Porphyric insecticides. IV: Structure‐activity study of substituted phenanthrolines

The porphyric‐insecticide‐modulating activities of 1,10‐phenanthroline and eight of its analogs were investigated. The insecticidal efficacy of these compounds was closely associated with their ability to enhance the conversion of exogenous δ‐aminolevulinic acid (ALA) to protoporphyrin IX (Proto). As observed for photodynamic herbicidal effects in plants, the presence of nitrogen atoms at positions 1 and 10 of the macrocycle was essential for porphyric insecticidal activity. This was evidenced by the very limited activity of phenanthrene, in which positions 1 and 10 are occupied by carbon instead of nitrogen atoms. On the other hand, enhancement of Proto formation and porphyric insecticidal activity were maintained following methyl, chloro and nitro group substitution at the periphery of 1,10‐phenanthroline. In contrast, Proto levels and photodynamic toxicity were reduced by hydroxy and phenyl substitution at the same positions. Benzyl substitution at the 2–3 and 8–9 positions was also inhibitory. Quantitative structure‐activity calculations suggested a relationship between peripheral group substitution and physicochemical properties of the substituted compounds. Electron density changes in 1,10‐phenanthroline and its analogs that appeared to be related to reduced efficacy included (a) appearance of positive charge‐binding volumes at positions 4 and 7 of the 1,10‐phenanthroline macrocycle, which flanks positive charge‐repelling volumes, (b) a dramatic increase in superdelocalisability (i.e. electron density) over some unoccupied molecular orbitals, and (c) electronic charge at positions 1 and 10 of the macrocycle. Large increases in van der Waals volumes also exerted negative effects on insecticidal efficacy.