Strain Energies as a Steric Descriptor in QSAR Calculations
Catherine J. Williford, Erland P. Stevens · QSAR & Combinatorial Science · 2004
Abstract The difference between the calculated heats of formation of gauche and anti conformers of monosubstituted propanes was determined and used as a new steric parameter (AG60 value) in QSAR calculations. The dihedral angle of the gauche conformation was fixed at 60° during the calculation to force interaction of the gauche groups. AG60 values are a thermodynamically determined steric measure in contrast to the Taft steric parameter, which is based upon kinetic measurements of ester hydrolyses. In comparisons to published QSAR studies, AG60 values correlated steric effects and biological activities very similarly to the Taft parameter. The average of r2 values from five QSAR studies for the Taft parameter was 0.887, while AG60 values averaged 0.883. Direct comparison of the Taft parameter and AG60 values showed a poor correlation (r2=0.300), indicating the two parameters are fundamentally different methods of measuring steric bulk.