Surface area, molecular

As this chapter has attempted to elucidate, deriving design rules for reduced hazard to particular species is, indeed, not only possible, but likely to be transformative in the way in which we design new molecules that have no desired biological activity. The amount of toxicity and property data available in the public domain that can be used to derive more design guidelines is substantial. We can expect to see much development in this field in the near future and, hopefully, application of these simple heuristic rules to the design of new industrial chemicals. 

Agency for Toxic Substances and Disease Registry ToxFAQs for Benzene (2007) http //www.atsdr.cdc.gov/substances / toxsubstance.asp toxid=14, (last accessed 8 March 2012). 

U S Environmental Protection Agency National Center for Computational ToxicologyAggregated Computational Toxicology Resrouce Database (ACToR) http //actor.epa.gov/ (last accessed 29 April 2010). 

Russom, C.L. et al. (1997) Predicting modes of toxic action from chemical structure acute toxicity in the fathead minnow (Pimephales promelas). Environ. Toxicol. Chem., 16 (5), 948-967. Henderson, R.F. (2001) Species differences in the metabolism of olefins implications for risk assessment. Chem.-Biol. Interact., 135, 53-64. 

Csanady, G.A., Laib, R.J., and Filser, J.G. (1995) Metabolic transformation of halogenated and other alkenes - a theoretical approach - estimation of metabolic reactivities for in-vivo conditions. Toxicol. Lett., 75 (1-3), 217-223. 

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UNIQUAC is significant because it provides a means to estimate multicomponent interactions using no more than binary interaction experimental data, bond angles, and bond distances. There is an implicit assumption that the combinatorial portion of the model, ie, the size and shape effects, can be averaged over a molecule and that these can be directly related to molecular surface area and volume. This assumption can be found in many QSAR methods and probably makes a significant contribution to the generally low accuracy of many QSAR prediction techniques. 

Values for hydrocarbons other than alkynes and alkadienes can be predicted by the method of Suzuki et al. The best model includes the descriptors T, P, the parachor, the molecular surface area (which can be approximated by the van der Waals area), and the zero-order connectivity index. Excluding alkynes and alkadienes, a studv for 58 alkanes, aromatics, and cycloalkanes showed an average deviation from experimental values of about 30 K. 

Subscript i identifies species, and J is a dummy index all summations are over all species. Note that Xp however, when i = J, then Xu = = 1. In these equations / (a relative molecular volume) and (a relative molecular surface area) are pure-species parameters. The influence of temperature on g enters through the interaction parameters Xp of Eq. (4-261), which are temperature dependent ... 

Molecular volume Molecular shape Molecular surface area Substructure shape ... 

The form and shape of a molecule (i.e. its steric and geometric features) derive directly from the molecular genotype , but they cannot be observed without a probe. Furthermore, they vary with the conformational, ionization and tautomeric state of the compound. Thus, the computed molecular volume can vary by around 10% as a function of conformation. The same is true of the molecular surface area, whereas the key (i.e. pharmacophoric) intramolecular distances can vary much more. 

Clark, D. E. Rapid calculation of polar molecular surface area and its application to the prediction of transport phenomena. 2. Prediction of blood-brain barrier penetration. J. Pharm. Sci. 1999, 88, 815-821. 

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. 

Clark, D. E. Rapid calculation of polar molecular surface area and its application to the prediction of transport phenomena. 

Pearlman, R. S. Molecular surface areas and volumes and their use in structure-activity relationships. In Physical Chemical... 

Kelder, J., Grootenhuis, P. D. J.. Bayada, D. M., Delbressine, L. P. C., Ploeman, J.-P. Polar molecular surface area as a dominating determinant for oral absorption and brain permeation of drugs. Pharm. Res., 1999, 16, 1514-1519. 

Haeberlein, M., Brinck, T. Prediction of water-octanol partition coefficients using theoretical descriptors derived from the molecular surface area and the electrostatic potential. J. Chem. Soc. 

It is advantageous with a new drug substance to be able to estimate what its solubility will be prior to carrying out dissolution experiments. There are several systems of solubility prediction, most notably those published by Amidon and Yalkowsky [14-16] in the 1970s. Their equation for solubility of p-aminobenzo-ates in polar and mixed solvents is a simplified two-dimensional analog of the Scatchard-Hildebrand equation and is based on the product of the interfacial tension and the molecular surface area of the hydrocarbon portion of a molecule. 

Brinck, T., J. S. Murray, and P. Politzer. 1993. Octanol/Water Partition Coefficients Expressed in Terms of Solute Molecular Surface Areas and Electrostatic Potentials. J. Org. Chem. 58, 7070. 

The promising results obtained with the PTSAs, together with the previously published relationships between molecular surface areas and other physicochemical... 

In conclusion, descriptors of molecular surface area, such as PSA, NPSA and PTSAs, are important molecular descriptors influencing different properties such... 

Multidrug resistant-related protein family Polar molecular surface area Solubilization ratio Scale-up and post-approval changes... 

As the molecular weight of unbranched alkanes increases, so too does the molecular size, and even more importantly molecular surface areas. 

Amidon, G. L., Yalkowsky, S. H., Anik, S. T., Leung, S. (1975) Solubility of nonelectrolytes in polar solvents. V. Estimation of the solubility of aliphatic monofunctional compounds in water using a molecular surface area approach. J. Phys. Chem. 9, 2239-2245. 

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