Synthesis and computational characterization of aryl-fluorinated thiazoles: Experimental, DFT and molecular coupling studies

Three series of fluorinated aromatic thiazoles were synthesized through the Hantzsch reaction. This occurred between the corresponding fluorinated aromatic carbothioamides and the semi aromatic alpha-halo ketones. The structures of the synthesized compounds were elucidated by spectroscopic studies such as infrared spectroscopy (IR), nuclear magnetic resonance (H-1 and F-19-NMR) and mass spectrometry (HR-MS). Global reactivity descriptors such as absolute electronegativity (chi), hardness (eta), softness (S) and chemical potential (mu) were calculated by means of the density functional theory (DFT), from which the compounds substituted with nitro group display the best reactivity indicators. A molecular coupling study was carried out using the rat enzyme tyrosine hydroxylase (1toh) to test the biological activity of our compounds against Toxoplasma gondii, where the 5d compound shows binding energies and inhibition constants that suggest inhibitory activity on this enzyme.