Among the endo-N cages, the Pt 2 L 4 cage emerges as the most promising candidate for encapsulation applications since its volume is close to that of the Pd 2 L 4 cage, which has already demonstrated successful performance in cisplatin encapsulation (Table ). The similarity in volume indicates that Pt 2 L 4 could offer comparable conditions for effective drug encapsulation. On the other hand, the Ni 2 L 4 cage with 2.182% smaller volume than Pd 2 L 4 cage, while slightly smaller in volume, ranks as the second-best alternative for Pd 2 L 4 cage. However, the 2.182% reduced volume of the Ni 2 L 4 cage might limit its effectiveness, particularly in accommodating the drug (Table ). Also, the failure of Cu 2 L 4 to complete the geometry optimization for this cage indicates significant structural instability or distortion, which could severely impact its ability to encapsulate cisplatin. This makes Cu 2 L 4 the least suitable option for encapsulation applications, as its compromised geometry will likely lead to inadequate binding and premature drug release. In addition, the endo-N Au 2 L 4 cage, which is 6.369% larger than the Pd 2 L 4 cage, presents a unique case with its larger internal volume (Table ). While this larger volume might suggest increased capacity, it also poses a risk of premature drug release due to weaker host-guest interactions. This could potentially compromise the effectiveness of the drug delivery system.