where V i QM is the electrostatic potential generated by the partitioned atomic electron density at a sample point i, V i M M is the corresponding quantity calculated using the point charge model, including any off-centre charge(s), and n is the total number of sample points (located between 1.4 to 2.0 times the van der Waals radius of the atom). By using the atomic, rather than the molecular, electron density, the method scales easily to larger molecules. To limit the search space, off-site charges were restricted to positions determined by the symmetry of the atom's bonding environment. For example, for halogens bonded to a single atom, the search direction is along the bond vector, and for oxygen bonded to two neighbours, the search direction is along the bisector of the two bonds. Similar arguments can be made for positioning two virtual sites. A similar protocol is followed in the current work. Key differences are discussed here and full implementation details are provided in the Supporting Information Section S2.