Bisphosphoramidate derivatives: synthesis, crystal structure, anti-cholinesterase activity, insecticide potency and QSAR analysis

A series of temephos (Tem) derivatives with the general structure of P(O)NH–X–NHP(O) (1–22) were synthesized and characterized by 31P, 13C, 1H NMR and FT-IR spectral techniques. The electron density (ρ) value at the bond critical point (bcp) of P(1′)–O(1′)···(1)H–N(1) (0.040 e Å−3) P(1)–O(1)···(1′)H–N(1′) (0.031 e Å−3) as well as the stabilization energy of electronic delocalization of results of NBO analysis showed the hydrogen bonding energy in P(1′)–O(1′)···(1)H–N(1) model (E 2 = −72.15 kJ mol−1) and P(1)–O(1)···(1′)H–N(1′) (E 2 = −45.67 kJ mol−1) of the crystal cluster 7. The activities of Tem derivatives were evaluated using the modified Ellman’s method on cholinesterase (ChE) enzymes. The insecticide activity of Tem analogous appraised for the elm leaf beetle in which the 18 had more effective than the other compounds in inhibition α-esterase of insect. Principal component analysis–quantitative structure activity relationship (PCA–QSAR) models indicated that it was deduced that the frontier molecular orbital energy parameters in PC1 are predominated from those related to electronic in PC2 and structural parameters in PC3 equation. Multiple linear regressions–QSAR models clarified that the molecular descriptors like an integrated net charge of nitrogen atom (Q N), polarizability (PLN–H) and lowest unoccupied molecular orbital (E LUMO) proved important in defining the activity of the candidates.