Structural and spectroscopic analysis of the Cis-Trans isomers of the captopril in the gaseous and aqueous phases

Abstract

• Cis and trans isomers of captopril found by scan around a dihedral angle. • Comparison of the molecular frontier orbitals and chemical descriptors of captopril. • Comparative analysis of captopril vibrational spectra in cis and trans conformations. • Comparative analysis of MEP and Mulliken charges distribution of captopril isomers. Captopril is a drug widely used in hypertension treatment. This molecule has two isomeric forms ( cis and trans ) according to the dihedral angle ω (O4C18N5C15). In the present study, we theoretically rotated the dihedral angle in steps of 5° in the range of -180° to 180°, using the DFT calculation with the functional B3LYP and the basis set 6–31 G ++(d, p) both in a gaseous environment and in an aqueous solution. In each environment, we were able to find a minimum energy structures, calculate the energy of the frontier orbitals (HOMO and LUMO) for the captopril in the gas phase and in aqueous solution, as well as calculate their vibrational spectra. When analyzing the HOMO and LUMO orbitals, all conformations presented HOMO around the sulfur atom. LUMO, on the other hand, presented a higher concentration around the aromatic ring and the carboxyl group, mainly in aqueous solution. Although trans conformers have a larger energy gap, the cis conformers showed a better reactive index. The cis and trans conformers showed similar MEP. In addition, the Raman and infrared spectroscopy proved to be an excellent technique to identify the isomeric form of the captopril molecule, observing the stretching modes of the carbonyl groups. The geometry and surfaces of the molecular potentials provide support for identifying the formation of the hydrogen bond.