Scheme 2 . Sites considered in the BDE calculations for R, RI and RII.
The proportion of neutral vs. charged species for molecules with acid-base bahaviour is ruled by the pKa-pH relationship. Thus, acid constants, expressed as pKa, were calculated for the subset of the most promising R, RI and RII derivatives. A fitted parameters approach (FPA) was used for that, because it was already proven as reliable.160, 161 The calculated data was compared with a reference set of molecules, previously used for similar purposes.142 The computational protocol described here is known as CADMA-Chem.140