The defined synthesis of OMS in MOFs is the basis for targeted functionalization through grafting, the coordination of weakly binding species and increased (supramolecular) interactions with guest molecules.

Herein, we report a pre‐synthetic pore environment design strategy to achieve stable methyl‐functionalized metal–organic frameworks (MOFs) for preferential SO₂ binding and thus enhanced low (partial) pressure SO₂ adsorption and SO₂/CO₂ separation. The enhanced sorption performance is for the first time attributed to an optimal pore size by increasing methyl group densities at the benzenedicarboxylate linker in [Ni₂(BDC‐X)₂DABCO] (BDC‐X=mono‐, di‐, and tetramethyl‐1,4‐benzenedicarboxylate/terephthalate; DABCO=1,4‐diazabicyclo[2,2,2]octane). Monte Carlo simulations and first‐principles density functional theory (DFT) calculations demonstrate the key role of methyl groups within the pore surface on the preferential SO₂ affinity over the parent MOF. The SO₂ separation potential by methyl‐functionalized MOFs has been validated by gas sorption isotherms, ideal adsorbed solution theory calculations, simulated and experimental breakthrough curves, and DFT calculations.