How is the interaction of a chloride channel blocker with phospholipids influenced by divalent metal ions? Effect of unsaturation on the lipid side chain

Abstract The present study reveals the effect of various divalent ions (Ca2+, Mg2+and Zn2+) on the binding interaction of a prospective chloride channel blocker, 9-methylanthroate (9MA), with liposome membranes, namely, dimyristoylphosphatidylcholine (DMPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC). The liposome membranes DMPC and POPC differ in the unsaturation of the side-chain. The drug (9MA) is found to experience a greater degree of partitioning into the POPC lipid bilayer (containing unsaturated side-chain) in comparison to DMPC (containing saturated side-chain). The stronger 9MA-POPC binding interaction is found to be only nominally perturbed by the presence of metal salts. On the contrary, the 9MA-DMPC binding interaction is found to be significantly perturbed by the presence of metal salts and is manifested on the environment-responsive spectroscopic properties of the drug. The steady-state and picosecond-resolved fluorescence spectroscopic results reveal the effect of metal ions on DMPC bilayer to follow the trend Ca2+