Erzeugung hochsensitiver molekularer Biomarker für die 19F Hoch- und Tieffeld-NMR durch Transfer der Parawasserstoff-induzierten Hyperpolarisation von 1H auf 19F
Final Report Abstract
Buntkowsky group. The first focus was the study of PHIP in special solvents and the use of immobilized and hybrid catalysts for PHIP. Besides for biomedicine the results open up new potential for technical applications. Ionic liquids (ILs) and supported ionic liquid phase (SILCs) allow a better separation of catalyst and substrate, which is not only necessary for potential medical applications but also advantageous for certain technical processes. For the first time PHIP was detected in ILs. Immobilized catalysts provide another approach but leaching of the catalysts can lead to poisoning when applied to living organisms. Applying liquid and solid state NMR techniques it was found that leaching may create hyperpolarized substrates as even very simple solvatized transition metals as Rh or Ir generally used in PHIP catalysts enable the generation of PHIP in solution. For reduction of leaching a new class of immobilized catalyst systems based on inorganic/organic hybrid supports (Polymer-based Wilkinson’s Type immobilized catalyst) was developed and studied. PHIP could be demonstrated using hydrogenation of styrene, and it was shown that the polymer-based hybrid systems showed better stability than the direct grafted ones while exhibiting practically no substantial leaching. In a further new approach time domain NMR at low fields (0.54 T) was employed. Using a sequence (45°-τ-180° with τ=1/4J) the anti-phase was transformed into an in-phase signal preventing the cancellation of both signals and leading to a strong signal enhancement in the echo. This technique opens up new pathways to produce hyperpolarized molecules for the use in industry, foodscience and biochemistry, and represents a hot area of research for MRI. To gain more insight into solidstate PHIP applications theoretical considerations supported by simulations were performed. The results suggest that it is possible to do PHIP in the solid-state under PASADENA conditions and that these results may be important for understanding the PHIP enhancement generated by hydrogenations employing metal nanoparticles (MNPs). In an intense joint cooperation between all working groups a series of novel PHIP markers was developed, which are based on Dehydro-Amino-Acids, Carboxylic Acids, Propargyl-Glycine bearing oligopeptides and F labeled bio-compatible molecules (perfluorocarbones). Fmoc-L-propargylglycine was applied as a building block to incorporate an alkyne moiety into the desired position of a growing peptide chain (up to 10 peptides) upon solid phase peptide synthesis (SPPS). The resulting constructs possess an unsaturated pattern, and PHIP enhancements were observed in the hydrogenation experiments with para-hydrogen in the first hydrogenation step (alkyne to alkene). The other markers are described in detail in the contributions of the WGs Bernarding and Bommerich.
Publications
- Para-hydrogen induced polarization in homogenous phase – an example how ionic liquids affect homogenization and thus activation of catalysts. Phys. Chem. Chem. Phys., 11, (2009), 9170–9175
T. Gutmann, M. Sellin, H. Breitzke, A. Stark, G. Buntkowsky
- Hyperpolarized 19F-MRI: para-hydrogen induced polarization and field variation enabling 19F-MRI at low spin density. Phys.Chem.Chem.Phys., 12, (2010), 10309-10312
U. Bommerich, T. Trantzschel, S. Mulla-Osman, G. Buntkowsky, J. Bargon, J. Bernarding
- Understanding the leaching Properties of heterogenized Catalysts: a combined Solid-State and PHIP NMR Study. Solid-State NMR., 38, (2010), 90-96
T. Gutmann; T. Ratajczyk; Y. Xu; H. Breitzke; A. Gruenberg; S. Dillenberger; U. Bommerich; Th. Trantzschel; J. Bernarding, G. Buntkowsky
- New investigations of technical rhodium and iridium catalysts in homogeneous phase employing Para-Hydrogen Induced Polarization.Solid-State NMR.,40, (2011), 88–90
T. Gutmann, T. Ratajczyk, S. Dillenberger, Y. Xu, A. Grünberg, H. Breitzke, U. Bommerich, T. Trantzschel, J. Bernarding, G. Buntkowsky
- Para-hydrogen induced polarization in face of ketoenoltautomerism: proof of concept with hyperpolarized ethanol. Phys. Chem. Chem. Phys., 14, (2012), 5601-5604
Th. Trantzschel, J. Bernarding, M. Plaumann, D. Lego, T. Gutmann, T. Ratajczyk, S. Dillenberger, G. Buntkowsky, J. Bargon, U. Bommerich
(See online at https://doi.org/10.1039/c2cp40272f) - Time Domain Para-Hydrogen Induced Polarization. Solid-State NMR., 43-44, (2012), 14-21
T. Ratajczyk, T. Gutmann, S. Dillenberger, S. Abdulhussaein, J. Frydel, H. Breitzke, U. Bommerich, Th. Trantzschel, J. Bernarding, P. Magusin, G. Buntkowsky
(See online at https://doi.org/10.1016/j.ssnmr.2012.02.002) - Application of Para-hydrogen Induced Polarization to Unprotected Dehydroamino Carboxylic Acids. Appl. Magn. Res., 44, (2013), 267-278
Th. Trantzschel, M. Plaumann, J.Bernarding, D.Lego, T. Ratajczyk, S. Dillenberger, G. Buntkowsky, J. Bargon, U. Bommerich
(See online at https://doi.org/10.1007/s00723-012-0391-0) - NMR Studies of the Reaction Path of the o-H2/p-H2 Spin Conversion Catalyzed by Vaska's Complex in the Solid-State; Appl. Magn. Res., 44, (2013), 247-265
J. Matthes, S. Gründemann, G. Buntkowsky, B. Chaudret, H.-H. Limbach
(See online at https://doi.org/10.1007/s00723-012-0395-9) - Parahydrogen-Induced Polarization Transfer to 19F in Perfluorocarbons for 19F NMR and MRI. Chem. Eur. J. 19, 6334 – 6339
M. Plaumann, U. Bommerich, T. Trantzschel, D. Lego, S. Dillenberger, G. Sauer, J. Bargon, G. Buntkowsky, J. Bernarding
- PHIP-Label: Parahydrogen-Induced Polarization in Propargylglycine-Containing Synthetic Oligopeptides, Chem.Comm. (2013), 49,7839-7841
M. Tischler, G. Sauer, A.Heil, D. Nasu, M. Empting, D. Tietze, S. Voigt, H. Weidler, T. Gutmann, O. Avrutina, H. Kolmar, T. Ratajczyk, G. Buntkowsky
(See online at https://doi.org/10.1039/c3cc43978j) - Parahydrogen-induced polarization of carboxylic acids: a pilot study of valproic acid and related structures. NMR Biomed., (2014), 27, 810 – 816
D. Lego, M.Plaumann ,T.Trantzschel, J. Bargon, H. Scheich, G. Buntkowsky, T. Gutmann, G. Sauer, J. Bernarding, U. Bommerich
(See online at https://doi.org/10.1002/nbm.3123) - Synthesis, Solid State NMR-Characterization and Application of a novel Wilkinson’s type immobilized Catalyst for hydrogenation reactions, Chemistry Eur.J., (2014), 20, 1159-1166
S. Abdulhussain, H. Breitzke, T. Ratajczyk, A. Grünberg, M. Srour, D. Arnaut, H. Weidler, U. Kunz, H.J. Kleebe, U. Bommerich, J. Bernarding, T. Gutmann, G. Buntkowsky
(See online at https://doi.org/10.1002/chem.201303020)
