Hydroxyphenylamine phosphonate derivatives: Synthesis, X-ray crystallographic analysis, and evaluation of theirs anti-Alzheimer effects and antioxidant activities

The present study deals with the synthesis and characterization by single-crystal X-ray analysis, UV-Vis and FT-IR spectroscopy of two new alpha-aminophosphonates molecules: ((2-Hydroxy-5-methyl-phenylamino)-phenyl-methyl)-phosphonic acid diethyl ester (MAPH) and ((2-Hydroxy-5-nitrophenylamino)-phenyl-methyl)-phosphonic acid diethyl ester (NAPH), based on the Kabachnik-Fields three component reaction. The structures of MAPH and NAPH have been determined by single-crystal X-ray diffraction analyses. Crystal structure analysis shows that the molecules MAPH and NAPH are connected into a dimeric chains and two-dimensional layers lying parallel to the (1-10) plane respectively, formed through O-H center dot center dot center dot O and C-H center dot center dot center dot O hydrogen bonds. These layers are further extended into a three-dimensional network via C-H center dot center dot center dot pi interactions. Then, the synthesized molecules were screened for their antioxidant potential utilizing seven in vitro assays: ABTS(center dot+), DPPH center dot, GOR, Bleaching of beta-carotene/linoleic acid, CUPRAC, O-phenanthroline and reducing power which exhibited excellent activity particularly with compound MAPH for all the antioxidants assays. Anti-cholinesterase activity method used to estimate the anti-Alzheimer effect in vitro of the two molecules, shows a potent AChE and BCHE, inhibition particularly with compound MAPH. Hence, the molecule (MAPH) may be useful for the oxidative damage related disease treatment. Furthermore, the electronic and thermodynamic properties of the two molecules were evaluated theoretically by DFT calculations. The stable structures were optimized using the hybrid method B3LYP / 6-31G and the different properties were analyzed and compared. The global and local reactivity descriptors of the two molecules were also calculated and discussed. (C) 2020 Elsevier B.V. All rights reserved.

Automated summary

This study synthesized and characterized two new alpha-aminophosphonates molecules, MAPH and NAPH, using single-crystal X-ray analysis, UV-Vis, and FT-IR spectroscopy. These molecules displayed excellent antioxidant potential in various in vitro assays, particularly MAPH, and showed promising anti-Alzheimer effects through inhibition of AChE and BCHE. The electronic and thermodynamic properties of the molecules were evaluated theoretically using DFT calculations, with global and local reactivity descriptors calculated and discussed.