Periodic Reporting for period 1 - DNP-NMR (Easy DNP Enhanced Solid-State NMR: High Sample Temperatures and Low Microwave Powers)
Berichtszeitraum: 2021-04-01 bis 2023-03-31
Nuclear magnetic resonance (NMR) spectroscopy is an indispensable tool in chemical science to study atomic-level structures and dynamics, which is at the heart of rational design of materials for targeted applications. A number of critical research areas that impact society rely on structural characterization techniques like NMR spectroscopy, such as the development of materials for carbon-capture and sustainable energy (e.g. photovoltaics, batteries, catalysts, thermoelectrics etc.), pharmaceuticals research that involves urgent, new chemical modalities for drugs and vaccines, and biochemistry where the function of large biomolecules is linked to their atomic structures.
However, NMR suffers from an intrinsically low sensitivity, resulting in long experiment times on the order of days for advanced experiments, prohibiting more complex experiments and high throughput. Dynamic nuclear polarization (DNP) is a promising approach to address this problem as it provides large gains in signal-to-noise ratio by a factor of 100-200 in NMR spectra. The sensitivity gains provided by DNP have enabled critical questions to be answered in several research areas. However, DNP currently requires cryogenic temperatures (−170 °C) and expensive specialized equipment, with only around 55 DNP instruments worldwide at present. To enable widespread adoption of DNP, it is critical to develop this technology further and extend the range of possible samples and temperatures. The primary bottleneck for improved DNP is the efficacy of the polarizing agents that are added to the sample to provide the greater sensitivity.
The objective of this project was to develop robust DNP polarizing agents and DNP methods at higher temperatures (–70 to 30 °C), that will allow DNP-enhanced NMR to become the tool of choice for chemists, material scientists and biologists.
However, NMR suffers from an intrinsically low sensitivity, resulting in long experiment times on the order of days for advanced experiments, prohibiting more complex experiments and high throughput. Dynamic nuclear polarization (DNP) is a promising approach to address this problem as it provides large gains in signal-to-noise ratio by a factor of 100-200 in NMR spectra. The sensitivity gains provided by DNP have enabled critical questions to be answered in several research areas. However, DNP currently requires cryogenic temperatures (−170 °C) and expensive specialized equipment, with only around 55 DNP instruments worldwide at present. To enable widespread adoption of DNP, it is critical to develop this technology further and extend the range of possible samples and temperatures. The primary bottleneck for improved DNP is the efficacy of the polarizing agents that are added to the sample to provide the greater sensitivity.
The objective of this project was to develop robust DNP polarizing agents and DNP methods at higher temperatures (–70 to 30 °C), that will allow DNP-enhanced NMR to become the tool of choice for chemists, material scientists and biologists.
The work performed towards the objectives of the project was divided into the following areas: (1) development of improved polarizing agents for DNP-enhanced NMR, (2) development of sample formulations that maintain favorable conditions for DNP-enhanced NMR at high temperatures, and (3) development of room temperature DNP in liquids.
(1) Development of polarizing agents: Significant work was carried out to better understand the function of DNP polarizing agents and develop strategies to improve them. DNP is typically performed with organic radical dopants, but the relationship between their atomic-structure and the overall DNP efficiency is not clearly understood. A major milestone towards this goal was accomplished (Angew. Chem. Int. Ed. 2023, e202304844). In this study, the mechanism of NMR signal enhancement via the so-called ‘cross effect’ in the polarizing agent ‘TEKPol’ was studied, which led to the invention of the best-performing polarizing agent in organic solvents to date, dubbed ‘NaphPol’. In addition, work was carried out to evaluate the factors that determine the overall sensitivity provided by DNP using a series of polarizing agents, and strategies to design new DNP polarizing agents. Our results provide new polarizing agents that are effective in both organic and water-based solvents, demonstrating their high versatility.
On the other hand, Gadolinium (Gd)-based polarizing agents are promising for DNP due to their stability in highly reactive chemical environments. However, previously reported Gadolinium polarizing agents perform poorly in comparison to organic radicals. We developed a model that clearly establishes the relationship between the symmetry of the environment around the metal center in Gd complexes and the DNP enhancement (J. Phys. Chem. C 2022, 126, 11310-11317). These results will guide the design of improved Gd-based polarizing agents.
(2) The efficacy of DNP at high temperatures (–70 to 30 °C) depends largely on the solvent used to disperse the polarizing agent. We evaluated the factors that limit the overall DNP efficiency at room temperature in polymers which include the concentration of hydrogen atoms, impurities, and dissolved polarizing agent, which are critical for high DNP enhancements. Our results will provide a recipe for enabling DNP at high temperatures.
(3) Finally, room temperature DNP was successfully achieved in liquids (J. Phys. Chem. Lett. 2022, 13, 7749-7755). While previous research in this area was primarily limited to carbon nuclei in organic molecules, a strategy to transfer polarization to the highly abundant hydrogen atoms was developed. This result opens new possibilities to study challenging systems that contain hydrogen atoms, at room temperature.
In addition to the above, DNP was applied to address challenges in materials science such as the atomic-level characterization of cementitious materials and growth mechanism of shells on nanoparticles. These results impact the development of sustainable materials for society.
(1) Development of polarizing agents: Significant work was carried out to better understand the function of DNP polarizing agents and develop strategies to improve them. DNP is typically performed with organic radical dopants, but the relationship between their atomic-structure and the overall DNP efficiency is not clearly understood. A major milestone towards this goal was accomplished (Angew. Chem. Int. Ed. 2023, e202304844). In this study, the mechanism of NMR signal enhancement via the so-called ‘cross effect’ in the polarizing agent ‘TEKPol’ was studied, which led to the invention of the best-performing polarizing agent in organic solvents to date, dubbed ‘NaphPol’. In addition, work was carried out to evaluate the factors that determine the overall sensitivity provided by DNP using a series of polarizing agents, and strategies to design new DNP polarizing agents. Our results provide new polarizing agents that are effective in both organic and water-based solvents, demonstrating their high versatility.
On the other hand, Gadolinium (Gd)-based polarizing agents are promising for DNP due to their stability in highly reactive chemical environments. However, previously reported Gadolinium polarizing agents perform poorly in comparison to organic radicals. We developed a model that clearly establishes the relationship between the symmetry of the environment around the metal center in Gd complexes and the DNP enhancement (J. Phys. Chem. C 2022, 126, 11310-11317). These results will guide the design of improved Gd-based polarizing agents.
(2) The efficacy of DNP at high temperatures (–70 to 30 °C) depends largely on the solvent used to disperse the polarizing agent. We evaluated the factors that limit the overall DNP efficiency at room temperature in polymers which include the concentration of hydrogen atoms, impurities, and dissolved polarizing agent, which are critical for high DNP enhancements. Our results will provide a recipe for enabling DNP at high temperatures.
(3) Finally, room temperature DNP was successfully achieved in liquids (J. Phys. Chem. Lett. 2022, 13, 7749-7755). While previous research in this area was primarily limited to carbon nuclei in organic molecules, a strategy to transfer polarization to the highly abundant hydrogen atoms was developed. This result opens new possibilities to study challenging systems that contain hydrogen atoms, at room temperature.
In addition to the above, DNP was applied to address challenges in materials science such as the atomic-level characterization of cementitious materials and growth mechanism of shells on nanoparticles. These results impact the development of sustainable materials for society.
The objective to develop robust DNP polarizing agents and methods has resulted in the best DNP-polarizing agent in organic solvents to-date, i.e. ‘NaphPol’, that yield significantly improved performance compared to the previous state of the art. A set of optimal, stable DNP polarizing agents were developed for both organic and water-based solvents, and systematically analysed. Strategies to rationally design novel polarizing agents were developed. The roadmap laid out in our work on Gadolinium-based polarizing agents provides a clear route to improve their DNP efficiency. These results go beyond the state-of-the-art in this field and set new standards for research in this area for the coming decades. The results from this project take a big step forward towards our ultimate goal, which is to develop DNP-enhanced NMR into a robust tool for a plethora of applications, that will in turn benefit society.