Heavy Pnictogenium Cations as Transmembrane Anion Transporters in Vesicles and Erythrocytes

Abstract

This work introduces a new approach to transmembrane anion transport based on lipophilic and Lewis acidic tetraarylstibonium and tetraarylbismuthonium cations. The stibonium cations are particularly appealing given that they readily transport hydroxide, fluoride, and chloride anions in synthetic vesicles. When combined with human erythrocytes, the most active stibonium cation uncovered in this study quickly localizes in the cell membranes and induces hemolysis when fluoride is present. This effect is assigned to the transporter-facilitated influx of toxic fluoride anions.

Phosphonium Boranes for the Selective Transport of Fluoride Anions across Artificial Phospholipid Membranes

“…It remains that all four cations display elevated activity. These EC 50 values are in the same range as those measured for other very active fluoride anion transporter including the stibonium and bismuthonium cations A and B or the strapped calix[4]pyrrole such as C developed by Gale …”

“…Defining the ratio of these values as the selectivity factors S F , we conclude that [ 2 ] + and [ 3 ] + are 23.8 and 22.6 times more selective for the fluoride anion than the chloride anion. These selectivity factors are one order of magnitude higher than those for the group 15 cations A ( S F =EC 50 (Cl − )/EC 50 (F − )=0.6/0.41=1.8) and B ( S F =EC 50 (Cl − )/EC 50 (F − )=3.77/1.24=3) which were evaluated in egg yolk phosphatidylcholine vesicles . A comparison can also be made with the selectivity factor of the calix[4]pyrrole C ( S F =EC 50 (Cl − )/EC 50 (F − )=1.6/0.9=1.8) which was measured in POPC vesicles .…”

“…Recent efforts in this area of science have led to the development of transporters that interact with the anion via a Lewis acidic main‐group element from the Groups 15–17 . Our contribution to this research area has focused on fluoride anion transporters as useful tools for cell biology studies or as functional models of fluoride transport proteins present in organisms adapted to life in fluoride rich environments . Our efforts to date have established that lipophilic stibonium and bismuthonium cations such as A and B are particularly active as fluoride anion transporters .…”

“…Our contribution to this research area has focused on fluoride anion transporters as useful tools for cell biology studies or as functional models of fluoride transport proteins present in organisms adapted to life in fluoride rich environments . Our efforts to date have established that lipophilic stibonium and bismuthonium cations such as A and B are particularly active as fluoride anion transporters . The properties of these molecules, which can be correlated to the fluoridophilic nature of the heavy Group 15 cations, are reminiscent of those of strapped calix[4]pyrrole such as C which interact with fluoride anions via H‐bond interactions …”

Phosphonium Boranes for the Selective Transport of Fluoride Anions across Artificial Phospholipid Membranes

“…These effects can be used to easily tune the Lewis acidity of these compounds over almost three pK R þ units, which is considerable. The trend observed in the pK R þ of these compounds also correlates with their fluoride anion affinity which could be determined in aqueous solution (H 2 O/MeOH v/v = 9:1, pH 4.9) in the case of [1] + - [3] Figure S47). Fluoride anion complexation was further confirmed by isolation and structural characterization of 3-F ( Figure 3; Supporting Information, Figures S9-S13).…”