Zwitterionic or Not? Fast and Reliable Structure Determination by Combining Crystal Structure Prediction and...

Area of Science:

• Solid-state chemistry
• Crystallography
• Spectroscopy

Background:

• Crystal Structure Prediction (CSP) offers insights into solid-state packing without diffraction data.
• Coupling CSP with solid-state NMR (SSNMR) enhances predictive accuracy, forming CSP-NMR crystallography (CSP-NMRX).
• Determining the solid-state form (zwitterionic or not) of molecules like pyridine dicarboxylic acids is crucial.

Purpose of the Study:

• To apply the CSP-NMRX method for accurate crystal structure determination of three pyridine dicarboxylic acid isomers.
• To investigate the zwitterionic nature and solid-state structures of quinolinic, dipicolinic, and dinicotinic acids.
• To validate the efficacy of CSP-NMRX in predicting and confirming crystal structures.

Main Methods:

• Utilized mono- and bidimensional SSNMR experiments (e.g., 1H MAS, 13C/15N CPMAS, 1H DQ MAS, 1H-13C HETCOR) to ascertain molecular structure and arrangement.
• Employed advanced SSNMR techniques (14N-1H PM pulse, RESPDOR) for precise N-H distance measurements.
• Performed CSP calculations and used Root Mean Square Errors (RMSEs) of computed vs. experimental chemical shifts for structure selection.

Main Results:

• Successfully determined the crystal structures of quinolinic (zwitterionic), dipicolinic (non-zwitterionic), and dinicotinic acids (exhibiting a zwitterionic-non-zwitterionic continuum).
• Confirmed the hybrid nature of dinicotinic acid with a shared proton using refined SSNMR experiments.
• Demonstrated a strong agreement between CSP-NMRX selected structures and experimental data, with RMSEs aiding in accurate structure selection.

Conclusions:

• CSP-NMRX is a highly effective method for precise crystal structure determination, especially for complex molecules like pyridine dicarboxylic acids.
• SSNMR provides essential molecular input, reducing CSP computational load and enabling reliable structure selection.
• The study highlights the nuanced solid-state behavior of dinicotinic acid, showcasing a proton sharing phenomenon.