All steric descriptors were computed using the MORFEUS program. These include Sterimol parameters, buried volume, distal volume, Cipso-H bond length in ArHet-H, and Cipso-Ccarbonyl bond lengths in ArHet-CO2H and ArHet-CO2 -. Sterimol parameters, developed by Verloop, describe substituent size. The Sterimol length (L) is the vector length from the hydrogen on the ipso carbon of ArHet-H through the carbon to the tangent of the van der Waals (vdW) surface. B1 and B5 are the minimum and maximum widths, defined by the shortest and longest vectors from the ipso carbon to the vdW surface and perpendicular to L. Buried volume was originally developed to quantify the steric hindrance caused by ligands in transition metal complexes. Here, the fraction buried volume (VBur) was calculated from the percentage of space occupied by the ArHet substituent within a sphere of 3.5 Å radius centred on the ipso carbon (Fig. ). The distal volume describes the volume occupied by ArHet outside of this sphere. Using this approach, the computed steric descriptors could distinguish between different regioisomers (e.g., 3-bromo-2-pyridyl vs. 3-bromo-4pyridyl, Fig. ). The universal quantitative dispersion descriptor (Pint) was derived by constructing a molecular vdW surface and calculating dispersion coefficients using Grimme's D3 dispersion correction method. The solvent-accessible surface area (SASA) of the ipso carbon of ArHet was determined using the double cubic lattice method (DCLM) algorithm, which applies a constant surface density of points using a 1.4 Å probe. The volume enclosed by this solvent-accessible surface is also computed. 57