Many devices of interest to sustainable chemistry and climate change have functions that depend on the underlying materials, ranging from the average long-range structure, down to more local environments of specific atoms and ions, whether the structure is ordered/disordered, and whether it is dynamic. Of particular interest are paramagnetic materials, since these lend many unique properties due to the unpaired electrons of their paramagnetic metal ions. The characterization of the structural environments of these metal ions is key to understanding the functions and limitations of these materials. Whilst some structural information is provided by X-ray, and neutron diffraction, and electron microscopy techniques, these methods often fail to appreciate the complexity of the all-important local structure, how this local structure varies throughout the material, and thus how these important features affect performance of the corresponding devices. Solid-state paramagnetic nuclear magnetic resonance (pNMR) is a key method for understanding this atomic-level structure, but the unpaired electrons result in broad, low intensity signals that are very difficult to excite, resolve, and interpret using standard NMR methods. We will develop new pNMR and computational methods for paramagnetic materials, on three themes. Firstly, we will develop new NMR methods for the broadband excitation and resolution of NMR signals from quadrupolar nuclei close to paramagnetic metal ions. We will also test new density-functional theory (DFT) protocols to enable unambiguous assignment. Secondly, we will push the boundaries of dynamic nuclear polarization (DNP) to the intrinsic metal ions to enhance the pNMR sensitivity in the immediate vicinity of the metal ions, and in parallel reduce shift dispersion by perturbing the measured paramagnetic shifts. Thirdly, we will take pNMR from the atomic to the nano-scale and develop a protocol based on bulk magnetostatics to characterize the distributions of shapes/sizes of paramagnetic nano/micro particles, and lengthscales of the surface layers deposited on these particles. The methods developed around these three themes will then be put into action enabling us to fourthly, solve the complete local and global structure of three materials with important applications in sustainable energy, and to link these structures to the performances of the corresponding devices.

In this project I will develop new spectroscopy approaches that will allow one to obtain unprecedented structural information of drug molecules throughout the whole pharmaceutical process. High resolution structure determination ideally of unmodified drugs (i) in their free form, but also (ii) in complex dosage formulations, as well as (iii) during their delivery and target engagement in cells represents one of today’s major challenges in pharmaceutical industry, key to ensure productive drug uptake and improved efficacy. Current routine characterisation methods (such as detection of drugs in cells) often require sample modification (e.g. tagging with fluorescent labels) which may alter the behaviour of the drug. Here I will make use of the fact that a increasingly growing percentage (currently about 30%) of Active Pharmaceutical Ingredients (API) contain at least one fluorine atom, while hardly any excipients and no endogenous biomolecules in human cells do. By implementing innovative 19F solid state Nuclear Magnetic Resonance (NMR) approaches under fast Magic-Angle Spinning (MAS) and Dynamic Nuclear Polarisation (DNP) techniques, I will develop a new analytical tool with enhanced resolution and sensitivity, which will allow one to overcome the above mentioned challenges and to obtain structural information of unmodified drug molecules in complex and diverse formulation, in vitro and in cellular environments, as well as their interactions with various substrates (excipients, biological targets). The 19F NMR observables will be correlated with those of other nuclei (1H, 13C and 15N at natural abundance), using multidimensional 19F detected methods to distinguish between the drug molecule and excipients or cell background. The methods will be benchmarked on a variety of pharmaceutically relevant molecules and will concern both their pure constituents and their delivery systems.

Conventional high field liquid state nuclear magnetic resonance (NMR) is a powerful method but experiments need to be performed in a specific environment (inside a highly homogeneous magnetic field), which prevents its use in many applications. Coupling magnetic resonance at zero- to ultralow field (ZULF) [1] with hyperpolarization [2] by dissolution-dynamic nuclear polarization (dDNP) [3–5] allows for sensitive high resolution magnetic resonance with arbitrary molecules in challenging environments like metal containers and porous media with high magnetic susceptibility heterogeneities. This requires a robust experimental setup combining the two techniques. Boosting NMR at zero field with dDNP is challenging because of relaxation induced by paramagnetic agents. We believe that this limitation will be lifted by the use of hyperpolarizing matrices recently introduced by the French co-applicant. We will use the combination of hyperpolarization and ZULF NMR to investigate catalytic hydrogenation of unsaturated compounds, heterogeneous enzymatic processes and oligomerization and polymerization processes. In particular, this will enable the comparison of homogeneous vs. heterogeneous catalytic processes by NMR.

Singlet oxygen, an excited state of molecular oxygen is a highly reactive species, relevant for an array of applications, ranging from sustainable oxidation catalysis to photodynamic therapy (PDT). The development of tailored materials capable of precisely controlling the generation and manipulation of singlet oxygen is paramount for advancing these applications. PDT, in particular, serves as a compelling example highlighting the importance of controlled singlet oxygen management. It relies on the interplay between a photosensitizer (PS), light, and ground state oxygen (3O2), producing highly reactive oxygen species such as the cytotoxic singlet oxygen (1O2) that is used to destroy cancer and microbial pathogens. Currently PDT faces two key limitations: the control of oxygen supply and limited light penetration inside the tissues. MOFSONG project addresses these limitations by proposing innovative materials capable of decoupling the light irradiation and the 1O2 release steps. The proposed approach involves the design and synthesis of porous Metal Organic Frameworks (MOFs) combining two types of organic linkers: arenes and porphyrins in a single porous structure. Porphyrins are excellent PSs capable of generating 1O2, and arenes are aromatic molecules capable of trapping this 1O2 in their structure upon a cycloaddition reaction and endoperoxide (EPO) formation, while porosity favors the concentration and fast diffusion of oxygen species. Thus, MOFs containing EPO can be generated by illumination at the optimum porphyrin excitation wavelength and stored at low temperature until being used to controllably release 1O2 in a desired environment upon heating. The project objectives involve the synthesis of molecular building units, the development of porous materials assisted by the design of experiments and robotic synthesis, comprehensive structural and spectroscopic investigations and the study of 1O2 dynamics. The success of the project is assured through an interdisciplinary consortium of five research partners providing all the necessary expertise and state of the art facilities.

Aluminum-hydroxide-based adjuvants can absorb protein antigens from an aqueous solution and it is these adjuvants, as well as those based on aluminum phosphate, that are now widely used in vaccine formulation because of their immunostimulant behavior. The limited data in the literature show that the immune response of a vaccine formulation is related to (i) the structure of the adjuvant, (ii) the surface properties and (iii) the nature of the interaction with antigens and highlight the lack of thorough understanding of the molecular forces driving absorption/release. The objective of this project is to characterize protein/adjuvant interactions at a fundamental level using a model antigen and implementing state-of-the-art solid-state NMR approaches to describe the protein-adjuvant interface with atomic resolution.