Microwave-assisted synthesis, DFT theoretical study and biological activities evaluation of two phosphonylated m-toluidine derivatives

Abstract

An easy and efficient microwave-assisted method has been developed for the synthesis of two phosphonylated molecules: α-aminophosphonic acid (MTA) and α-aminophosphonate ester (MTE). To achieve these, we have synthesized the products from m-toluidine, under microwave conditions. All of the obtained compounds were characterized by Microanalysis, UV–Vis, FT-IR, and 1H, 13C and 31P NMR spectroscopic methods. The spectral results are in good line with the proposed structures. Density Functional theory (DFT) calculations were carried out using Gaussian09 program package, using 6–31G++(d,p) basis set. The frontier orbital energies were presented and have been used to predict global reactivity indices. Results showed that MTE is more reactive and less stable than MTA. The Mulliken atomic charges, dipole moment and thermodynamic proprieties were also calculated and discussed. In addition, the target compounds were evaluated for their in vitro antioxidant, antimicrobial and antienzymatic activities. The biological assays indicated that these compounds displayed potent inhibitory activity toward acetylcholinesterase (MTE: 92.71±0.91%, MTA: 67.32±0.52%) and butyrylcholinesterase (MTE: 79.16±0.47% and MTA 34.80±0.76%). It was also found that they act as excellent antiradical agents (ABTS: MTA/226.077±0.29 μg/ml, MTE/ 535,993±0.30 μg/ml and DPPH: MTA/311.853 ± 0.14 μg/ml, MTE/621.627 ± 0.12 μg/ml). In addition, these compounds exhibited the highest antibacterial and antifungal properties.