Total polar surface area

There are, in addition to these simple functional group filters, a number of property-based filters that may be applied. These fdters take the form of calculated metrics, such as the Lipinski Rule of Five (LRoF Hydrogen-bond donors. Hydrogen-bond acceptors, Lipophilicity, Molecular weight). Solubility, total Polar Surface Area (tPS A), Blood-brain-barrier (BBB) Permeability, calculated metabolic filters (cADMET Absorption-Distribution-Metabolism-Excretion-Toxicity) and Bioavailability. 

It is the total polar surface area (TPSA) divided by the total molecular solvent-accessible surface area (5A5/1), i.e. 

Of the physicochemical descriptors, lipophilicity (as described by clogP and Topological Polar Surface Area (TPSA) gave the strongest overall correlation to incidence of adverse in vivo outcomes, whether analyzed in terms of free or total drug threshold concentrations. In the case of free drug threshold analysis, a Random Forest statistical method indicated that there was a higher chance of a compound with TPSA <70... 

PSA Percent polar surface area of the total molecular surface area... 

Hydrogen bonding descriptors the counts of hydrogen bond acceptors (HAG) or donors (HDO) the number of polar atoms, Pjt [34] the polar surface area in (PSA) and normalized to the total surface area (%PSA) ... 

The combination of SAXS and WAXS employed here provides information not only on the total internal surface area in highly microporous systems but also on the nature and distribution of polar or non-polar molecules in the pores. The method is especially valuable in situations where the adsorption process may be slow, such as with water vapour. 

In unhomogenized dairy cream the natural phospholipids contribute to the whipping properties of the cream. However, after homogenization the particle size of the fat globules decreases, and the total fat surface area increases. This means that the interfacial concentration of polar lipids decreases because milk serum proteins adsorb at the newly formed interfaces, and the whipping properties are lost. Consequently, additional polar lipids or emulsifiers are needed to obtain good whipping properties in most industrially manufactured products. 

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... 

As has been discussed recently (Murphy etal., 1992), the formalism developed by Lee (1991) predicts not only the convergence behavior discussed by the author (i.e., when the apolar and polar contributions to the enthalpy are identical). For the case in which the buried polar area per residue is constant it also predicts convergence at the point at which the apolar contribution to the enthalpy is zero. In Fig. 3 we have plotted AH0 versus ACp normalized either per residue (Fig. 3a) or per buried total surface area (Fig. 3b), in order to compare the results of the two approaches. It is clear that the linearity is better when the data are normalized to the number of residues than when they are normalized to the buried surface area. This is presumably due to variabilities in the surface area calculation. The slope of the line in Fig. 3a is —72.4, which corresponds to a convergence temperature, Th, of 97.4°C for this set of proteins. If the above analysis is correct, then this temperature corresponds to The value of AH is 1.32kcal (mol res)-1 or 33.6 cal (mol A2)-1 of polar surface area. 

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... 

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. ... 

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... 

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