Conformational profile, vibrational assignments, NLO properties and molecular docking of biologically active herbicide1,1-dimethyl-3-phenylurea

Abstract

1,1-Dimethyl-3-phenylurea (known as fenuron) which is a phenyl urea-based widely used herbicide exhibits interesting structural and conformational properties and a notable biological activity. A detailed analysis on the vibrational, molecular and electronic characteristics of fenuron has been carried out. Potential energy scans (PESs) performed at the B3LYP/6-311++G(d,p) level of theory predicted two possible minima corresponding to the optimized anti and synforms resulting from the internal rotation about the N-C bond. The presence of an auxochrome together with the interaction with DMSO solvent exhibited a blue shift corresponding to the C=O orbitals. Delocalization of HOMO and LUMO orbital facilitated the charge transfer effect in the molecule. The calculated HOMO-LUMO energies, chemical potential, energy gap and global hardness suggested a low softness value for the compound while its biological activity was described by the value of electrophilicity. Chlorine substitution in the phenyl ring influenced the orbital delocalization for ortho and para substitutions but that of meta remained unaffected. NLO properties were noticed to increase due to chlorine substitution in the parent molecule. The docking results suggested that the compound exhibits an inhibitory activity against mitochondrial ubiquinol-cytochrome-c reductase and can be developed as a potential anticancer agent.

Keywords: DFT; Fenuron; Molecular docking; NBO; NLO; Organic chemistry; Pharmaceutical chemistry; Theoretical chemistry.

Fig. 1

FT-IR spectrum of fenuron.

Fig. 2

FT-Raman spectrum of fenuron.

Fig. 3

Optimized geometry of fenuron.

Fig. 4

Potential energy scan resulting from the rotation of H₁₁N₁₀-C₁₂O₁₃ dihedral angle.

Fig. 5

Potential energy scan resulting from the rotation of H₁₁N₁₀-C₃C₂ dihedral angle.

Fig. 6

Potential energy scan resulting from the rotation of O₁₃C₁₂-N₁₄C₁₅ dihedral angle.

Fig. 7

VCD spectrum of fenuron.

Fig. 8

TG/DTG spectrum of Fenuron.

Fig. 9

UV spectrum of Fenuron.

Fig. 10

HOMO-LUMO plots of (a) fenuron (b) ortho chlorine (c) meta chlorine (d) para chlorine.

Fig. 11

MEP plots of (a) fenuron (b) ortho chlorine (c) meta chlorine (d) para chlorine.

Fig. 12

Ramachandran plot PDB ID 3I73.

Fig. 13

Main chain parameters of PDB ID 3I73 (a) Ramanchandran plot quality assessment (b) peptide bond planarity-omega sd (c) Measure of bad non-bonded interactions (d) Alpha carbon tetrahedral distortion (e) Hydrogen bond energies (f) Overall G-factor.

Fig. 14

2D interactive plot of ligand with the residues of themitochondrialubiquinol-cytochrome-c reductase of (a) fenuron (b) ortho chlorine (c) meta chlorine (d) para chlorine.

Fig. 15

The docked ligand at the active site of mitochondrial ubiquinol-cytochrome-c reductase of (a) fenuron (b) ortho chlorine (c) meta chlorine (d) para chlorine.