Long-lived states to sustain hyperpolarized magnetization

Major breakthroughs have recently been reported that can help overcome two inherent drawbacks of NMR: the lack of sensitivity and the limited memory of longitudinal magnetization. Dynamic nuclear polarization (DNP) couples nuclear spins to the large reservoir of electrons, thus making it possible to detect dilute endogenous substances in magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI). We have designed a method to preserve enhanced ("hyperpolarized") magnetization by conversion into long-lived states (LLS). It is shown that these enhanced long-lived states can be generated for proton spins, which afford sensitive detection. Even in complex molecules such as peptides, long-lived proton states can be sustained effectively over time intervals on the order of tens of seconds, thus allowing hyperpolarized substrates to reach target areas and affording access to slow metabolic pathways. The natural abundance carbon-13 polarization has been enhanced ex situ by almost four orders of magnitude in the dipeptide Ala-Gly. The sample was transferred by the dissolution process to a high-resolution magnet where the carbon-13 polarization was converted into a long-lived state associated with a pair of protons. In Ala-Gly, the lifetime TLLS associated with the two nonequivalent H glycine protons, sustained by suitable radio-frequency irradiation, was found to be seven times longer than their spin-lattice relaxation time constant (TLLS/T1 = 7). At desired intervals, small fractions of the populations of long-lived states were converted into observable magnetization. This opens the way to observing slow chemical reactions and slow transport phenomena such as diffusion by enhanced magnetic resonance.

J1−J2 square-lattice Heisenberg antiferromagnets with 4d1 spins: AMoOPO4Cl (A=K,Rb)

Peter Babkevich, Henrik Moodysson Rønnow

Magnetic properties of AMoOPO4Cl (A=K,Rb) with Mo5+ ions in the 4d1 electronic configuration are investigated by magnetization, heat capacity, and nuclear magnetic resonance (NMR) measurements on single crystals, combined with powder neutron diffraction experiments. The magnetization measurements reveal that they are good model compounds for the spin-1/2 J1−J2 square-lattice magnet with the first and second nearest-neighbor interactions. Magnetic transitions are observed at around 6 and 8 K in the K and Rb compounds, respectively. In contrast to the normal Néel-type antiferromagnetic order, the NMR and neutron diffraction experiments find a columnar antiferromagnetic order for each compound, which is stabilized by a dominant antiferromagnetic J2. Both compounds realize the unusual case of two interpenetrating J2 square lattices weakly coupled to each other by J1.

2017

Study of fast exchanging processes by NMR Spectroscopy

Estel Canet Martinez

Nuclear magnetic resonance (NMR) spectroscopy is one of the most powerful and informative methods to probe molecular dynamics. Specifically, chemical exchange is an important phenomenon and one of the earliest and most vigorously investigated in NMR spectroscopy. Its effects can be observed in many NMR spectra; lines in a spectrum are broadened or averaged because the nuclei are exchanging magnetic environments. A wide variety of experimental methods exists to determine exchange rates of protons that hop between amino acids and water in the slow or intermediate exchange regime. However, so far there is a lack of methods to investigate hydrogen exchange in the fast exchange regime. In this thesis, we focus on the determination of very fast chemical exchange rates from the effects of scalar relaxation on a coupled nucleus. We quantify the effects of scalar relaxation caused by exchanging hydrogens, by detecting the decay of a 15N coherence under a multiple-refocusing Carr-Purcell-Meiboom-Gill (CPMG) pulse train in the presence or absence of hydrogen decoupling. In particular, we have adapted to the case of deuterium a method that was originally designed to study the exchange rate of the indole proton of tryptophan in water as a function of pH and temperature. We will present the exchange rates of the indole deuterium in tryptophan with solvent heavy water. After that, the proton exchanges rates have been compared with the deuterium exchange rates in order to describe the kinetic isotope effect. In a similar manner, we have quantified the proton exchange rates in pure water by using multiple refocusing of transverse 17O magnetization as a function of pH and temperature. Such measurements are widely used to obtain valuable information about molecular dynamics and structure of proteins, protein complexes and nucleic acids. The knowledge of the kinetic isotope effect may contribute to the characterization of reaction mechanisms and other dynamic parameters that can give insight into the stability of hydrogen bonded secondary structures in biomolecules. This information could form a foundation for a more thorough theoretical or modeling development of a number of long and outstanding fundamental questions. In the second part of the thesis, we combine fast exchange with dissolution dynamic nuclear polarization (D-DNP) to study intrinsically disordered proteins (IDPs). IDPs constitute a very large and functionally important class of proteins that lack stable secondary and tertiary structures. As a consequence of the broad dynamics and flexibility of IDPs, and specially under physiological conditions, the NMR spectra of IDPs typically show a strong signal overlap and broadening due to proton exchange. We present a method to overcome these limitations by means of hyperpolarized HDO produced by D-DNP. We could study the effects of conformational adaptations in Osteopontin (OPN), a metastasis- associated intrinsically disordered protein (IDP) by chemical exchange. The magnetization from hyperpolarized water is transferred to the rapidly exchanging protons of the solvent-exposed residues of the protein. The exchange with hyperpolarized water boosts the signals of fast exchanging residues above the detection limits. This allows one to follow individual resonances and draw conclusions regarding conformational adaptations due to ligand binding under physiological conditions. Thus, with our approach, exchange with the solvent is turned into an advantage

EPFL2017

Methods for nuclear magnetic resonance (NMR) or magnetic resonance imaging (MRI) measurements using long-lived states

Geoffrey Bodenhausen, Arnaud Comment, Sami Jannin, Riddhiman Sarkar, Paul Romeo Vasos

A method for nuclear magnetic resonance (NMR) or magnetic resonance imaging (MRI) measurements, includes creation of enhanced polarization of nuclei of a first kind within a sample in a magnetic field at cryogenic temperatures and transfer of the polarized sample to room temperature. The enhanced polarization of nuclei of the first kind is thereby transformed into long-lived states (LLS) of nuclei of a second kind and these LLS are sustained. The LLS is at least partially converted into observable magnetization and an NMR or MRI measurement is carried out. The method allows one to extend the time needed between hyperpolarized magnetization and NMR detection.

2013

Study of fast exchanging processes by NMR Spectroscopy

Estel Canet Martinez

EPFL2017