Test-set reduction in the screening step definition of a chiral separation strategy in polar organic solvents chromatography

The last decades, many efforts have been made to design and develop chiral separation strategies for different analytical techniques. To ensure that these strategies are broadly applicable rather large test-sets of molecules with very diverse molecules are used. The most enantioselective and complementary separation systems are then used as screening conditions in separation strategies. Potential changes in conditions e.g. implementation of new chiral selectors, requires screening of the entire set to retain the most enantioselective systems. A rational reduction of the test-sets may open new perspectives for developing and updating separation strategies. In the present work, it is investigated whether the screening step of an existing separation strategy in polar organic solvents chromatography can be reconstructed based on reduced test-set results Therefore, the structures of the 58 molecules of the test-set are digitally drawn and their optimal geometrical conformations calculated. From these conformations 3D-molecular descriptors are calculated. The test-set reduction is performed using the Kennard and Stone algorithm: compounds with the most diverse descriptors are selected. The test-sets are gradually reduced with 10% starting from 90% to 30% of the initial size. The results pointed out that with some reduced test-sets the same chromatographic systems are selected. A test-set reduction with 30% (41 remaining compounds) seems possible without losing information on the global enantioselectivity and compleinentarity of the tested chiral stationary phases. (C) 2012 Elsevier B.V. All rights reserved.