The HetPCM method was implemented in a locallymodified version of Q-Chem, where it can be used alongside the PEqS algorithm from Ref. 21 and the isotropic SwiG-PCM algorithm from Ref. 76. PEqS solvation energies for various molecules and basis sets can be found in Tables , which serve to document the implementation for reproducibility, and analogous data for HetPCM can be found in Tables S7-S10. A code to generate the Voronoi-PEqS grids (introduced in Section 3 .1 .2 below) is available. 3.1. Permittivity Models. PEqS calculations require specification of the permittivity function ε(r) in threedimensional space. This procedure was originally introduced for use with a van der Waals (vdW) molecular cavity, i.e., a sharp dielectric interface (as in eq. 1), defined by atomic spheres, somewhat smoothed for the numerical reasons discussed in Section 2 .3. We will call this the "vdW-PEqS" approach, for which the construction of ε(r) is described in Section 3 .1 .1. Alternatively, the "Voronoi-PEqS" method introduced in Section 3 .1 .2 uses atom-centered dielectric regions to define ε(r), as a model that can be compared to HetPCM.