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

• Published in: Journal of the Iranian Chemical Society Vol. 14; no. 2; pp. 427 - 442
• Main Authors: Gholivand, Khodayar, Ebrahimi Valmoozi, Ali Asghar, Salahi, Mina, Taghipour, Fatemeh, Torabi, Elham, Ghadimi, Saied, Sharifi, Mahboobeh, Ghadamyari, Mohammad
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.02.2017; Springer Nature B.V
• Subjects: Analytical Chemistry; Biochemistry; Chemical synthesis; Chemistry; Chemistry and Materials Science; Cholinesterase; Critical point; Crystal structure; Electron density; Hydrogen bonding; Hydrogen-based energy; Inorganic Chemistry; Insecticides; Insects; Mathematical models; Molecular orbitals; Nitrogen; NMR; Nuclear magnetic resonance; Organic Chemistry; Original Paper; Parameters; Physical Chemistry; Principal components analysis; Spectral methods; Temephos; QSAR; Cholinesterase inhibitor; Bisphosphoramidate; Hydrogen bond
• ISSN: 1735-207X; 1735-2428
• DOI: 10.1007/s13738-016-0991-y

A series of temephos (Tem) derivatives with the general structure of P(O)NH–X–NHP(O) ( 1–22 ) were synthesized and characterized by 31 P, 13 C, 1 H 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 PC 1 are predominated from those related to electronic in PC 2 and structural parameters in PC 3 equation. Multiple linear regressions–QSAR models clarified that the molecular descriptors like an integrated net charge of nitrogen atom ( Q N ), polarizability (PL N–H ) and lowest unoccupied molecular orbital ( E LUMO ) proved important in defining the activity of the candidates.