Computational Procedures

Lipophilicity has been expressed by means of manifold descriptors mainly based on partition coefficients or similar thermodynamic features. Relationships between individual scales are, apart from some exceptions, very close. These descriptors can be obtained by a number of computational routines; they receive attention in this book. Fragmentai constants, i.e., contributions of individual molecular fragments to the overall value of a descriptor, are roughly additive and thus afford quick predictions of lipophilicity from molecular structures. In this way, some problems and limitations associated with the experimental assessment of substituent constants can be overcome [17]. From a visual point of view, this property has been simulated as a dynamic process, exhibiting the characteristics observed experimentally [18].

From a practical point of view, lipophilicity descriptors are important for at least two reasons. First, they may predict unsatisfactory drug candidates and avoid, in a simple way, an extensive experimentation. This relates to both transport properties and intrinsic activity of the potentially interesting substances. Second, they enable to investigate structure-property relationships, in particular intermolecular forces and intramolecular interactions. These relationships are of utmost importance in drug design. It would be, for example, of little use to design a highly hydrophilic substance if it is targeted to the central nervous system.

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