Development and Application of Novel Parahydrogen based NMR Techniques

• Applicant: Professor Dr. Gerd Buntkowsky
• Subject Area: Physical Chemistry of Molecules, Liquids and Interfaces, Biophysical Chemistry
• Term: from 2019 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 405811162

Parahydrogen is one of the most efficient sources to generate hyperpolarization for sensitivity enhancements in nuclear magnetic resonance (NMR or MRI). With PHIP or SABRE, it is feasible to boost the NMR signals by several orders of magnitude. However, the formation of PHIP or SABRE type hyperpolarization is a complex interplay of spin dynamics and chemical kinetics, which is still not fully quantitatively understood. This lack of knowledge is a serious problem for the application of PHIP or SABRE in structural or quantitative analytics. The first target of the research project is accordingly a detailed analysis of the PHIP and SABRE formation in general and in particular an in-depth investigation of the role of para-ortho-conversions in this process, as the latter can strongly reduce the possible sensitivity gain. Based on this analysis an extended theoretical description of the process will be developed, implemented and experimentally validated by experiments on model compounds. In parallel robust and efficient techniques for the conversion of the PHIP hyperpolarization into net-magnetization will be developed. This net-magnetization is the prerequisite for the development of efficient PHIP-protocols. Employing it, we want to develop (i) ultra-fast PHIP or SABRE enhanced 2D-NOESY and 2D-TOCSY protocols, which have the potential to record a full 2D-NMR spectrum for structural analysis in a single scan with unprecedented sensitivity; (ii) robust techniques for the transfer of the hyperpolarization from the protons to heteronuclei for 1D- and 2D-NMR; (iii) new and improved techniques for SABRE at high-field, i.e. without the need of field-cycling and (iv) experimental protocols for the preservation of the created hyperpolarization via long-lived spin-states in specially designed PHIP markers. In parallel we will continue our work on the PANEL experiment, which permits the ultrasensitive detection of transient hydrogen-catalyst complexes, and apply it to a series of PHIP and SABRE active catalysts. Initially, all these techniques are develop employing small model molecules with an unsaturated bond in the case of PHIP or a simple pyridine derivate in the case of SABRE. Later we will validate those employing oligo-peptides, containing PHIP or SABRE active groups in the side chain, the back-bone or at the N-terminus.

• DFG Programme: Research Grants
• International Connection: Russia
• Partner Organisation: Russian Science Foundation
• Cooperation Partner: Professor Dr. Konstantin Ivanov