Previous NMR studies on triazole-containing macrocycles have shown that decreasing the ring size can increase preorganisation by slowing down the interconversion of conformers. However, increasing ring strain may also impact the success of macrocyclization to form the desired macrocycle. To determine whether the smaller macrocycle 2 is pre-organised for Cl -anion binding, we computed a 2D free energy landscape as a function of the torsional angles of the iodotriazole-nitrobenzene linkage using well-tempered metadynamics (WTMetaD 37 ) in explicit DMSO solvent at 300 K (Figure ). The system was described with the General Amber Force Field (GAFF), 38 using an extra particle (EP) point charge during the RESP charge fitting procedure to account for the anisotropy of the halogen atom. The iodine's Lennard-Jones parameters were also modified to better reproduce QM binding distances (See §8 SI and Table for details).