Pair distribution function “feat.” solid-state NMR in a combined approach for structure determination of organic molecules
Abstract
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 ¹ H- ¹³ C double cross polarization and ¹ H double quantum/ ¹ H 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.
Related
- ToSCA: Total Scattering Conditioned Variational Autoencoder for Atomic Structure Prediction from Pair Distribution Function Data
- Ab initio phasing based on topological restraints: automated determination of the space group and the number of molecules in the unit cell
- Rapid and accurate solubility determination of poorly soluble drug molecules by co-solvent extrapolation
- Determination of Hydroquinone Clathrate Stability for Different Guest Molecules Using NPH Ensemble Molecular Dynamics.
- Rapid chromatography combined with trapped ion mobility mass spectrometry for analysis of derivatized small molecules
BibTeX
@article{rosso2026pair,
title = {{Pair distribution function “feat.” solid-state NMR in a combined approach for structure determination of organic molecules}},
author = {Chiara Rosso and Toms Rekis and Michele R. Chierotti and Federica Bravetti},
journal = {Communications Chemistry},
year = {2026},
month = oct,
doi = {10.1038/s42004-026-02233-x},
url = {https://www.nature.com/articles/s42004-026-02233-x},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Pair distribution function “feat.” solid-state NMR in a combined approach for structure determination of organic molecules
AU - Chiara Rosso
AU - Toms Rekis
AU - Michele R. Chierotti
AU - Federica Bravetti
PY - 2026
DA - 2026/10/06
JO - Communications Chemistry
DO - 10.1038/s42004-026-02233-x
UR - https://www.nature.com/articles/s42004-026-02233-x
AB - 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 ¹ H- ¹³ C double cross polarization and ¹ H double quantum/ ¹ H 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.
SN - 2399-3669
ER -