Molecular Mobility of Different Forms of Ketoprofen Based on DFT Calculation Data
Kapitolina A. Logacheva, Α. V. Belushkin, P. Gergelezhiu, Alexander B. Eresko, Sergey N. Malakhov, Елена Владимировна Ракша, Liudmila I. Savostina, Dorota M. Chudoba · 2024
Ketoprofen is a representative of the group of non-steroidal anti-inflammatory drugs widely used in modern medical therapy.The intramolecular dynamics of ketoprofen are of particular importance, since the mobility of its main structural fragments is one of the key factors determining the efficiency of drug binding to the enzyme.Investigations of such processes taking into account the acid-base properties of ketoprofen have not been carried out.DFT calculations for molecular, anionic and ion pair forms of ketoprofen were performed at the BP86/def2-TZVP level of theory using ORCA software.The intramolecular dynamics of the main structural fragments were investigated for the molecular, anionic and ion pair forms of ketoprofen.The most stable conformers were revealed for all considered forms, and the barriers of intramolecular rotation were estimated.It was shown that the structures of the ketoprofen forms studied are labile but characterized by different mobility.