Assessing B12N12 and Al12N12 nanocages as potential vehicles for 1-(phthalazin-1(2 <i>H</i> )-one)[(pyridin-2-yl)ethylidene]hydrazine, against onchocerciasis: a DFT study

This work explores the potential of B₁₂N₁₂ and Al₁₂N₁₂ nanocages as carriers for 1-(phthalazin-1(2<i>H</i>)-one)[(pyridin-2-yl)ethylidene]hydrazone (APN). Density functional theory (DFT) calculations at M06/def2-SVP were conducted for energy minimization and at M06/def2-TZVP level for property calculations. Molecular electrostatic surface potential (ESP) analysis of APN identified two potential adsorption sites: the pyridine nitrogen (confA) and the azomethine nitrogen (confB). Thermochemical analysis indicates that the APN-nanocage complexes are energetically favorable, spontaneous and exothermic with confA complexes exhibiting the highest stability. Global reactivity studies indicate that complexation especially <i>via</i>confA significantly presents enhanced reactivity as evidenced by their lower HOMO-LUMO energy gaps and favourable electron transfer properties. QTAIM and NCI analyses show that the main interactions in the complexes are intermediate and non-covalent. Drug likeness analysis was equally performed and APN has a promising drug-like profile and could be a suitable candidate for further development as an orally bioavailable drug. Conclusively, both nanocages show promise as carriers for APN in the treatment of onchocerciasis.