Synthesis and applications of helical polymers with dynamic and static memories of helicity

Abstract

This review mainly highlights our studies on the synthesis of one-handed helical polymers with a static memory of helicity based on the noncovalent helicity induction with a helical-sense bias and subsequent memory of the helicity approach that we developed during the past decade. Apart from the previous approaches, an excess one-handed helical conformation, once induced by nonracemic molecules, is immediately retained (“memorized”) after the complete removal of the nonracemic molecules, accompanied by a significant amplification of the asymmetry, providing novel switchable chiral materials for chromatographic enantioseparation and asymmetric catalysis as well as a highly sensitive colorimetric and fluorescence chiral sensor. A conceptually new one-handed helix formation in a racemic helical polymer composed of racemic repeating units through the deracemization of the pendants is described.

1. Introduction

Since the discoveries of the right-handed α-helix and double-helix for proteins and DNA, respectively, in the early 1950s, chemists have made an enormous effort to synthesize preferred-handed helical polymers through polymerization of monomers not only to mimic sophisticated biological helices and elaborate functions in living systems but also to develop helical polymer-based advanced chiral materials for sensing and separation of enantiomers and for asymmetric catalysis.^1),2) Thus far, a wide variety of preferred-handed helical polymers with different backbones consisting of different repeating monomer units has been synthesized, as comprehensively reviewed elsewhere.^1)–10) Figure 1 summarizes the leading and recent examples of synthetic helical polymers showing an optical activity solely due to an excess one-handed helical conformation, which can be categorized into two types, namely, static and dynamic helical polymers based on their high and low helix-inversion barriers, respectively.^1),2),4) Static and dynamic helices are used here to refer to thermally stable and thermally metastable helices, respectively, and they possess a long helical persistence length (see Fig. 1B). Optically active static and dynamic helical polymers have been synthesized either by the helix-sense-selective polymerization of achiral bulky monomers with chiral catalysts or initiators (Fig. 1A) or by the polymerization of optically active monomers or copolymerization of chiral/achiral or nonracemic monomers (Fig. 1B), respectively.

Fig. 1.

Static (A) and dynamic (B) helical polymers and their representative structures. (C) Dynamic helical copolymers of isocyanates showing “sergeants-and-soldiers (S&S)” effect and “majority rule (MR)”.

In 1979, Okamoto and coworkers, for the first time, succeeded in the synthesis of a one-handed helical, fully isotactic vinyl polymer (1) by the helix-sense-selective polymerization of achiral but bulky triphenylmethyl methacrylate (TrMA) using chiral anionic initiators complexed with (−)-sparteine (Fig. 1A).^3),11) Subsequently, they discovered that single-handed helical 1 resolved a variety of racemic compounds when used as a chiral stationary phase (CSP) for high-performance liquid chromatography (HPLC)^4),12) and it has been commercialized since 1982. An analogous vinyl polymer (2),¹³⁾ polychloral (3),^14),15) polyisocyanides bearing bulky t-butyl (4)¹⁶⁾ or aromatic substituents (8),¹⁷⁾ poly(carbodiimide)s (5),¹⁸⁾ poly(quinoxaline-2,3-diyl)s (6),¹⁹⁾ poly(phenylacetylene)s (7),²⁰⁾ and polycarbenes (9)²¹⁾ are static helical polymers due to their sufficiently high helix-inversion barriers (Fig. 1A). Hence, the excess one-handed helical polymers (2–9) have also been synthesized by the helix-sense-selective polymerization of the corresponding achiral monomers bearing bulky substituents with a chiral catalyst or initiator under kinetic control. The stability of the helical conformations of the static helical polymers significantly depends on the structures of the repeating monomer units and chain length or molecular weight of the polymers. Their helical conformations tend to be more stable as the molecular weight increases or gradually racemize in solution at ambient temperature with time.^1)–4) Static helical polymers (1 and 4) and oligomers (2, 3, and 6) with a certain degree of polymerizations maintain their one-handed helical conformations in solution. Hence, both right (P)- and left (M)-handed helices can be isolated from the corresponding optically inactive racemic mixtures by chiral chromatography at ambient temperature, which provides convincing evidence for the static helical conformation.^{1)–4),15),16),19)} The activation energy (E_a) values for the helix-sense inversion (racemization) of some static helical polymers and oligomers have been estimated, which were summarized in a review article¹⁾ (e.g., the E_a of a low molecular-weight static helical polymer (2) was estimated to be 96 kJ mol⁻¹).

Another unique dynamic helical polymer was discovered by Green and coworkers in 1988 for polyisocyanates.²²⁾ The helix-inversion barriers of polyisocyanates composed of achiral isocyanates, such as 10 and 11, are very low so that they consist of an equal mixture of interconvertible long (P)- or (M)-handed helical segments (i.e., long helical persistence length (l)) separated by energetically unfavorable few helical reversals (Fig. 1B).^5),23) Therefore, dynamic helical polymers in dynamic equilibrium are not achiral but inherently chiral, that is, dynamically racemic. Hence, it seems impossible to separate dynamically racemic helical polymers into both helices with optical activity by chiral chromatography. However, when a small amount of optically pure isocyanates is copolymerized with achiral isocyanates or (R)- and (S)-isocyanates with low enantiomeric excess (ee) values are copolymerized, almost one-handed helical polyisocyanates can be produced under thermodynamic control by the significant amplification of the asymmetry.²⁴⁾ These unique amplification phenomena are called the “sergeants-and-soldiers (S&S)” effect²⁵⁾ and “majority rule (MR)”²⁶⁾ (Fig. 1C), respectively, and have been accepted as a universal concept that is valuable and applicable to other helical systems, including supramolecular helical assemblies or polymerization.^27)–34) A similar S&S effect and/or MR has been observed in other dynamic helical polymers, such as poly(phenyl isocyanate)s (12),⁴⁾ polysilanes (13),⁶⁾ poly(quinoxaline-2,3-diyl)s (14),³⁵⁾ poly(carbodiimide)s (15),³⁶⁾ and polyacetylenes (16).^1),2),7) As shown in Fig. 1A,B, certain helical polymers composed of identical polymer backbone structures, such as poly(carbodiimide)s (5, 15),^18),36) poly(quinoxaline-2,3-diyl)s (6, 14),^19),35) and poly(mono-substituted acetylene)s (7, 16),^{7),20),37),38)} have been reported to show both static and dynamic helical properties when the chiral or achiral substituents in their monomer structures are modified, as summarized in review articles.^1),2)

Unlike previously reported synthetic approaches (Fig. 1), in 1995,³⁹⁾ we developed a unique and versatile method to induce either a P- or M-handed helical conformation in dynamically racemic helical cis-poly(acetylene)s (PAs), including the cis-poly(phenylacetylene)s (cis-PPAs) prepared after the polymerization of achiral acetylenes carrying functional groups at the pendants, such as acidic residues (17–19), through noncovalent interactions with chiral molecules, such as chiral amines, which was accompanied by a significant amplification of the asymmetry (Fig. 2A).¹⁾ The cis-polyene geometry of PAs and PPAs synthesized using commercially available rhodium (Rh) catalysts, such as [Rh(nbd)Cl]₂ (nbd: norbornadiene),^40)–42) has been proven to be important for helix formation,^43)–45) along with the excellent enantioselectivities and chiral recognition abilities when used as an asymmetric catalyst⁴⁶⁾ and a CSP for HPLC,⁴⁷⁾ respectively. In 1999, we discovered the unprecedented one-handed helicity memory induced in 17,⁴⁸⁾ 18,^49),50) and 19⁵¹⁾ in solution after the complete removal of the chiral amines and replacement with achiral amines (Fig. 2A). In the absence of achiral amines, the induced helicity memory is immediately lost because the induced helical conformation is dynamic; thus, it is called the “dynamic memory of helicity”.

Fig. 2.

Helical polymers with dynamic (A) and static (B) memories of macromolecular helicity and their representative structures. (C) Static helix formation of racemic helical polymers through the deracemization of the racemic pendants.

In contrast to the previously reported optically active static (Fig. 1A) and dynamic helical copolymers (Fig. 1C), the “helicity induction and dynamic memory of helicity” approach (Fig. 2A) requires neither chiral monomers nor chiral catalysts and initiators for producing excess one-handed helical polymers during polymerization but the use of achiral amines is essential for the dynamic memory of the induced helicity in 17–19, which interferes with practical applications. In 2014, we discovered the “static memory of helicity”, which is different from the first-generation “dynamic memory of helicity” such that preferred-handed helicity induced by nonracemic molecules can be subsequently memorized not only in solution but also in the solid state with a significant amplification of the asymmetry, leading to a long-lasting helicity memory (Fig. 2B).^2),52) Hence, replacement with achiral molecules is no longer necessary. This second-generation “static memory of helicity” has been successfully applied to the developments of unique chirality sensors⁵³⁾ as well as switchable CSP and asymmetric catalysis, through which the elution orders of enantiomers⁵²⁾ and the chirality of the products⁵⁴⁾ can be reversibly switched.

In this review, a class of novel helical polymers with dynamic and static memories of helicity (Fig. 2A,B)^2),55) and a racemic monomer-based one-handed helix formation through the deracemization of racemic pendants (Fig. 2C),⁵⁴⁾ along with their applications to chiral materials that we have developed during the past decade, are described. A related topic of chiral memory effect^56)–60) observed in supramolecular systems is not described in this review, which has been comprehensively reviewed elsewhere.^1),2)

2. Macromolecular helicity induction in poly(phenylacetylene)s (PPAs) and its dynamic memory of helicity (first generation of helicity memory)

As briefly described above (Fig. 2A), a dynamically racemic helical cis-PPA derivative, such as 17 bearing carboxy groups, formed a one-handed helical conformation in the presence of optically active amines, such as (R)-21 (Fig. 3A).³⁹⁾ The ion-paired 17–(R)-21 complex showed a characteristic circular dichroism (CD) induced in the π-conjugated polyene backbone regions in dimethyl sulfoxide (DMSO) (Fig. 3B).⁴⁵⁾ The excess one-handed helical conformation of 17 biased by (R)-21 was not static but dynamic. Therefore, the induced CD (ICD) instantly disappeared when (R)-21 was removed from the polymer by exposure to trifluoroacetic acid. However, the excess one-handed helicity induced in 17 was retained, that is, “memorized”, after ion-paired (R)-21 was completely removed and replaced with achiral amines, such as 22a and 22b, by size-exclusion chromatography (SEC) using DMSO containing 22a or 22b as the mobile phase, followed by the isolation of helicity-memorized 17 (Fig. 3A).^48),61) The isolated 17 complexed with achiral 22a or 22b showed an intense ICD comparable to that before the SEC fractionation with memory efficiency values of 87% (Fig. 3B) and 82%, respectively. The dynamic memory of helicity of 17 lasted for an extremely long time with a half-life time of over two years because of the free ion formation of the carboxy groups of 17 with achiral amines (22), resulting in an increase in the helix-inversion barrier by the intramolecular electrostatic repulsion between the neighboring negatively charged carboxylate groups (Fig. 3A, right).⁶¹⁾ As a result, the thermodynamically controlled, dynamic helical conformations of cis-PPAs (17–19 in Fig. 2A) with an excess one-handedness assisted by chiral amines were locked, transforming into kinetically trapped static helical cis-PPAs with a dynamic memory of helicity. Such a conformational helicity memory has been reported for poly(hydroxyphenylacetylene)s,⁶²⁾ syndiotactic polystyrene,⁶³⁾ and doped polyaniline derivatives⁶⁴⁾ but in the solid state.

Fig. 3.

(A) One-handed helicity induction in 17 with (R)-21 through ion pair formation, followed by its dynamic memory of helicity after replacement with achiral amines 22 through free ion formation. (B) CD spectra of the 17–(R)-21 complex (red) and the isolated 17 (blue) by SEC fractionation. The memory efficiencies of the isolated 17 were estimated based on the ICD intensity changes before and after the SEC fractionation. Reproduced with permission from Ref. 61. Copyright 2004, American Chemical Society.

Conversely, the direct observation and elucidation of the helical structures of synthetic helical polymers by microscopy have been a long-standing problem in polymer science.^1),2) In 2006, we directly observed for the first time the helical structures, including the helical pitch, handedness (P or M), helix-sense excess (hse), and helical reversal, using high-resolution atomic force microscopy (AFM) coupled with organic solvent vapor exposure combined with X-ray diffraction (XRD) studies of oriented films derived from lyotropic nematic and cholesteric liquid crystalline (LC) helical PPA derivatives.^65),66) The rod-like cholesteric LC helical D-23 bearing D-Ala residues with a long n-decyl chain as the side groups self-assembled on highly-oriented pyrolytic graphite (HOPG) upon exposure to benzene vapors, thus forming two-dimensional (2D) helix bundles (2D crystals) on the flat monolayers of D-23 on HOPG. The high-resolution AFM images, along with the XRD results, enabled the direct determination of the helical structure of D-23, which possessed an M-handed 11 unit/5 turn (11/5) helix with a helical pitch of 2.3 nm (Fig. 4B, left),⁶⁷⁾ and D-23 had an opposite P-handed helical array with respect to the pendant arrangements. The helical sense of M-handed D-23 in nonpolar solvents, such as toluene and CCl₄, inverted into the opposite P-helix (M-handed helical array of the pendant arrangements) in polar solvents, such as chloroform and THF (Fig. 4B, right), showing mirror-imaged CD spectra, due to the on and off switching of the intramolecular hydrogen-bonding networks, respectively. The persistence length (q), a useful measure to evaluate the stiffness of rigid rod polymers, changed from 126 nm in toluene to 19 nm in THF (Fig. 4A).⁶⁸⁾ The direct evidence for such an intriguing helix inversion of D-23 in different solvents was also visualized by high-resolution AFM upon exposure to each solvent vapor (Fig. 4B).^69),70)

Fig. 4.

(A) Helix inversion of D-23 in dilute solution regulated by switching on and off the intramolecular hydrogen bonding. The dotted lines (left) represent intramolecular hydrogen-bonding networks. (B) AFM images of 2D self-assembled P-handed helical D-23 with an M-handed helical array of the pendants spin cast on HOPG from a dilute THF solution (right), followed by helix inversion after benzene vapor exposure, producing 2D self-assembled M-handed helical D-23 with a P-handed helical array of the pendants (left). Reproduced with permission from Ref. 69. Copyright 2006, American Chemical Society.

Given the success in visualizing the one-handed helical structures of D-23 by high-resolution AFM through the 2D crystal formation on a substrate, we have successfully observed the helical structures of other helical polymers,^65),66) such as poly(phenyl isocyanide)s,^71)–73) chiral/achiral copolymers of phenylacetylenes,^70),74) the stereocomplex of isotactic PMMA and st-PMMA,^75),76) complementary double-stranded helical polymers,⁷⁷⁾ helical foldamers,⁷⁸⁾ and supramolecular helical polymers formed with small chiral/achiral molecules.^79),80) Helical structures of a series of optically active helical PPAs have also been successfully observed using AFM by Freire, Riguera, and coworkers.^81),82)

3. Static memory of macromolecular helicity

3.1. Poly(biphenylylacetylene)s (PBPAs): second generation of helicity memory.

In 2014, we succeeded in inducing both the macromolecular helicity of the polymer backbone and axial chirality of the biphenyl pendants with a helical-sense bias in an analog of dynamic helical PPA, a poly(biphenylylacetylene) derivative (cis-PBPA in Fig. 2B) composed of achiral monomer units bearing methoxymethoxy (MOM) and n-dodecyloxy groups at the 2,2′- and 4′-positions of the biphenyl pendants, respectively (24a, Fig. 5A), in the presence of chiral alcohols, such as (S)- or (R)-25 as a helix inducer, showing an intense ICD (Fig. 5B).⁵²⁾ In contrast to the dynamic memory of helicity in the PPAs (Figs. 2A and 3), the induced one-handed helicity and axial chirality in 24a were automatically memorized, accompanied by the amplification of the asymmetry in solution and in the solid state after the complete removal of the chiral alcohols, leading to the second-generation “static memory of helicity” (Fig. 5A).⁵²⁾ Hence, the replacement of the chiral helix inducers with achiral molecules was no longer necessary for this static memory of helicity, which could be fully achieved in the solid state. A similar static memory of helicity but with a different mechanism was also observed in poly(4-carboxyphenyl isocyanide) (20 in Fig. 2B) through configurational isomerization around the C=N double bonds (syn–anti isomerization) into one single configuration^83),84) and st-PMMA through gelation in toluene (Fig. 2B).⁸⁵⁾ The helix-memorized st-PMMA formed crystalline inclusion complexes with a variety of chiral higher fullerenes,⁸⁶⁾ helical oligopeptides,⁸⁷⁾ and helical polylactides⁸⁸⁾ within the helical cavity of st-PMMA in a size-, enantio-, and/or helical-sense selective manner.

Fig. 5.

(A) Reversible switching and static memory of helicity of 24a and its axial chirality at the biphenyl pendants in the solid state as well as in solution. Structures of PBPAs with different substituents at the 2,2′- and 4′-positions of the biphenyl pendants showing the static memory effect (26–29) (A) and those of PBPA homopolymers (30–32) and copolymers (33) showing no memory effect (C) are also shown. (B) CD and absorption spectra of 24a with (S)-25 in n-hexane at 25 °C (i) and −10 °C (ii) after standing at 25 °C for 6 h, and the isolated 24a in n-hexane at −10 °C recovered from i (iii) and those in n-hexane at −10 °C after immersing 24a in (S)-25 at 25 °C for 6 h in the solid state, followed by isolation (iv) and subsequent immersion in (R)-25 at 25 °C for 6 h (v). Reproduced with permission from Ref. 52. Copyright 2014, Nature Publishing Group.

Interestingly, the helical handedness (P or M) and axial twist-sense of 24a could be readily switched and immediately memorized upon interactions with the opposite-handed alcohol in the solid state, followed by the removal of the chiral alcohol (Fig. 5A,B),⁵²⁾ thereby providing the first switchable CSP for separating enantiomers, such as 34a by HPLC. The elution orders of the 34a enantiomers could be switched in a reversible way by the sequential treatment of as-prepared 24a packed in a column with (S)- and (R)-25 (ee > 50%) in an alternating manner (Fig. 6A,B).

Fig. 6.

(A) A switchable CSP for the HPLC enantioseparation based on reversible M- and P-handed helicity induction and subsequent static memory of helicity in 24a by sequential treatment with (S)- and (R)-rich 25 (ee = 50%) in an alternating manner. (B) Chromatograms for the resolution of (−)-isomer-rich 34a on M-24a (a) and P-24a (b) prepared by treatment with (S)- and (R)-25, respectively. Reproduced with permission from Ref. 52. Copyright 2014, Nature Publishing Group. (C) Structures of 28b used as a CSP for HPLC and racemates (34 and 35) resolved on 28b.

To investigate the mechanism of this unique dual static memory, along with its substituent effect, we synthesized PBPAs carrying a series of different substituents at the 2,2′- and 4′-positions of the biphenyl groups (26–32) (Fig. 5A,C).^89)–92) The PBPA derivatives with the 2,2′-methoxy (30), -propoxy (31), and -methoxyethoxy groups (32) instead of the 2,2′-MOM ones as well as the copolymers (33a,b) showed no memory effect,^52),53) indicating the primary role of the 2,2′-alkoxymethoxy groups of the consecutive biphenyl units in the static helicity memory of PBPAs. We presumed that rotation around the axially chiral biphenyl units was coupled mechanically to the helicity of the polymer main chain so that the biphenyl pendants bearing alkoxymethoxy groups would act as a geared molecular brake, thus preventing the racemization of the helical polymer backbone. Therefore, various functional substituents, such as the alkoxycarbonyl (ester) (26a,b), acyloxy (27a,b), and carbamoyloxy (carbamate) (28a,b) groups, could be introduced at the 4′-position of 2,2′-MOM-bound PBPAs by keeping the static memory of helicity.^90),91),93) A similar static memory of helicity was also available for PBPAs with the 2,2′-acetyloxy groups (29).⁹²⁾ The enantioseparation abilities of the helicity-memorized PBPAs when used as CSPs for HPLC (24a, 26b, 27b, 28b, and 29b) significantly depended on the substituents at the 2,2′- and 4′-positions of the biphenyl groups, and 28b bearing 4′-carbamate groups showed an excellent resolving ability and separated various racemic compounds, such as axially chiral binaphthyl derivatives (34b–d) and metal acetylacetonate complexes (35) (Figs. 5A and 6C).^90),91),93)

The unique static helicity memory of the PBPAs showing a remarkable amplification of the asymmetry enabled us to directly sense the hardly detectable chirality of quaternary (36) and tertiary (37–42) hydrocarbons by CD using 24a as a powerful chirality sensor (Fig. 7).⁵³⁾ An excess of a single-handed helix induced in 24a in an extremely small amount of liquid (S)- or (R)-hydrocarbons was instantly memorized, resulting in an ICD after dilution. The Cotton effect signs could be used to determine the absolute configurations of the chiral hydrocarbons.

Fig. 7.

Structures of quaternary (36) and tertiary (37–42) chiral hydrocarbons and CD and absorption spectra of 24a dissolved in a small amount of (S)- and (R)-36 (30 µL), followed by heating at 50 °C and then diluting with n-hexane measured at −10 °C. Reproduced with permission from Ref. 53. Copyright 2018, American Chemical Society.

The fully one-handed helical 2,2′-MOM-bound PBPAs could also be synthesized by introducing optically active residues at the 4′-position through an ester or ether linkage,^92),94) e.g., (S)-43 (Fig. 8A), which showed an intense ICD even though the stereogenic centers were positioned far from the biphenyl pendants and further from the polymer main chain. The CD spectral pattern and intensity of (S)-43 were identical to those of 26a with a dual static memory induced by (R)- or (S)-25. The corresponding PPA derivative bearing the identical optically pure residue ((S)-44) (Fig. 8A) exhibited no CD in the polymer backbone, indicating the critical role of the axially chiral biphenyl pendants of 26a in the static memory of the induced helicity.⁹⁴⁾ Interestingly, unexpectedly strong S&S and MR effects were observed for the copolymers of chiral/achiral (45) and chiral/chiral (R/S) (46) monomers. The copolymers composed of 20 mol% chiral monomers and chiral monomers of 20% ee exhibited strong ICDs as intense as those of the (S)- or (R)-homopolymer (43) (Fig. 8B,C).⁹⁴⁾

Fig. 8.

Structures of PBPA homopolymers ((S)-43, 26a) (A) and chiral/achiral (45) and chiral/chiral (46) copolymers (B). The structure of PPA homopolymer ((S)-44) is also shown. (C) Plots of ICD intensity changes of 45 (left) and 46 (right) against the chiral unit content and % ee of the monomer unit, respectively (red circles), measured in methylcyclohexane (MCH) at 25 °C. ICD intensity changes of 45 (r = 0) (left) and rac-46 (% ee = 0) (right) (green circles) in the presence of (R)-25 (left) and (S)-25 (right) in MCH (MCH/25 = 80/20, v/v) measured at 25 °C after standing at 25 °C for 5 days are also shown (blue circles). Reproduced with permission from Ref. 94. Copyright 2019, American Chemical Society.

Taking advantage of the helicity induction and subsequent static memory of the helicity strategy observed in the PBPAs, fully one-handed P- and M-helices could be induced and memorized even in an optically inactive racemic PBPA (rac-46 (r = 0.5) or rac-47) consisting of completely racemic repeating units using enantiomeric helix inducers ((R)- or (S)-25) (Fig. 8B,C).^94),95) The resultant P- and M-helical PBPAs (P- and M-rac-47) could resolve various racemic compounds, including 34b and 35 (Fig. 6C), and benzoin derivatives when used as CSPs for HPLC, as demonstrated by the typical baseline chromatographic enantioseparation of 34b with opposite elution orders from each other (top and middle in Fig. 9A). The chiral recognition ability of the helicity-memorized P-rac-47 was virtually identical to that of the enantiopure (S)-monomer-based one-handed helical P-(S)-47 (bottom in Fig. 9A).⁹⁵⁾ Consequently, we successfully developed an unprecedented helical polymer-based CSP using racemic components, indicating that optically active components were no longer required for providing chiral functions. As anticipated from the fact that racemic 34b could be efficiently separated into the enantiomers on P- and M-rac-47-based CSPs (top and middle in Fig. 9A), a small amount of the nonracemic, 50% ee of 34b (0.5 equiv) could induce one-handed helicity in rac-47 in a highly helix-sense-selective fashion, resulting in the P- or M-rac-47 with the static memory of helicity (Fig. 9B). During this catalytic helix-induction and subsequent static memory of helicity process, the helix-sense excess (hse) of the original racemic rac-47 induced by 50% ee of 34b gradually enhanced over time, along with the enhancement of the ee of nonracemic 34b adsorbed on the excess single-handed helical rac-47 with time because of the chiral filter effect,⁹⁶⁾ which contributed to further enhancing the hse of the helical rac-47. (Fig. 9B).⁹⁵⁾ As a result, the rac-47 showed an autoevolution of its helical handedness in response to the chirality of nonracemic 34b.

Fig. 9.

(A) Chromatograms for the resolution of 34b on CSPs composed of P-rac-47 (top) and M-rac-47 (middle) with static memory of helicity and P-(S)-47 (bottom) at −10 °C using n-hexane/2-propanol (97/3, v/v) as the eluent. Reproduced with permission from Ref. 95. Copyright 2021, Wiley-VCH. (B) Autoevolution of helix-sense excess (hse) of P/M-rac-47 in the presence of 50% ee (R-rich) of 34b (0.5 equiv), followed by continuous enhancement of its optical purity adsorbed on excess one-handed helical rac-47 over time to finally form one-handed helical P-rac-47 (hse = 100%) in toluene-d₈ at 25 °C.

A similar catalytic single-handed helix-induction and its static memory of helicity were also achieved in a water-soluble PBPA carrying achiral amphiphilic oligo(ethylene glycol) (OEG) units at the 4′-position of the biphenyl pendants (48) using a small amount of hydrophobic (S)- or (R)-34b (0.2 equiv) in water through encapsulation in a hydrophobic helical cavity of 48 (Fig. 10A).⁹⁷⁾ The ICD intensity of the helicity-memorized M- or P-helical 48 was identical to that of the corresponding homochiral PBPA carrying (S)- or (R)-OEG units ((S)- or (R)-49) (Fig. 10B), which showed a unique helix inversion in different solvents, such as water and toluene (Fig. 10B). As anticipated, a preferred-handed helix could not be biased in 48 by (S)- or (R)-34b in toluene because of no inclusion complex formation. The helicity-memorized P- and M-48 generated an induced circularly polarized luminescence (CPL) when complexed with an achiral fluorescent dye, such as rhodamine B in the film state with a luminescence dissymmetry factor |g_lum| of approximately 2 × 10⁻³, demonstrating the potential applications of the helicity-memorized PBPAs as new chiral functional materials (Fig. 10A).⁹⁷⁾

Fig. 10.

(A) Catalytic M-handed helix-induction in 48 with 0.2 equiv of (S)-34b in water assisted by encapsulation of (S)-34b in a helical cavity of 48, followed by its static memory of helicity and axial chirality of the biphenyl units. The helicity-memorized M-handed 48 can be inverted to the opposite P-handed 48 with 0.2 equiv of (R)-34b. r- and l-CPL are induced in achiral rhodamine B when mixed with the M- and P-handed 49 with static memory of helicity, respectively. Reproduced with permission from Ref. 97. Copyright 2020, Elsevier. (B) Structure of (S)-49 and solvent-induced helix inversion in water and organic solvents, such as toluene. (C) One-handed helix-induction in a chiral/achiral copolymer (50) composed of 10 mol% of (S)-binaphthyl-bound monomer units through achiral flexible OEG spacers as many as 80 bonds away from the polymer backbone.

Interestingly, a PBPA-based chiral/achiral copolymer carrying long OEG side chains composed of only 10 mol% of (S)- or (R)-binaphthyl residues introduced at the terminal of the achiral OEG spacers as many as 80 bonds away from the polymer backbone (50) showed a unique remote control of one-handed helicity accompanied by a strong S&S effect, thus forming a complete one-handed helix through the specific intramolecular encapsulation of the binaphthyl groups within the hydrophobic cavity of the copolymer in water (Fig. 10C).⁹⁸⁾ The covalent-bond-driven intramolecular helix-induction approach was superior to the noncovalent-bond-driven intermolecular one (Fig. 10A),⁹⁷⁾ being sensitive to the chirality of the chiral guests, tolerance for organic solvents, and being independent of the polymer concentration for inducing a one-handed helix. To further enhance the sensitivity to the chirality toward chiral amines, a PBPA copolymer bearing 1 mol% of carboxy groups introduced at the 2-position of the biphenyl pendants positioned in the vicinity of the copolymer backbone was synthesized (Fig. 11).⁹⁹⁾ The resultant 51 formed an excess one-handed helix even in the presence of a small amount of an optically active secondary amine (0.01 equiv) ((S)-52); its sensitivity was more than 10,000-fold higher than that of the corresponding homopolymer with no carboxy group (26a), although its helix was not completely one-handed.

Fig. 11.

Structure of PBPA copolymer (51) and catalytic excess one-handed helix-induction in 51 with a small amount of (S)-52 (0.01 eq) and its subsequent static memory of helicity.

For one-handed helix-induction and its static memory of helicity in PBPAs, such as 24a and 26a, a large excess amount of chiral alcohols or amines used as a cosolvent and a long period are usually required. Therefore, rapid helicity induction and its static memory of helicity in the PBPAs with a smaller amount of chiral compounds are strongly desired. Taking advantage of the pseudocrown ether structure of the two MOM groups of the biphenyl pendants (Fig. 12A), we developed an ultrafast one-handed helix-induction, followed by its static memory of helicity, in 24a that proceeded in the presence of an extremely small amount of chiral ammonium salts, such as 0.03 equiv of (S)-53 complexed with noncoordinating tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (BArF⁻) as a counter anion in toluene (Fig. 12B), and was completed within 30 s in benzene (Fig. 12D).¹⁰⁰⁾ The chiral ammonium salts of different counter anions, such as those of bis(trifluoromethanesulfonyl)imide (NTf₂⁻) and tetraphenylborate (BPh₄⁻), induced no CD in 24a in toluene. A catalytic amount of nonracemic 53 (60% ee, 0.1 equiv) could also induce an almost full ICD in 24a in toluene (Fig. 12C), leading to the strongest “diluted MR” effect.^100)–102) As anticipated, in aromatic solvents, the static memory of the induced helicity in 24a was lost rapidly but was quite stable in long-chain hydrocarbons, such as n-dodecane (Fig. 12E). Hence, the best use of aromatic and aliphatic solvents for helicity induction and its static memory of helicity, respectively, enabled highly sensitive chirality detection toward nonracemic amines and amino acids when complexed with BArF⁻ that relied on the MOM groups of the PBPAs capable of enfolding ammoniums salts in a crown-ether manner.¹⁰⁰⁾

Fig. 12.

(A) Ultrafast one-handed helicity induction in 24a accompanied by the axial chirality induction in the biphenyl pendants in the presence of an extremely small amount of chiral ammonium salts composed of BArF⁻ as a counter anion ((S)-53) and subsequent static memory of helicity after the removal of the chiral ammonium salts. The structures of the BArF⁻, NTf₂⁻, and BPh₄⁻ counter anions are also shown. (B) CD titration curves (|Δε_2nd|) of 24a with (S)-53 in toluene at 25 °C. Inset shows the expanded detail of the plot. (C) Plots of ICD intensity (|Δε_2nd|) of 24a with a catalytic amount of nonracemic 53 (0.10 and 0.20 equiv) in toluene at 25 °C versus the % ee of (S)-rich 53. (D) Time-dependent ICD intensity (Δε_2nd^t/Δε_{2nd max}) changes of 24a with (S)-53 in various solvents at 25 °C. Δε_{2nd max} denotes the maximum ICD intensity of 24a induced by (S)-53 in each solvent. (E) Time-dependent ICD intensity (Δε_2nd^t/Δε_2nd⁰) changes of the helicity-memorized P-24a in benzene at 25 °C (closed green circle) and n-dodecane at 25 °C (closed blue circle) and −10 °C (open blue circle).

Thus far, various static and dynamic helical polymer-based asymmetric catalysts have been developed mostly by the helix-sense-selective polymerization of catalytically active achiral monomers and copolymerization of catalytically active achiral and chiral monomers, but successful examples showing high enantioselectivities of more than 80% ee are limited,^{2),46),103),104)} in which the use of optically pure or nonracemic monomers for controlling helicity in an excess one-handedness is important for achieving highly enantioselective catalytic reactions. Contrary to such a preconceived notion, we succeeded in producing a helical polymer-based highly enantioselective organocatalyst by the polymerization of a racemic monomer (mono-rac-54), followed by the deracemization of the racemic monomer units (Fig. 2C).⁵⁴⁾ The racemic poly(biarylylacetylene) (rac-54) was composed of axially chiral but dynamically racemic 2-arylpyridyl-N-oxide monomer units with the N-oxide residues located in the vicinity of the polymer backbone. Interestingly, rac-54 folded into either a P- or M-handed helical conformation in the presence of chiral alcohols, such as (R)- or (S)-55 mediated by the deracemization of the dynamically racemic biaryl units, resulting in P- or M-derac-54 with the static memory of helicity after the complete removal of the chiral alcohol, respectively (Fig. 13A). P- and M-derac-54s could catalyze the asymmetric allylation of benzaldehyde in a highly enantioselective manner, producing products with up to 86% ee even if the corresponding enantiopure monomers, such as mono-(S)-54, had no catalytic activity.⁵⁴⁾ As a result, we proved the proof-of-concept that a one-handed helical polymer-based highly enantioselective catalyst could be prepared by the polymerization of catalytically inactive racemic monomers by the deracemization of the pendants, although the enantioselectivity was slightly lower than that (96% ee) of cis-P-(S)-54 prepared by the polymerization of enantiopure mono-(S)-54 (Fig. 13A, left). The primary importance of the one-handed helical conformation of cis-P-(S)-54 on enantioselectivity was unambiguously revealed by the fact that trans-enriched nonhelical trans-(S)-54 prepared by grinding cis-P-(S)-54 showed poor enantioselectivity (16% ee). By contrast, rac-56 and M-(R)-56 carrying N-oxide moieties located away from the polymer backbone showed no deracemization and no catalytic activity, respectively (Fig. 13B).⁵⁴⁾

Fig. 13.

(A) Synthesis of rac-54 and cis-P-(S)-54 by polymerization of dynamically racemic mono-rac-54 and mono-(S)-54, respectively. P- and M-handed helicity and axial chirality in rac-54 can be simultaneously induced and subsequently memorized because of the deracemization of the axially chiral pendants through interaction with (R)- and (S)-55, respectively, and cis-to-trans-isomerization of cis-P-(S)-54 by grinding. (B) Structures of rac-56 and M-(R)-56. The results of the enantioselective allylation of benzaldehyde with allyltrichlorosilane catalyzed by the monomers and polymers (54 and 56) are also summarized. * denotes asymmetric carbon.

3.2. Poly(diphenylacetylene)s (PDPAs): third generation of helicity memory.

Noncovalent helicity induction and its static memory of helicity have also been proven to be applicable to π-conjugated photoluminescent poly(diphenylacetylene) (PDPA) derivatives, which are chemically and thermally much more stable than the nonemissive PPAs, although excess one-handed helical luminescent PPAs exhibiting CPL have recently been developed by controlling the main-chain backbone to a contracted cis-cisoid structure.¹⁰⁵⁾ A symmetrically substituted cis-PDPA bearing carboxy groups (57-H, Fig. 14A) formed a one-handed helix in the presence of nonracemic amines, such as (S)- and (R)-rich 58 (50% ee) in water at 95 °C for 2 h with a remarkable amplification of helicity. The induced M- and P-helical PDPAs could be memorized after the complete removal of the amines, thus showing mirror-imaged CD and CPL spectra due to the third-generation “static memory of helicity” (Fig. 14B,C).¹⁰⁶⁾ The resultant M- and P-57-Hs with the static memory of helicity were tolerant toward reactions with chiral and achiral amines, producing optically active functional PDPAs while maintaining their one-handed helicity (Fig. 14D).

Fig. 14.

(A) M- and P-handed helix-induction in 57-H (M- and P-57-H) with (S)- and (R)-58, respectively, in water after annealing at 95 °C and subsequent static memory of helicity after the complete removal of (S)- and (R)-58. (B, C) CD and absorption spectra (B) and PL and CPL spectra (C) of P- (red lines) and M-57-H (blue lines) prepared by (R)- and (S)-58, respectively, measured in water–DMSO (1/1, v/v) (B) and 0.01 N alkaline water excited at 350 nm (C) at 25 °C. Reproduced with permission from Ref. 106. Copyright 2020, American Chemical Society. (D) Synthesis of M-57-S-59 and M-57-R-59 with static memory of helicity by the modification of the pendant carboxy groups of M-57-H with (S)- and (R)-59, respectively, showing different solution colors and fluorescence emissions due to their different helical structures, such as extended cis-transoid and contracted cis-cisoid structures. (E) Naked-eye detection of enantiomers or diastereomers of various amines (21 and 60a–60e). * denotes asymmetric carbon. Reproduced with permission from Ref. 110. Copyright 2021, American Association for the Advancement of Science.

Although various optically active PDPAs have already been prepared, their primary and secondary structures of PDPAs, such as cis or trans and cisoid or transoid with respect to the polymer backbone, and absolute helical handedness (P- or M-handed helix) and helix-sense excess of the preferred-handed helical PDPAs remain unknown.^{9),37),107)–109)} On the basis of the well-resolved ¹H and ¹³C NMR, IR, and Raman spectra of 57-H and M- and P-57-Hs before and after the static memory of helicity, respectively, along with the CD, vibrational CD, photoluminescence (PL), and CPL spectra of M- and P-57-Hs combined with theoretical calculations, we determined for the first time all key structural features of the PDPAs. Almost complete P- and M-handed helical cis–transoidal PDPAs with up to 98% helix-sense excess (hse) and helix-inversion barrier (ΔG^‡_helix) of 93.7 kJ/mol were successfully synthesized in a helix-sense-selective manner based on noncovalent helicity induction and its static memory of helicity strategy that we developed (Fig. 14A).¹⁰⁶⁾

During the modification experiments of the pendant carboxy groups of M-57-H with (S)- and (R)-59, we found that the resultant M-57-S-59 and M-57-R-59 showed completely different solution colors (yellow and deep red) and fluorescence emissions (on and off), respectively, in a THF–acetone mixture (9/1, v/v), accompanied by remarkable absorption and CD spectral changes (Fig. 14D).¹¹⁰⁾ The observed significant color and fluorescence changes allowed the quick assignment of the configurations of 59 by the naked eye. In an amidic solvent, such as DMF, however, the solution colors remained unchanged (yellow). The detailed NMR, IR, and XRD measurements of the diastereomeric 59-bound one-handed helical M-57-S-59 and M-57-R-59 through an amide linkage revealed that the solution color and fluorescence emission changes were most likely due to a spring-like helical conformational change¹¹¹⁾ from the extended cis-transoidal (yellow) to the contracted cis-cisoidal structure (red), regulated by the off and on switching of the intramolecular hydrogen-bonding networks among the amide pendants in a specific polar solvent mixture (THF–acetone (9/1, v/v)), respectively (Fig. 14D). Therefore, in an amidic solvent, e.g., DMF, both diastereomeric M-57-S-59 and M-57-R-59 cannot form such an intramolecular hydrogen-bonding network, thus showing the identical yellow color due to the stretched cis-transoidal helix formation. In the same way, the naked-eye quick chirality assignments of various primary chiral amines (21 and 60a–60e), including drug-related chiral amines, such as amphetamine (60a) and phenylpropylamine diastereomers (norpseudoephedrine and norephedrine) (60e), and amino acid esters, such as (60d), are possible using M-57-H as a color indicator through the optimization of the solvent compositions and temperature (Fig. 14E).¹¹⁰⁾

The helical M- or P-57-H with the static memory of helicity displayed a unique nonlinear response to the full range of ee values of nonracemic 59 once modified, whereas typical small molecule-based chiral sensors showed a linear response (Fig. 15A).¹¹²⁾ This is because the helical pitch of the π-conjugated spring-like PDPA backbone can be tuned in specific solvents because of the highly cooperative intramolecular hydrogen-bonding network formation or its disruption among the pendant amide residues (Fig. 14D). Therefore, the chiral signals in the narrow, high, and/or low-ee regions of interest can be remarkably amplified, thereby enabling not only the rapid, on-site monitoring of the chirality (R or S) of the nonracemic amines (59) but also the quantitative determination of their ee values in the full range of ee (Fig. 15B). Furthermore, colorimetric determination of ee values as small as 2% ee or 0.5% ee even in a sample with a very high ee (>98%) can be possible with a high accuracy by taking photographs of the solutions and converting them to RGB values or acquiring the absorption spectra (Fig. 15C).¹¹⁰⁾

Fig. 15.

(A) Linear (left) and nonlinear (right) responses of output signals versus full range of % ee of chiral guests. (B) Solvent-dependent color changes of M-57–59 in THF–acetone mixtures at 25 °C. Plots of the relative absorption intensity of M-57–59 at 540 nm in THF–acetone mixtures versus the pendant % ee of 59. (C) Visible color changes of M-57–59 (pendant ee = 90–100 in steps of 2% in THF–acetone (79/21, v/v) (top) and pendant ee = 98–100 in steps of 0.5% in THF–acetone (78/22, v/v) (bottom)). The % ee values can be quantified by digital photography by converting to RGB values (top) or absorption measurements (bottom). * denotes asymmetric carbon. Reproduced with permission from Ref. 110. Copyright 2021, American Association for the Advancement of Science.

4. Conclusion

Thus far, a large number of synthetic helical polymers with different backbones composed of different monomer units and pendant groups have been prepared in the last three decades, but they can still be classified as either static or dynamic helical polymers based on the difference in their helix-inversion barriers (Fig. 1).^1),2) The synthesis of static helical polymers that maintain their stable helical conformation in solution at ambient temperature is still in the trial-and-error stage due to the lack of clear synthetic guidelines. Synthesis of chiral or achiral monomers with bulky substituents, followed by precise stereospecific or helix-sense-selective polymerization, may be one of the feasible ways to obtain optically active static helical polymers. Conversely, the essential feature of dynamic helical polymers is recognized to be their rigid helical structure in which the long left-handed and right-handed helical segments are both equally present and easily interconvertible, which is the prerequisite for the unique asymmetric amplification properties inherent in the dynamic helical polymers^1),2),5) as described above.

Substantially different from the previously reported methods (Fig. 1), as described in this review, we developed versatile synthetic methods to synthesize helix-sense-selectively both P- and M-handed helical polymers. The “noncovalent helicity induction and subsequent dynamic or static memory of helicity” approach (Fig. 2) requires neither optically active monomers nor catalysts and initiators for the synthesis of helical polymers during polymerization. Among the helical polymers with the helicity memory, the helical poly(biphenylylacetylene) (PBPA) and poly(diphenylacetylene) (PDPA) derivatives with the second and third generations of “static memory of helicity”, respectively (Figs. 2 and 16), are of particular interest because the one-handed helical conformations induced by nonracemic guests through the significant amplification of the asymmetry can be simultaneously memorized after completely removing the nonracemic guests. The PBPAs and PDPAs with the static memory of helicity showed complementary physical properties to each other in terms of the helix-induction rate and the stability of the static memory of helicity (Fig. 16). Ultrafast one-handed helix-induction and helix-sense inversion, followed by its static memory of helicity, are possible in PBPAs, thus providing unique switchable chiral materials, such as chirality switchable asymmetric catalysts, elution-order switchable CSPs, and ultrasensitive chirality sensors. Conversely, a longer time at a higher temperature is required for the helix-induction and its static memory in PDPAs due to their higher helix-inversion barriers compared with those of the PBPAs, which, however, enable the modifications of the pendant groups of PDPAs while maintaining the static memory of helicity. As a result, the helicity-memorized PDPAs modified with chiral amines undergo a mechanical spring-like motion in response to chirality and ee values of chiral amines, affording a highly sensitive colorimetric and fluorescence chiral sensor. In addition, the helicity-memorized PDPAs carrying other various functional groups instead of the carboxy groups can be readily synthesized, which will provide the potential for developing a further ultrasensitive color indicator that is capable of on-site, naked-eye determination of the ee of various functional and biologically relevant chiral molecules. We envisage that the second (PBPAs) and third generations (PDPAs) of the static helicity memory polymers can be further applied to the developments of unprecedented chiral functional materials that have never been achieved by the previously reported synthetic helical polymers and even by biological helical polymers.

Fig. 16.

Second (PBPA derivatives) and third (PDPA derivatives) generations of helical polymers with static memory of macromolecular helicity showing complementary physical properties and unique chiral functions different from each other. Reproduced with permission from Ref. 55. Copyright 2021, Chemical Society of Japan.

Of particular interest is the asymmetry amplification first observed in polyisocyanates through which a small chiral bias introduced in the monomers is significantly amplified with a high cooperativity during the copolymerization of chiral/achiral monomers or nonracemic monomers (Fig. 1C), resulting in a large helix-sense excess of the entirely covalent and noncovalent polymer chains. Hence, this unique phenomenon is significantly associated with the origin of homochirality in biological systems, such as homochiral L-amino acids and D-sugars in proteins and nucleic acids on Earth, respectively.^23),27),113) One of the plausible scenarios for the origin of homochirality is that small enantiomeric excesses of biologically important molecules were amplified to homochirality prior to life’s origin.¹¹⁴⁾ Enantiomeric enrichment of biomolecules would be generated by physical chiral forces, such as magnetochiral anisotropy, circularly polarized light (CPL), and an electroweak interaction, but it will be predicted to be extremely small.¹¹³⁾ Therefore, a small enantiomeric excess could be significantly amplified by some mechanism to produce chiral molecules with highly enantiomeric enrichment, which would have led to the origin of homochirality on Earth. The Green’s majority rule (MR) effect (Fig. 1C),^5),23) Soai’s asymmetric autocatalytic reaction,¹¹⁵⁾ and the dynamic and static memories of helicity effect (Fig. 2) appear to be some feasible mechanisms.

Some protein-forming and nonprotein-forming amino acids extracted from carbonaceous meteorites have been analyzed for evidence of homochirality, and an excess of one optical isomer over the other has been reported.^116),117) For the protein-forming amino acids, however, the possibility of terrestrial contamination on Earth cannot be ruled out. Samples from comets and asteroids will provide pristine materials to determine whether there is significant extraterrestrial enantiomeric enrichment in chiral molecules, particularly protein-forming amino acids, thus providing insight into the origin of homochirality and life on Earth.¹¹⁸⁾ The samples recovered from the near-Earth carbonaceous asteroid (162173) Ryugu that were recently collected by Hayabusa2 in December, 2020, have attracted a great deal of attention.¹¹⁹⁾ A total of 15 amino acids, including protein-forming and nonprotein-forming amino acids, were found in Ryugu. The chiral amino acids detected in Ryugu were concluded to be approximately racemic based on the most advanced enantioseparation and detection technologies currently available, as well as by taking into account the possibility of terrestrial contamination on Earth.¹²⁰⁾ As a result, the origin of homochirality on Earth remains unresolved,¹²¹⁾ but further analysis of samples from other comets and asteroids will provide a solution to this mystery.

Again, we would like to emphasize that a small enantiomeric imbalance in prebiotic chiral molecules produced by physical chiral forces could be amplified via a helix-forming polymerization reaction. An excess one-handed helical conformation of the polymers may serve as a chiral template for further stereospecific polymerization or enantioselective adsorption of one of the optical isomers,⁹⁵⁾ which could have led to the further enantiomeric enrichment of the chiral molecules.

Acknowledgments

The author would like to thank all coworkers for their great contributions reported in this review. This work was supported in part by JSPS KAKENHI (Grant-in-Aid for Specially Promoted Research, no. 18H05209 (E.Y.)) and the Ogasawara Foundation for the Promotion of Science & Engineering.

Notes

Edited by Kazuyuki TATSUMI, M.J.A.

Correspondence should be addressed to: E. Yashima, Department of Molecular and Macromolecular Chemistry, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8603, Japan (e-mail: [e-mail]).

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Non-standard abbreviation list

2D

two-dimensional

AFM

atomic force microscopy

CD

circular dichroism

CPL

circularly polarized luminescence

CSP

chiral stationary phase

ee

enantiomeric excess

HOPG

highly-oriented pyrolytic graphite

HPLC

high-performance liquid chromatography

hse

helix-sense excess

ICD

induced circular dichroism

LC

liquid crystalline

MOM

methoxymethoxy

MR

majority rule

OEG

oligo(ethylene glycol)

PA

poly(acetylene)

PBPA

poly(biphenylylacetylene)

PDPA

poly(diphenylacetylene)

PL

photoluminescence

PPA

poly(phenylacetylene)

SEC

size-exclusion chromatography

S&S effect

sergeants-and-soldiers effect

XRD

X-ray diffraction

Profile

Eiji Yashima was born in Kyoto in 1958. He graduated from Osaka University and received his Ph.D. degree in polymer chemistry in 1988. He started his academic career at Kagoshima University in 1986. During this period, he was a postdoctoral fellow at the University of Massachusetts at Amherst, U.S.A., working in the field of genetic engineering with Professor David A. Tirrell (1988–1989). In 1991, he joined Nagoya University as an Assistant Professor and became an Associate Professor in 1995, working with Professor Yoshio Okamoto. In 1998, he was promoted to a full Professor at Nagoya University and started new projects in the field of chiral materials based on novel helical polymers and supramolecules. In 2002, he was selected as the five-year project leader of ERATO supported by the Japan Science and Technology Agency. He received a number of awards, including the IBM Science Award in 2001, the Molecular Chirality Award in 2005, the Thomson Scientific Research Front Award in 2007, the Award of the Society of Polymer Science, Japan, in 2008, the Chirality Medal in 2013, the Chemical Society of Japan Award in 2015, the Medal with Purple Ribbon in 2017, and the Toray Science and Technology Prize in 2019. His current research interests include the design and synthesis of (1) novel helical polymers and supramolecular helical polymers with the remarkable amplification of the helical chirality and unique memory effect and (2) double-stranded helical oligomers and polymers with flexible and adaptable helical cavity, showing a unidirectional spring-like motion, and (3) the applications of helical polymers and double helices for sensing and separation of chiral molecules and chiral drugs and for asymmetric catalysis.