Periodic Reporting for period 2 - HIRES-MULTIDYN (Multiscale Dynamics with Ultrafast High-Resolution Relaxometry)
Période du rapport: 2021-10-01 au 2023-03-31
Nuclear magnetic resonance (NMR) has the power to investigate matter at atomic resolution. The separation of NMR signals by chemical shifts is proportional to the magnetic field so that high resolution in complex systems requires high magnetic fields. NMR relaxation probes dynamics at the resonance frequencies of nuclear spins so motions slower than a nanosecond require low fields, fundamentally incompatible with high resolution and high sensitivity. Multiscale dynamics and high-resolution NMR are thus deemed irreconcilable. Not anymore: in this proposal, we introduce a new science-based technological concept to investigate multiscale dynamics of matter at atomic resolution with NMR. We anticipate that this innovative technology will empower scientists in a variety of fields to discover new properties of complex systems and lead to relevant achievements in various areas: from drug design to materials chemistry, from food science to medical diagnostics. We will achieve this objective by combining ground-breaking instrumentation with a novel theoretical and computational framework for the analysis.
We have worked, in the first 2.5 years of the HIRES-MULTIDYN project, along the lines of the work packages: WP1, we have set the framework for the project, with the data management plan, the dissemination and exploitation plan, amended the grant agreement, as well as developed a website for the project (https://hires-multidyn.chimie.ens.fr) and accounts on social media, such as LinkedIn (https://www.linkedin.com/in/hires-multidyn/) and Twitter (https://twitter.com/HMultidyn). We held the first meeting of the International Advisory Board and prepared evaluated the market for potential end users. WP2: the development of instrumentation, mostly carried by the partner Bruker is well under way. The two shuttle have been installed at ENS (September 2022) and at CIRRMP (March 2023). Additional developments are under way. WP3: significant advances have been carried in the theory of nuclear spin relaxation at low magnetic field. A software for the analysis of high-resolution relaxometry has been developed and is available for download. WP4: tools have been developed to set up an analysis of motions in complex systems with NMR and molecular dynamics simulations. A model of motions of protein side-chain has been developed and used to analyze relaxometry data. WP5: The first applications on the internal dynamics of protein targets are promising. Several examples of interactions between small molecules and proteins have been conducted, setting the way for the use of relaxometry in drug development and delivery. WP6: an important proof od concept experiment has been developed and published on the investigation of interactions in complex media with high-resolution relaxometry. The analysis of dynamics in olive oil from relaxometry and molecular dynamics simulaitons is well under way.
Instrumentation developments clearly aim far beyond the current state of the art (but cannot be detailed for confidentiality reasons). Applications to the fields of drug development and delivery, health, food science and energy are expected benefit society by improving the design of new small-molecule drugs and drug delivery systems; by offering new tools for medical diagnostics; by introducing new methods to probe the quality and origin of food; and, finally, by accelerating the design of systems for energy storage.