Two conformational polymorphs of 4-methylhippuric acid.
Marilia Guillén1, Asiloé J Mora1, Lusbely M Belandria1
1Laboratorio de Cristalografía, Departamento de Química. Facultad de Ciencias, Universidad de Los Andes, Mérida, 5101, Venezuela.
Summary
This study reveals that 4-methylhippuric acid exhibits conformational polymorphism, with two distinct crystal structures (polymorphs I and II) arising from different molecular arrangements. These polymorphs differ in their crystal packing and intermolecular interactions.
Area of Science:
- Solid-state chemistry
- Crystallography
- Molecular structure analysis
Background:
- 4-Methylhippuric acid, a metabolite of p-xylene, possesses rotatable bonds, suggesting potential for multiple stable solid-state structures.
- Understanding polymorphism is crucial for predicting and controlling material properties.
Purpose of the Study:
- To investigate the conformational polymorphism of 4-methylhippuric acid.
- To characterize the distinct polymorphs and their crystal structures.
- To analyze the intermolecular interactions governing crystal packing.
Main Methods:
- Polymorph preparation via solvent evaporation (polymorph I) and mechanical grinding (polymorph II).
- Potential energy surface (PES) analysis to explore conformational landscapes.
- X-ray crystallography for structure determination.
- Hirshfeld surface analysis and Quantum Theory of Atoms in Molecules (QTAIM) for interaction analysis.
Main Results:
- Two true conformational polymorphs (I and II) of 4-methylhippuric acid were successfully prepared.
- PES analysis identified four conformational energy basins, correlating with observed polymorph structures.
- Polymorph I exhibits C(5) and C(7) chains, while polymorph II forms centrosymmetric R22(14) dimers.
- Hirshfeld analysis and QTAIM revealed the hierarchy of interactions, from strong hydrogen bonds to weaker C-H...O and C-H...π interactions.
Conclusions:
- 4-Methylhippuric acid displays conformational polymorphism, with distinct crystal structures driven by molecular conformation.
- Intermolecular interactions, including hydrogen bonding and van der Waals forces, dictate the observed crystal packing.
- The study provides insights into the structure-property relationships of this p-xylene metabolite.
Keywords:
DFT calculationsHirshfeld surface analysisQTAIM and NCI topological analysisconformational polymorphismhydrogen bondingnoncovalent interactionssingle-crystal X-ray diffractionMore Related Videos
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