Ultra-sensitive NMR in liquids

Informazioni relative al progetto

BetaDropNMR

ID dell’accordo di sovvenzione: 640645

DOI

10.3030/640645

Progetto chiuso

Data della firma CE 25 Marzo 2015

Data di avvio 1 Ottobre 2015

Data di completamento 31 Marzo 2022

Finanziato da

• EXCELLENT SCIENCE - European Research Council (ERC)

Costo totale

€ 1 500 000,00

Contributo UE

€ 1 500 000,00

Coordinato da

ORGANISATION EUROPEENNE POUR LA RECHERCHE NUCLEAIRE
Switzerland

Periodic Reporting for period 4 - BetaDropNMR (Ultra-sensitive NMR in liquids)

Periodo di rendicontazione: 2020-04-01 al 2022-03-31

Sintesi del contesto e degli obiettivi generali del progetto

Nuclear Magnetic Resonance (NMR) is an extremely sensitive technique used in many fields of research, including chemistry and biology where is is used to determine the structure and interactions of many different biomolecules. However, its main limitation is a very poor sensitivity. The aim of the betaDropNMR project is to transfer an ultrasensitive version of NMR, namely beta-detected NMR, from nuclear physics applications to chemistry and biology and to investigate with it the interaction of essential metal ions with biomolecules. Because beta-(detected) NMR requires up to a billion times fewer probe nuclei, studies which suffered from low NMR sensitivity might be now possible, e.g. investigation of zinc interaction with different proteins or interaction of Na+ and K+ ions with DNA G-quadruplex structures, which all play roles in the correct functioning of our organisms, and their malfunctioning, or are believed to be related to different diseases, including Parkinson's and Alzheimer’s.
The project has allowed for the 1st alkali-metal beta-NMR studies in liquid samples and to connect it to conventional NMR. This opens the possibility of using a much more sensitive approach to investigate metal ions and their interactions with different biomolecues via NMR, and thus learning new things about theses systems.

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

During the project, we built and upgraded a dedicated experimental setup at the CERN-ISOLDE facility allowing us to laser-polarize radioactive isotopes in their atomic form and to perform beta-asymmetry and beta-NMR studies with them. We have used it to perform beta-NMR studies on several short-lived Na and K isotopes in several solid and liquid hosts. The results show up to a billion-times higher sensitivity than conventional NMR on stable 23Na and 39,41K, as well as narrower resonances due to lower (or 0) quadrupole moment of the short-lived isotopes.
This achievement has already allowed us to determine the magnetic dipole moment of a short-lived nucleus with a hundred-fold better accuracy than possible before. We have also been able to characterise several interesting ionic-liquid hosts in high-vacuum environment, using beta-NMR and conventional NMR.
We are at present investigating the best liquid hosts to fold DNA G-quadruplexes around Na and K ions in vacuum conditions, with the aim to perform the 1st fully biological beta-NMR experiment in July 2022.

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

State of the art of conventional ultrasensitive NMR is based mostly on the Dynamic Nuclear Polarization approach, where the sensitivity can be increased by several orders of magnitude. Our liquid beta-NMR resonances required only about 1e8 Na nuclei, thus increasing the sensitivity of the technique by 8 to 9 orders of magnitude. No other present approach can achieve such an improvement.
In addition, we were the 1st team to introduce an in-situ ppm measurement of the magnetic field during the beta-NMR measurement. In combination with state-of-the-art quantum chemistry calculations, this allows us to determine accurate magnetic moments of short-lived nuclei and absolute NMR shielding linking beta-NMR with convetional NMR and theory.
Until the end of the project, we were successful in adding to the pallettee of NMR nuclei several short-lived isotopes of sodium and potassium. We could also achieve results in studies on ionic liquid hosts that were not possible with conventional NMR (e.g. by introducing directly Na or K atoms, and not a NaCl or KCl salt).
Shortly after the end of the project, we plan to perform the 1st biological studies using liquid-state beta-NMR.

First 26Na beta-NMR in a liquid sample and DNA-G quadruplex to be studies with this technique

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