Deconstruction of Taft's σ* parameter:: QSAR meets QALE

Taft's sigma* parameter has been mostly disregarded in QSAR (quantitative structure-activity relationships) analyses because it appears to reveal only simple field-inductive substituent effects. However, it can be shown that, when a reference reaction different from that adopted by Taft is used, the sigma* values reveal considerably more subtle features. This occurs when a reference reaction parameter, pK(a)', is used that is closely related to the Bronsted basicity of P-donor molecules and that is regarded in QALE (quantitative analyses of ligand effects) analyses as measuring the purely sigma-donor properties of the phosphines. Values of Taft's sigma* parameter for alkyl groups show an excellent linear correlation with pK(a)' but significant deviations from the correlation increase in the order CH2Ph (0.19) < Ph (0.46) <p-O-i-Pr (1.38) < OEt (1.44) < OMe (1.51) < OPh (1.82) < Cl (1.88), and the deviations for the p-YC6H4 groups increase linearly with decreasing pK(a)(') as Y changes in the order Me2N (0.29) < MeO (0.32) < Me (0.39) < F (0.41) < H (0.46) < Cl (0.50) < F3C (0.60). The new substituent effects for these 'deviant' groups that can be derived from the linear correlations of sigma* with pK(a)' are different (even in sign for the p-Me2NC6H4 group) from the original values of the Taft parameter, and they are much smaller than the additional effects detected here. These results show that sigma* values contain within themselves a variety of new features that should be compared with those shown by parameters used in more recent QSAR analyses, and that might be useful in such analyses. Copyright (C) 2004 John Wiley Sons, Ltd.