Single-chain technology using discrete synthetic ...fulltext.calis.edu.cn/nature/nchem/3/12/nchem.1175.pdfmolecular structures6–9. These novel approaches allow fine control over

NATURE CHEMISTRY | VOL 3 | DECEMBER 2011 | www.nature.com/naturechemistry 917

A wide variety of polymer materials — such as bulk phases, blends, block copolymer microphases, liquid crystals, gels, micellar assemblies, colloidal dispersions and layer-by-layer

assemblies — are used in contemporary technologies1–3. In all of these examples, the exploited properties result from the collective behaviour of multiple polymer chains. Indeed, long macromolecu-lar chains lead to cooperative intermolecular interactions, which are largely responsible for their unrivalled micro- and macroscopic properties. Hence, synthetic polymer materials are generally seen and studied as a whole. In other words, Aristotle’s principle “the whole is greater than the sum of its parts” prevails in current poly-mer science. This dominant mode of thinking is certainly justified.

In very recent years, however, an increasing number of studies have indicated that a polymer chain can be more than a modest component of a larger assembly. Indeed, if carefully engineered at the molecular level, a single polymer chain can behave as a discrete object with its own characteristics and function. This idea is actu-ally commonplace in molecular biology. Even though hierarchical self-assembly and dynamics play a central role in biological mate-rials, it is known that the macromolecular building blocks of life are complex structures with highly specific properties. Enzymes, antibodies, oxygen carriers and growth factors are classical exam-ples of nanomachines composed of one or a few polymer chains. However, comparable constructs are still missing in synthetic poly-mer science. An interesting step in that direction was undoubt-edly the discovery of dendrimers in the mid 1980s4. Indeed, these branched spherical macromolecules are generally regarded as individual nanoparticles. Moreover, dendrimers possess molecu-larly defined interiors, which can be used in performing advanced tasks such as catalysis, selective uptake or light harvesting5. In that regard, their discovery constituted a considerable step forward in applied materials science.

Within the past few years, it has been demonstrated that, apart from dendrimers, other types of synthetic macromolecule can be used to create individual functional objects. In particular, macro-molecules with controlled molecular architectures — such as star polymers, hyperbranched polymers and cyclic topologies — and also linear polymer chains can today be engineered into single-chain

Single-chain technology using discrete synthetic macromoleculesMakoto Ouchi1, Nezha Badi2, Jean-François Lutz2* and Mitsuo Sawamoto1*

Fundamental polymer science is undergoing a profound transformation. As a result of recent progress in macromolecular chemistry and physics, synthetic polymer chains are becoming much more than just the modest building blocks of traditional ‘plastics’. Promising options for controlling the primary and secondary structures of synthetic polymers have been proposed and, therefore, similarly to biopolymers, synthetic macromolecules may now be exploited as discrete objects with carefully engineered structures and functions. Although it is not possible today to reach the high level of complexity found in biomate-rials, these new chemical possibilities open interesting avenues for applications in microelectronics, photovoltaics, catalysis and biotechnology. Here, we describe in detail these recent advances in macromolecular science and emphasize the possible emergence of technologies based on single-chain devices.

devices. Much of this progress is due to recent advances in syn-thetic polymer chemistry. Indeed, modern methods of synthesizing polymers, such as living ionic polymerizations, controlled radical polymerizations, ligation chemistries or genetic engineering, allow the synthesis of tailor-made macromolecules with well-defined molecular structures6–9. These novel approaches allow fine control over macromolecular architecture but also, very importantly, over the tacticities and the primary structures of synthetic polymers10,11. Furthermore, these well-engineered synthetic polymer chains may be folded into tailored solution structures or precisely deposited onto planar substrates. In addition, new analytical tools enabling the visualization of single chains and their manipulation have been developed and optimized in recent years.

These new possibilities herald a new era in polymer science. Indeed, all of the necessary elements seem available for the emer-gence of unprecedented single-chain technologies. Yet this field of research is still in its infancy. In this context, the objective of this Perspective is to describe the current state of the art and possible future directions in this stimulating field of research.

Control of the primary structure of synthetic polymer chainsIn ‘artificial’ polymerizations, propagation is occasionally disturbed by termination, chain transfer and other side reactions to give non-uniform polymer chains with a variety of chain lengths, terminal groups and sequences. Living and controlled polymerizations, which are virtually free from such disturbance, enable us to synth-esize well-defined polymers through precise control over initiation and propagation. In particular, living radical polymerization has made a great contribution to the direct syntheses of well-defined macromolecular architectures with functional groups6,7,12. Thus, we can now express a synthetic polymer with a structural formula, although at the moment absolute reaction control is impossible.

Even if the control of polymer molecular weight and termi-nal structures approaches perfection, synthetic polymer chains are not yet autonomous; that is, even when functionalities are incorporated in the pendant groups, any single polymer molecule cannot function by itself (for example as a catalyst such as an enzyme), and they are therefore different from natural polymers,

1Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan. 2Precision Macromolecular Chemistry Group, Institut Charles Sadron, UPR22-CNRS, 23 rue du Loess, BP 84047, 67034 Strasbourg Cedex 2, France. *e-mail: [email protected]; [email protected]

PERSPECTIVEPUBLISHED ONLINE: 13 NOVEMBER 2011 | DOI: 10.1038/NCHEM.1175

© 2011 Macmillan Publishers Limited. All rights reserved

http://www.nature.com/doifinder/10.1038/nchem.1175

918 NATURE CHEMISTRY | VOL 3 | DECEMBER 2011 | www.nature.com/naturechemistry

most of which work perfectly as a single chain. This is mainly because the positions and sequences of these functionalities are totally random and uncontrolled and, worse, are not uniform among polymer chains within a single sample. As demonstrated in the highly controlled autonomous functions of natural poly-mers, there is almost no doubt that sequence control is essen-tial to provide single-chain technology. Noting this frontier of polymer science, some research groups have recently proposed sequence regulation strategies that could lead to the development of single-chain technologies. Let us first review the literature in terms of various approaches and the methodology. Figure 1 illus-trates a selective set of methods for sequence regulation in syn-thetic macromolecules.

Polymerization or chain extension of a preprogrammed monomer (for example X–AB–Y; A and B, repeat unit; X and Y, functionality) would lead to repetitive regular sequences (…–AB–AB–AB–AB–…) in the resultant polymer (Fig. 1a). Chain growth13,14, polyaddition15,16 and selective organic reactions (for example click reactions17,18, amidation17 or esterification19,20) have been examined as an extension methodology. Recently, for example, Satoh, Kamigaito and co-workers15 presented an elegant approach involving a unique molecular design: the monomers carry not only a set of monomer repeat units in a preprogrammed sequence but also reactive terminal functions (alkene and alkyl chloride) as well. Both end groups are designed to be active for metal-catalysed radi-cal (Kharash) addition for chain extension. These extension reac-tions, although different from simple propagation or addition, are designed to generate a vinyl chloride repeat unit, so that the back-bone is structurally equivalent to the sequence of repeat units from vinyl monomers.

Living polymerization can be a ‘base’ system to achieve sequence regulation (Fig. 1b), because it involves, by defini-tion, quantitative and undisturbed initiation and propaga-tion alone. A ‘living’ propagation step may therefore work as an extremely selective single-step reaction (sometimes called ‘mono-addition’) for connecting different monomer units one by one in a predetermined order (or sequence). For example, if the mono-addition of a pendant-functionalized monomer (X) to a ‘living’ chain end (~~~MMM*) gives a new terminal that can resume propagation of other monomers [~~~MMM* + X → ~~~MMM–X* →~~~MMM–X–MMMM* →→], the repetition of such ‘interrupting mono-addition’ would allow local functionali-zation of a polymer chain at a desired position21.

Another totally different approach calls for incorporation of a template for sequence regulation into an initiator, to achieve a sequential propagation of prearranged monomers (and their pendant functions) along the template through the selective rec-ognition of incoming monomers10,22–24. Ouchi, Sawamoto and co-workers25–27 first introduced this concept with metal-catalysed living radical polymerization (or atom-transfer radical polymeri-zation). The initiator (called the template initiator) was designed to place a template moiety (monomer-recognition site) spatially close to an initiating site for living mono-addition and/or repeti-tive propagation. This was done using a dually functional precursor with two active halogens, one for radical initiation and the other for cationic dissociation. The latter was first used to attach a tem-plate by means of the mono-addition of a bulky vinyl ether from which an anchoring site is generated. After monomer recognition (anchoring or tethering), the second halogen was activated by a metal catalyst to trigger a selective propagation along the template.

Via chain growth

Via step growth

Stereospecificpolymerization

Controlledmonomer addition

Interactionwith solvent

Selectivetermination

Templatedesign

Alternatingcopolymerization

Catalyst

Syndiospecificpolymerization

a Preprogrammed monomer

b Living polymerization d Catalyst

Template

X

R2R1 R3 R4 R5

Initiator for living polymerization

Living polymerization

R1

Conv. 25% 50% 75%

R2 R3

c Reactivity control

n

Figure 1 | Strategies for the synthesis of polymers with controlled primary structures. a, Polymerization or chain extension of preprogrammed monomer. b, Development from living polymerization. c, Reactivity control. Conv., conversion. d, Catalytic control.

PERSPECTIVE NATURE CHEMISTRY DOI: 10.1038/NCHEM.1175




In their first-phase feasibility study, Ouchi, Sawamoto and co-workers attached a single unit of amine25 or crown ether26 for the site-specific recognition of methacrylic acid or sodium meth-acrylate, respectively, and demonstrated highly selective radical reactions of these recognized monomers from the radical initiat-ing site with a ruthenium catalyst. It is particularly important that the template-assisted mono-addition of these recognizable meth-acrylates proceeds even in the presence of methyl methacrylate (their ester form), which shows that template recognition is highly specific. Template synthesis of well-defined sequences and the catalytic usage (reuse) of template systems are subjects of future research in this area.

To our knowledge, alternating copolymerization is the only example of sequence-regulated polymerization dictated simply by a clear difference between the reactivities inherent in a pair of monomers (Fig. 1c). The key to this method is, therefore, the selection of appropriate monomer pairs with an inherent differ-ence in reactivity or the use of an external control (such as sol-vation for example) to enhance the reactivity difference even further; the latter approach being far more difficult but much more interesting. Lutz and Pfeifer28,29 took advantage of alter-nating copolymerization to achieve ‘local’ functionalization of a polymer chain at a desired position. A typical example deals with a living radical polymerization of styrene where a functional maleimide is occasionally added at a certain time in an amount that is a slight molar excess over the living or dormant end. Owing to the alternation property (that is, the absence of homo-propa-gation), the added maleimide uniformly and preferentially adds to the growing polystyrene chains at the moment of the addition but does not propagate any further, leading to local ‘single-unit’ functionalization according to the polymerization time or the degree of propagation. In this approach, living polymerization is also essential. Lutz and co-workers30 furthermore demonstrated a facile synthesis of functional periodic copolymers by combin-ing sequence-controlled chain-growth polymerization with step-growth polymerization.

Although very elegant and perhaps ideal in the long run, it might be considerably difficult to regulate the sequence directly using a catalyst, as in DNA syntheses (Fig. 1d). Recently, however, the groups of Thomas and Coates presented an ingenious idea for the catalyst approach — one that uses catalyst stereoselectivity to control sequence regulation31,32. They developed a highly selec-tive metal catalyst for the syndioselective ring-opening polym-erization of a racemic β-lactone in which a pair of enantiomeric monomers (an equimolar mixture of (R)- and (S)-isomers) alter-nately polymerize (for example …–R–S–R–S–…). Consequently, an enantiopure pair of β-lactones with different pendant func-tionalities gave an alternating sequence for these groups along a poly(β-hydroxyalkanoate) backbone. Another example of exter-nal control was reported by Satoh, Kamigaito and co-workers33, who showed that a specific monomer–solvent interaction may induce a unique alternating sequence. The copolymerization of limonene (A), a naturally occurring terpene, with the maleim-ide (B) in a fluoroalcohol solvent gave an unprecedented ABB sequence, rather than the expected AB sequence. It is specu-lated that a bridging interaction with two carbonyl groups of the dimeric maleimide sequence promotes the unique propagation at the growing terminal.

For sequence regulation, the Merrifield solid-phase synthesis is still a powerful methodology in polymer and macromolecular synthesis10. However, the reaction is invariably heterogeneous over an insoluble resin support and, although quite useful for sepa-ration of intermediates and products, this feature in turn limits the range of applicable reactions. Lutz and co-workers used the terminal group of a well-defined polystyrene as a reactive site to achieve sequence-ordered reaction in the liquid phase17. A pair

of orthogonal efficient reactions, 1,3-dipolar cycloaddition and amidification, were coupled for chain extension (alternating prop-agation), and after each step unreacted reactants were removed by reprecipitation of the polymer.

Peptide synthesis by genetic engineering is also a fascinating approach to producing ‘artificial’ macromolecules with perfectly controlled sequences and primary structures, and, as emphasized by van Hest and Tirrell8, this is perhaps the most precise known method for sequence regulation, although the backbone is by defi-nition confined to polypeptides. In particular, technology (codon sets and other factors) has now been developed that can introduce non-canonical amino acids into genetically designed artificial pep-tides; thus, this methodology should increasingly contribute to the advance of single-chain func tions using defined sequences34.

Folding and compaction of synthetic polymer chainsAs highlighted in the previous paragraph, contemporary polymer chemistry allows fine control over the architectures and primary structures of synthetic polymer chains. However, as learned from biological polymers, precise covalent chemistry is a necessary but not sufficient aspect of single-chain design. Indeed, secondary and tertiary interactions also play a key role in molecular biology and allow folding of biopolymer chains into highly ordered structures. These construction principles can also be applied to synthetic mac-romolecules. For instance, both covalent and non-covalent asso-ciations can be exploited to compact synthetic polymer chains into complex unimolecular structures.

b

a

c

=

=

hν

=

∆

hν

O

HN

HN

N

N O

NO2

O NO

NO2

N

O

OHN

R

HN

O

R

O NO

Figure 2 | Reported strategies for compacting amorphous random coils into unimolecular nanoparticles. a, Isotropic covalent strategy using self-reacting benzocyclobutene motifs in dilute conditions43. b, Isotropic supramolecular strategy using the self-recognition of 2-ureidopyrimidinone motifs in dilute conditions45. c, Directional supramolecular strategy using the helical stacking of benzene-1,3,5-tricarboxamide motifs46.

PERSPECTIVENATURE CHEMISTRY DOI: 10.1038/NCHEM.1175




During the past two decades, significant efforts have been made to design non-natural foldable oligomers and polymers35. In such foldamers, supramolecular interactions such as hydrogen bonding, π-stacking, or metal–ligand coordination lead to the formation of ordered solution structures. For instance, naturally occurring sec-ondary structures such as helices, β-sheets or β-turns have been recreated with non-natural macromolecules36. However, synthetic foldamers are in most cases short oligomers synthesized by con-ventional organic synthesis routes. Examples of macromolecular foldamers are more scarce37. Folding of high-molecular-weight pol-ymers into helical or sheet conformations has been described18,37–41, but most of these reported examples remain limited to confor-mationally uniform secondary structures. Moore and co-work-ers introduced the term tyligomer to describe macromolecular objects containing distinct folding elements35 (that is, artificial ter-tiary structures). Although some examples of that sort have been reported42, this idea is still not fully realized.

Apart from the classical foldamer concept, other options for folding synthetic macromolecules into unimolecular objects have recently been described. In particular, isotropic interactions (that is, random intramolecular self-associations) can be exploited to transform polymer coils into globular entities. Such approaches are better described as ‘chain collapse’ or ‘chain compaction’ rather than ‘folding’. Nevertheless, they allow unimolecular engineering.

For example, Hawker and co-workers described the preparation of single-chain nanoparticles through the self-crosslinking of reactive macromolecules in dilute conditions43 (Fig. 2a). Similar results can also be obtained using non-covalent interactions. For instance, in some particular polymer architectures, hydrophobic interactions may lead to unimolecular micelles containing isolated subregions44. More-specific molecular recognition can also induce controlled chain compaction in dilute conditions45 (Fig. 2b). Very recently, Meijer and co-workers demonstrated that the directional self-assem-bly of supramolecular motifs may trigger the transformation of ran-dom coils into more-ordered solution structures46 (Fig. 2c). This interesting example is an intermediate situation between isotropic chain compaction and conventional foldamers. Yet, in this example and in the other two displayed in Fig. 2, the self-associating motifs were randomly incorporated in the polymer chains. These concepts could be developed by using polymers with controlled primary structures. The first steps in that direction have now been taken47–49.

Characterization and manipulation of single polymer chainsThe advanced macromolecular structures described in the two pre-vious paragraphs are sometimes too complex for standard polymer analytics. Classical methods such as size exclusion chromatogra-phy, NMR spectroscopy or scattering techniques measure aver-age information and therefore give only a general description of

d e

c

200 nm

PG5

PG4

PG3

PG1

PG2

a

150 nm

++ +

+ + + +

b b

100 nm

hν

100 nm

Figure 3 | AFM visualization and manipulation of synthetic polymer chains. a–c, Cartoons and images highlight some examples of synthetic single macromolecules, which can be imaged by AFM: polyelectrolytes53 (a); densely grafted macromolecular brushes56 (b); dendronized polymers54 (c). Each AFM image relates specifically to the cartoon displayed directly above. In the AFM image in c, PG1 to PG5 correspond to dendronized polymers with side dendrons of generations 1 to 5, respectively. d,e, An example of chemistry with single macromolecules. An azide-functionalized dendronized polymer (yellow segment) was reacted with a plasmid DNA (red segment) under ultraviolet irradiation: image obtained before reaction (d); visualization of macromolecular connection61 (e). Figures reproduced with permission from: a, ref. 53, © 2002 ACS; b,c,d, refs 56, 54, 61, © 2009, 2011, 2010 Wiley, respectively.





polymer properties. Recent advances in single-molecule spectros-copy and imaging open additional opportunities for characterizing and manipulating complex synthetic macromolecules. For example, single-molecule fluorescence spectroscopy, single-molecule force measurements and scanning tunnelling microscopy (STM) allow the visualization of discrete macromolecules but also give insight into the physics of single polymer chains, for example measure-ments of chain conformation, dynamics and micromechanics50. So far, these analytical methods have been used mainly to study pro-teins and nucleic acids. However, they have significant potential for the characterization of synthetic systems.

The first convincing examples of visualization of synthetic sin-gle chains have been obtained by atomic force microscopy51 (AFM). However, this technique is not universally applicable and is mostly efficient with relatively stiff macromolecules such as double-stranded DNA. Flexible synthetic polymers with short persistence lengths are more difficult to image with AFM and appear generally as com-pact globules52. Nevertheless, the chain length and the stiffness of synthetic polymers chains can be optimized for AFM imaging. For instance, polyelectrolytes53 (Fig. 3a), densely grafted macromolecu-lar brushes (Fig. 3b) and dendronized polymers54 (Fig. 3c) can be efficiently imaged as individual molecules. Interestingly, this single-chain visualization allows direct correlation to be made between polymer synthesis and observation. For instance, polydispersity, structural defects and side reactions can be directly evaluated from AFM images55,56. This is particularly useful for the examination of complex topological polymers55,57. Furthermore, polymer degrada-tion can be monitored by AFM. For instance, Matyjaszewski, Sheiko and co-workers58 recently described a fascinating example of mac-romolecular scission on planar surfaces.

Other than imaging, AFM also allows advanced micromanipu-lation and characterization of single polymer chains; for instance, controlled tip–sample interactions allow measurement of their mechanical properties59,60. Tip manipulation can also be used to perform chemical reactions with single molecules. For instance,

Fig. 3d,e shows an interesting example of single-chain chemistry in which a dendronized polymer was covalently bonded to a plasmid DNA segment61.

By comparison with other types of synthetic polymers, the sin-gle-chain physics of conducting polymers has been relatively well studied. In particular, the group of Barbara62 demonstrated that sin-gle-molecule spectroscopy opens a wide range of options for charac-terizing the molecular structure and the microphysics of single-chain conjugated polymers. More recently, Hecht, Grill and co-workers63 described an interesting approach to measuring the conductance of single polymer chains using STM. In their work, poly fluorene chains were synthesized on Au(111) surfaces (Fig. 4a,b). The indi-vidual manipulation of these chains by the STM tip allowed the length-dependent measurement of chain conductivity. STM tips can also be used to initiate and control the growth of single-chain molecular wires. For instance, Okawa and co-workers64 reported the controlled synthesis of polydiacetylene chains on graphite surfaces, demonstrating that this technique allows construction of molecular electronics (Fig. 4c,d). This example illustrates the feasibility and the relevance of single-chain polymer devices.

Single-chain functional devicesTailor-made macromolecules may be used to create single-chain polymer devices (that is, individual molecules with a given func-tion, such as artificial enzymes) or can be used as discrete com-ponents in complex assembled systems (for example individual wires or junctions in molecular circuits). This raises the question of what advantages single macromolecules have over conventional collective assemblies. Two obvious answers are size reduction and atom economy. The manipulation of single polymer chains makes it possible to work in a size range that is below the length scale of present nanotechnology. The example highlighted in Fig. 4c,d is a good illustration of this. Apart from miniaturization, single poly-mer chains have other advantages. For instance, they may allow the directional transfer of electrical, chemical or optical signals

Metal surface

a

PDA

5 nm

c d

STM tip

Molecular chain

b

Figure 4 | Manipulation of molecular wires by STM. a,b, Tip manipulation of single polyfluorene chains on Au(111) surfaces63. This measurement allows a length-dependent determination of conductance. The chain in b was obtained via a surface polymerization process. The arrows indicate covalent bonds formed during the polymerization. c,d, Tip-initiated polymerization of polydiacetylene (PDA) on surfaces64. Panel d shows the connection of the formed wire to a perpendicularly aligned phthalocyanine pentamer; the arrow indicates the phthalocyanine pentamer. Figures reproduced with permission from: a, ref. 63, © 2009 AAAS; b, ref. 64© 2011 ACS.





from one location to another. Alternatively, tailored synthetic chains containing distinct molecular regions may be used to confine, host or transport distinct molecular components.

Figure 5 shows an example of a light-harvesting molecular antenna mounted on a single polymer chain65. This macromolecule was syn-thesized by post-modification of amino-functionalized polystyrene and contains ruthenium-based chromophores, allowing light har-vesting and energy transfer along the chain, and a ruthenium-based reaction centre, which ultimately converts light energy into chemi-cal energy. Artificial photosynthesis was achieved with this synthetic antenna. Moreover, in this system, energy conversion was demon-strated to be an intramolecular process independent of polymer concentration. A comparable polymer scaffold was recently used by Hisaeda and co-workers66 in developing a photocatalytic single-chain device. In their work, the polymer was functionalized with a ruthe-nium-based photosensitizer and vitamin B12. The latter was used as a photocatalytic centre for the conversion of phenylethylbromide into ethylbenzene and styrene. Experiments at low polymer concentra-tions indicated that single-chain photocatalysis occurred efficiently. It should be noted, however, that in the two above examples the func-tional moieties were distributed randomly along the polymer back-bones. The precise positioning of functional groups in the polymer chains could possibly improve the efficiency of these devices67.

Single-chain polymers offer many other interesting possibilities for organic synthesis and catalysis. It has been known for some time that polymer chains can serve as reusable soluble supports68, but in the conventional approaches taken so far, polymer chains have generally been used only to attach and isolate components from a reaction mixture. Synthetic polymer chains with controlled pri-mary structures could have much broader applications. Indeed, as described earlier in this Perspective, these polymers could enable the spatial organization of individual components and the forma-tion of unimolecular objects containing distinct compartments.

A good example of these new possibilities was recently reported by Meijer and co-workers48,49. In their work, a linear polymer chain was constructed using three distinct building blocks: a water-soluble monomer, a benzene-1,3,5-tricarboxamide-substituted monomer allowing chain compaction through stacking, and a metal-coor-dinating monomer for catalysis. Using sequence-controlled polymerization strategies, the catalytic sites were incorporated in the middle of the chains, whereas the water-soluble and stacking

motifs were distributed along the polymer backbone. As a conse-quence of this primary structure design, in water the macromol-ecules folded into unimolecular objects containing a hydrophobic catalytic compartment stabilized by a hydrophilic shell. This simple enzyme mimic allowed efficient catalysis in an aqueous medium. This particular example illustrates that control over the primary and secondary structures of synthetic polymers is a viable option for the design of single-chain functional objects.

OutlookContemporary polymer chemistry offers robust options for con-trolling the molecular structures of synthetic macromolecules. For instance, the microstructures and architectures of synthetic polymers can be controlled using synthetic tools such as genetic engineering, controlled radical polymerization or living ionic polymerization. In this Perspective, we have emphasized that synthetic macromolecules can now be characterized and used as discrete entities. Indeed, intramolecular design (for example intra-molecular covalent chemistry and/or non-covalent intramolecular self-assembly) can be exploited to transform single polymer chains into individual folded objects. Alternatively, single macromolecules can be guided, manipulated, used in reactions or mounted into more complex assemblies.

These examples suggest that the fields of polymer self-assembly and polymer materials will evolve in the near future. In solution, for example, it is realistic to imagine self-assembled synthetic poly-mer systems consisting of distinct subdomains. Owing to the recent progress in single-molecule imaging, complex functional chain pat-terns may also become attainable on planar substrates. However, a significant amount of fundamental research is needed before these possibilities are fully realized. In particular, the promising options we have described here have to be developed over the next few years into mature disciplines. Macromolecular science is likely to become more exciting than ever.

Published online 13 November 2011

References1. Forrest, S. R. The path to ubiquitous and low-cost organic electronic appliances

on plastic. Nature 428, 911–918 (2004).2. Langer, R. & Tirrell, D. A. Designing materials for biology and medicine.

Nature 428, 487–492 (2004).

=

hν

= N N

OHN

N N

N N

Ru

N N

OHN

N N

N N

NS

N

N

Ru

Figure 5 | Single-chain photosynthetic antenna. In this structure, a ruthenium-based chromophore unit (left-most blue disk) acts as an antenna fragment. After excitation by visible light, this fragment transfers its energy to neighbouring chromophores until it reaches a ruthenium-based reaction centre (red disk). Ultimately, the light energy is converted into chemical energy in the reaction centre through a cascade of electron transfer steps. Scheme adapted from ref. 65.





3. Stuart, M. A. C. et al. Emerging applications of stimuli-responsive polymer materials. Nature Mater. 9, 101–113 (2010).

4. Tomalia, D. A., Naylor, A. M. & Goddard, W. A. Starburst dendrimers - molecular-level control of size, shape, surface-chemistry, topology, and flexibility from atoms to macroscopic matter. Angew. Chem. Int. Ed. Engl. 29, 138–175 (1990).

5. Hecht, S. & Fréchet, J. M. J. Dendritic encapsulation of function: applying nature’s site isolation principle from biomimetics to materials science. Angew. Chem. Int. Ed. 40, 74–91 (2001).

6. Ouchi, M., Terashima, T. & Sawamoto, M. Transition metal-catalyzed living radical polymerization: toward perfection in catalysis and precision polymer synthesis. Chem. Rev. 109, 4963–5050 (2009).

7. Matyjaszewski, K. & Tsarevsky, N. V. Nanostructured functional materials prepared by atom transfer radical polymerization. Nature Chem. 1, 276–288 (2009).

8. van Hest, J. C. M. & Tirrell, D. A. Protein-based materials, toward a new level of structural control. Chem. Commun. 1897–1904 (2001).

9. Hawker, C. J. & Wooley, K. L. The convergence of synthetic organic and polymer chemistries. Science 309, 1200–1205 (2005).

10. Badi, N. & Lutz, J.-F. Sequence control in polymer synthesis. Chem. Soc. Rev. 38, 3383–3390 (2009).

11. Brudno, Y. & Liu, D. R. Recent progress toward the templated synthesis and directed evolution of sequence-defined synthetic polymers. Chem. Biol. 16, 265–276 (2009).

12. Yamamoto, T. & Tezuka, Y. Topological polymer chemistry: a cyclic approach toward novel polymer properties and functions. Polym. Chem. 2, 1930–1941 (2011).

13. Hibi, Y. et al. Design of AB divinyl “template monomers” toward alternating sequence control in metal-catalyzed living radical polymerization. Polym. Chem. 2, 341–347 (2011).

14. Hibi, Y., Ouchi, M. & Sawamoto, M. Sequence-regulated radical polymerization with a metal-templated monomer: repetitive ABA sequence by double cyclopolymerization. Angew. Chem. Int. Ed. 50, 7434–7437 (2011).

15. Satoh, K. et al. Sequence-regulated vinyl copolymers by metal-catalysed step-growth radical polymerization. Nature Commun. 1, 6 (2010).

16. Seitz, M. E. et al. Nanoscale morphology in precisely sequenced poly(ethylene-co-acrylic acid) zinc ionomers. J. Am. Chem. Soc. 132, 8165–8174 (2010).

17. Pfeifer, S., Zarafshani, Z., Badi, N. & Lutz, J.-F. Liquid-phase synthesis of block copolymers containing sequence-ordered segments. J. Am. Chem. Soc. 131, 9195–9197 (2009).

18. Yu, T. B., Bai, J. Z. & Guan, Z. B. Cycloaddition-promoted self-assembly of a polymer into well-defined beta sheets and hierarchical nanofibrils. Angew. Chem. Int. Ed. 48, 1097–1101 (2009).

19. Li, J., Stayshich, R. M. & Meyer, T. Y. Exploiting sequence to control the hydrolysis behavior of biodegradable PLGA copolymers. J. Am. Chem. Soc. 133, 6910–6913 (2011).

20. Thomas, C. M. & Lutz, J.-F. Precision synthesis of biodegradable polymers. Angew. Chem. Int. Ed. 50, 9244–9246 (2011).

21. Tong, X., Guo, B.-h. & Huang, Y. Toward the synthesis of sequence-controlled vinyl copolymers. Chem. Commun. 47, 1455–1457 (2011).

22. Datta, B. & Schuster, G. B. DNA-directed synthesis of aniline and 4-aminobiphenyl oligomers: programmed transfer of sequence information to a conjoined polymer nanowire. J. Am. Chem. Soc. 130, 2965–2973 (2008).

23. Lin, N.-T. et al. From polynorbornene to the complementary polynorbornene by replication. Angew. Chem. Int. Ed. 46, 4481–4485 (2007).

24. Lo, P. K. & Sleiman, H. F. Nucleobase-templated polymerization: copying the chain length and polydispersity of living polymers into conjugated polymers. J. Am. Chem. Soc. 131, 4182–4183 (2009).

25. Ida, S., Terashima, T., Ouchi, M. & Sawamoto, M. Selective radical addition with a designed heterobifunctional halide: a primary study toward sequence-controlled polymerization upon template effect. J. Am. Chem. Soc. 131, 10808–10809 (2009).

26. Ida, S., Ouchi, M. & Sawamoto, M. Template-assisted selective radical addition toward sequence-regulated polymerization: lariat capture of target monomer by template initiator. J. Am. Chem. Soc. 132, 14748–14750 (2010).

27. Ida, S., Terashima, T., Ouchi, M. & Sawamoto, M. Selective single monomer addition in living cationic polymerization: sequential double end-functionalization in combination with capping agent. J. Polym. Sci. A 48, 3375–3381 (2010).

28. Pfeifer, S. & Lutz, J.-F. A facile procedure for controlling monomer sequence distribution in radical chain polymerizations. J. Am. Chem. Soc. 129, 9542–9543 (2007).

29. Pfeifer, S. & Lutz, J.-F. Development of a library of N-substituted maleimides for the local functionalization of linear polymer chains. Chem. Eur. J. 14, 10949–10957 (2008).

30. Lutz, J.-F., Schmidt, B. V. K. J. & Pfeifer, S. Tailored polymer microstructures prepared by atom transfer radical copolymerization of styrene and N-substituted maleimides. Macromol. Rapid Commun. 32, 127–135 (2011).

31. Kramer, J. W. et al. Polymerization of enantiopure monomers using syndiospecific catalysts: a new approach to sequence control in polymer synthesis. J. Am. Chem. Soc. 131, 16042–16044 (2009).

32. Lutz, J.-F. Polymer chemistry: a controlled sequence of events. Nature Chem. 2, 84–85 (2010).

33. Satoh, K., Matsuda, M., Nagai, K. & Kamigaito, M. AAB-sequence living radical chain copolymerization of naturally occurring limonene with maleimide: an end-to-end sequence-regulated copolymer. J. Am. Chem. Soc. 132, 10003–10005 (2010).

34. Connor, R. E. & Tirrell, D. A. Non-canonical amino acids in protein polymer design. Polym. Rev. 47, 9–28 (2007).

35. Hill, D. J. et al. A field guide to foldamers. Chem. Rev. 101, 3893–4012 (2001).36. Guichard, G. & Huc, I. Synthetic foldamers. Chem. Commun.

47, 5933–5941 (2011).37. Hecht, S. Construction with macromolecules. Mater. Today 8, 48–55 (2005).38. Ghosh, S. & Ramakrishnan, S. Aromatic donor–acceptor charge-transfer and

metal-ion-complexation-assisted folding of a synthetic polymer. Angew. Chem. Int. Ed. 43, 3264–3268 (2004).

39. van Gorp, J. J., Vekemans, J. & Meijer, E. W. Facile synthesis of a chiral polymeric helix; folding by intramolecular hydrogen bonding. Chem. Commun. 60–61 (2004).

40. Kumaki, J. et al. Molecular weight recognition in the multiple-stranded helix of a synthetic polymer without specific monomer–monomer interaction. J. Am. Chem. Soc. 130, 6373–6380 (2008).

41. Yashima, E. et al. Helical polymers: synthesis, structures, and functions. Chem. Rev. 109, 6102–6211 (2009).

42. Cornelissen, J. et al. β-helical polymers from isocyanopeptides. Science 293, 676–680 (2001).

43. Harth, E. et al. A facile approach to architecturally defined nanoparticles via intramolecular chain collapse. J. Am. Chem. Soc. 124, 8653–8660 (2002).

44. Zhou, Y., Jiang, K., Song, Q. & Liu, S. Thermo-induced formation of unimolecular and multimolecular micelles from novel double hydrophilic multiblock copolymers of N,N-dimethylacrylamide and N-isopropylacrylamide. Langmuir 23, 13076–13084 (2007).

45. Foster, E. J., Berda, E. B. & Meijer, E. W. Metastable supramolecular polymer nanoparticles via intramolecular collapse of single polymer chains. J. Am. Chem. Soc. 131, 6964–6966 (2009).

46. Mes, T., van der Weegen, R., Palmans, A. R. A. & Meijer, E. W. Single-chain polymeric nanoparticles by stepwise folding. Angew. Chem. Int. Ed. 50, 5085–5089 (2011).

47. Schmidt, B. V. K. J., Fechler, N., Falkenhagen, J. & Lutz, J.-F. Controlled folding of synthetic polymer chains through the formation of positionable covalent bridges. Nature Chem. 3, 234–238 (2011).

48. Terashima, T. et al. Single-chain folding of polymers for catalytic systems in water. J. Am. Chem. Soc. 133, 4742–4745 (2011).

49. Giuseppone, N. & Lutz, J.-F. Materials chemistry: catalytic accordions. Nature 473, 40–41 (2011).

50. Granick, S. et al. Single-molecule methods in polymer science. J. Polym. Sci. B 48, 2542–2543 (2010).

51. Kumaki, J., Nishikawa, Y. & Hashimoto, T. Visualization of single-chain conformations of a synthetic polymer with atomic force microscopy. J. Am. Chem. Soc. 118, 3321–3322 (1996).

52. Gromer, A., Rawiso, M. & Maaloum, M. Visualization of hydrophobic polyelectrolytes using atomic force microscopy in solution. Langmuir 24, 8950–8953 (2008).

53. Kiriy, A. et al. Cascade of coil-globule conformational transitions of single flexible polyelectrolyte molecules in poor solvent. J. Am. Chem. Soc. 124, 13454–13462 (2002).

54. Zhang, B. Z. et al. The largest synthetic structure with molecular precision: towards a molecular object. Angew. Chem. Int. Ed. 50, 737–740 (2011).

55. Sheiko, S. S., Sumerlin, B. S. & Matyjaszewski, K. Cylindrical molecular brushes: synthesis, characterization, and properties. Prog. Polym. Sci. 33, 759–785 (2008).

56. Schappacher, M. & Deffieux, A. Imaging of catenated, figure-of-eight, and trefoil knot polymer rings. Angew. Chem. Int. Ed. 48, 5930–5933 (2009).

57. Schappacher, M. & Deffieux, A. Synthesis of macrocyclic copolymer brushes and their self-assembly into supramolecular tubes. Science 319, 1512–1515 (2008).

58. Sheiko, S. S. et al. Adsorption-induced scission of carbon-carbon bonds. Nature 440, 191–194 (2006).

59. Rief, M., Oesterhelt, F., Heymann, B. & Gaub, H. E. Single molecule force spectroscopy on polysaccharides by atomic force microscopy. Science 275, 1295–1297 (1997).





60. Shi, W. Q. et al. Closed mechanoelectrochemical cycles of individual single-chain macromolecular motors by AFM. Angew. Chem. Int. Ed. 46, 8400–8404 (2007).

61. Barner, J., Al-Hellani, R., Schluter, A. D. & Rabe, J. P. Synthesis with single macromolecules: covalent connection between a neutral dendronized polymer and polyelectrolyte chains as well as graphene edges. Macromol. Rapid Commun. 31, 362–367 (2010).

62. Barbara, P. F., Gesquiere, A. J., Park, S.-J. & Lee, Y. J. Single-molecule spectroscopy of conjugated polymers. Acc. Chem. Res. 38, 602–610 (2005).

63. Lafferentz, L. et al. Conductance of a single conjugated polymer as a continuous function of its length. Science 323, 1193–1197 (2009).

64. Okawa, Y. et al. Chemical wiring and soldering toward all-molecule electronic circuitry. J. Am. Chem. Soc. 133, 8227–8233 (2011).

65. Sykora, M., Maxwell, K. A., DeSimone, J. M. & Meyer, T. J. Mimicking the antenna-electron transfer properties of photosynthesis. Proc. Natl Acad. Sci. USA 97, 7687–7691 (2000).

66. Shimakoshi, H. et al. Photocatalytic function of a polymer-supported B-12 complex with a ruthenium trisbipyridine photosensitizer. Chem. Commun. 47, 6548–6550 (2011).

67. Alstrum-Acevedo, J. H., Brennaman, M. K. & Meyer, T. J. Chemical approaches to artificial photosynthesis. 2. Inorg. Chem. 44, 6802–6827 (2005).

68. Dickerson, T. J., Reed, N. N. & Janda, K. D. Soluble polymers as scaffolds for recoverable catalysts and reagents. Chem. Rev. 102, 3325–3344 (2002).

AcknowledgmentsJ.-F.L. thanks the CNRS, the University of Strasbourg, the International Center for Frontier Research in Chemistry (FRC, Strasbourg) and the European Research Council (Project SEQUENCES – ERC grant agreement no. 258593) for financial support. M.S. and M.O. thank the Ministry of Education, Culture, Sports, Science and Technology, Japan, for financial support through a Grant-in-Aid for Creative Science Research (18GS0209).

Additional informationThe authors declare no competing financial interests. Reprints and permissions information is available online at http://www.nature.com/reprints. Correspondence should be addressed to J.-F.L. or M.S.



mailto:[email protected]

mailto:[email protected]


Documents

Single-chain technology using discrete synthetic ...fulltext.calis.edu.cn/nature/nchem/3/12/nchem.1175.pdfmolecular structures6–9. These novel approaches allow fine control over