Transmembrane Nanopores from Porphyrin Supramolecules

Satake, Akiharu; Yamamura, Mika; Oda, Masafumi; Kobuke, Yoshiaki

doi:10.1021/ja801129a

Cited by 65 publications

(56 citation statements)

References 18 publications

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“…Note that, although other strategies (e.g., internal charge repulsion) 18 have been used with success, rigidity of the building blocks is a key factor in keeping synthetic nanopores from collapsing. [3][4][5][6][7][8][9] We hypothesized that the same solvophobic driving force in the folding of the linear oligocholates 17 would prompt 1 to stack in the z-direction (Scheme 1, right). In a largely nonpolar solvent mixture, the polar solvent molecules should phase-separate into the middle of the macrocycle and solvate the inward-facing polar groups.…”

Section: Resultsmentioning

confidence: 99%

Water-Templated Transmembrane Nanopores from Shape-Persistent Oligocholate Macrocycles

2010

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Hydrophobic interactions normally are not considered a major driving force for self-assembling in a hydrophobic environment. When macrocyclic oligocholates were placed within lipid membranes, however, the macrocycles pulled water molecules from the aqueous phase into their hydrophilic internal cavities. These water molecules had strong tendencies to aggregate in a hydrophobic environment and templated the macrocycles to self-assemble into transmembrane nanopores. This counterintuitive hydrophobic effect resulted in some highly unusual transport behavior. Cholesterol normally increases the hydrophobicity of lipid membranes and makes them less permeable to hydrophilic molecules. The permeability of glucose across the oligocholate-containing membranes, however, increased significantly upon the inclusion of cholesterol. Large hydrophilic molecules tend to have difficulty traversing a hydrophobic barrier. The cyclic cholate tetramer, however, was more effective at permeating maltotriose than glucose. Abstract: Hydrophobic interactions normally are not considered a major driving force for self-assembling in a hydrophobic environment. When macrocyclic oligocholates were placed within lipid membranes, however, the macrocycles pulled water molecules from the aqueous phase into their hydrophilic internal cavities. These water molecules had strong tendencies to aggregate in a hydrophobic environment and templated the macrocycles to self-assemble into transmembrane nanopores. This counterintuitive hydrophobic effect resulted in some highly unusual transport behavior. Cholesterol normally increases the hydrophobicity of lipid membranes and makes them less permeable to hydrophilic molecules. The permeability of glucose across the oligocholate-containing membranes, however, increased significantly upon the inclusion of cholesterol. Large hydrophilic molecules tend to have difficulty traversing a hydrophobic barrier. The cyclic cholate tetramer, however, was more effective at permeating maltotriose than glucose.

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Section: Resultsmentioning

confidence: 99%

Water-Templated Transmembrane Nanopores from Shape-Persistent Oligocholate Macrocycles

2010

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“…Although a number of designs are available, the noncovalent forces utilized in the self-assembling are mostly limited to hydrogen bonds, 29−32 aromatic interactions, 33,34 and metal−ligand coordination. 35,36 The main evidence for the hydrophobically driven pore formation came from leakage assays and various control experiments. 25,26 Although a pyrene-labeled macrocycle provided spectroscopic support for the pore formation, 25 we were interested in gaining further insight into the aggregational process.…”

Section: ■ Introductionmentioning

confidence: 99%

Effects of Amphiphile Topology on the Aggregation of Oligocholates in Lipid Membranes: Macrocyclic versus Linear Amphiphiles

Widanapathirana

Zhao

2012

Langmuir

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A macrocyclic and a linear trimer of a facially amphiphilic cholate building block were labeled with a fluorescent dansyl group. The environmentally sensitive fluorophore enabled the aggregation of the two oligocholates in lipid membranes to be studied by fluorescence spectroscopy. Concentration-dependent emission wavelength and intensity revealed a higher concentration of water for the cyclic compound. Both compounds were shown by the red-edge excitation shift (REES) to be located near the membrane/water interface at low concentrations, but the cyclic trimer was better able to migrate into the hydrophobic core of the membrane than the linear trimer. Fluorescent quenching by a water-soluble (NaI) and a lipid-soluble (TEMPO) quencher indicated that the cyclic trimer penetrated into the hydrophobic region of the membrane more readily than the linear trimer, which preferred to stay close to the membrane surface. The fluorescent data corroborated with the previous leakage assays that suggested the stacking of the macrocyclic cholate trimer into transmembrane nanopores, driven by the strong associative interactions of water molecules inside the macrocycles in a nonpolar environment. Disciplines Chemistry CommentsReprinted (adapted) with permission from Langmuir 28 (2012) ABSTRACT: A macrocyclic and a linear trimer of a facially amphiphilic cholate building block were labeled with a fluorescent dansyl group. The environmentally sensitive fluorophore enabled the aggregation of the two oligocholates in lipid membranes to be studied by fluorescence spectroscopy. Concentration-dependent emission wavelength and intensity revealed a higher concentration of water for the cyclic compound. Both compounds were shown by the red-edge excitation shift (REES) to be located near the membrane/water interface at low concentrations, but the cyclic trimer was better able to migrate into the hydrophobic core of the membrane than the linear trimer. Fluorescent quenching by a water-soluble (NaI) and a lipid-soluble (TEMPO) quencher indicated that the cyclic trimer penetrated into the hydrophobic region of the membrane more readily than the linear trimer, which preferred to stay close to the membrane surface. The fluorescent data corroborated with the previous leakage assays that suggested the stacking of the macrocyclic cholate trimer into transmembrane nanopores, driven by the strong associative interactions of water molecules inside the macrocycles in a nonpolar environment.

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“…23,24 In recent years, the β-barrel pores constructed from oligo(phenylene) derivatives by Matile and coworkers 25À27 proved particularly versatile and useful in many applications including sensing 26 and catalysis. 27 Other examples include the porphyrin-based nanopores by Satake and Kobuke, 28 Gong's π-stacked aromatic heterocycles, 29 the metal-coordinated nanopores by Fyles, 30 and the guanosine quartet-based giant ion channels by Davis. 31 Whereas the majority of the synthetic nanopores in the literature relied on hydrogen bonds and metalÀligand coordination for pore formation, we recently reported amphiphilic macrocyclic oligocholates (1À3) that formed nanopores through hydrophobic interactions, a noncovalent force normally expected to work in water instead of a hydrophobic environment (Figure 1).…”

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confidence: 99%

Translocation of Hydrophilic Molecules across Lipid Bilayers by Salt-Bridged Oligocholates

Cho

Zhao

2011

Langmuir

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Macrocyclic oligocholates were found in a previous work (Cho, H.; Widanapathirana, L.; Zhao, Y. J. Am. Chem. Soc.2011, 133, 141−147) to stack on top of one another in lipid membranes to form nanopores. Pore formation was driven by a strong tendency of the water molecules in the interior of the amphiphilic macrocycles to aggregate in a nonpolar environment. In this work, cholate oligomers terminated with guanidinium and carboxylate groups were found to cause efflux of hydrophilic molecules such as glucose, maltotriose, and carboxyfluorescein (CF) from POPC/POPG liposomes. The cholate trimer outperformed other oligomers in the transport. Lipid-mixing assays and dynamic light scattering ruled out fusion as the cause of leakage. The strong dependence on chain length argues against random intermolecular aggregates as the active transporters. The efflux of glucose triggered by these compounds increased significantly when the bilayers contained 30 mol % cholesterol. Hill analysis suggested that the active transporter consisted of four molecules. The oligocholates were proposed to fold into "noncovalent macrocycles" by the guanidinium−carboxylate salt bridge and stack on top of one another to form similar transmembrane pores as their covalent counterparts. Disciplines Chemistry CommentsReprinted ( Synthetic transmembrane pores with an inner diameter of 1 nm or larger have attracted a great deal of attention in recent years. 1,2 Part of the motivation comes from the fact that their biological congeners, membrane-associated pore-forming proteins, are involved in critical functions such as signaling, metabolism, and bacterial or viral infection. 3À7 Since it is notoriously difficult to obtain detailed structural information for complex membrane proteins, chemists have sought to construct simpler biomimetic nanopores and study their behavior under more easily controlled conditions. Knowledge generated from such studies not only is useful to the understanding of biological pore formation but also helps create materials with potential applications ranging from single-molecule detection of DNAs and RNAs 8À14 to drug delivery. 15 Crown ethers and open chain compounds, which worked extremely well for ion channels, 16À21 normally are too flexible for nanopore formation. To keep the pore open, the structure must be able to withstand the external membrane pressure when incorporated into a bilayer. 22 Despite the significant efforts devoted to synthetic nanopores, limited designs exist currently. An early example was Ghadiri's cyclic D/L-peptides, which self-assembled into transmembrane pores large enough for glucose and glutamic acid to pass through. 23,24 In recent years, the β-barrel pores constructed from oligo(phenylene) derivatives by Matile and coworkers 25À27 proved particularly versatile and useful in many applications including sensing 26 and catalysis. 27 Other examples include the porphyrin-based nanopores by Satake and Kobuke, 28 Gong's π-stacked aromatic heterocycles, 29 the metal-coordinated nanopores by Fy...

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Transmembrane Nanopores from Porphyrin Supramolecules

Cited by 65 publications

References 18 publications

Water-Templated Transmembrane Nanopores from Shape-Persistent Oligocholate Macrocycles

Water-Templated Transmembrane Nanopores from Shape-Persistent Oligocholate Macrocycles

Effects of Amphiphile Topology on the Aggregation of Oligocholates in Lipid Membranes: Macrocyclic versus Linear Amphiphiles

Translocation of Hydrophilic Molecules across Lipid Bilayers by Salt-Bridged Oligocholates

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