Structure determination of enalapril maleate form II from high-resolution X-ray powder diffraction data

✍ Scribed by Y.-H. Kiang; Ashfia Huq; Peter W. Stephens; Wei Xu

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: English
• Weight: 205 KB
• Volume: 92
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.10430

✦ Synopsis

The crystal structure of polymorphic Form II of enalapril maleate, a potent angiotensin-converting enzyme inhibitor, was determined from high-resolution X-ray diffraction data using the direct space method. Enalapril maleate Form II crystallizes in space group P2 1 2 1 2 1 , Z ¼ 4, with unit cell parameters a ¼ 33.9898(3) A ˚, b ¼ 11.2109(1) A ˚, c ¼ 6.64195(7) A ˚, and V ¼ 2530.96(5) A ˚3. By treating the molecules as rigid bodies and using the bond lengths and angles obtained from the X-ray single crystal structures of Form I, which were solved almost 20 years ago, the total degrees of freedom of enalapril maleate were reduced from 25 to 12. This reduction in total degrees of freedom allowed the simulated annealing to complete within a reasonable computation time. In the crystal structure of Form II, the crystal packing, hydrogen-bonding pattern, and conformation of enalapril maleate resemble those in the structure of Form I. The crystal packing and conformation of enalapril maleate in the two polymorphic forms may explain the similarity of the thermal properties, 13 C nuclear magnetic resonance, Fourier transform infrared, and Raman spectra of Forms I and II. In both structures, the conformations of the main peptide chains, which are considered responsible for binding the active angiotensin-converting enzyme sites, remain largely unchanged. Lattice energy calculation showed that Form II is slightly more stable than Form I by 3.5 kcal/mole.