¹H Detected Relayed Dynamic Nuclear Polarization

Abstract

Recently, it has been shown that methods based on the dynamics of 1 H nuclear hyperpolarization in magic angle spinning (MAS) NMR experiments can be used to determine mesoscale structures in complex materials. However, these methods suffer from low sensitivity, especially since they have so far only been feasible with indirect detection of 1 H polarization through dilute heteronuclei such as 13 C or 29 Si. Here we combine relayed-DNP (R-DNP) with fast MAS using 0.7 mm diameter rotors at 21.2 T. Fast MAS enables direct 1 H detection to follow hyperpolarization dynamics, leading to an acceleration in experiment times by a factor 16. Furthermore, we show that by varying the MAS rate, and consequently modulating the 1 H spin diffusion rate, we can record a series of independent R-DNP curves that can be analyzed jointly to provide an accurate determination of domain sizes. This is confirmed here with measurements on microcrystalline l -histidine·HCl·H 2 O at MAS frequencies up to 60 kHz, where we determine a Weibull distribution of particle sizes centered on a radius of 440 ± 20 nm with an order parameter of k = 2.2.

Imaging Radial Distribution Functions of Complex Particles by Relayed Dynamic Nuclear Polarization

“…Using 1 H saturation recovery experiments, the polarization build-up of the different components (components 1 and 2 and the DNP solvent) can then be monitored as a function of the polarization delay, with and without μwave irradiation of the sample, either directly in the 1 H spectrum if the chemical shifts are resolved, 28 or indirectly through transfer to 13 C, 15 N, or some other convenient probe nucleus. 35 The DNP enhancement as a function of the polarizing time for the different components can then be determined by calculating the ratio between signal intensities with and without μwaves for each component (Figure 1d).…”

“…24,25,28,29 Notably these models have been used to measure domain sizes in organic solids, 16,24,25,28 including at high magnetic fields and fast magic-angle spinning (MAS), up to 60 kHz. 35 The transport of DNP enhanced polarization by 1 H spin diffusion in a multi-component particle can be described by solving the spin diffusion eq 1. 24,25,28,29…”

“…The spontaneous transfer of hyperpolarization in the sample can be accurately described using thermodynamic models analogous to heat or mass transfer. ,,, Notably these models have been used to measure domain sizes in organic solids, ,,, including at high magnetic fields and fast magic-angle spinning (MAS), up to 60 kHz …”

“…Typically, this might be the case, for example, for pharmaceutical amorphous solid dispersions, which are becoming increasingly important . Finally, the imaging method introduced here should become faster and more robust with the development of DNP at high magnetic fields and fast MAS (up to 65 kHz MAS), allowing 1 H detected R-DNP imaging to be implemented …”

PyrroTriPol: a semi-rigid trityl-nitroxide for high field dynamic nuclear polarization

“…For organic solvents, HyTEK-2, 37 a BDPA-nitroxide, has recently been reported as an efficient polarizing agent with DNP enhancement factors of up to 200 and a buildup time of 8 s using a 32 mM radical concentration in a 0.7 mm rotor at 21.1 T. 45 A major drawback of BDPA-based biradicals is their limited solubility in aqueous solutions and apparent low persistence even in organic solvents, 37,[45][46][47][48][49] although new BDPA derivatives with improved properties have recently been reported. 48 Tritylnitroxide structures for organic solvents were also prepared and generated enhancements of z50 using 15 mM solution, however their performance was only assessed at 9.4 T. 50,51 Here we introduce a new trityl-nitroxide family, dubbed Pyrro-TriPol, that can be used in aqueous and non-aqueous based media.…”