It is known that the total sum of all polar regions of a molecule's surface correlates well with various bioavailability related properties, such as intestinal absorption, and blood brain barrier penetration. If the contributions of all polar atoms being exposed to the molecule's surface sum up to an area beyond 80 or 100 Å², then the molecules likelyhood to pass membranes easily is significantly reduced.
Originally, the polar surface area was calculated from representative conformations of the chemical structure. P. Ertl and P. Selzer showed that an atom type based increment system can be used instead without loosing much accuracy and serves equally well, if used for the prediction of membrane penetration. To distinguish the calculation method from the original 3D based one, they introduced the term topological polar surface area. We use their method published in J. Med. Chem. 2000, 43, 3714-3717.