Co-reporter:Dr. Indrek Reile;Ruud L. E. G. Aspers;Jean-Max Tyburn;Dr. James G. Kempf;Dr. Martin C. Feiters; Floris P. J. T. Rutjes;Dr. Marco Tessari
Angewandte Chemie International Edition 2017 Volume 56(Issue 31) pp:9174-9177
Publication Date(Web):2017/07/24
DOI:10.1002/anie.201703577
AbstractDOSY is an NMR spectroscopy technique that resolves resonances according to the analytes’ diffusion coefficients. It has found use in correlating NMR signals and estimating the number of components in mixtures. Applications of DOSY in dilute mixtures are, however, held back by excessively long measurement times. We demonstrate herein, how the enhanced NMR sensitivity provided by SABRE hyperpolarization allows DOSY analysis of low-micromolar mixtures, thus reducing the concentration requirements by at least 100-fold.
Co-reporter:Dr. Indrek Reile;Ruud L. E. G. Aspers;Jean-Max Tyburn;Dr. James G. Kempf;Dr. Martin C. Feiters; Floris P. J. T. Rutjes;Dr. Marco Tessari
Angewandte Chemie 2017 Volume 129(Issue 31) pp:9302-9305
Publication Date(Web):2017/07/24
DOI:10.1002/ange.201703577
AbstractDOSY is an NMR spectroscopy technique that resolves resonances according to the analytes’ diffusion coefficients. It has found use in correlating NMR signals and estimating the number of components in mixtures. Applications of DOSY in dilute mixtures are, however, held back by excessively long measurement times. We demonstrate herein, how the enhanced NMR sensitivity provided by SABRE hyperpolarization allows DOSY analysis of low-micromolar mixtures, thus reducing the concentration requirements by at least 100-fold.
Co-reporter:Frank H.T. Nelissen, Marco Tessari, Sybren S. Wijmenga, Hans A. Heus
Progress in Nuclear Magnetic Resonance Spectroscopy 2016 Volume 96() pp:89-108
Publication Date(Web):August 2016
DOI:10.1016/j.pnmrs.2016.06.001
•Isotope labeling strategies for obtaining stable isotope labeled DNA are reviewed.•Labeling design of rNTPs and dNTPs using in vitro biosynthesis is described.•The utility of the labeling strategies is demonstrated by heteronuclear NMR experiments.NMR is a powerful method for studying proteins and nucleic acids in solution. The study of nucleic acids by NMR is far more challenging than for proteins, which is mainly due to the limited number of building blocks and unfavorable spectral properties. For NMR studies of DNA molecules, (site specific) isotope enrichment is required to facilitate specific NMR experiments and applications. Here, we provide a comprehensive review of isotope-labeling strategies for obtaining stable isotope labeled DNA as well as specifically stable isotope labeled building blocks required for enzymatic DNA synthesis.
Co-reporter:Niels K. J. Hermkens, Nan Eshuis, Bram J. A. van Weerdenburg, Martin C. Feiters, Floris P. J. T. Rutjes, Sybren S. Wijmenga, and Marco Tessari
Analytical Chemistry 2016 Volume 88(Issue 6) pp:3406
Publication Date(Web):February 22, 2016
DOI:10.1021/acs.analchem.6b00184
When dealing with trace analysis of complex mixtures, NMR suffers from both low sensitivity and signal overlap. NMR chemosensing, in which the association between an analyte and a receptor is “signaled” by an NMR response, has been proposed as a valuable analytical tool for biofluids and natural extracts. Such chemosensors offer the possibility to simultaneously detect and distinguish different analytes in solution, which makes them particularly suitable for analytical applications on complex mixtures. In this study, we have combined NMR chemosensing with nuclear spin hyperpolarization. This was realized using an iridium complex as a receptor in the presence of parahydrogen: association of the target analytes to the metal center results in approximately 1000-fold enhancement of the NMR response. This amplification allows the detection, identification, and quantification of analytes at low-micromolar concentrations, provided they can weakly associate to the iridium chemosensor. Here, our NMR chemosensing approach was applied to the quantitative determination of several flavor components in methanol extracts of ground coffee.
Co-reporter:I. Reile, N. Eshuis, N. K. J. Hermkens, B. J. A. van Weerdenburg, M. C. Feiters, F. P. J. T. Rutjes and M. Tessari
Analyst 2016 vol. 141(Issue 13) pp:4001-4005
Publication Date(Web):11 May 2016
DOI:10.1039/C6AN00804F
NMR spectroscopy is one of the most powerful techniques to simultaneously obtain qualitative and quantitative information in chemical analysis. Despite its versatility, the applications of NMR in the study of biofluids are often limited by the insensitivity of the technique, further aggravated by the poor signal dispersion in the 1H spectra. Recent advances in para-H2 induced hyperpolarization have proven to address both these limitations for specific classes of compounds. Herein, this approach is for the first time applied for quantitative determination in biofluid extracts. We demonstrate that a combination of solid phase extraction, para-hydrogen induced hyperpolarization and selective NMR detection quickly reveals a doping substance, nikethamide, at sub-μM concentrations in urine. We suggest that this method can be further optimized for the detection of different analytes in various biofluids, anticipating a wider application of hyperpolarized NMR in metabolomics and pharmacokinetics studies in the near future.
Co-reporter:Nan Eshuis;Bram J. A. vanWeerdenburg;Dr. Martin C. Feiters;Dr. Floris P. J. T. Rutjes;Dr. Sybren S. Wijmenga ;Dr. Marco Tessari
Angewandte Chemie 2015 Volume 127( Issue 5) pp:
Publication Date(Web):
DOI:10.1002/ange.201411678
Co-reporter:Nan Eshuis;Bram J. A. vanWeerdenburg;Dr. Martin C. Feiters;Dr. Floris P. J. T. Rutjes;Dr. Sybren S. Wijmenga ;Dr. Marco Tessari
Angewandte Chemie International Edition 2015 Volume 54( Issue 5) pp:1481-1484
Publication Date(Web):
DOI:10.1002/anie.201409795
Abstract
Signal amplification by reversible exchange (SABRE) is an emerging nuclear spin hyperpolarization technique that strongly enhances NMR signals of small molecules in solution. However, such signal enhancements have never been exploited for concentration determination, as the efficiency of SABRE can strongly vary between different substrates or even between nuclear spins in the same molecule. The first application of SABRE for the quantitative analysis of a complex mixture is now reported. Despite the inherent complexity of the system under investigation, which involves thousands of competing binding equilibria, analytes at concentrations in the low micromolar range could be quantified from single-scan SABRE spectra using a standard-addition approach.
Co-reporter:Nan Eshuis;Bram J. A. vanWeerdenburg;Dr. Martin C. Feiters;Dr. Floris P. J. T. Rutjes;Dr. Sybren S. Wijmenga ;Dr. Marco Tessari
Angewandte Chemie International Edition 2015 Volume 54( Issue 5) pp:
Publication Date(Web):
DOI:10.1002/anie.201411678
Co-reporter:Nan Eshuis;Ing. Ruud L. E. G. Aspers;Bram J. A. vanWeerdenburg;Dr. Martin C. Feiters;Dr. Floris P. J. T. Rutjes;Dr. Sybren S. Wijmenga ;Dr. Marco Tessari
Angewandte Chemie International Edition 2015 Volume 54( Issue 48) pp:14527-14530
Publication Date(Web):
DOI:10.1002/anie.201507831
Abstract
Nuclear magnetic resonance is often the technique of choice in chemical analysis because of its sensitivity to molecular structure, quantitative character, and straightforward sample preparation. However, determination of trace analytes in complex mixtures is generally limited by low sensitivity and extensive signal overlap. Here, we present an approach for continuous hyperpolarization at high magnetic field that is based on signal amplification by reversible exchange (SABRE) and can be straightforwardly incorporated in multidimensional NMR experiments. This method was implemented in a 2D correlation experiment that allows detection and quantification of analytes at nanomolar concentration in complex solutions.
Co-reporter:Nan Eshuis;Bram J. A. vanWeerdenburg;Dr. Martin C. Feiters;Dr. Floris P. J. T. Rutjes;Dr. Sybren S. Wijmenga ;Dr. Marco Tessari
Angewandte Chemie 2015 Volume 127( Issue 5) pp:1501-1504
Publication Date(Web):
DOI:10.1002/ange.201409795
Abstract
Signal amplification by reversible exchange (SABRE) is an emerging nuclear spin hyperpolarization technique that strongly enhances NMR signals of small molecules in solution. However, such signal enhancements have never been exploited for concentration determination, as the efficiency of SABRE can strongly vary between different substrates or even between nuclear spins in the same molecule. The first application of SABRE for the quantitative analysis of a complex mixture is now reported. Despite the inherent complexity of the system under investigation, which involves thousands of competing binding equilibria, analytes at concentrations in the low micromolar range could be quantified from single-scan SABRE spectra using a standard-addition approach.
Co-reporter:Nan Eshuis;Ing. Ruud L. E. G. Aspers;Bram J. A. vanWeerdenburg;Dr. Martin C. Feiters;Dr. Floris P. J. T. Rutjes;Dr. Sybren S. Wijmenga ;Dr. Marco Tessari
Angewandte Chemie 2015 Volume 127( Issue 48) pp:14735-14738
Publication Date(Web):
DOI:10.1002/ange.201507831
Abstract
Nuclear magnetic resonance is often the technique of choice in chemical analysis because of its sensitivity to molecular structure, quantitative character, and straightforward sample preparation. However, determination of trace analytes in complex mixtures is generally limited by low sensitivity and extensive signal overlap. Here, we present an approach for continuous hyperpolarization at high magnetic field that is based on signal amplification by reversible exchange (SABRE) and can be straightforwardly incorporated in multidimensional NMR experiments. This method was implemented in a 2D correlation experiment that allows detection and quantification of analytes at nanomolar concentration in complex solutions.
Co-reporter:Nan Eshuis ; Niels Hermkens ; Bram J. A. van Weerdenburg ; Martin C. Feiters ; Floris P. J. T. Rutjes ; Sybren S. Wijmenga
Journal of the American Chemical Society 2014 Volume 136(Issue 7) pp:2695-2698
Publication Date(Web):January 29, 2014
DOI:10.1021/ja412994k
SABRE is a nuclear spin hyperpolarization technique based on the reversible association of a substrate molecule and para-hydrogen (p-H2) to a metal complex. During the lifetime of such a complex, generally fractions of a second, the spin order of p-H2 is transferred to the nuclear spins of the substrate molecule via a transient scalar coupling network, resulting in strongly enhanced NMR signals. This technique is generally applied at relatively high concentrations (mM), in large excess of substrate with respect to metal complex. Dilution of substrate ligands below stoichiometry results in progressive decrease of signal enhancement, which precludes the direct application of SABRE to the NMR analysis of low concentration (μM) solutions. Here, we show that the efficiency of SABRE at low substrate concentrations can be restored by addition of a suitable coordinating ligand to the solution. The proposed method allowed NMR detection below 1 μM in a single scan.
Co-reporter:Niels K.J. Hermkens, Martin C. Feiters, Floris P.J.T. Rutjes, Sybren S. Wijmenga, Marco Tessari
Journal of Magnetic Resonance (March 2017) Volume 276() pp:
Publication Date(Web):1 March 2017
DOI:10.1016/j.jmr.2017.01.011
•EXSY experiment combined with 1H para-H2 hyperpolarization at high field.•This experiment provides the substrate dissociation rates in asymmetric SABRE complexes.•100-fold reduction in measuring time is obtained compared to standard methods.SABRE (Signal Amplification By Reversible Exchange) is a nuclear spin hyperpolarization technique based on the reversible concurrent binding of small molecules and para-hydrogen (p-H2) to an iridium metal complex in solution. At low magnetic field, spontaneous conversion of p-H2 spin order to enhanced longitudinal magnetization of the nuclear spins of the other ligands occurs. Subsequent complex dissociation results in hyperpolarized substrate molecules in solution. The lifetime of this complex plays a crucial role in attained SABRE NMR signal enhancements. Depending on the ligands, vastly different dissociation rates have been previously measured using EXSY or selective inversion experiments. However, both these approaches are generally time-consuming due to the long recycle delays (up to 2 min) necessary to reach thermal equilibrium for the nuclear spins of interest. In the cases of dilute solutions, signal averaging aggravates the problem, further extending the experimental time. Here, a new approach is proposed based on coherent hyperpolarization transfer to substrate protons in asymmetric complexes at high magnetic field. We have previously shown that such asymmetric complexes are important for application of SABRE to dilute substrates. Our results demonstrate that a series of high sensitivity EXSY spectra can be collected in a short experimental time thanks to the NMR signal enhancement and much shorter recycle delay.Download high-res image (124KB)Download full-size image
![Methyl (3s,4r)-3-benzoyloxy-8-methyl-8-azabicyclo[3.2.1]octane-4-carboxylate](http://img.cochemist.com/ccimg/100/50-36-2.png)
![Methyl (3s,4r)-3-benzoyloxy-8-methyl-8-azabicyclo[3.2.1]octane-4-carboxylate](http://img.cochemist.com/ccimg/100/50-36-2_b.png)
![2H-Imidazol-2-ylidene,1,3-dihydro-1,3-bis(tricyclo[3.3.1.13,7]dec-1-yl)-](http://img.cochemist.com/ccimg/131100/131042-77-8.png)
![2H-Imidazol-2-ylidene,1,3-dihydro-1,3-bis(tricyclo[3.3.1.13,7]dec-1-yl)-](http://img.cochemist.com/ccimg/131100/131042-77-8_b.png)
