Dynamic polar molecular surface area

Palm, K., Luthman, K., Ungell, A.-L., Strandlund, G., Beigi, F., Lundahl, P., Artursson, P. Evaluation of dynamic polar molecular surface area as predictor of drug absorption comparison with other computational and experimental predictors. J. Med. Chem. 1998, 41, 5382-5392. 

PSAd, dynamic polar molecular surface area If specific capacity factor, for details see ref 55. 

Palm K, Luthman K, Ungell A-L, Strandlund G, Beigi F, Lundahl P, et al. Evaluation of dynamic polar molecular surface area as a predictor of drug absorption ... 

K. Palm, K. Luthman, A.-L. Ungell, G. Strandlund, F. Beigi, P. Lundahl, and P. Artursson, ]. Med. Chem., 41, 5382 (1998). Evaluation of Dynamic Polar Molecular Surface Area as Predictor of Drug Absorption Comparison with Other Computational and Experimental Predictors. 

In addition, the results of absorption studies for a series of (i-adrenoceptor blockers in vitro using Caco-2 monolayers and rat intestinal segments have been used to test new descriptors [55]. For this purpose, the authors calculated dynamic molecular surface properties considering all low-energy conformations. Molecular mechanics were used to consider the flexibility of the molecules, and the van der Waals volume (vdW) and water-accessible surface areas were also calculated (Table 4.18 and 4.19). When the dynamic polar vdW surface areas were used in regression analysis to describe cell permeability data obtained in Caco-2 cells and in rat ileum, excellent correlations were obtained (r2 = 0.99 and 0.92 respectively). 

Recent applications of CPSA descriptors include QSAR investigations of the genotoxicity of thiophene derivatives (Mosier et al., 2003) as well as of secondary and aromatic amines (Mattioni et al., 2003) and a study to classify phenols with respect to toxic modes of action (Aptula et al., 2003). A somewhat different route has been explored with the concept of dynamic molecular surface areas (Lipkowitz et al., 1989) that represent Boltzmann-weighted means of surface areas of different conformations within a preset energy window (e.g., within an excess of 10.5 kJ/mol above the lowest energy found for the particular molecule). Following this strategy, so-called dynamic polar... 

Most of the commercial molecular modeling systems also provide some property calculations, which range from simply calculating the polar surface area of a structure to a full range of topological and physicochemical descriptors. These may be based on fragment additivity, like most of the programs mentioned above, or they may involve correlations with quantum mechanical or even molecular dynamics-based calculations. 

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