Raphael Kircher

• Nuclear magnetic resonance (NMR) spectroscopy is an excellent tool for reaction and process monitoring. Process monitoring is often carried out online on flowing samples. Benchtop NMR spectrometers are especially well-suited for these applications because they can be installed close to the studied process. However, it is a challenge to analyze a fast-flowing liquid with NMR spectroscopy because short residence times in the magnetic field of the spectrometer result in inefficient polarization build-up and thus poor signal intensity. This is particularly problematic for benchtop NMR spectrometers because of their compact design. Therefore, different methods to counteract this prepolarization problem in benchtop NMR spectroscopy were studied experimentally in the present work. Established approaches that were studied gave only poor results at high flow velocities. To overcome this, signal enhancement by Overhauser DNP (ODNP) was used, which is based on polarization transfer from unpaired electron spins to nuclear spins and happens on very short time scales, resulting in high signal enhancements, also in fast-flowing liquids. A corresponding set-up was developed and used for the studies: the line leading to the 1 Tesla benchtop NMR spectrometer first passes a fixed bed of a radical matrix which is placed in a Halbach magnet equipped with a microwave cavity to facilitate the polarization transfer. With this ODNP set-up, excellent results were obtained also for the highest studied flow velocities. This shows that ODNP is an enabler for fast-flow benchtop NMR spectroscopy. ODNP requires the presence of unpaired electrons in the sample which is usually accomplished by addition of stable radicals. However, radicals affect the nuclear relaxation times and can hamper the NMR detection. This was circumvented by immobilizing radicals in a fixed bed, allowing for the measurement of radical-free samples when using ex situ DNP techniques (DNP build-up and NMR detection happen at different places) with flow-induced separation of the hyperpolarized liquid from the radicals. Therefore, the synthesis of robust and chemically inert immobilized radical matrices is mandatory. This was accomplished by immobilizing the radical glycidyloxy-tetramethylpiperidinyloxyl (GT) with a polyethyleneimine (PEI) linker on the surface of controlled porous glasses (CPG). Both the porosity of the CPGs and also the size of the PEI-linker were varied resulting in a set of distinct radical matrices for continuous-flow ODNP. The study shows that CPGs with PEI linkers provide robust, inert, and efficient ODNP matrices. Another method to address the prepolarization problem in continuous-flow NMR applications is paramagnetic relaxation enhancement (PRE) by using a T1 relaxation agent. In the present work, a PRE agent was developed that was again based on PEI-grafted CPGs with PEI-linker and GT. Here, the interaction of the studied liquid with this PRE agent significantly accelerates the buildup of nuclear polarization prior to NMR detection, which enables quantitative measurements in continuous-flow benchtop NMR applications. The results show that the flow regime for quantitative measurements can be greatly extended by the use of the synthesized PRE agent.