Investigating the biological activities of N-(halophenyl)-1-(naphthalen-2-yl)methanimine compounds: Synthesis, crystal structures, DFT computational, In vitro antidiabetes, and antioxidant studies

• Six new N-(halophenyl)-1-(naphthalen-2-yl)methanimine compounds were synthesized and characterized by conventional means. • Crystal structures of N1, N2 and N6 were obtained, indicating that the naphthalene ring and the phenyl ring are almost in the same plane. • Hirshfeld surface analyses was also carried out and showed that H···H intermolecular interactions are dominant. • Compounds N2 and N6 displayed good antioxidant activity. • All compounds showed poor to fair antidiabetes activity. Compounds N1 – N6 with a general nomenclature of N-(halophenyl)-1-(naphthalen-2-yl)methanimine [where halo = 2-fluoro ( N1 ), 4-fluoro ( N2 ), 2‑chloro ( N3 ), 3‑chloro-4-fluoro ( N4 ), 2‑bromo ( N5 ) and 4‑bromo ( N6 )] were synthesized and elucidated by exploring FT-IR, UV–Vis, ( 1 H & 13 C) NMR and mass spectra while the purity of the compounds was ascertained by exploring elemental analysis. The C9―C8―C7―N1 dihedral angle for N1, N2 and N6 are 175.53(2)°, 171.37(2)° and 170.78(2)° respectively and this indicates that the naphthalene ring and the halogenated phenyl ring are almost in the same plane. Hirshfeld surface analysis showed that, H ‧‧‧ H intermolecular interactions are dominant among all the short contacts present in the crystal lattice of N1 (40.4 %), N2 (35.4 %) and N6 (32.8 %). The results for the quantum chemical calculations revealed that, N3 and N6 have the same and lowest energy bandgap (∆E) of 3.88 eV and this poses them to be the most chemically reactive and less stable among all the synthesized compounds. Compound N2 and N6 displayed good 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity with IC 50 values of 0.23 mM and 0.54 mM respectively while catechin (reference drug) has an IC 50 value of > 2.0 mM. These two compounds ( N2 and N6 ) also exhibited good nitric oxide radical (NO • ) scavenging ability, outshining catechin. However, all the compounds showed poor to fair antidiabetes potential with none of the compounds showing superior activity over acarbose. All the compounds comply with Lipinski's Ro5 rule indicating that, they are orally bioavailable and less toxic.