Charged Polar Surface Area

The MEP at the molecular surface has been used for many QSAR and QSPR applications. Quantum mechanically calculated MEPs are more detailed and accurate at the important areas of the surface than those derived from net atomic charges and are therefore usually preferable [Ij. However, any of the techniques based on MEPs calculated from net atomic charges can be used for full quantum mechanical calculations, and vice versa. The best-known descriptors based on the statistics of the MEP at the molecular surface are those introduced by Murray and Politzer [44]. These were originally formulated for DFT calculations using an isodensity surface. They have also been used very extensively with semi-empirical MO techniques and solvent-accessible surfaces [1, 2]. The charged polar surface area (CPSA) descriptors proposed by Stanton and Jurs [45] are also based on charges derived from semi-empirical MO calculations. 

HCPSA high-charged polar surface area... 

Log of the aqueous solubility Molecular refractivity Total negative partial charge Total positive partial charge Relative negative partial charge Relative positive partial charge Polar surface area... 

The descriptor uses readily calculable physicochemical properties from the topological structure. The descriptors used in this study were atomic weight, hydropho-bicity, molecular refractivity, atomic charge, polar surface area, hydrogen bond acceptors, and hydrogen bond donors. The authors note that Martin et al. [32] applied a similar approach for the design of diverse combinatorial libraries. 

Cells Binding, adsorption, partitioning Physical dimensions Metabolism Monolayer integrity Membrane domain characteristics (polarity) surface area transporters, receptors lipid composition charge Cell phenotype and culture conditions... 

More recently the H-bonding potential (an estimate of hydrophilicity) and surface charge characteristics of a molecule have been used as predictors of passive Pm and intestinal absorption [17, 18], Theoretical models based on the determination of polar surface area (PSA) have been utilised to reasonable... 

Empirical, semiempirical, and ab initio methods have been used extensively to calculate molecular descriptors. These molecular property descriptors help capture important characteristics of compounds such as bioavailability and receptor affinity. Descriptors such as octanol-water partition coefficient (log P), HOMO/LUMO energies, hammett a, total energy, heats of formation, ionization potential, atomic charges, electron densities, dipole/quadrupole moments, volume, and polar surface area are common examples. For an excellent review of physicochemical descriptors, the reader is directed to the following reference. ... 

Martin proposed a bioavailability score based on several molecular properties including polar surface area (PSA), rule-of-5, and molecular charged state. With the descriptors used, this is an example aiming to estimate oral absorption and not bioavailability [19] hence, the title of this work is misleading. A score was developed to assign the probability that a compound has an F more than 10% in the rat. We do not consider this as a meaningful cutoff. Better would be F more than 30% in man [30]. 

Computationally derived descriptors (e.g., molecular weight, size, shape, polarity, electrostatic interactions, charge, lipophilicity, hydrogen bonding capacity, polar surface area). 

Among the several CODESSA descriptors, implemented in the homonymous software CODESSA (Comprehensive DEscriptors for Structural and Statistical Analysis) [Katritzky and Gordeeva, 1993 CODESSA- Katritzky, Lobanov et al., 1996 Katritzky, Lobanov et al, 1996], are molecular weight, molecular volume, —> count descriptors, —> topological indices, charge descriptors, shadow indices, charged partial surface area descriptors, quantum-chemical descriptors, and —> electric polarization descriptors. 

A special class of electrostatic descriptors [charged partial surface area (abbreviated as CPSA) descriptors] has been proposed by Jurs et al. [28-30] in terms of the surface area of the whole molecule or its fragments and in terms of the charge distribution in the molecule. These descriptors, listed in the table, should account for the polar interactions between molecules. 

---