Yes, there can be a link between electron density and TPSA, as both affect how molecules interact with surfaces. Electron density impacts a molecule’s reactivity and polarity, while TPSA reflects the distribution of polar groups, which is important for interactions with adsorbents like activated carbon. Even though TPSA is often used in pharmaceutical studies, it can still help explain adsorption in other molecules, like pesticides, because both factors play a role in how they bind to surfaces.

I do not understand your prejudice against TPSA. It is regular physical parameter, consistently and clearly defined for any molecule. The fact that the only application so far is the medicinal chemistry is of no importance. Chemists in other branches just lack the knowledge. Any calculation pipeline/software can calculate it.

Yes, there is roughly proportional dependance between electron density and TPSA, but not simple, as TPSA does not distinct between types of polar atoms, so TPSA of some aza-analogue will be very close to its oxo-counterpart (N and O diameters are not very different), but electron density will be very different. Also phosphorus and sulfur containing compounds will show big discrepancy. These atoms are big, so they generate big TPSA, but electron density is actually much lower than for O, N containing compounds.

Yes, from the point of theoretical physics, the TPSA is not briliant concept. But keep in mind it was developed as numerical descriptor for multidimensional similarity searches in drug-like compound libraries, not as physical parameter.

More interesting is the question, why it corelates with absorption rate at graphite structure. I believe, the TPSA describes inversely the actual relative amount of hydrocarbon scaffold in each molecule, which is actually interacting with charcoal.

They are two distinct terms, electron density is a probability of finding electron within a region of space around an atom or a molecule while Topographical Polar Surface Area is a measurement of a surface area that is accessible to solvent, particularly water I.e it is a measurement polar (hydrophilic) surface area of a molecule....

With this simple definition, we will realise that the terms were not related in any manner. Electron density focus on distribution of electron within the molecule while TPSA focus on surface area that is accessible to solvent, typically water.

Thanks for the contribution Bello Ibraheem Qozeem Matej Babjak