VIBRATIONAL SPECTROSCOPIC INVESTIGATION AND MOLECULAR STRUCTURE OF a 5α-Reductase INHIBITOR: FINASTERIDE

Abstract

By way of Density Functional Theory (DFT)-based computational methods with commercially available software, the computational work of which about the molecular properties, the vibrational modes and vibrational frequencies of finasteride were accomplished for the first time. In order to gain a deeper and more thorough understanding of the molecular structure and infrared spectrum of finasteride, the equilibrium geometry harmonic vibrational frequencies and geometric parameters (bond lengths, bond angles and dihedral angles) were calculated by Generalized Gradient Approximations (GGAs) with five different density functional methods (PBE, RPBE, HCTH, PW91 and BLYP), using Material Studio 8.0 program. Theoretical vibrational frequencies and theoretical optimized geometric parameters were compared with the corresponding experimental data, which concluded that the GGA/PW91 method were shown to be in a good agreement with the results of experiment. In addition, the highest occupied molecular orbital (HOMO) energies, the lowest unoccupied molecular orbital (LUMO) energies and electron density isosurface calculations were done with an aim at a better understanding of the stability and reactivity of the molecule, indicating that the alkene and lactam conjugated system on the ring A is more likely to interact with other species. And, the atomic charge distribution was also calculated to understand the charge effect caused by electronegative atoms, which shows that the possible active-sites in chemical reactions are N 1 and O 1 .

Harmonic Vibrational Frequency Simulation of Pharmaceutical Molecules via a Novel Multi-Molecular Fragment Interception Method

“…However, up to the present, all of the research works have been optimized and frequency-calculated by constructing single-molecular structures with different functionals and basis sets [ 23 , 24 ]. The molecules were placed in a vacuum environment, and no heed was given to the spatial configuration and hydrogen bonding of the molecules.…”