Supra-Amphiphiles: A New Bridge Between Colloidal Science and

Invited Feature Article pubs.acs.org/Langmuir

Supra-Amphiphiles: A New Bridge Between Colloidal Science and Supramolecular Chemistry Yuetong Kang, Kai Liu, and Xi Zhang* The Key Lab of Organic Optoelectronics & Molecular Engineering, Department of Chemistry, Tsinghua University, Beijing 100084, PR China ABSTRACT: In addition to conventional amphiphiles, an emerging research area is supra-amphiphiles, which are constructed on the basis of noncovalent interactions and dynamic covalent bonds. In this feature article, we have provided a general introduction to the concept, design principles, and topologies of supra-amphiphiles, starting from some rationally tailored building blocks. In addition, we highlight some progress in the functional assembly of supraamphiphiles, such as responsive nanoscale carriers, antibacterial and antitumor agents, fluorescent-based chemical sensors, and enzyme mimics. The supra-amphiphile is a new bridge between colloidal science and supramolecular chemistry, and it is a field where we can make full use of our imaginative power.

1. INTRODUCTION Amphiphiles are molecules that contain both hydrophilic and hydrophobic parts, and the two parts are usually connected by covalent bonds. As shown in Figure 1, there are many ways to

function of supra-amphiphiles. It is highly anticipated that supra-amphiphiles establish a new bridge between colloidal science and supramolecular chemistry. The study of supraamphiphiles can enrich traditional colloidal science. Moreover, supra-amphiphiles can function as new building blocks for controlled self-assembly and disassembly, leading to supramolecular materials with tailored-made architecture and function.

2. WHAT ARE SUPRA-AMPHIPHILES? Supra-amphiphiles refer to amphiphiles that are constructed on the basis of noncovalent interactions such as electrostatic interaction, π−π stacking, charge-transfer interaction, hydrogen bonding, and host−guest interaction.1−5 Some dynamic and reversible covalent bonds such as imine and disulfide bonds, which are similar to noncovalent interactions under certain conditions, can also be used to drive the formation of supraamphiphiles.6−10 The building blocks of supra-amphiphiles are diverse and may vary from synthetic molecules to natural ones, from small molecules to polymeric components. Different terminologies should be clarified before discussing the architecture and function of supra-amphiphiles. Superamphiphiles, or giant surfactants, are amphiphiles that are large in size and built by covalent synthesis.11,12 Noncovalent amphiphiles or noncovalent surfactants are a kind of supraamphiphile in which driving forces are based on noncovalent interactions.13 However, supra-amphiphiles can be fabricated on the basis of noncovalent interactions as well as dynamic covalent bonds. In our previous work, we have used the

Figure 1. Evolution from amphiphiles to supra-amphiphiles.

covalently link the hydrophilic and hydrophobic parts, leading to amphiphiles with different topologies. The study of these conventional amphiphiles and their synthesis, properties, and behavior not only reveal principles of the microscopic world but also give rise to various applications, such as detergents, emulsifiers, foaming, drug delivery, and template synthesis. Amphiphiles were, are, and will always be among the highlights of colloidal and interface science. In contrast to conventional amphiphiles, the field of supraamphiphiles is formed on the basis of noncovalent interactions and dynamic covalent bonds (Figure 1). In this feature article, we aim to give an introduction to the concept, fabrication, and © 2014 American Chemical Society

Received: January 24, 2014 Revised: March 5, 2014 Published: March 11, 2014 5989

dx.doi.org/10.1021/la500327s | Langmuir 2014, 30, 5989−6001

Langmuir

Invited Feature Article

Figure 2. Single-chain head-to-tail supra-amphiphiles. (a) Reproduced from ref 14. Copyright 2002 Wiley-VCH Verlag GmbH & Co. KGaA. (b) Reproduced from ref 15. Copyright 2013 American Chemical Society.

Figure 3. Photoresponsive pseudo-rotaxane-type single-chain head-to-tail supra-amphiphile.

provide more possibilities for the fine modulation of architectures and functions.

concepts of superamphiphile and supra-amphiphile in a confusing way. Supra-amphiphiles can be superamphiphiles, in cases where polymeric components are involved, because they are large amphiphiles but are fabricated on the basis of noncovalent interactions and dynamic covalent bonds. The dynamic nature of noncovalent interactions and dynamic covalent bonds endows supra-amphiphiles with several advantages. First, tedious chemical synthesis can be reduced to some extent, and some special topology can be relatively easily achieved. Moreover, functional moieties can be introduced into the systems in a facile way, and the systems may be sensitive to the external signals. Additionally, the fabrication of supraamphiphiles can be considered to be the primary assembly, and the resulting supra-amphiphiles can be regarded and utilized as building blocks to construct hierarchical assemblies, which may

3. HOW ARE SUPRA-AMPHIPHILES CONSTRUCTED? According to the type of building blocks, there are two main strategies for fabricating supra-amphiphiles. One is to combine the hydrophilic part and the hydrophobic part by noncovalent interactions or dynamic covalent bonds, creating amphiphilicity. The other is to modulate covalent amphiphiles noncovalently, thus leading to changes in physical−chemical properties such as amphiphilicity and the packing parameter. For conventional amphiphiles, different topologies can lead to different physical−chemical properties and applications. This holds true for supra-amphiphiles, and we will discuss the construction of supra-amphiphiles in terms of topology as well. Note that some of the supra-amphiphiles are similar to their 5990


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Figure 4. Schematic illustration of a peptide-containing multichain head-to-tail supra-amphiphile with pH responsiveness. Reproduced from ref 25. Copyright 2009 American Chemical Society.

inclusion within α-CD as a result of size complementarity. As shown in Figure 3, α-CD capped the azobenzene end, enhancing the hydrophilicity of the amphiphile, and no apparent assembly was observed. Upon 365 nm UV light irradiation, the azobenzene was isomerized to the cis form, forcing α-CD to shift to the alkyl moiety in the middle, leading to the formation of supra-amphiphiles and consequently vesicle-like aggregates. When UV irradiation was halted, αCD again encapsulated the azobenzene moiety as the cisazobenzene moiety gradually returned to the trans form, resulting in the disassembly of aggregates. Moreover, visible light accelerated this process. In this way, the reversible modulation of the amphiphilicity of the supra-amphiphile was used to realize controlled self-assembly and disassembly. A similar strategy can be applied to the pillar[6]arene-based photoresponsive host−guest system for controlled selfassembly.17 Additionally, it can be transferred onto a solid surface, allowing for the reversible tuning of surface wettability.18 Besides host-enhanced charge-transfer interactions, combined interactions of charge-transfer interaction and electrostatic attraction can also be used to drive the formation of single-chain head-to-tail supra-amphiphiles.19,20 For example, we have employed a viologen-bearing amphiphile and a pyrene derivative to fabricate supra-amphiphiles. An interesting finding is that the nanofibers formed by the self-assembly of this supraamphiphile display pH responsiveness. At pH 9, the nanofibers show curled structures, whereas the structure can be straightened with the change in pH from 9 to 10.19 3.2. Multichain Head-to-Tail Supra-Amphiphiles. The single-chain head-to-tail topology can be logically extended to

covalent conventional counterparts in topology. Moreover, some of the supra-amphiphiles are unique in topology, which cannot be easily obtained via conventional amphiphiles. 3.1. Single-Chain Head-to-Tail Supra-Amphiphiles. The supra-amphiphile with single-chain head-to-tail topology has been constructed on the basis of host-enhanced chargetransfer interactions. For example, as shown in Figure 2a, Jeon et al. utilized an amphiphilic viologen derivative, naphthalene diol, and curcubit[8]uril(CB[8]) to prepare a supra-amphiphile in a facile manner.14 The amphiphilic alkyl viologen itself selfassembled in aqueous solution to form micelles. However, when naphthalene diol was added, a 1:1 charge-transfer complex was formed inside the cavity of CB[8], leading to the formation of a supra-amphiphile with single-chain head-totail topology. After complexation, the size of the hydrophilic viologen headgroup increased, leading to a decrease in the packing parameter and further resulting in the transformation from micelles to vesicles. Similarly, as shown in Figure 2b, we have employed a similar strategy to fabricate functional supraamphiphiles. In doing so, the supramolecular glycolipid was fabricated through the complexation of an alkyl viologen, a naphthalene glycol, and CB[8].15 The supramolecular glycolipid formed spherical vesicle-like aggregates with a sugar unit on the outer surface for the specific affinity to Concanavalin A. Taking advantage of the concept of molecular shuttle, we have fabricated a pseudorotaxane-type supra-amphiphile composed of an azobenzene-containing amphiphile and αCD.16 The strength of the host−guest interaction between αCD and azobenzene was significantly determined by the configuration of azobenzene. Trans-azobenzene was favored for 5991


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Figure 5. Bola-form supra-amphiphiles based on the charge-transfer interaction. Reproduced from ref 31. Copyright 2011 Wiley-VCH Verlag GmbH & Co. KGaA.

the multichain head-to-tail structure. In these kinds of supraamphiphiles, either the hydrophobic part has multiple tails, similar to lecithin and cardiolipin in organisms, or the hydrophilic moiety can be composed of multiple tails or both hydrophilic and hydrophobic parts contain multiple tails. The number of tails can vary according to the rational design and/or the synthetic convenience.21−23 For example, Zou et al. employed host−guest interaction to fabricate a supraamphiphile with triple hydrophobic tails.24 First, they designed and synthesized a molecule bearing three hydrophobic alkyl chains and one hydrophobic azobenzene headgroup. The supra-amphiphile was then fabricated by mixing the molecule with α-CD. Through the supramolecular complexation of transazobenzene with α-CD, the introduction of hydrophilic α-CD made the hydrophobic headgroup hydrophilic. As a result, a supra-amphiphile with triple hydrophobic tails and one hydrophilic head was constructed. Upon UV irradiation, the trans-azobenzene could be converted to the cis form, leading to the disassembly of the supra-amphiphile. Host−guest interactions can also be used to drive the formation of peptide-containing supra-amphiphiles. As depicted in Figure 4, Versluis et al. utilized a modified amphiphilic β-CD and an adamantane-terminated octapeptide to form multichain head-to-tail supra-amphiphiles via the strong and specific host− guest interaction between β-CD and adamantane groups.25 The octapeptide contained valine and aspartic acid moieties alternately. Under neutral and basic conditions, the aspartic acid groups would deprotonate and repulse each other, and the supra-amphiphiles self-assembled to form vesicles. When the pH was lowered to 5.0, the aspartic acid could recover and the random coils of octapeptides would transform to β-sheet

domains. During the structural transformation of the assemblies, the cargo molecules encapsulated in vesicles are released, indicating the potential application of this system in drug delivery. 3.3. Bola-Form Supra-Amphiphiles. The bola-form amphiphile refers to the amphiphile possessing two hydrophilic headgroups, one on each end and a hydrophobic skeleton in between. Compared to a conventional single-chain head-to-tail amphiphile, a bola-form amphiphile generally displays a lower critical aggregation concentration and a higher thermal stability.26,27 In contrast to bola-form amphiphiles based on covalent bonds, we are able to employ various intermolecular interactions to fabricate bola-form supra-amphiphiles.28,29 As shown in Figure 5a, by mixing electron-poor linkers (DNB) and amphiphiles bearing electron-rich moieties (PYR), the charge-transfer interaction could be used to link two hydrophobic skeletons to form bola-form supra-amphiphiles.30 Before complexation, the amphiphiles self-assembled to form rodlike structures. After complexation, the bola-form supra-amphiphiles self-assembled to form stable vesicle-like structures. Besides traditional bola-form amphiphiles with two hydrophilic headgroups and one hydrophobic skeleton, supraamphiphiles with special topologies can be readily tailored by the elaborate design of their building blocks. For example, Xand H-shaped supra-amphiphiles, which are difficult to realize with conventional amphiphiles, have been fabricated on the basis of directional charge-transfer interactions, as shown in Figure 5b.31 Considering that the charge-transfer interaction between naphthalene and naphthalene diimide is directional (i.e., the donor and acceptor aromatic rings adopt a “facecentered” packing arrangement (Figure 5) and they stack 5992


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Figure 6. UV-responsive polymeric supra-amphiphile constructed via electrostatic interactions between a hydrophilic polymer and a small molecule. Reproduced from ref 43. Copyright 2011 American Chemical Society.

alternatively along the direction of π−π interactions), the topology of the resulting supra-amphiphiles can be well controlled. By mixing naphthalene diimide derivative (BNDI) with a 1,5-substituted naphthalene derivative (BNAPH), we fabricated X-shaped supra-amphiphiles, which further selfassembled into 1D nanostructures. However, if the substitution positions of the two alkyl chains on naphthalene were changed from 1,5 positions (BNAPH) to 2,6 positions (IBNAPH), Hshaped supra-amphiphiles could be constructed that selfassembled into 2D nanostructures. Notably, a small change in the building blocks of the supra-amphiphile might cause a large change in the structures of the self-assemblies. Along this line of research, we kept the moiety in the middle the same as in the previous case but replaced headgroups of pyridine by viologen. When the pyrene derivative was added to the solution, dual charge-transfer interactions took place, leading to the change from nanosheets to nanofibers.32 Therefore, supra-amphiphiles are ideal building blocks for the supramolecular engineering of well-defined nanostructures. 3.4. Polymeric Supra-Amphiphiles. In the examples shown above, the supra-amphiphiles are all based on small organic molecules. There are, however, a large number of polymeric supra-amphiphiles or supra-amphiphilic polymers that have also been designed and fabricated. The introduction of polymeric building blocks may endow the supra-amphiphiles

with higher stability and structural diversity while the dynamic nature is maintained. Similar to small molecular counterparts, polymeric supraamphiphiles can be prepared by connecting two or several polymeric segments through noncovalent interactions.33−36 The polymeric segments can be block copolymers as well as homopolymers.37 Under certain conditions, the hydrophilicity of the polymeric segments varies, generating supra-amphiphiles. Taking advantage of atom-transfer radical polymerization and click chemistry, Liu and co-workers synthesized adamantineterminated poly(2-(diethylamino)ethyl methacrylate) (AdPDEA) and β-CD-terminated poly(N-isopropylacrylamide) (β-CD-PNIPAM), dissolved them together in dimethylformamide, and then dialyzed the mixture against water. At pH 4 and 25 °C, the two components formed a double hydrophilic supramolecular block copolymer (DHSBC) by the host−guest complexation of adamantine and β-CD moieties. When the temperature rose to 50 °C, which is above the lower critical solution temperature of PNIPAM, the PNIPAM segments collapsed and became hydrophobic, and then DHSBC was transformed to a polymeric supra-amphiphile, which selfassembled to vesicles. If the pH was changed to 9, then PDEA was deprotonated and became hydrophobic, followed by the formation of another polymeric supra-amphiphile that assembled to PDEA-core micelles. Therefore, by the non5993


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Figure 7. pH-responsive polymeric supra-amphiphile constructed via a dynamic imine bond. Reproduced from ref 44. Copyright 2011 Wiley-VCH Verlag GmbH & Co. KGaA.

Figure 8. Surface tension varied by the formation and disassociation of supra-amphiphiles tuned by pH. Reproduced from refs 45 and ref 46. Copyright 2011 and 2012 American Chemical Society, respectively.

architecture and functional assembly. We have demonstrated successfully that polymeric supra-amphiphiles can be fabricated through electrostatic complexation between poly(ethylene glycol)-block-poly(L-lysine chloride) (PEG-b-PLKC) and a malachite derivative with a sulfonic acid group (MG2), as depicted in Figure 6.43 Upon UV irradiation, the photoresponsive malachite moiety became positive charged. Therefore, the polymeric supra-amphiphiles became more hydrophilic, followed by the disassociation of the supra-amphiphiles and disassembly of the aggregates.

covalent linking of two functional polymeric segments, they obtained a smart system that was responsive to both pH and temperature and exhibited different assembly behavior upon each stimulus. Besides covalent components, the fabrication of polymeric supra-amphiphiles can also involve supramolecular polymeric species.38 Polymeric supra-amphiphiles can be constructed by the complexation of polymers and small molecules.39−42 In addition, stimuli-responsive properties can be introduced by loading responsive moieties on both the polymeric components and the small organic moieties, thus combining molecular 5994


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Figure 9. Redox-responisve nanocarriers based on selenium-containing supra-amphiphiles. Reproduced from ref 50. Copyright 2010 American Chemical Society.

to solvent. Under certain circumstances, supra-amphiphiles may be more stable in their assemblies than in the bulk solution, where they are more prone to disassociate. For instance, the disassociation of the imine bond can be promoted by water. In other words, the aggregates, in which water is repelled, favor the formation of the imine bond. Therefore, compared to the covalent counterpart, the supra-amphiphiles may form similar aggregates while exhibiting quite different surface activity. Surface activity itself can be modulated by the controllable formation of supra-amphiphiles. For instance, we employed two conventional amphiphiles with amino end groups and aromatic aldehyde end groups, respectively, to generate a bola-form supra-amphiphile through a dynamic imine bond (Figure 8).45 The supra-amphiphile system inherited the pH-responsiveness of the imine bond. The bola-form supra-amphiphiles were stable under basic conditions. When the pH was acidic, the supra-amphiphiles were hydrolyzed to form the two precursors, which were better at lowering the surface tension, probably because of the more favorable interfacial packing. Moreover, we modified the previous bola-form supra-amphiphile to form the more confined H-shape structure by utilizing a diamine and a bola-form amphiphile containing an aromatic aldehyde group.46 It showed that the H-shaped supra-amphiphiles had a stronger tendency to assemble and the imine bond could withstand more acidic conditions than had been reported previously. Additionally, the H-shaped supra-amphiphiles displayed a lower surface activity than their bola-form amphiphile precursor, which might be due to their twisted conformation at the liquid−gas interface.

Along with intermolecular interactions, the dynamic covalent bond can be used to fabricate supra-amphiphiles that display responsive properties under certain conditions. For instance, as shown in Figure 7, under basic conditions p-(decyloxy)benzaldehyde (DBA) spontaneously attached to PEG-b-PLKC via a dynamic imine bond between the aldehyde group and the amino group, converting the hydrophilic polylysine part to a hydrophobic section, generating brush-type supra-amphiphiles. These polymeric supra-amphiphiles were able to form spherical aggregates by self-assembly.44 When the pH was changed from 7.4 to 6.5, the imine bond was broken; as a result, the spherical aggregates disassociate concomitantly. Considering that this change occurs in a very mildly acidic environment, it is highly anticipated that such aggregates formed by the polymeric supraamphiphile may find application in drug-delivery systems.

4. WHY ARE SUPRA-AMPHIPHILES SO INTERESTING? 4.1. Emerging Areas in Colloidal Science. Conventional covalent amphiphiles are always a crucial research area in colloidal science. The birth of supra-amphiphiles enriches the family of amphiphiles and broadens the area of colloidal science. “Amphiphile” is usually regarded as a synonym of “surfactant”. The chemical structure of conventional covalent amphiphiles in bulk solution is identical to that in aggregates such as micelles, vesicles, and nanotubes. However, theoretically, this is not always the case for supra-amphipiles. As noted above, supra-amphiphiles are constructed via noncovalent interactions or dynamic covalent bonds, which are sensitive 5995


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Figure 10. Supramolecular photosensitizer with enhanced antibacterial efficiency. Reproduced from ref 51. Copyright 2013 Wiley-VCH Verlag GmbH & Co. KGaA.

4.2. Building Blocks for Functional Assemblies. Function originates from property, which is ultimately determined by structure. Because noncovalent interactions and dynamic covalent bonds in isolation are always weaker than conventional covalent bonds, supra-amphiphiles may be reversible, dynamic, and sensitive to the environment. Therefore, we can employ the stimuli-responsiveness of noncovalent interactions or dynamic covalent bonds in the supraamphiphiles to realize functional assemblies. In addition, one can introduce stimuli-responsive building blocks as needed and fabricate stimuli-responsive supra-amphiphiles for functional assemblies. 4.2.1. Responsive Nanoscale Carriers. As discussed above, many supra-amphiphile systems can undergo morphological transformation, especially from assembly to disassembly. If certain compounds can be purposely encapsulated inside the aggregates and released under specific external stimulus, then the supra-amphiphile systems may act as responsive nanoscale carriers. Such carriers may match the demands of several applications, such as drug/gene delivery systems, which may contribute to therapeutic tactics ranging from saturation bombing to a precise strike, involving a lower dose and fewer side effects. Because of the differences in extracellular and intracellular environments between healthy cells and pathological cells, several factors can be selected as the corresponding stimuli for aggregates formed by supra-amphiphiles, such as enzymes and redox. For example, because the concentration and activity of phosphatase is abnormally high in tumor tissues, we fabricated a phosphataseresponsive supra-amphiphile model based on the electrostatic complexation between PEG-b-PLKC and adenosine triphosphate (ATP).47 The latter component carrying multi-negative charge was the typical substrate of phosphatase and could be hydrolyzed into single negatively charged phosphate and neutral adenosine. This process deprived the system of electrostatic cross-linking, resulting in the disassembly of the

polymeric supra-amphiphiles and their aggregates, leading to the release of encapsulated molecules. Similar strategies can be extended to other systems to enable responsiveness to other enzymes.48,49 Apart from the variation in enzyme activity, the redox state also usually differs between healthy and pathological cells. Hence, we have fabricated a redox-responsive polymeric supraamphiphile by mixing a hydrophilic diblock copolymer (PEG-bPAA) and a selenium-containing amphiphile (SeQTA), as shown in Figure 9.50 The two building blocks self-assembled to form micellar aggregates via electrostatic interaction and the hydrophobic effect. When the selenium moiety was oxidized to selenoxide, SeQTA was more prone to interact with water rather than PEG-b-PAA. Therefore, the micelles disassociated when oxidants were added, because selenium is very redoxsensitive, and oxidants as weak as 0.1% hydrogen peroxide are sufficient to trigger the disassembly process. 4.2.2. Antibacterial and Antitumor Agents. As noted in the previous paragraph, assemblies formed by supra-amphiphiles can load specific compounds and release them selectively, thus leading to applications as antibacterial and antitumor agents. For example, we have taken advantage of a tetra-substituted porphyrin (TPOR) and CB[7] as building blocks to fabricate a supramolecular photosensitizer. 51 The binding constant between CB[7] and the naphthalene moiety is as high as 6.6 × 10 7 M−1 ; therefore, supra-amphiphiles with precise stoichiometry can be fabricated. We demonstrated that the aggregation of porphyrin was inhibited because of the introduction of the bulky CB[7] headgroups in the supraamphiphiles. Upon light irradiation, it was favorable for energy transfer to occur from porphyrin to triplet oxygen in aqueous solution, significantly enhancing the ability to generate singlet oxygen. As a result, the antibacterial efficiency against E. coli increased from 17% in the case of TPOR to 97% in the case of the supra-amphiphile functioning as the supramolecular photosensitizer (Figure 10). When adding competitive 5996


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Figure 11. Dumbbell-shaped supra-amphiphile as a fluoresence sensor of spermine. Reproduced from ref 53. Copyright 2013 Nature Publishing Group.

Figure 12. Supra-amphiphile-based nanotubes as a copper ion sensor. Reproduced from ref 55. Copyright 2012 Wiley-VCH Verlag GmbH & Co. KGaA.

molecules with a higher association to CB[7], such as adamantane amine, the supra-amphiphiles would be deprived 5997


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Figure 13. Nanotubes with glutathione peroxidase activity built on supra-amphiphiles. Reproduced from ref 56. Copyright 2010 Wiley-VCH Verlag GmbH & Co. KGaA.

constructed on the basis of host−guest interactions, selfassembled into well-defined nanostructures with strong fluorescence in water. The bulky CB[7] heads of the supraamphiphile were used to weaken the π−π interactions between perylene diimide (PDI) moieties, thus preventing the fluorescence quenching of the chromophores in the assemblies. However, the competitive binding of CB[7] and spermine, an important biomarker, led to the dissociation of the supraamphiphiles and the quenching of the fluorescence of PDI. Therefore, the dumbbell-shaped supra-amphiphiles were employed for sensing spermine in terms of the change in fluorescence. Notably, both the sensitivity and the selectivity toward spermine are very good, which are crucial for real-time biological applications; for example, the early diagnosis of malignant tumors. In the previous case, the mechanism used to detect the analyte is via supramolecular complexation. In addition, the supra-amphiphile-based assemblies can also just act as platforms on which specific moieties are loaded and functioning. For instance, Lee et al. synthesized a hydrophobic dendron, having four alkyl tails and attaching a pyrene moiety on the other end.54 When pyrene was included in β-CD, which is hydrophilic on the outer surface, the hydrophobic dendron was noncovalently transformed to a supra-amphiphile, followed by the formation of nanotubes. As depicted in Figure 12, by introducing a coumarin-Gly-His dipeptide into the host molecule, β-CD, the nanotubes were utilized as a copper ion sensor, and the specific binding between the copper ion, Cu2+, and the Gly-His dipeptide induced the fluorescence quenching of the coumarin moiety.55 4.2.4. Enzyme Mimics. The assemblies formed by supraamphiphiles can provide well-defined nanostructures in a controlled way. In cases where suitable catalytically active sites are introduced, the assemblies may function as enzyme mimics with tunable activities. The assemblies formed by supra-amphiphiles can act as templates and may be equipped with artificial glutathione

of CB[7], returning to the low antibacterial state. Therefore, this supramolecular photosensitizer is anticipated to improve the efficiency of photodynamic therapy under mild conditions. The supra-amphiphiles can be adapted to different targets by supramolecular engineering. For example, Jiao et al. reported a fluorescence switch with tunable toxicity fabricated in a supraamphiphile approach.52 They exploited a hydrophilic pyreneterminal peptide, a viologen-functionalized lipid, and CB[8]. On the basis of cooperative host−guest and charge-transfer interactions, a 1:1:1 pyrene−viologen−CB[8] ternary complex was constructed, resulting in the formation of supraamphiphiles. Because the freely dispersed viologen moiety is fatal to living cells and the remaining components are much less poisonous, the cytotoxicity of the system could be modulated by the type of competitive guest additives. If naphthalene diol was added, it would replace the pyrene moiety, leaving the viologen inside the cavity of CB[8], showing no cytotoxicity. If the competitive guest molecule was adamantane amine, which was much bulkier and has a stronger association with CB[8], then the viologen derivative would be driven out along with the pyrene moiety, become dispersed, and display toxicity. 4.2.3. Fluorescence-Based Chemical Sensors. To determine the existence and the concentration of certain chemicals, information on chemical compounds is usually transferred to physical signals that can be detected by certain instruments or even human sensory perception. In this respect, the stimuliresponsiveness of noncovalent interactions or dynamic covalent bonds in the supra-amphiphiles facilitates the sensitive detection of certain analytes. The noncovalent interaction can be designed to be sensitively disrupted by some target analytes, leading to the dissociation of supra-amphiphiles and the simultaneous change in their physical properties (e.g., optoor electronic properties) that can be regarded as the output signal of the sensors. We have fabricated a new kind of dumbbell-shaped supraamphiphile with switchable photophysical properties.53 As shown in Figure 11, the dumbbell-shaped supra-amphiphile, 5998


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peroxidase (GPx) after rational modification and regulation. For instance, as depicted in Figure 13, Tang et al. constructed giant nanotubes triggered by the self-assembly of a multichain supra-amphiphile consisting of β-CD and an adamantine-ended trioxyalkyl benzene.56 The narrowly dispersed tubelike aggregates appeared to be 20 μm in length and nearly 500 nm in outer diameter, with walls consisting of about 10 bilayers of supra-amphiphiles. By linking selenium groups as active sites and guanidine moieties as recognition units for β-CD, they obtained nanotubes with the peroxidase function directly by the self-assembly process. In addition, applying molecular imprinting techniques, they preorganized the guanidine-CD with the conjugate of glutathione and seleno-CD, orienting the active sites and the recognition sites on the nanotubes to a better imitation of the natural GPx, thus achieving higher catalytic activity.

Yuetong Kang received his B.Sc. from the Department of Chemistry, Tsinghua University. Since 2012, he has been a Ph.D. student in Prof. Xi Zhang’s group in the Department of Chemistry, Tsinghua University, Beijing. His research is focused on polymeric supraamphiphiles for controlled assembly.

5. CONCLUSIONS AND PERSPECTIVE We have provided a general introduction to the concepts, fabrication, properties, and applications of supra-amphiphiles and assemblies formed by them. The noncovalent interactions forming supra-amphiphiles endow them with dynamic and adaptive properties, which are their key features. The emergence and development of supra-amphiphiles not only supplement the range of amphiphiles in traditional colloid and interface science but may also be anticipated to serve a purpose in various applications, as mentioned above. Nevertheless, there are still many problems that need to be solved, and this field can be limited only by imagination. (1) There are many of examples of assemblies formed by supra-amphiphiles; however, a general rule to guiding and predicting the construction of supra-amphiphiles and their assemblies with tailor-made architectures and functions is still absent. This question may be answered if experimental and simulation studies are effectively combined. (2) In most supra-amphiphile systems, some physicochemical properties remain absent in reporting, such as the surface tension, the viscosity coefficient, and the aggregation number. A systematic investigation of these physicochemical properties analogous to that of conventional amphiphiles would shed new light on the rational design of supra-amphiphiles with desired properties and applications. (3) The spatiotemporal relation between the formation process and the higher-ordered assembly process of supra-amphiphiles, which is crucial for further investigations on chemical dynamics and rheology, is still unclear. The incorporation of lowtemperature characterization methods may help. (4) Though many supra-amphiphiles exhibit interesting properties, it is still limited at the laboratory stage. For practical applications of supra-amphiphiles, readily available and cheap building blocks (e.g. some natural or artificial bulk chemicals) should be considered.

■

Kai Liu received his B.Sc. from the College of Chemistry, Jilin University. In 2009, he joined Prof. Xi Zhang’s group as a Ph.D. student in the Department of Chemistry, Tsinghua University, Beijing. Currently, his research is focused on supramolecular systems from molecular architecture, fine-tuning to functional assembly.

Xi Zhang is a full professor in the Department of Chemistry, Tsinghua University. His research interests are focused on supra-amphiphiles, supramolecular polymers, selenium-containing polymers, layer-bylayer assembly, and single-molecule force spectroscopy. He serves as a senior editor of Langmuir and is a member of the Advisory Board of several journals, including Accounts of Chemical Research and Small. In 2007, he was selected as a member of the Chinese Academy of

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Notes

The authors declare no competing financial interest. 5999


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Sciences. Currently, he is the vice president of the Chinese Chemical Society.

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ACKNOWLEDGMENTS

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REFERENCES

This research was supported by the National Basic Research Program of China (2013CB834502), the NSFC (21274076), and the Foundation for Innovative Research Groups of the NSFC (21121004). We are grateful to Qishui Chen from Columbia University and Emma-Rose Janeček from Cambridge University for their kind help in revising the English.

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