title: Molecular structure and stability of perindopril erbumine and perindopril L-arginine complexes.
abstract: The methods of theoretical chemistry have been used to elucidate molecular properties of the antihypertensive, cardiovascular protective and antithrombotic 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). The geometries and energies of various neutral and ionized complexes of perindopril erbumine and perindopril l-arginine have been computed using HF/6-31G(d) and Becke3LYP/6-31G(d) methods. The calculations showed that in both, the isolated state and water solution perindopril erbumine exists as a neutral complex. In the gas-phase perindopril l-arginine both neutral and ionic complexes are, at the HF level of theory, almost equally stable. The B3LYP level of theory slightly favors single proton transfer complex perindopril l-arginine (by about 14 kJ mol(-1)). In polar solvents like water, the ionized form of perindopril l-arginine becomes much more favored. According to our calculations l-arginine is bound to perindopril more strongly (by about 25 kJ mol(-1)) than erbumine.
authors.affiliation: Comenius University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Odbojarov 10, SK-832 32 Bratislava, Slovakia. remko@fpharm.uniba.sk
authors.forename: Milan
authors.initials: M
authors.lastname: Remko
mesh_terms: D000959:Antihypertensive Agents / Q000737:chemistry*; D001120:Arginine / Q000737:chemistry*; D004355:Drug Stability; D007477:Ions; D008958:Models, Molecular; D015394:Molecular Structure; D020913:Perindopril / Q000737:chemistry*; D012995:Solubility; D012997:Solvents; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D000959:Antihypertensive Agents; D007477:Ions; D012997:Solvents; D001120:Arginine; D020913:Perindopril