Measuring Nano- to Microstructures from Relayed Dynamic Nuclear Polarization NMR

Abstract

We are grateful to Matthew Conley and Christophe Coperet from ETH Zurich for providing the mesoporous silica materials. We are grateful to Prof. P. Tordo, Dr. O. Ouari, and Dr. G. Casano (Aix-Marseille Universite, France) for providing the biradicals used in the DNP NMR experiments.International audienceWe show how dynamic nuclear polarization (DNP) NMR can be used in combination with models for polarization dynamics to determine the domain sizes in complex materials. By selectively doping a source component with radicals and leaving the target undoped, we Can measure experimental polarization buildup curves which can be compared with simulations based on heterogeneous distributions of polarization-within the sample. The variation of the integrated DNP enhancement as a function of the polarization time is found to be characteristic of the geometry. We demonstrate the method experimentally on four different systems where we successfully determine domain sizes between 200 and 20 000 nm, specifically in powdered histidine hydrochloride monohydrate) pore lengths of mesoporous silica materials, and two domain sizes in two component polymer film coatings. Additionally, we find that even in the apparently homogeneous frozen solutions used as polarization sources in most DNP experiments, polarization is relayed from protons near the radicals to the bulk of the solution by spin diffusion, which explains the experimentally observed buildup times in these samples

DNP‐enhanced solid‐state NMR spectroscopy of active pharmaceutical ingredients

“…The spin diffusion model also predicts that the magnetization buildup can be fit with stretched exponential functions and that the apparent magnitude of the DNP enhancement will decrease as the polarization time is increased (Figure c). Both of these predictions have been confirmed by experiments . Larger enhancements are obtained at shorter polarization times because the buildup of DNP‐enhanced polarization at the surface of the particles accelerates the diffusion of polarization into the particles, resulting in shorter signal buildup time constants in the DNP‐enhanced NMR experiments as compared to the thermally polarized NMR experiments.…”

“…Models of 1 H spin diffusion have been widely applied in solid‐state NMR spectroscopy to understand diverse phenomena such as enhanced longitudinal relaxation and mixing and segregation of solid phases and to estimate the sizes of domains or particles . Numerical and analytical models of 1 H spin diffusion can be used to obtain a fundamental understanding of the factors that determine the magnitude of the DNP enhancements in relayed DNP experiments . As we describe in the applications section below, measurements of DNP enhancements can be combined with models of 1 H spin diffusion to estimate the diameter of API particles or domains within formulated pharmaceuticals.…”

“…Consequently, larger DNP enhancements are usually measured at short polarization delays, and DNP enhancement usually decreases as the polarization time is increased in relayed DNP NMR experiments. Note that in glassy frozen solutions where the radical PA is homogeneously distributed, the CE DNP enhancement usually shows no variation with the polarization delay …”

“…This plot is useful to estimate the magnitude of the relayed DNP enhancement if the particle size and proton T 1 of the solid are known. Recently, Pinon et al have described phenomenological relations between ε ∞ and the radius of a spherical analyte ( R ): …”

Targetable Tetrazine-Based Dynamic Nuclear Polarization Agents for Biological Systems

“…4, SI Fig.5). [37][38] To this end, we compared the buildup behavior of a sample prepared with 15 mM dispersed TOTAPOL and samples containing 1 mM or 50 μM Ub-TTz. While the dispersed sample displayed a monoexponential buildup curve with a 5.8 s time constant, the behavior of the Ub-TTz samples appeared more complex.…”