Activity of synthetic ion channels is influenced by cation–π interactions with phospholipid headgroups

Abstract

A suite of synthetic hydraphile ion channels has been used to probe the possibility of cation-π interactions between the channel and the phospholipid bilayer. The hydraphiles selected for this study contained either no sidearm, aliphatic sidearms or aromatic sidearms that varied in electron-richness. An ion selective electrode (ISE) method was used to evaluate the ion transport ability of these hydraphiles across synthetic bilayers. Transport was dependent on sidearm identity. Ion transport activity for the aromatic sidechained compounds was greatest when the sidearms were electron rich and vesicles were prepared from 100% DOPC (trimethylammonium cation headgroup, overall neutral). When the lipid headgroups were made more negative by changing the composition from DOPC to 70 : 30 (w/w) DOPC : DOPA, transport by the aromatic-sidechained channels was reduced. Fluorescence studies showed that when the lipid composition changed, the headgroups experienced a different polarity, suggesting reorientation. The data are in accord with a stabilizing cation-π interaction between the aromatic sidearm of the hydraphile channel and the ammonium phospholipid headgroup.

Aggregation and Supramolecular Membrane Interactions that Influence Anion Transport in Tryptophan‐Containing Synthetic Peptides

“…Compound wGG is positioned so that the DOPA headgroup resides in the cavity known to interact with Cl À in the published study. [40] As noted above (Figure 4), there is no difference in the isotherms observed for WGG and DOPC in the presence or absence of DOPA. This might seem unreasonable considering that DOPA is negatively charged and DOPC is neutral (zwitterionic).…”

“…[39] Third, we have shown that synthetic ion transporters show varying efficacies when cation-p interactions between DOPC and aromatic side chains can occur. [40] These effects are not observed when DOPC is mixed with DOPA, which helps to neutralize the formers ammonium headgroup charge.…”

Coordination and transport of alkali metal cations through phospholipid bilayer membranes by hydraphile channels

“…13, the correlation between transport rate and substituent constant is good. The slope (reaction constant ρ) of the line is -0.86 and the correlation coefficient (R 2 ) is also 0.86 [73]. A negative slope is expected for the interaction of a cation with a Lewis basic donor such as tertiary nitrogen.…”

Conformational mobility of 7,16-bis(4-methoxybenzyl)-1,4,10,13-tetraoxa-7,16-diazacyclooctadecane in molecular and proton-transfer complexes: X-ray and DFT studies

“…The metal ion complexing abilities of crown ethers can be improved significantly by their functionalization with ligating side arms that enhance the cation selectivity and transport through liquid membranes. 3 The C-or N-pivot, bibracchial (two arms) lariat ethers (BiBLEs) 4,5 were modeled on valinomycin complexation and designed to be flexible and dynamic when unbound and enveloping when a guest is complexed. 6 The historically first synthesized N,N 0 -dibenzyl-1,7,10,16-tetraoxo-4,13-diazacyclooctadecane (N,N 0 -dibenzyldiaza-18-crown-6, 2) 4,5,7 has been studied in detail, and it has manifested itself as a good complexing agent for a wide range of metals, both inside the cavity acting in its neutral form and in an outer-sphere coordination.…”