Captopril and its dimer captopril disulfide: comparative structural and conformational studies

Abstract

The crystal structures of captopril {systematic name: (2S)-1-[(2S)-2-methyl-3-sulfanylpropanoyl]pyrrolidine-2-carboxylic acid}, C 9 H 15 NO 3 S, (1), and its dimer disulfide metabolite, 1,1 0 -{disulfanediylbis[(2S)-2-methyl-1-oxopropane-3,1-diyl]}bis-lproline, C 18 H 28 N 2 O 6 S 2 , (2), were determined by single-crystal X-ray diffraction analysis. Compound (1) crystallizes in the orthorhombic space group P2 1 2 1 2 1 , while compound (2) crystallizes in the monoclinic space group P2 1 , both with one molecule per asymmetric unit. The molecular geometries of (1) and (2) are quite similar, but certain differences appear in the conformations of the five-membered proline rings and the side chains containing the sulfhydryl group. The proline ring adopts an envelope conformation in (1), while in (2) it exists in envelope and slightly deformed half-chair conformations. The conformation adopted by the side chain is extended in (1) and folded in (2). A minimum-energy conformational search using Monte Carlo methods in the aqueous phase reveals that the optimized conformations of the title compounds differ from those determined crystallographically, which depend on their immediate environment. Intermolecular O-HÁ Á ÁO and relatively weak C-HÁ Á ÁO interactions seem to be effective in both structures and, together with S-HÁ Á ÁO and C-HÁ Á ÁS contacts, they create three-dimensional networks.

Surfactant-Free Chitosan/Cellulose Acetate Phthalate Nanoparticles: An Attempt to Solve the Needs of Captopril Administration in Paediatrics

“…The peaks in the pattern of CAT coincide with Powder Diffraction File No. 35-1916 of captopril (Figure 5), which crystallises in the orthorhombic system, space group P2 (1) 2 (1) 2 (1) [38]. CAP is an amorphous material, in agreement with literature data [39,40].…”

Self-Assembly of Angiotensin-Converting Enzyme Inhibitors Captopril and Lisinopril and Their Crystal Structures

“… 24 Captopril crystals were also obtained by slow evaporation from acetone or tetrahydrofuran–water solutions. 26 Lisinopril crystals were obtained by the vapor-diffusion technique using water as a solvent and acetonitrile as the precipitant. 27 Other groups explored the controlled dehydration of lisinopril crystals by recrystallizing the material from water solutions.…”

Bioconjugation of Captopril–Light Subunit of <i>Agaricus bisporus</i> Mushroom Tyrosinase: Characterization and Potential Use as a Drug Carrier for Oral Delivery

“…Unfortunately, these angiotensin-converting enzyme (ACE) inhibitors also show poor absorption, low bioavailability, and short half-lives. 16) On the other hand, captopril is reactive, and can form reversible disulfide bonds with components of the blood, such as albumin, L-cysteine, and glutathione. Thus, captopril appears appealing upon selection of drug model for disulfide bond facilitated conjugation.…”