The Development of DNP-NMR

Dynamic Nuclear Polarization (DNP) uses the large thermal polarization of the electron spin reservoir of a paramagnetic polarizing agent to provide a sensitivity boost for NMR experiments—by several orders of magnitude. In a DNP experiment, the electron polarization is transferred to the nuclei by microwave/terahertz radiation of its electron paramagnetic resonance (EPR) transition.

The Development of Dynamic Nuclear Polarization NMR Spectroscopy

The technique is not new; DNP was first proposed in 1953 by Albert E. Overhauser and experimentally confirmed by Carver and Slichter the same year. However, while over the last decades NMR experiments were performed at increasingly high magnetic fields to gain resolution and sensitivity, the advances in microwave and millimeter wave technology could not keep up with the trend to higher frequencies and relegated DNP as an exotic method.

The first application of DNP started in the early 1960’s to generate polarized targets for solid-state physics experiments. Almost all known DNP mechanisms that are still in use today, namely the solid-effect (SE), the cross-effect (CE), thermal-mixing (TM) and the Overhauser-Effect (OE) were discovered in these early years of DNP spectroscopy. At the same time, theoretical descriptions of the mechanisms were developed based on the spin-temperature concept.

In the 1970’s DNP was extensively used in solution state NMR experiments to study molecular motions and interactions in solutions (work by Hausser/Stehlik and Mueller Warmuth). These experiments were typically limited to frequencies up to 60 MHz (1H) corresponding to an electron Larmor frequency of 39 GHz.

While NMR spectroscopy migrated to ever-higher magnetic fields, DNP couldn’t keep up due to the slower pace of advances in microwave technology. However, during the 1980’s and 1990’s, the interest in solid-state DNP grew to enhance the sensitivity in solid-state (magic-angle spinning) NMR experiments (work by Schaefer to study polymers and Wind to study coal).

The modern DNP area started in 1993 with the first use of a gyrotron as a high-frequency/high-power source. For the first time the method was no longer limited by the availability of high-power THz sources. The initial focus was to enhance solid-state NMR experiments for structural biology—with one of the first examples being DNP-enhanced ssNMR experiments to study membrane proteins.

At the same time new polarizing agents were developed. Until the early 2000’s stable, organic (mono-) radicals (e.g. BDPA, nitroxides) were typically used, with reasonable performance. However, a better understanding of the involved polarizing mechanisms lead to the development of bi-radicals, with TOTAPOL a polarizing agent that is soluble in aqueous media, giving much larger DNP enhancements compared to nitroxide-based mono-radicals.

The recent improvements in instrumentation and the availability to perform DNP-enhanced ssNMR at high magnetic fields has led many scientists to revisit the technique, and applications in structural biology and material science have been reported. This can be seen by the numbers of research articles published in the field; since the early 2000’s this number has been exponentially growing.

The challenges in high-field, solution-state DNP experiments are even bigger than in ssNMR spectroscopy due to the high ohmic losses of the sample and the heating effects associated with it. For in-situ experiments, THz resonators are required to separate the electric and magnetic field components of the THz radiation. At high frequencies, the physical dimensions of these resonators become very small, making it a very challenging task to fabricate them.

Alternative methods for polarization were developed in the early 2000’s with dissolution DNP being one of the most successful concepts currently employed. Improvements in THz and RF technology have led to new solution-state probe designs and in-situ OE solution-state DNP experiments were very recently reported in which the sample is directly polarized at 400 MHz (9.5 T, 268 GHz e-) using a very small resonator.

Further reading

Please note: The list of references that is given throughout the text above is by no means complete. For the interested reader, here is a list of recent reviews giving a broad overview of the field of solution and solid-state DNP-NMR Spectroscopy: