Constitutional Dynamic MaterialsâToward Natural Selection of Function

Review pubs.acs.org/CR

Constitutional Dynamic MaterialsToward Natural Selection of Function Yan Zhang and Mihail Barboiu* Adaptive Supramolecular Nanosystems Group, Institut Européen des MembranesUMR CNRS 5635, Place Eugène Bataillon, CC 047, F-34095 Montpellier, France adapt to the system constraints, for example, allowing selection events driven by molecular recognition and self-assembly or in response to external stimuli. For example, an external target can be used to select the functional system, from a dynamic library, allowing an efficient and highly simplified screening process.8−10 Using this strategy, the final system(s) is (are) amplified, due to the adaptative modular recognition process, facilitating detection and amplification of the fittest architectures. Component dynamic libraries prepared by using this strategy show special interest. If libraries are generated in the presence of a receptor or a CONTENTS target, new active systems can be selected. In this way, new, potentially useful functional systems can be generated.4−6 1. Introduction 809 CDC considers the chemical libraries on molecular and 2. Dynamic PolymersDynamers 810 supramolecular scales, by using the reversible covalent bonds 2.1. Molecular Dynamers 811 and noncovalent intermolecular forces, respectively, as 2.1.1. Molecular Dynamers with Acylhydraconnecting interactions.1−3 It confers to chemical systems a zone Formation 811 fifth dimension, that of constitution, that may be added to the 2.1.2. Molecular Dynamers with Imine For4D spatial and temporal chemical space.2 The self-assembly of mation 813 the components across size scales is controlled by mastering 2.1.3. Molecular Dynamers with Other Revermolecular affinities and allows the flow of structural behaviors sible Reactions 817 from the molecular to the nanoscale level.14−17 It is strongly 2.2. Supramolecular Dynamers 819 dependent on the structural factors of the library components, 2.2.1. Supramolecular Dynamers with Hydrosuch as shape, valency, orientation, and flexibility of former gen Bonding 819 components.16−18 Within this context, CDC is inspiring more 2.2.2. Supramolecular Dynamers with Hydroand more interest in Dynamic constitutional systems (DCS), phobic Connections 821 which undergo controlled exchanges through dissociation/ 2.2.3. Supramolecular Dynamers with Host− reconstitution of different architectures through multiple Guest Connections 821 processes.4 These concepts have been related to “chemical 2.3. Dynamers with Both Supramolecular and collectivism” 21 or “chemical Darwinism”.1 They are subjected to Molecular Exchanges 823 objects of different blocks formed in coupled equilibria 3. Dynamic Constitutional Frameworks 825 characterized by their aptitude to organize and comunicate 4. Conclusion 827 continuously at the molecular level toward the macroscopic Author Information 829 level for the generation of the functional complex systems.22 Corresponding Author 829 Natural systems have emerged as complex evolutive Notes 829 functions over a long period of time.23 The actual challenges Biographies 829 are to implement DCS to give to non-natural systems the Acknowledgments 830 features of natural selection and functional emergence. They References 830 extend over the vast field of scientific challenges related to the property (function)-driven generation of adjustable (adaptive) artificial systems, and they are directed toward understanding 1. INTRODUCTION the fundamental aspects of the self-organization, involving, in Constitutional dynamic chemistry (CDC)1−7 and its applicaparticular, controlled matter generation, adaptation, and tion, Dynamic combinatorial chemistry (DCC),8−18 are replication processes. They open up wide perspectives to emergent approaches to generate chemical diversity. In contrast to the classical combinatorial techniques,19,20 these Special Issue: Frontiers in Macromolecular and Supramolecular dynamic approaches allow for the simple generation of large Science chemical libraries from sets of building blocks, based on reversible exchanges between the components (Figure 1). Received: March 20, 2015 Moreover, the molecular and supramolecular libraries can Published: July 16, 2015 © 2015 American Chemical Society

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DOI: 10.1021/acs.chemrev.5b00168 Chem. Rev. 2016, 116, 809−834

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supramolecular interactions or molecular reversible reactions. The selection pressure can provide internal stability, or external stimuli, such as temperature, pH, and light, can produce changes. Moreover, the components’ reshuffling induced by the selection pressure may lead to various materials with interesting adaptive character.

2. DYNAMIC POLYMERSDYNAMERS Compared with classical polymers, in which the momomers once added one by one in a controlled manner to the polymeric backbone cannot be exchanged via reversible processes22 (Figure 2a), a dynameric system may change its constitution via reversible exchanges of monomeric constituents within its backbone. This gives rise to new dynameric entities that present modulation of their structure at the

Figure 1. Molecular and supramolecular chemistries, leading toward Dynamic constitutional chemistry.

imagining a fundamental transition from molecular design toward constitutional self-selection approaches, which may also have great potential in valuable applications. The dynamics of interactions between components of a DCS is an important condition, and accordingly, the reversible exchanges might favor the emergence system states, which mutually may adapt their geometry during the simultaneous formation of self-organized domains of the system. The extension of this approach to the nanoscale would allow selfcontrol at multiple length scales within networks and variations in their sizes and shapes. Moreover the use of biorecognition groups can be investigated in relation to the emergence of dynamic biostructures. A next logical development is related to the development of dynamic constitutional frameworks (DCFs).24 The key concept is to explore multivalent recognition and self-assembly by using tridimensional platforms of functional activity and constitutional behaviors. A specific nanospace in which the systems are evolving in the presence of the external physical stimuli or internal interactions should offer protocols for the self-formation of functional systems with a la carte properties. The possibility of self-formation of adaptive architectures should make possible investigations of collective multiple functions applied to final products. The present review discusses some of the most important advances in the field of dynamic materials and systems, focusing on various strategies for understanding the constitutional propagation of structural information toward functional materials and constitutional networks. The contributions presented here open new horizons, shortening the essential steps from molecular to macroscopic functional materials and systems. In this review, various examples will be illustrated according to their connecting type, through supramolecular polyassociation or molecular reversible polycondensation. Extending the concept of CDC to polymer science established dynamic polymers dynamerspolymers that are linked through reversible connections and able to respond to internal or external factors by exchange of components.25,26 The incipient developements of the field have been previously reviewed.27,28 Their dynamic nature can come from either

Figure 2. Comparison between mixtures of (a) classical polymers, in which the monomers are irreversibly included, and (b) dynamers, which are able to exchange reversibly their monomeric subunits.26 Reproduced with permission from ref 26. Copyright 2008 Elsevier.

molecular level, in response to internal structural constraints or to external stimuli or experimental factors (Figure 2b). Dynameric systems are able to undergo exchange, incorporation, or decorporation of their monomeric subunits, based on constitutional affinities between the former components.1,27,28 This might play an important role in the ability to finely control the functional domains. Using this strategy, recognition domains (Figure 2c) may be constitutionally self-generated via interactional, exchange, and repairing mechanisms. On the basis of these statements, the constitutional strategies open interesting possibilities for the generation of high-density materials29 in which functional properties are expressed through the molecular control of the material domains.30 The more significant challenge is to reduce the size and increase the density of these domains of the material at the molecular level. It would give the possibility to achieve the molecular limit control for highly functional behaviors specifically of interest for the material sciences (Figure 3).30 Within this context, the dynamers, obtained from reversibly interacting monomeric units, may be generated as highly homogeneous systems of addressable domains based on interactional behaviors between the former components. In dynamers, the reversible interaction between components occurs in such a manner that the self-assembled domains are the result of all energetically favorable structural combinations and constitutional affinity between the monomeric components. In such a case, the adaptive combination of components 810


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might self-repair undesired defects and use the constitution as a guide to the formation of the distinct domains of precise behaviors. The driving force is related to the internal structural

Figure 5. Evident color change and emergence of fluorescence upon heating of superimposed polyacylhydrazone dynameric films with conjugated chromophoric groups P1 and P2.33 Reproduced with permission from ref 33. Copyright 2007 Royal Society of Chemistry.

Figure 3. Structural behaviors of macromolecular block copolymers and of ultradense dynamer domains self-constructed at the molecular level.31 Reproduced with permission from ref 31. Copyright 2013 Wiley-VCH.

interactions or affinities between components. This mediates the dynamic self-organization toward low-size, addressable domains of high density and order within the macroscopic materials (Figure 3). 2.1. Molecular Dynamers

Dynamers generated by reversible covalent reactions have expanded the range of supramolecular polymers. Compared to the traditional supramolecular polymers generated via the noncovalent bonding strategy, molecular dynamers are based on reversible covalent reactions. They inherent the same dynamic character, but with stronger bond interactions and more reaction varieties. In this part, recently developed molecular dynamers will be classified according to their reaction type and their dynamic and responsive properties, and their applications will be exemplified as well. 2.1.1. Molecular Dynamers with Acylhydrazone Formation. The polycondensation of dialdehydes with dihydrazides generates polyacylhydrazones. The formed acylhydrazone functionality confers molecular features of both the supramolecular amide H-bonding behaviors and the imino bond reversibility, respectively.

Figure 6. Structures of glycomonomers 5a,b and 6a,b. Variable fluorescence and emission spectra of the same samples of the glycodynamers resulting from combination of 5a,b and 6a,b.36 Reproduced with permission from ref 36. Copyright 2010 American Chemical Society.

Variable monomers are able to reversibly exchange, thus generating constitutional dynamic diversity. Following the first example by Skene and Lehn,25 of acylhydrazone component exchange within dynamers, the reversible acylhydrazone formation reaction has been applied in various polymers. Generated from bis-hydrazide monomers (1 and 2) and dialdehydes (3 and 4), neat dynamers were found to blend at room temperature under acid catalysis (Figure 4).32 They lead to crossover recombination of components as homogeneous polymers, regenerating after exchange of randomized copoly-

Figure 4. Structures of monomers applied for dynamer blending.32 Reproduced with permission from ref 32. Copyright 2005 Royal Society of Chemistry. 811


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mers or providing access to useful strategies for modification or hybridization of completely novel polymeric backbones without solvents. The same dynamic molecular exchange at solid-phase interfaces was realized by using polyacylhydrazone dynamers with conjugated chromophoric groups, resulting in color and fluorescence modifications at the interface by simply superposing two different films in the solid state (Figure 5).33 Using the reversible acylhydrazone formation reaction, dynamic analogues of glycopolymers with high molecular weight have been generated (Figure 6).34 Their dynamic character has been displayed by NMR35 as well as fluorescence spectroscopy. Furthermore, these glycopolymers were studied for their binding to a lectin, peanut agglutinin (PNA), and the results suggested better affinity than those of corresponding monomers, shedding light on important multivalent interactions, like in biological systems.36 Dynamic polypeptoid biodynamers have been generated by polycondensation of bis-aldehyde 7 and amino acid-derived component 8. Their polymerization is driven by self-assembly of appended amino acid lateral arms (Figure 7).37 A continuous selection of the most suitable hydrophobic amino acid building block (i.e., tryptophan) is occurring with an increased rate. Higher molecular weight polymers are displaying nucleation elongation behaviors driven via hydrophobic effects. Similar “peptoid hybrid networks” (Figure 8), resulting from self-assembly of the heteropolysiloxanes bearing amino acid appended arms, have the ability to create transporting pathways and self-organized superstructures in hybrid membrane materials.38 They are important in the diffusion processes and in the selectivity of the transport of alkali cations. Although these pathways do not cross the micrometric films from one side to the other of the membrane, they are well-assembled along nanometric distances, presenting poly-

Figure 8. “Peptoid” heteropolysiloxanes 9a−e used for the synthesis of “peptoid hybrid networks”. TEM images of the hybrid material. Crystal packing of peptoid systems in stick representation with a soft surface.38 Reproduced with permission from ref 38. Copyright 2008 Wiley-VCH.

Figure 9. Structures of nucleobase monomers for DyNA dynamers.43 Schematic representation of the formation of polycationic dynamic covalent polymers from functionally complementary monomers; B represents a nucleobase. Reproduced with permission from ref 43. Copyright 2006 Wiley-VCH.

oligonucleotide base pairing are well-behaved. These systems are intrinsically modular and therefore amenable to variable adaptive superstructures, based on base-pairing H-bonding and reversible covalent interaction between the components, leading to concomitant synergistic changes in the properties of the assemblies.44 Stimuli-induced dynamic constitutional exchange, as a great feature of dynamers, was investigated in polyacylhydrazone polymers.45 A good example is the hydrophobically driven selection of secondary structures using aromatic fluorescent dialdehyde (15 and 16) or dihydrazide (17 and 18) structures as monomers. Rodlike morphologies have been obtained, while the most stable superstructure has been selectively selfassembled via hydrophobic stacking (Figure 10). Thermally induced chain elongation has been observed for amphiphilic polyacylhydrazones (21)46 (Figure 11). With increased temperatures, both below and above the lower critical solution (LCS) temperature, the dynamers obtained from 19 and 20 aggregated into longer bundles of larger molecular weight. Moreover, this phenomenon only happens under acidic conditions kinetically favoring the reversible

Figure 7. Polypeptide-type dynamic biopolymers with a globular morphology:37 HG(CH2CH2O)6CH3. Reproduced with permission from ref 37. Copyright 2012 American Chemical Society.

morphic oriented nanodomains within the hybrid thin layer matrix.39 Nucleic acids or shorter nucleosides and nucleotides were also used as target biomolecules for dynamic selection to bind to DNA,40 generating a dynamic polymer involving reversible bonds.41,42 Moreover, monomers bearing nucleobase groups (10 and 11) were used to generate dynamic nucleic acid (DyNA) dynamers in aqueous medium (Figure 9).43 Their ability of constitutional exchange, together with electrostatic interactions with polyanionic entities, was studied and showed promising application in nucleic acid recognition and analysis.43 Reversible polymeric systems based on 812


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covalent exchanges and maximizing the hydrophobic interactions between chains, These processes are displaying double control of the dynamer state: tempereature and pH. As well as linear polymers, the pH-responsive property has also been studied with branched dynamers generated from bishydrazide (22) and trialdehyde (23) monomers (Figure 12).47

Figure 13. Structures of the dialdehydes 24 and 25 and of the bishydrazide monomers 26−29 used for the preparation of dynamers P1−P7. (b) Structures and glass transition temperatures (Tg) of the homopolymer (P1−P4) and heteropolymeric (P5−P7) membranes.26 Reproduced with permission from ref 26. Copyright 2008 Elsevier.

Figure 10. Monomer used in the study and the generated secondary structures [HG(CH2CH2O)6CH3].45 Reproduced with permission from ref 45. Copyright 2009 Wiley-VCH.

case of simple mixing (P5) or ones completely different from those of the parent homopolymers P1 or P2 in the case of chemical exchange (P6 and P7). This proves that the nature of the resulting membrane films is an adjustable function of the variable use of external stimuli. The transport of Na+ and K+ under competitive conditions through the membranes P1−P7 presents a nonlinear saturation behavior, reminiscent of a strong affinity of the membrane toward the solutes. Upon constitutional exchange, the resulting heteropolymeric membranes differed a lot from their original homopolymeric one, possessing increased permeabilities, while ionic salt selectivity was preserved. This result shows that the traditional trade off in the balance between low permeability and high selectivity or vice versa is not observed for these dynameric membranes of tunable structures, as is generally observed for glassy polymers used for separations.48−50 2.1.2. Molecular Dynamers with Imine Formation. Schiff base formation via amino−carbonyl/imine reversible chemistry has been widely used in CDC for various applications, including the material science of dynamers.51−53 The reversible formation of a Schiff base is an advantageous reaction for generating DCLs, because the imine formation and component imino-interchange processes are faster in acidic aqueous solutions and also possible in a series of different solvents. However, the quantitative analysis of the data concerning the final mixture became sometimes very complicate and time-consuming, when a large number of building blocks is used. The dynameric materials preparation involves molecular or low macromolecular amino constituents and dialdehyde core connectors in order to constitutionally generate dynameric macromolecular backbones. Fluorene-based dynamers have been constructed by imine formation between dialdehyde 30 and different diamines (e.g., 31−33) (Figure 14).54 They can be tuned by the effects of acidity and ZnII metal ions, thus triggering the component reshuffling. Furthermore, this selection process has been

Figure 11. Acid-catalyzed dynamic polymerization of dialdehyde 19 and diacylhydrazine 20 to give polyacylhydrazone 21.46 Reproduced with permission from ref 46. Copyright 2011 American Chemical Society.

Figure 12. Bis-hydrazide and trialdehyde monomers used for a pHcontrolled sol−gel transition.47 Reproduced with permission from ref 47. Copyright 2010 American Chemical Society.

Accompanied by a pH-controlled reversible sol−gel transition, a self-healing effect was also investigated. By applying the dynamic covalent chemistry to membrane materials, functional dynamers for ion transport have be designed and synthesized on the basis of acylhydrazone formation (Figure 13).26 The possibility of bond exchange and component recombination was demonstrated by the use of P1 and P2 polymer blends. They were simply physically mixed (P5) or chemically exchanged via reversible hydrazone bond exchangings (P6, P7). The resulting heteropolymers present mechanical properties of the flexible P2 homopolymer in the 813


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Figure 14. Bis-hydrazide and bis-aldehyde monomers for fluorenebased dynamers used for constitutional self-sensing.54 Reproduced with permission from ref 54. Copyright 2006 Wiley-VCH. Figure 16. Bis-amine and bis-aldehyde monomers used for crystallization-driven constitutional change in dynamers.60 Reproduced with permission from ref 60. Copyright 2007 Royal Society of Chemistry.

accompanied by a change of UV−visible absorption and fluorescence optical properties in response to the formation of ZnII-coordinated amplified species. From a conceptual point of view, it represents a “constitutional dynamic self-sensing process”, expressing a synergistic adaptative behavior: the addition of the ZnII external effector drives the formation of that polymeric species presenting a (optical) signal and indicating the presence of the ZnII effector that promoted its generation in the first place. In other words, the effector induces the upregulation of its own detector.54,55 Similarly, constitutional self-instructed membranes were developed and used for mimicking the adaptive structural functionality of natural ion-channel systems.56 For this reason, columnar silica mesopores can be used as a scaffolding matrix to orient artificial ion-channel systems.57,58 These membranes are based on dynamic hybrid materials in which the self-organized H-bonded macrocycles are reversibly connected within the inorganic silica mesopores through hydrophobic interactions (Figure 15a). The structure of the confined columnar ion-channel architectures can be determined within silica mesopores and morphologically tuned by binding of alkali salts. The dynamic character related to reversible interactions between the components makes possible their control via external ionic stimuli and their self-adjustment to form the most efficient transporting ion-channel superstructure selected from a set of various architectures that can form in the mixture by self-assembly, in the presence of the external cation. Evidence has been presented that such a membrane emerges its internal pore structure so as to optimize its ion-transport properties: the noncovalently bonded macrocycles generate adaptive ion channels that can be structurally tuned during the transport experiments or the conditioning steps. From the conceptual point of view, these membranes show that the addition of the fittest alkali cation drives a constitutional emergence of the membrane structure toward the selection and amplification of the selective transporting superstructure of the cation that promoted its generation in the first place. This led to the self-implementation of the functional architectures under confined conditions, evolving from a mixture of reversibly exchanging components via ionic stimuli so as to self-improve membrane ion transport properties. These phenomena might be considered as the emergence of the most adapted superstructure, enhancing the membrane efficiency and the selectivity by binding the ion

Figure 15. (a) Dynamic hybrid materials may be prepared via the hydrophobic confinement of ureido-macrocyclic receptors within silica mesopores. It generates the directional pathways for ion conduction that can be structurally tuned by alkali salts templating. (b) It results in the reorganization of the membrane configuration, evolving an improved response in the presence of the solute that produced this change in the first place.59 Reproduced with permission from ref 59. Copyright 2015 Wiley-VCH.

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with membranes for which the transport is controlled by the gas diffusivity (glassy polymers) or by gas solubility (rubbery polymers). The most important advances in this field are related to the molecular control of the materials performing gas separation. The combination of glassy polymers with crystalline frameworks [e.g., metal−organic frameworks (MOFs), zeolitic imidazolate frameworks (ZIFs), zeolites]64 provides gas transport through the porous free volume and high selectivity related to heterogeneous “selectivity centers” interacting with the gas molecules. Despite the related progress, important difficulties are observed in obtaining homogeneously dense and mechanically stable thin layer MOFs on various supports. High permeabilities for gas molecules, versatile synthesis and processing, and high mechanical stability have been previously observed with the rubbery polymeric membranes.65 It was recently proved that the rubbery organic frameworks (ROFs) may be used as an alternative to crystalline MOFs and ZIFs for gas separation through membrane systems. Dynameric materials based on imine formation were used to build ROFs and further applied in gas separation.31 This type of framework was generated from low molecular weight macromolecular constituents (40 and 42) and dialdehyde core components (41) (Figure 18). By tuning constitutional interactions within the dynameric matrix, a high selectivity

effectors. Simply, the templating ion is itself preparing the most selective membrane for its own separation (Figure 15b).57 In addition to the chemical-stimuli-induced constitutional rearrangement, physical stimuli also have an impact on the composition of dynamers. Changes of neat/solution conditions, for example, have led to crystallization-driven constitutional changes of imine dynamers.60 By blending polymers 35· 36 and 34·37, the solution state gave a randomized formation containing all four monomeric components (34, 35, 36, and 37), while the neat state provided derandomized mixtures of only polymers 34·36 and 35·37. This is the result of the selection pressure derived from crystalline copolymer 35·37, which presents as an organized phase (Figure 16). The driving force for dynamer exchange can come from the specific internal interactions, under internal constitutional pressure. Aggregation-induced reversible formation of conjugated polymers has been exemplified in water solution.43 In this case, π-conjugated dialdehydes 38 and diamines 39 were adopted to generate reversible polymers through imine formation. The aggregation of terthiophene fragment assisted to stabilize the imine bonds, leading to much faster equilibrium

Figure 17. Bis-hydrazide and bis-aldehyde monomers used for aggregation-induced dynamer assembly.61 Reproduced with permission from ref 61. Copyright 2013 Wiley-VCH.

rates and a higher degree of polymerization (Figure 17). Moreover, the pH- and temperature-responsive properties have been observed in the obtained polymers.61 Dynachromes, dynamic electrochromic polymers, were obtained from nonelectroactive polymers through constitutional component exchange.62 The resulting dynamers were able to tune functional material preparation and surface patterning for optoelectronic applications. Other applications of dynamers have been reported. One type of dynamer based on reversible imine formation has been found to be doubly degradable.63 Water can hydrolyze the imine bonds and break up the polymer chains into oligomers, followed by secondary biodegradation into CO2 and water. Noteworthy, the residual oligomers after water disintegration can be self-healed by evaporation of the water, making the original dynamers recoverable. Dynameric membranes for gas separation have been recently developed.31 High permeability and a good selectivity are the most important challenges in developing efficient membranes for gas separation. Optimal performances are usually obtained

Figure 18. (a) Synthesis and (b) schematic representation of ROFs combining polyTHF (40; red line) and polyMePEG (42; green star), connected via dialdehyde cores (41; blue circle). Variable matrices are generated: (left) linear compact (40), (center) free volume matrix (maximum diffusivity at 33% of 42), and (right) highly cross-linked (42). (c) Photos of self-standing ROF dynameric membranes of elastomeric behaviors.31 Reproduced with permission from ref 31. Copyright 2013 Wiley-VCH. 815


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The imine formation reactions take place when concentrated hydrogel or solid-state phase organization and solution−gel− solid state transition events occur.20 Moreover, hydrophobic aldehydes with low solubilty in water react “out of water” with an amazingly high conversion. Both cases lead to the important

for CO2/N2 up to 40 and competitive permeance up to 200 Barrer can be reached. In contrast with classical rubbery polymeric membranes, the ROFs’ performances are unequivocally controlled by the diffusion of the gas molecules through the network. For all gases, a precise molecular composition of a mixture of macromonomers generates an optimal free volume for selective diffusion through the molecularly controlled matrix.31 This example shows that the gas transport in ROF membrane films can be controlled by diffusion and mutual constitutional interactions between the gas molecules and the dynameric network at the molecular level. Adequate selection of ROFs’ constitutive components makes possible the generation of compact linear or highly cross-linked domains, without external guidance. This allows the precise control of the gas difussion at the molecular level, by controlling the composition of rubbery membrane materials based on constitutional features of the interacting components in the membrane matrix. This opens promising perspectives to use this fundamental transition from macromolecular design toward molecular selection approaches, in order to achieve the molecular limit control of the gas permeable membranes. The natural biopolymer chitosan (2-amino-2-deoxy-(1→4)β-D-glucopyranan) highly interested the scientific community due to its multiple properties: biocompatibility, antimicrobial, nonantigenicity, fungistatic, spermicidal, hemostatic, immunoadjuvant, antitumoral, depressant, and accelerator of bone formation.67,68 In order to improve and vary its properties, many reactional strategies for chitosan modification have been explored. By using the imine formation on chitosan backbones,

Figure 20. Solid-phase-induced formation of imine-chitosan biodynamers, showing the increase in imine formation, when the reaction is occurring via phase changes toward solid films (red) as compared to the reaction operated in aqueous solution (blue). Pictures of the resulting biodynameric films.66 Reproduced with permission from ref 66. Copyright 2012 Royal Society of Chemistry.

emergence of imino-substituted chitosans, affording almost quantitative yields of 80−90% (Figure 20). The color of the dynameric systems can be modified via imino-bond exchanges resulting in the chromophoric component exchange and recombination at the interfaces between superposed hydrogel and the solid films (Figure 21). This indicates the use of these dynamic adaptative gels or films as constitutional systems for sensing and delivery devices. Indeed, upon contacting colored chitosan hydrogels of C4 or C8 on colorless hydrogels of C7 (Figure 21a), the color migration is observed in time (Figure 21b). Moreover, superimposing the brown solid films of C8 on the light yellow films of C6 transfers the color only in the regions where the two films are in contact and have been previously humidified with water or dried under atmospheric conditions (Figure 21c). Interestingly, the color transfer is not possible when the used films were dried under vacuum. The color transfer is also favored by temperature, as observed with films superposed at 70 °C, and strongly accelerated in the presence of acidic water or acetic acid, proving that the mechanisms for migration of components are determined via the constitutional imine exchanges at the interfaces of the

Figure 19. Chitosan biodynamers via reversible covalent imino bonding of aldehyde lateral arms.66 • = point of attachment of CHO. Reproduced with permission from ref 66. Copyright 2012 Royal Society of Chemistry.

substituted chitosans were synthesized as hydrogels or films (Figure 19).66 Contrary to existing literature reporting the formation of imino-chitosan derivatives under acidic experimental conditions in water, unsatisfactory conversion degrees, in the range of 1−12%, can be obtained via imine bond formation. 816


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Figure 21. (a) The exchange of the aromatic components in biodynameric chitosans results in the emergence of different optical absorption properties. (b) Time-dependent changes between colored hydrogels of C4 (left) or C8 (right) on colorless hydrogels of C7. (c) Visual color modification upon superimposing the brown slices of C8 on the light yellow films of C6.66 Reproduced with permission from ref 66. Copyright 2012 Royal Society of Chemistry.

Figure 22. Inhibitory effect of chitosan-vanillin (CnV) biopolymeric films on C. albicans. The diameter (mm) of the inhibition zone is calculated as the difference between the diameter of the colony-free zone and the diameter of the film.69 Reproduced with permission from ref 69. Copyright 2013 Royal Society of Chemistry.

hydrogels and the solid-state films. We may conclude that the dynamic covalent exchanges of components with chitosan backbones can be controlled and are, in principle, tunable. Chitosan biodynamers, adapting their structure in response to external stimuli, present an affinity for biological targets. The design of novel bioactive systems for medicine became of interest. Among these biomaterials, the chitosan-vanillin biopolymeric films present interesting antifungal activity against Candida albicans, which might lead to their implementation as thin-layer protecting systems for medical devices (Figure 22).69 The progressive incorporation of vanillin via imine bond formation onto hydrophilic chitosan chains produces the separation of the polymeric backbones of chitosan by breaking the strong H-bonding, resulting in the formation of globular particles of increased sizes. The hydrophobic interactions of vanillin residues at the interfaces reach a critical point, resulting in the formation of lamellar morphologies. The bicomponent self-association of alternate layers of hydrophilic chitosan and hydrophobic vanillin dynamers is responsible for the compact organization of particles. The vanillin hydrophobic region, defined along the chitosan backbone, has a protecting effect against the hydrolysis of the imino bonds. Interestingly on the same line, the cinnamimino-chitosan C/ Cy biodynamer shows constitutional synergetic self-organization through two stages: the first molecular one is imine formation “in water” to yield a low-ordered hydrogel; the supramolecular second “out-of-water” step was triggered by hydrophobic self-assembly of cinnamaldehyde layers to form highly ordered microporous morphologies (Figure 23).70 In this process, the amount of chitosan and cinnamaldehyde components had an impact on the morphology of the resulted gels. 2.1.3. Molecular Dynamers with Other Reversible Reactions. The reversible Diels−Alder (DA) reaction

Figure 23. Dynamic constitutional gelation process of cinnamiminochitosan biodynamer (C/Cy) generates time-adaptive macroscopic organization across macroscopic scales.70 Reproduced with permission from ref 70. Copyright 2014 Wiley-VCH.

normally requires harsh conditions, such as high temperatures, to react with a relatively fast equilibrium rate, but it may cause thermal decomposition of the formed polymers. Lehn and co-workers have investigated dynamers based on DA reactions reversibly occurring at room temperature.71 In order to achieve this, heavily substituted bis(tricyanoethylene carboxylate) (45) was chosen for its high reactivity toward bis(fulvene)dienes (46), leading to cycle formation within a polymer (Figure 24). The presented polydispersed molecules gave Tg values below room temperature and showed interesting self-healing properties Quantitative shape memory fixation and high shape memory recovery have been identified with dynameric networks.72 Diels−Alder reactions between specific monomers were investigated, indicating that the cross-linked dynameric networks may be successfully prepared and recycled via the retroDiels−Alder reaction upon heating (Figure 25). They exhibit a ductile plastic fracture feature with the appearance of yielding 817


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Figure 24. Monomers used for room-temperature DA polymers.71 Reproduced with permission from ref 71. Copyright 2009 WileyVCH.

Figure 26. Block polymers for generation of dynamers based on the DA reaction.73 Reproduced with permission from ref 73. Copyright 2013 Wiley-VCH.

phenomenon and/or show the rubber property with large elongation at break. Thermally stable block polymers were generated via the DA reversible reaction between furan groups (47 and 48) and bifunctional maleimide cross-linker (49) (Figure 26).73 Although very high temperatures (155 °C) and long equilibrium times (up to 17 h) were required, the obtained dynamers can undergo reversible cross-linking/de-cross-linking processes and are capable of self-healing, for example, complex scratch patterns on the surface. Oxime condensation is reversible under acidic conditions,74 and its utility in polymer preparation has been illustrated in recent years. On the basis of the oxime condensation, several dynamers were constructed from furanose derivatives carrying a masked aldehyde group and/or aminooxy group (50−52), through in situ deprotection−polycondensation.35 The dynamic exchange of the components was clearly demonstrated, and the resulting oligoarabino-furanoside biodynamers may be of great importance in various biological applications (Figure 27). Oxime linkage was also used as a robust tool for the generation of pH-sensitive dynamers.75 Consisting of both a hydrophilic poly(ethylene glycol) (PEG) block (53) and a hydrophobic oxime-tethered polycaprolactone (OPCL) block (54), the designed polymer 53·54·53 can be self-assembled

Figure 27. Furanose-based building blocks for oxime-linked dynamers.35 Reproduced with permission from ref 35. Copyright 2008 Wiley.

into micelles in aqueous media and further used as drug carrier to encapsulate doxorubicin (DOX) (Figure 28). Once located in acid environment, this oxime-linked polymer was disassembled, resulting in controlled-release behavior. By introducing olefin metathesis into polymer networks such as cross-linked polybutadiene (PBD), adaptive dynamers were generated.76 In this case, the Grubbs’ second-generation Ru catalyst was added into the system to catalyze the metathesis reaction between the alkylidene at ambient

Figure 25. Monomers used for shape memory DA polymers.72 Reproduced with permission from ref 72. Copyright 2014 American Chemical Society. 818


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Urea-based compounds have been widely used in supramolecular constructions through H-bonding.85−88 The adaptive crown ether artificial ion channels, self-organized via urea H-bonding, can be “fixed” in hybrid dense materials by the sol−gel process, resulting in the formation of the thin-layer membranes. They contain nanometric channels that define a particularly attractive functional transport device that encodes Figure 28. Building blocks for oxime-linked hydrophilic poly(ethylene glycol) (PEG) block and hydrophobic oxime-tethered polycaprolactone (OPCL) block dynamers.75 Reproduced with permission from ref 75. Copyright 2011 American Chemical Society.

temperature. Compared to the catalyst-free control samples, the resulted polymer showed malleability without compromising its mechanical properties. By using the metathesis reaction, the dynamic exchanges of reversible covalent bonds allow the processes to occur, but unlike the previous examples in this section, there is no competing pathway that might allow monomer exchange. This leads to the “dynamic” nature of exchanging polymeric components that cannot revert to the dynamic pool of monomers. Other routes to synthesize dynamic covalent polymers were also reported. For example, novel polymer scrambling was observed between two covalent polymers (55 and 56).77 This Figure 30. Macrocyclic hybrid membrane materials: self-organization in solution and sol−gel transcription of heteropolysiloxane crown ether ribbons into a hybrid membrane material.59 Reproduced with permission from ref 59. Copyright 2015 Wiley-VCH.

the required information for both cation (tubular macrocycles) and anion (sandwich-urea) directional-diffusion transport mechanisms through the hybrid membrane (Figure 30).89−92 The resulting membranes form directional translocation pathways similar to the channel proteins that assist ion diffusion through the cell membrane. These hybrid membranes have been used to transport highly hydrophilic adenosine triphosphate (ATP2−) anions, through a ion-driven mechanism, activated via a Na+ concentration gradient.59 The Lehn group has recently introduced a condensed trisurea motif, providing continues six hydrogen-bonding ureido sites along the resulting polymeric backbones.93 The synthesis

Figure 29. Dynamers generated for alkoxyamine scrambling.77 Reproduced with permission from ref 77. Copyright 2003 American Chemical Society.

can be attributed to crossover reactions between the alkoxyamines in the polymer main chain (Figure 29). 2.2. Supramolecular Dynamers

Supramolecular dynamers are polymers connected via noncovalent interactions, such as hydrogen bonding, electrostatic interactions, metal ion coordination, van der Waals, and host− guest recognition.78 With the implanted functional groups that are complementary to each other, the generated dynamers may show the potential for some interesting properties. Until now, there were extensive studies in this area, and here we only include the recent examples of this type of dynamer in this review. 2.2.1. Supramolecular Dynamers with Hydrogen Bonding. Hydrogen bonding is one of the most known interactions occurring in biological systems and also very useful to build complex artificial superstructures. Upon inserting complementary H-bonding groups into monomeric building blocks, the assembled supramolecular polymers can show adaptive reversible features, such as self-healing, thermoresponsive, and self-regulation.79−85

Figure 31. Structures of self-healing dynamers 57 and 58.93 Reproduced with permission from ref 93. Copyright 2013 WileyVCH.

of this motif was easily obtained by the reaction of carbohydrazide with an isocyanate derivative. Further preparation of polymer films 57 and 58 (Figure 31) was achieved by the incorporation of polydimethylsiloxane (PDMS) chains. Owning to the extensive hydrogen-bonding network, such materials showed very interesting self-healing behaviors at a mechanically cut surface on a short time scale, without any use of other external physical or chemical agents. The same strategy of using hydrogen-bonding supramolecular polymers to result in the observation of important self-healing effects has been adopted by Bao and coauthors for silicon microparticle (SiMP) anodes in lithium ion batteries.94 819


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The 2-ureidopyrimidinone (UPy) motif was also incorporated into one of the low Tc polymers, poly(phthalaldehyde) (PPA) (Figure 33).96 As the UPy motif and PPA backbone both contain hydrogen-bonding elements, the generated dynamers (61) are not only responsive to concentrations but also depolymerizable to monomer under appropriate conditions. Another supramolecular material, N-(6-(3-(2,4-dioxo-3,4dihydropyrimidin-1(2H)-yl)propanamido)pyridin-2-yl)undec10-enamide (U-DPy), was recently synthesized by the Chang group. Incorporated with PEG chain, the constructed dynamers (62 and 63) can self-organize in lamellar crystalline phases with a high association constant (Ka > 107 M−1)97 (Figure 34). Meanwhile, they can be also self-assembled into spherical structures: cyclic oligomers at low concentration and linear polymers at high concentration.

In this case, urea-motif-connected self-healing dynamers were used to coat the silicon electrode and to repair spontaneously any mechanical damage in the electrode, providing efficient SiMPs with much longer cycle life. One of the biggest advantages of dynamers is that they may be responsive to various stimuli. The Meijer group reported the mechanically induced gelation of supramolecular polymers.95 In this study, two different aggregated states of

Figure 32. Structures of dynamers 59 and 60 for stimuli-induced aggregation.95 Reproduced with permission from ref 95. Copyright 2014 American Chemical Society.

urethane-functionalized ditopic ureidopyrimidinone (UPy) compounds (59 and 60; Figure 32) were prepared. While the hydrogen bonds between the UPy and the backfolded chain trapped the liquid state, continuous stirring disrupts the interactions and fibrous gels are formed by molecular stacking. Both states can be obtained by controlling temperature and mechanical forces.

Figure 35. Structure of the hydrophobic guanine motif used in assembly/reassembly tuning of dynameric G-ribbon and G-quartet dynamers of surfaces.98 Reproduced with permission from ref 98. Copyright 2010 Wiley-VCH.

Starting from a hydrophobic guanine (G) motif, the reversible assembly/reassembly process of corresponding dynamers has been successively tuned between highly ordered G-quartets and G-ribbons on surfaces (Figure 35).98,99 By adding potassium picrate solution, the initial ribbonlike motif was transformed to a G-quartet supramolecular motif;

96

Figure 33. Structure of UPy-functionalized PPA polymers. Reproduced with permission from ref 96. Copyright 2014 Royal Society of Chemistry.

Figure 34. Structures of U-DPy-functionalized dynamers.96 Reproduced with permission from ref 96. Copyright 2012 Royal Society of Chemistry. 820


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subsequent addition of [2.2.2]cryptand can sequester the potassium ion and switch the structure back to a ribbon. The regeneration of the G-quartet assembly was realized by adding trifluoromethanesulfonic acid (HTf), which can release the potassium ions via protonation of the [2.2.2]cryptand. The subsquent addition of the triethylamine will deprotonate the [2.2.2]cryptand, and cycles of mechanical changes on the surface may be further controlled via acid−base addition processes. Furthermore, the whole process was visualized by STM at the solid−liquid interface on pyrolitic graphite (HOPG) surfaces. 2.2.2. Supramolecular Dynamers with Hydrophobic Connections. Hydrophobic nonspecific interactions are of fundamental importance for many biological functions. The spatial positionings of hydrophobic residues within the protein sequences can tune their self-assembly and determine their self-assembly and folding behaviors.100 Compared to hydrogen bonds, hydrophobic effects are less used in self-assembly because of their nondirectionality and nonspecificity. Because of the high significance of the related processes, the design of synthetic bioinspired self-assembly processes driven by the hydrophobic effects has become an area of expanding interest.101 Related approaches are based on lipophilic systems demonstrating the efficiency of integrated self-assembly, but the prediction of the resulting structured aggregate remains challenging.102 Hydrophilic and directional interactions (Hbonding, electrostatic or coordination interactions, etc.) also play an important role in reinforcing the dissipative hydrophobic self-assembly of artificial superstructures, mostlty when water is used as the solvent.103 A rational design of supramolecular dynamers based on hydrophobic interactions has been realized in recent years.104 Hexasubstituted benzene scaffolds decorated with amphiphilic perylene diimides (64 or 65) were observed to self-assembly into supramolecular polymers through pairwise hydrophobic/ π-stacking interactions in aqueous medium (Figure 36). The association constants of 65 were determined to be as strong as 109 M−1. Meanwhile, this type of supramolecular polymer obtained from monomers 64 and 65 showed different photonic properties, leading to excitation confinement and localized emission. Dispersion forces can also be used in supramolecular polymers, but with typically lower molecular weights (MW).106 By combining π−π, charge-transfer, and van der Waals interactions, a supramolecular polymer was obtained based on a monomer (66) incorporated with a C60 derivative and an exTTF-based macrocycle (Figure 37). On the basis of the donor−acceptor interaction and the preorganization effect, a remarkably high degree of polymerization was recorded with MW > 150 kDa in solution. 2.2.3. Supramolecular Dynamers with Host−Guest Connections. Host−guest interactions have been widely used in the generation of supramolecular polymers recently. Crown ether-based molecular recognition is one good example among them. The Huang group has developed dynameric structures by connecting dibenzo[24]crown-8 and its complementary guest ammonium salt at the two ends of one molecule (67), leading to pH-responsive and thermoresponsive abilities (Figure 38).107 The monomer 67 also showed a blending property with other similar low molecular weight molecules to form micro- and macroscopic aggregates.108 Instead of dibenzo[24]crown-8, benzo-21-crown-7 was also employed to generate a 3D supramolecular polymer network

Figure 36. Structures of hexasubstituted benzene monomers for dynameric scaffolds with directional hydrophobic interactions.104 Reproduced with permission from ref 104. Copyright 2011 American Chemical Society.

Figure 37. Structure of monomer used for dynamers with dispersion interactions.105 Reproduced with permission from ref 105. Copyright 2015 Royal Society of Chemistry.

upon the addition of bisammonium salt to form [2]pseudorotaxane host/guest linkages.109 The resulted dynamer presented dual thermal- and cation-responsive gel−sol transitions. Moreover, a quadruple-responsive supramolecular polymer with pH-, thermal-, cation-, and metal-induced gel− sol transitions was investigated by the incorporation of palladium(II) into the same type of monomers (68) (Figure 821


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Figure 38. Structure of monomer 67 with dibenzo[24]crown-8.107 Reproduced with permission from ref 107. Copyright 2011 Wiley-VCH.

Figure 39. Structure of monomer 68 with benzo-21-crown-7.110 Reproduced with permission from ref 110. Copyright 2012 Wiley-VCH.

Various similar supramolecular polymers related to crown ether host−guest recognition have been reported lately.105,111−116 Combining metal−ligand coordination or hydrogen-bonding interactions, all formed dynamers showed multiresponsive properties. One of them is a branched molecule attached with three dibenzo[24]crown-8 groups (69) and further connected by bis-pyridinium salts (70) to form a supramolecular polymer, which was endowed with better material properties than linear dynamers (Figure 40).113 Linear fluorescent supramolecular polymers formed by crown ether-based host−guest interactions were prepared using tetraphenylethylene (TPE) as the chromophore. The supramolecular polymer exhibits aggregation-induced emission properties in solution and in the solid state. Moreover, the fluorescence intensity decreased dramatically on the addition of PdII, which allows the fluorescent supramolecular polymer to be applied as a fluorescent sensor for PdII.116 The construction of artificial molecular machines is of central interest in order to mimic their biological counterparts. The objective is to engineer dynamic devices and functional materials effecting molecular motion.117−127 The Giuseppone group reported that the amplification by 4 orders of magnitude of the mechanical output of thousands of molecular machines linked within a single-stranded macromolecular chain, going from nanometers to tens of micrometers, is accessible by combining molecular synthesis, supramolecular engineering, and polymerization processes (Figure 41).117

Figure 40. Structures of monomers applied for branched macrocyclic bis-pyridinium dynamers.113 Reproduced with permission from ref 113. Copyright 2014 Royal Society of Chemistry.

39).110 Thus, metal−ligand interactions also contributed to the construction of cross-linked dynamers.

Figure 41. General principle of (a) a bistable [c2]daisy chain rotaxane and (b) the supramolecular polymer. The stoppers are ligands that can also bind to metal ions to produce coordination polymers. The integrated translational motion of the supramolecular polymer chain is the product of the individual contractions and extensions of each molecular machine by the degree of polymerization.117 Reproduced with permission from ref 117. Copyright 2012 Wiley-VCH. 822


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Figure 42. Dynamic acylhydrazone polymers for metal coordination.128 Reproduced with permission from ref 128. Copyright 2007 Wiley-VCH.

Moreover the access to macroscopic responses has been recently acquired by varying the persistence length of the single-chain polymers, resulting in their bundling and orienting in stiffer fibers, just as myofibrils do in muscles. The integration of the light-driven unidirectional molecular rotors as reticulating units in a polymer gel makes it possible to amplify their individual motions to achieve macroscopic contraction of the materials.127 2.3. Dynamers with Both Supramolecular and Molecular Exchanges

Combining supramolecular noncovalent interactions with reversible covalent reactions of molecular components allows dynamic component exchange at both supramolecular and molecular levels. By incorporating metal−ligand coordination in the dynameric frameworks, it is usually possible to modulate the properties of the dynamers, and different examples have been illustrated in the literature. One such metallodynamer has been prepared by adding metal cations (Zn2+ and Ni2+) into the acylhydrazone-connected organic polymers (71−73) (Figure 42).128 The blending and interchanging properties of the neat dynamers have been confirmed by the transformation of their mechanical and optical properties. For example, the metal ion binding by acyl hydrazones has been used for the generation of photo- and thermoresponsive crystalline assemblies.129 In addition to the heating causing gradual dissolution, the photoirradiation stimulated a config-

Figure 44. Oligodynamer and hydrogen-bonding complementary entity for supramolecular dynamers.130 Reproduced with permission from ref 130. Copyright 2013 American Chemical Society.

from the oligodynamer (75) that was formed through a reversible covalent reaction (Figure 44).130 By adding compound 76, possessing hydrogen-bonding recognition, to the ends of oligomers, supramolecular dynamers with a higher degree of polymerization were obtained. The other example started from monomers of low molecular weight that contain both hydrogen-bonding entities and aldehyde/hydrazide groups for acylhydrazone formation.131 The targeted double dynamers can be generated through different approaches: both noncovalent polyassociation and covalent polycondensation. As previously presented, tuning the microphase density and morphology of the functional domains play an important role in the production of effcient membrane materials. The main objective is to push the constitutional affinity of the gas molecules for the material toward the molecular limit. For this reason, specific sites (amines, ionic liquids, metal ions, etc.) can be used to facilitate the transport of the gas molecules. On the other hand, the vital importance of interactions between the gas molecules and the metal ions in biomacromolecular systems is well-known. Similarly, we know that the gas−metal ion interactions can be considered crucial for the gaspartitioning properties within the membranes. Metallodynamers (77−79), constructed via imine reversible covalent and metal ion coordination reactions, may allow the gas transport diffusion due to specific structural behaviors of the dynameric matrix and via the specific binding of the gas molecules to metal ions. By incorporation of different metal ions into dynameric matrixes generated by imine formation, the membranes showed interesting properties upon the change of the macromonomeric components and metallic ions used

Figure 43. Configuration change between (E)-74 and (Z)-74.129 Reproduced with permission from ref 129. Copyright 2013 WileyVCH.

uration change from (E)-74 to (Z)-74, leading to the disappearance of the fiberlike assemblies. These processes are reversible, and the regeneration of the crystalline assemblies can be achieved by simple cooling or thermal treatment, thereby returning to the (E)-configuration (Figure 43). Attaching hydrogen-bonding complementary groups to the moieties that are capable of reversible covalent reactions can also provide dynamic constitutional diversity on both supramolecular and molecular levels. This combination can start 823


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the CO2 and interesting CO2/light gas selectivities (Figure 46). The combinatorial screening of the transport performances of such metallodynameric membranes allows one to designate easily future selective candidates of optimal composition. The rapid identification can be easily applicable to build more complex membranes containing the most optimal components for enhanced transporting behaviors. The structural behaviors of the membranes may be controlled by varying the constitutive backbone components (i.e., macromonomeric segments) and binding sites (i.e., metal ions centers). Their choice would regulate the free volume of the matrix as well as the gas-binding properties of the membrane material, which are both pivotal for controlling the gas diffsuion. Among these membranes, ZnII metallodynamers facilitate the transport of CO2 with selectivity.133 The ZnII metal ions, used as fixed sites, showed that the role of metal ions is particularly interesting.With an increasing amount of ZnII in the membrane, the transport experiments confirm that the facilitated transport of CO2 is related to two effects: the increase of the solubility of CO2 via ZnII binding and the increase of the diffusivity due to the ZnII complexation by the matrix. This results in an increase of the free space between the linear chains of macromonomers, allowing better diffusion of the gas molecules through the ZnII membrane films (Figure 47). However, the strong binding of the CO2 by the ZnII ions has a negative effect on the transport and cannot be compensated by its higher solubility due to the increasing ZnII content. Such a “multifunctional formulation” can certainly be very useful in the future for the generation of dynamic membranes for gas separation from highly diverse combinations of macromonomers, coordination core centers, and metal ions. In view of the simplicity of the preparation methods, the “metallodynameric approach” offers a rich palette of structural variations toward complex membrane materials or “systems membranes”, which defines the field of membrane materials obtained from mixtures of components via reversible interaction that are designed to self-interact or to react with external partners in order to yield novel transporting and recognition properties different from what is expected as a result of the sum of the propeties of former components at a whole system level. Of special interest is the design of membranes in which the diffusional solutes are interacting within specific directional pathways. One may suppose that development of such systems is crucial for the directional control of the transport functions. The combination of soft permeable with hard components may result in formation of segregated microdomains with improved mass transfer behaviors.134,135 The dynamers combining molecular and supramolecular connections may be useful to implement permeable directional supramolecular and dynamic covalent polymers.136 When the ureido group is present in the dynamic covalent polymers, hydrogen bonding can also have an effect on the self-assembly of membranes, leading to double dynameric membranes.136 Dynameric supramolecular systems have been obtained by using bisureido-dialdehyde H-bonded polymers and covalent macromonomers, which incorporate both noncovalent supramolecular and reversible covalent imine connections. They might contain linear (85−87) or cross-linked, startype (88), soft, permeable domains connected via reversible imino bonds and aligned along hard bis-ureido supramolecular domains formed by self-assembly via hydrogen bonding of the

Figure 45. Metallodynamers generated from imine formation and metal coordination.132 Reproduced with permission from ref 132. Copyright 2012 Royal Society of Chemistry.

Figure 46. Combinatorial screening of dynameric and metallodynameric membranes: (a) Pure gas permeabilities and (b) pure CO2/N2, O2/N2, and CO2/H2 selectivities.132 Reproduced with permission from ref 132. Copyright 2012 Royal Society of Chemistry.

(Figure 45).132 As a general trend, the metallodynameric membranes based on 77−79 show significant permeability for 824


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Figure 47. Experimental profiles of (a) pure gas permeabilities and (b) pure CO2/He(H2) and CO2/N2 selectivities at 298 K and 1.0 × 10−5 Pa. (c) Mechanistic consideration of diffusion-controlled transport of CO2 through different membranes of variable constitution: (left) linear compact (no or low content of Zn2+), (center) free volume matrix (maximum value of diffusivity at 1/Zn2+ = 0.5 and maximum value of selectivity at Zn2+ = 1.0), and (right) highly CO2 absorbent Zn2+ dynameric matrix (high content of Zn2+).133 Reproduced with permission from ref 133. Copyright 2012 Royal Society of Chemistry.

formation in the presence of metal ions. The dynamic behaviors of these noncovalent dynameric assemblies can be exploited to create combinatorial libraries of dendrimers. These supramolecular dendrimers showed thermoresponsive behaviors that can be tuned by varying the number of guanines in the oligonucleotide strand or the templating cations.139 Other related applications of such hybrid dynamic systems include the formation of triple-stranded poly-nanocage dynamers that installed the dynamic imine bonds in the structures, driven by heteroleptic aggregation.140 Another approach combines inorganic nanobuilding blocks of titanium oxo-clusters bearing four hydrogen-bond acceptors and a telechelic PDMS with two hydrogen-bond donors (Figure 50). These simple components are used to generate new hybrid dynamers combining the individual behaviors of the inorganic system (photochromism) and good mechanical properties, due to the cross-linking of the polymer backbones via supramolecular interactions.141

bisureido segments (Figure 48). While the dynamic imine formation is controlling the mutual distribution of different segments within the membrane, the ribbon-type connection between the disureido hard segments can enforce the gas transport performances, diffusing along directional pathways and making possible the CO2 permeability of 2685 Barrers and the CO2/N2 selectivity of 13:1. The H-bonded ureido ribbons reinforce and orient the soft conduction phases in a more molecularly controlled manner than that observed with the classical amorphous polymeric blends. G-quartet macroscopic hydrogen-bonded membrane films can be made by combining molecular reversible imine and boronic ester formation with metal coordination (Figure 49).137 In the first step, generation of oligomer 89 is based on imine and boronic ester formation. Followed by the addition of K+ ion, the supramolecular G-quartets or Gquadruplex dynamic architectures can be amplified, which also possess the ability of electron/proton transfer. These membrane films display fast electron/ion transfer via the formation of G-quadruplex tubular directional conduction pathways. Competitive Na+/K+ transport experiments enabled the better understanding of the diffusional selective ion exchanges along “fixed” G-quartet pathways. A similar case of multicomponent self-assembly of the G-quadruplex superstructures via H-bonding can be also achieved by using the reversible metathesis polymerization reaction and their inclusion in the liposomes, as demonstrated by Davis et al.138 This system is the first to demonstrate the ion conductance behavior of artificial G-quadruplex superstructures since these systems were discovered. On the same line of reasoning, short oligoguanosine strands linked via “click chemistry” to the central point of a dendron were used to control the self-assembly and G-quadruplex

3. DYNAMIC CONSTITUTIONAL FRAMEWORKS A further logical development of dynamic materials is related to the DCFs representing tridimensional multivalent dynamic networks of interexchanging components constructed by using a target-driven self-design strategy.2 The key concept is exploring multivalent molecular recognition and self-assembly by using adaptive platforms interacting with biological targets. The use of reversible interactions as dynamic interfaces between the target and DCF components will allow one to self-adjust the system’s tridimensional geometry and functional properties. A specific nanospace in which such systems are evolving in the presence of the external biotargets should offer rational protocols for the self-formation of functional 3Ddevices with a la carte properties. The possibility of spatial/ 825


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simultaneously to the DNA target and the cell membrane barrier.149 As for the rational design approaches, the constitutional selection strategy may generate the flow of structural information from the molecular level149 to the nanolevel. This concerns the use of nanometric DCFs24 composed by combinations of linear and/or cross-linked constitutive segments, reversibly interconnected via core centers and cationic head groups, synergistically interacting with DNA and bilayer membrane components (Figure 51c, bottom). Such dynamic adaptation has been observed for nanometric dynameric systems150,151and DCF.24 These systems present dynamic, reversible rearrangements of the components at the molecular level, striving toward a high level of adaptive selfconstruction of their supramolecular hypersurfaces upon interaction with the DNA biotarget and the cell membrane barrier. For example, polyspermine imidazole-4,5-imine dynamers have been obtained by condensing bis-formaldehyde imidazole with spermine, through pH-responsive bonds. This dynamer was used to condense small interfering RNAs (siRNAs) for delivery into cells and its release from endosomes. Cellular and in vivo assays indicated that the dynameric carrier is effective in silencing target genes with a biofriendly cytotoxicity.150 Hybrid polyacylhydrazone monomers that combine biscationic heads with ethylene oxide-containing segments have been designed for effective binding of double-stranded DNA (dsDNA) at N/P ratios comparable to that of polyethylenimines. The construction of dynamic covalent polymers via the incorporation of a reversible covalent bonds is therefore a promising strategy for generating effective vectors that allow multivalent interactions for dsDNA binding in biological media.151 DCFs24 are relevant in biological and medicinal research, especially when the biotargets, like DNA, contains a large number of members. Multifunctional core centers, linear poly(ethylene glycol) (PEG) macromonomers, and cationic heads have been used to generate DCFs for DNA binding (Figure 52). 1,3,5-Benzenetrialdehyde (90), poly(ethylene glycol)-bis(3-aminopropyl) (91), Girard’s reagent T (92), monoprotonated N,N-dimethylethylene amine (93), or aminoguanidine hydrochloride (94) are the constitutive blocks used to conceive DCF1−DCF5, via the amino−carbonyl/imine reversible chemistry. The DNA binding is clearly demonstrated for the guanidinium framework DCF5 (at N/P ratios

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