Social Molecules

At the levels discussed above, the molecules are described in isolation, although this is only partly correct since probes are necessary to define such attributes/properties as molecular volumes and molecular electrostatic potentials. This description "in the vacuum" has consequences as far as the corresponding attributes and properties are concerned. Indeed, attributes and properties corresponding to the elementary and geometric levels of description are environment-invariant, whereas electronic attributes/ properties are influenced by the molecular environment. It is only at the next level, namely the level of intermolecular interactions, that the complex interplay between a molecule and its environment (e.g., solvent, bulk liquid or crystal) is explicitly considered. At this level of highly complex description, two classes of molecular properties are encountered, many of which have biological importance. First, environment-influenced electronic attributes/properties express the fact that electrons, which are responsible for most intermolecular interactions, cannot remain unaffected by these interactions. These mutual influences are an essential factor accounting for many observable properties and they must be recognized for what they are.

Social molecules (i.e., molecules described at the level of intermolecular interactions) also display emergent properties, in other words properties not encountered at the previous levels of description. This is the case of such physicochemical properties as melting point, solvation, behavior in chromatographic systems, and the biologically essential property of lipophilicity. Colligative properties (i.e., concentration-dependent properties) also emerge at this level.

Lipophilicity is a popular and - as far as structure-activity relationships are concerned - remarkably successful property. Reasons for this are to be found in the richness and diversity of the structural information expressed in lipophilicity, which makes it dependent on all structural attributes pertaining to the levels A to C in Table 1. Indeed, lipophilicity results from a vast array of intermolecular interactions ranging from hydrophobic and van der Waals forces to ion-dipole interactions and hydrogen bonds, the latter contributing as significantly to lipophilicity as they do to biochemical recognition [3]. This property and its significance constitute the topic of the present review.

Biological properties (i.e., biological responses) do not belong to a description of chemical structure stricto sensu. Nevertheless, "interactions with a biological environment" have been added to Table 1 to indicate that a continuum exists between this level of properties and the previous one, namely that of intermolecular interactions, as documented by the telling example of membrane/water partition coefficients which can be viewed as both a physicochemical and a biological property.

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