"Dynamic Nuclear Polarization at Millimeter Wavelengths"

Dr. Robert Guy Griffin, Arthur Amos Noyes Professor of Chemistry

MIT, Department of Chemistry

Hosted by: Aaron Rossini & Frédéric A. Perras

Abstract: In the 1950’s dynamic nuclear polarization (DNP) was demonstrated to enhance sensitivity of NMR
spectra by Overhauser and Slichter. Nevertheless, DNP remained a latent technique, because of the 
paucity of high frequency (>140 GHz) microwave sources available to perform experiments at high 
fields (>5 T). To address this issue, we introduced gyrotron oscillators as scalable frequency sources 
that enable DNP at arbitrarily high fields/frequencies. Currently, there are about 70 gyrotron oscillators 
operating in DNP spectrometers around the globe at frequencies up to 593 GHz and there are plans 
to operate them at 790 GHz (28.2 T).

One of the main thrusts of DNP was to provide increased sensitivity for magic angle spinning (MAS)
spectroscopy of membrane and amyloid protein experiments. A problem frequently encountered in 
these experiments is the broadened resonances that occur at low temperatures when motion is 
quenched. In some cases, protein spectra are homogeneously broadened, and therefore that higher 
Zeeman fields and faster spinning is required to recall the resolution. We show this is the case for 
MAS DNP spectra of Ab1-42 amyloid fibrils where the resolution at 100 K is identical to that at room 
temperature. Furthermore, we compare the sensitivity of DNP and 1
H detected experiments and find that DNP, even with a modest ℇ=22, is ~x6.5 times more sensitive. Bacteriorhodopsin is the 
archetypical membrane protein and studies of its photocycle intermediates have been possible 
because of the signal enhancements provided by DNP.

Recently, we have also investigated time domain DNP/EPR experiments, such as time optimized 
pulsed (TOP) DNP, the frequency swept-integrated solid effect (FS-ISE) and two recently discovered 
variants – the stretched solid effect (SSE) and the adiabatic solid effect (ASE). We find that the latter 
two experiments can give up to a factor of ~2 larger enhancement than the FS-ISE. The SSE and ASE 
experiments should function well at high fields.

Finally, we discuss two new instrumental advances. First, a frequency swept microwave source 
that permits facile investigation of field profiles. It circumvents the need for a B0 sweep coil and the 
compromise of field homogeneity and loss of helium associated with such studies. This 
instrumentation has permitted us to elucidate the polarization transfer mechanism of the Overhauser 
effect and also revealed interesting additional couplings (ripples) in field profiles of cross effect 
polarizing agents. We have recently extended the approach to 800 MHz/527 GHz. Second, to improve
the spinning frequency in DNP experiments, we have developed MAS rotors laser machined from 
single crystal diamonds. Diamond rotors should permit higher spinning frequencies, improved
microwave penetration, and sample cooling.

Bio:
Since assuming an independent position in 1972, my scientific goals have been twofold: (1) to develop new 
methods based on solid state NMR to determine the structure and function of biological systems, and (2) to apply 
these techniques to interesting problems involving the structure and function of proteins, membranes, nucleic
acids and macromolecular systems. We focus on problems that are largely inaccessible to XRD and solution 
NMR techniques. We were one of the first groups to initiate biological solid state NMR experiments, a field that 
is now a rapidly expanding scientific enterprise. 

Initially, we began by studying 2H and 31P spectra of static samples of membrane lipids, but the absence of resolution and low sensitivity stimulated us to develop (1) methods for magic angle spinning (MAS), (2) dipolar recoupling to measure distances and torsion angles, and 
(3) instrumentation for high frequency dynamic nuclear polarization (DNP) and EPR instrumentation to increase 
sensitivity by factors of 100-300. To date the primary applications of these techniques is to problems in structural 
biology of membrane and amyloid proteins. Our successful efforts in developing recoupling and high frequency 
DNP MAS experiments and applications to membrane and amyloid proteins were recently recognized by the 
following awards: the Günther Laukien Prize (2007), the Eastern Analytical Society Prize (2007), the International 
Society of Magnetic Resonance (ISMAR) Prize (2010), the Sacconi Medal (2011), election to the American 
Academy of Arts and Sciences (2012), the ACS E.B. Wilson Prize for Spectroscopy (2016), the EUROMAR R.R. 
Ernst Prize in Magnetic Resonance (2017) , the Bijvoet Medal (2018), election to the US National Academy of 
Sciences (2021), and the Zavoisky Award and the Bonhoffer Lecture (2024).

My academic responsibilities involve teaching quantum and statistical mechanics and thermodynamics to
MIT undergraduates and graduate students. 

Griffin Group – Spinning All The Hits