qXNMR - qNMR with Nuclei other than Protons and Carbons

Additional Supporting Information for the Following or Our qNMR Publications:

Besides protons and carbons, other nuclei amenable to NMR spectrocsopy can be used for quantitative analysis. The foremost examples are 31P (qPNMR) representing a nucleus found in a myriad of phosphorylated metabolites, and 19F (qFNMR) found in numerous drug molecules containing stabile -F and -CH3 functional groups.

While nitrogen is a very important nucleus from a life science and biomedical perspective, its direct observation is complicated by the low abundance of 15N and its long relaxation characteristics. Accordingly, while qNNMR is technically possible, its practical implementation is challenging and reports are sparse.

A selection of publications covering the qXNMR analysis of these nuclei follows.

Quantitative Fluorine NMR (qFNMR)

  • Martino, R.; Gilard, V.; Desmoulin, F.; Malet-Martino, M. Fluorine-19 or phosphorus-31 NMR spectroscopy: a suitable analytical technique for quantitative in vitro metabolic studies of fluorinated or phosphorylated drugs. J. Pharm. Biomed. Anal. 2005, 38, 871-891.
  • Tanabe, K.; Harada, H.; Narazaki, M.; Tanaka, K.; Inafuku, K.; Komatsu, H.; Ito, T.; Yamada, H.; Chujo, Y.; Matsuda, T.; Hiraoka, M.; Nishimoto, S.-i. Monitoring of Biological One-Electron Reduction by 19F NMR Using Hypoxia Selective Activation of an 19F-Labeled Indolequinone Derivative. J. Amer. Chem. Soc. 2009, 131, 15982-15983.
  • Deng, D.; Deng, P.; Wang, X.; Hou, X. Direct Determination of Sodium Fluoride and Sodium Monofluorophosphate in Toothpaste by Quantitative 19F-NMR: A Green Analytical Method. Spectrosc. Lett. 2009, 42, 334-340.
  • Farrant, R. D.; Hollerton, J. C.; Lynn, S. M.; Provera, S.; Sidebottom, P. J.; Upton, R. J. NMR quantification using an artificial signal. Magn. Reson. Chem. 2010, 48, 753-762.
  • Turco, L.; Provera, S.; Curcuruto, O.; Bernabe, E.; Nicoletti, A.; Martini, L.; Castoldi, D.; Cimarosti, Z.; Papini, D.; Marchioro, C.; Dams, R. Detection, identification and quantification of a new de-fluorinated impurity in casopitant mesylate drug substance during late phase development: An analytical challenge involving a multidisciplinary approach. J. Pharm. Biomed. Anal. 2011, 54, 67-73.
  • Tanaka, K.; Kitamura, N.; Chujo, Y. Bimodal Quantitative Monitoring for Enzymatic Activity with Simultaneous Signal Increases in 19F NMR and Fluorescence Using Silica Nanoparticle-Based Molecular Probes. Bioconjugate Chem. 2011, 22, 1484-1490.
  • Do, N. M.; Olivier, M. A.; Salisbury, J. J.; Wager, C. B. Application of Quantitative 19F and 1H NMR for Reaction Monitoring and In Situ Yield Determinations for an Early Stage Pharmaceutical Candidate. Anal. Chem. 2011, 83, 8766-8771.
  • Bapiro, T. E.; Richards, F. M.; Goldgraben, M. A.; Olive, K. P.; Madhu, B.; Frese, K. K.; Cook, N.; Jacobetz, M. A.; Smith, D.-M.; Tuveson, D. A.; Griffiths, J. R.; Jodrell, D. I. A novel method for quantification of gemcitabine and its metabolites 2',2'-difluorodeoxyuridine and gemcitabine triphosphate in tumour tissue by LC-MS/MS: comparison with 19F NMR spectroscopy. Cancer Chemother. Pharmacol. 2011, 68, 1243-1253.
  • Mutlib, A.; Espina, R.; Atherton, J.; Wang, J.; Talaat, R.; Scatina, J.; Chandrasekaran, A. Alternate Strategies to Obtain Mass Balance without the Use of Radiolabeled Compounds: Application of Quantitative Fluorine (19F) Nuclear Magnetic Resonance (NMR) Spectroscopy in Metabolism Studies. Chem. Res. Toxicol. 2012, 25, 572-583.
  • Pourcelle, V.; Le Duff, C. S.; Freichels, H.; Jerome, C.; Marchand-Brynaert, J. Clickable PEG conjugate obtained by "clip" photochemistry: Synthesis and characterization by quantitative 19F NMR. Journal of Fluorine Chemistry 2012, 140, 62-69.
  • Howe, P. W. A. Fluorine-proton correlation from isolated trifluoromethyl groups using unresolved J-couplings. Magn. Reson. Chem. 2012, 50, 705-708.
  • Moghimi, A.; Omrani, I.; Nabid, M. R.; Mahmoodi, M. Quantification of hydroxyl group in polymers containing trace water by 19F NMR spectroscopy. Eur. Polym. J. 2013, 49, 228-234.
  • Takaoka, Y.; Kioi, Y.; Morito, A.; Otani, J.; Arita, K.; Ashihara, E.; Ariyoshi, M.; Tochio, H.; Shirakawa, M.; Hamachi, I. Quantitative comparison of protein dynamics in live cells and in vitro by in-cell 19F-NMR. Chem. Commun. 2013, 49, 2801-2803.
  • Schwarz, J. C.; Hoppel, M.; Kaehlig, H.; Valenta, C. Application of quantitative 19F nuclear magnetic resonance spectroscopy in tape-stripping experiments with natural microemulsions. J. Pharm. Sci. 2013, 102, 2699-2706.
  • Jaeger, C.; Hemmann, F. EASY: A simple tool for simultaneously removing background, deadtime and acoustic ringing in quantitative NMR spectroscopy-Part I: Basic principle and applications. Solid State Nucl. Magn. Reson. 2014, 57-58, 22-28.
  • Liu, Y.; Wei, N.-y.; Zhang, Q.; Li, X.-d.; He, L.; Yang, H.-x. Quantitative analysis of gemigliptin tartrate sesquihydrate by 19F quantitative NMR (19F-qNMR). Yaowu Fenxi Zazhi 2014, 34, 1197-1199.
  • Xu, L.; Shi, X.; Hu, K. Quantification of multiple compounds containing heterogeneous elements in the mixture by one-dimensional nuclear magnetic resonance spectroscopy of different nuclei using a single universal concentration reference. Magn. Reson. Chem. 2014, 52, 779-782.
  • Zhang, F.-F.; Jiang, M.-H.; Sun, L.-L.; Zheng, F.; Dong, L.; Shah, V.; Shen, W.-B.; Ding, Y. Quantitative analysis of sitagliptin using the 19F-NMR method: a universal technique for fluorinated compound detection. Analyst 2015, 140, 280-286.
  • Hennig, A.; Dietrich, P. M.; Hemmann, F.; Thiele, T.; Borcherding, H.; Hoffmann, A.; Schedler, U.; Jaeger, C.; Resch-Genger, U.; Unger, W. E. S. En route to traceable reference standards for surface group quantifications by XPS, NMR and fluorescence spectroscopy. Analyst 2015, 140, 1804-1808.
  • Liu, Y.; Wei, N.-y.; Yue, R.-q.; He, L.; Yang, H.-x. Application of novel 19F quantitative NMR (19F-qNMR) in assay of droperidol. Zhongguo Xinyao Zazhi 2014, 23, 1960-1962.
  • Vlasiou, M.; Drouza, C. 19F NMR for the speciation and quantification of the OH-molecules in complex matrices. Anal. Meth. 2015, 7, 3680-3684.
  • Kong, N.; Zhou, J.; Park, J.; Xie, S.; Ramström, O.; Yan, M. Quantitative Fluorine NMR To Determine Carbohydrate Density on Glyconanomaterials Synthesized from Perfluorophenyl Azide-Functionalized Silica Nanoparticles by Click Reaction. Anal. Chem. 2015, 87, ASAP

Quantitative Phosphorus NMR (qPNMR)

  • Martino, R.; Gilard, V.; Desmoulin, F.; Malet-Martino, M. Fluorine-19 or phosphorus-31 NMR spectroscopy: a suitable analytical technique for quantitative in vitro metabolic studies of fluorinated or phosphorylated drugs. J. Pharm. Biomed. Anal. 2005, 38, 871-891.
  • Martino, R.; Gilard, V.; Malet-Martino, M. Fluorine-19 or phosphorus-31 NMR spectroscopy: a powerful technique for biofluid metabolic studies and pharmaceutical formulation analysis of fluorinated or phosphorylated drugs. In: NMR Spectroscopy in Pharmaceutical Analysis, Holzgrabe, U.; Wawer, I.; Diehl, B.; Elsevier Ltd.: 2008; pp 369-406.
  • Jasiukaityte, E.; Kunaver, M.; Crestini, C. Lignin behavior during wood liquefaction-Characterization by quantitative 31P, 13C NMR and size-exclusion chromatography. Catal. Today 2010, 156, 23-30.
  • Lenevich, S.; Distefano, M. D. Nuclear magnetic resonance-based quantification of organic diphosphates. Anal. Biochem. 2011, 408, 316-320.
  • Molaabasi, F.; Talebpour, Z. Enantiomeric Discrimination and Quantification of the Chiral Organophosphorus Pesticide Fenamiphos in Aqueous Samples by a Novel and Selective 31P Nuclear Magnetic Resonance Spectroscopic Method Using Cyclodextrins as Chiral Selector. J. Agric. Food Chem. 2011, 59, 803-808.
  • Mazzei, P.; Piccolo, A. Quantitative Evaluation of Noncovalent Interactions between Glyphosate and Dissolved Humic Substances by NMR Spectroscopy. Environ. Sci. Technol. 2012, 46, 5939-5946.
  • Garrido, R.; Puyada, A.; Fernandez, A.; Gonzalez, M.; Ramirez, U.; Cardoso, F.; Valdes, Y.; Gonzalez, D.; Fernandez, V.; Verez, V.; Velez, H. Quantitative Proton Nuclear Magnetic Resonance evaluation and total assignment of the capsular polysaccharide Neisseria meningitidis serogroup X. J. Pharm. Biomed. Anal. 2012, 70, 295-300.
  • Brinkmann-Trettenes, U.; Stein, P. C.; Kloesgen, B.; Bauer-Brandl, A. A method for simultaneous quantification of phospholipid species by routine 31P NMR. J. Pharm. Biomed. Anal. 2012, 70, 708-712.
  • Zhang, A.; Chen, Z.; Chen, L.; Liang, W. Method for detecting phosphorous component in soil via sodium bicarbonate-sodium dithionite (bd) treatment and liquid 31P NMR. CN102818813A, 2012.
  • Kollo, M.; Kudrjasova, M.; Kulp, M.; Aav, R. Methylphosphonic acid as a 31P-NMR standard for the quantitative determination of phosphorus in carbonated beverages. Anal. Meth. 2013, 5, 4005-4009.
  • Melone, F.; Saladino, R.; Crestini, C. Tannin Structural Elucidation and Quantitative 31P NMR Analysis. 1. Model Compounds. J. Agric. Food Chem. 2013, 61, 9307-9315.
  • Melone, F.; Saladino, R.; Crestini, C. Tannin Structural Elucidation and Quantitative 31P NMR Analysis. 2. Hydrolyzable Tannins and Proanthocyanidins. J. Agric. Food Chem. 2013, 61, 9316-9324.
  • Lagutin, K.; MacKenzie, A.; Houghton, K. M.; Stott, M. B.; Vyssotski, M. The identification and quantification of phospholipids from Thermus and Meiothermus bacteria. Lipids 2014, 49, 1133-1141.
  • Weber, M.; Hellriegel, C.; Rueck, A.; Wuethrich, J.; Jenks, P.; Obkircher, M. Method development in quantitative NMR towards metrologically traceable organic certified reference materials used as 31P qNMR standards. Anal. Bioanal. Chem. 2015, 407, 3115-3123.
  • Xu, L.; Shi, X.; Hu, K. Quantification of multiple compounds containing heterogeneous elements in the mixture by one-dimensional nuclear magnetic resonance spectroscopy of different nuclei using a single universal concentration reference. Magn. Reson. Chem. 2014, 52, 779-782.
  • Al-Shukri, S. M. 31P NMR spectroscopy for quantification of moieties present in the backbone of poly(aryloxycyclotriphosphazene). J. Mol. Struct. 2015, 1084, 148-154.
  • Doolette, A. L.; Smernik, R. J. Quantitative analysis of 31P NMR spectra of soil extracts - dealing with overlap of broad and sharp signals. Magn. Reson. Chem. 2015, 53, 679-685.
  • Moata, M. R. S.; Smernik, R. J.; Doolette, A. L.; McNeill, A. M.; MacDonald, L. M. Improving Sensitivity of Solution 31P NMR Analysis in Australian Xeralfs. Communications in Soil Science and Plant Analysis 2015, 46, 1034-1043.
  • Fujita, K. Quantification method for organic phosphorus compound contained in the metal salt. JP2015145821A, 2015.

Quantitative Nitrogen NMR (qNNMR)