High Frequency Dynamic Nuclear Polarization

Abstract

Conspectus During the three decades 1980–2010, magic angle spinning (MAS) NMR developed into the method of choice to examine many chemical, physical and biological problems. In particular, a variety of dipolar recoupling methods to measure distances and torsion angles can now constrain molecular structures to high resolution. However, applications are often limited by the low sensitivity of the experiments, due in large part to the necessity of observing spectra of low-γ nuclei such as the I = ½ species 13C or 15N. The difficulty is still greater when quadrupolar nuclei, like 17O or 27Al, are involved. This problem has stimulated efforts to increase the sensitivity of MAS experiments. A particularly powerful approach is dynamic nuclear polarization (DNP) which takes advantage of the higher equilibrium polarization of electrons (which conventionally manifests in the great sensitivity advantage of EPR over NMR). In DNP, the sample is doped with a stable paramagnetic polarizing agent and irradiated with microwaves to transfer the high polarization in the electron spin reservoir to the nuclei of interest. The idea was first explored by Overhauser and Slichter in 1953. However, these experiments were carried out on static samples, at magnetic fields that are low by current standards. To be implemented in contemporary MAS NMR experiments, DNP requires microwave sources operating in the subterahertz regime — roughly 150–660 GHz — and cryogenic MAS probes. In addition, improvements were required in the polarizing agents, because the high concentrations of conventional radicals that are required to produce significant enhancements compromise spectral resolution. In the last two decades scientific and technical advances have addressed these problems and brought DNP to the point where it is achieving wide applicability. These advances include the development of high frequency gyrotron microwave sources operating in the subterahertz frequency range. In addition, low temperature MAS probes were developed that permit in-situ microwave irradiation of the samples. And, finally, biradical polarizing agents were developed that increased the efficiency of DNP experiments by factors of ~4 at considerably lower paramagnet concentrations. Collectively these developments have made it possible to apply DNP on a routine basis to a number of different scientific endeavors, most prominently in the biological and material sciences. This Account reviews these developments, including the primary mechanisms used to transfer polarization in high frequency DNP, and the current choice of microwave sources and biradical polarizing agents. In addition, we illustrate the utility of the technique with a description of applications to membrane and amyloid proteins that emphasizes the unique structural information that is available in these two cases.

Overhauser effects in insulating solids

“…In addition, in the case of SA-BDPA and BDPA there is a strong positive enhancement at the center of the field profile due to the Overhauser effect with ZQ relaxation dominating and yielding a positive enhancement. We also have observed a weak negative OE (ε = −0.6) when using d 21 -BDPA ( Figure 1(c)), a result that is consistent with DQ relaxation dominating the enhancement.…”

“…Figures 1(a)-1(c) show 1 H DNP-MAS enhancement field profiles obtained from samples containing the polarizing agents trityl OX063, SA-BDPA, BDPA, and perdeuterated BDPA (d 21 -BDPA) at 9.4 T using 9 W of microwave power (see Figures 2 and 3 for the molecular structures and EPR spectra, respectively). The data were recorded by observing the intensity of the dilute 1 H signals with and without μw irradiation.…”

“…These approaches have resulted in large signal enhancements and have enabled many experiments that would otherwise be impossible. [19][20][21][22][23] by Overhauser 25 and confirmed by Carver and Slichter, 26 has not been identified or utilized during the course of this renaissance. Although the possibility of an OE in insulator was discussed by Abragam, 27 the conventional wisdom is that Overhauser DNP is important only in systems with mobile electrons such as conductors (metals and low dimensional conductors) or in liquid solution.…”

“…These approaches have resulted in large signal enhancements and have enabled many experiments that would otherwise be impossible. [19][20][21][22][23] Nevertheless, with the exception of an early example on a 1D conductor, 24 the Overhauser effect (OE), which was the initial DNP mechanism proposed a) Current address: Institute for Physical and Theoretical Chemistry, Institute for Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University Frankfurt, 60438 Frankfurt am Main, Germany.…”

Unprecedented Carbon Signal Enhancement in Liquid‐State NMR Spectroscopy

“…Any increase by technical means will significantly extend the possibility range of NMR application.”1 This quotation from Richard Ernst's Nobel prize lecture sets the stage for numerous studies and approaches to improve the signal‐to‐noise‐ratio (S/N) in NMR. In recent years, many different methods, including PHIP,2 SABRE,2 hyperpolarized noble gases,3 MAS DNP,4 nitrogen vacancies in diamonds,5 dissolution DNP,6 and DNP in the solid‐state,7 have been developed, and a summary of these can be found in a recent review article in Angewandte Chemie 8…”