As cis-Pd2L2L'2 MOCs were being targeted specifically, the heteroleptic assemblies requiring computational investigation were straightforward to enumerate. cis-and trans-[Pd2(1)2( )2] 4+ cage models for all 12 heteroleptic ligand combinations were built 38 using stk based on ligand conformers generated with the ETKDG algorithm in RDKit. These were initially optimised using UFF in the General Utility Lattice Program (GULP), 40 followed by semi-empirical GFN2-xTB 41 methods and subsequently by DFT (PBE0/Def2-SVP/D3BJ/PCM(DMSO)). From these, single-point energies (SPEs) for the minimised structures were calculated. Importantly, if the xTB data could be shown to reliably replicate those of DFT methods, the significantly cheaper semi-empirical methods could be used for high-throughput screening.