On the other hand, atom-in-a-molecule QM properties can provide important insight into the distinct chemical environments within large drug-like molecules. To illustrate this, Fig. (a) shows the 2D property space defined by Hirshfeld charges q H and atomic polarizabilities α s (i.e., (q H , α s )-space) for the 59, 783 conformations in AQM-gas and AQM-sol. For comparison, the values corresponding to QM7-X equilibrium molecules are also plotted (green circles). These properties largely lack correlation presenting |ρ| values of 0.05 and 0.07 for gas-phase and solvated molecules. However, one can see the existence of well-defined clusters that are mostly related to a specific atom type (see arrows in Fig. ). In addition to offering a broader coverage of this property space when compared to QM7-X molecules, the regions representing the different local chemical environments in AQM molecules appear to overlap. This is a clear example of the need to develop more robust geometric and electronic descriptors capable of effectively representing the intricate chemical environments in large drug-like molecules for ML applications. Furthermore, our findings have revealed that implicit solvation has a pronounced influence on q H values, particularly for heavier atoms such as P, S, and Cl-relevant atoms in the design of pharmaceutical compounds as well as in the determination of their physicochemical and biological properties. Certainly, the molecule-solvent interaction has a stronger effect on the local properties compared to global ones, as illustrated by the correlation plots in Fig. ). This becomes more evident by analyzing the atomic forces F tot , where the significant variations in values can strongly affect the accuracy of ML force fields when applied to run the dynamics of large molecules.