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Bram van Weerdenburg

PhD student

Room: HG 03.101
Lab: HG 03.130
Phone: +31 (0)24 36 52083
Email: This e-mail address is being protected from spambots. You need JavaScript enabled to view it

UltraSense NMR project: development of a ultrasensitive hyperpolarization NMR platform for biomarker discovery and metabolic tracing.

Since its discovery NMR has become a powerful analytical tool which is intensively used in the area of chemistry, material science and medicine. However, NMR is very insensitive compared to other analytical methodologies, like mass spectrometry. To overcome this insensitivity Para-Hydrogen Induced Polarization (PHIP) techniques are applied, resulting in dramatically enhanced NMR signals.

In general PHIP requires a fast chemical reaction between the para-spin isomer of molecular hydrogen (p-H2) and an organic substrate. For this purpose hydrogenation reactions can be used, converting an alkyne or an alkene to the respective alkene or alkane (Fig. 1).1 In this reaction not only the freshly introduced H nuclei are hyperpolarized, but the polarization can also be transferred to even less sensitive nuclei like 13C. Depending on the magnetic field strength during this reaction, PHIP experiments are classified as PASADENA (high field) or ALTADENA (low field).

figure1

Figure 1: PHIP by hydrogenation of biomolecules

The scope of this PHIP phenomenon has recently been greatly enlarged by the so called Signal Amplification by Reversible Exchange (SABRE) experiments (Fig. 2).2 An organic substrate with some coordination ability and p-H2 can undergo reversible association with a transition metal complex in low magnetic field, resulting in the hyperpolarization of this substrate without any chemical modification.

figure2

Figure 2: Signal Amplification by Reversible Exchange

Both methods will be investigated. The resulting high sensitivity will be used for specific visualization of very low amounts of metabolites in body fluids. The detection of these metabolites might result in early diagnosis for instance metabolic diseases or (prostate)cancer, having a great impact for the treatment of these diseases.

1 F. Reineri et. al., J. Am. Chem. Soc. 2010, 132, 7186
2 R.W. Adams et. al., Science 2009, 323, 1708

Publications

  • K. Koch, B. J. A. van Weerdenburg, J. M. M. Verkade, P. J. Nieuwland, F. P. J. T. Rutjes, J. C. M. van Hest, "Optimizing the Deprotection of the Amine Protecting p-Methoxyphenyl Group in an Automated Microreactor Platform", Org. Process Res. Dev. 2009, 13, 1003-1006. direct link
  • B.J.A. van Weerdenburg, S. Gloggler, N. Eshuis, A.H.J. Engwerda, J.M.M. Smits, R. de Gelder, S. Appelt, S.S. Wymenga, M. Tessari, M.C. Feiters, B. Blumich, F.P.J.T. Rutjes, "Ligand effects of NHC-iridium catalysts for signal amplification by reversible exchange (SABRE)", Chem. Commun. 2013, 49, 7388-7390. direct link
  • N. Eshuis, N. Hermkens, B.J.A. van Weerdenburg, M.C. Feiters, F.P.J.T. Rutjes, S.S. Wijmenga, M. Tessari, "Toward Nanomolar Detection by NMR Through SABRE Hyperpolarization", J. Am. Chem. Soc. 2014, 136, 2695-2698. direct link