A DFT-based QSARs study of protoporphyrinogen oxidase inhibitors: phenyl triazolinones.

The equilibrium geometries, electronic structures, and electrostatic potentials of a series of substituted phenyl triazolinones, a kind of important protoporphyrinogen oxidase (Protox) inhibitors, had been investigated using density functional theory (DFT) method at the B3LYP/6-31G(d,p) basis set. The quantum chemical descriptors, such as energy difference (DeltaE) between the lowest unoccupied molecular orbital and the highest occupied molecular orbital, electrophilic and nucleophilic frontier electron density (f(i)(E) and f(i)(N)), and net atomic charge (Q(i)), were computed at the same DFT level. Based on these useful quantum chemical descriptors, the quantitative structure-activity relationships was carried out and the results showed that descriptors, Q(C11), f(N5)(E), f(C10)(N), f(O6)(E), f(C11)(N), and DeltaE, were most likely to be responsible for the in vitro biological activity and the greenhouse pre-emergence activity of phenyl triazolinones. The descriptors accounted for 77-86% of the variation in the in vitro biological activity among the herbicidal phenyl triazolinone analogs 1-26 (except compounds 19 and 20). The results of the regression analysis showed that the activity was parabolically related not only with the descriptor f(O6)(E), but also with the descriptor f(C11)(N) . The optimum values of the terms f(O6)(E) and f(C11)(N) were about 11.15 and 0, respectively. Studies also showed that compound 19 exhibiting the highest in vitro activity mimicked the three-ring portion of protoporphyrinogen IX (Protogen). The present work had proved that the DFT-based quantum chemical descriptors could lead to the better correlation relationship than that the PM3-based electronic descriptors, therefore, DFT-based QSARs could be expected to help facilitate the design of additional substituted phenyl triazolinone derivatives of Protox inhibitors with good biological activity.