Solubility three-dimensional descriptors

Several research groups have built models using theoretical desaiptors calculated only from the molecular structure. This approach has been proven to be particularly successful for the prediction of solubility without the need for descriptors of experimental data. Thus, it is also suitable for virtual data screening and library design. The descriptors include 2D (two-dimensional, or topological) descriptors, and 3D (three-dimensional, or geometric) descriptors, as well as electronic descriptors. 

The fundamental idea of QSAR consists of the possibility of a relationship between a set of descriptors, which are derived from molecular structure, and a molecular response. Within this scope, several molecular descriptors, which discretely parameterize a given molecular set, have been devised. From the early work of Cross [1], where a relationship between toxicity and water solubility was observed, several other parameters have been proposed, such as Hammett s sigma [5], which accounts for electronic effects due to molecular backbone substitution, or the octanol/water partition coefficient [6], widely used to describe lipophilicity. Later on, other frameworks have been formulated in order to include molecular shape, size, polarizability, and many other structural features, also based on the three-dimensional molecular character. A number of reviews have been published [7-9], concerning the historical development, descriptor generation, and their application into the QSAR field. 

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