Comparative molecular field analysis as a tool to evaluate mode of action of chemical hybridization agents

The 3D-QSAR method of comparative molecular field analysis (CoMFA) was appl ied to three patent families of chemical hybridization agents (CHAs) in the MON21200 class of chemistry. The models for each CHA family gave good corr elations between the variations in log percent male sterility and in the st eric-electrostatic properties of the patent set. For all CHA. families, obs erved sterility rates are generally higher for the sodium salts than for th e corresponding esters. This is consistent with our CoMFA models which show that negative charge is favored in the region of the carboxylate group. Th e CoMFA models also indicated that for the MON21200 family increased steric bulk at the 4-position on the phenyl ring is associated with enhanced acti vity. However, for the RH0007 and the HYBRID families, male sterility is ge nerally enhanced with increased steric bulk at the 2- or S-position on the phenyl ring. Although the models cannot provide unambiguous conclusions abo ut a common mode of action, similarities in the CoMFA contour maps provided some clues for a common agrophore for these three CHA families.