PORPHYRIC INSECTICIDES .4. 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 enhan ce the conversion of exogenous delta-aminolevulinic acid (ALA) to prot oporphyrin IX (Proto). As observed for photodynamic herbicidal effects in plants, the presence of nitrogen atoms at positions 1 and 10 of th e macrocycle was essential for porphyric insecticidal activity. This w as evidenced by the very limited activity of phenanthrene, in which po sitions 1 and 10 are occupied by carbon instead of nitrogen atoms. On the other hand, enhancement of Proto formation and porphyric insectici dal activity were maintained following methyl, chloro and nitro group substitution at the periphery of 1,10-phenanthroline. In contrast, Pro to levels and photodynamic toxicity were reduced by hydroxy and phenyl substitution at the same positions. Benzyl substitution at the 2-3 an d 8-9 positions was also inhibitory. Quantitative structure-activity c alculations suggested a relationship between peripheral group substitu tion and physicochemical properties of the substituted compounds. Elec tron density changes in 1,10-phenanthroline and its analogs that appea red to be related to reduced efficacy included (a) appearance of posit ive charge-binding volumes at positions 4 and 7 of the 1,10-phenanthro line macrocycle, which flanks positive charge-repelling volumes, (b) a dramatic increase in superdelocalisability (i.e. electron density) ov er some unoccupied molecular orbitals, and (c) electronic charge at po sitions 1 and 10 of the macrocycle. Large increases in van der Waals v olumes also exerted negative effects on insecticidal efficacy.