Ultrathin crown ether-based polyamide membrane for ion-ion separations

Domain: biology
Published: 2026-03-20
Editorial outcome: minor_revision

Abstract
Membrane-based liquid separations that selectively extract valuable ionic species from water can enhance resource circularity across industries. However, commercial membranes lack the selectivity required to target specific ions. Here we design crown-ether-based polymeric membranes for ion–ion separations using principles inspired by biological ion channels. Ultrathin membranes (~6 nm) are fabricated via interfacial polymerization of crosslinked 18-crown-6 units. The membranes preferentially sorb and transport potassium, which forms the most stable complexes with the crown ether motifs. Sorption experiments show strong potassium preference in mixed-salt environments, where competitive interactions increase selectivity. Transport measurements demonstrate selective permeation of potassium over competing monovalent and divalent cations, with selectivities of ~4 over cesium and lithium. The combination of ultrathin architecture, high crosslinking degree, and high binding-site density enables this behavior. This work establishes interfacial polymerization as a strategy to incorporate macrocycles into membranes for precise ion separation.

Introduction
Membrane-based liquid separations capable of selectively extracting valuable ionic species from water sources have the potential to enhance circularity across industries, such as metals recovery for clean energy technologies1,2. However, state-of-the-art commercial membranes currently lack the solute selectivity required to target specific valuable ions, limiting their effectiveness in such applications. While such membranes separate solutes from water and enable water purification, they fail to selectively recover valuable solutes present in these streams. Therefore, there is a pressing need to develop next-generation membranes capable of differentiating between solutes to selectively extract valuable materials from streams3,4. Single-ion selective membranes, which can preferentially permeate a targeted ion while rejecting others of similar charge, hydration shell, and size, are particularly attractive. These membranes could be pivotal in the recovery of valuable ions from waste streams and various applications, including fertilizer recovery from urine, copper recovery in the mining industry, lithium recovery from produced water and brines, and rare earth element recovery from e-waste and ores1–4. Single-ion selective membranes also hold potential for applications in batteries and sensors.

Inspired by the selectivity filters of biological ion channels, which exhibit near-perfect ion selectivity and rapid ion transport5, synthetic ionophores such as crown ethers have been explored to replicate these features in membranes6. Crown ethers are a class of macrocyclic ligands that bind to different cations, with their selectivity influenced partly by the match between the cavity size and the target ion's size7,8. Crown ether’s selective and reversible complexation to ions is a feature that can be leveraged for selective ion transport if they are properly incorporated into a nanochannel, allowing for uninterrupted interactions where ions can reversibly "hop" from one binding site to the next as they traverse through the pore9–11. In confined spaces like nanopores, additional factors such as solvation shell rearrangement12, changes in dielectric properties due to confinement13, the arrangement of ion-interacting points (including neighboring crown ethers, other functional groups, and fixed charges)14,15, and crown ether flexibility16,17, also play important roles. Proof-of-concept experiments, where crown ethers were embedded in lipid bilayer vesicles15,18–20 or confined within single solid-state nanopores10, have demonstrated their ability to selectively transport ions in a manner similar to biological ion channels, albeit with less selectivity. In these studies, the ion that selectively complexed with the crown ether building block was transported at faster rates than other ions with the same charge and valence.

Moving from proof-of-concept experiments to functional synthetic membranes that leverage the inherent ability of crown ethers to selectively complex with ions has proven challenging. Only a few complex crystalline channels have successfully harnessed this ability to selectively transport the target ion. For instance, UiO-66 crystals grown inside long and narrow polyethylene terephthalate nanochannels were functionalized with 4′-aminobenzo-15crown-5 ethers to create artificial sodium channels21. In this system, the crown ethers are confined within the pores of the MOF, and despite not all cavities being functionalized, the crystallinity of the MOF provides a somewhat repetitive spacing and order between the crown ether moieties. This structured arrangement enhances the consistency of ion interactions and enables the selective transport of Na+ ions, which form more stable complexes with the 15-crown-5 moieties compared to other ions. The proposed transport mechanism favors Na+ over K+ due to the synergistic effects of size exclusion, charge selectivity, local hydrophobicity, and preferential binding. Another example involves precipitating porous crown-ether crystals inside the ~20 µm tip of a quartz micropipette22. A solution containing 1,10-diaza-18-crown-6-ether and Zn(NO3)2·6H2O forms a composite upon drying, consisting of 1,10-diaza-18-crown-6-ether-nitrate crystals with densely packed 0.26-nm-wide Na+-selective pores, and ion-impermeable zinc hydroxide nitrate crystals that provide mechanical stability. The interconnected 1,10-diaza-18-crown-6-ether-nitrate crystals create pathways for Na+ ions, which form selective complexes with 1,10-diaza-18-crown-6-ether and permeate faster than other monovalent ions. However, fabricating continuous membranes composed entirely of these crystalline channels remains difficult, as grain boundaries typically dominate ion transport rather than the intended selective pathways.

Unlike proof-of-concept experiments and crystalline channels where ions preferentially interacting with crown ethers exhibited selective transport, the few crown ether-containing polymeric membranes made to date show the opposite effect. In these membranes, ions that bind strongly to crown ethers experience hindered transport compared to others. For example, micrometer-thick polynorbornene copolymer films were designed with distinct blocks: 12-crown-4 ligands for ion selectivity, poly(ethylene oxide) side chains for water regulation, and a crosslinker for structural stability23. In the water-swollen matrix, Na+ ions, which bind strongly to the crown ether, show slower transport than Li+. Molecular dynamics simulations confirmed this behavior, attributing it to 12-crown-4’s stronger affinity for Na+, which reduces Na+ mobility relative to Li+ in aqueous environments. A separate study synthesized a polymer of intrinsic microporosity incorporating dibenzo-18-crown-6 units, so that every repeating unit contained a potential cation-binding site24. The high free-volume linear polymer was processed into micrometer-thick films, and the transport of various monovalent and divalent cations was measured. While the membranes achieved good Li+/Mg2+ selectivity—the target of the study—they did not preferentially permeate K+ ions, despite K+ forming the most stable complexes with the crown ether building blocks used. Instead, higher transport rates were observed for all other monovalent cations tested, indicating a behavior similar to the previous work where the ion that complexes most strongly with the crown ether units in the membrane exhibited reduced mobility.

In this work, we demonstrate that crown ether’s inherent selectivity can be leveraged in a disordered polymeric system, such as the selective layer of a membrane, to transport the preferred ion selectively. We chose 18-crown-6, which preferentially complexes with K+ ions, as our model crown ether (Figure 1A). This selection is ideal because K+ lies consistently between Li+ and Cs+ in terms of bare ionic size, hydrated size, hydration energy, and diffusion coefficient in water. While Li+ and Cs+ switch positions depending on the property, K+ remains in the middle across all these parameters (Figure 1B). Enhanced K+ transport compared to Li+ and Cs+ would highlight the role of 18-crown-6's preferential complexation with K+. To create ultrathin polymeric films from 18-crown-6, we functionalized dibenzo-18-crown-6 with amino groups (Figure 1C) and reacted it with trimesoyl chloride (TMC) at the aqueous/hexane interface, forming thin crosslinked ionophore films (Figure 1D). The films were thoroughly characterized using microscopy, scattering, and spectroscopic techniques to unravel their structure and composition. We then tested their selective binding of K+ ions in both single-salt and mixed-salt adsorption experiments. Finally, we performed transport studies to confirm that K+ is selectively transported through the films compared to other ions such as Li+, Cs+, and Mg2+.

Results
Engineering crown ether-based polymeric membranes
Design guidelines can be derived from our current understanding of how biological ion channels differentiate between ions of the same charge and nearly identical size, selectively transporting the preferred ion thousands of times faster than others4. MacKinnon and colleagues’ studies on the K+-channel are particularly insightful in this regard5,25,26. They found that to transport potassium ions 10,000 times faster than sodium ions, the selectivity filter must: i) be ultrathin, about 12 Å in the case of the K+-channel; ii) have a pore size smaller than the hydrated ion but larger than its dehydrated form; and iii) provide ion-binding sites along the pore walls to stabilize the dehydrated ion. The narrow pore allows only dehydrated ions to pass, and the binding sites favorably interact with K+ ions. The spatial arrangement of these sites stabilizes K+ but not the smaller Na+ ions. Additionally, the close spacing of the binding sites causes adjacent K+ ions to repel each other, lowering the energy barrier for K+ permeation5,27. Synthetic membranes that mimic these biological principles—being thin, with subnanometer pores capable of dehydrating ions as they pass, functional groups that selectively bind the target ion with moderate binding energy, and optimal spacing between these groups—are promising candidates for achieving similarly high ion selectivity and transport rates4.

Interfacial polymerization (IP) using crown ether molecules as building blocks (Fig. 1D) offers a promising route to fabricate membranes that align with the key design parameters derived from biological ion channels: being thin, possessing subnanometer pores capable of dehydrating ions as they pass, containing functional groups that selectively bind the target ion with moderate binding energy, and having adequate spacing between these groups. Specifically, first, IP is a self-limiting reaction that enables the fabrication of thin selective polymer films. Second, by selecting the appropriate crown ether building block, we can introduce functional groups that selectively bind targeted ions with moderate binding energy. Third, the highly crosslinked nature of polymeric structures produced via IP, when using at least one trifunctional monomer, can create membranes with pore sizes small enough to promote partial dehydration of ions during transport. Last, the average spacing between crown ether binding sites can be tuned by adjusting the size and connectivity of the acyl chloride monomer in the organic phase.

To effectively incorporate crown ether building blocks into the membrane's selective layer via IP, they must be functionalized with multiple reactive groups—either amine groups to form polyamide layers or hydroxyl groups for polyester layers. This functionalization enables the crown ethers to react with acyl chloride monomers in the organic phase, forming a crosslinked polymer film at the interface of two immiscible phases. IP is the gold-standard technique for fabricating commercial reverse osmosis and nanofiltration membranes, typically relying on small monomers such as m-phenylenediamine or piperazine in the aqueous phase and TMC in the organic phase28.

The integration of large macrocycles like crown ethers as building blocks introduces challenges due to their limited solubility in the aqueous phase, steric hindrance that can reduce reactivity, and slower diffusion rates to the reaction zone. Despite these challenges, several recent studies have demonstrated the feasibility of incorporating crown ether–based monomers into polymeric thin films via interfacial polymerization, primarily targeting separations such as monovalent–divalent ion pairs29, proton conduction pathways30, or pharmaceutical purifications31. In these studies, crown ether moieties are largely exploited as macrocyclic cavities that introduce well-defined sub-nanometer free volume absent in analogous linear or non-macrocyclic polyether monomers, thereby creating additional and more uniform transport pathways that enhance the transport of only certain molecules. Related work has also shown that other bulky macrocycles, including cyclodextrins and trianglamines, can be successfully integrated into ultrathin IP-derived membranes, where their intrinsic porosity similarly enhances solute–solute selectivity32–34. Here, we show that the ion-coordination properties of crown ethers can also be harnessed to achieve selective transport between closely related monovalent ions, revealing a distinct transport regime in which selective complexation governs ion–ion selectivity.

The crown ether building block used in this work, trans-di(aminobenzo)-18-crown-6 (DAB18C6), was synthesized in high yield (68% relative to the starting material, dibenzo-18-crown-6) following a previously reported method35 (Fig. 1C, and Supplementary Fig. 1). A major challenge in using this monomer for IP was its poor water solubility at neutral or basic pH. Solubility was only achievable at acidic pH due to the protonation of the amine groups, though this protonation reduced their reactivity, preventing the formation of high-quality films at pH levels where DAB18C6 was soluble (Supplementary note 1). This issue was resolved by using a co-solvent: DAB18C6 is readily soluble in DMF, and suitable aqueous solutions for IP were prepared by first dissolving the monomer in DMF, then diluting with water to achieve the target concentration of 0.2% (w/v) in a solvent mixture of 20% DMF and 80% water (v/v). Contacting this solution with a 0.2% (w/v) TMC solution in hexane led to the immediate precipitation of a thin film at the interface. Shaking the vial renewed the interfacial area within fractions of a second, promoting the formation of a gel-like material and further illustrating the rapid reaction rate through visible precipitation. This material was easily recovered by filtration. After thorough washing with water and isopropanol, followed by drying, FTIR analysis confirmed the expected polyamide structure (Fig. 2A). Compared to the DAB18C6 monomer, the resulting material exhibited new peaks at 1650 and 1705 cm-1, corresponding to the carbonyl (C=O) stretching vibrations of amide and carboxylic acid groups, respectively. Additionally, the characteristic asymmetric and symmetric N-H stretching peaks of the primary amine groups in the DAB18C6 monomer disappeared after polymerization, replaced by a broad peak in the 3000–3600 cm-1 region in the polyamide film spectrum, likely due to absorbed moisture.

The thinness of crown ether-containing membranes is crucial when aiming to leverage the reversible and selective interactions of crown ether groups for ion transport. In such membranes, where selective transport relies on these reversible interactions, we hypothesize that the dominant transport resistance for the target ion arises from the movement through the network of binding sites4,36. This process is governed by the repeated reversible binding and release of the ion as it traverses the membrane. A thicker membrane is therefore expected to slow this process, as the ion would need to undergo more interactions before crossing to the other side. Conversely, for competing ions that interact weakly with the binding sites, transport is not selectively facilitated and may be governed by interfacial partitioning into the membrane, such that increasing thickness has a comparatively smaller effect on their transport36,37. As membrane thickness increases, the transport of the target ion—selectively binding with the functional groups—can be penalized more strongly than that of competing ions. We recently demonstrated this using a model system containing a high density of Cu2+-selective iminodiacetate groups, where membrane thickness could be precisely controlled and increasing thickness led to a decline in copper selectivity36.

The selected reaction conditions (0.2 w/v % of each monomer, with a solvent mixture of 20% DMF and 80% water (v/v) for the aqueous phase, and hexane for the organic phase) led to the synthesis of ultrathin films. The self-limiting nature of interfacial polymerization was evident, as the membranes reached a maximum thickness of approximately 6 nm, even with extended reaction times (Fig. 2B). Since a 5-minute reaction was sufficient to achieve this thickness (Fig. 2C, D), we conducted all subsequent studies using a 5-minute reaction time. This approach consistently produced smooth films with a low surface roughness of only 2.4 nm (Fig. 2E) and a moderately hydrophilic surface, as indicated by a water contact angle of 67 ± 3°. The thinness of these films is well-suited to leverage the selective complexation of 18-crown-6, minimizing the number of binding events required for ion permeation across the membrane.

The appropriate binding energy—neither too strong nor too weak—and the spatial arrangement of crown ethers within the selective layer are also critical for effective ion transport14. Strong, irreversible complexation may promote selective partitioning but can trap the target ions, allowing competing ions to permeate faster despite their lower partitioning. Notably, most crown ethers form reversible complexes with ions, and the stability of these complexes is ion-specific38. Studies embedding synthetic crown ether channels into lipid bilayer vesicles have shown that ion binding preferences dictate selective ion transport and ions transport via ion hopping from one crown ether site to the next15,18–20. Channels composed of 21-crown-7 molecules preferentially transported Cs+ ions, while those made of 18-crown-6 or 15-crown-5 selectively transported K+ and Na+ ions, respectively18.

Accordingly, dibenzo-18-crown-6 was selected as the membrane-forming building block because its cavity size and donor functionality are well matched to K+ and are known to retain preferential K+ coordination even when conformational freedom compared to 18-crown-6 is reduced. Its cavity size and functional groups allow it to form stable, selective complexes with K+, as shown in Fig. 1A, which is based on data from Dong et al24. Through proton NMR titration, Dong et al. monitored the chemical shift changes in dibenzo-18-crown-6 as it interacted with various metal ions. The binding strength difference was significant for Cs+ and Li+ compared to K+, whereas the preference for K+ over Na+ was relatively minor.

In the prepared ultrathin films, selective complexation with K+ ions is anticipated. Crown ethers free in solution can adapt their conformation to optimize coordination with a given ion; however, when incorporated into a densely crosslinked polyamide network, this flexibility is constrained, and the idealized cavity geometry may be distorted. As a result, ion coordination within the membrane should not be viewed as occurring through discrete pores of fixed size, but rather through locally constrained coordination environments defined by the crown ether moieties and the surrounding polymer matrix. These constrained sites likely exhibit reduced selectivity compared to free crown ethers in solution, consistent with prior observations of crown ethers under restricted conformational freedom15.

The optimal spacing between crown ethers, where effective ion hopping occurs, has been identified to be within 6–11 Å in vesicle-type studies18. Ottis et al. observed that a 6 Å spacing was ideal for Na+ ion hopping, with effective transport up to 11 Å18. These distances are comparable to those in biological ion channels, such as the 11.6 Å between ion-relay sites in gramicidin A39 and the 7.5 Å between K⁺ ions in the KcsA K⁺ channel5. In other systems, such as the one proposed here, the optimal distance may differ due to factors like confinement and the chemical environment, but it is likely to be within a similar range. Overall, the spacing between crown ethers should be sufficiently short to promote ion-ion repulsion but not so short that it encourages less selective, sandwich-type complexes. When crown ethers are spaced closer than ~5 Å, these sandwich-like complexes form, disrupting intrinsic selectivity15. For example, while 15-crown-5 generally favors Na+ ions, the formation of such complexes shifts its selectivity towards larger K+ ions15,19.

Confining bulky molecules such as crown ethers into a 6 nm space could force some order in the structure, as has been previously observed for ultra-thin polyamide membranes made with, albeit bulkier, cyclodextrin building blocks33,40. To investigate whether similar ordering occurred in our films, we performed grazing-incidence wide-angle X-ray scattering (GIWAXS). The GIWAXS data revealed only a broad, diffuse scattering pattern without distinct Bragg peaks, indicative of an amorphous arrangement rather than any ordered crystalline or semi-crystalline structure (Fig. 2F, and Supplementary Fig. 3). This suggests that, despite the ultra-thin configuration and the presence of bulky crown ether groups, the polyamide chains remain randomly oriented in the membrane, confirming the amorphous nature of the material.

While the average distance between crown ether units could not be directly measured, a simple structural estimation suggests it is likely within an attractive range for ion hopping. Assuming a perfectly flat and linear structure, the maximum separation between two crown ether centers in the polyamide would be approximately 1.5 nm. However, considering the random and crosslinked nature of the structure, along with the flexibility of the amide bonds, the actual spacing in the 3D structure is likely less than 1 nm, which would be conducive to ion hopping (Supplementary Fig. 4). In our prepared membranes, crown ether molecules are arranged randomly, and while aligning them could improve ion hopping efficiency20,41, it is not necessary for selective ion transport. For example, Siwy and coworkers randomly attached crown ethers to the walls of a sub-2 nm solid-state pore and achieved K⁺/Na⁺ selectivities close to 8010, demonstrating that an ordered assembly is not a prerequisite for successful ion transport.

K+ selective polyamide thin-film made from crosslinked 18-Crown-6 building blocks.
The formation of a crosslinked polyamide network made of crown ether moieties was confirmed through XPS characterization. Thin polyamide films were transferred to gold-coated substrates for XPS analysis, providing detailed insights into the bonding environments within the membrane. The O1s core-level spectrum displayed distinct binding energies indicative of C-O-C bonds from the crown ether structure, along with amide linkages, confirming the formation of the intended crosslinked network (Fig. 2G). Notably, the spectrum revealed both amide and carboxylic acid groups in nearly equivalent concentrations. This high concentration of carboxylic acid groups, resulting from the hydrolysis of unreacted acyl chloride groups from TMC upon contact with water in the aqueous phase, aligns with the slower reaction kinetics expected for the bulky crown ether monomer. The slower diffusion rates and pronounced steric hindrance of this larger monomer limit amine availability at the reaction interface, thereby increasing susceptibility to acyl chloride hydrolysis. By contrast, smaller monomers commonly used in interfacial polymerization, such as m-phenylenediamine and piperazine, react more rapidly due to their compact size and higher mobility, thus minimizing acyl chloride hydrolysis during membrane formation. The N1s core-level spectrum provides additional evidence of successful crosslinking of the crown ether monomers, showing a single dominant nitrogen environment corresponding to amide nitrogen formed by reaction of acyl chloride with amine groups (Fig. 2H).

Cryogenic scanning and transmission electron microscopy (S/TEM) analysis of the freestanding 6-nm-thick crown ether-based polyamide films demonstrated their mechanical robustness as they spanned micrometer-sized openings in Quantifoil grids (Fig. 2I). Moreover, the films displayed high flexibility, with no signs of cracking, even in areas with visible folds. Cryogenic low-angle annular dark-field (LAADF) STEM imaging revealed evenly distributed crystallites throughout the films (Fig. 2J and Supplementary Figure 5), which appeared as aggregated nanoparticle-like structures upon closer inspection (Fig. 2K). Tilting the sample during imaging produced contrast fluctuations characteristic of polycrystalline regions (Supplementary Fig. 6). LAADF-STEM was crucial in identifying these crystallites, as they appeared as indistinct blobs in bright-field imaging (BF) (Fig. 2K, left). These crystallites are likely precipitates of the DAB18C6 monomer, which has poor water solubility. While the majority of the membrane was amorphous, the crystallites were consistently dispersed throughout the structure.

Ion sorption experiments revealed a distinct preference for K+ over Cs+ in the crown ether-based polyamide films (Fig. 3), despite both ions having nearly identical hydrated sizes (Fig. 1A). The experiments were conducted at low pH to ensure protonation of all carboxylic acid groups within the membrane42, thereby minimizing their contribution to ion adsorption. Real-time quartz crystal microbalance (QCM) tracking showed significant mass changes upon exposure to 0.5 M solutions of CsCl and KCl (Fig. 3B), with frequency decreases corresponding to ion uptake. The calculated molar areal uptake from these single ion sorption experiments confirmed a higher affinity for K+ (Fig. 3C), though this affinity was less pronounced than anticipated based on the large difference in equilibrium constants for the crown ether building block when free in solution (Fig. 1B). Selectivity tests using mixed ion solutions, quantified by XPS, revealed an even more pronounced preference for K+ (Fig. 3D). This heightened selectivity likely arises from the competitive environment created when both K+ and Cs+ ions are present, with K+ demonstrating a stronger affinity for the crown ether binding sites. When K+ ions are selectively complexed by the crown ether moieties, they also effectively repel Cs+ ions from entering the polymeric structure and interacting with sites that would have otherwise been accessible in single-ion sorption experiments.

Selective ion transport in crown ether-based polyamide films.
Selective ion transport measurements showed that the crown ether-based polyamide films preferentially transported K+ over other monovalent and divalent cations (Fig. 4). To assess this selectivity, a series of experiments were conducted in a diffusion cell. In each experiment, the feed solution contained a binary salt mixture with equimolar amounts of KCl and the chloride salt of a competing cation at pH 6, while the receiving side was filled with deionized water (Fig. 4A). The concentration of each ion in the receiving side was monitored over time to determine their respective transport rates. The competing cation in the binary mixture was varied between experiments, allowing us to evaluate K+ selectivity relative to different monovalent and divalent cations. In these experiments, the crown ether-based polyamide films were mounted on isotropic anodic aluminum oxide (AAO) membranes with 20–30 nm pores for mechanical support. To enhance adhesion and prevent delamination, the AAO supports were first coated with a 1.5 bilayer polyelectrolyte gutter layer prior to film transfer. AAO supports were used as a rigid, well-defined model substrate to enable transport measurements of the ultrathin selective layer; they are not intended to represent pressure-bearing supports for practical membrane operation. SEM surface analysis of the composite membrane shows the thin crown ether-based polyamide film positioned over the polyelectrolyte-coated AAO pores (Fig. 4B). The thinness of both the crown ether-based polyamide film and the polyelectrolyte layer allowed the electron beam to penetrate through them, enabling imaging of the underlying AAO pores.

To assess the support’s contribution to ion transport, we first measured the selectivity and ion flux of the polyelectrolyte-coated AAO support alone for each cation pair of interest. These baseline measurements allowed us to compare the performance of the support with and without the crown ether-based polyamide selective layer (Supplementary Fig. 7). Upon covering the polyelectrolyte-coated AAO with the crosslinked crown ether-based polyamide film, we observed a substantial decrease in ion flux and a marked increase in ion selectivity, as expected. Specifically, the ion flux dropped by approximately two orders of magnitude, and K+ selectivity increased across all ion pairs tested. These results confirm that the crown ether layer governs the transport of ionic species, with minimal contribution from the support.

To place the reduced ion flux in context, we compared the K+ flux and selectivity of the present membrane with those of reported K+-selective membranes (Supplementary Table 5). While the K+ flux of the crown ether–based polyamide is lower than that of many reported systems, it falls within a range expected for polymeric membranes that rely on binding-mediated selectivity rather than continuous ion-conducting pathways. The reduced flux reflects transport through a dense, highly crosslinked polyamide network with a non-ordered distribution of crown ether binding sites, some of which may not be accessible during ion transport.

Ion transport through the crown ether-based polyamide film can occur via two primary pathways: (i) through interconnected channels or free-volume elements within the polyamide matrix and (ii) through specific, reversible interactions with the crown ether moieties (Fig. 4C). In an ideal membrane with perfectly arranged crown ether sites and optimal confinement, the latter pathway would dominate. However, in the prepared membranes where there is a random arrangement, both pathways likely contribute. K+ ions can utilize both transport pathways, while competing ions such as Li+, Cs+, and Mg2+ primarily rely on the free-volume pathway due to their weaker affinity for 18-crown-6, resulting in lower flux. Furthermore, in multisalt tests, when K+ ions selectively bind to the crown ether cavities, they will induce charge repulsion effects that further limit available transport pathways for competing cations.

Testing a crown ether-based polyamide membrane with various cation pairs revealed selectivity for most pairs, except K+/Na+, for which it was not selective (Fig. 4D). The inability of the membrane to differentiate between potassium and sodium ions is not surprising given the relatively low affinity of dibenzo-18-crown-6 for K+ over Na+ (Fig. 1A). The K+/Mg2+ selectivity was conservatively estimated to be >300, based on the instrument’s detection limit, as no Mg2+ was detected on the receiving side after three days of testing. The measured K+/Li+ and K+/Cs+ selectivities were 3.8 and 4.4, respectively. Achieving such high selectivities between similar monovalent ions, where charge-based mechanisms offer no advantage, is rare in polymeric membranes. The minimal differences in their hydrated radii—only 1.02 Å between K+ and Li+, and 0.04 Å between K+and Cs+ (Fig. 1A)—make size-based differentiation exceptionally challenging. A separation mechanism involving partial dehydration, where water molecules are removed to reduce ion size, could favor either Li⁺ or Cs⁺ depending on the average pore size, as K⁺ occupies an intermediate position in both bare ion size and dehydration energy. The precise separations we observe, favoring K⁺, likely result from molecular recognition through coordination chemistry, enabled by a facilitated transport mechanism.

The K⁺ ion flux was significantly higher when Mg2+ was the competing cation (1 × 10-8 mol cm-2 min-1) than when the competing cations were monovalent (1.7, 0.6, 1.1 × 10-9 mol cm-2 min-1 for Li+, Na+, and Cs+, respectively). This increase results from the higher Cl− concentration in the feed and the membrane’s high K+/Mg2+selectivity. The elevated Cl− flux generates a membrane potential that drives the transport of cations—primarily K+ due to the high selectivity—across the membrane to maintain charge neutrality. Consistent with this, the lowest K⁺ flux was observed for the least selective ion pair (K+/Na+), where both cations could readily transport through the membrane to maintain electroneutrality.

Preparing polyamide films at a free interface and then transferring them to a support, as done in this study, enables characterization using multiple techniques (AFM, TEM, XPS, GI-WAXS, QCM) on the same selective layer used for transport studies. However, a key drawback of this method is that defects introduced during transfer can significantly impact transport studies, even though they do not affect other characterization techniques. For example, a crack in the film during transfer or debris on the porous support that stretches the film upon drying can create pinholes, resulting in non-selective transport pathways that dominate ion transport (Supplementary Fig. 8). To obtain statistically significant data on the transport properties of the prepared films, we fabricated enough membranes to secure at least three high-quality samples for each of the two key transport tests: mixed salt diffusion experiments for K+/Cs+ and K+/Li+. These tests were specifically selected to confirm that the crown ether building blocks impart selective transport properties to the membrane, favoring ions with which they form stronger complexes (i.e., K+). High-quality films were identified as those showing a K+ flux more than an order of magnitude lower than that of the bare support during K+/Cs+ and K+/Li+ experiments (Supplementary Fig. 7). The full transport data for all measured membranes, including those not meeting the integrity criterion, are provided in the Supporting Information (Supplementary Tables 1–3). Results indicated that K+ flux ranged from 0.6 to 2 × 10-8 mol cm-2 min-1 in these membranes (Fig. 4E), with average mixed salt selectivities of 3.5 for K+/Li+ and 3.7 for K+/Cs+ (Fig. 4F).

When benchmarked against commercial polyamide membranes made by interfacial polymerization (e.g., FilmTec™ NF270 and NF90), the ultrathin crown ether-based polyimide films prepared here demonstrated higher monovalent ion selectivity, attributed to the crown ether moieties (Fig. 4G). Previous efforts to use crown ether molecules as building blocks for ion-selective polymeric membranes have leveraged complexation at crown ether sites as “sinks” where ions forming the most energetically favorable complexes are delayed, often resulting in inverse selectivities towards the ion that formed the most favorable complex with the crown ether building block (Fig. 4G). This effect is likely due to the large thickness of these membranes (on the order of tens of micrometers), which allows for numerous reversible ion–crown ether interactions before an ion can cross to the opposite side. The "sink" effect was further intensified, in some cases, by a low density of crown ether moieties, which hindered efficient ion hopping. In contrast, the crown ether-based polyamide films prepared here are only 6 nm thick, meaning that an ion traveling a direct path would interact fewer than 18 times with crown ether sites—18 being the theoretical maximum if all crown ether moieties were perfectly aligned, which is not the case in our system. This minimal path length, combined with the high density of crown ether sites, enabled the films to selectively partition and efficiently transport the ion that forms the most favorable complex with the crown ether building blocks, achieving greater transport efficiency than competing monovalent and divalent ions. As a result, these polymeric membranes exhibited monovalent ion-ion selectivity toward the ion with the strongest crown ether complexation (Fig. 4G).

To assess the behavior of the crown ether–based selective layer under pressure-driven conditions, membranes were also fabricated directly on porous polyacrylonitrile polymeric supports using identical interfacial polymerization conditions. Water permeance and salt rejection measurements were performed in a stirred cell at 3.5 bar, and high rejection of Rose Bengal (>95%) was observed, confirming complete surface coverage and the absence of macroscopic defects in the selective layer. As summarized in Supplementary Table 4, these membranes exhibit water permeances of approximately 1.3 L m-2 h-1 bar-1, and a moderate rejection of Mg²⁺ (~32%), while showing low rejection (8–10%) for monovalent K+ and Li+ ions under both single-salt and mixed-salt conditions. The pressure-driven transport behavior observed here is consistent with that of conventional nanofiltration-type polyamide membranes, including those reported by Alhazmi et al., who employed the same amino-functionalized crown ether monomer in interfacial polymerization on polymeric supports and optimized fabrication conditions to leverage the intrinsic macrocyclic cavity for pharmaceutical separations31. These results indicate that under pressure-driven operation, convective solvent transport can dominate ion transport, limiting discrimination among ions of similar size and charge.

Methods
Materials
Anodic aluminum oxide (AAO) membranes with a diameter of 25 mm and an average pore size of less than 20 nm were obtained from Hefei Pu-Yuan Nanotechnology Ltd. Dibenzo-18-crown-6, hydrazine monohydrate, palladium on carbon (10 wt.% Pd/C), and N,N-dimethylformamide (DMF) were supplied by Sigma-Aldrich. 1,3,5-Benzenetricarbonyl chloride (TMC) was acquired from Thermo Scientific Chemicals. Lithium chloride (LiCl) was sourced from Acros Organics; sodium chloride (NaCl) and potassium chloride (KCl) were obtained from Sigma-Aldrich; cesium chloride (CsCl) and magnesium chloride (MgCl₂) were purchased from Thermo Scientific Chemicals. Poly(ethyleneimine) (PEI) solution (50 wt.% in water, average molecular weight ~750,000 g/mol) and polyacrylic acid (PAA) solution (35 wt.% in water, average molecular weight ~100,000 g/mol) were purchased from Sigma-Aldrich. All aqueous solutions were prepared using ultrapure water from a Milli-Q purification system.

Synthesis of trans-di(aminobenzo)-18-crown-6 (DAEB18C6)
The synthesis of DAB18C6 was performed following the methodology reported by Patel et al., starting from commercially available dibenzo-18-crown-635. The process involved two main steps: the nitration of dibenzo-18-crown-6 to obtain trans-di(nitrobenzo)-18-crown-6, followed by the reduction of the nitro groups to yield the target compound, DAB18C6. All reactions were carried out under a nitrogen atmosphere unless otherwise specified, and the progress of the reactions was monitored by thin-layer chromatography (TLC) where applicable. NMR spectra were recorded in CDCl3, and chemical shifts (δ) are reported in parts per million (ppm). This synthesis route effectively converts dibenzo-18-crown-6 into an amino-functionalized crown ether, providing the key building block for our studies.

Step 1: Synthesis of trans-di(nitrobenzo)-18-crown-6. Dibenzo-18-crown-6 (10 g, 27.8 mmol) was dissolved in dichloromethane (DCM, 150 mL). Acetic acid (120 mL) was added sequentially to the solution. Concentrated nitric acid (69%, 15 mL) was then added dropwise under continuous stirring at room temperature. The reaction mixture was stirred for 48 hours at room temperature during which nitration of the aromatic rings produced a mixture of cis- and trans-di(nitrobenzo)-18-crown-6 isomers. Owing to its significantly lower solubility in the reaction medium, the trans isomer selectively precipitated from solution35. The precipitated product was collected by filtration and washed sequentially with DCM (100 mL) and deionized water (50 mL). The solid was dried under vacuum at 70 °C for 24 hours to afford trans-di(nitrobenzo)-18-crown-6 as a white powder (9.6 g, 77% yield, 1H/13C NMR spectrum available in Supplementary Figure 1A/B). 1H NMR (400 MHz, CDCl3, δ): 7.85 (d, 2H; J = 9 Hz), 7.68 (s, 2H), 7.12 (d, 2H; J = 9 Hz), 4.18 (br, 8H), 3.82 (br, 8H). 13C NMR (100 MHz, CDCl3, δ): 154.2, 148.1, 141.0, 118.0, 111.7, 107.0, 68.8-6.84. The 1H and 13C NMR data are consistent with previously reported characterization for this compound35.

Step 2: Synthesis of DAB18C6. Trans-di(nitrobenzo)-18-crown-6 (5 g, 11.1 mmol) and 10% palladium on carbon (Pd/C, 450 mg) were added to ethanol (150 mL) under a nitrogen atmosphere. Hydrazine monohydrate (NH2NH2·H2O, 30 mL) was then added to the mixture. The reaction mixture was heated to reflux at 90 °C and stirred for 5 hours. Upon completion, the hot mixture was immediately filtered to remove the catalyst and prevent crystallization of the product. The filtrate was concentrated using a rotary evaporator to remove the solvent. The resulting solid was dried under vacuum at 80 °C for 24 hours to obtain DAB18C6 as a powder (3.8 g, 88% yield, 1H/13C NMR spectrum available in Supplementary Figure 1C/D). 1H NMR (400 MHz, CDCl3, δ): 6.59 (d, 2H; J = 8 Hz), 6.20 (s, 2H), 6.02 (d, 2H; J = 8 Hz), 4.63 (s, 4H), 3.90 (m, 8H), 3.75 (m, 8H). 13C NMR (100 MHz, CDCl3, δ): 149.5, 143.8, 139.6, 116.0, 105.8, 101.3, 69.6-68.2. The 1H and 13C NMR data are consistent with previously reported characterization for this compound35.

Synthesis of crown ether-based polyamide membranes
Preparation of Solutions: DAB18C6 was initially dissolved in dimethylformamide (DMF) to prepare a 1% (w/v) stock solution. This stock solution was then diluted with Milli-Q water to achieve a final concentration of 0.2% (w/v), using a solvent mixture of 20% DMF and 80% water (v/v). Similarly, trimesoyl chloride (TMC) was dissolved in hexane to prepare a 0.2% (w/v) solution and stirred for 30–60 minutes to ensure complete dissolution.

Film Formation: A silicon wafer with a rod attached perpendicularly at one corner was placed inside a Petri dish. Approximately 7–10 mL of the DAB18C6 solution was poured into the dish to fully cover the silicon wafer, ensuring a solution depth of at least ~1 cm. Three to five milliliters of the TMC/hexane solution were then carefully poured from the side of the Petri dish to minimize disturbance of the interface during the pouring process. After a defined reaction time, the crown ether-based polyamide membrane formed at the interface.

Film Collection and Drying: The interfacial membrane was carefully retrieved using the silicon wafer by manipulating it via the attached rod. The wafer was approached to the interface with a continuous movement while maintaining a slight angle to facilitate the lifting of the membrane. Once the film adhered to the wafer and was taken out of the Petri dish, it was transferred to a large Milli-Q water bath to float freely. After 5–10 minutes, the floating thin films were collected onto different substrates: porous substrates for transport studies, gold-coated glass slides for XPS, silicon wafers for AFM, and Quantifoil R 1.2/1.3 Holey Carbon grids for TEM. The supported films were dried overnight at room temperature to ensure good adhesion to the substrates.

Post-Treatment: For XPS and AFM analyses, the samples were further rinsed sequentially with hexane, water, and isopropanol, followed by an additional drying step. The samples intended for transport studies were used after the initial drying step, within one week of preparation.

Porous Supports Used for Transport Studies: To provide additional mechanical reinforcement to the ultrathin crown ether-based polyamide membrane, we utilized AAO membranes with small pores. To improve the interaction between the membrane and the AAO supports, we coated the AAO with a "cushion" polyelectrolyte layer. We observed that directly depositing the film onto AAO supports without the polyelectrolyte layer resulted in poor adhesion; the film would often delaminate from some sections when immersed in water after drying. The polyelectrolyte "cushion" has high permeance to ions, allowing us to effectively probe the transport properties of the crown ether-based polyamide membrane. To coat the AAO with the polyelectrolyte layer, the AAO membrane surface underwent 1.5 cycles of successive treatments with polyelectrolytes—specifically poly(acrylic acid) (PAA) and poly(ethyleneimine) (PEI)—following the surface coating procedures described in the literature43,44. Each full cycle consisted of sequential deposition of 0.1 wt% PAA (pH ~3.5) for 10 minutes and 0.1 wt% PEI (pH ~10.6) for 15 minutes onto the surface. After each polyelectrolyte deposition, the membrane was immersed in ultrapure water for 5 minutes to remove any unbound molecules. The half cycle involved a final deposition of PAA only.

Notes: The ultrathin films are delicate, and the manual handling process decreases the success rate. Cracks in the films were often observed during manipulation, leading us to discard these samples immediately. In some cases, however, cracks were only detected after conducting transport studies, as evidenced by an ion flux one to two orders of magnitude higher than when a continuous film covered the pores. As expected, no ion selectivity was observed for films with cracks. An example of the defects present in these films is shown in Supplementary Figure 8.

Ion adsorption studies
The freestanding crown ether-based polyamide membranes were transferred onto 5 MHz gold QCM sensors (QSX 301, Biolin Scientific) for single ion sorption studies using QCM, and onto gold-coated glass for mixed ion sorption studies using XPS.

Single ion: The coated QCM sensors were first equilibrated in ultrapure water before being sequentially exposed to 0.5 M CsCl and 0.5 M KCl solutions, with ultrapure water washes in between (all solutions at pH 3.2). The frequency changes upon exposure to the ion-containing solutions were monitored using a Q-sense flow module with four parallel channels (Biolin Scientific). Each experiment involved two coated sensors and two bare sensors as blanks, running in parallel. To account for viscosity and density variations in the solutions, the frequency shifts observed with the bare sensors were subtracted from those of the coated sensors. The corrected frequency changes were then used to calculate the mass adsorbed by the crown ether-based polyamide membranes in response to CsCl and KCl solutions, applying the Sauerbrey equation:
Δf = - (2f0^2 / A * sqrt(ρq * μq)) * Δm (1)
where Δm is the change in mass adsorbed (kg) on the sensor, Δf is the change in frequency (Hz), f0 is the resonant frequency (Hz) of the sensor, A is the piezoelectrically active area (m2), ρq is the density of quartz (kg m-3), and μq is the shear modulus of the quartz (Pa).

Mixed ion: Gold substrates coated with crown ether-based polyamide membranes were immersed in a mixed ion solution of KCl and CsCl (0.25 M each, pH 3.2) for two days. After removal, they were briefly rinsed in ultrapure water to remove excess solution and left to dry at room temperature overnight. XPS analysis (VersaProbe II, Physical Electronics) was then conducted to quantify the amounts of Cs and K absorbed by the crown ether-based polyamide membranes.

Ion transport studies
Diffusion Cell Setup: A custom-made diffusion cell with two 60 mL chambers and a water jacket was used for membrane performance testing. The membrane was initially positioned between two stainless steel washers, each featuring a circular opening of 0.4 cm2. To ensure a proper seal, a rubber gasket was placed on both sides of the membrane. The entire assembly was then secured using binder clips, which facilitated easier handling. It was then positioned between the two chambers with its active layer facing the feed solution. The exposed area of the membrane (active area) was 0.4 cm2. The water jacket was maintained at 25 °C using a cooling/heating recirculator (Cole-Parmer Polystat) to control the internal solution temperature. Prior to testing, approximately 20 minutes were allowed for the recirculator to stabilize the diffusion cell temperature.

Testing Procedure: All tests done were multisalt tests. The feed solution contained 0.1 M of two salts: KCl and either NaCl, CsCl, LiCl, or MgCl2, while the receiving solution contained deionized water. Each chamber was continuously stirred with a magnetic stir bar to ensure uniform concentration throughout the solution. At specific time intervals, 5 mL aliquots were withdrawn from the receiving chamber to measure ion concentrations. The samples were analyzed using ion chromatography (IC) (940 Professional IC Vario, Metrohm). The peak areas obtained from the IC signals were converted to salt concentrations by referencing calibration curves established for each specific ion pair. Between tests with different ion pairs on the same membrane, a thorough rinse was performed by flushing both sides of the diffusion cell with deionized water three times. The final rinse involved stirring in deionized water for over an hour.

The ion flux (Jc) was calculated using Equation (2):
Jc = (Cc * V) / (A * t) (2)
where: Cc is the ion concentration in the receiving solution, V is the volume of the receiving solution, A is the active membrane area during testing, and t is the duration of the experiment.

Ion selectivity was subsequently determined using Equation (3):
Selectivity = (Ji / Jj) * (Cj / Ci) (3)
where: Ji and Jj are the fluxes of the target ion and the competing ion, respectively, and Ci and Cj are the concentrations of the target ion and the competing ion in the feed solution. In this study, potassium ion (K+) was selected as the target ion due to its highest binding affinity to 18-crown-6, while the other cations (i.e., Cs+, Li+, Mg2+) served as competing ions.

Characterizations
FTIR: To prepare the crosslinked crown ether-based polyamide samples for FTIR, 10 mL of a 0.2% (w/v) TMC solution in hexane was contacted with 10 mL of a 0.2% (w/v) DAB18C6 solution in DMF-water (20/80 v/v) and shaken for 1 hour to continuously generate a new interface. The crosslinked polyamide that formed at the interface was then recovered via filtration and thoroughly washed with hexane and isopropanol. DAB18C6 powder was used as is. Both samples were dried at 60°C for 24 hours before FTIR measurements were performed using a Shimadzu IRTracer-10 with 20 scans at a resolution of 2 cm-1.

XPS: To prepare the samples for XPS, crown ether-based polyamide membranes were formed at a free interface, as described in the methods section, with a reaction time of 5 minutes, and then transferred onto a gold-coated glass slide. The membranes were thoroughly washed with hexane, water, and isopropanol, followed by drying for at least 24 hours. XPS analysis was performed using a VersaProbe II (Physical Electronics). Elemental signals were collected with a 200-µm X-ray beam, 50 W power, and 15 kV electron beam energy. A survey scan was conducted five times for each membrane to identify elements, using a pass energy of 187.85 eV and a step size of 0.8 eV. High-resolution scans were taken for carbon, oxygen, nitrogen, and, for ion adsorption studies, potassium and cesium, with each scan repeated 5, 10, 20, and 20 times, respectively. The pass energy and step size for these scans were set to 23.5 eV and 0.1 eV. All data were processed using CasaXPS (Version 2.3.25PR1.0), with calibration based on the C 1s peak at 284.4 eV. Bond deconvolution for oxygen, nitrogen, and silicon followed literature guidelines45.

SEM: A field emission scanning electron microscope (FE-SEM, Hitachi SU-70, Hitachi High Technologies America) was used for sample imaging. Before imaging, all samples were coated with an 8 nm iridium layer using a Cressington 208 sputter coater (Ted Pella). SEM images were acquired at 5 kV with a working distance of 10–15 mm.

TEM: Cryo-S/TEM imaging was performed using a JEOL JEM-2100F transmission electron microscope (TEM). Cryo-TEM images were formed on a Gatan ORIUS SC1000 charge-coupled device (CCD) camera. Cryogenic low-angle annular dark-field scanning transmission electron microscopy (LAADF-STEM) images were collected using a Gatan Model 805 detector with a 12 – 20 cm camera length. Cryogenic HAADF-STEM and BF-STEM images were collected using JEOL detectors (EM-24560 and EM-24541SIOD, respectively) with a camera length of 3 – 10 cm. For all STEM imaging, dwell times between 20 – 25 s were used with the preset 1 nm spot size. All imaging was performed at cryogenic temperatures using a Simple Origin Model 215 cryo transfer holder. In all cases, the holder was loaded into the TEM column then cooled to cryogenic temperature. TEM images were collected at magnifications below 40,000x. STEM images were collected at magnifications of 60,000 – 600,000x with a scan size of 1,024 x 1,024 pixels.

AFM: To prepare the samples for AFM, crown ether-based polyamide membranes were formed at a free interface, as detailed in the methods section, with varying reaction times, and then transferred onto Si-wafers. The membranes were thoroughly washed with hexane, water, and isopropanol, dried for at least 24 hours, and then scratched with a needle. AFM measurements were performed using a Bruker Dimension FastScan with a FastScan-B tip (5 nm tip radius, Bruker, Billerica, MA) in tapping mode. For each condition, at least eight height measurements were recorded. Data processing was carried out using Gwyddion software. The images were flattened prior to height measurements.

GI-WAXS: The crown ether-based polyamide film was transferred to a Si wafer, washed with hexane, water, and isopropanol, then dried overnight prior to measurement. Measurements were conducted using a Xenocs Xeuss 3.0 equipped with a microfocus sealed-tube Cu 30 W/30 μm X-ray source (Cu K-α, λ = 1.54 Å).

Data availability
All data that support the findings of this study are available within the paper and its Supplementary Information or from the corresponding authors upon request.

Peer review rounds
[{"round": 1, "reviewer_comments": {"reviewer_1": "This manuscript focuses on the fabrication of crown ether polyamide membranes for ion separation. Crown ethers have\nbeen of research interest for molecular separation due to the intrinsic pore structures. The authors demonstrated ultrathin\nmembranes prepared via interfacial polymerisation, a common method for commercial polyamide membranes. Their novel\ninvestigation and characterisation techniques achieve high separation performance for K+ ions, though the experimental\nscope is limited. Further investigations are recommended as per the comments below to validate the findings.\n- There’re different types of crown ethers with the different number of atoms in the ring. The selection criteria for dibenzo-18-\ncrown-6-ether should be clarified, considering that while 18-crown-6-ether binds K+ ions, the non-planar structure of\npolyamide films and polyamide bonds may affect the pore size.\n- Water contact angle data is critical for understanding membrane permeation behaviour in aqueous ion separation\napplications.\n- The nitration of dibenzo-18-crown-6 should yield both cis- and trans-DAB18C6. The methodology for their separation and\nthe rationale for using only trans-DAB18C6 in this study should be detailed.\n- Have you tried the same polyamide membranes from cis- DAB18C6? How were the results?\n- The polyelectrolyte gutter layer is essential in this study for preventing membrane cracks and leakage. Additional\ncharacterisation, including thickness and water and ion permeability, is necessary. Why was a 1.5-layer coating of PEI and\nPAA selected?\n- The crown-ether polyamide layer demonstrated stability on PVDF porous support (Fig S2d). Was a gutter layer also\napplied to this sample?\n- The mechanical properties of the selective layer are critical for membrane separation applications, despite minimised\nhydraulic pressure on ion separations. Can the membrane withstand pressure on an AAO substrate?\n- How does membrane performance vary with thickness? A thicker layer might decrease permeance but enhance selectivity.\n- Ion permeability performance along with selectivity should be compared with existing literature data.\n- The current fabrication method is complex. Given that interfacial polymerisation (IP) for RO membranes is directly applied\nto substrates for simplicity, can this crown ether polyamide layer also be directly applied? If so, how does it affect separation\nperformance.", "reviewer_2": "In this manuscript, the authors developed an ultra-thin, crown ether functionalized membrane using interfacial\npolymerization. Due to the specific interaction between 18-crown-6 and K+ ions, along with the ultra-low membrane\nthickness of 6.6 nm, the membrane shows good selectivity between monovalent cations of 3.8 for K+/Li+ and 4.4 for K+/Cs+.\nThe proposed mechanism involves reversible complexation between the crown ether sites and K⁺ ions. Overall, the work\npresents an interesting concept that could appeal to the membrane community. However, there are still some major issues\nthat need to be addressed before considering its publication in Nature Communications.\n1. Figure 2h shows a rather low signal-to-noise ratio, which makes it difficult to clearly support the presence of unreacted –\nNH2 groups. Additionally, the authors should consider discussing the potential impact of hydrolyzed –COOH or protonated –\nNH3+ groups (under low pH conditions) on ion flux and selectivity, as these groups could facilitate the transport of anions or\ncations.\n2. In Figure 3d, the author used XPS to quantify the adsorption of different ions. However, since XPS only probes the top few\ntens of nanometers, it mainly reflects surface information. It’s strongly recommended to use ICP or other bulk\ncharacterization methods to support this analysis.\n3. The transfer process after interfacial polymerization introduces defects and hinder scalability. Could direct polymerization\non a porous membrane (polymeric or ceramic) achieve comparable selectivity? In addition, on Page 9, line 22, the author\nmentions testing three “high-quality” samples for selectivity. How were these samples selected? Were they the top-\nperforming membranes, or was there another criterion?\n4. The author mentions the membrane’s mechanical robustness. Could this claim be supported up by experimental data, like\nAFM measurements?\n5. The ion absorption tests were done at low pH, were the selectivity measurements performed under the same acidic\nconditions? Also, would this low pH cause amide group hydrolysis and decrease long-term stability?\n6. Even though the membrane is very thin, the flux dropped by 1-2 orders of magnitude compared to the bare AAO substrate,\nthis might be because it lacks ion-conducting groups. How does this flux performance compare to other ion-selective\nmembranes? Also, could the authors suggest possible ways to improve the flux without compromising selectivity?\n7. Given the extensive literature on the use of crown ethers in interfacial polymerization for ion-selective membranes\n[Angewandte Chemie, 2023, 62(18): e202300167; Journal of Materials Chemistry A, 2025, 13(16): 11732-11748; Journal of\nMembrane Science, 2025, 714: 123372], the novelty and uniqueness of this study should be further clarified and\nemphasized.", "reviewer_3": "The paper describes the preparation and characterization of interfacial polymerized\nthin-film composite membranes with an amino-functionalized crown ether as hydrophilic monomer. The key finding of the\nwork is the preferential K+ transport over other monovalent cations. The ion-ion selectivities of approximately 4 for\nmonovalent cation pairs (K+/Cs+ and K+/Li+) is impressive. The conclusions are supported by the well-described\nexperiments.\nThe paper would have more relevance for applications if the IP films would have been prepared on a polymeric support\nmembrane. Here the support was an anodic aluminium oxide membrane. These membranes are brittle and prevent\napplications under any mechanical stress like pressure filtration. In addition they are not compatible with the polymeric IP\nfilm. This required a polyelectrolyte inter layer which influences the cation transport. The ions transport properties were not\nmeasured under filtration condition but in a diffusion cell, which has little relevance for practical applications. The authors\nshould have cited the work of Alhazmi et al. (ref. 32) in a correct way. The membrane preparation part in this reference is\nvery similar, also using interfacial polymerisation and amino-functionalized crown ether as hydrophilic monomer. But they\nuse a polmeric support membrane and pressure filtration for transport characterisation. This should have been discussed in\nthis work.\nThe authors describe on page 5 that thin membranes favor the high selectivity because the rate limiting step for the transport\nof the non-favored ion is the partitioning into the membrane, whereas the rate limiting step for the target ion is its movement\nthrough the network of binding sites. For me it is not convincing hat the solution of the not complexed ion into the water-\nswollen membrane is rate liming."}, "author_response": "Response to Reviewers\nColor coding used in this document:\n• Reviewer comments are shown in black.\n• Blue text indicates the authors’ responses to reviewer comments.\n• Orange text highlights text that was added or modified in the revised manuscript in response to the reviewers’\nsuggestions.\nReviewer #1 (Remarks to the Author):\nThis manuscript focuses on the fabrication of crown ether polyamide membranes for ion separation. Crown ethers\nhave been of research interest for molecular separation due to the intrinsic pore structures. The authors demonstrated\nultrathin membranes prepared via interfacial polymerisation, a common method for commercial polyamide\nmembranes. Their novel investigation and characterisation techniques achieve high separation performance for K+\nions, though the experimental scope is limited. Further investigations are recommended as per the comments below\nto validate the findings.\nR: We thank the reviewer for their careful assessment and constructive comments. We appreciate their recognition of\nthe novelty of our approach and the separation performance achieved for K+ ions, and we have taken their suggestions\ninto account by addressing the recommended points to further strengthen and validate the study.\n1. There’re different types of crown ethers with the different number of atoms in the ring. The selection criteria for\ndibenzo-18-crown-6-ether should be clarified, considering that while 18-crown-6-ether binds K+ ions, the non-planar\nstructure of polyamide films and polyamide bonds may affect the pore size.\nR: We thank the reviewer for this insightful comment. Dibenzo-18-crown-6 was selected as a model building block\nto test a fundamental hypothesis: whether a disordered polymeric assembly of crown ether motifs embedded within a\ncross-linked polyamide network can collectively give rise to ion-selective transport. Our objective was not to optimize\nK+ separation specifically but rather to assess, at a fundamental level, whether this design strategy is viable and merits\nbroader consideration for polymeric ion-selective membranes.\nDibenzo-18-crown-6 was chosen because its size and coordination geometry are well matched to K+ in solution, it is\nchemically robust, and its diamine-functionalized derivatives are well established, enabling straightforward\nincorporation via interfacial polymerization without introducing additional synthetic variables. This allowed us to\nfocus on structure–transport relationships rather than monomer development.\nWe agree with the reviewer that incorporation into a non-planar, densely cross-linked polyamide network can distort\nthe ideal crown-ether geometry and effectively rigidify the macrocycle. As a result, the binding environment\nexperienced by ions in the membrane differs from that of isolated crown ethers in solution. Consistent with this, our\nadsorption measurements show that dibenzo-18-crown-6 retains a preference for K+ after incorporation, although the\nselectivity is reduced relative to the free macrocycle. This behavior is consistent with prior supramolecular studies\nshowing that immobilization and increased rigidity reduce conformational adaptability while preserving size-based\nrecognition[1].\nAccordingly, ion transport in these membranes should not be interpreted as occurring through discrete, idealized\ncrown-ether pores, but rather through a three-dimensional polymer network in which locally constrained crown motifs,\npolymer chain packing, and cooperative interactions collectively define the effective transport pathways. We have\nclarified this point in the revised manuscript.\nAdded text to methods section: In the prepared ultrathin films, selective complexation with K+ ions is anticipated.\nCrown ethers free in solution can adapt their conformation to optimize coordination with a given ion; however, when\nincorporated into a densely crosslinked polyamide network, this flexibility is constrained, and the idealized cavity\ngeometry may be distorted. As a result, ion coordination within the membrane should not be viewed as occurring\nthrough discrete pores of fixed size, but rather through locally constrained coordination environments defined by the\ncrown ether moieties and the surrounding polymer matrix. These constrained sites likely exhibit reduced selectivity\ncompared to free crown ethers in solution, consistent with prior observations of crown ethers under restricted\nconformational freedom42.\n2. Water contact angle data is critical for understanding membrane permeation behaviour in aqueous ion separation\napplications.\nR: We thank the reviewer for this suggestion. Water contact angle measurements were performed and are now reported\nin the main text to complement the surface morphology characterization and to provide context for aqueous permeation\nbehavior. Specifically, the sentence below was added.\nAdded text to the results section: This approach consistently produced smooth films with a low surface roughness\nof only 2.4 nm (Fig. 2E) and a moderately hydrophilic surface, as indicated by a water contact angle of 67 ± 3°.\n3. The nitration of dibenzo-18-crown-6 should yield both cis- and trans-DAB18C6. The methodology for their\nseparation and the rationale for using only trans-DAB18C6 in this study should be detailed.\nR: We thank the reviewer for this excellent comment and fully agree that polyamide films prepared from cis- and\ntrans-DAB18C6 are expected to exhibit different structural and transport properties. Differences between cis and trans\nmonomers are well known to influence network connectivity, chain packing, free volume, and transport behavior in\npolyamide systems, and similar effects are anticipated for crown ether–based polyamides.\nAs noted by the reviewer, nitration of dibenzo-18-crown-6 yields both cis and trans isomers. In this work, we followed\nwell-established synthetic and separation procedures reported in the literature, in which the two regioisomers are\nseparated based on their different solubilities during recrystallization from acetic acid, a step that selectively isolates\nthe trans isomer with high purity . We have now explicitly specified this purification step in the manuscript and cited\nthe appropriate literature to clarify how the trans isomer was obtained.\nThe primary objective of this study was to demonstrate that the selective complexation inherent to crown ethers can\nbe translated into selective ion transport in an ultrathin polymeric membrane, rather than to systematically explore\nhow monomer stereochemistry tunes membrane microstructure. For this reason, we focused exclusively on a single,\nwell-defined isomer. We fully agree that comparing cis and trans crown ether monomers represents an important\nopportunity to further tune membrane structure and transport properties, and we have highlighted this direction in the\nDiscussion section of the revised manuscript to guide future studies.\nAdded text to methods section: during which nitration of the aromatic rings produced a mixture of cis- and trans-\ndi(nitrobenzo)-18-crown-6 isomers. Owing to its significantly lower solubility in the reaction medium, the trans\nisomer selectively precipitated from solution35.\nAdded to the discussion section: In addition, the use of different crown ether regioisomers (e.g., cis versus trans)\noffers an unexplored handle to tune network topology, local packing, and ion–ligand accessibility in polymeric\nmembranes. Likewise, varying the structure of the acid chloride comonomer, such as its rigidity or length, could\nprovide a means to systematically control the spacing and packing density of crown ether units within the polyamide\nnetwork. Together, these approaches offer complementary strategies to engineer crown ether–based membranes with\nhigher degrees of molecular order and, consequently, enhanced ion selectivity and ion transport, while preserving the\npractical advantages of interfacial polymerization.\n4. Have you tried the same polyamide membranes from cis- DAB18C6? How were the results?\nR: We did not fabricate membranes using cis-DAB18C6 in this study. Exploring the use of cis versus trans crown\nether monomers as a strategy to tune membrane microstructure, crosslinking topology, and transport selectivity is an\nimportant and interesting direction, but we believe it falls outside the scope of the present work. We have therefore\nadded this point to the Discussion section of the manuscript to explicitly highlight monomer stereochemistry as a\npromising design parameter for future studies.\n5. The polyelectrolyte gutter layer is essential in this study for preventing membrane cracks and leakage. Additional\ncharacterisation, including thickness and water and ion permeability, is necessary. Why was a 1.5-layer coating of PEI\nand PAA selected?\nR: We agree with the reviewer that characterization of the polyelectrolyte gutter layer is important to decouple its\ncontribution from the observed membrane performance. We therefore direct the reviewer to Figure S7 in the\nSupporting Information, which reports the ion transport properties of the gutter layer alone. These measurements show\nthat the gutter layer exhibits high ion permeability and minimal ion–ion selectivity, in stark contrast to the crown\nether–based polyamide selective layer. This striking difference demonstrates that the observed ion selectivity in the\ncomposite membranes originates from the ultrathin crown ether polyamide layer, while the gutter layer primarily\nserves a mechanical stabilization role.\nThe dry thickness of the gutter layer, estimated by depositing it directly onto a smooth Si wafer and measuring the\nresulting film, was below 2 nm, as reported in our previous manuscript[2]. We note, however, that this value should be\nregarded as an approximation, as the actual thickness on AAO supports is expected to differ due to the dependence of\nlayer-by-layer deposition on substrate properties such as surface charge and surface roughness. Using planar Si wafers\nto approximate the dry thickness of ultrathin layer-by-layer films is a common practice in the polyelectrolyte literature,\nbut it represents a known limitation.\nThe choice of a 1.5-layer PEI/PAA coating reflects a balance between providing a smooth and chemically compatible\nsurface for deposition of the ultrathin selective layer, while minimizing additional transport resistance. Similar to the\nrole of PDMS gutter layers widely used in gas separation membranes due to their high gas permeance and\ncompatibility with a wide variety of substrates and selective layers, here we sought a gutter layer that offers minimal\nresistance to the species of interest, namely ions. Polyelectrolyte multilayers are well suited for this role because they\ncan be deposited conformally on rough supports, strongly adhere to both the substrate and the selective layer, and\nallow precise thickness control through the number of deposited layers.\nAmong polyelectrolyte systems, PEI/PAA is one of the most widely studied and best understood, with well-established\ndeposition protocols and predictable growth behavior, which reduces uncertainty in membrane fabrication. As a result,\nthe gutter layer does not impose a significant barrier to ion transport and does not contribute to ion selectivity,\nconfirming that the observed separation performance originates from the crown ether–based polyamide layer.\n6. The crown-ether polyamide layer demonstrated stability on PVDF porous support (Fig S2d). Was a gutter layer\nalso applied to this sample?\nR: We thank the reviewer for this comment. The SEM image shown in the Supporting Information for the crown\nether–based polyamide layer on a PVDF porous support (Fig. S2D) does not include a gutter layer. However, similar\ndelamination issues to those observed in the AAO-supported crown ether polyamide system were also observed for\nthe PVDF-supported composite films upon immersing them in water. This indicates that, if transport studies were to\nbe conducted using a PVDF support, the inclusion of a gutter layer would likewise be necessary to ensure stability\nduring testing.\n7. The mechanical properties of the selective layer are critical for membrane separation applications, despite\nminimised hydraulic pressure on ion separations. Can the membrane withstand pressure on an AAO substrate?\nR: We thank the reviewer for raising this important point. We attempted to assess the mechanical robustness of the\ncrown ether–based selective layers after transfer onto AAO substrates under applied transmembrane pressure. Owing\nto the extreme thinness of the films (~6 nm) and the rigidity and surface roughness of the AAO support, the transferred\nmembranes could not withstand pressure-driven testing.\nThis limitation, together with the reviewer’s other comments, motivated us to explore direct fabrication of the selective\nlayer on polymeric porous supports, where mechanical compliance and interfacial adhesion are more favorable. We\nhave revised the manuscript accordingly to clarify the mechanical limitations of free-standing films on AAO supports\nand to avoid overstating their pressure stability, and we now discuss alternative fabrication strategies that are better\nsuited for pressure-driven membrane applications.\nText modified in the abstract: Despite their minimal thickness, the flexible films with a structure formed by\nrandomly arranged crown ether units could be handled and transferred for structural and transport characterization.\nText added to the results section: AAO supports were used as a rigid, well-defined model substrate to enable\ntransport measurements of the ultrathin selective layer; they are not intended to represent pressure-bearing supports\nfor practical membrane operation.\nNote: Results for the newly fabricated crown ether–based membranes on PAN supports were added to the\nmanuscript and are described in detail in the response to the final comment.\n8. How does membrane performance vary with thickness? A thicker layer might decrease permeance but enhance\nselectivity.\nR: We thank the reviewer for this comment. In this system, the self-limiting nature of interfacial polymerization, as\nevidenced in Figure 2b where increasing reaction time does not lead to thicker films, prevented us from fabricating\nselective layers with systematically varied thicknesses while preserving comparable microstructure. Although thicker\nfilms could, in principle, be obtained by altering monomer concentrations, introducing additives, or changing the\nsolvents, such changes are well known to simultaneously affect cross-linking density, free volume, and chemical\nheterogeneity of polyamide films. As a result, any observed changes in permeance or selectivity would be convoluted\nwith microstructural effects rather than reflecting thickness alone.\nMore broadly, as shown in our prior work[3], the effect of thickness on selectivity in binding-mediated membranes\ncould depend on whether ion transport is limited by entry into the membrane or by diffusion through the membrane\nvia repeated complexation–decomplexation events. In that study, the thickness of layer-by-layer membranes\ncontaining coordination sites could be systematically varied. At high densities of coordination sites, weakly binding\nions are largely excluded at the membrane–solution interface, making their permeance relatively insensitive to\nthickness. In contrast, ions that bind more strongly can enter the membrane and permeate through successive binding\nand release steps, rendering their transport increasingly diffusion-limited as thickness increases. As a result, increasing\nthickness could preferentially penalize the flux of the selectively bound ion, which could reduce (rather than enhance)\nselectivity. This framework helps explain why simply increasing membrane thickness does not necessarily improve\nseparation performance and why many micrometer-thick membranes incorporating ion-complexing groups fail to\nexhibit meaningful selectivity. It also reinforces the rationale for focusing on ultrathin selective layers, where binding-\nmediated discrimination can be exploited without imposing excessive diffusive resistance.\n9. Ion permeability performance along with selectivity should be compared with existing literature data.\nR: We thank the reviewer for this comment. Although achieving the highest membrane performance was not the\nprimary objective of this study, we agree that comparison with existing literature is important for benchmarking,\nparticularly given the scattered nature of reported ion permeability and selectivity data. We have therefore added a\ncomparison with relevant literature in the Supporting Information and cited it in the main text.\nAdded text to SI: Tables S5: Comparison of K+/X+ selectivity (where X+ denotes other monovalent cations) and K+\nflux for the ultrathin crown ether–based polyamide membrane and reported membranes.\nAdded text to the results section: To place the reduced ion flux in context, we compared the K+ flux and selectivity\nof the present membrane with those of reported K+-selective membranes (Table S5). While the K+ flux of the crown\nether–based polyamide is lower than that of many reported systems, it falls within a range expected for polymeric\nmembranes that rely on binding-mediated selectivity rather than continuous ion-conducting pathways. The reduced\nflux reflects transport through a dense, highly crosslinked polyamide network with a non-ordered distribution of crown\nether binding sites, some of which may not be accessible during ion transport.\n10. The current fabrication method is complex. Given that interfacial polymerisation (IP) for RO membranes is directly\napplied to substrates for simplicity, can this crown ether polyamide layer also be directly applied? If so, how does it\naffect separation performance\nR: We thank the reviewer for raising this important point. For a fundamental investigation focused on ion–ion\nselectivity and binding-mediated transport, we intentionally fabricated the selective layers at a free interface. This\napproach enables clean characterization of the intrinsic chemistry, thickness, and morphology of the ultrathin selective\nlayer using AFM, TEM, XPS, and QCM, and allows ion transport to be examined under diffusion-dominated\nconditions that exclude convective flow and minimize concentration polarization effects. Such conditions are critical\nfor isolating ion–membrane interactions and mechanistic selectivity, which can be obscured under pressure-driven\noperation.\nMotivated by the reviewer’s comment, we also explored direct interfacial polymerization of the crown ether polyamide\nlayer on polymeric porous supports, analogous to conventional RO membrane fabrication. As widely documented, the\nproperties of the support (surface chemistry, pore structure, and monomer uptake) strongly influence interfacial\npolymerization, and thus the resulting selective layer is not expected to be identical to films formed at a free interface.\nUsing identical reaction conditions, we obtained continuous, mechanically robust membranes that could be evaluated\nunder applied pressure.\nUnder pressure-driven stirred-cell testing, these membranes exhibited water permeances comparable to reported\npolyamide membranes and high rejection (>95%) of Rose Bengal, confirming complete coverage and the absence of\nmacroscopic defects. However, no measurable selectivity between K⁺ and other monovalent ions was observed. Under\nthese conditions, convective solvent transport and concentration polarization can dominate ion transport and obscure\nbinding-mediated selectivity mechanisms, particularly for ions of similar size and charge.\nThese results demonstrate that while direct fabrication on porous supports is feasible and yields mechanically robust\nmembranes suitable for pressure-driven operation, the manifestation of ion selectivity depends strongly on the\ntransport regime. We have added this discussion to the manuscript to clarify the distinction between intrinsic material\nselectivity and performance under pressure-driven operation.\nAdded text to the results section: To assess the behavior of the crown ether–based selective layer under pressure-\ndriven conditions, membranes were also fabricated directly on porous polyacrylonitrile polymeric supports using\nidentical interfacial polymerization conditions. Water permeance and salt rejection measurements were performed in\na stirred cell at 3.5 bar, and high rejection of Rose Bengal (>95%) was observed, confirming complete surface coverage\nand the absence of macroscopic defects in the selective layer. As summarized in Table S4, these membranes exhibit\nwater permeances of approximately 1.3 L m-2 h-1 bar-1, comparable to conventional polyamide membranes, and a\nmoderate rejection of Mg²⁺ (~32%), while showing low rejection (8–10%) for monovalent K+ and Li+ ions under both\nsingle-salt and mixed-salt conditions. The pressure-driven transport behavior observed here is consistent with that of\nconventional nanofiltration-type polyamide membranes, including those reported by Alhazmi et al., who employed\nthe same amino-functionalized crown ether monomer in interfacial polymerization on polymeric supports and\noptimized fabrication conditions to leverage the intrinsic macrocyclic cavity for pharmaceutical separations31. These\nresults indicate that under pressure-driven operation, convective solvent transport can dominate ion transport, limiting\ndiscrimination among ions of similar size and charge.\nAdded text to the discussion section: In this context, more stringent control over free volume distribution and crown\nether alignment, such that continuous water pathways allowing ions to be transported together with water molecules\nare suppressed, may enable binding mediated ion selectivity to persist under pressure driven conditions.\nAdded text to the SI: Table S4.\nReviewer #2 (Remarks to the Author):\nIn this manuscript, the authors developed an ultra-thin, crown ether functionalized membrane using interfacial\npolymerization. Due to the specific interaction between 18-crown-6 and K+ ions, along with the ultra-low membrane\nthickness of 6.6 nm, the membrane shows good selectivity between monovalent cations of 3.8 for K+/Li+ and 4.4 for\nK+/Cs+. The proposed mechanism involves reversible complexation between the crown ether sites and K⁺ ions.\nOverall, the work presents an interesting concept that could appeal to the membrane community. However, there are\nstill some major issues that need to be addressed before considering its publication in Nature Communications.\nR: We thank the reviewer for their careful evaluation and constructive feedback. We appreciate their recognition of\nthe conceptual interest of our work and its relevance to the membrane community, and we have addressed the\nidentified concerns in detail to strengthen the manuscript accordingly.\n1. Figure 2h shows a rather low signal-to-noise ratio, which makes it difficult to clearly support the presence of\nunreacted –NH2 groups. Additionally, the authors should consider discussing the potential impact of hydrolyzed –\nCOOH or protonated –NH3+ groups (under low pH conditions) on ion flux and selectivity, as these groups could\nfacilitate the transport of anions or cations.\nR: We thank the reviewer for their comments. In Figure 2h, the N1s spectrum was deconvoluted into amine- and\namide-related components to justify that the presence of -NH would be negligible if there was any. As the reviewer\n2\ncorrectly pointed out, we believe the presence of unreacted -NH was minimal, which is consistent with our statement\n2\nin the original manuscript. For improved clarity, we have revised the statement in the original manuscript as follows:\n“The N1s core-level spectrum provides additional evidence of successful crosslinking of the crown ether\nmonomers, showing a single dominant nitrogen environment corresponding to amide nitrogen formed by reaction of\nacyl chloride with amine groups (Fig. 2H).”\nBased on the XPS analysis, the primary charged functional groups under experimental conditions were -COO–. It is\nnoteworthy that under experimental conditions, ionization of -COOH happened to a very limited extent. Our previous\nwork[2] has demonstrated that the role of -COO– in selective ion transport is complicated, involving four-body\ninteractions among cations, anions, water molecules, and functional groups across bulk and confined environment at\nthe partitioning and diffusion step, respectively. Therefore, we avoid over-interpreting the specific contribution of –\nCOO–. However, we indeed confirmed the essential role of crown ethers in achieving a high ion-ion selectivity through\nlow-pH QCM and XPS ion adsorption experiments (Figure 3).\n2. In Figure 3d, the author used XPS to quantify the adsorption of different ions. However, since XPS only probes the\ntop few tens of nanometers, it mainly reflects surface information. It’s strongly recommended to use ICP or other bulk\ncharacterization methods to support this analysis.\nR: We thank the reviewer for this comment. Although XPS is generally regarded as a surface-sensitive technique, this\nlimitation is not relevant in our case because the selective layers are ultrathin (~6 nm). To ensure that the entire film\nis probed and to calibrate the measurements, XPS samples were prepared on Au-coated glass substrates. The clear\npresence of the Au signal in the XPS spectra confirms (Figure R1) that the full thickness of the selective layer lies\nwithin the XPS sampling depth and also allows the Au peak to be used for energy calibration.\nFigure R1. XPS of a ~6nm-thick crownether-based polyamide film atop a gold substrate.\n3. The transfer process after interfacial polymerization introduces defects and hinder scalability. Could direct\npolymerization on a porous membrane (polymeric or ceramic) achieve comparable selectivity? In addition, on Page\n9, line 22, the author mentions testing three “high-quality” samples for selectivity. How were these samples selected?\nWere they the top-performing membranes, or was there another criterion?\nR: We thank the reviewer for raising these important points. For this fundamental study, the selective films were\nprepared at a free interface to enable clean characterization of the ultrathin selective layer without interference from\nthe support. This approach allows direct correlation between the intrinsic chemistry, thickness, and morphology of the\ncrown ether–based polyamide layer and its transport behavior using AFM, TEM, XPS, and QCM, and enables\ndiffusion-dominated measurements that isolate binding-mediated ion selectivity.\nMotivated by this comment, and in parallel with a related suggestion from Reviewer #1, we also explored translating\nthe fabrication to direct interfacial polymerization on porous polymeric supports, analogous to conventional RO\nmembrane fabrication. As widely documented for interfacial polymerization, the porous support influences the\nreaction through surface chemistry, pore structure, and monomer uptake; consequently, the resulting selective layer is\nnot expected to be identical to films formed at a free interface. Using identical reaction conditions, we obtained\ncontinuous polyamide layers that were mechanically robust and suitable for pressure-driven testing. Under pressure-\ndriven operation, these membranes exhibited water permeances comparable to reported polyamide membranes and\nshowed high rejection (>95%) of Rose Bengal, confirming complete surface coverage and the absence of macroscopic\ndefects. However, no measurable selectivity between K+ and other monovalent ions was observed under these\nconditions. Under these conditions, convective solvent transport and concentration polarization can dominate ion\ntransport and obscure binding-mediated selectivity mechanisms, particularly for ions of similar size and charge. These\nresults demonstrate that while direct fabrication on porous supports is feasible and yields mechanically robust\nmembranes suitable for pressure-driven operation, the manifestation of ion selectivity depends strongly on the\ntransport regime. We have added this discussion to the manuscript to clarify the distinction between intrinsic material\nselectivity and performance under pressure-driven operation.\nRegarding sample selection, the membranes used for selectivity analysis were not chosen based on peak performance.\nInstead, an objective integrity-based criterion was applied. Any membrane exhibiting a K+ flux at least one order of\nmagnitude lower than that of the bare polyelectrolyte-coated AAO support in the corresponding mixed-salt\nexperiments was classified as “high-quality” and retained for analysis. This criterion ensures that measured transport\nreflects an intact crown ether–based selective layer rather than defects or pinholes. All membranes meeting this\ncriterion were included, and the complete raw transport data have now been added to the Supporting Information\n(Tables S1–S3).\nAdded text to the results section: To assess the behavior of the crown ether–based selective layer under pressure-\ndriven conditions, membranes were also fabricated directly on porous polyacrylonitrile polymeric supports using\nidentical interfacial polymerization conditions. Water permeance and salt rejection measurements were performed in\na stirred cell at 3.5 bar, and high rejection of Rose Bengal (>95%) was observed, confirming complete surface coverage\nand the absence of macroscopic defects in the selective layer. As summarized in Table S4, these membranes exhibit\nwater permeances of approximately 1.3 L m-2 h-1 bar-1, comparable to conventional polyamide membranes, and a\nmoderate rejection of Mg²⁺ (~32%), while showing low rejection (8–10%) for monovalent K+ and Li+ ions under both\nsingle-salt and mixed-salt conditions. The pressure-driven transport behavior observed here is consistent with that of\nconventional nanofiltration-type polyamide membranes, including those reported by Alhazmi et al., who employed\nthe same amino-functionalized crown ether monomer in interfacial polymerization on polymeric supports and\noptimized fabrication conditions to leverage the intrinsic macrocyclic cavity for pharmaceutical separations31. These\nresults indicate that under pressure-driven operation, convective solvent transport can dominate ion transport, limiting\ndiscrimination among ions of similar size and charge.\nAdded text to the results section #2: The full transport data for all measured membranes, including those not meeting\nthe integrity criterion, are provided in the Supporting Information (Tables S1–S3).\nAdded text to the discussion section: In this context, more stringent control over free volume distribution and crown\nether alignment, such that continuous water pathways allowing ions to be transported together with water molecules\nare suppressed, may enable binding mediated ion selectivity to persist under pressure driven conditions.\nAdded text to SI: Tables S1 to S4\n4. The author mentions the membrane’s mechanical robustness. Could this claim be supported up by experimental\ndata, like AFM measurements?\nR: We thank the reviewer for this comment, which helped us clarify the scope of the mechanical robustness claims in\nthe manuscript. In the revised version, we removed ambiguous statements regarding mechanical stability and directly\nevaluated whether the ultrathin crown ether–based films transferred onto AAO supports could operate under applied\nhydraulic pressure. These films were not able to withstand pressure-driven testing, reflecting the extreme thinness of\nthe selective layer and the mechanical mismatch with the rigid AAO support.\nWe note that crown ether–based polyamide films fabricated directly on polymeric porous supports were mechanically\nrobust and could be tested under applied pressure. However, under pressure-driven operation these membranes did\nnot exhibit measurable ion–ion selectivity, indicating that convective water transport can dominate ion transport and\nobscure binding-mediated selectivity. In addition, selective layers formed directly on porous supports are inherently\ndifferent from those prepared at a free interface, as interfacial polymerization is strongly influenced by support\nproperties such as surface chemistry, pore structure, and monomer uptake.\nAccordingly, we have revised the manuscript to avoid overstating mechanical robustness and to clearly distinguish\nbetween structural integrity under handling, mechanical stability under pressure, and the transport regimes under\nwhich ion selectivity is observed.\nText modified in the abstract: Despite their minimal thickness, the flexible films with a structure formed by\nrandomly arranged crown ether units could be handled and transferred for structural and transport characterization.\nText added to the results section: AAO supports were used as a rigid, well-defined model substrate to enable\ntransport measurements of the ultrathin selective layer; they are not intended to represent pressure-bearing supports\nfor practical membrane operation.\n5. The ion absorption tests were done at low pH, were the selectivity measurements performed under the same acidic\nconditions? Also, would this low pH cause amide group hydrolysis and decrease long-term stability?\nR: We thank the reviewer for pointing out that the pH used in the permeation experiments was not clearly stated. All\npermeation and selectivity measurements were performed at pH 6, and this information has now been added to the\nmanuscript.\nThe ion sorption experiments were conducted at a lower pH by design. Under acidic conditions, electrostatic\ncontributions to ion sorption arising from ionizable carboxylic acid groups in the polyamide are minimized. This\nallowed us to better isolate and assess ion sorption originating specifically from crown ether coordination rather than\nfrom electrostatic interactions associated with other functional groups in the polymer matrix.\nRegarding stability, amide bond hydrolysis occurs at appreciable rates only under much more extreme acidic or basic\nconditions than those employed here. In addition, the ion sorption experiments were short in duration (less than two\ndays). Under these conditions, hydrolysis of the polyamide backbone is not expected, and we therefore do not\nanticipate any impact on the measured ion sorption or selectivity.\nText modified in the the results section: In each experiment, the feed solution contained a binary salt mixture with\nequimolar amounts of KCl and the chloride salt of a competing cation at pH 6, while the receiving side was filled with\ndeionized water (Fig. 4A).\n6. Even though the membrane is very thin, the flux dropped by 1-2 orders of magnitude compared to the bare AAO\nsubstrate, this might be because it lacks ion-conducting groups. How does this flux performance compare to other ion-\nselective membranes? Also, could the authors suggest possible ways to improve the flux without compromising\nselectivity?\nR: We thank the reviewer for this important comment. We acknowledge that, despite the ultrathin nature of the\nselective layer, the K+ flux of the DB18C6-based polyamide membrane is substantially reduced relative to the bare\nAAO substrate.\nTo place this observation in context, we have included in the revised manuscript a comparison of K⁺/X⁺ selectivity\nand K⁺ flux with reported ion-selective membranes (Table S5). The reduced flux reflects transport through a dense,\nhighly crosslinked polyamide network with a non-ordered array of crown ether binding sites, some of which may not\nbe accessible during transport, rather than through continuous ion-conducting pathways. This comparison highlights\nthe well-known tradeoff between binding-mediated ion selectivity and permeability.\nWe also discuss strategies to improve ion flux without compromising selectivity, including promoting crown ether\nalignment, controlling free volume distribution, and tuning network topology through monomer design, as outlined in\nthe revised Discussion section.\nAdded text to SI: Tables S5: Comparison of K+/X+ selectivity (where X+ denotes other monovalent cations) and K+\nflux for the ultrathin crown ether–based polyamide membrane and reported membranes.\nAdded text to the the results section: To place the reduced ion flux in context, we compared the K+ flux and\nselectivity of the present membrane with those of reported K+-selective membranes (Table S5). While the K+ flux of the\ncrown ether–based polyamide is lower than that of many reported systems, it falls within a range expected for polymeric\nmembranes that rely on binding-mediated selectivity rather than continuous ion-conducting pathways. The reduced\nflux reflects transport through a dense, highly crosslinked polyamide network with a non-ordered distribution of crown\nether binding sites, some of which may not be accessible during ion transport.\nModified text in the discussion section: While the monovalent ion selectivity achieved by the prepared membranes\nis impressive for a polymeric system, it falls short of the higher selectivities observed in highly ordered crystalline\nchannels such as crown ether-functionalized MOFs22, where the spatial arrangement of crown ether molecules is\nprecisely controlled. However, translating these crystalline channels into continuous membranes remains challenging,\nas ion transport in polycrystalline systems is typically dominated by grain boundaries and defects rather than by the\nintrinsic selectivity of the channels. In contrast, polymeric membranes are readily scalable, which motivates efforts to\nenhance their selectivity and transport rates to approach those of crystalline systems. Bridging the performance gap\nbetween highly ordered but difficult-to-scale crystalline systems and polymeric membranes fabricated via scalable\ninterfacial polymerization could be achieved by aligning crown ether molecules during polymerization. Recent\nadvances with cyclodextrin-based building blocks have demonstrated that functionalizing them to promote their\nalignment at the water/organic interface during interfacial polymerization can produce crosslinked films of aligned\nmacrocycle molecules with significantly improved solute-solute selectivities compared to disordered films33.\nApplying similar alignment strategies to crown ether building blocks could enhance the molecular ordering in the\nresulting membranes, narrowing the selectivity gap while preserving the scalability and processability that make\npolymeric systems so attractive. In this context, more stringent control over free volume distribution and crown ether\nalignment, such that continuous water pathways allowing ions to be transported together with water molecules\nare suppressed, may enable binding mediated ion selectivity to persist under pressure driven conditions.\nIn addition, the use of different crown ether regioisomers offers an unexplored handle to tune network topology,\nlocal packing, and ion–ligand accessibility in polymeric membranes. Likewise, varying the structure of the acid\nchloride comonomer, such as its rigidity or length, could provide a means to systematically control the spacing and\npacking density of crown ether units within the polyamide network. Together, these approaches offer complementary\nstrategies to engineer crown ether–based membranes with higher degrees of molecular order and, consequently,\nenhanced ion selectivity and ion transport, while preserving the practical advantages of interfacial polymerization.\n7. Given the extensive literature on the use of crown ethers in interfacial polymerization for ion-selective membranes\n[Angewandte Chemie, 2023, 62(18): e202300167; Journal of Materials Chemistry A, 2025, 13(16): 11732-11748;\nJournal of Membrane Science, 2025, 714: 123372], the novelty and uniqueness of this study should be further clarified\nand emphasized.\nR: We thank the reviewer for highlighting the growing body of literature on crown ether–based membranes fabricated\nvia interfacial polymerization. We have revised the manuscript to more clearly position the present work within this\ncontext and to clarify its distinct contribution.\nWhile recent studies have successfully incorporated crown ether and other macrocyclic monomers into IP-derived thin\nfilms, these efforts have primarily leveraged macrocycles as rigid, bulky building blocks that introduce sub-nanometer\nfree volume to enhance solute transport or solute–solute selectivity, targeting monovalent–divalent ion separations,\nproton conduction, or organic solute purification. In contrast, the present study demonstrates a fundamentally different\ntransport mechanism, in which the ion-coordination chemistry of crown ethers, rather than their role as static pore\nformers, governs selective transport between closely related monovalent ions.\nSpecifically, our work reveals a binding-mediated transport regime in which reversible ion coordination within a\ndensely crosslinked polymer matrix biases ion–ion selectivity even in the absence of well-defined crystalline channels.\nThis distinction, together with the use of ultrathin films and diffusion-dominated transport measurements to isolate\nintrinsic ion–crown ether interactions, differentiates the present study from prior IP-based crown ether membranes.\nWe have emphasized this point in the revised manuscript and added the references suggested by the reviewer to clearly\ndelineate how our work advances beyond existing approaches.\nText added to the results section: Despite these challenges, several recent studies have demonstrated the feasibility\nof incorporating crown ether–based monomers into polymeric thin films via interfacial polymerization, primarily\ntargeting separations such as monovalent–divalent ion pairs29, proton conduction pathways30, or pharmaceutical\npurifications31. In these studies, crown ether moieties are largely exploited as macrocyclic cavities that introduce well-\ndefined sub-nanometer free volume absent in analogous linear or non-macrocyclic polyether monomers, thereby\ncreating additional and more uniform transport pathways that enhance the transport of only certain molecules. Related\nwork has also shown that other bulky macrocycles, including cyclodextrins and trianglamines, can be successfully\nintegrated into ultrathin IP-derived membranes, where their intrinsic porosity similarly enhances solute–solute\nselectivity32-34. Here, we show that the ion-coordination properties of crown ethers can also be harnessed to achieve\nselective transport between closely related monovalent ions, revealing a distinct transport regime in which selective\ncomplexation governs ion–ion selectivity.\nReviewer #3 (Remarks to the Author):\nThe paper describes the preparation and characterization of interfacial polymerized\nthin-film composite membranes with an amino-functionalized crown ether as hydrophilic monomer. The key finding\nof the work is the preferential K+ transport over other monovalent cations. The ion-ion selectivities of approximately\n4 for monovalent cation pairs (K+/Cs+ and K+/Li+) is impressive. The conclusions are supported by the well-\ndescribed experiments.\nR: We thank the reviewer for their positive and thoughtful assessment. We appreciate their recognition of the\nsignificance of the observed K+ selectivity and their acknowledgment that the conclusions are well supported by the\nexperimental results\n1. The paper would have more relevance for applications if the IP films would have been prepared on a polymeric\nsupport membrane. Here the support was an anodic aluminium oxide membrane. These membranes are brittle and\nprevent applications under any mechanical stress like pressure filtration. In addition they are not compatible with the\npolymeric IP film. This required a polyelectrolyte inter layer which influences the cation transport. The ions transport\nproperties were not measured under filtration condition but in a diffusion cell, which has little relevance for practical\napplications.\nR: We thank the reviewer for this thoughtful and detailed comment. We agree that preparing interfacial polymerized\nfilms directly on polymeric supports and evaluating them under pressure-driven conditions is essential for assessing\napplication-oriented membrane performance. In the present work, however, our primary objective was to establish\nand interrogate the intrinsic ion–ion selectivity arising from crown ether coordination within an ultrathin polymeric\nselective layer.\nTo this end, the selective films were intentionally prepared at a free interface and transferred onto AAO supports. This\napproach enabled clean structural and chemical characterization of the ultrathin selective layer using AFM, TEM,\nXPS, and QCM, and allowed ion transport to be examined under diffusion-dominated conditions that minimize\nconvective flow and concentration polarization. These conditions are critical for isolating binding-mediated ion\nselectivity, which can be difficult to resolve under pressure-driven operation. The AAO support was used as a rigid,\nwell-defined model substrate to enable transport measurements and is not intended to represent a pressure-bearing\nsupport for practical applications.\nMotivated by this comment, and to directly assess the feasibility of translating the fabrication to application-relevant\narchitectures, we also explored direct interfacial polymerization of the crown ether–based selective layer on polymeric\nporous supports, analogous to conventional RO membrane fabrication. As widely documented, the properties of the\nporous support strongly influence interfacial polymerization through surface chemistry, pore structure, and monomer\nuptake; consequently, the resulting selective layer is not expected to be identical to films formed at a free interface.\nUsing identical reaction conditions, we obtained continuous polyamide layers that were mechanically robust and\nsuitable for pressure-driven testing.\nUnder pressure-driven stirred-cell operation, these membranes exhibited water permeances comparable to reported\npolyamide membranes and showed high rejection (>95%) of Rose Bengal, confirming the absence of macroscopic\ndefects. However, no measurable selectivity between K+ and other monovalent ions was observed under these\nconditions, indicating that pressure-driven transport emphasizes solvent flow and can obscure binding-mediated ion\ndiscrimination for closely related ions.\nTogether, these results demonstrate that while direct fabrication on polymeric supports is feasible and yields\nmechanically robust membranes suitable for pressure-driven operation, the manifestation of ion selectivity depends\nstrongly on the transport regime. We have revised the manuscript to clarify this distinction and to explicitly\ndifferentiate between intrinsic, binding-mediated selectivity probed under diffusion-dominated conditions and\nperformance under pressure-driven operation. Additional pressure-driven transport data on polymeric supports have\nbeen added to the Results and Supporting Information (Table S4), and this discussion has been incorporated into the\nrevised manuscript.\nAdded text to the results section: To assess the behavior of the crown ether–based selective layer under pressure-\ndriven conditions, membranes were also fabricated directly on porous polyacrylonitrile polymeric supports using\nidentical interfacial polymerization conditions. Water permeance and salt rejection measurements were performed in\na stirred cell at 3.5 bar, and high rejection of Rose Bengal (>95%) was observed, confirming complete surface coverage\nand the absence of macroscopic defects in the selective layer. As summarized in Table S4, these membranes exhibit\nwater permeances of approximately 1.3 L m-2 h-1 bar-1, comparable to conventional polyamide membranes, and a\nmoderate rejection of Mg²⁺ (~32%), while showing low rejection (8–10%) for monovalent K+ and Li+ ions under both\nsingle-salt and mixed-salt conditions. The pressure-driven transport behavior observed here is consistent with that of\nconventional nanofiltration-type polyamide membranes, including those reported by Alhazmi et al., who employed\nthe same amino-functionalized crown ether monomer in interfacial polymerization on polymeric supports and\noptimized fabrication conditions to leverage the intrinsic macrocyclic cavity for pharmaceutical separations31. These\nresults indicate that under pressure-driven operation, convective solvent transport can dominate ion transport, limiting\ndiscrimination among ions of similar size and charge.\nAdded text to the discussion section: In this context, more stringent control over free volume distribution and crown\nether alignment, such that continuous water pathways allowing ions to be transported together with water molecules\nare suppressed, may enable binding mediated ion selectivity to persist under pressure driven conditions.\nAdded text to the SI: Table S4.\n2. The authors should have cited the work of Alhazmi et al. (ref. 32) in a correct way. The membrane preparation part\nin this reference is very similar, also using interfacial polymerisation and amino-functionalized crown ether as\nhydrophilic monomer. But they use a polmeric support membrane and pressure filtration for transport characterisation.\nThis should have been discussed in this work.\nR: We thank the reviewer for pointing this out. The manuscript has been revised to correctly cite and explicitly discuss\nthe work of Alhazmi et al. (ref. 31 in the updated manuscript).\nAdded text #1 to the results section: Despite these challenges, several recent studies have demonstrated the\nfeasibility of incorporating crown ether–based monomers into polymeric thin films via interfacial polymerization,\nprimarily targeting separations such as monovalent–divalent ion pairs29, proton conduction pathways30, or\npharmaceutical purifications31. In these studies, crown ether moieties are largely exploited as macrocyclic cavities that\nintroduce well-defined sub-nanometer free volume absent in analogous linear or non-macrocyclic polyether\nmonomers, thereby creating additional and more uniform transport pathways that enhance the transport of only certain\nmolecules.\nAdded text #2 to the results section: The pressure-driven transport behavior observed here is consistent with that of\nconventional nanofiltration-type polyamide membranes, including those reported by Alhazmi et al., who employed\nthe same amino-functionalized crown ether monomer in interfacial polymerization on polymeric supports and\noptimized fabrication conditions to leverage the intrinsic macrocyclic cavity for pharmaceutical separations31.\n3. The authors describe on page 5 that thin membranes favor the high selectivity because the rate limiting step for the\ntransport of the non-favored ion is the partitioning into the membrane, whereas the rate limiting step for the target ion\nis its movement through the network of binding sites. For me it is not convincing hat the solution of the not complexed\nion into the water-swollen membrane is rate liming.\nR: We thank the reviewer for this insightful comment. Our intent was not to claim a definitive rate-limiting step, but\nrather to propose a plausible hypothesis for how ion–ion selectivity may arise in the ultrathin, binding-mediated crown\nether–based membranes studied here.\nRecent studies have identified ion partitioning at the membrane–solution interface as a key determinant of ion–ion\nselectivity in several polymeric membrane systems[3–5]. Within this framework, the effect of membrane thickness on\nselectivity depends on whether ion transport is limited primarily by entry into the membrane or by diffusion through\nthe membrane.\nAs demonstrated in our prior work[3], thickness-controlled layer-by-layer membranes containing coordination sites\nprovide a useful model to examine these effects. In those systems, weakly binding ions are largely excluded at the\nmembrane–solution interface, rendering their permeance relatively insensitive to thickness. In contrast, more strongly\nbinding ions can enter the membrane and permeate through successive binding and release steps, such that their\ntransport becomes increasingly diffusion-limited as membrane thickness increases. As a result, increasing thickness\ncan preferentially penalize the flux of the selectively bound ion and reduce, rather than enhance, overall selectivity.\nWe hypothesize that a similar transport picture applies to the present ultrathin interfacially polymerized membranes,\nwhere selective coordination enhances the effective mobility of the target ion relative to competing ions. However,\nbecause interfacial polymerization does not allow independent control of membrane thickness without simultaneously\naltering membrane chemistry and internal structure, this mechanism cannot be directly verified through thickness-\ndependent measurements in the present system. We have therefore revised the manuscript to explicitly present this\ntransport picture as a hypothesis and to clarify the language so that it is not interpreted as a demonstrated rate-limiting\nprocess.\nText modified in the results section: The thinness of crown ether-containing membranes is crucial when aiming to\nleverage the reversible and selective interactions of crown ether groups for ion transport. In such membranes, where\nselective transport relies on these reversible interactions, we hypothesize that the dominant transport resistance for the\ntarget ion arises from the movement through the network of binding sites4,36. This process is governed by the repeated\nreversible binding and release of the ion as it traverses the membrane. A thicker membrane is therefore expected to\nslow this process, as the ion would need to undergo more interactions before crossing to the other side. Conversely,\nfor competing ions that interact weakly with the binding sites, transport is not selectively facilitated and may be\ngoverned by interfacial partitioning into the membrane, such that increasing thickness has a comparatively smaller\neffect on their transport36,37. As membrane thickness increases, the transport of the target ion—selectively binding\nwith the functional groups—can be penalized more strongly than that of competing ions. We recently demonstrated\nthis using a model system containing a high density of Cu2+-selective iminodiacetate groups, where membrane\nthickness could be precisely controlled and increasing thickness led to a decline in copper selectivity36.\nResponse to Reviewers References:\n[1] Z. Liu, S. K. M. Nalluri, J. F. Stoddart, Chem. Soc. Rev. 2017, 46, 2459.\n[2] J. Zhang, L. F. Villalobos, J. Lee, M. Zhong, M. Elimelech, ACS Appl. Mater. Interfaces 2025, 17, 30817.\n[3] R. M. DuChanois, M. Heiranian, J. Yang, C. J. Porter, Q. Li, X. Zhang, R. Verduzco, M. Elimelech, Science\nAdvances 2022, 8, 1.\n[4] R. S. Kingsbury, M. A. Baird, J. Zhang, H. D. Patel, M. J. Baran, B. A. Helms, E. M. V. Hoek, Matter 2024, 7,\n2161.\n[5] Y. Guo, J. He, J. Zhang, M. Sheng, Z. Wang, M. Elimelech, L. Wang, Science Advances 2025, 11, eadu8302."}, {"round": 2, "reviewer_comments": {"reviewer_1": "All comments the reviewer addressed were carefully discussed in the revised manuscript. No further comments and\nobjections to publishing this work.", "reviewer_2": "The authors have addressed my comments and concerns. The revised version is recommended for publication.", "reviewer_3": "The authors have addressed my concerns in detail. In particular, it has been clarified that the high selectivity for monovalent\ncations could not be observed under pressure-driven conditions. While this does reduce the practical relevance of the work,\nthe impressive selectivity under diffusion-controlled conditions nonetheless clearly justifies publication. My critical comment\nregarding the choice of the support membrane is now also discussed appropriately. In my view, the manuscript can be\npublished without further revisions.\nKlaus-V. Peinemann"}, "author_response": ""}]

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