Pair distribution function "feat." solid-state NMR in a combined approach for structure determination of organic molecules.

Investigating the local structure of molecular solids is critical for establishing structure-property relationships and controlling material performance. Pair distribution function (PDF) analysis probes poorly crystalline, nanocrystalline and amorphous materials, yet its application to organic compounds remains limited. The recently developed Global-PDF-Fit method enables ab initio crystal structure determination of organic molecules, although intrinsic limitations can complicate unique structure identification. Here, we present a synergistic workflow integrating Global-PDF-Fit with solid-state NMR (SSNMR), demonstrating how restraints and intermolecular proximity constraints from 1D magic angle spinning (MAS) and 2D 1H-13C double cross polarization and 1H double quantum/1H single quantum MAS SSNMR experiments reduce computational time, guide structure ranking, and increase reliability, enabling unambiguous structure determination. Demonstrated on 5-aminosalicylic acid and S-naproxen (crystallite sizes of 50-55 nm), the approach provides a robust strategy for structure determination and represents a significant advance in the field of local-structure elucidation of poorly crystalline and nanocrystalline organic solids, where conventional diffraction techniques fail.