Topological Polar Surface Area tPSA and Blood-Brain-Barrier Permeability Log BB

10 Topological Polar Surface Area (tPSA) and Blood-Brain-Barrier Permeability (Log BB) 

These two functions are not truly independent parameters, since both correlate with the compound s log P value. Indeed, Log BB has also been calculated using PSA alone, as well as several other solvation and free energy methods. - After Young showed that experimental Log P values could be correlated with experimental Log BB data algorithms were developed to calculate Log BB based on tPSA and c Log P (c Log P is a computed Log P value, based on a calculation of the contributions of the individual atoms and fragments in a molecule to its overall partition coefficient).  

One correlation between PSA and Log BB was provided by Clark et who proposed the following, extremely simplistic, calculation  

This equation relies on a PSA value generated from a single conformer. More recent methods include variations from Feher et al, and Kelder et al, the latter group proposed a more direct correlation between Log BB and a so-called dynamic PSA (dPSA). The dPSA is challenging to obtain, since it is determined from a Boltzmann-weighted ensemble of molecular conformations. Note that, in Kelder et al. s formulation of Log BB, c Log P is not considered at all  

Moreover, these authors were able to simplify their calculation by correlating dPSA with static PSA values  

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