Synthesis, characterization, DFT and molecular docking analysis of N-phenyl-2-((4-(3-phenylthioureido)phenyl)selanyl)acetamide

Abstract

In this study, we disclose the synthesis of a new organoselenium (OSe) candidate, N-phenyl-2-((4-(3-phenylthioureido)phenyl)selanyl)acetamide (5), achieved in three synthetic steps starting from the commercially available chemical, aniline. The chemical structure of the target OSe compound 5 was characterised using NMR, IR, and mass spectrometry. The DFT calculations were performed. The results reveal that compound 1 demonstrates the lowest HOMO energy (-5.03 eV) and the most significant energy gap (3.62 eV), indicating high stability and low reactivity. In contrast, compound 2 shows the highest HOMO energy (-3.62 eV) and the smallest energy gap (1.31 eV), confirming its high reactivity and low stability. HB168 and compound 3 demonstrate intermediate properties with moderate reactivity and stability. The Dipole Moment analysis highlights strong polarity in HB168 (6.47 Debye) and weak polarity in S2 (0.27 Debye). Additionally, compound 1 displays the highest electronegativity (3.22 eV) and lowest electrophilicity index (2.86 eV), further supporting its stability and low reactivity. Conversely, compound 2 exhibits the highest electrophilicity index (6.71 eV), indicating a strong electrophilic character. The prepared OSe compound was docked against three bacterial strain protein targets: Escherichia coli (ID: 5L3J) as gram-negative bacteria, whereas Bacillus Subtilis (ID: 7S3L) and Staphylococcus aureus (ID: 3BL6) was chosen as the gram-positive bacteria. Also, molecular docking were performed against three drugs as a reference drug Ampicillin as a wide spectrum antibiotic and Ebselen, Diphenyl diselenide as a Selenium containing drugs.