Laser-induced twisting of phosphorus functionalized thiazolotriazole as a way of cholinesterase activity change

Herein, the synthesis, design, and the physicochemical characterization of phosphorus functionalized thiazolotriazole (PFT) compound are presented. The PFT tests on the biological activity revealed butyrylcholinesterase inhibition that was confirmed and explained with molecular docking studies. The pronounced reduction of optical density and biological activity was found as a result of irradiation of the PFT water solution with laser beam at wavelength 266 nm. The observed phenomenon was explained on the base of molecular dynamics, docking, and density functional theory modeling by the formation of PFT conformers via laser-induced phosphonate group twisting. The reorganization of the PFT geometry was found to be a reason of butyrylcholinesterase inhibition mechanism change and the site-specificity loss. These results demonstrate that PFT combines photoswitching and bioactive properties in one molecule that makes it promising as a molecular basis for the further design of bioactive substances with photosensitive properties based on the mechanism of the phosphonate group phototwisting. [Display omitted] •Phosphorus functionalized thiazolotriazole (PFT) inhibits butyrylcholinesterase (BChE).•Laser irradiation of PFT results in BChE inhibition decrease.•Laser irradiation leads to formation of PFT conformers associated with the phosphonate group twisting.•Laser-induced PFT geometry reorganization results in BChE inhibition mechanism change.•PFT combines photoswitching and bioactive properties in one molecule.