Supramolecular Self-Assembly into Biofunctional Soft Nanotubes

Subscriber access provided by UNIV OF NEBRASKA - LINCOLN

Invited Feature Article

Supramolecular self-assembly into bio-functional soft nanotubes: From bilayers to monolayers Toshimi Shimizu, Naohiro Kameta, Wuxiao Ding, and Mitsutoshi Masuda Langmuir, Just Accepted Manuscript • DOI: 10.1021/acs.langmuir.6b01632 • Publication Date (Web): 01 Jun 2016 Downloaded from http://pubs.acs.org on June 12, 2016

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a free service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are accessible to all readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

Langmuir is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 68

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

Supramolecular self-assembly into bio-functional soft nanotubes: From bilayers to monolayers Toshimi Shimizu,*a Naohiro Kameta,b Wuxiao Ding,b and Mitsutoshi Masudab a

AIST Fellow, National Institute of Advanced Industrial Science and Technology (AIST),

Tsukuba Central 5, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan b

Research Institute for Sustainable Chemistry, Department of Materials and Chemistry, AIST,

Tsukuba Central 5, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan

ABSTRACT The inner and outer surfaces of bilayer-based lipid nanotubes can be hardly modified selectively by a favorite functional group. Monolayer-based nanotubes display a definitive difference in the inner and outer functionalities, if bipolar wedge-shaped amphiphiles, so-called bolaamphiphiles, as a constituent of the monolayer membrane pack in a parallel fashion with head-to-tail interface. In order to exclusively form the unsymmetrical monolayer lipid membranes, we focus on herein rational molecular design of the bolaamphiphiles and variety of self-assembly processes into tubular architectures. We first describe the importance of polymorph and polytype control and then discuss diverse methodologies utilizing polymer template, multiple hydrogen bonds, binary and ternary co-assembly, and two-step self-assembly. Novel biologically important functions of the obtained soft nanotubes, brought only by completely unsymmetrical inner and

ACS Paragon Plus Environment

1

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 2 of 68

outer surfaces, are discussed in terms of protein refolding, drug nanocarriers, lectin detection, chiral inducer for achiral polymers, tailored fabrication of polydopamine, and spontaneous nematic alignment.

1. INTRODUCTION

In 1977, Kunitake and Okahata reported for the first time on a totally synthetic bilayer membrane, in which didodecyldimethylammonium bromide well self-assembles in water to form spherical vesicles.1 Everyone will admit to the idea that this opened up new possibilities to create simple and functionalizable membrane structures.2 Since then, many organic chemists have developed extensive studies on a large number of bilayer- and monolayer-based molecular assemblies that display interesting biology-related properties.3-4 Above all, it is noteworthy that Kunitake et al. conducted a pioneering work on the spontaneous formation of tubular architectures from chiral double-chain ammonium amphiphiles5-6 via chiral molecular selfassembly.7-8 At almost the same time, Ihara’s research group,9-11 and Yager, Shoen, and others1216

discovered the self-assembly of double-chain glutamic acid amphiphiles or diacetylenic

phospholipids into tubular morphologies, respectively. In the dawn of lipid nanotube history, measured dimensions were much larger than those discussed herein, being in a range of 200−500-nm outer diameters, 100−200-nm inner diameters, and 50−200-µm length. Multiple bilayer membranes of several tens-nm thickness then stabilize the membrane wall.7 Meanwhile, Fuhrhop et al. discovered for the first time the self-assembly of lipid nanotubes with relatively smaller inner diameters and membrane thickness. In the membrane wall, bolaamphiphiles with


2

Page 3 of 68

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

two hydrophilic terminal groups at both ends2, 17 constitute a single monolayer membrane and stabilize the molecular assembly.18 Strongly inspired by unique structure and function of the biomembranes in nature, a large number of studies on supramolecular soft nanotubes (hereinafter referred to as “SNTs”) have been performed to elucidate the relationship of the component structure and resultant nanotube function.7, 19-26 There have already been excellent and comprehensive reviews on the progress and outlook of (i) SNTs achieved by 20057 and for 2005-2014,20 (ii) SNTs via helical intermediates,8 (iii) utilization and functionalization of the SNT’s inner and outer surfaces,19 and (iv) supramolecular SNTs from other molecular constituents.16, 27-32 However, little research has addressed the detailed analyses of molecular arrangement within the constituent curved membranes. In this paper, we discuss our recent work on monolayer-based nanotube architectures as compared to bilayer-based counterparts. Among them, we especially focus on the methodology and the structural identification for selective formation of monolayer membranes from 1,ω-bipolar, wedge-shaped amphiphiles (so-called “unsymmetrical bolaamphiphiles”), in which the constituent molecules pack in a completely parallel fashion within the membrane. The brought effect by unsymmetry of the SNT’s inner and outer surfaces2, 33

should be very advantageous to give diverse biological applications. Accordingly, we then

address biologically related or bioinspired functions, which will be exhibited only by monolayerbased SNTs with completely different inner and outer surfaces (hereinafter referred to as “unsymmetrical SNTs”).

2. TOWARD MONOLAYER-BASED SNTs 2.1 Bilayer- and Monolayer-based SNTs


3

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 4 of 68

A big structural difference between eubacteria and archaea in nature is the components of cell membranes. Bilayer-based membranes of phospholipid, which has aliphatic hydrocarbons carrying phosphoric acid via ester linkage, form the cell membrane of eubacteria (Figure 1-a). On the other hand, the membrane of archaea forms monolayer-based membranes that consist of phospholipid with ether linkage, leading to be alive even in harsh aqueous environment under high-pH, -temperature, or -acidic conditions (Figure 1-b). In a synthetic system, bilayer- and monolayer-based SNTs display a definitive difference in functional properties of the inner and outer surfaces. The both surfaces of the bilayer-based SNTs can be hardly modified selectively by a favorite functional group (Figure 1-c). Moreover, it is generally difficult to freely control the SNT’s inner diameter sizes even by changing the self-assembly conditions.7, 19, 34-35 These situations lead to a low yield of passive encapsulation efficiency for guest substances such as biopolymers and nanoparticles.7 In contrast, if the unsymmetrical bolaamphiphiles pack in a parallel fashion (Figure 1-d), the membrane system results in possessing different inner and outer functionalities.19-20 The unsymmetrical SNTs produced in this way can be subjected to selective chemical modification of the inner or outer surfaces of the nanotubes.19-20 It means that we are able to modify only the nanotube inner surface to be anionic,36-38 cationic,39-44 or hydrophobic feature.37, 45 More interestingly, rational molecular design of bolaamphiphiles results into the formation of hollow cylinders with homogeneous diameters. As a result, the obtained SNTs with different surface characters at both surfaces are able to efficiently encapsulate diverse biomolecules and nanostructures.


4

Page 5 of 68

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

Figure 1. The structures of natural lipids that form cell membranes in (a) eukaryote and eubacteria, and (b) archaea. Self-assembly of a (c) bilayer-based SNT from a single-head, singlechain amphiphile and (d) monolayer-based counterpart from an unsymmetrical bolaamphiphile.

2.2 Control of Polymorph and Polytype For the selective self-assembly of the SNTs with complete different inner and outer surfaces, both rational optimization of the molecular structures and control of polymorph and polytype during self-assembly process are of great importance. Figure 2 shows the formation of monolayer lipid membranes (MLMs) from unsymmetrical bolaamphiphiles, in which two hydrophilic headgroups with different sizes or functionalities are connected to both ends of a hydrophobic chain of the molecule, and also shows the additional stacking structures of each MLM. The MLMs can be generally classified into two categories, unsymmetrical and symmetrical MLMs, depending on whether their component bolaamphiphiles are packed in a


5

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 6 of 68

parallel or antiparallel fashion, respectively (polymorph; Figures 2-a and 2-b). Two additional kinds of membrane stacking motifs can be defined, depending on the molecular orientation at the interface between the two surfaces, that is, head-to-tail or head-to-head (head: relatively larger headgroup and tail: smaller headgroup) (polytype; Figures 2-c, 2-d, 2-e, and 2-f). The dipole moment and spatial void, originating from the relatively bulky headgroup, are best compensated by an antiparallel molecular packing. Actually, all the packing feature of unsymmetrical bolaamphiphiles which we have known until 2001 fell into this symmetrical MLMs (Figure 2b).46-47 Even if an unsymmetrical MLM was formed in a solid state, each membrane stacked with a head-to-head interface, as shown in Figure 2-d.48 We then demonstrated the first example of unsymmetrical MLMs with a head-to-tail interface (Figure 2-c) in a single crystal structure of the unsymmetrical bolaamphiphile 1.49-50 However, aiming at the self-assembly into unsymmetrical SNTs in aqueous media, we found it extremely difficult to selectively form unsymmetrical MLMs with a head-to-tail stack.


6

Page 7 of 68

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

Figure 2. Four possible types of MLMs from an unsymmetrical bolaamphiphile, produced by polymorph of a single MLM and succeeding polytype of the stacked MLMs. (a) Unsymmetrical and (b) symmetrical MLMs.

Chart 1. (molecular structures are shown at the end)

2.3 Strategy and Tactics Toward Unsymmetrical MLMs The hollow cylindrical shape and molecular arrangement of tobacco mosaic virus (TMV), self-assembled from 2130 pieces of TMV proteins,51 greatly inspired us how we should simply design the molecular structures of bolaamphiphiles. The protein molecule as a building block, consisting of 158 amino acids, takes a wedge-shape conformation and then self-assembles into a tubular architectures mounted around a single strand RNA as a high-axial-ratio core chain. Learning not only from the wedge-like shape of the protein molecules but interior hoop effect by the RNA chain, we made the research strategy and tactics as shown in Figure 3. Our final target is to form unsymmetrical MLMs with a head-to-tail interface. One can employ unsymmetrical bolaamphiphiles as described above.33, 36 As already noted, Fuhrhop et al. conducted an innovative work on the nanotube formation from a peptide-based unsymmetrical bolaamphiphile, although the molecular packing feature was unclear.18 We focused on an interesting nature that once obtained polymorph, such as an antiparallel packing as a seed for the next self-assembly, should be preserved in the nanostructures even after the self-assembly (Figure 3-a). Templating the unsymmetrical MLMs with a polymer chain will further enable the head-to-tail stack of the MLMs (Figure 3-b). Figures 3-c−3-g-2 illustrate other strategy and tactics that we applied to stabilize and selectively formed unsymmetrical MLMs. The first attempt is to incorporate


7

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 8 of 68

oligoglycine moieties, which exhibit forming ability of multiple hydrogen bonds, near by the terminal hydrophilic headgroup (Figure 3-c). In some cases, endo-complexation of the terminal carboxylate group with an anti-cancer metallo-drug enabled not only the nanotube formation but efficient immobilization of the drug (Figure 3-d). Binary co-assembly of triglycine-involving unsymmetrical bolaamphiphiles with hydrophobic group- or fluorescent probe-appended counterpart successfully resulted in the partial immobilization of the characteristic hydrophobic functionalities on the inner surfaces (Figure 3-e). In addition, selective localization of a ligand for anticancer metallo-drugs was achievable by two-step self-assembly using three components (Figure 3-f-1). Two compounds of the three can commit the formation of multiple hydrogen bond networks. Similar strategy was also efficient to anchor a glucose headgroup via an ethylene glycol (EG) spacer chain on the outer surfaces (Figure 3-f-2). Finally, ternary co-assembly of unsymmetrical bolaamphiphiles together with other two different functional counterparts gave unique unsymmetrical MLMs. Such MLMs have been unknown so far from the perspective of controlled positioning of additional two functionalities (Figures 3-g-1 and 3-g-2).


8

Page 9 of 68

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

Figure 3. Various strategy and tactics effective for the selective formation of unsymmetrical MLMs from unsymmetrical bolaamphiphiles. (a) Polymorph control, (b) polymer template, (c) multiple hydrogen bond, (d) endo-complexation, (e) binary co-assembly, (f-1 and f-2) two-step


9

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 10 of 68

self-assembly, and (g-1 and g-2) ternary co-assembly. The notation of (out) and (in) means outer and inner surfaces of the curved MLM, respectively.

2.4 Identification of Polymorph and Polytype It is almost impossible to prove precise molecular arrangement and orientation within the MLMs in aqueous media even if microscopic evidence was given for the nanometer-scale selfassemblies. However, if multiple hydrogen bond networks stabilize the lateral interactions between the bolaamphiphile headgroups within single MLMs, we can lyophilize and store the resultant self-assemblies as dry nano-materials.2 The crystalline nature of the reported SNTs in aqueous media should present similar molecular arrangement and orientation as those in a lyophilized state. Moreover, such an advantage of the solid-like SNTs enables us to utilize diverse experimental tools for solid analyses, including scanning-, and transmission-electron microscopy (SEM and TEM, respectively), infrared spectroscopy (IR), powder X-ray diffraction (XRD), and single crystal X-ray analysis, in addition to cryo-TEM and atomic force microscopy (AFM) under aqueous conditions. Actually, our careful studies by AFM, SEM, and TEM have proved that the morphologies and dimensions of the SNTs in aqueous media are conserved even in a lyophilized state.36, 41 Interestingly, cryo-TEM observation for the SNT hydrogel revealed the exactly same morphologies and dimensions as the SNT xerogel, which were measured by SEM and TEM.52 Table 1 summarizes experimental tools and decisive criteria, which we employed to identify the polymorph and polytype of obtained MLMs within the self-assemblies. TABLE 1 First, when discussing about the MLMs consisting of bolaamphiphiles, it is essential to investigate the possibility for the existence of U-shaped bolaamphiphiles.2, 53-56 IR spectroscopic


10

Page 11 of 68

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

measurement strongly suggested that all the reported SNTs herein contain molecules with an alltrans conformation, namely, no U-shaped conformations in the oligomethylene spacer chains. The νas(CH2) and νs(CH2) stretching vibrations for the oligomethylene chains absorb strongly around 2916−2928 cm-1 and 2848−2860 cm-1, respectively. As the gauche/trans conformer ratio in the spacer chains increases, for example, upon the gel-to-liquid crystalline phase transition, the frequencies of the νas(CH2) and νs(CH2) bands shift from 2916 and 2848 cm-1 to 2923 and 2853 cm-1, respectively.57-60 We have never observed major or even shoulder peaks of the νas(CH2) and νs(CH2) IR bands at relatively higher frequencies attributable to a gauche conformation36, 41 Second, IR spectroscopic measurement also gave a direct evidence to prove a symmetrical or unsymmetrical MLM within the reported assemblies. The differentiation of the triclinic (T//) and orthorhombic (O⊥) subcell structure makes it definite to assign the corresponding membranes to unsymmetrical and symmetrical MLMs, respectively. The reason is because the subcell structure of both MLMs were actually observed in a single crystal structure.49-50 The presence of two separate δ(CH2) scissoring band (~1463 and ~1473 cm-1) should indicate an orthorhombic (O⊥) structure, whereas a single sharp peak (~1464 cm-1) of the δ(CH2) band should be compatible with a triclinic (T//) type.61-62 A single sharp peak of the γ(CH2) rocking vibration at 719 cm-1 is also suggestive of the triclinic (T//) structure.61-62 Moreover, the CH deformation and skeletal IR bands for polyglycine chain afford a decisive probe to assign the unsymmetrical MLMs.63-67 As discussed later, the self-assembled nanofibers from monoglycine- or diglycine-containing bolaamphiphiles were, then, observed to involve a mixture of unsymmetrical and symmetrical MLMs.42 Third, it is also of great importance to prove the formation of completely unsymmetrical SNTs. In addition to the IR spectroscopic criteria mentioned above, powder XRD and X-ray


11

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 12 of 68

crystallography (if possible) are conclusive to identify the polymorph and polytype of MLMs. On the basis of careful analyses for the SNTs from a series of unsymmetrical bolaamphiphiles, we found a determinate rule that the relationship between d-spacing (d) of MLMs and the extended molecular length (L) by calculation can predict each molecular packing motif.36, 41 If the d values for the obtained SNTs are almost equal to L or slightly shorter than L, the MLM type should be unsymmetrical in a parallel fashion. Multiple unsymmetrical MLMs with a head-to-tail interface can be supported by the d-values much shorter than L. If the d values are slightly larger than L, a symmetrical MLM type in an antiparallel fashion should exist. Furthermore, unsymmetrical MLM type with a parallel packing with head-to-head can be induced by the fact that two times the d-values are larger than L.36 Fourth, we have carried out various macroscopic and spectroscopic experiments to prove the complete selectivity in modifying the inner and outer surfaces of the reported SNTs. All the observed novel functions, including encapsulation, release, diffusion, stabilization, and refolding of guest proteins, can prove the complete selective functionalization on the inner and/or outer surfaces. Every phenomena can never be approved unless we assume unsymmetrical MLMs. The details on each characteristic function are mentioned elsewhere.19-20 In the following sections, we describe the details more about the strategy and tactics by referring to our recent achievements.

2.5 Polymorph Control Using Simple Unsymmetrical Bolaamphiphiles In our earlier studies aiming at the formation of monolayer-based SNTs, we first synthesized the unsymmetrical bolaamphiphiles 2-(n) (n = 12, 14, 16, 18, and 20) as building blocks, in which 1-β-N-glucosamide moiety is connected with carboxylic acid group via longchain hydrocarbon spacers.36 The bolaamphiphiles 2-(n) self-assembled in water to give a


12

Page 13 of 68

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

mixture of both nanotubes with inner diameters of 7.7−22.2 nm and microtubes with hollow cylinders of 80 nm sizes. The obtained nanotubes consist of two to three layers of unsymmetrical MLMs, in which the bolaamphiphiles pack in a parallel fashion. On the other hand, the microtubes had three different types of molecular arrangements including unsymmetrical MLMs with head-to-head and head-to-tail interfaces, and a symmetrical MLM.36 Relatively longer oligomethylene spacers were observed to stabilize the unsymmetrical MLM structure in both nano- and microtube structures. In a similar manner to the molecular design of 2-(n), we then synthesized the unsymmetrical bolaamphiphiles 3-(n) of different molecular length, in which 1-β-N-glucosamine and amino headgroups are linked to both ends of an oligomethylene spacer via amide linkage.39, 41

We varied the carbon numbers (n) of the spacer from 12 to 14, 16, 17, 18, and 20. The self-

assembled morphologies from each film, prepared by the solvent evaporation of the dimethylformamide (DMF) solution, strongly depended on the length of the oligomethylene spacers. The short chain bolaamphiphiles 3-(n) (n = 12, 14, 16, and 17) produced nanotape structures with 80−250 nm widths, while the long chain 3-(n) (n = 18 and 20) self-assembled to form nanotube structures with inner diameters of 70−100 nm (Figure 4). The measured membrane thickness of 15 nm for the SNTs from 3-(18) and 8 nm for the SNTs from 3-(20) corresponded to four and two MLMs, respectively. Differential scanning calorimetry (DSC), polarized light microscopy (LM), variable-temperature X-ray diffraction (VT-XRD), and variable-temperature infra-red (VT-IR) spectroscopy evidenced that all the results can be explained by classifying each bolaamphiphile into two categories: the short chain 3-(n) (n = 12, 14, 16, and 17) and long chain 3-(n) (n = 18 and 20) groups. Figure 5 shows the δ(CH2) bands obtained for the self-assemblies from 3-(n) and plausible molecular packing of MLMs. The


13

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 14 of 68

nanotapes, obtained from the short chain 3-(n) (n = 12, 14, 16, and 17), displayed double peaks in the δ(CH2) IR band, meaning that the subcell structure is of the orthorhombic (O⊥) type to take a symmetrical MLM.61-62 The single peak, obtained for the long chain 3-(n) (n = 18 and 20) in the δ(CH2) IR band, indicated that the nanotubes take the triclinic (T//) subcell structure to form an unsymmetrical MLM.61-62 All the polymorph obtained for the resultant self-assemblies was good agreement with that of the corresponding solid film prepared as a self-assembly seed. On the other hand, the XRD patterns for the self-assembled nanotapes and nanotubes clearly showed a single sharp peak in the small angle region, which is assignable to the long d-spacing of each MLM (Figure 6). The obtained d values for the nanotapes are longer than the values of corresponding extended molecular length (L), indicating that the nanotapes consist of symmetrical MLMs. The nanotubes consist of unsymmetrical MLMs since the d values are shorter than the L values (Figure 7).

Figure 4. Scanning transmission electron microscopic (STEM) images of the resultant selfassembled nanotapes and nanotubes from 3-(n) (n = 12, 14, 16, and 17) and 3-(n) (n = 18 and 20), respectively (negatively stained with phosphotungstate). The hollow cylinder space of the


14

Page 15 of 68

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

nanotubes 3-(n) (n = 18 and 20) can be visualized by the dark staining. (Reprinted with permission from ref 41. Copyright 2007 American Chemical Society).

Figure 5. δ(CH2) IR bands of the (a) nanotapes and (b) nanotubes self-assembled from 3-(n) (n = 12, 14, 16, and 17) and 3-(n) (n = 18 and 20), respectively. (Reprinted with permission from ref 41. Copyright 2007 American Chemical Society). (c) Orthorhombic (O⊥) and (d) triclinic (T//) subcell structures of the oligomethylene chain of 3-(n) and the resultant symmetrical and unsymmetrical MLMs, respectively.


15

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 16 of 68

Figure 6. XRD patterns of the nanotapes and nanotubes self-assembled from 3-(n) (n = 12, 14, 16, and 17) and 3-(n) (n = 18 and 20), respectively. (Reprinted with permission from ref 41. Copyright 2007 American Chemical Society).


16

Page 17 of 68

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

Figure 7. MLM stacking periodicities (d) of the self-assemblies from 3-(n), estimated by XRD, plotted against the chain length (n) of the oligomethylene spacer. The extended molecular length (L) of 3-(n) is also plotted.

Detailed analyses by VT-XRD and VT-IR for the solid films strongly suggested that the long chain bolaamphiphiles 3-(n) (n = 18 and 20) tend to prefer unsymmetrical MLMs upon heating from room temperature.41 Figure 8 illustrates the thermal phase transition behavior and the molecular packing within the MLMs of 3-(n) on heating. The long chain bolaamphiphiles 3(n) (n = 18 and 20) pack with an unsymmetrical MLM and exhibit the Cr1, Cr2 crystal morphism, and smectic (Sm) liquid crystalline phases before isotropic melting. In particular, we confirmed the preservation of the unsymmetrical MLM even after allowing the smectic mesophase to gradually cool. The short chain 3-(n) (n = 12, 14, 16, and 17) pack with a symmetrical MLM and only give a single Cr1 crystalline phase on heating. As shown in Figure 3-a, all collective data from experiments of 3-(n) show that the polymorph such as the antiparallel or parallel molecular packing in the initial solid films are essentially maintained even in the self-assembled nanostructures in water.41 Namely, the self-assembly process of the film in water allowed the symmetrical MLM of the short chain bolaamphiphiles to convert into the


17

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 18 of 68

nanotapes with a symmetrical MLM. Similarly, the unsymmetrical MLM films of the long chain bolaamphiphiles are transformed into the unsymmetrical MLM nanotubes.

Figure 8. Variation of the molecular packing of 3-(n) on thermal phase transition and selfassembly in water. (Photograph) A fan-like texture, observed using LM, for the smectic liquid crystal of 3-(20) at 173 °C on cooling from the isotropic phase. (Reprinted with permission from ref 41. Copyright 2007 American Chemical Society).

2.6 Utilization of Polymer Template In order to produce parallel molecular packing that is critical for unsymmetrical SNTs, we utilized synthetic poly(thiopheneboronic acid) (PTB) (4) [Mn = 710 and Mw/Mn = 1.83] in line with the polymer template strategy in Figure 3-b.43 The polymer chain of 4 as a template can involve in the association/dissociation interaction with the glucosamide diol groups of 3-(n). The


18

Page 19 of 68

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

powder of the unsymmetrical bolaamphiphiles 3-(n) and 0.5 or 1.0 equiv. of 4 were mixed and dissolved in DMF with heating. Evaporation of the DMF solution at 100oC in vacuo yielded a precursor lamellar film as a dehydration product. Hot aqueous solutions of the film, which was adjusted to pH 10 with NaOH and then refluxed at 100oC, were gradually cooled to room temperature. The hydration process gave a targeting self-assembled nanostructures that can be separated from the polymer template by centrifugation. As shown in the left of Figure 9-a, molecular packing analyses by using XRD and FT-IR spectroscopy uncovered that the starting Film-A of 3-(n) complexed with 1 equiv. of the boronic acid moiety of 4 [3-(n)/4 = 1/1, mol] takes a symmetrical MLM motif. In contrast, the MLMs of the starting Film-B [3-(n)/4 = 2/1, mol] containing 0.5 equiv. of the boronic acid moiety of 4 take a parallel molecular packing (right in Figure 9-a).43 Dissociation process of PTB (4) based on hydrolysis of the boronate esters in the complex resulted into the self-assembly of nanotapes and nanotubes from the Film-A and Film-B, respectively. Interestingly, we also found that the nanotapes and nanotubes memorize the initial antiparallel and parallel molecular packing of the starting films, respectively. Thus, the similar template methodology to the RNA chain in TMV (Figure 3-b) enabled the maintenance of the polymorph structure, leading to the control of polytype with a head-to-tail arrangement. This methodology for 3-(n), by using PTB (4) with appropriate composition, can get rid of the spacer-length dependence of the molecular packing (Figure 9-b) on self-assembly of the single component in the absence of the template.41


19

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 20 of 68

Figure 9. (a) Molecular packing of the starting Film-A and Film-B, and the resultant selfassemblies of 3-(n) in water after dissociation of PTB (4) from the films. (b) Molecular packing of the starting Film-3-(n) and the resultant self-assemblies in water in the previous work.41

2.7 Utilization of Multiple Hydrogen Bond Network Taken together, all the previous findings obtained for the bolaamphiphiles 2-(n) or 3-(n) revealed that diverse self-assembled morphologies including nanotapes, nanotubes, and microtubes, were produced with rather favorable symmetrical as well as unsymmetrical MLMs.36, 39, 41

Notably, 2-(n) or 3-(n) with relatively shorter oligomethylene spacers have a tendency to

self-assemble into microtubes of 80-nm inner diameters with diverse polymorph and polytype or into nanotape structures, respectively.36, 41 Thus, the control of polymorph using such simple unsymmetrical bolaamphiphiles remained as a big issue for the exclusive formation of SNTs,


20

Page 21 of 68

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

characterized by both unsymmetrical MLMs and single-nm inner diameters. Aiming at the stabilization by multiple hydrogen bonding around the nanotube inner surfaces (Figure 3-c), we designed novel unsymmetrical bolaamphiphiles 5a-(n) (n = 1, 2, and 3) having both 1-β-Nglucosamide and oligoglycine headgroups connected to a relatively short oligomethylene spacer at each end.42 We employed mono-, di-, and tri-glycine residues as a terminal amino group. Figure 10 shows typical TEM images of the self-assembled nanostructures from 5a-(n) in water. Sensitively depending on the number of the glycine residue, the bolaamphiphiles 5a-(1) and 5a(2) self-assembled into helical nanofibers with 10–25-nm width, whereas 5a-(3) gave targeting SNTs with 7–9-nm inner diameters and 3–4-nm membrane thickness. This result exactly means that the substitution of triglycine unit for related amino terminal group in 3-(n) enabled the selfassembly into selective formation of the nanotube structure consisting of a single monolayer system. Different from the case of the nanofibers from 5a-(1) and 5a-(2), the prominent occurrence of the CH skeletal vibration band at 1026 cm-1 as well as the CH deformation band at 1420 cm-1 (Figure 11) strongly suggested the formation of polyglycine-II-type hydrogen bonds6367

among the triglycine residues (Figure 12). The increase in the number of glycine residues

were found to contribute the stabilization of polymorph, in which each molecule form an unsymmetrical MLM. Furthermore, worth noting is the spontaneous formation of the solid SNTs, characterized by both a single monolayer and single-nm inner diameters, from the glucosamide triglycine bolaamphiphiles.42


21

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 22 of 68

Figure 10. TEM images of the self-assembled one-dimensional (1-D) nanostructures from 5a(n) (n = 1, 2, and 3), negatively stained with phosphotungstate. The hollow cylinder space of the nanotubes from 5a-(3) can be visualized by relatively darker image than surrounding. (Reprinted with permission from ref 42. Copyright 2007 The Chemical Society of Japan).

Figure 11. The CH deformation and skeletal vibration IR bands for the oligoglycine moieties in the self-assembled 5a-(n) (n = 1, 2, and 3).


22

Page 23 of 68

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

Figure 12. A schematic model for the SNT consisting of a single, unsymmetrical MLM of 5a(3) stabilized by polyglycine-II-type hydrogen bond networks among triglycine residues.

2.8 endo-Complexation with Metal Ions Cisplatin [cis-dichlorodiamineplatinum (II), CDDP] (6) is widely used as a chemotherapeutic metal complex, exhibiting antitumor activity. Substitution of the CDDP chloride ligands with carboxylate groups has been giving many spherical nanostructures68-70 as well as nanofibers.71 The endo-complexation methodology noted in Figure 3-d allowed a discovery for the first example of CDDP-encapsulated SNTs, of which outer and inner surfaces were differently covered with hydroxyl groups and CDDP, respectively (Figure 13-a).38 The SNTs were gradually transformed from nanofibers of the sodium salt of 2-N-glucosamide tetraglycine bolaamphiphile 7 in water, in 8 to 48 hours after the addition of CDDP. Interestingly, the complexation of the carboxyl group of 7 with CDDP, occurring exclusively on the nanotube inner surface, was accompanied with the self-assembly into metallo-drug-incorporated SNTs. The STEM images clearly showed a uniform tubular nanostructure with 14-nm outer diameter and 6.7-nm inner diameter (Figure 13). In the IR spectrum, the disappearance of the shoulder peak around 1610 cm-1, assignable to the COO− stretching vibration (peak B in Figure 14),


23

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 24 of 68

strongly suggested the metal-complex formation of platinum in CDDP with the COOΝa group of 7. Time-dependent association studies also revealed that one CDDP molecule associates with two carboxylate anions via metal-complex formation. The CH deformation band of the tetraglycine moiety (peak D in Figure 14) evidenced the formation of polyglycine-II-type hydrogen bond networks that ensure unsymmetrical MLM within a single layer. Figure 13-b clearly indicated that the measured stacking periodicity (d = 3.85 nm) of the CDDP-coordinated SNTs is well compatible with that (3.7 nm) estimated by STEM observation. The XRD studies also suggested the existence of a single monolayer membrane (MLM) with each molecule tilted by 32.8o. Metal-complexation of various tube-forming peptidic amphiphiles have been already well-known to provide unique SNTs.72-73 However, the nanotubes self-assembled so far are metal-complexed SNTs with identical inner and outer surfaces covered with metal cations.20 In this way, we were able to demonstrate the unique metal complexation-assisted self-assembly of the SNT with both a single monolayer and an unsymmetrical MLM from the bolaamphiphile 7.


24

Page 25 of 68

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

Figure 13. (a) A schematic illustration of endo-complexation-triggered self-assembly into a nanotube. (b) STEM images of the CDDP-complexed SNTs, negatively stained with 2%phosphotungstate. O.d., i.d., and m.t.: outer diameter, inner diameter, and membrane thickness of the SNT, respectively.

Figure 14. IR spectra of the mixture solution containing sodium salt of 7 and CDDP (molar ratio of 1/1) after 0 and 48 h incubation. The peaks A, B, C, and D are assignable to the amide I, COO− stretching vibration, amide II, and C–H deformation of tetraglycine. (Reprinted with permission from ref 38. Copyright 2012 The Royal Society of Chemistry).

2.9 Binary Co-Assembly By rationally combining the polymorph control, achieved by triple hydrogen bonds, with co-assembly methodology using a pre-functionalized amphiphile, we can easily modify inner or outer surfaces of the resultant SNTs independently (Figure 3-e). It should be noted that by tuning the initial mixing ratio of the tube-forming mother and doped pre-functionalized amphiphiles we can control the degree of functionalization over a wide range. The initial and typical example of


25

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 26 of 68

the binary co-assembly was achieved for the inner surface of the unsymmetrical SNTs from 5a(3) (8 nm i.d.).74 A large fluorescent probe such as the recognition probe Alexa for a target guest protein was found to cover only the inner surface. Figure 15-a indicates that strong intermolecular interaction by multiple hydrogen bonds occurs between 5a-(3) and a small amount of the doped derivative 5b-(3) labeled with Alexa. The formation of intermolecular hydrogen-bonding similar to the polyglycine-II-type hydrogen-bond networks was confirmable by the two peaks at 1420 cm-1 (the CH deformation band) and 1026 cm-1 (the CH skeletal vibration band) in the IR spectrum of the Alexa-immobilized SNTs (Figure 15-b). This situation should induce the parallel molecular packing within a single monolayer of the Alexa-SNT. A single sharp peak of the γ(CH2) rocking vibration at 719 cm-1 also suggested a triclinic (T//) structure in the lateral chain packing of the oligomethylene spacer. Consequently, the Alexa moiety turns to be located on the inner surface of the nanotubes without exception. We then succeeded in detecting the encapsulation and releasing feature of a guest protein by utilizing endo-sensing74-75 system. Such a binary co-assembly methodology was further developed to enable the partial hydrophobization on the nanotube inner surfaces by benzyloxycarbonyl (Cbz) or tert-butyloxycarbonyl (t-Boc) group.37, 45 Of particular note is the precise controllability for the hydrophobicity of the inner surfaces, which allowed slow drug release37 and structural optimization of SNTs toward artificial chaperone activity.45


26

Page 27 of 68

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

Figure 15. (a) Polyglycine-II-type hydrogen bond networks between 5a-(3) and Alexaappended 5b-(3). (Left) Glucose triglycine bolaamphiphile 5a-(3), (middle) side view, and (right) view from the inside. (b) IR spectrum of the lyophilized Alexa-SNT prepared by binary co-assembly of 5a-(3) with 5b-(3).

2.10 Two-Step Self-Assembly A two-step self-assembly process, constructed by combining the tube-forming unsymmetrical bolaamphiphile (8 or 10), triglycine derivative (11) bearing a pyridine carboxylate unit as a ligand, and the tube-forming glucosamide, single-head amphiphile 12-(n) (n = 15 and 17), resulted in the formation of self-assembled SNTs or nanotapes (Figure 16).44 Both the nanotubes and nanotapes were confirmed to consist of an unsymmetrical MLM that was functionalized with the coordination site for an anticancer Pt complex. Each single component 8 or 10 self-assembles into tubular structures with an inner diameter of 8 nm, a wall thickness of 4 nm independently.44 Binary co-assembly of 8 and 11, or 10 and 11 gave nanotubes or nanotapes, respectively. The obtained gel-to-liquid crystalline phase transition temperature (Tg-l = 51oC and


27

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 28 of 68

64oC) for the conjugated 8/11 nanotube and 10/11 nanotape, respectively, was remarkably lower when compared to that of the single component (Tg-l >115 oC). This indicated that the nanotubes or nanotapes surely consist of 8 and 11, or 10 and 11, respectively, with sharing common triglycine moieties. The lower Tg-l and thereby lower thermal stability for the nanotubes and nanotapes were ascribable to the lack of a long alkyl chain and glucose headgroup. Notably, the addition of the third glycolipid 12-(n) (n = 15 and 17) component via two-step self-assembly, as shown in Figure 3-f-1, was observed to well compensate this unfavorable situation. In actual, the obtained Tg-l of over 115 oC for the hybrid nanotubes of 8, 11, and 12-(17), or 10, 11, and 12(15) is compatible with the fact that the glycolipid 12-(n) well fill the void spaces within the molecular packing of the nanotube and nanotape (Figure 16).


Figure 16. Plausible molecular packing within the MLMs of the conjugated (a) 8/11/12-(17) nanotube and (b) 10/11/12-(15) nanotape, which were prepared via two-step self-assembly.


28

Page 29 of 68

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

Yellow bands show the intermolecular hydrogen bond networks. TEM images of the (c) nanotubes and (d) nanotapes, which were negatively stained with phosphotungstate. The nanochannel of the nanotube is visible and characterized by a relatively darker contrast to the background.

The occurrence of the two peaks at 1420 and 1026 cm-1 for the 8/11/12-(17) nanotube strongly suggested the stabilization by polyglycine-II-type hydrogen bond, in which the molecules 8 and 11 should pack in parallel with the triglycine sequence (Figure 16-a). In contrast, the 10/11/12-(15) nanotape showed no remarkable peaks in the same IR band regions. The frequency of the C=O stretching vibration band (1619 m-1) of the 10/11/12-(15) nanotape was lower than that of the polyglycine-II-type hydrogen bonding of the 8/11/12-(17) nanotube (1663 cm-1). Such a low frequency of 1619 cm-1 rather indicates the occurrence of the polyglycine-Itype hydrogen bonding (like a typical parallel β-sheet structure) of polyglycine (1630 cm-1). Thus, the molecules of 10 and 11 should pack in an antiparallel fashion (Figure 16-b). Consequently, the polyglycine-II-type hydrogen bonds between 8 and 11 in the binary selfassembly resulted into the selective formation of the tubular structures. Conversely, antiparallel β-sheet type hydrogen bonds between 10 and 11 led to the formation of nanotape morphology. Furthermore, the occurrence of single sharp peaks at 1465 and 719 cm-1 for the δ(CH2) scissoring and γ(CH2) rocking vibration bands, respectively, clearly indicated that the subcell structure of 8/11/12-(17) and 10/11/12-(15) takes a triclinic (T//) molecular packing.74-75 Here we should note that the mode of intermolecular hydrogen bond networks within the MLMs determine the resultant nanostructure morphologies.


29

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 30 of 68

As shown in Figure 3-f-2, two-step self-assembly were also performed to effectively anchor a Concanavalin A (Con A) recognition site onto the SNT’s outer surface. The binary coassembly process of the tube-forming bolaamphiphile 5a-(3)42 with a triglycine derivative 13 gave nanotubes, of which dimensions were similar to the SNTs from the single component 5a(3).76 Void spaces in the molecular packing of the hybrid 5a-(3)/13 nanotubes, probably due to the lack of the long alkyl chain and the glucose headgroup in 13, induced lower Tg-l (= 52oC) in water than that (Tg-l = 67oC) of the single counterpart of 5a-(3). However, we found that the second step, in which the hybrid 5a-(3)/13 nanotube were heated with the glucose derivatives 14(n) (n = 1, 3, and 5), increased the Tg-l to 65−67oC. This result can explain that the molecules 14(n) with spacer chains of ethylene glycol (EG) well fill the void spaces within the MLM (Figure 3-f-2). The two CH deformation (1420 cm-1) and skeletal (1026 cm-1) vibration bands for the triglycine moieties in the IR spectroscopy (Figure 17-a) indicated that the sharing triglycine moieties of 5a-(3) and 13 forms polyglycine-II-type hydrogen bond network.65-67 Furthermore, single sharp peaks at 1465 and 719 cm-1 assignable to the δ(CH2) scissoring and γ(CH2) rocking vibration bands, respectively, evidenced that the lateral chain packing of the oligomethylene spacer in 5a-(3) and 14-(n) takes a triclinic (T//) type.41-44 All the results indicate that the glucose moiety bonded to the EG chain of 14-(n) (n = 1, 3, and 5) was surely located only on the outer surface of the ternary hybrid nanotubes (Figure 17-b).


30

Page 31 of 68

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

Figure 17. (a) The CH deformation (1420 cm-1) and skeletal (1026 cm-1) vibration bands for the triglycine moieties in the single component nanotube from (A) 5a-(3) , (B) the hybrid nanotubes from 5a-(3), 13, and 14-(1) , (C) from 5a-(3), 13, and 14-(3), and (D) from 5a-(3), 13, and 14(5). (b) A monolayer-based SNT made of 5a-(3), 13 (10 mol% against 5a-(3)), and 14-(n) (10 mol% against 5a-(3)).

2.11 Ternary Co-Assembly The functional modification by the co-assembly system was also of benefit for the incorporation of two additional different functionalities. As we can imagine from the positioning of the functional groups in Figures 3-f-1 and 3-f-2, a final challenging goal should be their simultaneous localization at the inner and outer, or only to the outer surfaces of SNTs. Figure 3g-1 indicates a schematic image, in which a PEG chain and ligand for metal ions are localized on each outer hydroxyl- and inner amino-group-covered surface. For that purpose, we attempted to


31

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 32 of 68

adopt ternary co-assembly procedure. By utilizing the tube-forming bolaamphiphile 15,37 the PEG-tethered analogue 16 (10 mol%), and the unsymmetrical bolaamphiphile 17 (10 mol%) with tetraazacyclododecane tetraacetic acid (DOTA) group as a headgroup, we successfully obtained uniform SNTs with 7−9-nm inner and 16−18-nm outer diameters.77 The DSC and XRD studies for the binary co-assembled SNT with 15 and 16 suggested that up to 10 mol% of the PEG amphiphile 16 can be completely incorporated into the resultant SNTs. Dramatically improved dispersibility of the PEGylated SNTs and ternary co-assembled SNTs with the DOTA ligand in a phosphate-buffered saline (PBS, pH 7.4) suggested that the PEG chain is anchored onto the outer surface of each SNT as required. In a similar manner, by employing ternary co-assembly of the mother amphiphile 2-(18) with other two different functional amphiphiles 18 and 19 (Figure 3-g-2), we were able to modify the outer surfaces with cationic arginine residues and PEG chains (Figure 18-a).78 The amphiphiles 18 and 19 function to accelerate DNA association onto the SNT surface and to improve the dispersibility of the SNT−DNA complex. Both the binary co-assembly of 2-(18) and 18, and the ternary co-assembly of 2-(18), 18, and 19 gave nanotube structures in homogeneous aqueous dispersions (Figures 18-b and 18-c), while homo-assembly of 18 or 19 nanotapes or spherical structures, respectively. The surface charges of the binary and ternary co-assemblies, clarified by zeta potential measurement, displayed a mono-dispersed positive peak at +37.7 and +21.3 mV, respectively, while that of the homo-assemblies from 2-(18) gave a negative peak at −25.8 mV (Figure 19). These changes in the surface charge well suggest that both the arginineand PEG-functionalized amphiphiles 18 and 19, respectively, are strictly anchored and the PEG layer slightly shields the surface charges on the outer surface of the SNTs.79 FT-IR spectroscopy further confirmed an unsymmetrical MLM motif in the arginine- and PEG-arginine SNTs,


32

Page 33 of 68

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

indicating the presence of a single δ(CH2) scissoring band peak at 1471 cm−1 characteristic of triclinic (T//) subcell structure.78

Figure 18. (a) Binary and ternary co-assembly approach by using 2-(18), 18, and 19. STEM images of (b) self-assembled arginine-SNTs prepared by the binary co-assembly of 2-(18) and 18 and (c) PEG-arginine SNTs prepared by the ternary co-assembly of 2-(18), 18, and 19. The nanotubes were negatively stained with phosphotungstate. Insets in (b) and (c): Macroscopic appearance in a glass vial and nanotubes at higher magnification. The outer diameter and membrane thickness (in parentheses) of the nanotubes were indicated by arrows.


33

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 34 of 68

Figure 19. Zeta potential graph of the (A) mother SNT from 2-(18), (B) PEG-arginine SNT prepared by the ternary co-assembly of 2-(18), 18, and 19 and (C) arginine-SNT prepared by the binary co-assembly of 2-(18) and 18, as measured in Milli-Q water. (Reprinted with permission from ref 78. Copyright 2011 ELSEVIER).

3. BIO-FUNCTIONAL PROPERTIES As described above, the rational molecular design and polymorph/polytype control for the unsymmetrical bolaamphiphiles ensured their self-assembly into crystalline tubular architectures having structurally and functionally different inner and outer surfaces.19-20 This unsymmetrical feature of the nanotube surfaces makes the SNTs to considerably excel as nanocontainers and nanocarriers, as compared to bilayer-based nanotubes. More importantly, the nanotube morphologies are thermally stable since the melting temperatures are relatively high or do not exist within a measurement range. The hollow cylinder sizes are also optimizable by rational molecular design.36, 40, 43 No flip-flop phenomena occurs for the bolaamphiphiles. All the advantages are of vital importance when considering effective encapsulation, stabilization, release, and diffusion of relatively large molecules like proteins in the hollow cylinder.19-20 The


34

Page 35 of 68

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

use of localized inner or outer functional surfaces, thereby ensures the expression of characteristic endo-45, 74-75 and exo-sensing.76, 78 We discuss hereafter diverse bio-functional properties that can be hardly realized with bilayer-based nanotube architectures.

3.1 Refolding of Proteins The SNT hydrogel material was produced,52 which consists of the self-assembled nanotubes (inner diameters of 8−10 nm and membrane thickness of 3 nm) from glucose triglycine bolaamphiphile 9. We demonstrated that the SNT hydrogel exhibits artificial molecular chaperone activity for denatured proteins (GFP: green fluorescent protein, CAB: carbonic anhydrase, and CS: citrate synthase)45 without the need of certain additive reagents80-81 (Figure 20). In order to gain better understanding about the influence of hydrophobicity of the inner surface and the diameter size of the hollow cylinder, we prepared different types of nanotube hydrogels by the self-assembly of 9 (i.d. = 10 nm) and co-assembly of 9 and 20 (or 21) (i.d. = 10 nm). Consequently, we found that the incorporation of the hydrophobic functionalities such as the Cbz or t-Boc group remarkably enhance both the encapsulation of GFP or CAB and chaperone ability (84% of refolding ratio for CAB). A reason for that will be the hydrophobic interactions between the exposed hydrophobic amino acid residues of these denatured proteins and partly hydrophobized inner surfaces of the SNTs (Figures 20-d and 21). The confinement in the nanotube hollow cylinder, by size balance between the inner diameters and the encapsulated protein, proved to be also critical to efficient refolding activity. Actually, the SNTs showed no high chaperone activity against CS (4−9 nm).45 In this way, the precise controllability for the nanochannel diameters as well as the rational surface functionality ensured fine tuning of the molecular chaperon activity.


35

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 36 of 68

Figure 20. (a) A photograph of the SNT hydrogel that hierarchically self-assembled from 9 and the corresponding (b) TEM and (c) SEM images. (d) Refolding of a denatured protein into the native state, which takes place in the SNT hollow cylinder with a partly hydrophobized inner surface.


36

Page 37 of 68

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

Figure 21. Time dependence of the total refolding ratio of CAB that released from the SNT hydrogels, obtained by binary co-assembly of 9 and 20, or 9 and 21, and self-assembly of 9, into the recovery solution. [Encapsulated CAB] = 13 µg. Part (38%−46%) of the encapsulated CAB was refolded in advance in the nanotube channel.45 (Reprinted with permission from ref 45. Copyright 2012 American Chemical Society).


3.2 Properties as Drug Nanocarriers Slow release behavior of anticancer drugs,37-38, 44, 82 poorly water-soluble medicines,83 and genes78 from the open ends or outer functional surfaces of self-assembled SNTs is of great interest in terms of alternatives to a variety of soft nanomaterials for drug delivery systems.80, 8487

One of potential merits for the tubular morphologies as a drug nanocarrier was demonstrated

by the fact that high-axial-ratio polymer nanocarriers indicated much longer persistence in blood than do spherical polymersomes.88 The binary co-assembly methodology for 15 with 22 demonstrated remarkable incorporation effect of the Cbz group at the SNT’s inner surface of 15 on a drug release rate. When the molar ratio of 15/22 was increased to 6:5, the amount of anticancer drug doxorubicin (DOX) (23) hydrochloride, released after 48 h at pH 7.4, decreased dramatically from 60% to less than 10% (Figure 22).37 The CDDP (6)-complexed SNTs from 7, successfully prepared by endo-complexation, also indicated a remarkably slow release of 6 through a ligand exchange reaction.38 The nanotapes and nanotubes with the 10/11/12-(15) and 8/11/12-(17) composition, respectively, prepared by two-step self-assembly as well as the motif control of hydrogen bond networks, were also able to coordinate the anticancer Pt complex


37

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 38 of 68

(DACH-Pt) (24) in water. They can release 24 even in biological media such as PBS.44 Interestingly, the obtained nanotube was superior to the nanotape in terms of the sustainable and slow release of 24.

Figure 22. (a) Self-assembly of SNTs from 15 and via binary co-assembly of 15 with 22. Release behavior of DOX from each SNT is also shown. (b) Release of DOX from the mother SNTs from 15 and the SNTs from 15 and 22 with partly hydrophobized inner surfaces in HEPES [4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid]-buffered saline of pH 7.4. The parentheses mean the molar ratio of 15 and 22.

The PEGylated, cationic SNTs on the outer surfaces, which were prepared by the ternary co-assembly of 2-(18) with 18 and 19, acted as nonviral gene transfer vector. The dual functionalized SNTs strongly complexed with anionic DNA while maintaining their tubular


38

Page 39 of 68

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

morphology. We found that among those SNTs of different tube lengths, relatively shorter nanotubes of 400−800 nm in length were efficiently internalized in the cytoplasm to deliver DNA more effectively (Figure 23).78 Moreover, by using inductively coupled plasma-atomic emission spectroscopy (ICP-AES), we conducted the in vivo quantitative detection of another dual functionalized SNTs from 15, 16, and 17 in mouse tissues.77 Outer and inner surfaces of those SNTs are partly covered with PEG chain and DOTA-gadolinium complex, respectively. As a result, the PEGylation strikingly improved the tissue distribution of the SNTs and improved the persistence time in the blood circulation in mice. In addition, the SNTs from 7, that is currently a commercially available bolaamphiphile, was also found to function as an alternative pharmaceutical excipient, enhancing the bioavailability of poorly water-soluble drugs such as hydrocortisone 25 and phenytoin 26.83

Figure 23. Histogram of the length distribution of the PEGylated, cationic SNTs (a) before and (b) after sonication treatment. Confocal microscopic images of KB cells incubated for 2 h with those (c) long and (d) short SNTs, prepared by the ternary co-assembly of 2-(18) with 18 and 19 and labelled with rhodamine, and subsequent heparin wash.


39

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 40 of 68

3.3 Naked-Eye Detection of Con A Con A exhibits high affinities to mannose and glucose. As already noted, the unsymmetrical bolaamphiphile 5a-(3) self-assembles into single monolayer-based SNTs with an inner diameter of 8 nm and lengths of up to several micrometers.42 Two-step self-assembly of 5a-(3), by combining the triglycine derivative 13 and the glucose derivative 14-(n) (n = 1, 3, and 5) with EG spacer chains, successfully produced monolayer-based SNTs. Such SNTs possess Con A recognition sites anchored on the outer surface through the EG chains (Figure 3-f-2 and Figure 17) .76 The resultant nanotubes with three different lengths of recognition sites are well dispersed in water to give clear solutions. Upon addition of Con A, the single-component SNT from 5a-(3) never recognized Con A to maintain the clear solution, even though the outer surfaces are occupied by glucose hydroxyl groups. In contrast, the hybridized nanotubes consisting of 5a-(3), 13, and 14-(n) showed remarkable phase changes depending on the length (the value of n) of the EG chain (Figure 24). It is also noteworthy that the nanotubes hierarchically organize into a naked-eye-detectable liquid crystal or a hydrogel depending on the concentration of Con A.76 Thus, the two-step self-assembly technique enabled the optimization for the EG chain lengths that can exactly anchor the Con A recognition sites onto the SNT’s outer surface.


40

Page 41 of 68

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

Figure 24. Photographs of nanotube dispersions (1 ml) in the absence and presence of Con A (= 0, 20, or 80 nmol) at pH 7.6, [NaCl] = 10 mM: (a) Single component SNT (5a-(3) = 1.8 mM) and hybridized SNTs from (b) 5a-(3)/13/14-(1), (c) 5a-(3)/13/14-(3), and (d) 5a-(3)/13/14-(5) [5a-(3) = 1.8 µmol, 13 = 0.2 µmol, 14-(n) =0.2 µmol]. (e) A schematic illustration for side-byside alignment of the hybridized SNTs complexed with Con A. (f) Phase behaviors for the aqueous dispersions of the single component SNT from 5a-(3) and hybridized SNT dispersions from 5a-(3), 13, and 14-(n) (n = 1, 3, and 5) in response to different concentrations of Con A. (Reprinted with permission from ref 76. Copyright 2015 The Royal Society of Chemistry).

3.4 Chiral Induction for Achiral Polymers As already discussed several times, the bolaamphiphile 5a-(3) gave single monolayerbased SNTs having nanochannels of 7−9 nm diameters.42, 76 We have recently found that the binary co-assembly of 5a-(3) with the diglycine derivative 5a-(2) or monoglycine derivative 5a-


41

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 42 of 68

(1) enabled not only the exclusive formation of nanotube architectures but also tuning of the inner diameters, surface functionalities, and chirality of the resulting SNTs.89 Typically obtained inner diameters of the SNTs are in a range of 2−3 nm or 4−5 nm from the combination of 5a-(3) and 5a-(1) or 5a-(3) and 5a-(2), respectively. Induced vacant space in the monolayer packing, due to the difference in the number of glycine residues between 5a-(3) and 5a-(1) or 5a-(2), should have promoted membrane twisting and thereby enhanced the MLM curvature.7, 20, 89 On the other hand, each single component of 5a-(1) or 5a-(2) self-assembled into only nanofiber morphologies with widths of 10–25 nm. All the three different sized nanotubes possess single, solid-state (i.e. crystalline) monolayers consisting of the 5a-(3)/5a-(1) or 5a-(3)/5a-(2) molecules with unsymmetrical MLMs. The moderate rigidity of those SNTs, when compared with, for example, flexible schizophyllan tubular hosts,90-92 benefited us to discuss the confinement effect on encapsulated polymer chains like PTB (4). In actual, all the nanotubes were able to encapsulate the achiral polymer 4 (Mn = 7,680 and 24,300) through the binary co-assembly process in the presence of the polymer. Strongly depending on the inner diameter sizes of the obtained SNTs (2−3, 4−5, and 7−9 nm), the conjugated PTB (4) (Mn = 7,680) took a 1-D extension, random-coil conformation, and aggregated state in the nanochannels, respectively (Figure 25). Particularly, the encapsulated polymer chain of 4 in the smallest 2−3-nm SNTs showed both a red-shifted absorption band at 452 nm and a split-type induced circular dichroism (CD) band at the same wavelength (Figure 26). This finding means that the PTB chain takes a stretched conformation with a left-hand helicity, which eventually leads to the exhibition of chiral recognition abilities for D, L-sugars.89 Thus, the obtained SNTs acted as a confinement effecter and chirality inducer for the achiral PTB in response to the inner diameter sizes.


42

Page 43 of 68

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

Figure 25. Schematic illustrations of (a) 1-D extension, (b) random-coil conformation, and (c) aggregation of PTB (4) chains that were confined by encapsulation into the nanochannels of the co-assembled 5a-(3)/5a-(1), co-assembled 5a-(3)/5a-(2), and self-assembled 5a-(3) SNTs, respectively.


43

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 44 of 68

Figure 26. (a) Absorption and (b) CD of free PTB (4) in water/DMSO (v/v = 90/10) and that of 4 encapsulated in three different sized SNTs dispersed in water/DMSO (v/v = 90/10). [Free 4] = [encapsulated 4] = 2.0 x 10-5 M. (Reprinted with permission from ref 89. Copyright 2016 The Royal Society of Chemistry).

3.5 Tailored Shaping of Polydopamine Nanofibers Mussel-inspired chemistry has promoted extensive studies on polydopamine (PDA) (27) (shown as one of plausible polymer structures)93 as a promising biomimetic and biomedical materials in any surface, cell, and tissue engineering.94-96 However, morphological control of the PDA nanostructures is still a big challenge in case of 1-D PDA morphologies such as nanofibers, nanocoils, and nanotapes.97 By using two different types of SNTs that function as templates for polymerization of dopamine 28, we have recently succeeded in fabricating helically coiled and linear PDA nanofibers separately, as shown in Figure 27.98 In particular, the liner PDA nanofibers were formed in the hollow cylindrical nanospace (8-nm diameters) covered with carboxylate anion, which were created by unsymmetrical bolaamphiphile 15 (Figure 27-a).37 Under the aqueous condition at pH 8.6, dopamine (28) was preferentially adsorbed on the anionic inner surface of the SNT through electrostatic interaction. STEM observation for the PDA-nanotube hybrid showed many dumbbell- and match-like nanostructures at a high contrast without staining (Figure 28). We also observed that PDA nanoparticles of 30–40 nm capped the nanotube ends. These results really evidenced the occurrence of polymerization of 28 not only in the cylindrical nanospace but also at the open ends of the nanotubes (PDA/nanotube = 0.6 : 1, w/w) (Figure 27-a). However, when compared to the linear PDA nanofibers, the helically coiled PDA, prepared by templating bilayer-based SNTs from 29 and oleic acid (Figure 27-b),


44

Page 45 of 68

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

demonstrated morphological advantages from the viewpoint of higher light absorbance and photothermal conversion effect.98 At a concentration of 0.8 mg/mL, the coiled PDA hybrid showed a significant temperature increase (∆T) of 52.3oC after 10-min laser irradiation, whereas the linear PDA and spherical PDA nanoparticles (PDA-NP)99 showed moderate temperature increases of 19.7 and 23.4oC, respectively, as shown in Figure 29.

Figure 27. Fabrication of (a) linear and (b) helically coiled PDA nanofibers by using the selfassembled monolayered and binary co-assembled, bilayered SNTs, respectively, as a polymerization template. All the PDA nanofibers are shown in gray color.


45

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 46 of 68

Figure 28. (a) STEM images of dumbbell- and match-like nanostructures obtained by the selfassembly of 15 and subsequent addition of dopamine (28). (b) STEM image for the separated PDA nanofibers98 (white arrow) from the nanotubes (red arrow).

Figure 29. (a) Photothermal effect of the dispersions of coiled-, linear-PDA-hybridized SNTs, and spherical PDA nanoparticles at a PDA concentration of 0.8 mg/mL.


46

Page 47 of 68

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

3.6 Spontaneous Nematic Alignment Rod-shaped viruses,100-101 nanofibers,102 and lipid tubules103-104 tend to exhibit spontaneous alignment by themselves if the excluded volume effect of those 1-D nanostructures functions.105 When considering a potential approach for industrial or practical structuring of SNTs in liquid media, we should note such properties. As already shown in Figure 24-f, we found the liquid crystal (LC) formation of the hybridized 5a-(3)/13/14-(3) nanotubes in response to the Con A concentration.76 On the other hand, the SNTs self-assembled from 15 was observed to yield a stable colloidal dispersion in their dilute aqueous solutions. Furthermore, the SNTs also displayed spontaneous liquid crystal (LC) alignment in a pH region of 6.3−9.4, strongly depending on the nanotube concentration as shown in Figure 30.106 Morphological robustness of the nanotubes, enforced by intermolecular multiple hydrogen bond networks between the tetraglycine residues, stabilize the LC formation in mixed solvents of water/ethanol, water/acetone, and water/tetrahydrofuran (1:1 by volume) and even at temperatures of up to 90°C in water. These features remarkably contrast to those of bilayer-based nanotubes selfassembled from related glycolipids.107 Notably, the obtained minimum LC formation concentration of 2 mg/mL is 5-fold and 11-fold lower than those of phospholipid tubules [10 mg/mL, axial ratio (AR) > 60]108 and TMV (23 mg/mL, AR ≈ 17)109, respectively. Figure 31 shows the plot for the minimum concentrations of LC formation against the 1/AR values, indicating that the minimum concentration is roughly inversely proportional to the AR values. Interestingly, the result is in moderately consistent with the theory of nematic phase formation in rod-shaped colloid systems.105


47

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 48 of 68

Figure 30. (a) Photographs for concentration-dependent LC formation of SNTs from 15; (a) without crossed polarizers and (b) with crossed polarizers. (c) LM image of an aqueous SNT dispersion (5 mg/mL) on a glass slide. (d) STEM image of the dried SNTs from a 2 mg/mLdispersion on a carbon grid, clearly showing the cylindrical nanochannels and side-by-side alignment of the SNTs. (Reprinted with permission from ref 106. Copyright 2015 American Chemical Society).


48

Page 49 of 68

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

Figure 31. (a) Relationship between the AR and minimum LC concentration. The AR values were calculated from the peak lengths in the distributions shown below and the SNT diameter (∼16 nm). (b) Length distributions of sonicated SNTs (sonication times of 5, 10, 20, and 30 s). The lengths were measured from the STEM images. (Reprinted with permission from ref 106. Copyright 2015 American Chemical Society).

4. CONCLUSIONS AND OUTLOOK Over the last decade of research, we have demonstrated the self-assembly of unsymmetrical bolaamphiphiles into nanotube architectures by utilizing various self-assembly strategy and tactics. Table 2 summarizes representative dimensions for the obtained SNTs in our laboratory from various bolaamphiphiles. Those SNTs are not occasional products but inevitable self-assemblies, possessing homogeneous dimensions including inner and outer diameters, and


49

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 50 of 68

membrane thickness. High resolution TEM and cryo-TEM observation also gave a direct evidence for the absence of any other nanometer-scale assemblies except for nanofibers or nanotubes. Moreover, UV/Vis and IR measurements revealed that no lipid molecules remain in the resultant filtrate after the filtration of self-assemblies-containing solutions. Of particular note is that in our research we have focused on the elucidation of polymorph and polytype of the MLM by taking the advantages of their crystalline properties of the nanotube. Simple unsymmetrical bolaamphiphiles with a bio-inspired wedge-shape gave various self-assembled SNTs made of 2−3 monolayers, even though diverse polymorph and polytype of the constituting MLMs form the membrane wall of each nanotube. Moreover, the preservation and polymer templating of the polymorph such as unsymmetrical MLMs were able to give SNTs made of 2−4 monolayers. In a sharp contrast, rationally designed bolaamphiphiles having oligoglycine moieties self-assembled into considerably homogeneous nanotubes characterized by a single monolayer and 3−4-nm inner diameters. In case of glucose tetraglycine bolaamphiphile as a carboxylate-terminated derivative, the self-assembly into the nanotubes simultaneously accompanies endo-complexation with anticancer platinum drug (CDDP). Binary and ternary coassembly, even though the procedure has been widely applied in the preparation of natural and synthetic bilayer-based membrane systems, were very efficient to localize a certain functionality for sensing, detecting, coordinating, and anchoring onto the inner or outer, or both surfaces at an appropriate distance. It is of great interest that the binary co-assembly combining glucose oligoglycine bolaamphiphiles with different numbers of glycine residue produced monolayerbased SNTs with inner diameters of 2−3 nm. Two-step self-assembly is also of great use to anchor a ligand site for metals or sensing site for Con A near around the inner or outer surfaces of SNTs, respectively. A single-chain, single-head glucose amphiphile or glucose amphiphile


50

Page 51 of 68

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

with a PEG chain as the third component functioned to drive a wedge into the void space of a preformed monolayer. TABLE 2 All the outstanding structures and novel functions of the unsymmetrical SNTs are currently making a great progress. The state of the art of intriguing SNTs will be the isolated nanochannels of 2−3-nm diameters in terms of nanofluidic devices.89 Those give the smallest self-assemblies among the lipid nanotubes reported so far. Amazing fluidic properties should emerge when the channels are smaller than 10 nm.110 Spatially confined and controllable hydrophilic inner surfaces are considerably favorable to study single-molecule-synthesis, transportation, -sequencing, and -sensing. Therefore, the SNTs with differentiable functionalities on the inner and outer surface can present a potential counterpart of hydrophobic carbon111-112 or inorganic nanotube channels.113 The diameter sizes comparable to single molecules, morphological robustness durable at relatively high temperatures (up to 90oC), and controllable dimensions also serve to explore novel phenomena expressed in confined volume spaces.110, 114115

The next challenging aspect is to freely manipulate and fabricate nanofluidic platforms to attain the purposes mentioned above. Aligning various 1-D nanostructures including nanowires, nanorods, and nanotubes is currently an emerging area of interest.116 A lot of work on the hierarchical structuring of SNTs on various solid substrate have also been achieved by the employment of various procedures including capillarity force,117 Langmuir-Blodget membrane,118 photolithography microfabrication,119 inkjet printing,120 solvent evaporation,121 vapor deposition,122 host−guest complexes,123-124 micro-extrusion,125 high-frequency AC electric field,126 and dielectrophoresis processes.127-128 However, the SNTs involved were almost formed


51

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 52 of 68

from multiple bilayers and the inner diameters are in a range of 50 nm−sub-µm.7 Frusawa et al. explored the state-of-the-art fabrication technique for nanofluidic device, which is based on offchip assembly system using plug-in electrode needles.128 Such a method enables the electrical moulding of 105 pieces of unsymmetrical SNTs (40-nm inner diameters and 6-µm lengths in average) into a separate film consisting of parallel SNT arrays. The reported unsymmetrical SNTs are able to accommodate outstandingly small liquid volumes on the order of attoliters.114 Benefitting from such situation, we have demonstrated the trapping of very limited number of molecules and nanostructures in the nanochannels. The third state of the art of the SNTs is the function as confinement effecters and chirality inducers for conjugated linear polymers.89 One cannot expect such encapsulation features for carbon, inorganic, and metal nanotubes. In contrast, by using, typically, cyclodextrins129-130 and polysaccharides such as schizophyllan,90-92 researchers have performed a large number of studies to address interesting molecular functions as a 1-D host. We are currently challenging ourselves to exploring the single-nm-scale host−guest-science, -chemistry, and -engineering by molecular assemblies, which are intended for linear polymers including proteins and DNAs. Summarizing the above, we do believe that the unsymmetrical SNTs should function as key soft devices and tools in nanomedicine, nanobiology, and nanomechanics.


52

Page 53 of 68

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

1 2-(n): n = 12, 14, 16, 18, and 20

3-(n): n = 12, 14, 16, 17, 18, and 20

4

5a-(n): n = 1, 2, and 3 (R = H)

5b-(3): R =

CDDP (6)

7

Chart 1. Molecular structures of unsymmetrical bolaamphiphiles and related compounds.


53

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 54 of 68

8: n = 18 9: n = 16

10

11

12-(n): n = 15 and 17

13

14-(n): n = 1, 3, and 5

15

16

17

18

19

Chart 2. Molecular structures of unsymmetrical bolaamphiphiles and related compounds.


54

Page 55 of 68

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

20: R =

21: R =

22 O HO

OH OH

H H

H

O

DOX (23)

DACH-Pt (24)

27

25

26

28

29

Chart 3. Molecular structures of unsymmetrical bolaamphiphiles and related compounds


55

Langmuir

TABLE 1. Experimental Tools and Various Criteria Utilized for the Identification of Polymorph and Polytype of Solid MLMs. polymorph & polytype

IR νas(CH2)a νs(CH2)b (cm-1)

TEM

ref.

single monolayer

bilayer of U-shaped molecules

36, 41, 57-60 2923~ 2928

IR δ(CH2)c (cm-1)

IR γ(CH2)d (cm-1)

IR CH def.e CH skl.f (cm-1)

XRD

single cryst. analysis

61-62

61-62

63-67

36, 41

46-50

− 2853~ 2860 (a)g

h

i

t ~L

2916~ 2920 2848~ 2850

(b) g

~1464 (single) T//j

719 (single) T// j

1420 1026

~1464 (single) T// j

t >> Li (e)

g

−

−

d l > Li/2

reported

719 (single) T// j

(d) g

h

d l~ Li d l < Li d l > Li

~1463 & ~1473 (double) O⊥ k

(c) g

multiple monolayers

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 56 of 68

2916~ 2920 2848~ 2850 ~1463 & ~1473 (double) O⊥ k

reported

(f) g

a

Antisymmetric stretching band. bSymmetric stretching band. cScissoring band. dRocking band. Deformation band. fSkeletal band. gThe same numbering as that in Figure 2. hMembrane thickness. iExtended molecular length calculated on the basis of molecular modelling. jTriclinic subcell structure. kOrthorhombic subcell structure. ld-spacing. e


56

Page 57 of 68

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

TABLE 2. Representative Dimensions of Unsymmetrical SNTs Self-assembled from Unsymmetrical Bolaamphiphiles via Various Strategy and Tactics. strategy and tacticsa

previous results

amphiphile

2-(n)

n

outer diameter

inner diameter

membrane thickness

numbers of layer

inner functional group

12

32.8b

20.6+1.9

6.1

2

−COOH

14

30.2 b

17.7+1.6

6.3

2

−COOH

16

31.6

b

18.7+1.6

6.5

2

−COOH

42.2

b

20.8+2.3

10.7

3

−COOH

35.6

b

22.3+2.1

6.7

2

−COOH

110

80

15

4

−NH2c

41

18

32 b

20

9

2

−NH3+, d

40

20

110~120

70~100

8

2

−NH2c

41

67.9

e

~36

~12

−NH2

e

~28

~8

−NH2

18 20

(a)

3-(n)

12

∼105

ref.

36

14

∼100

69.1

16

∼110

74.3 e

~35

~10

−NH2

17

∼95

79.2 e

~15

~4

−NH2

18

110

79.6 e

15

4

−NH2

20

∼98

82 f

8

2

−NH2

5a-(3)

13~17

7~9

3~4

1

−NH2

42

8

16

8

4

1

−NH2

44

9

15

9

3

1

−NH2

10

16

8

4

1

−COOH

45, 52 44

19

15~16

7.0~7.5

4.3

1

−COOH

37

7+6

14

6.7

3.7

1

-Pt(NH2)2

38

8 + 11

16

8

4

1

44

5a-(3) + 5b-(3)

15∼18

9~10

3~4

1

5a-(3) +13

13~17

7~9

3~4

1

−NH2 + pyridine carboxylate −NH2 + −NH(Alexa) −NH2

76

5a-(3) + 5a-(1)

6∼11

2~3

2~4

1

−NH2

89

5a-(3) + 5a-(2)

8∼13

4~5

2~4

1

−NH2

89

(f-1)

8 + 11 + 12-(17)

16

8

4

1

44

(f-2)

5a-(3) + 13 + 14(n)

13~17

7~9

3~4

1

−NH2 + pyridine carboxylate glucose (−OH) with EG chaing

16~18

7~9

3~4

1

(b)

(c)

(d)

(e)

(g-1)

3-(n) + 4

15 + 16 + 17

1, 2, and 3

−COOH + PEGg + DOTA

43

74

76

77


57

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

(g-2)

2-(18) + 15 + 16

32.8

15.0

Page 58 of 68

8.9

~3

−NH2 + Arg + EGg

78

a

Strategy and tactics: (a) polymorph control, (b) polymer template, (c) multiple hydrogen bond, (d) endo-complexation, (e) binary co-assembly, (f-1 and f-2) two-step self-assembly, and (g-1 and g-2) ternary co-assembly. bOuter diameter measured for a certain piece of SNT. cUpon selfassembly at < pH 10. dUpon self-assembly at < pH 6. eAverage inner diameters obtained from measured 100 pieces of SNTs. fMeasured by atomic force microscopy. All other values except for the 3-(20)/PTB hybrid were measured by STEM. gFunctional groups are located on the outer surface.

AUTHOR INFORMATION Corresponding Author *Tel: +81-29-861-6265; Fax: +81-29-861-4545. E-mail address: [email protected] Author Contributions The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. Notes The authors declare no competing financial interest.

ACKNOWLEDGMENT We thank our colleagues, including Drs. Hiroyuki Minamikawa, Masaki Kogiso, and Masaru Aoyagi of AIST, for their enthusiastic collaboration.

ABBREVIATIONS


58

Page 59 of 68

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

SNT, soft nanotube; MLM, monolayer lipid membrane; TMV, tobacco mosaic virus; EG, ethylene glycol; PEG, polyethylene glycol; SEM, scanning electron microscopy; TEM, transmission electron microscopy; IR, infrared spectroscopy; XRD, X-ray diffraction; AFM, atomic force microscopy; DMF, dimethylformamide; DSC, differential scanning colorimetry, LM, polarized light microscopy; VT-XRD, variable-temperature X-ray diffraction; VT-IR, variable-temperature infra-red spectroscopy; STEM, scanning transmission electron microscopy; PTB, poly(thiopheneboronic acid); 1-D, one-dimensional; Cbz, benzyloxycarbonyl; t-Boc, tertbutyloxycarbonyl; Tg-l, gel-to-liquid crystalline phase transition temperature; Con A, Concanavalin A; DOTA, tetraazacyclododecane tetraacetic acid; PBS, phosphate-buffered saline; GFP, green fluorescent protein; CAB, carbonic anhydrase; CS, citrate synthase; DOX, doxorubicin; HEPES, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid, ICP-AES, inductively coupled plasma-atomic emission spectroscopy; CD, circular dichroism; DMSO, dimethyl sulfoxide; PDA, polydopamine.


59

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 60 of 68

REFERENCES (1) (2)

(3) (4) (5) (6) (7) (8) (9)

(10)

(11) (12) (13)

(14)

(15) (16) (17) (18)

Kunitake, T.; Okahata, Y. A Totally Synthetic Bilayer Membrane. J. Am. Chem. Soc. 1977, 99, 3860−3861. Fuhrhop, J. H.; Koening, J. Membranes and Molecular Assemblies: The Synkinetic Approach. In Monographs in Supramolecular Chemistry, Stoddart, J. F., Ed. The Royal Society of Chemistry: Cambridge, 1994. Kunitake, T. Synthetic Bilayer Membrane: Molecular Design, Self-Organization, and Application. Angew. Chem., Int. Ed. Engl. 1992, 31, 709−726. Fuhrhop, J. H.; Helfrich, W. Fluid and Solid Fibers Made of Lipid Molecular Bilayers. Chem. Rev. 1993, 93, 1565−1582. Nakashima, N.; Asakuma, S.; Kim, J. M.; Kunitake, T. Helical Superstructures Are Formed from Chiral Ammonium Bilayers. Chem. Lett. 1984, 13, 1709−1712. Nakashima, N.; Asakuma, S.; Kunitake, T. Optical Microscopic Study of Helical Superstructures of Chiral Bilayer Membranes. J. Am. Chem. Soc. 1985, 107, 509−510. Shimizu, T.; Masuda, M.; Minamikawa, H. Supramolecular Nanotube Architectures Based on Amphiphilic Molecules. Chem. Rev. 2005, 105, 1401−1443. Barclay, T. G.; Constantopoulos, K.; Matisons, J. Nanotubes Self-Assembled from Amphiphilic Molecules via Helical Intermediates. Chem. Rev. 2014, 114, 10217−10291. Yamada, K.; Ihara, H.; Ide, T.; Fukumoto, T.; Hirayama, C. Formation of Helical Super Structure from Single-Walled Bilayers by Amphiphiles with Oligo-L-Glutamic Acid-Head Group. Chem. Lett. 1984, 13, 1713−1716. Ihara, H.; Fukumoto, T.; Hirayama, C.; Yamada, K. Formation and Metamorphosis of Superstructures from Single-Walled Bilayer Membranes by Acidic Polymino Acids. Journal of The Chemical Society of Japan, Chemistry and Industrial Chemistry 1987, 3, 543−549. Ihara, H.; Takafuji, M.; Hirayama, C.; O'Brien, D. F. Effect of Photopolymerization on the Morphology of Helical Supramolecular Assemblies. Langmuir 1992, 8, 1548−1553. Yager, P.; Schoen, P. E. Formation of Tubules by Polymerizable Surfactant. Mol. Cryst. Liq. Cryst. 1984, 106, 371−381. Schoen, P. E.; Yager, P. Spectroscopic Studies of Polymerized Surfactants: 1,2-Bis(10,12tricosadiynoyl)-sn-glycero-3-phosphocholin. J. Polym. Sci., Polym. Phys. Ed. 1985, 23, 2203−2216. Georger, J. H.; Singh, A.; Price, R. R.; Schnur, J. M.; Yager, P.; Schoen, P. E. Helical aneTubular Microstructures Formed by Polymerizable Phosphatidylchholimes. J. Am. Chem. Soc. 1987, 109, 6169−6175. Rudolph, A. S.; Calvert, J. M.; Ayers, M. E.; Schnur, J. M. Water-Free Self-Assembly of Phospholipid Tubules. J. Am. Chem. Soc. 1989, 111, 8516−8517. Schnur, J. M. Lipid Tubules: A Paradigm for Molecularly Engineered Structures. Science 1993, 262, 1669−1676. Fuhrhop, J. H.; Bartsch, H.; Fritsch, D. Colored, Unsymmetric and Light-Sensitive Vesicle Membranes. Angew. Chem., Int. Ed. Engl. 1981, 20, 804−805. Fuhrhop, J. H.; Spiroski, D.; Boettcher, C. Molecular Monolayer Rods and Tubules Made of α-(L-Lysine),ω-(Amino) Bolaamphiphiles. J. Am. Chem. Soc. 1993, 115, 1600−1601.


60

Page 61 of 68

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

(19) Kameta, N.; Minamikawa, H.; Masuda, M. Supramolecular Organic Nanotubes: How to Utilize the Inner Nanospace and the Outer Space. Soft Matter 2011, 7, 4539−4561. (20) Shimizu, T.; Minamikawa, H.; Kogiso, M.; Aoyagi, M.; Kameta, N.; Ding, W. X.; Masuda, M. Self-Organized Nanotube Materials and Their Application in Bioengineering. Polym. J. 2014, 46, 831−858. (21) Delclos, T.; Aime, C.; Pouget, E.; Brizard, A.; Huc, I.; Delville, M. H.; Oda, R. Individualized Silica Nanohelices and Nanotubes: Tuning Inorganic Nanostructures Using Lipidic Self-assemblies. Nano Lett. 2008, 8, 1929−1935. (22) Oda, R.; Artzner, F.; Laguerre, M.; Huc, I. Molecular Structure of Self-Assembled Chiral Nanoribbons and Nanotubules Revealed in the Hydrated State. J. Am. Chem. Soc. 2008, 130, 14705−14712. (23) Aida, T.; Meijer, E. W.; Stupp, S. I. Functional Supramolecular Polymers. Science 2012, 335, 813−817. (24) Sendai, T.; Biswas, S.; Aida, T. Photoreconfigurable Supramolecular Nanotube. J. Am. Chem. Soc. 2013, 135, 11509−11512. (25) Komatsu, T. Protein-based Nanotubes for Biomedical Applications. Nanoscale 2012, 4, 1910−1918. (26) Gubitosi, M.; Travaglini, L.; di Gregorio, M. C.; Pavel, N. V.; Tato, J. V.; Sennato, S.; Olsson, U.; Schillen, K.; Galantini, L. Tailoring Supramolecular Nanotubes by Bile Salt Based Surfactant Mixtures. Angew. Chem. Int. Edit. 2015, 54, 7018−7021. (27) Gao, X. Y.; Matsui, H. Peptide-based Nanotubes and Their Applications in Bionanotechnology. Adv. Mater. 2005, 17 , 2037−2050. (28) Fang, J. Y. Ordered Arrays of Self-assembled Lipid Tubules: Fabrication and Applications. J. Mater. Chem. 2007, 17, 3479−3484. (29) Gazit, E. Self-assembled Peptide Nanostructures: the Design of Molecular Building Blocks and Their Technological Utilization. Chem. Soc. Rev. 2007, 36, 1263−1269. (30) Yamamoto, T.; Fukushima, T.; Aida, T. Self-Assembled Nanotubes and Nanocoils from πConjugated Building Blocks. In Self-Assembled Nanomaterials II: Nanotubes 2008, 220, 1−27, Shimizu, T., Ed. Springer: Berlin, 2008. (31) Liu, G. J. Block Copolymer Nanotubes Derived from Self-Assembly. In Self-Assembled Nanomaterials II: Nanotubes 2008, 220, 29−64, Shimizu, T., Ed. Springer: Berlin, 2008. (32) Lizana, L.; Konkoli, Z.; Bauer, B.; Jesorka, A.; Orwar, O. Controlling Chemistry by Geometry in Nanoscale Systems. Annu. Rev. Phys. Chem. 2009, 60, 449−468. (33) Fuhrhop, J. H.; Wang, T. Bolaamphiphiles. Chem. Rev. 2004, 104, 2901−2938. (34) Markowitz, M. A.; Schnur, J. M.; Singh, A. The Influence of the Polar Headgroups of Acidic Diacetylenic Phospholipids on Tubule Formation, Microstructure Morphology and Langmuir Film Behavior. Chem. Phys. Lipids 1992, 62, 193−204. (35) Singh, A.; Wong, E. M.; Schnur, J. M. Toward the Rational Control of Nanoscale Structures Using Chiral Self-assembly: Diacetylenic Phosphocholines. Langmuir 2003, 19, 1888−1898. (36) Masuda, M.; Shimizu, T. Lipid Nanotubes and Microtubes: Experimental Evidence for Unsymmetrical Monolayer Membrane Formation from Unsymmetrical Bolaamphiphiles. Langmuir 2004, 20, 5969−5977.


61

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 62 of 68

(37) Ding, W. X.; Kameta, N.; Minamikawa, H.; Wada, M.; Shimizu, T.; Masuda, M. Hybrid Organic Nanotubes with Dual Functionalities Localized on Cylindrical Nanochannels Control the Release of Doxorubicin. Adv. Healthcare Mater. 2012, 1, 699−706. (38) Ding, W. X.; Wada, M.; Minamikawa, H.; Kameta, N.; Masuda, M.; Shimizu, T. CisplatinEncapsulated Organic Nanotubes by endo-Complexation in the Hollow Cylinder. Chem. Commun. 2012, 48, 8625−8627. (39) Kameta, N.; Masuda, M.; Minamikawa, H.; Goutev, N. V.; Rim, J. A.; Jung, J. H.; Shimizu, T. Selective Construction of Supramolecular Nanotube Hosts with Cationic Inner Surfaces. Adv. Mater. 2005, 17, 2732−2736. (40) Kameta, N.; Masuda, M.; Minamikawa, H.; Mishima, Y.; Yamashita, I.; Shimizu, T. Functionalizable Organic Nanochannels Based on Lipid Nanotubes: Encapsulation and Nanofluidic Behavior of Biomacromolecules. Chem. Mater. 2007, 19, 3553−3560. (41) Kameta, N.; Masuda, M.; Minamikawa, H.; Shimizu, T. Self-Assembly and Thermal Phase Transition Behavior of Unsymmetrical Bolaamphiphiles Having Glucose- and AminoHydrophilic Headgroups. Langmuir 2007, 23, 4634−4641. (42) Kameta, N.; Mizuno, G.; Masuda, M.; Minamikawa, H.; Kogiso, M.; Shimizu, T. Molecular Monolayer Nanotubes Having 7−9 nm Inner Diameters Covered with Different Inner and Outer Surfaces. Chem. Lett. 2007, 36, 896−897. (43) Kameta, N.; Ishikawa, K.; Masuda, M.; Shimizu, T. Control of Self-assembled Morphology and Molecular Packing of Asymmetric Glycolipids by Association/Dissociation with Poly(thiopheneboronic acid). Langmuir 2013, 29, 13291−13298. (44) Kameta, N.; Lee, S. J.; Masuda, M.; Shimizu, T. BiologicallyResponsive, Sustainable Release from Metallo-Drug Coordinated 1D Nanostructures. J. Mater. Chem. B 2013, 1, 276−283. (45) Kameta, N.; Masuda, M.; Shimizu, T. Soft Nanotube Hydrogels Functioning as Artificial Chaperones. Acs Nano 2012, 6, 5249−5258. (46) Aigouy, P. T.; Costeseque, P.; Sempere, R.; Senac, T. Caractérisation Structurale et Évolution Thermiquue de I’acide Amino-11-undécanoïque(C11H23NO2.1,5H2O). Acta Cystallogr. 1995, B51, 55−61. (47) Szafran, M.; Dega-Szafran, Z.; Katrusiak, A.; Buczak, G.; Glowiak, T.; Sitkowski, J.; Stefaniak, L. Electrostatic Interactions and Conformations of Zwitterionic Pyridinium Alkanoates. J. Org. Chem. 1998, 63, 2898−2908. (48) Sim, G. A. The Crystal Structure of 11-Amino-Undecanoic Acid Hydrobromide Hemihydrate. Acta Crystallogr. 1955, 8, 833−840. (49) Masuda, M.; Shimizu, T. Multilayer Structure of Unsymmetrical Monolayer Lipid Membrane with Head-to-Tail Interface. Chem. Commun. 2001, 2442−2443. (50) Masuda, M.; Yoza, K.; Shimizu, T. Polymorphism of Monolayer Lipid Membrane Structures Made from Unsymmetrical Bolaamphiphiles. Carbohydr. Res. 2005, 340, 2502−2509. (51) Stubbs, G. Molecular Structures of Viruses from the Tobacco Mosaic Virus Group. Semin. Virol. 1990, 1, 405−409. (52) Kameta, N.; Yoshida, K.; Masuda, M.; Shimizu, T. Supramolecular Nanotube Hydrogels: Remarkable Resistance Effect of Confined Proteins to Denaturants. Chem. Mater. 2009, 21, 5892−5898.


62

Page 63 of 68

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

(53) Moss, R. A.; Fujita, T.; Okumura, Y. Dynamics of a Bolaamphiphilic Lipid in a Bilayer Liposome. Langmuir 1991, 7 , 2415−2418. (54) Gu, Q.; Zou, A. H.; Yuan, C. W.; Guo, R. Effects of a Bolaamphiphile on the Structure of Phosphatidylcholine Liposomes. J. Colloid Interface Sci. 2003, 266, 442−447. (55) Kohler, K.; Meister, A.; Dobner, B.; Drescher, S.; Ziethe, F.; Blume, A. TemperatureDependent Aggregation Behavior of Symmetric Long-Chain Bolaamphiphiles at the AirWater Interface. Langmuir 2006, 22, 2668−2675. (56) Baek, K.; Kim, Y.; Kim, H.; Yoon, M.; Hwang, I.; Ko, Y. H.; Kim, K. Unconventional UShaped Conformation of a Bolaamphiphile Embedded in a Synthetic Host. Chem. Commun. 2010, 46, 4091−4093. (57) Masuda, M.; Vill, V.; Shimizu, T. Conformational and Thermal Phase Behavior of Oligomethylene Chains Constrained by Carbohydrate Hygrogen-Bond Networks. J. Am. Chem. Soc. 2000, 122, 12327−12333. (58) Snyder, R. G.; Hsu, S. L.; Krimm, S. Vibrational-Spectra in C-H Stretching Region and Structure of Polymethylene Chain. Spectrochim. Acta A 1978, 34, 395−406. (59) Snyder, R. G.; Strauss, H. L. C-H Stretching Modes and the Structure of n-Alkyl Chains. 1. Long, Disordered Chains. J. Phys. Chem. 1982, 86, 5145−5150. (60) Mantsch, H. H.; McElhaney, R. N. Phospholipid Phase Transtions in Model and Biological Membranes as Studied by Infrared Spectroscopy. Chem. Phys. Lipids 1991, 57, 213−226. (61) Garti, N.; Sato, K. Crystallization and Polymorphism of Fats and Fatty Acids. Marcel Dekker: 1988. (62) Yamada, N.; Okuyama, K.; Serizawa, T.; Kawasaki, M.; Oshima, S. Periodic Change in Absorption Maxima due to Different Chain Packing Between the Bilayers of Amphiphiles Possessing Even and Odd Numbers of Carbons in the Hydrophobic Chain. J. Chem. Soc., Perkin Trans. 2 1996, 2707−2714. (63) Blout, E. L.; Linsley, S. G. Infrared Spectra and the Structure of Glycine and Leucine Peptides. J. Am. Chem. Soc. 1952, 74, 1946−1951. (64) Elliott, A.; Malcolm, B. R. Infra-Red Studies of Polypeptides Related to Silk. Trans. Faraday Society 1956, 52, 528−536. (65) Crick, F. H. C.; Rich, A. Structure of Polyglycine II. Nature 1955, 176, 780−781. (66) Bamford, C. H.; Brown, L.; Cant, E. M.; Elliott, A.; Hanby, W. E.; Malcolm, B. R. Structure of Polyglycine. Nature 1955, 176, 396−397. (67) Shimizu, T.; Kogiso, M.; Masuda, M. Noncovalent Formation of Polyglycine II-Type Structure by Hexagonal Self-Assembly of Linear Polymolecular Chains. J. Am. Chem. Soc. 1997, 119, 6209−6210. (68) Nishiyama, N.; Yokoyama, M.; Aoyagi, T.; Okano, T.; Sakurai, Y.; Kataoka, K. Preparation and Characterization of Self-Assembled Polymer-Metal Complex Micelle from cis-Dichlorodiammineplatinum(II) and Poly(ethylene glycol)-poly(α,β-aspartic acid) Block Copolymer in an Aqueous Medium. Langmuir 1999, 15, 377−383. (69) Paraskar, A. S.; Soni, S.; Chin, K. T.; Chaudhuri, P.; Muto, K. W.; Berkowitz, J.; Handlogten, M. W.; Alves, N. J.; Bilgicer, B.; Dinulescu, D. M.; Mashelkar, R. A.; Sengupta, S. Harnessing Structure-Activity Relationship to Engineer a Cisplatin Nanoparticle for Enhanced Antitumor Efficacy. Proc. Natl. Acad. Sci. U.S.A. 2010, 107, 12435−12440.


63

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 64 of 68

(70) Zhu, W.; Li, Y. L.; Liu, L. X.; Chen, Y. M.; Wang, C.; Xi, F. Supramolecular Hydrogels from Cisplatin-Loaded Block Copolymer Nanoparticles and α-Cyclodextrins with a Stepwise Delivery Property. Biomacromolecules 2010, 11, 3086−3092. (71) Kim, J. K.; Anderson, J.; Jun, H. W.; Repka, M. A.; Jo, S. Self-Assembling Peptide Amphiphile-Based Nanofiber Gel for Bioresponsive Cisplatin Delivery. Mol. Pharm. 2009, 6, 978−985. (72) Kogiso, M.; Zhou, Y.; Shimizu, T. Instant Preparation of Self-Assembled MetalComplexed Lipid Nanotubes That Act as Templates to Produce Metal Oxide Nanotubes. Adv. Mater. 2007, 19, 242−246. (73) Mukai, M.; Aoyagi, M.; Minamikawa, H.; Asakawa, M.; Shimizu, T.; Kogiso, M. A Simple N-Acyl-L-amino Acid Constructed Metal-Complexed Organic Nanotube Having an Inner Diameter below 10 nm. Chem. Lett. 2011, 40, 218−220. (74) Kameta, N.; Masuda, M.; Mizuno, G.; Morii, N.; Shimizu, T. Supramolecular Nanotube endo Sensing for a Guest Protein. Small 2008, 4, 561−565. (75) Kameta, N.; Minamikawa, H.; Someya, Y.; Yui, H.; Masuda, M.; Shimizu, T. Confinement Effect of Organic Nanotubes Toward Green Fluorescent Protein (GFP) Depending on the Inner Diameter Size. Chem.-Eur. J. 2010, 16, 4217−4223. (76) Kameta, N.; Masuda, M.; Shimizu, T. Two-Step Naked-Eye Detection of Lectin by Hierarchical Organization of Soft Nanotubes into Liquid Crystal and Gel Phases. Chem. Commun. 2015, 51, 6816−6819. (77) Ding, W. X.; Minamikawa, H.; Kameta, N.; Shimizu, T.; Masuda, M. Effects of PEGylation on the Physicochemical Properties and in vivo Distribution of Organic Nanotubes. Int. J. Nanomed. 2014, 9, 5811−5823. (78) Ding, W. X.; Wada, M.; Kameta, N.; Minamikawa, H.; Shimizu, T.; Masuda, M. Functionalized Organic Nanotubes as Tubular Nonviral Gene Transfer Vector. J. Controlled Release 2011, 156, 70−75. (79) Meyer, O.; Kirpotin, D.; Hong, K. L.; Sternberg, B.; Park, J. W.; Woodle, M. C.; Papahadjopoulos, D. Cationic Liposomes Coated with Polyethylene Glycol as Carriers for Oligonucleotides. J. Biol. Chem. 1998, 273, 15621−15627. (80) Sasaki, Y.; Asayama, W.; Niwa, T.; Sawada, S.; Ueda, T.; Taguchi, H.; Akiyoshi, K. Amphiphilic Polysaccharide Nanogels as Artificial Chaperones in Cell-Free Protein Synthesis. Macromol. Biosci. 2011, 11, 814−820. (81) Sasaki, Y.; Akiyoshi, K. Nanogel Engineering for New Nanobiomaterials: From Chaperoning Engineering to Biomedical Applications. Chemical Record 2010, 10, 366−376. (82) Wakasugi, A.; Asakawa, M.; Kogiso, M.; Shimizu, T.; Sato, M.; Maitani, Y. Organic Nanotubes for Drug Loading and Cellular Delivery. Int. J. Pharm. 2011, 413, 271−278. (83) Moribe, K.; Makishima, T.; Higashi, K.; Liu, N.; Limwikrant, W.; Ding, W. X.; Masuda, M.; Shimizu, T.; Yamamoto, K. Encapsulation of Poorly Water-Soluble Drugs into Organic Nanotubes for Improving Drug Dissolution. Int. J. Pharm. 2014, 469, 190−196. (84) Immordino, M. L.; Dosio, F.; Cattel, L. Stealth Liposomes: Review of the Basic Science, Rationale, and Clinical Applications, Existing and Potential. Int. J. Nanomed. 2006, 1, 297−315.


64

Page 65 of 68

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

(85) Andresen, T. L.; Jensen, S. S.; Jorgensen, K. Advanced Strategies in Liposomal Cancer Therapy: Problems and Prospects of Active and Tumor Specific Drug Release. Prog. Lipid Res. 2005, 44, 68−97. (86) Pasut, G.; Veronese, F. M. Polymer-Drug Conjugation, Rrecent Achievements and General Strategies. Prog. Polym. Sci. 2007, 32, 933−961. (87) Kataoka, K.; Harada, A.; Nagasaki, Y. Block Copolymer Micelles for Drug Delivery: Design, Characterization and Biological Significance. Adv. Drug Deliver Rev. 2012, 64, 37−48. (88) Geng, Y.; Dalhaimer, P.; Cai, S. S.; Tsai, R.; Tewari, M.; Minko, T.; Discher, D. E. Shape Effects of Filaments versus Spherical Particles in Flow and Drug Delivery. Nat. Nanotechnol. 2007, 2, 249−255. (89) Kameta, N.; Masuda, M.; Shimizu, T. Soft Nanotubes Acting as Confinement Effecters and Chirality Inducers for Achiral Polythiophenes. Chem. Commun. 2016, 52, 1346−1349. (90) Li, C.; Numata, M.; Bae, A. H.; Sakurai, K.; Shinkai, S. Self-Assembly of Supramolecular Chiral Insulated Molecular Wire. J. Am. Chem. Soc. 2005, 127, 4548−4549. (91) Numata, M. Creation of Unique Supramolecular Nanoarchitectures Utilizing Natural Polysaccharide as a One-Dimensional Host. J. Incl. Phenom. Macrocycl. Chem. 2010, 68, 25−47. (92) Numata, M.; Shinkai, S. Supramolecular Wrapping Chemistry by Helix-Forming Polysaccharides: a Powerful Strategy for Generating Diverse Polymeric NanoArchitectures. Chem. Commun. 2011, 47, 1961−1975. (93) Liebscher, J.; Mrowczynski, R.; Scheidt, H. A.; Filip, C.; Hadade, N. D.; Turcu, R.; Bende, A.; Beck, S. Structure of Polydopamine: A Never-Ending Story? Langmuir 2013, 29, 10539−10548. (94) Liu, Y. L.; Ai, K. L.; Lu, L. H. Polydopamine and Its Derivative Materials: Synthesis and Promising Applications in Energy, Environmental, and Biomedical Fields. Chem. Rev. 2014, 114, 5057−5115. (95) Perikamana, S. K. M.; Lee, J.; Lee, Y. B.; Shin, Y. M.; Lee, E. J.; Mikos, A. G.; Shin, H. Materials from Mussel-Inspired Chemistry for Cell and Tissue Engineering Applications. Biomacromolecules 2015, 16, 2541−2555. (96) Yang, H. C.; Luo, J. Q.; Lv, Y.; Shen, P.; Xu, Z. K. Surface Eengineering of Polymer Membranes via Mussel-Inspired Chemistry. J. Membrane Sci. 2015, 483, 42−59. (97) Yu, X.; Fan, H. L.; Wang, L.; Jin, Z. X. Formation of Polydopamine Nanofibers with the Aid of Folic Acid. Angew. Chem. Int. Edit. 2014, 53, 12600−12604. (98) Ding, W. X.; Chechetka, S. A.; Masuda, M.; Shimizu, T.; Aoyagi, M.; Minamikawa, H.; Miyako, E. Lipid Nanotube Tailored Fabrication of Uniquely Shaped Polydopamine Nanofibers as Photothermal Converters. Chem.-Eur. J. 2016, 22, 4345−4350. (99) Jiang, X. L.; Wang, Y. L.; Li, M. G. Selecting Water-Alcohol Mixed Solvent for Synthesis of Polydopamine Nano-Spheres Using Solubility Parameter. Sci. Rep. 2014, 4, 6070 DOI: 10.1038/srep06070. (100) Zweckstetter, M.; Bax, A. Characterization of Molecular Alignment in Aqueous Suspensions of Pf1 Bacteriophage. J. Biomol. NMR 2001, 20, 365−377. (101) Leferink Op Reinink, A. B. G. M.; van den Pol, E.; Petukhov, A. V.; Vroege, G. J.; Lekkerkerker, H. N. W. Phase Behaviour of Lyotropic Liquid Crystals in External Fields and Confinement. Eur. Phys. J-Spec. Top. 2013, 222, 3053−3069.


65

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 66 of 68

(102) Pomerantz, W. C.; Yuwono, V. M.; Pizzey, C. L.; Hartgerink, J. D.; Abbott, N. L.; Gellman, S. H. Nanofibers and Lyotropic Liquid Crystals from a Class of Self-Assembling β-Peptides. Angew. Chem. Int. Edit. 2008, 47, 1241−1244. (103) Lu, M. H.; Rosenblatt, C. Observation of a Nematic Phase in an Aqueous Suspension of Phospholipid Tubules. Mol. Cryst. Liq. Cryst. 1992, 210, 169−177. (104) Jean, B.; Oss-Ronen, L.; Terech, P.; Talmon, Y. Monodisperse Bile-Salt Nanotubes in Water: Kinetics of Formation. Adv. Mater. 2005, 17, 728−731. (105) Onsager, L. The Effects of Shape on the Interaction of Colloidal Particles. Ann. N.Y. Acad. Sci. 1949, 51, 627−659. (106) Ding, W. X.; Minamikawa, H.; Kameta, N.; Wada, M.; Masuda, M.; Shimizu, T. Spontaneous Nematic Alignment of a Lipid Nanotube in Aqueous Solutions. Langmuir 2015, 31, 1150−1154. (107) John, G.; Minamikawa, H.; Masuda, M.; Shimizu, T. Liquid Crystalline Cardanyl β-DGlucopyranosides. Liq. Cryst. 2003, 30, 747−749. (108) Terech, P.; Jean, B.; Ne, F. Hexagonally Ordered Ammonium Lithocholate SelfAssembled Nanotubes with Highly Monodisperse Sections. Adv. Mater. 2006, 18, 1571−1574. (109) Fraden, S.; Maret, G.; Caspar, D. L. D. Angular-Correlations and the Isotropic-Nematic Phase-Transition in Suspensions of Tobacco Mosaic-Virus. Phys. Rev. E 1993, 48, 2816−2837. (110) Bocquet, L.; Charlaix, E. Nanofluidics, From Bulk to Interfaces. Chem. Soc. Rev. 2010, 39, 1073−1095. (111) Oh, J.; Kim, G.; Mattia, D.; Noh, H. A Novel Technique for Fabrication of Micro- and Nanofluidic Device with Embedded Single Carbon Nanotube. Sensor Actuat. B-Chem. 2011, 154, 67−72. (112) Guo, S. R.; Meshot, E. R.; Kuykendall, T.; Cabrini, S.; Fornasiero, F. Nanofluidic Transport through Isolated Carbon Nanotube Channels: Advances, Controversies, and Challenges. Adv. Mater. 2015, 27, 5726−5737. (113) Siria, A.; Poncharal, P.; Biance, A. L.; Fulcrand, R.; Blase, X.; Purcell, S. T.; Bocquet, L. Giant Osmotic Energy Conversion Measured in a Single Transmembrane Boron Nitride Nanotube. Nature 2013, 494, 455−458. (114) Shimizu, T. Self-Assembled Organic Nanotubes: Toward Attoliter Chemistry. J. Polym. Sci. Polym. Chem. 2008, 46, 2601−2611. (115) Mawatari, K.; Kazoe, Y.; Shimizu, H.; Pihosh, Y.; Kitamori, T. Extended-Nanofluidics: Fundamental Technologies, Unique Liquid Properties, and Application in Chemical and Bio Analysis Methods and Devices. Anal. Chem. 2014, 86, 4068−4077. (116) Su, B.; Wu, Y. C.; Jiang, L. The Art of Aligning One-Dimensional (1D) Nanostructures. Chem. Soc. Rev. 2012, 41, 7832−7856. (117) Zhao, Y.; Fang, J. Y. Direct Printing of Self-Assembled Lipid Tubules on Substrates. Langmuir 2008, 24, 5113−5117. (118) Zhao, Y.; Fang, J. Y. Positioning and Alignment of Lipid Tubules on Patterned Au Substrates. Langmuir 2006, 22, 1891−1895. (119) Sopher, N. B.; Abrams, Z. R.; Reches, M.; Gazit, E.; Hanein, Y. Integrating Peptide Nanotubes in Micro-Fabrication Processes. J. Micromech. Microeng. 2007, 17, 2360−2365.


66

Page 67 of 68

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

(120) Adler-Abramovich, L.; Gazit, E. Controlled Patterning of Peptide Nanotubes and Nanospheres Using Inkjet Printing Technology. J. Pept. Sci. 2008, 14, 217−223. (121) Reches, M.; Gazit, E. Controlled Patterning of Aligned Self-Assembled Peptide Nanotubes. Nat. Nanotechnol. 2006, 1, 195−200. (122) Adler-Abramovich, L.; Aronov, D.; Beker, P.; Yevnin, M.; Stempler, S.; Buzhansky, L.; Rosenman, G.; Gazit, E. Self-Assembled Arrays of Peptide Nanotubes by Vapour Deposition. Nat. Nanotechnol. 2009, 4, 849−854. (123) Banerjee, I. A.; Yu, L.; Matsui, H. Application of Host-Guest Chemistry in NanotubeBased Device Fabrication: Photochemically Controlled Immobilization of Azobenzene Nanotubes on Patterned α-CD Monolayer/Au Substrates via Molecular Recognition. J. Am. Chem. Soc. 2003, 125, 9542−9543. (124) Zhao, Z.; Matsui, H. Accurate Immobilization of Antibody-Functionalized Peptide Nanotubes on Protein-Patterned Arrays by Optimizing Their Ligand-Receptor Interactions. Small 2007, 3, 1390−1393. (125) Guo, Y.; Yui, H.; Fukagawa, A.; Kamiya, S.; Masuda, M.; Ito, K.; Shimizu, T. Alignment of Glycolipid Nanotubes on a Planar Glass Substrate Using a Two-Step Microextrusion Technique. J. Nanosci. Nanotechno. 2006, 6, 1464−1466. (126) Hirano, K.; Aoyagi, M.; Ishido, T.; Ooie, T.; Frusawa, H.; Asakawa, M.; Shimizu, T.; Ishikawa, M. Measuring the Length Distribution of Self-Assembled Lipid Nanotubes by Orientation Control with a High-Frequency Alternating Current Electric Field in Aqueous Solutions. Anal. Chem. 2009, 81, 1459−1464. (127) de la Rica, R.; Mendoza, E.; Lechuga, L. M.; Matsui, H. Label-Free Pathogen Detection with Sensor Chips Assembled from Peptide Nanotubes. Angew. Chem. Int. Edit. 2008, 47, 9752−9755. (128) Frusawa, H.; Manabe, T.; Kagiyama, E.; Hirano, K.; Kameta, N.; Masuda, M.; Shimizu, T. Electric Moulding of Dispersed Lipid Nanotubes into a Nanofluidic Device. Sci. Rep. 2013, 3, 2165 DOI: 10.1038/srep02165. (129) Harada, A.; Takashima, Y.; Yamaguchi, H. Cyclodextrin-Based Supramolecular Polymers. Chem. Soc. Rev. 2009, 38, 875−882. (130) Hashidzume, A.; Harada, A. Recognition of Polymer Side Chains by Cyclodextrins. Polym. Chem. 2011, 2, 2146−2154.


67

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 68 of 68

Table of Contents Graphic and Synopsis

KEYWORDS Supramolecular self-assembly, soft nanotube, bilayer, monolayer, organic nanotube, bolaamphiphile, unsymmetrical monolayer membrane, polymorph, polytype


68

Supramolecular Self-Assembly into Biofunctional Soft Nanotubes

Recommend Documents