In this paper, we use the Zn4O-based IRMOF (isoreticular metal-organic frameworks) family as 95 exemplar materials. These MOFs have the same framework topology but by extending the length of the linkers, e.g. using biphenyldicarboxylate (IRMOF-10) instead of benzenedicarboxylate (IRMOF-1), the cavity diameter increases from ca. 12 to 17 Å and the window diameter between cavities from ca. 8 to 11 Å. Alternatively, the window diameter can be artificially reduced by adding bulky side chains to the linker molecules. We simulate the energetics of desorption as a function of solvent and 100 framework properties, providing clear mechanistic explanation for the phenomenon and hence tools to aid synthetic route planning for experimental researchers.