Partitioned total surface areas PTSAs

This led to the concept of fragmentation of the total molecular surface area in combination with multivariate analysis (Stenberg et al. 2001) towards predictive models of drug permeability for more complex datasets. Permeability models were established based on so-called partitioned total surface area (PTSA) descriptors. Each of the PTSA descriptors corresponds to the surface of a certain atom type, differentiated by hybridisation, which results in individual descriptors for e.g. sp3, sp2, and sp carbon atoms. The resulting permeability model based on 19 descriptors finally consisted of oxygen, nitrogen and polar hydrogen surfaces, while the main contribution for prediction of Caco-2 permeability was attributed to PSA. In addition some more lipophilic contributions... 

Considering the importance of the surface interactions of solute and solution, Bergstrom developed partitioned total surface area (PTSA) as an extension of PSA (polar surface area) [20], PTSA calculates surface areas corresponding to particular types of atoms (i.e., sp, sp2, and sp3 hybridized... 

The introduction of more complex datasets used for model development has pointed at the need for several descriptors and multivariate data analysis (Table 16-3). For instance, combinations of PSA and nonpolar surface area (NPSA) proved to predict the permeability of a series of peptides when PSA alone failed [41], Moreover, the introduction oflarger structures and structures with larger flexibility showed that the partitioned total surface areas (PTSAs), that is, the surface area of the molecule occupied by a specific atom, and/or descriptors related to the flexibility of the molecule are in the permeability predictions [42, 43],... 

Fig. 15.3. Examples of partitioned total surface comprised of PTSAs of oxygen atoms, nitrogen areas (PTSAs) included in the multivariate data atoms and hydrogen atoms bound to these analysis. The PTSAs represent the surface heteroatoms. All other atom types are included...

---