Crystal and molecular structure of perindopril erbumine salt

The crystal structure of perindopril (2S,3aS,7aS)-1-[(2S)-2-[[(2S)-1-ethoxy-1-oxopentan-2-yl]amino]propanoyl]-2,3,3a,4,5,6,7,7a-octahydroindole-2-carboxylic acid) erbumine salt C23H43N3O5, angiotensin-converting enzyme inhibitor, was determined from single-crystal X-ray diffraction data. The compound crystallizes in the triclinic, non-centrosymetric space group P1, with unit cell dimensions a = 6.575(3), b = 12.165(5), c = 16.988(8) Å and α = 97.153(4), β = 94.417(4), γ = 90.349(4)°, Z = 2. The structure was refined by full matrix least squares methods to R = 0.037. In the solid state ionized molecules of perindopril and erbumine are linked together forming a complex via O⋯HN+ hydrogen bonds between the positively charged amino groups of the erbuminium cations and oxygen atoms of the perindopril carboxylate groups. Intermolecular NH⋯O and CH⋯O contacts seem to be effective in the stabilization of the structure, resulting in the formation of a three-dimensional network.The gas-phase structure of perindopril–erbumine complex was optimized by the HF/6-31G(d) and Becke3LYP/6-31G(d) methods. The conformational behavior of this salt in water was examined using the CPCM and Onsager models. In both the gas phase and water solution the perindopril erbumine will exist in prevailing triclinic form.

► Triclinic structure of perindopril erbumine.
► The crystal packing is stabilized by intermolecular NH⋯O and CH⋯O hydrogen-bond interactions.
► In the isolated state triclinic form of perindopril erbumine exists as a neutral complex.
► The monoclinic form of salt is formed by two symmetrical ionic hydrogen bonds of the NH3+⋯−OOC type.
► In both the gas phase and water solution the perindopril erbumine will exist in prevailing triclinic form.