Yoshio Furusho

Helical Polymers: Synthesis, Structures, and Functions

2.2.1. Polyisocyanates 6117 2.2.2. Polysilanes 6118 2.2.3. Polyacetylenes 6120 2.3. Foldamer-Based Helical Polymers 6124 2.3.1. Click Polymerization 6126 2.3.2. Ring-Closing Reaction 6126 2.4. Other Types of Helical Polymers 6127 2.4.1. π-Conjugated Helical Polymers 6127 2.4.2. Metallosupramolecular Helical Polymers 6128 2.5. Induced Helical Polymers 6130 2.5.1. Induced Helical Polyacetylenes 6130 2.5.2. Other Induced Helical Polymers and Oligomers 6132

Single- and Double-Stranded Helical Polymers: Synthesis, Structures, and Functions

Biological macromolecules, such as DNA and proteins, possess a unique and specific ordered structure, such as a right-handed double helix or a single alpha-helix. Those structures direct the sophisticated functions of these molecules in living systems. Inspired by biological helices, chemists have worked to synthesize polymers with controlled helicity, not only to mimic the biological helices but also to realize their functions. Although numerous synthetic polymers that fold into a single-handed helix have been reported, double-stranded helical polymers are almost unavailable except for a few oligomers. In addition, the exact structures of most helical polymers remain obscure. Therefore, the development of a conceptually new method for constructing double-stranded helical polymers and a reliable method for unambiguously determining the helical structures are important and urgent challenges in this area. In this Account, we describe the recent advances in the synthesis, structures, and functions of single- and double-stranded helical polymers from our group and others and provide a brief historical overview of synthetic helical polymers. We found unique macromolecules that fold into a preferred-handed helix through noncovalent bonding interactions with specific chiral guests. During the noncovalent helicity induction process, these guest molecules significantly amplified chirality in a dynamic helical polymer. During the intensive exploration of the helicity induction mechanism, we observed an unusual macromolecular helical memory in dynamic helical polymers. Furthermore, we found that rigid-rod helical poly(phenylacetylene)s and poly(phenyl isocyanide)s showing a cholesteric or smectic liquid crystal self-assemble to form two-dimensional crystals with a controlled helical conformation on solid substrates upon exposure to solvent vapors. We visualized their helical structures including the helical pitch and handedness by atomic force microscopy (AFM). We propose a modular strategy to construct complementary double helices by employing chiral amidinium-carboxylate salt bridges with m-terphenyl backbones. The double-stranded helical structures were characterized by circular dichroism in solution and X-ray diffraction of the crystals or the direct AFM observations. Serendipitously, we found that oligoresorcinols self-assemble into well-defined double helices resulting from interstrand aromatic stacking in water. These oligoresorcinols bound cyclic and linear oligosaccharides in water to form rotaxanes and hetero-double helices, respectively. The examples presented in this Account demonstrate the notable progress in the synthesis and structural determination of helical polymers including single- and double-stranded helices. Not only do we better understand the principle underlying the generation of helical conformations, but we have also used the knowledge of these unique helical structures to develop novel helical polymers with specific functions.

Double-stranded helical polymers consisting of complementary homopolymers.

Two complementary homopolymers of chiral amidines and achiral carboxylic acids with m-terphenyl-based backbones were synthesized by the copolymerization of a p-diiodobenzene derivative with the diethynyl monomers bearing a chiral amidine group and a carboxyl group using the Sonogashira reaction, respectively. Upon mixing in THF, the homopolymer strands assembled into a preferred-handed double helix through interstrand amidinium-carboxylate salt bridges, as evidenced by its absorption, circular dichroism, and IR spectra. In contrast, when mixed in less polar solvents, such as chloroform, the complementary strands kinetically formed an interpolymer complex with an imperfect double helical structure containing a randomly hybridized cross-linked structure, probably because of strong salt bridge formations. This primary complex was rearranged into the fully double helical structure by treatment with a strong acid followed by neutralization with an amine. High-resolution atomic force microscopy revealed the double-stranded helical structure and enabled the determination of the helical sense.

Sequence-and Chain-Length-Specific Complementary Double-Helix Formation

The artificial sequential strands consisting of two, three, or four m-terphenyl groups joined by diacetylene linkers with complementary binding sites, either the chiral amidine (A) or achiral carboxyl (C) group, were synthesized in a stepwise manner. Using circular dichroism and (1)H NMR spectroscopies along with liquid chromatography, we showed that, when three dimeric molecular strands (AA, CC, and AC) or six trimeric molecular strands (AAA, CCC, AAC, CCA, ACA, and CAC) were mixed in solution, the complementary strands were sequence-specifically hybridized to form one-handed double-helical dimers AA.CC and (AC) 2 or trimers AAA.CCC, AAC.CCA, and ACA.CAC, respectively, through complementary amidinium-carboxylate salt bridges. Upon the addition of CCA to a mixture of AAA, AAC, and ACA, the AAC.CCA double helix was selectively formed and then isolated from the mixture by chromatography. Moreover, the homo-oligomer mixtures of amidine or carboxylic acid from the monomers to tetramers (A, AA, AAAA, C, CC, and CCCC) assembled with a precise chain length specificity to form A.C, AA.CC, and AAAA.CCCC, which were separated by chromatography.

Thermodynamic and Kinetic Stabilities of Complementary Double Helices Utilizing Amidinium–Carboxylate Salt Bridges

A series of dimer strands consisting of m-terphenyl backbones bearing complementary chiral or achiral amidines and achiral carboxylic acid residues connected by various types of linkers, such as diacetylene, Pt(II)-acetylide, and p-diethynylbenzene linkages, were synthesized by a modular strategy, and their chiroptical properties on the complementary double helix formations were investigated by absorption, circular dichroism (CD), and (1)H NMR spectroscopies. The thermodynamic and kinetic stabilities of the complementary double helices assisted by amidinium-carboxylate salt bridges are highly dependent on their linkages, and the thermodynamic analyses of the dimer duplexes revealed that the association constants increased in the order: Pt(II)-acetylide linker < p-diethynylbenzene linker < diacetylene linker, which is in agreement with the reverse order of their bulkiness. The substituents on the amidine groups were also found to affect the stabilities on the duplexes and the association constants increased in the order: isopropyl < (R)-1-phenylethyl < cyclohexyl. In addition, the introduction of electron-donating and/or electron-withdrawing substituents at the phenyl groups of the p-diethynylbenzene linkers connecting the amidine and carboxylic acid units, respectively, tends to stabilize the complementary double helices, especially in polar solvents, such as DMSO, due to the attractive charge-transfer interactions between the aromatic linkers, although the salt bridge formation is hampered in DMSO. Furthermore, the kinetic analyses of the chain exchange reactions for the duplexes bearing diacetylene and p-diethynylbenzene linkages showed that these were slow processes with negative ΔS([symbol: see text]) values, meaning that the chain exchange reactions proceed via direct exchange pathways. In contrast, those for the duplexes bearing Pt(II)-acetylide linkages were fast processes supported by positive ΔS([symbol: see text]) values, suggesting that the chain exchange reactions proceed via dissociation-exchange ones. The helix-inversion kinetics investigated for the racemic dimer duplexes composed of achiral amidines based on variable-temperature (1)H NMR measurements indicated that the barriers for the helix-inversion increased in the order: Pt(II)-acetylide linker, p-diethynylbenzene linker < diacetylene linker.

Synthesis and Function of Double-Stranded Helical Polymers and Oligomers

The design and synthesis of artificial helical polymers and oligomers has attracted much interest, in connection with fascinating biological helices and their sophisticated functions as well as possible applications in novel chiral materials. The last half-century has seen a significant advancement in the synthesis of single-stranded helical polymers and oligomers, since the discovery of the helical structure of isotactic polypropylene. In contrast, the chemistry of double-stranded helical counterparts is still premature. This paper highlights our recent achievements in the synthesis, structures, and functions of double-stranded helical polymers and oligomers, stressing an important role of supramolecular chemistry in the design and synthesis of double helices with a controlled helical sense.

Amidinium Carboxylate Salt Bridges as a Recognition Motif for Mechanically Interlocked Molecules: Synthesis of an Optically Active [2]Catenane and Control of Its Structure†

Journal Club 2010.07.22 Eri Nishiyama Amidinium Carboxylate Salt Bridges as a Recognition Motif for Mechanically Interlocked Molecules: Synthesis of an Optically Active [2]Catenane and Control of Its Structure Yuji Nakatani, Yoshio Furusho*, Eiji Yashima* Angew. Chem. Int. Ed. Early view DOI: 10.1002/anie.201002382

Double-Stranded Supramolecular Assembly through Salt Bridge Formation between Rigid and Flexible Amidine and Carboxylic Acid Strands

A series of monomeric strands consisting of m-terphenyl backbones with chiral rigid C-linked (3) and flexible N-linked (5) formamidines and achiral carboxylic acid (4) and flexible carboxymethyl (6) residues were synthesized, and their duplex formations through amidinium-carboxylate salt bridges were investigated by NMR, circular dichroism (CD), and UV-visible spectroscopies. The salt bridge-derived duplex formation was largely dependent on the structures of the formamidine and carboxylic acid strands, and the C-linked formamidine strand 3 formed a more stable duplex with the complementary carboxylic acid strands (4 and 6) than did the flexible N-linked formamidine strand 5. The single crystal X-ray analysis revealed that the duplex 5.4 has a skewed right-handed double helical structure. A complementary duplex dimer was also synthesized from the dimers of 5 and 4 joined by diacetylene linkers. Variable-temperature CD measurements indicated that the duplex possesses a dynamic double helical structure resulting from the flexible N-linked formamidine units.

Diastereoselective Imine-Bond Formation through Complementary Double-Helix Formation

Optically active amidine dimer strands having a variety of chiral and achiral linkers with different stereostructures are synthesized and used as templates for diastereoselective imine-bond formations between two achiral carboxylic acid monomers bearing a terminal aldehyde group and racemic 1,2-cyclohexanediamine, resulting in a preferred-handed double helix stabilized by complementary salt bridges. The diastereoselectivity of the racemic amine is significantly affected by the chirality of the amidine residues along with the rigidity and/or chirality of the linkers in the templates. NMR and kinetic studies reveal that the present imine-bond formation involves a two-step reversible reaction. The second step involves formation of a preferred-handed complementary double helix assisted by the chiral amidine templates and determines the overall reaction rate and diastereoselectivity of the amine.

Double helix formation of poly(m-phenylene)s bearing achiral oligo(ethylene oxide) pendants and transformation into an excess of one-handed single helix through cholate binding in water

A water-soluble poly(m-phenylene) bearing an achiral oligo(ethylene oxide) chain at the 5-position was synthesized by the Ni(0)-mediated homo-coupling polycondensation of a 3,5-dibromophenol monomer. The poly(m-phenylene) adopted a single helical conformation in protic media and self-assembled into a double helix in water through aromatic interaction, while it took a random-coil conformation in chloroform. Upon the addition of sodium cholate in water, the double helical poly(m-phenylene) was transformed into single strands, which bound the cholate molecules to form an excess of one-handed single helix.