title: Computational study of influence of diffuse basis functions on geometry optimization and spectroscopic properties of losartan potassium.
abstract: The work was aimed at investigating the influence of diffusion of basis functions on the geometry optimization of molecule of losartan in acidic and salt form. Spectroscopic properties of losartan potassium were also calculated and compared with experiment. Density functional theory method with various basis sets: 6-31G(d,p) and its diffused variations 6-31G(d,p)+ and 6-31G(d,p)++ was used. Application of diffuse basis functions in geometry optimization resulted in significant change of total molecule energy. Total molecule energy of losartan potassium decreased by 112.91kJ/mol and 114.32kJ/mol for 6-31G(d,p)+ and 6-31G(d,p)++ basis sets, respectively. Almost the same decrease was observed for losartan: 114.99kJ/mol and 117.08kJ/mol respectively for 6-31G(d,p)+ and 6-31G(d,p)++ basis sets. Further investigation showed significant difference within geometries of losartan potassium optimized with investigated basis sets. Application of diffused basis functions resulted in average 1.29Å difference in relative position between corresponding atoms of three obtained geometries. Similar study taken on losartan resulted in only average 0.22Å of dislocation. Extensive analysis of geometry changes in molecules obtained with diffused and non-diffuse basis functions was carried out in order to elucidate observed changes. The analysis was supported by electrostatic potential maps and calculation of natural atomic charges. UV, FT-IR and Raman spectra of losartan potassium were calculated and compared with experimental results. No crucial differences between Raman spectra obtained with different basis sets were observed. However, FT-IR spectra of geometry of losartan potassium optimized with 6-31G(d,p)++ basis set resulted in 40% better correlation with experimental FT-IR spectra than FT-IR calculated with geometry optimized with 6-31G(d,p) basis set. Therefore, it is highly advisable to optimize geometry of molecules with ionic interactions using diffuse basis functions when accuracy of results is a priority.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznań, Poland.
authors.forename: Mikołaj
authors.initials: M
authors.lastname: Mizera
authors.affiliation: Institute of Molecular Physics, Polish Academy of Science, 60-179 Poznań, Poland.
authors.forename: Kornelia
authors.initials: K
authors.lastname: Lewadowska
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznań, Poland.
authors.forename: Alicja
authors.initials: A
authors.lastname: Talaczyńska
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznań, Poland. Electronic address: jpiontek@ump.edu.pl.
authors.forename: Judyta
authors.initials: J
authors.lastname: Cielecka-Piontek
mesh_terms: D003198:Computer Simulation; D019808:Losartan / Q000737:chemistry*; D008958:Models, Molecular; D017550:Spectroscopy, Fourier Transform Infrared; D013059:Spectrum Analysis, Raman
chemical_list: D019808:Losartan
keywords: DFT; FT-IR; Losartan potassium; NBO; Raman spectroscopy; UV