3.2. Importance of improper dihedral parameters involving metals. Proper and improper dihedral parameters involving metal centers are rarely considered as they are expected to have a negligible influence on geometry. However, while testing the [Pd2L4] 4+ cage in implicit solvent, we observed during the MD simulation structures where linkers were stacked on top of each other (Figure ). As a result, the donor atom connected to the metal deviates from the expected planar position. This made us wonder if such an artefact was due to the omission of dihedral parameters around the metal. Indeed, including improper dihedrals centred on the donor atom yielded structures similar to those obtained from QM in implicit solvent (Figure ). Interestingly, these parameters can be omitted in explicit solvent, likely due to the dominant effect of solvent-solute interaction over solute-solute stacking interactions. For example, during 100 ns MD simulation in explicit dimethylsulfoxide (DMSO), when no metalinvolved improper dihedrals are included, less than 10% of the configurations adopted a staggered configuration compared to 50% in implicit solvent (Figure ).