Complementing the shape group method : assessing chirality

Abstract

The Shape Group method is a powerful tool in the analysis of the shape of molecules, and in the correlation of molecular shape features to molecular properties in Quantitative Shape-Activity Relationship (QShAR) studies. However, the main disadvantage inherent in the method is that mirror image molecules are considered to be "exactly" similar. As such, the method requires a complementary chirality measure to allow for complete analysis where chirality is involved.

In this work, two methods of creating chirality measures to complement the Shape Group method are presented. The first is based upon the assigning of handedness values to each array point of the computer file that contains specific property information and uses the parallels between a lattice animal inscribed in a Jordan curve, and the array points inscribed in an isodensity contour. Each array point can then be treated as a face-labelled cube, which is often a chiral object that can have an assigned handedness value. Grouping of these handedness values allows for the creation of chirality measures.

In the second method, the Shape Group method is applied to electron density representations created by subtracting one fragmentary electron density from others and analysing the shape similarities of the resultant difference densities. With both methods, chirality information that is already embedded within the shape descriptions of electron density representations is emphasized.

The Shape Group method and the developed chirality measures are then used to simply correlate the shape and chirality of the stereogenic carbon of molecules to optical rotation and rotational strengths of various classes of molecules.