NMR relaxation of paramagnetic systems and biomolecules

Nuclear Magnetic Resonance (NMR) stands as one of the most powerful techniques for offering key information on a wide variety of systems, ranging from small molecules to materials and biologically relevant macromolecules. To no surprise, it has a pivotal role in structural biology as well as in applications related to food and health sciences. Among NMR-based methods, relaxometry emerges as the main option to explore multiscale dynamics. Fast Field Cycling (FFC) relaxometry, which exploits a wide magnetic field range from a few kHz to MHz (proton Larmor frequency), makes it possible to investigate molecular dynamics across timescales from picoseconds to microseconds. In typical situations, FFC relaxometry allows for the measurement of the longitudinal relaxation time of all protons within the sample under investigation, however the field inhomogeneity and the low detection field intrinsically limit the resolution. At the end of the last century, to address the limitations of FFC relaxometry, Bryant and Redfield pioneered the cycling between high and low fields in commercial high-field spectrometers. Subsequent applications of the so called High Resolution Relaxometry (HRR) proved successful, allowing for high-resolution measurements of nuclear relaxation at variable fields. Recently, two prototypes carrying a new technology for HRR, called Fast Shuttle System (FSS), have been installed at ENS in Paris and at CERM in Florence. Thanks to the high-field detection, this cutting-edge shuttle system enables to perform high-resolution relaxometry measurements with resolution. The technology harnesses the stray field of a high field spectrometer as a variable relaxation field, giving a whole new flavor to relaxation measurements. This doctoral thesis includes several projects in which I have been engaged. My primary focus has been on applying FFC relaxometry across diverse systems and objectives. Specific examples are outlined here, notably showing how relaxometry has been exploited to evaluate possible therapeutic and contrast agents (CAs) for Magnetic Resonance Imaging (MRI), to assess the supramolecular organization of a viscous diamagnetic system and to characterize the multiscale dynamics of biologically relevant proteins. More recently, I had the privilege to work on both FSS prototypes, not only in terms of technique validation but also for employing them to investigate protein-ligand interactions and dynamics in a complex liquid system.