PhD defense: Ioan STROIA – 3/9/2026

Ioan STROIA

defended his PhD on 3 september 2026

 

Highly selective biomimetic transmembrane transport of water and ions

 

Front of the jury composed of:

M. Mihail BARBOIU, Directeur de Recherche, CNRS, IEM, Université de Montpellier, directeur de thèse
Mme. Emilie MOULIN, Directrice de Recherche, CNRS, ICS, Université de Strasbourg, rapportrice
M. Olivier SIRI, Directeur de Recherche, CNRS, Aix-Marseille Université, rapporteur
Mme. Niculina HADADE, Professeur, Babeș-Bolyai University, examinatrice
Mme. Mona SEMSARILAR, Directrice de Recherche, CNRS, IEM, Université de Montpellier, examinatrice

 

 

Abstract:

Transmembrane transport of water, ions and other physiologically relevant species is a fundamental process in all known forms of life. Specialized transmembrane transport proteins orchestrate the passage of these solutes with exquisite selectivity in response to diverse stimuli, including electrochemical gradients, light, temperature and chemical signalling. Biomimicking the function of natural channels represents a challenging and cutting-edge strategy for treating diseases associated with dysfunctional transport proteins, while also advancing emerging industrial technologies in water purification, energy production and storage. Although significant progress has been made in the development of biomimetic water and ion transport systems, the selectivity of artificial transporters still remains far below that of natural transport proteins. In biomedical applications, for example, the precise role and importance of transporter selectivity are still not fully understood. In parallel, for seawater reverse osmosis desalination, only a limited number of artificial water channels (AWCs) have succeeded in partially overcoming the classical permeability/selectivity trade-off.

In this thesis, different de novo design biomimetic strategies of selective carriers and self-assembled channels are implemented to achieve highly efficient transmembrane transport of nitrate, potassium, and water.

Specifically, Chapter 2 explores the weakening of hydrogen-bond (HB) donor strength from N–H to tunable C–H donors using simple cyanostilbene-based scaffolds. This strategy suppresses Cl^– transport due to insufficient compensation of its dehydration penalty, while retaining efficient NO₃^– transport owing to its lower dehydration energy, leading to NO₃^–/Cl^– selectivities exceeding 200 in some cases. Interestingly, further weakening of the C–H donor strength suppresses even NO₃^– transport, shifting toward selective water translocation. The self-assembled cyanostilbene superstructures generate both anion- and water-conducting pathways, where water clusters are transiently stabilized through C–H···OH₂ interactions. Importantly, this chapter demonstrates for the first time how subtle modulation of binding strength and binding mode can directly govern water and anion permselectivity.

Chapter 3 explores the transmembrane transport activity of the simple molecular C–H donor hexachlorocyclohexane (HCH) diastereoisomers. Interestingly, among α-, β-, γ-, and δ-HCH isomers, only β- and δ-HCH exhibit significant anion transport activity despite showing similar anion-binding properties in solution. Specifically, only δ-HCH mediates Cl^– transport, whereas both β- and δ-HCH transport Br^– and NO₃^–, with δ-HCH displaying substantially higher activity. These striking differences arise from subtle steric variations between the two diastereoisomers. Steric hindrance in β-HCH prevents the formation of highly cooperative multivalent assemblies required to compensate for the dehydration penalty of chloride, thereby suppressing Cl^– transport. In contrast, δ-HCH forms highly cooperative supramolecular complexes that efficiently stabilize chloride during translocation. Overall, this chapter demonstrates how subtle steric effects can critically govern transmembrane transport permselectivity.

In Chapter 4, ultra-selective K⁺ transmembrane transport is achieved using simple molecular tweezers comprising benzo-15-crown-5 ether (benzo-15C5) recognition motifs appended to dipicolinamide or isophthalamide cores. This strategy enables co-facial K⁺ binding (i.e., sandwiching) between two benzo-15C5 units, efficiently stabilizing via a complete dehydration and shielding the cation within the hydrophobic membrane environment during its carrier-mediated translocation. In contrast, Na⁺ transport is suppressed because the smaller cation equatorially binds within the central cavity of a single 15C5 macrocycle, leaving axial positions exposed to the membrane and preventing the efficient sandwich-type stabilization observed for K⁺. Importantly, the exceptionally high K⁺/Na⁺ selectivity (~200), together with K⁺/H⁺ selectivity approaching 100, surpasses the selectivity limits reported to date for synthetic K⁺ transporters. These remarkable permselectivity properties are reflected in both passive and secondary-active K⁺ transport, culminating in long-term membrane potential responses reminiscent of natural K⁺ channels such as KcsA.

Chapter 5 discloses a family of shape-persistent macrocycles designed to accommodate a single water molecule through mutual donor-acceptor H bonding, and for water-water interaction within the macrocyclic channel. Their negative curvature (i.e., saddle-shaped) facilitates directional (columnar) self-assembly, driven mainly by π–π stacking interactions, generating highly confined water channels in which water molecules adopt unique dipolar orientation dictated by the supramolecular stacking pattern. Specifically, syn stacking induces syn-oriented water dipoles, whereas anti stacking promotes anti-oriented dipole arrangements. These stacking modes are in part controlled by the substituents appended to the macrocyclic scaffolds. The resulting channels exhibit moderate-to-high water permeability together with excellent salt rejection, rendering these derivatives promising candidates for seawater desalination applications. This potential is further strengthened by the anticipated compatibility of the aromatic macrocycles with polyaromatic membrane matrix.

Overall, this thesis combines the molecular design of simple and potentially large-scale accessible biomimetic transporters with exceptionally high NO₃^–, K⁺, and water transport selectivity, thereby opening new opportunities for biological and seawater desalination applications. Through the introduction of new concepts and valuable mechanistic insights, this work provides a source of inspiration for the development of increasingly diverse and selective biomimetic transport systems aimed at further advancing their medical and non-medical applications.