New Molecular Descriptors to Identify Surfactants and Solubilizers from Electron Density Distributions

In many applications, such as substitution of nonrenewable molecules by renewable ones in formulations or screening of pharmaceutical compounds, knowing whether molecules have associating properties in the liquid phase (i.e., if they are surfactants, hydrotropes, cosolvents, solvosurfactants, or cosurfactants) prior to any experiment may be useful. In this work, two new molecular properties derived from local surface polarity of molecules, denoted as polarity moment and heteropolarity, are proposed. It is shown that when predicted from Density Functional Theory (DFT)‐conductor‐like screening model (COSMO) polarization charge densities, polarity moment, heteropolarity, and polarity can help determine whether molecules are surfactants or solubilizers (hydrotropes, cosolvents, and solvosurfactants) prior to any experimental measurements. Results also indicate that these molecular properties predict cosurfactant behavior, as fatty esters and long‐chain fatty alcohols appear to cluster in a distinct region of the two‐dimensional map built by the two molecular properties. In particular, for complex molecular structures, modeling interfacially relevant conformations appeared as an important step to avoid misclassification in the process of calculating the polarity moment.