Nanostructure of Materials Determined by Relayed Paramagnetic Relaxation Enhancement

Abstract

Particle and domain sizes strongly influence the properties of materials. Here we present an NMR approach based on paramagnetic relaxation enhancement (PRE) relayed by spin diffusion (SD), which allows us to determine lengths in the nm−μm range. We demonstrate the method on multicomponent organic polymer mixtures by selectively doping one component with a paramagnetic center in order to measure the domain size in a second component. Using this approach we determine domain sizes in ethyl cellulose/hydroxypropyl cellulose film coatings in pharmaceutical controlled release formulations. Here we measure particle sizes ranging from around 50 to 200 nm.

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

“…Therefore, with the analysis of the DNP enhancements and signal buildup times, it was possible to measure the size of the EC domains (Figure ). Simulation of the variation in the relayed DNP enhancements with polarization time indicated that the length of the EC domains was 0.2 μm, in good agreement with measurements of the EC domain size made using paramagnetic relaxation enhancement …”

“…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 .…”

“…Relaxation and spin diffusion solid‐state NMR experiments have been broadly applied to probe the macroscopic structure and ordering or mixing within solid materials such as polymers . In the context of pharmaceutical formulations, analysis of T 1 relaxation time constants, rotating‐frame longitudinal relaxation times ( T 1ρ ), and spin diffusion rates are commonly used to assess the degree of mixing between excipients, polymers, coformers, and APIs .…”

Measuring Nano- to Microstructures from Relayed Dynamic Nuclear Polarization NMR

“…16−19 It has also been shown that the selection process can be replaced by selective doping of one of the domains of the diamagnetic system with paramagnetic species and using paramagnetic relaxation enhancement to estimate the domain sizes. 20 In these approaches, the initial out-of-equilibrium state is achieved by selective doping followed by either comparison with spin diffusion dynamics in an undoped sample or comparison to a state in which the doped region is hyperpolarized. The curves obtained through comparison of the two initial states for different recovery times in saturationrecovery experiments can then be interpreted using numerical solutions of the diffusion equations.…”

Linear-scaling ab initio simulations of spin diffusion in rotating solids

“…The exponential scaling of spin dynamics simulations drastically limits the size of the spin systems that can be studied; as a result, researchers have developed innovative approximate solutions to the many-body dynamics involved in large groups of spins. Notable examples include the concept of spin temperature, 25 the modeling of spin diffusion using classical diffusion equations [26][27][28][29][30] or as a multistep rate process, [31][32][33][34] and the simulation of DNP in large spin systems using a kinetic Monte Carlo algorithm. [35][36][37] Recent efforts have been increasingly directed at reducing the size of the density matrix by removing unimportant, or unpopulated, states from the basis set such that fully ab initio spin dynamics simulations can be performed in spin systems containing hundreds of spin-1/2 nuclei.…”