Topological Polymer Chemistry Designing Complex Macromolecular

Article Cite This: Acc. Chem. Res. 2017, 50, 2661-2672

pubs.acs.org/accounts

Topological Polymer Chemistry Designing Complex Macromolecular Graph Constructions Yasuyuki Tezuka* Department of Organic and Polymeric Materials, Tokyo Institute of Technology, Meguro-ku, Tokyo 152-8552, Japan

CONSPECTUS: The precision design of topologically intriguing macromolecular architectures has continuously been an attractive challenge in polymer science and polymer materials engineering. A class of multicyclic polymer topologies, including three subclasses of spiro, bridged, and f used forms, are particularly unique not only from a topological geometry viewpoint but also from their biochemical relevance to programmed folding structures. In this Account, we describe recent progress in constructing this class of macromolecules, in particular by means of an electrostatic self-assembly and covalent f ixation (ESA-CF) protocol, in which ion-paired polymer self-assemblies are employed as key intermediates. All three dicyclic constructions having either 8 (spiro), manacle (bridged), or θ ( f used) forms, as well as a tricyclic trefoil (spiro) graph, have been constructed by the ESA-CF process. Moreover, a triply f used-tetracyclic macromolecular K3,3 graph has been constructed using a uniform-size dendritic polymer precursor having six cyclic ammonium salt end groups carrying two units of a trifunctional carboxylate counteranion. Remarkably, the K3,3 graph is known in topological geometry as a prototypical nonplanar graph and has been identified as topologically equivalent to some multicyclic polypeptides (cyclotides) produced through the intramolecular S−S bridging with cysteine residues. A series of single cyclic (ring) polymers having one, two, and even three designated functional groups at the prescribed positions along their cyclic backbone segment (kyklo-telechelics) have also been obtained by the ESA-CF protocol. And in conjunction with a tandem alkyne−azide addition (i.e., click) and an olefin metathesis (i.e., clip) reaction, the precision design of complex multicyclic macromolecular architectures has been achieved. Thus, a series of tri-, tetra-, and even hexacyclic polymer topologies of spiro- and bridged-forms and three doubly f used-tricycle (β-, γ-, and δ-graph) forms, as well as a triply f used-tetracyclic and a quadruply f used-pentacyclic form (unfolded tetrahedron-graph, and “shippo”-form, respectively) were effectively constructed. Furthermore, the hybrid multicyclic polymer constructions comprised of three subclasses of spiro, bridged, and f used units have been produced using complementary pairs of single cyclic and dicyclic kyklo-telechelic precursors obtainable by the ESA-CF process. Upon these synthetic developments, we are now entering into an exciting new era of polymer science and polymer materials engineering based on the precision design of polymer topologies, which appears comparable to the “Cambrian explosion period” experienced in the evolution of life systems. simply based on their forms, that is, topology.5,6 Sufficiently long and flexible polymer chains to adopt random coil conformation are consistent with the topological geometry conjectures and are characterized by their terminus (chain end) and junction (branching point) numbers as key invariant geometric parameters.7 The total number of branches at each junction and the connectivity of each junction are also taken as invariant parameters, while the distance between the two adjacent

1. INTRODUCTION A number of recent formidable breakthroughs in synthetic polymer chemistry have now allowed the far wider choice of macromolecular structures beyond conventional forms of linear or randomly branched ones. Thus, a variety of precisely controlled cyclic and multicyclic topologies have now emerged as an important new class of polymer constructions.1−4 These developments together with ongoing progress in the modeling and simulation, as well as in the characterization and structural analysis techniques, now offer unique opportunities in polymer materials design to uncover innovative properties and functions © 2017 American Chemical Society

Received: July 6, 2017 Published: August 22, 2017 2661

DOI: 10.1021/acs.accounts.7b00338 Acc. Chem. Res. 2017, 50, 2661−2672

Article

Accounts of Chemical Research

Figure 1. A ring family tree mandala, from monocyclic (in black) to tricyclic and selected tetracyclic constructions (spiro-, bridged-, f used-, and their hybrid-forms are given in green, in blue, in red, and in pink, respectively).

Moreover, a variety of kyklo-telechelics, that is, cyclic polymer precursors having complementary reactive groups at the prescribed location of single and multicyclic polymer segment frameworks, have newly been produced through the ESA-CF process.1,13 A series of multicyclic polymers having spiro-, bridged-, and f used-forms and their hybrid-forms (Figure 1) have subsequently been constructed in conjunction with alkyne− azide addition (click) and olefin metathesis (clip) reactions.

junctions and that between the junction and the terminus are taken as variable geometric parameters.7 Accordingly, a topological geometry (soft geometry) approach could provide important insights to elucidate basic properties of linear and, in particular, nonlinear polymer molecules, in contrast to small chemical compounds conceived upon Euclidian geometry (hard geometry) principles. Indeed, topological geometry and graph theory have been a versatile basis to elucidate biological properties of topologically unique DNAs having cyclic, knot, or link forms,8 which have now been applied in DNA-based nanotechnology.9 More recently, moreover, topologically remarkable branching and folding structures are identified in a class of proteins and polypeptides containing the S−S bridging of a selected cysteine pair located along the cyclic polypeptide backbone segments.10 And their precise spatial 3D structures are considered crucial for their unusual biofunctions, covering chemical, thermal, and enzymatic stabilities and beyond.10 Topological geometry and graph theory will provide valuable insights on such folding processes of a linear polymer chain into branched or cyclized forms, to hint at their biological evolution process, eventually leading to new concepts for polymer materials design. In this Account, an electrostatic self-assembly and covalent f ixation (ESA-CF) protocol is demonstrated,1,11 as a versatile synthetic means to produce complex polymers having, in particular, cyclic and multicyclic structures, listed in Figure 1 as “a ring family tree”. The precision design of this class of macromolecules is attained especially by employing telechelic precursors having cyclic ammonium salt end groups. In order to highlight the current frontier of topological polymer chemistry, the ESA-CF construction of a tetracyclic, triply f used-K3,3 graph polymer topology is presented as a showcase example.12

2. THE ESA-CF PROTOCOL FOR TOPOLOGICAL POLYMER CHEMISTRY 2.1. Electrostatic Self-Assembly by Telechelic Polymers

Hydrophobic polymers containing a small amount of ionic groups exhibit unique properties both in bulk and in solution, as observed typically in ionomers.14 In nonpolar organic solutions as well as in bulk, they tend to form aggregates (self-assembly) through the Coulombic interaction of ionic groups located along hydrophobic polymer backbone. The location of ionic groups, in addition to their content, dictates their aggregation and self-assembly behaviors. Accordingly, a class of telechelic polymers having ionic groups exclusively at the chain ends are considered a prototypical model of ionomers. Notably, in a diluted solution, they are thermodynamically induced to form self-assemblies, comprising the smallest number of polymer precursor units where cations and anions balance the charges. Thus, a linear polymer having two ionic end groups carrying two monofunctional or one difunctional counterion tends to form, by dilution, an electrostatic selfassembly comprising a single polymer component (Figure 2). With tetra- and hexafunctional counterions, on the other hand, the resulting self-assemblies include two and three polymer 2662


Article


oxonium, sulfonium, and ammonium salts and carboxylates have extensively been studied as a routine process to give a variety of ether ester, thioether ester, and amino ester compounds.1 In these reactions, the ring strain of the cyclic onium salt species at the ground state has intuitively been considered as a decisive parameter to cause the selective ringopening reaction. Thus, in most of the ESA-CF processes, 5membered ring, N-phenylpyrrolidinium salt groups have been introduced at the chain ends of a variety of polymers, as the selective and quantitative ring-opening esterification by carboxylate anions takes place at an elevated temperature around 70 °C as a versatile covalent conversion treatment in practice17 (Scheme 1). Scheme 1. SN2 Ring-Opening and Ring-Emitting Processes of 5-, 6-, and 7-Membered Ring, Cyclic Ammonium Salt Groups on the Telechelic poly(THF)s by Carboxylate Counteranions

Figure 2. Self-assemblies by a telechelic polymer having ionic groups accompanying di-, tetra-, and hexafunctional counteranions, their disassembly by dilution, and the subsequent covalent conversion.

components, respectively, under dilution, to keep the balance of the charges between the cations and anions and to maintain the smallest number of polymer components in the selfassemblies.1 (Figure 2) With a trifunctional counteranion, moreover, an electrostatic polymer self-assembly is formed by combining three units of a linear difunctional precursor and two units of trifunctional carboxylate counteranions, to balance the charges between cations and anions, which produces subsequently an isomer pair of a bridged-dicyclic manacle-form and a f used-dicyclic θform polymer15 (Figure 3). The relevant electrostatic self-

Figure 3. An electrostatic self-assembly by a telechelic polymer having two ionic groups accompanying trifunctional counteranions, and the subsequent covalent conversion to produce an isomer pair of manacleand θ-form polymers.

During the course of the ESA-CF studies, however, we have uncovered a counterintuitive regioselectivity in the SN2 esterification reactions involving 5-, 6-, and 7-membered cyclic ammonium salts18,19 (Scheme 1). Thus, in contrast to the quantitative ring-opening reaction with the 5-membered cyclic ammonium salts by carboxylate anions, the 7-membered counterpart was found to cause predominant SN2 ring-emitting reaction, occurring at the exo-position, that is, the N-adjacent methylene unit on the polymer chain, despite their ground-state ring strains being comparable to each other (both 25.9 kJ/mol, for cyclopentane and cycloheptane).18 The DFT analysis of the SN2 ring-opening transition state has subsequently been conducted to show the transformation of the skeletal 5membered ring, azacyclopentane conformation at the ground state into a hypothetical 6-membered, strain-free azacyclohexane ring structure (Figure 4). DFT has also shown that the 7membered azacycloheptane ring conformation rearranges into a hypothetical 8-membered ring, thus further strained azacyclooctane structure, at the ring-opening transition state. These results clearly indicate that the steric frustration at the transition state rather than the ring strain energy at the ground state is dictating the regioselectivity in these SN2 reactions involving cyclic ammonium salts18 (Figure 4).

assembly is formed alternatively by combining the two units of a star-shaped trifunctional precursor and three units of bifunctional carboxylate counteranions.16 By taking advantage of this unique characteristic of electrostatic polymer self-assemblies formed in nonpolar media, we have developed the ESA-CF protocol by making use of telechelic polymer precursors having moderately strained cyclic onium salt groups, in which the equilibrated (temporal) electrostatic polymer self-assemblies are subjected to covalent conversion to produce robust polymer products of topologically unique architectures.1,11 2.2. Ring-Opening versus Ring-Emitting in the Covalent Conversion Process

The ionically linked polymer self-assemblies comprised of the telechelic precursor components have been converted to the covalently linked polymer products through the nucleophilic ring-opening reaction of cyclic ammonium or sulfonium groups by carboxylate counteranions.1 The relevant ring-opening reactions using a series of 3-, 4-, and 5-membered cyclic 2663


Article


Figure 4. DFT-optimized skeletal 5-, 6-, and 7-membered ring azacycloalkane conformations at their ground states and at their ring-opening transition states and their relevant cycloalkanes.

Scheme 2. ESF Synthesis of a Cyclic Poly(THF) with a Simple Ester Linkage by a Telechelic Poly(THF) Having N-Phenyl-3,3dimethylpiperidinium Salt Groups

2.3. Construction of a K3,3 Graph Topology

The predominant ring-emitting reaction (80−90%) was also observed for the SN2 reaction of the 6-membered ring, Nphenylpiperidinium salt end groups, by carboxylate anions, occurring at the exo-position, that is, the N-adjacent methylene unit of the polymer chain.19,20 The regioselectivity in this SN2 ring-emitting/ring opening reaction was elucidated by the DFT technique, to consistently confirm the sterically frustrated 7membered ring, hypothetical azacycloheptane conformation, at the ring-opening transition state, in contrast to the strain-free 6membered ring, azacyclohexane structure, at the ground state19 (Figure 4). Notably, the ring-emitting SN2 reaction of carboxylate anions with the 6-membered ring, N-phenylpiperidinium end groups, could produce the polymer products having a simple and robust ester linkage, in contrast to the conventional ESA-CF technique through the ring-opening SN2 process by the 5membered ring counterpart, to form amino ester units.19,20 And further DFT study has indicated that the 1,3-diaxial interaction on the 6-membered ring, azacyclohexane unit, could affect pronouncedly the SN2 energy profile at the transition state to promote the quantitative ring-emitting reaction with N-phenyl3,3-dimethylpiperidinium salts.19 Thus, a telechelic poly(THF) having N-phenyl-3,3-dimethylpiperidinium salt groups was newly synthesized. The subsequent ESA-CF process caused indeed an exclusive ring-emitting esterification, and a cyclic polymer having simple ester linkage was produced with a biphenyl dicarboxylate counteranion, which is hard to obtain through an alternative alcohol/acid condensation or other nucleophile/electrophile esterifications19 (Scheme 2).

The construction of a series of mono-, di-, and tricyclic polymer topologies has been achieved by means of the ESA-CF process, using a linear telechelic poly(THF) precursor having Nphenylpyrrolidinium salt groups accompanying either a di-, tetra-, or hexafunctional carboxylate counteranion, obtainable through a simple precipitation of a poly(THF) precursor, initially accompanying triflate counteranions, into an aqueous solution containing an excess amount of the corresponding carboxylates as sodium salts1,11 (Figure 2). The 1H NMR analysis of the recovered products with di-, tetra-, and hexafunctional carboxylate counteranions confirmed the balance of the charges between the cationic ammonium salt groups and the carboxylate anions in the ion-exchanged polymer products.11 The ionically linked self-assemblies were then subjected to covalent conversion by heat treatment either in bulk or in solution. In bulk or in concentrated solutions, the chainextended polymer products having higher MWs (with a difunctional carboxylate counteranion) or insoluble gel products (with a tetra- or a hexafunctional carboxylate counteranion) were produced. On the other hand, the soluble products were quantitatively recovered under higher dilution. And remarkably, the SEC profiles of the crude products approached uniformity as the linear polymer precursor analogue, prepared separately from the telechelic precursor carrying monofunctional benzoate counteranions. Based on these results, it was confirmed that the unique electrostatic polymer assemblies were formed under dilution, comprising 2664


Article


Figure 5. ESA-CF synthesis of a f used-dicyclic, θ-shaped poly(THF) by electrostatic self-assembly of a star telechelic polymer accompanying a trifunctional carboxylate counteranion.

salt end groups was prepared to form an electrostatic polymer self-assembly with two units of trifunctional carboxylate counteranions, to maintain the balance of charges between the cations and the anions (Figure 7). The subsequent covalent conversion was performed under dilution at an elevated temperature to cause the ring-opening reaction of the 5membered ring cyclic ammonium salt groups by carboxylate counteranions. The mixture of two constitutional isomer products, namely, a K3,3 graph product together with a ladder form component, both having a complete graph construction having 9 edges (segments) and 6 vertices (junctions), were thus obtained, and subsequently resolved by means of a preparative recycling SEC technique, as the hydrodynamic volume of the K3,3 product is remarkably contracted in comparison with the ladder isomer12 (Figure 7).

either one, two, or three units of the polymer precursor and one unit of di-, tetra-, or hexafunctional carboxylate counteranion, respectively. And the subsequent heat treatment could produce selectively the corresponding mono-, di-, and tricyclic polymer products, through covalent fixation by the ring-opening reaction of N-phenylpyrrolidinium salt end groups10 (Figure 2). In a similar manner, a trifunctional star telechelic poly(THF) precursor was employed in the ESA-CF process, to produce selectively a f used-dicyclic, θ-shaped poly(THF) product21 (Figure 5). The ESA-CF protocol has now been applied to construct a topologically significant, triply f used-tetracyclic macromolecular K3,3 graph architecture, known as a typical nonplanar graph like link (catenane) and knot constructions, which cannot be embedded in the plane in such a way that their edges intersect only at their end points.7 (Figure 6) And the K3,3 is regarded as

3. THE CLICK AND CLIP REACTIONS IN CONJUNCTION WITH THE ESA-CF PROCESS 3.1. kyklo-Telechelics by the ESA-CF Protocol

Cyclic and multicyclic polymer precursors having functional groups at designated positions are termed kyklo-telechelics (Greek, kyklos, means cyclic) and are important macromolecular building blocks to construct complex macromolecular architectures containing cyclic polymer units.1,13 The ESA-CF method has been conveniently applied to prepare kyklo-telechelics, since the efficient polymer cyclization is attainable by employing the linear or branched telechelic precursors accompanying carboxylate counteranions, possessing prescribed functional groups at the designated positions either within the polymer segment or in the carboxylate components. A variety of kyklo-telechelics so far reported include not only single cyclic polymers having one specific or multiple (identical or different) functional groups but also cyclic macromonomers having a polymerizable group, tadpole polymers having functional groups at the designated positions within a ring with a branch construction, and multicyclic polymers having functional groups at the prescribed positions within their segment frameworks.1 As a prototypical example, a linear telechelic poly(THF) having N-phenylpyrrolidinium salt groups accompanying a counteranion of a hydroxy-functionalized dicarboxylate, that is, 5-hydroxyisophthalate, was prepared by the ion-exchange reaction through the simple precipitation treatment.13 The

Figure 6. K3,3 construction by various graph presentations.

a primary form in nonplanar graph constructions, as it intrinsically contains a single intersection, in comparison to the three in a trefoil knot and the two in a Hopf link (2catenane). Interestingly, moreover, such intersection of the edges in the K3,3 graph can be avoided by expressing on the torus surface.7 Remarkably, a topologically equivalent construction to the K3,3 graph has recently been identified in a number of internally bridged cyclic polypeptides (cyclotides) from diverse sources,10,22 in which three sets of intramolecular S−S bridging by pairs of cysteine residues are contained within a cyclic polypeptide framework structure.10,22 And the resulting K3,3 equivalent folding structure of the triply f used-tetracyclic construction is essential for their extraordinary stability and bioactivity.10 Therefore, it is an attractive challenge to construct a K3,3 graph polymer to explore how such unique topological properties in basic graph theories can direct any fundamental characteristics of flexible polymer molecules. Thus, a uniform-size dendritic polymer precursor of eicosanediol (C20) segments having six N-phenylpyrrolidinium 2665


Article


Figure 7. ESA-CF synthesis of a K3,3 graph polymer product by electrostatic self-assembly of a dendritic telechelic precursor accompanying trifunctional counteranions and the recycling SEC fractionation of the K3,3 graph polymer product from its ladder-form isomer.

Figure 8. ESA-CF synthesis of mono- and difunctional kyklo-telechelics by electrostatic self-assemblies with a functional polymer precursor and a functional counteranion.

biphenyl dicarboxylate, to give the relevant kyklo-telechelic poly(THF) having a hydroxyl group derived from the polymer precursor13 (Figure 8). These kyklo-telechelic polymer precursors having a hydroxyl group were further esterified with appropriately functionalized carboxylic acids to produce a series of kyklo-telechelic poly(THF)s having bromophenyl, pentynoyl, or phenylboronate groups, applicable to Suzuki and Sonogashira coupling reactions.23 By combining the two complementary ESA-CF approaches above, a variety of homo- and heterodifunctional kyklotelechelic precursors having either two identical or two different functional groups at the opposite positions have been produced

obtained ion-exchanged product was then subjected to the covalent conversion by the heat treatment under dilution to produce effectively a cyclic poly(THF) having a hydroxyl group initially located on the dicarboxylate counteranion (Figure 8). Alternatively, a kentro-telechelic poly(THF), which carries not only N-phenylpyrrolidinium salt groups at both chain ends but also an additional hydroxyl group at the center position of the polymer segment, was prepared by the living polymerization of THF using an initiator having a protected hydroxyl unit, and the subsequent end-capping with N-phenylpyrrolidine. The obtained kentro-telechelic poly(THF) was then subjected to the ESA-CF process with a dicarboxylate counteranion, typically 2666


Article


Figure 9. ESA-CF synthesis of mono- and difunctional kyklo-telechelics having alkyne or azide groups.

Figure 10. ESA-CF synthesis of mono- and difunctional kyklo-telechelics having an olefinic group in addition to an alkyne or an azide group.

Figure 11. Construction of spiro-multicyclic polymer topologies by the ESA-CF in conjunction with the click process by using kyklo-telechelic precursors having alkyne or azide groups.

(Figure 8). Thus, the kentro-telechelic polymer precursor having a hydroxyl group at the center position carrying a 5hydroxyisophthalate counteranion was prepared to give a homodifunctional kyklo-telechelic poly(THF) having two hydroxyl groups at the opposite positions.13 Similarly, a kentro-telechelic poly(THF) carrying a 5-allyloxyisophthalate counteranion was prepared to give a heterodifunctional cyclic poly(THF) having a hydroxyl and an allyloxy group at the opposite positions.13 (Figure 8) Notably, in particular, a series of mono- and difunctional kyklo-telechelic poly(THF)s having either an alkyne or an azide group, as well as those having either two alkyne groups at the

opposite positions or a pair of an alkyne and an azide group at the opposite positions were newly prepared for subsequent alkyne−azide click reaction24 (Figure 9). Furthermore, a series of homo- and heterodifunctional kyklotelechelic poly(THF)s having an olefinic group in addition to an alkyne or an azide group were also obtained by the ESA-CF process using a kentro-telechelic poly(THF) having N-phenylpyrrolidinium salt end groups and an olefinic group at the center position of the polymer chain, accompanying a dicarboxylate counteranion having either an alkyne or an azide group25 (Figure 10). These kyklo-telechelic poly(THF)s were then used for click coupling reactions and the subsequent 2667


Article


Figure 12. Construction of bridged-multicyclic polymer topologies by the ESA-CF in conjunction with the click process by using kyklo-telechelic precursors having alkyne or azide groups.

3.3. bridged-Multicyclic Constructions

metathesis condensation (clip) reactions, as detailed in the following sections.

A bridged-dicyclic manacle-shaped polymer topology was selectively constructed through the click coupling of a kyklotelechelic precursor having an alkyne group, obtainable through the ESA-CF protocol, with a difunctional linear telechelic precursor having azide groups24 (Figure 12). Notably, on the other hand, a isomeric pair of a bridged-dicyclic manacle-shaped polymer together with a f used-θ-shaped counterpart was produced, as described in section 2, through the ESA-CF process with the electrostatic polymer self-assembly composed of three units of a linear difunctional poly(THF) carrying two units of trifunctional carboxylate counteranion, or with another composed of two units of a star-shaped trifunctional poly(THF) carrying three units of bifunctional carboxylate counteranions15,16 (Figure 3). The relevant pair of dicyclic topological isomers were also formed through the metathesis clip process using an H-shaped precursor having allyloxy end groups at each chain end.32 A bridged-tricyclic, three-way paddle-shaped polymer was obtained also by the relevant click coupling reaction between a star-shaped trifunctional poly(THF) having azide groups with a cyclic poly(THF) having an alkyne groups as shown in Figure 12.24 Furthermore, a bridged-tetracyclic quatrefoil polymer topology was effectively constructed through the click linking reaction by employing a kyklo-telechelic poly(THF) having an azide group and a complementary reactive, four-armed star telechelic poly(THF) having four alkyne end groups.29 Moreover, a variety of topological block copolymers comprised of alternative cyclic/linear or cyclic/star sequences are produced by the click polyaddition involving a difunctional kyklo-telechelic poly(THF) having two alkyne groups and either linear or star telechelic poly(THF)s having azide end groups24 (Figure 12).

3.2. spiro-Multicyclic Constructions

spiro-Dicyclic 8-shaped and spiro-tricyclic trefoil polymer constructions were produced directly by the ESA-CF process, as described in section 2, by employing the electrostatic polymer self-assemblies containing two or three units of the linear telechelic precursor carrying one unit of tetra- or hexacarboxylate counteranion, respectively1,11,26 (Figure 2). The relevant 8-shaped polymer products were obtained alternatively through a double-metathesis condensation (clip) with a four-armed star telechelic prepolymer having allyloxy end groups27 or a single clip process either with a twin-tailed tadpole polymer precursor having two allyloxy groups at the tail-end positions or with a ring polymer precursor having two allyloxy groups at opposite positions.28 A tandem spiro-tricyclic polymer topology was constructed through the click linking of a pair of complementary reactive kyklo-telechelic poly(THF) precursors, one having two alkyne groups at the opposite positions of the ring unit and another having an azide group, both obtainable by the ESA-CF technique.24 In addition, a tandem spiro-tetracyclic polymer topology was similarly constructed through the click coupling between an 8-shaped dicyclic prepolymer having two alkyne groups at the opposite positions of the two ring unit and another single cyclic precursor having an azide group24 (Figure 11). Another type of a spiro-tetracyclic, quatrefoil polymer topology was effectively constructed through the click linking of a kyklo-telechelic precursor having an azide group, obtained through the ESA-CF process, and a complementary reactive pentaerythritol derivative having four alkyne units29 (Figure 11). Moreover, an iterative click reaction was conducted to cause the polymer chain extension and the subsequent polymer cyclization, to prepare kyklo-telechelic polymer precursors having multiple azide or alkyne groups and to produce eventually spiro-multicyclic polymer topologies having up to penta- and heptacyclic polymer units.30,31 (Figure 11)

3.4. fused-Multicyclic Constructions

A singly f used-dicyclic θ-shaped polymer topology was selectively constructed by the ESA-CF process with a threearmed star telechelic precursor carrying a tricarboxylate counteranion,21 as described in section 2 (Figure 5). The θshaped polymer was also obtainable together with its manacle2668


Article


Figure 13. Construction of f used-multicyclic polymer topologies by the ESA-CF in conjunction with the click and clip processes by using kyklotelechelic precursors having olefinic, alkyne, or azide groups.

shaped isomer through the analogous ESA-CF process11,15,16 or by the metathesis clip reaction32,33 using the relevant polymer precursors having olefinic groups. A series of doubly f used-tricyclic polymer topologies, corresponding to α-, β-, γ-, and δ-graph constructions shown in Figure 1 were constructed through the ESA-CF process in conjunction with the click and clip protocols.34,35 Thus, a δgraph poly(THF) was obtained with an 8-shaped kyklotelechelic poly(THF) having two allyl groups at the opposite positions in the two ring units, which was prepared through the ESA-CF process using a kentro-telechelic poly(THF) having an allyl group at the center position of the polymer segment accompanying a tetrafunctional carboxylate counteranion34 (Figure 13). The obtained 8-shaped kyklo-telechelic poly(THF) was subjected to the metathesis clip condensation under dilution in the presence of the Grubbs catalyst to produce the δ-graph polymer product.34 Other members of doubly f usedtricyclic γ-graph and β-graph polymer topologies were constructed from the prescribed kyklo-telechelic poly(THF)s prepared by the tandem ESA-CF, click coupling, and the subsequent olefin metathesis clip folding processes35 (Figure 13). Thus, a bridged-dicyclic (manacle) kyklo-telechelic poly(THF) precursor and another having additional two emanating linear segments, both having two allyloxy groups at the opposite positions of the ring units or the emanating chain ends, were prepared through the ESA-CF in conjunction with the click process. The subsequent intramolecular clip reaction under dilution in the presence of the Grubbs catalyst produced γ-graph and β-graph polymer products, which were finally isolated by means of the preparative SEC fractionation technique.35 Besides the K3,3 graph shown in section 2, the triply f usedtetracyclic polymer topology includes an unfolded tetrahedron graph, having a p4m symmetry and named also as a D4 graph.25

Moreover, the quadruply f used-pentacyclic counterpart includes a homologous “shippo” graph, frequently encountered in traditional design arts in Japan.36 These significant polymer topologies were constructed by employing the ESA-CF protocol in conjunction with the relevant click and clip processes25,36 (Figure 13). Thus, a tandem tricyclic and a tandem tetracyclic spiro-type kyklo-telechelic poly(THF) precursors commonly having two allyloxy groups at the opposite positions of the three and four cyclic polymer units, respectively, were prepared by the click linking process using single-cyclic and dicyclic kyklo-telechelics having complementary alkyne and azide groups at the designated positions of cyclic and dicyclic units, which were obtained by the ESA-CF procedure.25,36 The subsequent intramolecular olefin metathesis reaction, that is, the clip folding, was conducted under dilution by repeated addition of the Grubbs catalyst to produce respective triply f used-tetracyclic and quadruply fused-pentacyclic poly(THF)s.36 (Figure 13) These products were finally isolated by means of the preparative SEC fractionation technique and unequivocally characterized by means of 1H NMR, MALDITOF mass, and SEC techniques.25,36 3.5. hybrid-Multicyclic Constructions

The three subclasses of spiro, bridged, and f used forms are included in multicyclic polymer topologies, as seen in Figure 1, where the corresponding three dicyclic constructions are 8, manacle, and θ forms, respectively. On the other hand, a class of hybrid-multicyclic polymer topologies are included in the tricyclic and further multicyclic constructions, as seen also in Figure 1. These polymer topologies have been constructed by taking advantage of the click polymer linking in conjunction with the ESA-CF process, which could afford a complementary reactive 2669


Article


Figure 14. Construction of hybrid-multicyclic polymer topologies by the ESA-CF in conjunction with the click process by using kyklo-telechelic precursors having alkyne or azide groups.

pair of kyklo-telechelic poly(THF)s having either an alkyne or an azide group at the designated positions37,38 (Figure 14). Thus, first, a set of dicyclic kyklo-telechelic θ- and 8-shaped poly(THF)s both having an alkyne group at the junction position were prepared by the ESA-CF procedure. A series of complementary reactive linear and kyklo-telechelic poly(THF)s having azide groups include a monocyclic poly(THF) having an azide group, as well as a linear-cyclic (tadpole) and a lineardicyclic (twin-head tadpole) counterparts, both having an azide groups at the tail-end position, which were obtainable through the tandem click reactions between the respective mono- and dicyclic 8-shaped kyklo-telechelic poly(THF)s having an alkyne group and a linear asymmetric telechelics having azide and hydroxyl groups, followed by the esterification with 4azidobenzoic acid.37 A variety of hybrid-tricyclic polymer topologies composed of dicyclic (θ- or 8-shaped) and monocyclic (simple ring or tadpole-shaped) units and, moreover, an unprecedented hybrid-tetracyclic topology combined with all three elementary dicyclic units of θ-, 8-, and manacle-forms were subsequently constructed through the effective click-linking of complementarily reactive kyklo-telechelic precursors37 (Figure 14). Furthermore, tetracyclic and hexacyclic spiro/bridged hybrid polymer topologies, having either a double-8 or a double-trefoil forms, were obtained by the alkyne−azide click polymer linking process between the complementary reactive kyklo-telechelic precursors, where the adversarial kinetic effects by sterically demanding polymer reagents and by the low concentration of reactive groups were apparently overcome.38

employed to construct complex multicyclic macromolecular architectures, including a series of tri-, tetra-, and even hexacyclic polymer topologies of spiro- and bridged-forms and three doubly f used-tricyclic (β-, γ-, and δ-graph) forms, as well as triply f used-tetracyclic and quadruply f used-pentacyclic forms, in addition to hybrid-multicyclic polymer constructions comprised of three subclasses of spiro, bridged, and f used units. Numerous future opportunities are anticipated in topological polymer chemistry to extend the ongoing developments. Together with the progress in theories and simulations,39 we will become able to achieve unique topological control in static and dynamic properties relying on topological geometry conjectures, sometimes counterintuitive to the commonsense recognition from Euclidian geometry conjectures. And as a variety of topologically defined but complex polymers have now become available systematically, any topological effects in polymer materials will be uncovered for eventual applications in practice. Thus, we are now entering into an exciting era of polymer science and polymer materials engineering based on the precision design of polymer topologies, which is comparable to the “Cambrian explosion period” experienced in the evolution of life systems. Topological polymer chemistry will certainly contribute to opening such a new exciting paradigm.

■

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

4. CONCLUSIONS AND PERSPECTIVES In this Account, the ongoing developments of topological polymer chemistry have been outlined by showing recent achievements in the precision design of topologically significant macromolecular architectures, with a particular emphasis on a class of multicyclic polymer topologies, including three subclasses of spiro, bridged, and f used forms. The ESA-CF protocol is shown as a powerful means for topological polymer chemistry, to provide not only three dicyclic constructions having either 8 (spiro), manacle (bridged), or θ (f used) forms, as well as a tricyclic trefoil (spiro) construction, but also a formidably complex, triply f used-tetracyclic macromolecular K3,3 graph construction, which is known as a prototypical nonplanar graph in topological geometry and has been identified as topologically equivalent to naturally occurring cyclic polypeptides (cyclotides). Furthermore, the ESA-CF protocol in conjunction with tandem click and clip reactions was

Yasuyuki Tezuka: 0000-0001-5264-9846 Notes

The author declares no competing financial interest. Biography Yasuyuki Tezuka is a Professor at Tokyo Institute of Technology. He obtained a B.S. (1976) and a M.S. (1978) degree in synthetic chemistry at The University of Tokyo. He moved to Ghent University (Belgium) in 1979 as a fellowship student of Belgian (Flemish) government and completed his doctorate study in Belgium in 1982. He then returned to Japan to start an academic carrier as an assistant professor at Nagaoka University of Technology and was promoted to associate professor in 1991. In 1994, he moved to Tokyo Institute of Technology (Department of Organic and Polymeric Materials), where he has been a full professor since 2003. He received Tokyo Tech Award of Best Teacher, 2004, and The Award of the Society of 2670


Article


(16) Tezuka, Y.; Tsuchitani, A.; Oike, H. Synthesis of Polymeric Topological Isomers through Electrostatic Self-Assembly and Covalent Fixation with Star Telechelic Precursors. Macromol. Rapid Commun. 2004, 25, 1531−1535. (17) Oike, H.; Imamura, H.; Imaizumi, H.; Tezuka, Y. Tailored Synthesis of Branched and Network Polymer Structures by Electrostatic Self-Assembly and Covalent Fixation with Telechelic Poly(THF) Having N-Phenylpyrrolidinium Salt Groups. Macromolecules 1999, 32, 4819−4825. (18) Kimura, A.; Kawauchi, S.; Yamamoto, T.; Tezuka, Y. SN2 Regioselectivity in the Esterification of 5- and 7-Membered Azacycloalkane Quaternary Salts: A DFT Study to Reveal the Transition State Ring Conformation Prevailing over the Ground State Ring Strain. Org. Biomol. Chem. 2014, 12, 6717−6724. (19) Kimura, A.; Takahashi, S.; Kawauchi, S.; Yamamoto, T.; Tezuka, Y. Regioselective Ring-Emitting Esterification on Azacyclohexane Quaternary Salts: A DFT and Synthetic Study for Covalent Fixation of Electrostatic Self-Assemblies. J. Org. Chem. 2013, 78, 3086−3094. (20) Adachi, K.; Takasugi, H.; Tezuka, Y. Telechelics Having Unstrained Cyclic Ammonium Salt Groups for Electrostatic Polymer Self-Assembly and Ring-Emitting Covalent Fixation. Macromolecules 2006, 39, 5585−5588. (21) Tezuka, Y.; Tsuchitani, A.; Yoshioka, Y.; Oike, H. Synthesis of θShaped Poly(THF) by Electrostatic Self-Assembly and Covalent Fixation with Three-armed Star Telechelics Having Cyclic Ammonium Salt Groups. Macromolecules 2003, 36, 65−70. (22) Craik, D. J. Seamless Proteins Tie Up Their Loose Ends. Science 2006, 311, 1563−1564. (23) Tezuka, Y.; Komiya, R.; Ido, Y.; Adachi, K. Synthesis and Palladium-mediated Cross-coupling Reaction of Cyclic (kyklo-) and Open-chain (kentro-) Telechelic Precursors. React. Funct. Polym. 2007, 67, 1233−1242. (24) Sugai, N.; Heguri, H.; Ohta, K.; Meng, Q.; Yamamoto, T.; Tezuka, Y. Effective Click Construction of Bridged- and SpiroMulticyclic Polymer Topologies with Tailored Cyclic Prepolymers (kyklo-Telechelics). J. Am. Chem. Soc. 2010, 132, 14790−14802. (25) Sugai, N.; Heguri, H.; Yamamoto, T.; Tezuka, Y. A Programmed Polymer Folding: Click and Clip Construction of Doubly Fused Tricyclic and Triply Fused Tetracyclic Polymer Topologies. J. Am. Chem. Soc. 2011, 133, 19694−19697. (26) Oike, H.; Hamada, M.; Eguchi, S.; Danda, Y.; Tezuka, Y. Novel Synthesis of Single and Double Cyclic Polystyrenes by Electrostatic Self-Assembly and Covalent Fixation with Telechelics Having Cyclic Ammonium Salt Groups. Macromolecules 2001, 34, 2776−2782. (27) Hayashi, S.; Adachi, K.; Tezuka, Y. ATRP-RCM Synthesis of 8shaped Poly(methyl acrylate) Using a 4-Armed Star Telechelics. Polym. J. 2008, 40, 572−576. (28) Tezuka, Y.; Komiya, R.; Washizuka, M. Designing 8-Shaped Polymer Topology by Metathesis Condensation with Cyclic Poly(THF) Precursors Having Allyl Groups. Macromolecules 2003, 36, 12− 17. (29) Ko, Y. S.; Yamamoto, T.; Tezuka, Y. Click Construction of Spiro- and Bridged-Quatrefoil Polymer Topologies with KykloTelechelics Having an Azide Group. Macromol. Rapid Commun. 2014, 35, 412−416. (30) Wada, H.; Yamamoto, T.; Tezuka, Y. Concise Click/ESA-CF Synthesis of Periodically-Positioned Trifunctional kyklo-Telechelic Poly(THF)s. Macromolecules 2015, 48, 6077−6086. (31) Hossain, Md. D.; Jia, Z.; Monteiro, M. J. Complex Polymer Topologies Built from Tailored Multifunctional Cyclic Polymers. Macromolecules 2014, 47, 4955−4970. (32) Tezuka, Y.; Takahashi, N.; Satoh, T.; Adachi, K. Synthesis of Polymeric Topological Isomers Having Theta- and ManacleConstructions with Olefinic Groups at Designated Positions. Macromolecules 2007, 40, 7910−7918. (33) Tezuka, Y.; Ohashi, F. Synthesis of Polymeric Topological Isomers through Double Metathesis Condensation with H-Shaped Telechelic Precursors. Macromol. Rapid Commun. 2005, 26, 608−612.

Polymer Science, Japan (2010). His current research is focused on topological polymer chemistry, designing topologically unique macromolecular architectures, and uncovering their topology effects. He currently serves as an Editor of Reactive and Functional Polymers.

■

ACKNOWLEDGMENTS The author is grateful to many co-workers, whose names appear in the references, for their enthusiastic collaboration. This work was supported in part by a grant from the Ministry of Education, Science and Culture, Japan, through the Japan Society of Promotion of Science, Generative Research Fields (26310206) to be extended with Grant-in-Aid for Scientific Research on Innovative Areas (17H06463).

■

DEDICATION This Account is dedicated to Professor Eric Goethals to celebrate his 80th birthday.

■

REFERENCES

(1) Tezuka, Y., Ed. Topological Polymer Chemistry: Progress of cyclic polymers in syntheses, properties and functions; World Scientific: Singapore, 2013. (2) Grayson, S. M., Getzler, Y. D. Y. L., Zhang, D. Eds. Cyclic polymers: New developments, Special issue of Reactive and Functional Polymers, 2014; vol. 80. (3) Josse, T.; De Winter, J.; Gerbaux, P.; Coulembier, O. Cyclic Polymers by Ring-Closure Strategies. Angew. Chem., Int. Ed. 2016, 55, 13944−13958. (4) Brown, H. A.; Waymouth, R. M. Zwitterionic Ring-Opening Polymerization for the Synthesis of High Molecular Weight Cyclic Polymers. Acc. Chem. Res. 2013, 46, 2585−2596. (5) Yamamoto, T.; Tezuka, Y. Cyclic Polymers Revealing Topology Effects upon Self-assemblies, Dynamics and Responses. Soft Matter 2015, 11, 7458−7468. (6) Verbraeken, B.; Hoogenboom, R. Cyclic Polymers: From Scientific Curiosity to Advanced Materials for Gene Delivery and Surface Modification. Angew. Chem., Int. Ed. 2017, 56, 7034−7036. (7) Tezuka, Y.; Oike, H. Topological Polymer Chemistry: Systematic Classification of Nonlinear Polymer Topologies. J. Am. Chem. Soc. 2001, 123, 11570−11576. (8) Shimokawa, K.; Ishihara, K.; Grainge, I.; Sherratt, D. J.; Vazquez, M. FtsK-dependent XerCD-dif Recombination Unlinks Replication Catenanes in a Stepwise Manner. Proc. Natl. Acad. Sci. U. S. A. 2013, 110, 20906−20911. (9) Seeman, N. C. Nanomaterials Based on DNA. Annu. Rev. Biochem. 2010, 79, 65−87. (10) de Veer, S. J.; Weidmann, J.; Craik, D. Cyclotides as Tools in Chemical Biology. Acc. Chem. Res. 2017, 50, 1557−1565. (11) Oike, H.; Imaizumi, H.; Mouri, T.; Yoshioka, Y.; Uchibori, A.; Tezuka, Y. Designing Unusual Polymer Topologies by Electrostatic Self-Assembly and Covalent Fixation. J. Am. Chem. Soc. 2000, 122, 9592−9599. (12) Suzuki, T.; Yamamoto, T.; Tezuka, Y. Constructing a Macromolecular K3,3 Graph through Electrostatic Self-Assembly and Covalent Fixation with a Dendritic Polymer Precursor. J. Am. Chem. Soc. 2014, 136, 10148−10155. (13) Oike, H.; Kobayashi, S.; Mouri, T.; Tezuka, Y. KykloTelechelics: Tailored Synthesis of Cyclic Poly(tetrahydrofuran)s Having Two Functional Groups at Opposite Positions. Macromolecules 2001, 34, 2742−2744. (14) Pineri, M., Eisenberg, A., Eds. Structure and Properties of Ionomers; Kluwer: Dordrecht, 1986. (15) Tezuka, Y.; Tsuchitani, A.; Oike, H. Synthesis of Polymeric Topological Isomers through Electrostatic Self-Assembly and Covalent Fixation with Telechelic Poly(THF) Having Cyclic Ammonium Salt Groups. Polym. Int. 2003, 52, 1579−1583. 2671


Article

Accounts of Chemical Research (34) Tezuka, Y.; Fujiyama, K. Construction of Polymeric δ-Graph: A Doubly Fused Tricyclic Topology. J. Am. Chem. Soc. 2005, 127, 6266− 6270. (35) Igari, M.; Heguri, H.; Yamamoto, T.; Tezuka, Y. Folding Construction of Doubly Fused Tricyclic, β- and γ-Graph Polymer Topologies with kyklo-Telechelic Precursors Obtained through an Orthogonal Click/ESA-CF Protocol. Macromolecules 2013, 46, 7303− 7315. (36) Heguri, H.; Yamamoto, T.; Tezuka, Y. Folding Construction of a Pentacyclic Quadruply f used Polymer Topology with Tailored kykloTelechelic Precursors. Angew. Chem., Int. Ed. 2015, 54, 8688−8692. (37) Tomikawa, Y.; Fukata, H.; Ko, Y. S.; Yamamoto, T.; Tezuka, Y. Construction of Double-Eight and Double-Trefoil Polymer Topologies with Core-Clickable kyklo-Telechelic Precursors. Macromolecules 2014, 47, 8214−8223. (38) Tomikawa, Y.; Yamamoto, T.; Tezuka, Y. Construction of Hybrid-Multicyclic Polymer Topologies Composed of Dicyclic Structure Units by Means of An ESA-CF/Click-linking Protocol. Macromolecules 2016, 49, 4076−4087. (39) Uehara, E.; Deguchi, T. Statistical and Hydrodynamic Properties of Topological Polymers for Various Graphs Showing Enhanced Short-range Correlation. J. Chem. Phys. 2016, 145, 164905.

2672


Topological Polymer Chemistry Designing Complex Macromolecular

Recommend Documents