Deriving a quantitative chirality measure from molecular similarity indices

A versatile new method has been developed as a continuous symmetry measure for chiral compounds. The application of principal component analysis (PCA) to the complete N x N pairwise similarity matrices (electrostatic potentia l and shape indices) of a series of dihydropyridine calcium channel antagon ists allowed to single out a chirality component and to compute a chirality score in terms of the between-enantiomers difference on the component valu e. The possibility to have chirality defined continuously at the series lev el could be of importance in eudismic analyses where the relative potency o f two enantiomers is studied as well as in QSAR studies dealing with chiral molecules in order to improve the power of the generated models.