Total molecular surface area

De Bruijn, J., Hermens, J. (1990) Relationships between octanol/water partition coefficients and total molecular surface area and total molecular volume of hydrophobic organic chemicals. Quant. Struct.-Act. Relat. 9, 11-21. 

Doucette, W. J., Andren, A. W. (1987) Correlation of octanol/water partition coefficients and total molecular surface area for highly hydrophobic aromatic compounds. Environ. Sci. Technol. 21, 521-524. 

Lande, S.S., Hagen, D.F., Seaver, A.E. (1985) Computation of total molecular surface area from gas phase ion mobility data and its correlation with aqueous solubilities of hydrocarbons. Environ. Toxicol. Chem. 4, 325-334. 

Dickhut, R.M., Miller, K.E., Andren, A.W. (1994) Evaluation of total molecular surface area for predicting air water partitioning properties of hydrophobic aromatic chemicals. Chemosphere 29, 283-297. 

They were developed with the idea of paralleling important physico-chemical properties such as boiling point, mobility on chromatographic columns, enthalpies of formation, and total molecular surface areas. 

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

Villar et al. developed an atomic hydrophobicity contribution that depends on the molecular conformation. The hydrophobicity parameters were calculated by including charge densities, atomic contributions to the total molecular surface area and the molecular dipole moment [47, 48]. This method is implemented in the SPARTAN software. 

Amidon et al. [39] have correlated the aqueous solubility of 127 aliphatic hydrocarbons, alcohols, ethers, aldehydes, ketones, fatty acids, and esters with their total molecular surface area ... 

Dickhut, R. M., K. E. Miller, and A. W. Andren, Evaluation of Total Molecular Surface Area for Predicting Air-Water Partitioning Properties of Hydrophobic Aromatic Chemicals. Chemosphere, 1994 29, 283-297. 

Fugate (1989) reported the following relationship between total molecular surface area (TSA) and log Koc for 36 nonpolar organic compounds, including chlorobenzenes, PAHs, and PCBs ranging from 1.44 to 5.95 in log Koc ... 

Fugate, H.N. 1989. Using total molecular surface area in quantitative structure activity relationships to estimate environmental fate and transport parameters. Master s thesis, Utah State University, Logan, UT. 

Among further CPSA descriptors are the differences between PPSA and PNSA, and fractional values as ratios of PPSA or PNSA and the total molecular surface area. For the original list of 25 CPSA descriptors as well as for recent extensions, the reader is referred to the literature (Stanton and Jurs, 1990 Aptula et al., 2003 Mattioni et al., 2003 Mosier et al., 2003). It should be further noted that, in contrast to the initially introduced electrostatic molecular surface interaction terms (Grigoras, 1990), the CPSA descriptors were actually defined using solvent accessible surface areas instead of simple van der Waals surface areas (Stanton and Jurs, 1990), a fact that is ignored in the present discussion for the sake of simplicity. 

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... 

It is the charged surface area of both hydrogens which can be donated and hydrogen acceptor atoms relative to the total molecular surface area ... 

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