4-Alkynylphenylsilatranes: Insecticidal activity, mammalian toxicity, and mode of action

4-Ethynyl- and 4-(prop-1-ynyl)phenylsilatranes [N(CH2CH2O)3SiR, R = C6H4-4-C triple-bond CH or C6H4-4-C triple-bond CCH3] are highly toxic to houseflies (pretreated with piperonyl butoxide) and milkweed bugs (topical LD50s 3-14 μg/g) and to mice (intraperitoneal LD50s 0.4-0.9 mg/kg), and they are moderately potent inhibitors of the [35S]-tert-butylbicyclophosphorothionate or TBPS binding site (GABA-gated chloride channel) of mouse brain membranes. Scatchard analysis indicates noncompetitive interaction of 4-ethynylphenylsilatrane with the TBPS binding site. Phenylsilatrane analogues with 4-substituents of H, CH3, Cl, Br, and C triple-bond CSi(CH3)3 are highly toxic to mice but have little or no activity in the insect and receptor assays. Radioligand binding studies with [4-3H]phenylsilatrane failed to reveal a specific binding site in mouse brain. Silatranes with R = H, CH3, CH2Cl, CH double-bond CH2, OCH2CH3, and C6H4-4-CH2CH3 are of little or no activity in the insect and mouse toxicity and TBPS binding site assays as are the trithia and monocyclic analogues of phenylsilatrane. 4-Alkynylphenylsilatranes are new probes to examine the GABA receptor-ionophore complex of insects and mammals