The hemolytic toxicity of some new aminophosphonates.

A series of ten aminophosphonate derivatives were assayed for their hemolytic activity as a preliminary screening for the detection of herbicides. The data obtained indicate: 1. A clear correlation between the hemolytic capacity of the test compounds and their plant growth inhibition and an increase in membrane fluidity was demonstrated. 2. It was found that the most active compounds revealed at least one of the following structural features: an iso-propyl substituent at the phosphorus atom, a tert-butyl group attached to their hexane ring or a long hydrocarbon chain. 3. Ring substituents at the phosphorus (phenyl ring), carbon or nitrogen atoms (hexane) removed the hemolytic activity of compounds. 4. It may be concluded that the hemolytic toxicity of the aminophosphonates studied is related to their ability to incorporate and fuse into the lipid phase of the erythrocyte membrane. The general conclusion is that both stereochemistry and hydrophobicity are deciding factors for the efficiency of the interaction of the studied compounds studied with erythrocytes, and that the most possible location of the aminophosphonates is in the lipid phase of the RBC membrane.

Physiological activity of some organophosphorous compounds and their influence on mechanical properties of erythrocytes.

Hemolysis and fluidization of erythrocytes (RBC) membranes by some newly synthesized aminophosphonates as well as their potency to induce electrolyte efflux from cucumber (Cucumis sativus cv "Wisconsin") cotyledons were studied. Also, the chlorophyll content in aminophosphonate-treated cotyledons was affected. The compounds studied differed mainly in hydrophobicity of their substituents at the carbon, nitrogen and phosphorus atoms. It was found that aminophosphonate potency to fluidize RBC membranes depended on the combination of its overall lipophilicity and/or the kind of substituent at the P atom. Especially, iso-propyl groups enhanced that potency. The sequence of aminophosphonates that exhibited the strongest fluidization activity was paralelled by their physiological and hemolytic activities; in the latter case for these compounds that hemolyzed RBC under used concentrations. A general conclusion is that both the stereochemistry and lipophilicity determine the efficiency of the aminophosphonates studied. This efficiency is most probably related to the interaction of aminophosphonates with the lipid phase of biological objects.