2025-04-10 早稲田大学
<関連情報>
サリドマイドのエナンチオマー結晶とラセミ結晶の格子定数、分子構造、反応空洞に温度変化がどのように影響するか How Temperature Change Affects the Lattice Parameters, Molecular Conformation, and Reaction Cavity in Enantiomeric and Racemic Crystals of Thalidomide
Ayaka Matsumoto,Kenta Nakagawa,Takuya Nakanishi,Akiko Sekine,Sosuke Kojo,Mizuki Kira,Sota Sato,Norio Shibata,and Toru Asahi
Journal of the American Chemical Society Published: March 27, 2025
DOI:https://doi.org/10.1021/jacs.4c18394
Abstract
For the single crystals of thalidomide (C13H10N2O4, TD) grown by the solvent evaporation method, the temperature dependences of the crystal structures have been investigated over a wide temperature range between 100 and 423.15 K. Comparing the α-form of a racemic TD crystal, which consists of symmetric heterochiral dimers and belongs to P21/n space group, with the enantiomeric TD crystal, which belongs to P21 and consists of asymmetric (pseudosymmetric) homochiral dimers, there have been clear differences in the temperature-dependent changes of the lattice parameters, the isobaric linear thermal expansion coefficients (along the crystallographic and the principal Cartesian axes), the volumetric expansion coefficients of the unit cell, and the structures of hydrogen-bonded dimer in the crystal such as intra- and intermolecular dihedral angles, cavities (reaction cavities), and the hydrogen-bond length. In the asymmetric homochiral dimers, one monomer with a larger reaction cavity changes its intramolecular dihedral angle with temperature, while the other monomer with a smaller cavity does not. In contrast, in the symmetric heterochiral dimers, two monomers with the same cavity volume similarly change their intramolecular dihedral angles with the temperature. Such differences in the temperature-dependent conformational changes between asymmetric and symmetric dimers cause differences between enantiomeric and racemic crystals.
