Synthesis, solid state self-assembly driven by antiparallel π⋯π stacking and {⋯H-C-C-F} 2 dimer synthons, and in vitro acetyl cholinesterase inhibition activity of phenoxy pendant isatins.

A series of novel phenoxy pendant isatins PI1-12 have been synthesized in excellent yields by a simple nucleophilic substitution reaction involving isatins and 1-(2-bromoethoxy)-4-substituted benzenes, and characterized by their FT-IR, 1 H NMR, 13 C NMR and GC-MS data, and in the case of PI4 by its single crystal X-ray analysis. The solid-state structure of PI4 showed an intriguing and unique 1D-supramolecular chain-based self-assembled structure, the driving force of which is mainly the strong antiparallel π⋯π stacking and {⋯H-C-C-F} 2 dimer synthons. This compound not only highlights the potential of the isatin moiety in forming strong antiparallel π⋯π stacking interactions but also provides a platform to have considerable insight into the nature, strength and directionality of much debated π-π and C-H⋯F-C interactions. The in vitro biological studies revealed that three phenoxy pendant isatins PI1, PI2 and PI4 are highly potent inhibitors of acetylcholinesterase enzyme with IC 50 values of 0.52 ± 0.073 μg ml -1 , 0.72 ± 0.012 μg ml -1 and 0.68 ± 0.011 μg ml -1 , respectively, showing comparable activity to the standard drug, donepezil (IC 50 = 0.73 ± 0.015 μg ml -1 ). A simple and efficient synthesis of phenoxy pendant isatins PI1-12 from inexpensive and commercially available starting materials, and their high potential of acetyl cholinesterase inhibition provide an attractive opportunity to find more effective medication for Alzheimer's disease (AD).