Transmembrane Transport of Bicarbonate Unravelled

L. Martinez-Crespo, S. H. Hewitt, N. A. De Simone, V. Sindelar, A. P. Davis, S. Butler, and H. Valkenier

Chem. Eur. J. 2021, 27, 7367-7375


Anion receptors can be used to transport ions across lipid bilayers, which has potential for therapeutic applications. Synthetic bicarbonate transporters are of particular interest, as defects in transmembrane transport of bicarbonate are associated with various diseases. However, no convenient method exists to directly observe bicarbonate transport and study the mechanisms involved. Here, an assay is presented that allows the kinetics of bicarbonate transport into liposomes to be monitored directly and with great sensitivity. The assay utilises an encapsulated europium(III) complex, which exhibits a large increase in emission intensity upon binding bicarbonate. Mechanisms involving CO2 diffusion and the dissipation of a pH gradient are shown to be able to lead to an increase in bicarbonate concentration within liposomes, without transport of the anion occurring at all. By distinguishing these alternative mechanisms from actual bicarbonate transport, this assay will inform the future development of bicarbonate transporters.