Porphyric Insecticides - Chlorophyll Biosynthesis and Technological Applications - page 424

In the study of structure/function correlations the emphasis was placed on the
analysis of relationships between tetrapyrrole modulating activity, photodynamic
damage and alterations in the electrostatic field of various modulators. With this
approach the underlying hypothesis was structural complementarity between enzy-
matic receptor sites and modulators that favored electrostatic binding of various
modulators to or close to the receptor sites of enzymes that catalyze various
reactions of the heme biosynthetic pathway. It was conjectured that the detection
of exclusive positive or negative charge binding volumes in groups of analogs that
exhibited similar tetrapyrrole biosynthesis modulating activity may be an indication
that these analogs may exert their effects by binding to the same enzymatic receptor
site. In all cases the modulation of tetrapyrrole biosynthetic activity by various
analogs was related to the presence of unique positive charge binding or repelling
volumes. This in turn suggested that various modulators exerted their effects by
binding to specific negatively charged areas that may well be close to tetrapyrrole
biosynthetic enzyme reaction sites.
Early fourth-instar T . ni larvae were used in evaluating modulator effects on Proto
accumulation and larval mortality. Chemicals were incorporated into liquefied
Waldbauer's medium as described in section above in “IV”. Twenty six larvae
were placed in each diet cup and allowed to feed in darkness for 17 h. Following
dark incubation, six larvae were assayed for tetrapyrrole accumulation. Mortality of
the remaining 20 larvae was monitored prior to light exposure and daily thereafter,
for a period of 6 days. Modulators were evaluated alone and in combination with
ALA in a randomized complete block design with three replicates. Percent larval
mortality was arcsine transformed prior to statistical analysis. Structure-Activity
relationship of five selected modulators are reported below.
18.6.1 Structure-Activity Relationship
of Substituted Phenanthrolines
The porphyric insecticide modulating activity of Oph and eight of its analogs are
depicted in Table 18.12 . The insecticidal efficacy of Oph and its analogs was
closely associated with their ability to enhance the conversion of exogenous ALA
to Proto (Table 18.13 ). As was observed for photodynamic herbicidal effects in
plants, (Rebeiz et al. 1990b ) the presence of N atoms at position 1 and 10 of the
macrocycle was essential for porphyric insecticidal activity. This was evidenced by
the very limited activity of phenanthrene, in which position 1 and 10 are occupied
by carbon instead of N atoms (Fig. 18.5 , Table 18.12 , # 7, 8). On the other hand,
enhancement of Proto formation and porphyric insecticidal activity were main-
tained following peripheral methyl, chloro and nitro group substitution of Oph
(Table 18.12 , # 11-18). In contrast, enhancement of Proto formation and photody-
namic toxicity was diminished by phenyl or benzyl (data not shown) substitution
(Table 18.12 , # 5, 6, 9, 10).