Project

Dynamic Nuclear Polarization (DNP); Dissolution DNP in liquids; Slow dynamic processes; Long-lived spin states in liquids; ‘In situ' DNP in solids; Fast dynamic processes in solids; Nitrogen-14 NMR; nuclear magnetic resonance (NMR); enhanced polarisation; liquid state NMR; solid state NMR; long lifetimes; nitrogen-14

Lead
Lay summary
The main advantage of nuclear magnetic resonance (NMR) lies in its ability to differentiate between molecules or between different sites in a molecule based on their chemical environment. Its main drawback is the limited sensitivity, typically NMR measurements needing concentrations on the order of 10-3 M in half-ml volumes for liquid-state NMR and app. 10 mg of powder for solid-state NMR. These concentrations are often hard (or expensive) to obtain for samples of interest. Moreover, biologically relevant reactions occur at much lower concentrations.The sensitivity of NMR may be enhanced if nuclear spins are coupled to unpaired electron spins, which have a much higher polarization. This can be achieved in a sample where a paramagnetic radical is mixed with the molecule of interest via the effect known as Dynamic Nuclear Polarization (DNP). We aim to apply this method to both liquid and solid-state NMR, in the latter case namely for the study spin-1 nuclei such as nitrogen-14, which is present in most biomolecules in natural abundance.The short lifetimes of spin order in comparison to the characteristic time of biological reactions are a serious barrier in the way of applications of hyperpolarized magnetic resonance to liquid state NMR. The magnetization of nuclei with low gyromagnetic ratios has low relaxation rate constants, but the sensitivity for detection of such nuclei is limited. We plan to show that long lifetimes of enhanced magnetization may be obtained on the sensitive proton spins.

Direct link to Lay Summary

Last update: 21.02.2013

Number	Title	Start	Funding scheme

It is now widely accepted that processes that occur on a time-scale longer than the longitudinal (spin-lattice) relaxation time T1 can be characterized by using so-called long-lived states (LLS). In systems containing only two spins, these are also known as singlet states (SS), which decay with a time constant TS >> T1. These states can be populated and sustained by suitable pulse sequences that we have developed in recent years. Special techniques must be developed in systems with three and more spins,where the best long-lived states comprise non-trivial linear combinations ofcontributions from different spins. The long-lived states will serve: (i) to sense slow dynamic processes (translational diffusion of macromolecules, internal motions in proteins, conformational rearrangements of nucleic acids) and (ii) as vectors to transport enhanced nuclear polarisation, with applications to metabolic studies.Suitable equipment for microwave irradiation at 94 GHz and 1.5 K has recently been installed in our laboratory. The transfer from the prepolarizing magnet to the NMR magnet will be re-designed in part. Because dynamic nuclear polarization (DNP) yields unprecedented sensitivity (an enhancement on the order of 10’000 in signal/noise), we plan to use new methods for single-scan two-dimensional spectroscopy that we havealso developed in our laboratory.In solid-state NMR, we shall strive to improve the indirect detection of nitrogen-14 that we have developed at EPFL, particularly in conjunction with ‘in situ’ dynamic nuclear polarization (DNP) that has been pioneered at MIT and that we now plan to install at EPFL. Rather than exploiting residual dipolar splittings between nitrogen-14 and "spy" nuclei such as carbon-13, we now prefer to use so-called ‘recoupling’ methods, wherethe heteronuclear dipole-dipole interactions, which are normally eliminated by rapid spinning, are re-introduced by suitable pulse sequences. Various hetero- and homonuclear decoupling techniques will be implemented to improve the quality of the spectra. The resulting nitrogen-14 spectra feature powder line shapes that are mainly determined by second-order nitrogen-14 quadrupole interactions. These can provide insight into internal dynamic processes on an unusual time-scale in the vicinity of 100 ns which does not seem to be accessible to any other spectroscopic methods that offeratomic resolution.