Structural characterization and solution rotational isomerism of delapril hydrochloride, a dipeptide angiotensin-converting enzyme inhibitor

The solid state structure of delapil hydrochloride was determined by single-crystal X-ray diffraction analysis (monoclinic, P21, a=16.098(5), b=10.712(3), c=7.856(2) A , β=97.85(2)° . The comparison between delapril and other ACE inhibitors of the same family is discussed with regard to the geometry of the phenomenological active site of the enzyme. In the solid state the amide bond conformation resulted in being trans, whereas, in solution, NMR spectra indicate that the molecule exists as a mixture of rotational isomers trans and cis (approximately 70:30). The free energy of activation for the hindered rotation about the amide bond was determined by line-shape analysis. The attempt to isolate possible conformational polymorphs failed, indicating that the trans conformation is favored when molecules pack together in the crystal.