Balancing water solubility with membrane permeability in the design of a synthetic ionophore

11 April 2022, Version 2
This content is a preprint and has not undergone peer review at the time of posting.


Synthetic ionophores are promising therapeutic targets, yet current limitations associated with their lipophilicity and poor water solubility prevent the translation of this molecular technology into the clinic. In this work we report investigations into the cation transport ability of a series of antimicrobial supramolecular, self-associating amphiphiles (SSAs). We identify a member of this class of compounds to function as a K+ transporter in cooperative action with a known anionophore. This SSA is soluble in a range of organic solvents and in 100% water, retaining its transport activity when delivered from a purely aqueous solution – therefore overcoming current molecular delivery limitations. These findings shed light on a potential antimicrobial mechanism of action and inform the design of future therapeutic targets that can balance water solubility and membrane penetration.


Ion transport
Lipid bilayer

Supplementary materials

Supporting Information
Full experimental details and data for synthetic protocols, ion transport studies and conductance measurements.


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