We used LFMM parameters derived from density functional reference data for the description of the Nickel coordination as reported in ref [25]. Ligands and pillars are described using the general amber force field (GAFF), which we also employed for all guest molecules. Atomic charges of the MOF framework have been taken from ref [25] (calculated using the CM5 methodology). Atomic charges of the guest molecules were calculated using the ChElPG formalism 32 implemented in Gaus-sian09 using the TPSSh functional and a TZVP basis. Further details are available in Section 1.1 of the SI. An extended DL POLY Classic software was used for MD simulations. The NσT ensemble was used by employing a Nose-Hoover thermostat and a Hoover at 300 K (blue) and 400 K (red). Experimental references are given as green ranges if available. Reproduced under the terms of the Creative Commons Attribution 4.0 License. barostat (pressure of 1 atm). The total simulation time was 1 ns consisting of 2 × 10 6 simulation steps with a timestep of 0.5 fs. A 4x4x4 supercell of conformer B(op) containing a total of 4224 atoms was used in periodic boundary conditions for simulations. Guest molecules were loaded into the op phase inside spheres of radius 4 A with the help of the Packmol code. By employing a stepwise removal routine of the guest molecules (see SI for details) we ensured closing of the structures into the B(cl) o conformer. The maximum loading used here should in principle exceed the maximum amount that can be loaded in experiments, since the computational approach is not limited by pore accessibility and partially closed structures. Maximum loadings from experiments and the ones used here are given in Table in the SI. Analysis of the trajectories was performed using the Atomistic Simulation Environment (ASE) Python library. We separated the total system energy into three parts: The MOF energy (E MOF ), the guest energy (E Guest ), and the MOF-guest interaction energy (E MOF-Guest ). The former two are obtained by calculating single-point energies on the respective parts of the systems, while the MOF-guest interaction is calculated via