Magnetically recyclable CoFe₂O₄@HKUST-1 nanocatalyst for sustainable carbon–nitrogen coupling, and structure-affinity relationship study of the synthesized products via molecular docking

α-Ketoamides and their derivatives serve as critical foundational components in the fields of natural products, pharmaceutical research, and organic synthesis. In this investigation, we developed an environmentally sustainable Metal–Organic Framework (MOF)-based nanocomposite that functions as a multifunctional catalytic system for the production of α-Ketoamide derivatives. This heterogeneous nanocomposite, referred to as CoFe₂O₄@HKUST-1, was synthesized through a series of steps. In this regard, CoFe₂O₄ Magnetic Nanoparticles (MNPs) were synthesized by the co-precipitation process. Then, HKUST-1 was synthesized via an in-situ process. Afterward, CoFe₂O₄@HKUST-1 was functionalized by thioacetamide to obtain a Thioacetamide@CoFe 2 O 4 @HKUST-1 nanocatalyst. Various analytical techniques, including Energy-dispersive X-ray (EDX) spectroscopy, field-emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and vibrating sample magnetometer (VSM) have been employed to validate the structure of the synthesized catalyst. The Thioacetamide@CoFe 2 O 4 @HKUST-1 nanocatalyst system, characterized by the magnetic properties of CoFe 2 O 4 MNPs, allows for easy separation from the reaction mixture through the application of an external magnet. Notably, a modest quantity of the synthesized nanocatalyst (15 mol%) has demonstrated remarkable catalytic efficacy in the production of α-Ketoamide derivatives (63–98%) within a brief reaction period (1 h) at a temperature of 60 °C. The observed catalytic performance may be attributed to the cooperative contribution of the composite components and the surface functionalization induced by thioacetamide treatment. Overall, it can be contended that Thioacetamide@CoFe 2 O 4 @HKUST-1 warrants greater focus owing to its non-toxic nature, straightforward preparation process, excellent recyclability, and impressive catalytic efficiency. Molecular docking studies of the synthesized α-ketoamide compounds with aldose reductase (AR) revealed binding affinities ranging from − 5.72 to − 9.485 kcal/mol, with compound 1-(naphthalen-1-yl)-2-(piperidin-1-yl)ethane-1,2-dione (3bg) exhibiting near-equivalent affinity (− 9.485 kcal/mol) to the reference inhibitor Tolrestat (− 9.523 kcal/mol). These results demonstrate the potential of α-ketoamidesbased scaffolds to serve as competitive AR inhibitors, consistent with Tolrestat's mechanism of targeting catalytic residues (Tyr48, His110, Trp111, Cys303) via hydrogen bonding and hydrophobic interactions.