<p>Accessing metal–organic frameworks (MOFs) with wide mesopores or specific topologies sometimes requires the use of an additional ligand, termed centring structure-directing agent (cSDA), which does not alter the targeted framework’s periodicity. Here we report a general strategy to remove cSDAs post-synthetically, in a single-crystal to single-crystal fashion, enabling deliberate topology transformation often associated with substantial porosity enhancement. Such window opening can be achieved through two distinct routes. The first approach, guided by Pearson’s hard and soft acids and bases (HSAB) principle, uses acid treatment to release cSDAs from robust frameworks, yielding pore volumes for Cr-MOFs of up to 3.6 cm³ g⁻¹. The second, milder approach uses imidazole to selectively substitute cSDAs in MOFs within minutes. This strategy is applicable across various topologies (<b>sod</b>, <b>nia-d</b> and <b>pop</b>), confirming that cSDAs act as temporary architectural elements essential for framework formation and can be removed on demand. This work expands the scope of reticular chemistry by introducing another level of modularity.</p><p></p>