3D-QSAR study of insecticidal neonicotinoid compounds based on 3-way partial least squares model

A choice of an active conformer and the corresponding alignment rule is an important problem for determining the success of 3D-QSAR study. For flexible molecules, this problem is the most difficult one and construction of the method with appropriate chemometric tools has been required. Recently, Bro [J. Chemom., 10, 1996, 47–61] has proposed a trilinear PLS algorithm as the trilinear extension of standard bilinear PLS in the field of analytical chemistry. Broʹs 3-way PLS method seems to be suitable to the 3D-QSAR problem but only few attempts have so far been made at the subject. The object of this study is to investigate the ability of Broʹs 3-way PLS method for solving the conformer/alignment problem in 3D-QSAR study. The structure-activity data of insecticidal neonicotinoid compounds were used as a test example. The 3-way arrays were constructed from eight sample vectors and eight electrostatic similarity matrices derived from eight combinations of conformers and alignment rules. The correlation between the 3-way arrays and the insecticidal activity vector was investigated by Broʹs 3-way PLS method. The 3-way PLS model with three significant components was obtained, and from its PLS loading the best combination of conformer and alignment rule could be selected.