COMPARATIVE MOLECULAR-FIELD ANALYSIS (COMFA), SEMIEMPIRICAL (AM1) MOLECULAR-ORBITAL AND MULTICONFORMATIONAL MINIMAL STERIC DIFFERENCE (MTD) CALCULATIONS OF ANTHRAQUINONE DYE-FIBER AFFINITIES

Comparative molecular field analysis (CoMFA), a three-dimensional quantitative structure-activity approach, was used to interpret the affinity of a series of anthraquinone vat dyes to cellulose fibres. The excellent correlation obtained by this method - even when using a quite small number (five) of components in the partial least-squares analysis (cross-validated r(cv)(2) = 0.841, conventional r(2) = 0.992) - indicates that the dye-fibre interaction is largely dominated by steric and even more important electrostatic effects. Based on the CoMFA field contributions, suggestions for further activity enhancements can be made. Inclusion of molecular orbital (AM1) derived quantitative structure-activity relationship (QSAR) descriptors (epsilon(HOMO), epsilon(LUMO) and dipole moments mu) does not alter the picture derived from CoMFA fields alone. Of the molecular orbital descriptors, the LUMO orbital energy is found to yield the most important contribution. In addition, a multiconformational minimal steric difference (MTD) analysis, including several low-energy conformations of the investigated compounds, was done. This approach also indicated a good correlation with dye affinity (r(cv)(2) = 0.827, r(2) = 0.941). The optimized receptor map is in accordance with the CoMFA electrostatic contour maps.