Molecular shape descriptors

To explore the relevance of symmetry allowed conformations to chemically real structures it is necessary to locate steric-energy minima in a potential energy surface that spans all possible conformations. A variety of computational techniques [210] are available, commonly combined with experimental results retrieved from structural databases [211]. Such procedures have revealed the occurrence of countless different rotamers and conformers, arising from pseudorotation and conformational inversion under special environmental conditions. In addition, situations of disorder in the crystalline state are symptomatic in many cases, of the stabilization of variable intermediate forms. 

On this basis ring conformation is interpreted to depend on the environment, rather than on chemical bonding. The most regular predicted conformations occur only by way of rare exception, even for cyclic alkanes. Different conformations are routinely observed in different states of aggregation. In the gas phase the entire Boltzmann distribution of conformations is present at any given temperature. Molecular shape and conformation are therefore undefined in this instance. 

At another level molecular shape is linked to the external surface of a molecule. Although it is generally recognized that quantum-mechanically molecules do not have clearly defined surfaces, new definitions of molecular shape and surface appear in the literature on a regular basis. Variables such as molecular surface area and volume are useful in the analysis of molecular recognition and other surface-dependent properties that assume a clearly defined surface. 

One of the conceptually simplest representations of a molecule, also used in the construction of hard-sphere space filling models, is obtained by centring spheres of suitable Van der Waals radii at the positions of the atomic nuclei. To convey a feeling of size the aggregate is enclosed in a generating ellipsoid that circumscribes the atom most remote from the centre to define the volume of the Van der Waals body [212]. 

A more realistic outline of a molecular surface can be defined in terms of the outer contours of electron density according to Bader [173]. To avoid excessive computation the densities of large molecules may be built up from previously calculated densities of smaller fragments [213]. The most obvious approach, to approximate molecular density by the sum of atomic densities over the promolecule has also been explored [214]. This approach works well since the deformation density associated with bond formation is small compared to the total density [215]. The total density may therefore be represented by a sum over spherically averaged atomic densities, p(r) = Pa(t)- 

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Motoc, I., Marshall, G.R., Labanowski, J. Molecular shape descriptors. 3. Steric mapping ofbiological receptor. Z. Naturforsch. 1985, 40a, 1121-1127. 

This section reviews the molecular shape descriptors developed by Amoore, Allinger, Simon et al. and Testa and Purcell. The illustrative examples discussed refer to the odour similarity and cardiotoxic aglycones. One has stressed the methods based on the reference structure because, correctly formulated, these methods seem to offer promising perspectives to model the steric effects in biological systems. Finally, a short discussion of possible connections between steric and other substituent constants (relevant in the context of multicollinearity in QSAR) is included. 

Good AC, Ewing TJ, Gschwend DA, Knntz ID (1995) New molecular shape descriptors application in database screening. J Comput Aided Mol Des 9 1-12... 

In many chemical problems the comparisons of local molecular regions are more important than global comparisons. The presence of functional groups or other molecular moieties with specified shape properties often imply similar chemical behavior even if the molecules compared have very different global shapes. For this reason, local molecular shape descriptors and local shape codes are of major importance. 

Two arbitrary functions of the common overlap steric volume were also introduced as alternative molecular shape descriptors ... 

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