Selective Transport of Water Mediated by Porous Dendritic Dipeptides

Abstract

Synthetic channels and pores have been of increasing interest for their applications as antimicrobial agents, drug delivery, catalysts, and sensors. 1 Furthermore, the development of synthetic channels and pores that mimic porous proteins should contribute to a better understanding of the structure and function of natural transmembrane channels. 2 Here, we report a dendritic dipeptide that self-assembles into thermally stable helical pores. The helical pores are stable in phospholipid membranes and selectively transport water.There has been little progress in the area of synthetic water channels, pores, and transporters. 1 Natural channels such as Aquaporin selectively transport water through primarily hydrophobic pores. 2,3 Recently, water was shown to transport through hydrophobic nanotubes very efficiently. 4 Hydrophobic pore sizes of 13-20 Å transport water faster than diffusion models. 5 Protons are also translocated through hydrophobic pores via a Grotthusstype mechanism. 6 We have previously reported the dendritic dipeptide, (4-3,4-3,5)-12G2-CH 2 -Boc-L-Tyr-L-Ala-OMe, that self-assembles into helical pores in bulk, in solution, and in vesicles. 7 This dendritic dipeptide self-assembled into helical pores with a column diameter (D col ) of 71.3 Å and pore diameter (D pore ) of 12.8 ( 1.2 Å. These helical pores suffered from low thermal stability since at 22°C they were in dynamic equilibrium with the dendritic dipeptide. Further studies led to improvements in the stability of the helical pores by more complex strategies. 8 We decided to attempt the stabilization of helical pores through simple π-stacking interactions on the dendron periphery by replacing the benzyl group with a naphthyl group. This generated (6Nf-3,4-3,5)12G2-CH 2 -Boc-L-Tyr-L-Ala-OMe (1). 9 In the bulk state, 1 formed helical pores similar to previously reported dendritic dipeptides 7,8 with D col ) 82.3 Å and D pore ) 14.5 ( 1.5 Å (Figure 1) in the bulk state. D pore is within the range of sizes required to facilitate transport of water and protons. 4,5 Wideangle X-ray diffraction fiber patterns (Figure 1b and Supporting Information) showed strong 3.5 Å π-stacking interactions due to the naphthyl groups not seen in previous dendritic dipeptides. 7,8 Modifying the outer periphery from benzyl to naphthyl increased the melting temperature (T m ) in bulk from 95 to 139°C. Furthermore, 1 self-assembled into helical pores in organic solvents that mimic the aliphatic region of phospholipid membranes ( Figure 2a). The T m in solution and the molecular ellipticity were also higher compared to the benzyl dendritic dipeptide previously reported (T m ) 40 vs 22°C). 7 The enhanced stability of the pores formed from 1 allowed their improved assembly into phospholipid membranes (Figure 2b). The helical pores showed CD spectra when incorporated into vesicles similar to their solution spectra. Additionally, the helical pores did not disassemble at high temperatures. This improved stability is due to enhanced π-stacking interactions on their periphery a...

Highly permeable artificial water channels that can self-assemble into two-dimensional arrays

“…However, two fundamental questions remain: (i) Can artificial channels approach the permeability and selectivity of AQP water channels? (ii) How can such artificial channels be packaged into materials with morphologies suitable for engineering applications?Because of the challenges in accurately replicating the functional elements of channel proteins, the water permeability and selectivity of first-generation artificial water channels were far below those of AQPs (SI Appendix, Table S1) (20)(21)(22)(23)(24)(25). In some cases, the conduction rate for water was much lower than that of AQPs as a result of excess hydrogen bonds being formed between the water molecules and oxygen atoms lining the channel (20).…”

“…Thus, there is a critical need for a method to accurately measure single-channel permeability of artificial water channels to allow for accurate comparison with those of biological water channels. Furthermore, first-generation artificial water channels were designed with a focus on demonstrating water conduction and one-dimensional assembly into tubular structures (20)(21)(22)(23)(24), but how the channels could be assembled…”

Self-assembling subnanometer pores with unusual mass-transport properties

“…Nevertheless, the creation of synthetic channels and pores with structural uniformity and functional selectivity, such as transport of specific ions and molecules, still presents major challenges. In comparison to biological ion channels, most synthetic pores available are hydrophilic with poor ion selectivity, and only a few have demonstrated evidence for water transport 14,15 .…”

Nanoporous Membranes of Hydrogen‐bridged Smectic Networks with Nanometer Transverse Pore Dimensions

“…[23][24][25] For smaller dimensions supramolecular dendritic structures can self-assemble into pores with a well-controlled inner chemical nature. [26,27] Bottom-up methods that are especially appealing are based on the self-organization of liquid crystals and their polymers because they decrease the pore sizes down to the order of molecular length scales, for example, around 1 nm and below, while the assemblies themselves can have much larger dimensions. For instance, nanoporous systems made from polymerized lyotropic systems have proven themselves to be useful for purification and desalination of water [28,29] or gas separation, [30] where dimensions down to the molecular level are essential.…”