Dynamic polar surface area

Kelder et al. [25] also explored the role of PSA as a determinant for the transport of drugs through the BBB. Initially, they calculated and correlated the PSA of 45 drug molecules with their known brain-penetration data. A linear relationship was obtained between brain penetration and dynamic polar surface area (DPSA) as shown in Eq. 34 ... 

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. 

PSA Polar surface area (dynamic or static - calculated from 2D or 3D... 

The choice of descriptors is not always clear-cut. The time required to calculate elaborate descriptors by quantum methods is not always justified compared to the results obtained with simpler and more rapidly calculated descriptors. For example, Bergstrom [12] compared 2D polar surface area (PSA) with 3D PSA and static, instead of dynamic, calculations. No definitive gain was obtained by using the most sophisticated method(s) of calculating PSA descriptors. 

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. 

In the past few years, a range of solvation dynamics experiments have been demonstrated for reverse micellar systems. Reverse micelles form when a polar solvent is sequestered by surfactant molecules in a continuous nonpolar solvent. The interaction of the surfactant polar headgroups with the polar solvent can result in the formation of a well-defined solvent pool. Many different kinds of surfactants have been used to form reverse micelles. However, the structure and dynamics of reverse micelles created with Aerosol-OT (AOT) have been most frequently studied. AOT reverse micelles are monodisperse, spherical water droplets [32]. The micellar size is directly related to the water volume-to-surfactant surface area ratio defined as the molar ratio of water to AOT,... 

Example 12.1. The CMC of C12E7 is 0.083 mM at room temperature. By SANS and dynamic light scattering the mean hydrocarbon core radius was found to be 1.70 nm at a surfactant concentration of 2 mM [532], The mean aggregation number is 64. If we divide the total surface area of the core by the number of surfactants, we get the area per molecule at the core radius. It is 47r (1.7 nm)2 /64 = 0.57 nm2. The cross-sectional area of polyethylene oxide is below 0.2 nm2. So, more than half the core area is exposed to aqueous or at least to a polar medium. 

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

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). 

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