2016. 57, 6 – UDC 548.73:543.422:548.737 STRUCTURAL STUDY OF THE STABILITY OF THE CAPTOPRIL DRUG REGARDING THE FORMATION OF ITS CAPTOPRIL DISULPHIDE DIMER M.C. de Souza1, L.F. Diniz1, C.H. de Jesus Franco1, H.A. de Abreu2, R. Diniz1 1Departamento de Quнmica, ICE / Universidade Federal de Juiz de Fora – Campus Universitбrio, Brazil E-mail: renata.diniz@ufjf.edu.br 2Departamento de Quнmica, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil Received May, 5, 2015 Revised — April, 6, 2016 Captopril disulphide is obtained under hydrothermal conditions. <...> The IR and Raman spectra data are in agreement with the X-ray diffraction results. <...> The disappearance of the band at 2566 cm–1 ((SH)) in both spectra of captopril disulphide is consistent with the formation of the S—S bond. <...> The degradation of the captopril drug is investigated by Raman spectroscopy and the results indicate that after 6 weeks of air exposure, a band at 512 cm–1, assigned as (SS), is observed, suggesting the formation of captopril disulphide. <...> DFT calculations in the solid state are performed for captopril and captopril disulphide. <...> The results indicate that captopril disulphide is approximately 30 kcalmol–1 more stable than captopril. <...> The analysis of the total density of states (DOS) reveals that the captopril valence band contains a significant contribution from the S atom, whereas for captopril disulphide, the O atom is the most important for the valence band. <...> Captopril (1-[(2S)-3-mercapto-2-methylpropionyl]-L-proline) was the first nonpeptidic orally active ACE inhibitor utilized for the treatment of hypertension. <...> Captopril is an efficient ACE inhibitor via the oral route and is commonly used to treat high blood pressure, congestive heart failure, and cardiovascular disease. <...> However, it is highly susceptible to oxidation caused by high temperatures, humidity, air exposure or mixture with hygroscopic excipients. <...> The mechanism of the action of the captopril ACE inhibitor antihypertensive drug is related to the formation of a (in vivo) complex with the catalytic Zn2+ ion present at the active site of angiotensin I-converting enzyme. <...> In this complex, the coordination geometry of the Zn2+ ion is tetrahedral. <...> The Zn2+ centre is coordinated to two histidine molecules by two nitrogen atoms of the imidazole <...>