. , 2020, Progress in nuclear magnetic resonance spectroscopy.

[8]  P. Schmieder,et al.  Stereochemical Elucidation of Natural Products from Residual Chemical Shift Anisotropies in a Liquid Crystalline Phase. , 2019, Journal of the American Chemical Society.

[9]  I. Leito,et al.  On the Basicity of Organic Bases in Different Media , 2019, European Journal of Organic Chemistry.

[10]  C. Tormena,et al.  Enantiodiscrimination by matrix-assisted DOSY NMR. , 2019, Chemical communications.

[11]  Zhenchuang Xu,et al.  Molecular Sensors for NMR-Based Detection. , 2018, Chemical reviews.

[12]  E. Chen,et al.  Polymerization of Polar Monomers Mediated by Main-Group Lewis Acid-Base Pairs. , 2018, Chemical reviews.

[13]  the Acmg Seli committee,et al.  Laboratory analysis of organic acids, 2018 update: a technical standard of the American College of Medical Genetics and Genomics (ACMG) , 2018, Genetics in Medicine.

[14]  Hongping Xiao,et al.  A Self-Assembled Oligopeptide as a Versatile NMR Alignment Medium for the Measurement of Residual Dipolar Couplings in Methanol. , 2017, Angewandte Chemie.

[15]  C. Welch.  Are We Approaching a Speed Limit for the Chromatographic Separation of Enantiomers? , 2017, ACS central science.

[16]  C. Thiele,et al.  Synthesis of Poly-γ-S-2-methylbutyl-l-glutamate and Poly-γ-S-2-methylbutyl-d-glutamate and Their Use as Enantiodiscriminating Alignment Media in NMR Spectroscopy. , 2017, Chemistry.

[17]  Y. Okamoto,et al.  Efficient Separation of Enantiomers Using Stereoregular Chiral Polymers. , 2016, Chemical reviews.

[18]  Hyunwoo Kim,et al.  (1)H NMR chiral analysis of charged molecules via ion pairing with aluminum complexes. , 2015, Journal of the American Chemical Society.

[19]  H. Zimmermann,et al.  Enantiotopic discrimination in the NMR spectrum of prochiral solutes in chiral liquid crystals. , 2015, Chemical Society reviews.

[20]  D. Stephan.  Frustrated Lewis Pairs. , 2015, Journal of the American Chemical Society.

[21]  F. Mancin,et al.  Nanoparticle-assisted NMR detection of organic anions: from chemosensing to chromatography. , 2015, Journal of the American Chemical Society.

[22]  Eric V Anslyn,et al.  Rapid optical methods for enantiomeric excess analysis: from enantioselective indicator displacement assays to exciton-coupled circular dichroism. , 2014, Accounts of chemical research.

[23]  Cuirong Sun,et al.  Qualitative and quantitative analysis of enantiomers by mass spectrometry: application of a simple chiral chloride probe via rapid in-situ reaction. , 2014, Analytica chimica acta.

[24]  M. Pérez‐Trujillo,et al.  13C NMR spectroscopy for the differentiation of enantiomers using chiral solvating agents. , 2013, Analytical chemistry.

[25]  F. Mancin,et al.  "NMR chemosensing" using monolayer-protected nanoparticles as receptors. , 2013, Journal of the American Chemical Society.

[26]  J. Teichert,et al.  Chemical sensing of polyols with shapeshifting boronic acids as a self-contained sensor array. , 2013, Journal of the American Chemical Society.

[27]  Christian Wolf,et al.  Chirality sensing using stereodynamic probes with distinct electronic circular dichroism output. , 2013, Chemical Society reviews.

[28]  R. Mason,et al.  New frontiers and developing applications in 19F NMR. , 2013, Progress in nuclear magnetic resonance spectroscopy.

[29]  Yawen Wang,et al.  Emerging chirality in nanoscience. , 2013, Chemical Society reviews.

[30]  V. Schurig.  Differentiation of Enantiomers II , 2013 .

[31]  N. Suryaprakash,et al.  A versatile resolving agent for diffusion edited separation of enantiomers, complex mixtures and constitutional isomers , 2012 .

[32]  J. Seco,et al.  Assignment of the absolute configuration of polyfunctional compounds by NMR using chiral derivatizing agents. , 2012, Chemical reviews.

[33]  L. Pu.  Enantioselective fluorescent sensors: a tale of BINOL. , 2012, Accounts of chemical research.

[34]  T. Wenzel,et al.  Using NMR spectroscopic methods to determine enantiomeric purity and assign absolute stereochemistry. , 2011, Progress in nuclear magnetic resonance spectroscopy.

[35]  W C Guida,et al.  The significance of chirality in drug design and development. , 2011, Current topics in medicinal chemistry.

[36]  N. Garti,et al.  NMR chromatography using microemulsion systems. , 2011, Langmuir : the ACS journal of surfaces and colloids.

[37]  S. Caldarelli.  Chapter 5 - Chromatographic NMR , 2011 .

[38]  O. Hucke,et al.  Development of Specific “Drug‐Like Property” Rules for Carboxylate‐Containing Oral Drug Candidates , 2010, ChemMedChem.

[39]  B. Kasprzyk-Hordern.  Pharmacologically active compounds in the environment and their chirality. , 2010, Chemical Society reviews.

[40]  Sami Heikkinen,et al.  General chromatographic NMR method in liquid state for synthetic chemistry: polyvinylpyrrolidone assisted DOSY experiments. , 2009, Organic letters.

[41]  N. Garti,et al.  High-resolution NMR "chromatography" using a liquids spectrometer. , 2008, Journal of magnetic resonance.

[42]  S. Viel,et al.  Chromatographic NMR in NMR solvents. , 2008, Journal of magnetic resonance.

[43]  R. Berkecz,et al.  Application of chiral derivatizing agents in the high-performance liquid chromatographic separation of amino acid enantiomers: a review. , 2008, Journal of pharmaceutical and biomedical analysis.

[44]  T. Hoye,et al.  Mosher ester analysis for the determination of absolute configuration of stereogenic (chiral) carbinol carbons , 2007, Nature Protocols.

[45]  Takashi Sakai,et al.  Versatile and practical macrocyclic reagent with multiple hydrogen-bonding sites for chiral discrimination in NMR. , 2007, Journal of the American Chemical Society.

[46]  L. Ai,et al.  New macrocyclic compound as chiral shift reagent for carboxylic acids. , 2007, Organic letters.

[47]  A. Ellern,et al.  Facile synthesis of monomeric alumatranes. , 2006, Journal of the American Chemical Society.

[48]  S. Caldarelli,et al.  Simplified analysis of mixtures of small molecules by chromatographic NMR spectroscopy. , 2006, Angewandte Chemie.

[49]  Y. Suzuki,et al.  Organic acids and branched-chain amino acids in body fluids before and after multiple exchange transfusions in maple syrup urine disease , 1983, Journal of Inherited Metabolic Disease.

[50]  R. Bentley.  Role of sulfur chirality in the chemical processes of biology. , 2005, Chemical Society reviews.

[51]  J. Seco,et al.  The assignment of absolute configuration by NMR , 2004 .

[52]  S. Viel,et al.  Enhanced diffusion-edited NMR spectroscopy of mixtures using chromatographic stationary phases , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[53]  T. Wenzel,et al.  Chiral reagents for the determination of enantiomeric excess and absolute configuration using NMR spectroscopy. , 2003, Chirality.

[54]  H. C. Aspinall.  Chiral lanthanide complexes: coordination chemistry and applications. , 2002, Chemical reviews.

[55]  P. Cintas.  Chirality of living systems: a helping hand from crystals and oligopeptides. , 2002, Angewandte Chemie.

[56]  Y. Kim,et al.  Ion Pair Basicity of Some Amines in THF: Implications for Ion Pair Acidity Scales1 , 2000 .

[57]  J. Courtieu,et al.  Theoretical and experimental aspects of enantiomeric differentiation using natural abundance multinuclear nmr spectroscopy in chiral polypeptide liquid crystals , 2000 .

[58]  J. Seco,et al.  Choosing the Right Reagent for the Determination of the Absolute Configuration of Amines by NMR: MTPA or MPA?† , 1997 .

[59]  K. Nozaki,et al.  Highly Efficient Enantioselective Synthesis of Optically Active Carboxylic Acids by Ru(OCOCH3)2[(S)-H8-BINAP] , 1996 .

[60]  Karel Heremans,et al.  How to Minimize Certain Artifacts in Fourier Self-Deconvolution , 1995 .

[61]  D. Parker.  NMR Determination of Enantiomeric Purity , 1991 .

[62]  S. Roberts.  Chirality and its importance in drug development: a synthetic chemist's perspective. , 1991, Biochemical Society transactions.

[63]  S. Benson,et al.  Use of carboxylic acids as chiral solvating agents for the determination of optical purity of chiral amines by NMR spectroscopy , 1988 .

[64]  Laurence D. Barron,et al.  Symmetry and molecular chirality , 1986 .

[65]  H. Mantsch,et al.  Fourier transforms in the computation of self-deconvoluted and first-order derivative spectra of overlapped band contours , 1981 .

[66]  H. Mantsch,et al.  Noise in Fourier self-deconvolution. , 1981, Applied optics.

[67]  Douglas J. Moffatt,et al.  Fourier Self-Deconvolution: A Method for Resolving Intrinsically Overlapped Bands , 1981 .