Synthetic Molecular Sequences in Materials Science 9784431569329

Table of contents :
Cover
NIMS Monographs Series
Synthetic Molecular Sequences in Materials Science
Copyright
Preface
Contents
1. Introduction to the Science of Molecular Sequences
1.1 Molecular Sequences in Nature: The Strategy of Nature to Bring Diversity in Substances
1.2 Molecular Sequences in Synthetic Materials: A Less Conscious Point of View in Materials Science
Reference
2. Synthetic Strategies of Molecular Sequences Linked with Static Bonds
2.1 Binary Component Systems
2.1.1 Block Sequences
2.1.2 Alternating Sequences
2.1.3 Flexibly Designable Sequences
2.2 More-Than-Three Component Systems
2.2.1 Periodic Sequences
2.2.2 Flexibly Designable Discrete Sequences
2.2.3 Flexibly Designable Polymer Sequences
References
3. Synthetic Strategies of Molecular Sequences Linked with Dynamic Bonds
3.1 Binary Component Systems
3.1.1 Coexisting Homosequences
3.1.2 Block Sequences
3.1.3 Alternating Sequences
3.2 More-Than-Three Component Systems
3.2.1 Discrete Sequences
3.2.2 Polymer Sequences
References
4. Outcomes from Synthetic Molecular Sequences in Materials Science
4.1 Discrete Sequences
4.2 Coexisting Homosequences
4.3 Block Sequences
4.4 Alternating Sequences
4.5 Networked Sequences
References
5. Future Perspectives: Sequence-Based Point of View in Materials Science
References

Citation preview

NIMS Monographs

Kentaro Tashiro

Synthetic Molecular Sequences in Materials Science

NIMS Monographs Series Editor Naoki OHASHI,National Institute for Materials Science, Tsukuba, Ibaraki, Japan Editorial Board Mikiko TANIFUJI,National Institute for Materials Science, Tsukuba, Japan Takahito OHMURA,National Institute for Materials Science, Tsukuba, Ibaraki, Japan Yoshitaka TATEYAMA,National Institute for Materials Science, Tsukuba, Ibaraki, Japan Takashi TANIGUCHI,National Institute for Materials Science, Tsukuba, Ibaraki, Japan Kazuya TERABE,National Institute for Materials Science, Tsukuba, Ibaraki, Japan Masanobu NAITO,National Institute for Materials Science, Tsukuba, Ibaraki, Japan Nobutaka HANAGATA,National Institute for Materials Science, Tsukuba, Ibaraki, Japan Kenjiro MIYANO,National Institute for Materials Science, Tsukuba, Ibaraki, Japan

NIMS publishes specialized books in English covering from principle, theory and all recent application examples as NIMS Monographs series. NIMS places a unity of one study theme as a specialized book which was specialized in each particular field, and we try for publishing them as a series with the characteristic (production, application) of NIMS. Authors of the series are limited to NIMS researchers. Our world is made up of various “substances” and in these “materials” the basis of our everyday lives can be found. Materials fall into two major categories such as organic/polymeric materials and inorganic materials, the latter in turn being divided into metals and ceramics. From the Stone Ages - by way of the Industrial Revolution - up to today, the advance in materials has contributed to the development of humankind and now it is being focused upon as offering a solution for global problems. NIMS specializes http://www.nims.go.jp/ in carrying out research concerning these materials. NIMS: eng/index.html

Kentaro Tashiro

Synthetic Molecular Sequences in Materials Science

Kentaro Tashiro International Center for Materials Nanoarchitectonics National Institute for Materials Science Tsukuba, Ibaraki, Japan

ISSN 2197-8891 ISSN 2197-9502 (electronic) NIMS Monographs ISBN 978-4-431-56932-9 ISBN 978-4-431-56933-6 (eBook) https://doi.org/10.1007/978-4-431-56933-6 © National Institute for Materials Science, Japan 2023 This work is subject to copyright. All rights are reserved by the National Institute for Materials Science, Japan (NIMS), whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms, or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifically for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is permitted only under the provisions of applicable copyright laws and applicable treaties, and permission for use must always be obtained from NIMS. Violations are liable to prosecution under the respective copyright laws and treaties. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. NIMS and the publisher make no warranty, express or implied, with respect to the material contained herein. This Springer imprint is published by the registered company Springer Japan KK, part of Springer Nature. The registered company address is: Shiroyama Trust Tower, 4-3-1 Toranomon, Minato-ku, Tokyo 1056005, Japan

Preface

This monograph aims to provide a concise explanation on a newly emerging area of materials science based on synthetic compounds and their assemblies that possess a precisely determined sequence in their structure. After completing a book chapter entitled “Sequence Control of π-Electron Systems” in 2015, the author was annually invited by Springer to write another book. Considering also the presence of a scheme to promote the publication of a monograph in National Institute for Materials Science, the author decided to prepare a text that highlights a gradually spreading but still less popular concept of Synthetic Molecular Sequences in Materials Science. As exemplified by the research works selected in this monograph, researchers in diverse research fields have been independently pursuing the same direction based on a wide range of compounds at the same era. This would be an indication of growing interests in the remaining “terra incognita” in materials science; hence, the author believes that the publication of this monograph will be timely. It should also be mentioned that although there are excellent books and reviews focusing on sequence-regulated polymers, this monograph is expected to become a novel attempt to discuss the single common concept by the merge of the research works in that area with those in other research areas where sequence-regulated discrete systems have been targeted. It would bring great pleasure to the author if this monograph can contribute to the development of any scientific fields related to sequences. Tsukuba, Japan November 2021

Kentaro Tashiro

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Contents

1 Introduction to the Science of Molecular Sequences ................ 1.1 Molecular Sequences in Nature: The Strategy of Nature to Bring Diversity in Substances. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.2 Molecular Sequences in Synthetic Materials: A Less Conscious Point of View in Materials Science ............................. Reference . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1 1 3 5

2 Synthetic Strategies of Molecular Sequences Linked with Static Bonds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1 Binary Component Systems. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1.1 Block Sequences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1.2 Alternating Sequences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1.3 Flexibly Designable Sequences . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 More-Than-Three Component Systems. . . . . . . . . . . . . . . . . . . . . . . . . 2.2.1 Periodic Sequences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2.2 Flexibly Designable Discrete Sequences. . . . . . . . . . . . . . . . . . 2.2.3 Flexibly Designable Polymer Sequences. . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

7 8 8 10 12 14 14 17 21 28

3 Synthetic Strategies of Molecular Sequences Linked with Dynamic Bonds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1 Binary Component Systems. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1.1 Coexisting Homosequences . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1.2 Block Sequences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1.3 Alternating Sequences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2 More-Than-Three Component Systems. . . . . . . . . . . . . . . . . . . . . . . . . 3.2.1 Discrete Sequences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2.2 Polymer Sequences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

31 32 32 34 36 43 45 47 50

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Contents

4 Outcomes from Synthetic Molecular Sequences in Materials Science . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1 Discrete Sequences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2 Coexisting Homosequences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3 Block Sequences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.4 Alternating Sequences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.5 Networked Sequences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

53 53 54 58 61 62 64

5 Future Perspectives: Sequence-Based Point of View in Materials Science . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68

Chapter 1

Introduction to the Science of Molecular Sequences

The concept of “molecular sequences” initially appeared in the field of molecular biology [1],1 where their representative examples can be found in the primary structures of several biopolymers, e.g., peptides/proteins (1), DNA/RNA (2), and polysaccharides (3), which are composed of amino acids, nucleosides, and monosaccharides, respectively (Fig. 1.1). While each of their sequences serves quite different biological roles, all of them share common structural features: (1) they are composed of monomeric units with a limited number of variations, and (2) these units are arrayed to form perfectly regulated, specific sequences that are either periodic or non-periodic. The understanding on the fact that nature prefers such molecularly sequenced structures to maintain the activity of living species later inspired researchers out of the field of molecular biology to adopt this concept as the guiding principle for designing novel synthetic compounds. Consequently, the type of molecular sequence has been expanded from purely natural compounds to their synthetic analogues and even compounds far from those existing in nature, which allows researchers to find an increasing number of potential applications of this type of structure, such as information storage, sensors, medicine, nanostructure formations, control of phase behavior, energy conversions, and catalyst design.

1.1 Molecular Sequences in Nature: The Strategy of Nature to Bring Diversity in Substances It is intriguing that substances having the structural features of molecular sequences are ubiquitous in nature, which makes a good contrast with the general cases of synthetic compounds. An advantage of this molecular design strategy chosen by nature, from the synthetic point of view, is that it allows the creation of structures of great diversity from a small variety of particular building blocks, which can be 1

One of the earliest usages of the term “molecular sequence” in the manuscript title ever confirmed.

© National Institute for Materials Science, Japan 2023 K. Tashiro, Synthetic Molecular Sequences in Materials Science, NIMS Monographs, https://doi.org/10.1007/978-4-431-56933-6_1

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2

1 Introduction to the Science of Molecular Sequences

N H

H N O

O N H

H N O

O N H

OH

N

O

N

SH

H 2N

OH 1

OH HO OH O O O O HO AcHN OH HO OH HOOC O HO O O O AcHN O HO H HO 3

N N

N

O

N

O O P O O

O

O

O

O

H N

O O P O O

O O P O O

O

O

O NH

N O

NH 2

N

O O P O

N

N

NH 2

NH O

2

HO HO

OH O HO

O

R

Fig. 1.1 Examples of molecular structures of peptide (1), DNA (2), and polysaccharide (3)

overall more energy-saving as well as cost-effective and hence self-sustainable than conventional approaches to the preparation of synthetic compounds, which often require quite different starting materials for each target. On the other hand, since it is apparently not a target-oriented design strategy, generally, a library of products should necessarily be subjected to selection processes to reach the best-fit form among the candidates for a particular demand (Scheme 1.1), as exemplified in the on-going emergence of the more virulent mutants of the virus causing COVID-19 originating from the change of amino-acid sequences in its spike proteins. In the following step, the optimized sequence needs to be reproduced selectively, which is achieved via the sophisticatedly organized synthetic systems in nature (Scheme 1.2).

Scheme 1.1 Schematic representation of production processes for natural molecular sequences

1.2 Molecular Sequences in Synthetic Materials …

3

Scheme 1.2 Synthesis of some representative molecular sequences in nature

1.2 Molecular Sequences in Synthetic Materials: A Less Conscious Point of View in Materials Science Although putting the right components in the right positions is the key to fabricating smart products, it is sometimes still challenging to achieve this in the molecular scale. Construction of molecular sequences has been one of the high-level tasks to accomplish among such challenges in the field of synthetic chemistry, in which most of the conventional synthetic methodologies have been developed by targeting less complicated and more symmetric structures than sequences. Because of the high energy barrier that should be overcome to artificially synthesize molecular sequences, only a very small fraction of synthetic compounds ever reported can be counted as molecular sequences, most of which remain as analogues of bio-related sequences. Another factor that retards the development of materials sciences based on synthetic molecular sequences comes from the fact that their structure–property relationship is often unclear or not easy to understand at first glance, which makes the a priori design of a novel molecular sequence that exhibits better properties than its precedents for a particular purpose ineffective. Namely, it is not easy to correctly choose or even rationally guess the best sequence composed of n components of m varieties among the mn possible structural outcomes when m and n become relatively large, unless the attempt is accompanied by many cycles of sequence modification– performance evaluation. Consequently, certain fields of materials science, based on synthetic molecular sequences, have been much less explored and developed, especially when the sequences are composed of absolutely non-natural species such as metals, extensively π-conjugated systems, and monomers for conventional polymers. Therefore, it is understandable that the history of synthetic molecular sequences in materials science initially started with the preparation and usage of close mimics of natural molecular sequences. Over the past two decades, however, a new trend has started to appear, where the design and preparation of novel synthetic materials have been attempted by focusing

4

1 Introduction to the Science of Molecular Sequences

Fig. 1.2 Results of search of keywords with “synthetic molecular sequence” in the literature after excluding those containing “molecular sequence data” using SciFindern

on the particular effects or roles of the sequenced structures at the molecular level, as seen in the results of a keyword search using SciFindern (Fig. 1.2). Although most of the attempts along this line so far still mainly target the construction of novel sequence structures, there have been some indications of the superiorities of this type of compound compared with others. In addition, the concept of molecular sequence nowadays is broader, exceeding the single-molecule level, where the sequence in supramolecular assemblies is one of the currently hot research subjects in materials science. This current situation suggests the presence of rich, as yet undiscovered sciences related to synthetic molecular sequences. Considering the on-going emergence of a new area of science, this monograph is written for readers to have a good understanding of the state-of-the-art structural accessibility, characteristic features, and future potentials of synthetic molecular sequences. Chapters 2 and 3 summarize the precedent methodologies to prepare synthetic molecular sequences, which are classified into several categories on the basis of the nature of linkages and the variety of components in a single sequence, as both of them predominantly determine the requisites to be fulfilled for the successful construction of the target sequence. In the following chapters, both potential and realized outcomes of synthetic molecular sequences in materials science are described.

Reference

5

Reference 1. Beyer WA, Stein ML, Smith TF, Ulam SM (1974) Molecular sequence metric and evolutionary trees. Math Biosci 19:9–25

Chapter 2

Synthetic Strategies of Molecular Sequences Linked with Static Bonds

Regarding the controlled synthesis of molecular sequences, there may be two different concepts on this synthesis. The first concept on “control” is that the order of the monomeric components in a molecular sequence is fixed to fulfill a particular regulation so that typically that sequence has a clearly recognizable pattern, which is either periodic or non-periodic. Alternating sequences or linked multiple homosequences (block sequences) would be the most well-known examples, while the regulation determining the sequence can be apparently invisible in other cases (see Chap. 5), making the corresponding sequence look apparently random. Therefore, this point of view can be somewhat subjective. As the concept of alternating or block sequences originated from the field of polymer science, synthetic polymer chemists tend to focus on the development of synthetic methods for individual sequence patterns. The second concept on the controlled synthesis of molecular sequences is based on not the presence of patterns in the targeted sequences but rather the selective preparation of a unique target sequence without producing wrong sequences, which has been the more popular concept in the synthesis of shorter discrete sequences in research fields other than polymer science. Because of the presence of such multiple definitions of the controlled synthesis of molecular sequences, for example, sequence A–B–C–A–C–B will be regarded as an uncontrolled sequence in the first concept, while the same sequence can be a controlled one in the second concept if that sequence is selectively producible. Whichever the concept on the controlled synthesis of molecular sequences, however, the requisites for the preparation of a particular molecular sequence in a satisfactory pure form highly depend on the nature of the bonds that link components of that sequence, namely, whether it is static or dynamic. This chapter describes the synthetic strategies of molecular sequences that are constructed by the linkage of the monomeric components with static bonds. This chapter also considers the clear gap in the difficulty between the synthesis of sequences composed of only two types of monomeric component and that of sequences with more than three types of monomeric component. These topics on synthesis are discussed in the following two

© National Institute for Materials Science, Japan 2023 K. Tashiro, Synthetic Molecular Sequences in Materials Science, NIMS Monographs, https://doi.org/10.1007/978-4-431-56933-6_2

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2 Synthetic Strategies of Molecular Sequences Linked …

Sects. 2.1 and 2.2 both of which are further divided into three subsections (Sects. 2.1.1, 2.1.2, 2.1.3. and 2.2.1, 2.2.2, 2.2.3, respectively) focusing on the type of target sequence. Covalent linkages as well as certain types of metal coordination are representatives of static bonds. Once these “strong” bonds are formed, they cannot be cleaved easily; hence, they are advantageous for the preparation of thermodynamically less stable sequences as there is no concern on the reordering of their components to afford the mixtures of randomized sequences. In the synthesis of sequences linked with static bonds, precise control of the order of the bond-forming reactions between the monomeric components is the main issue, which is typically achieved through the sequential addition of monomers to the reaction mixture. Another approach to control a sequence is the preorganization of monomeric components by using a complementary template sequence, as in the case of the replication of DNA/RNA in nature. Examples of sequences linked with static bonds include covalently linked organic polymers and network structures, metallic nanorods, arrays of metal complexes, and coordination polymers, among others. The most difficult challenge often encountered is not the synthesis itself but demonstrating that the targeted sequence has actually been formed selectively in the products.

2.1 Binary Component Systems When the target sequence is composed of only two types of monomeric component, its synthesis can be more flexible than the synthesis of sequences composed of more than three types of monomer. For example, the use of a pair of heteroselectively reacting functionalities for the sequentialization of the monomers is sufficient to achieve alternating sequences. Thus, binary component sequences linked with static bonds have been the main targets in the early stage of the synthetic research on molecular sequences.

2.1.1

Block Sequences

Synthetic organic polymers have one of the longest histories of sequence-based research since they have been regarded as the counterpart compounds of biopolymers [1]. Among various sequence patterns of binary component systems, block sequences composed of multiple homosequences would be most easily constructed. A classic example of a commodity elastomer whose production has been industrialized for several decades is the polystyrene–polybutadiene–polystyrene (SBS) block copolymer (Fig. 2.1), which is nowadays prepared by the stepwise living anionic polymerization of styrene and butadiene. Block copolymers are obtained even from a single type of monomer if the tacticity in the corresponding polymers can be finely switched. By adding a Lewis acid (LA) such as yttrium trifluoromethanesulfonate at a

2.1 Binary Component Systems

9

n

m

n

Fig. 2.1 Molecular structure of polystyrene–polybutadiene–polystyrene (SBS) block copolymer

given time during the controlled radical polymerization of N,N-dimethylacrylamide, one can change the polymer tacticity from inherent atactic to isotactic (Scheme 2.1a) owing to the chelation of the LA added to the last two monomer units of a growing polymer chain (Scheme 2.1b), affording the attactic-isotactic stereoblock copolymers [2]. A Block sequence of Co and Fe complexes were also reported by using stepwise metallation and ligand coordination on gold electrode surface [3]. Since the efficient formation of Co complex requires an electrochemical oxidation step additionally, this approach might be applicable only for the block sequences starting with Co but not with Fe (Scheme 2.2). Scheme 2.1 Schematic representations of a the preparation of attactic–isotactic stereoblock polyacrylamides by using the addition of a Lewis acid (LA) in the polymerization and b interactions of the LA with the growing acrylamide polymer and its monomer to make the polymer tacticity isotactic

a) NR 2

NR 2 H

C=O

H

NR 2

NR 2 H

C=O

H

NR 2

C=O C=O H

NR 2

C=O C=O H

NR 2

NR 2

H

NR 2

NR 2

H

LA

C=O C=O H

C=O C=O H

b) NR 2 H

LA

C=O H O

H H

C

NR 2

H O

LA

C

NR 2

NR 2 H

NR 2

C=O

H

NR 2 NR 2 H C=O H C=O C=O

10

2 Synthetic Strategies of Molecular Sequences Linked … N N N

N N S

Co3+

N

N

N N

N

N

Fe 2+

N N

N N

N

N N

N

N

N

m

n

N N

N N

N

N

N

xm

N

Fe 2+

N N

N N S

Co3+

N

N

N N

N

N N

N

N

n

Electrochemical Oxidation

N N

N N

N

N

N

N

xn

Co2+

N N S

N

N N

Scheme 2.2 Stepwise metalation and ligand coordination on gold electrode surface to afford block sequences of Co(III) and Fe(II) metal complexes

2.1.2

Alternating Sequences

Another type of sequence whose construction has been extensively studied in detail is the ABABAB-type alternating sequence. Approaches to prepare this type of sequence from organic components include (1) introduction of heteroselective functionalities into the monomers such as amine/CO2 H [4], (2) use of electron-deficient and electron-rich monomer pairs such as styrene/maleimides for their alternating reactions (Scheme 2.3) [5], (3) smart design of the catalysts that allows the alternating insertion of two types of monomer into the catalytic sites (Scheme 2.4) [6], (4) polymerization of pre-prepared A–B heterodyads [7], and (5) solid-state polymerization of two types of monomer that are preorganized to afford their alternating arrangements in their cocrystals (Scheme 2.5) [8, 9]. Some alternating sequences have been prepared by using not only pure organic components but also metal-containing compounds, where these sequences were mostly obtained through solution-phase coordination polymerization. To construct such sequences, two different ligand structures are typically merged symmetrically or nonsymmetrically. As an example of the

2.1 Binary Component Systems

11

symmetrical design strategy, a newly designed bis-terpyridine (TPy)-functionalized dioxocyclam was metallated with Cu2+ to give the corresponding mononuclear complex having two vacant TPy moieties (Scheme 2.6) [10]. The product was then reacted with several dicationic transition metal ions (M2+ ) to leave the alternating (Cu2+ –M2+ )n sequences, as supported by the successful measurements of the electrospray ionization (ESI)-mass (MS) spectra assignable to the trinuclear fragments of the expected sequence. In the case of a nonsymmetrically designed bis-terpyridine organic linker, one of the terpyridines attached with dicarboxylate functionalities served as the coordination site for Eu3+ ions to form a 1:2 complex of Eu3+ and the ligand, which was then polymerized by the metallation of the other side of the ligand with Fe2+ in the following step (Scheme 2.7) [11]. The order of the complexation of two metal ions to the nonsymmetric bis-terpyridine ligand was found to be crucial for their successful polymerization, as the addition of Fe2+ to a methanol solution of uncomplexed ligand afforded no polymeric species but the 1:1 Fe2+ – ligand complex owing to the selective metallation at the bulky terpyridine site. Not only 1D infinite sequences but also their circularly closed discrete analogues have been prepared by the similar stepwise metallation of the ligand with two coordination sites, whereas bent-shaped ligand structures have been adopted to induce the cyclization (Scheme 2.8) [12]. As an analogue of alternating sequences, repetitive ABA sequences were constructed using a metal-containing template, where two styrene (S) and one 4-vinylpyridine (P) moieties were linked with a palladium complex of 2,6-dicarboxyamido-pyridine via covalent and coordination bonds, respectively (Scheme 2.9) [13]. After the polymerization of this preorganized SPS triad, the template part was cleaved and removed from the products, leaving polymers having the expected repetitive SPS sequences as supported by 13 C NMR spectroscopy. R

Scheme 2.3 Copolymerization of styrene and N-substituted maleimide to afford alternating styrene–maleimide sequences

Scheme 2.4 Alternating copolymerization of two types of enantiopure lactone monomer of opposite stereochemistries by using a syndiospecific catalyst

O

R +

O

N

N

O

O n

tBu N

O tBu

N

Y N(SiHMe 2)2 O

O O

tBu R1

O

tBu Syndiospecific Polymerization Catalyst

O R2

R1 O

R2

O O

O n

12

2 Synthetic Strategies of Molecular Sequences Linked … F

F

O

O

O

O

O

O

O

O

F

O

O

O

O O

O

O

O

F

O

O

O O

F

F O

O

F

O

hv

F

F F

F

O

F

O

O

F

F

F

F

O

F

O

F

F F

F

F

F

F

F

F

F F

F

F

F F

O

O

F F

F

O

O

F

F

F

F

F

Scheme 2.5 Photoinduced copolymerization of two types of alternatingly stacked diacetylene monomer in their cocrystal to afford their covalently linked sequence

N

N O

N N

O NH N

N

N

Cu2+

N

N

HN

N Cu

N

N

N O

N

N

N O

N

N

N N

N M 2+

O

M 2+ N

N N

N

N Cu

N

N O

n

M 2+ = Cu2+, Co2+, Fe 2+, Ni 2+

Scheme 2.6 Coordination polymerization of a metallated monomer having two vacant coordination sites to afford alternating sequences of two types of metal complex

2.1.3

Flexibly Designable Sequences

As described in Sect. 2.2.2, solid-phase synthesis allows the flexible design of molecular sequences, particularly if the monomers are based on bio-related compounds such as amino acids, nucleosides, and monosaccharides. Among the corresponding bio-related sequences, DNA would be the most frequently utilized scaffold to achieve the construction of another sequence owing to its high sequence programmability upon self-assembly, e.g., duplex formation. Two π-conjugated moieties, 2,5-bis(2thienyl)-pyrrole (4) and aniline (5), are sequence-specifically attached on the nucleobase of DNA to form their linear arrays in the DNA major groove of the doublestranded structure (Scheme 2.10) [14]. These monomers were oxidatively coupled by the treatment with horseradish peroxidase to afford sequence-regulated partial

2.1 Binary Component Systems

13

O N

N

O

OH

NO

N Eu 3+

N

N N

N

N N

OH

N

N

OH

O Eu O O

N

N N

N

N O

O

O

O NO Fe 2+ N N

O Eu O O

N

OH N N

N

N

N Fe 2+ N N

O

N

O n

Scheme 2.7 Stepwise metallation of a heteroditopic ligand with two types of metal ion to afford alternating sequences of two types of metal complex

MeO

N N

MeO

OMe

N Ru 2+ N N

Fe 2+

N N

N Ru 2+ N N N

N

N N

OMe

N N

N

N

N

N Fe 2+ N N

N

N

n n =3

Scheme 2.8 Stepwise metallation of a bent-shaped ditopic ligand with two types of metal ion to afford cyclic oligomers having alternating sequences of two types of metal complex

Scheme 2.9 Copolymerization of vinyl monomers S and P using a metal-containing template to afford repetitive SPS sequences

N N O

Pd N

V-70 F3C

N O

Template Removal CF3

OH

N NH2

NH2

n

structures of the conducting polymers. Another example of the DNA-supported sequentialization of non-biological components was found in the attempt to construct molecular sequences composed of metals or metal complexes by site-specific metal complexation on the pre-prepared sequence of two different types of coordination site in the DNA oligomers (Scheme 2.11). An artificial oligonucleotide bearing five salicylic aldehyde (S) moieties at particular positions instead of the intrinsic nucleobases was designed and prepared by solid-phase synthesis to form its duplex structure, where the resultant S–S pairs formed were covalently fixed by the crosslinking with ethylenediamine to serve as the coordination sites for Cu2+ ions at the first step

14

2 Synthetic Strategies of Molecular Sequences Linked …

of metallation [15]. The duplex also possessed five thymine–thymine (T–T) pairs that worked in the subsequent complexation with Hg2+ ions to selectively afford a single sequence composed of S–Cu2+ –S and T–Hg2+ –T complexes, which was confirmed by absorption spectroscopy as well as ESI–ion cyclotron resonance MS. If a combination of two different coordination sites is available for the highly sitespecific complexation with two types of metal ion, this can be regarded as an excellent approach that allows the flexible synthesis of any desired sequences composed of two metal complexes. Application of the same approach to the sequentialization of more than three types of metal complex would be much more challenging, however, because of the requirement for the coordination sites to achieve the selective complexation with one particular metal or metal ions in the presence of a more complicated mixture of metal species. An exceptional example of the site-specific metallation, as will be described in Sect. 2.2.3 for a dendrimer, might be an interesting reference for further development of the approach along this direction. As a definitely different approach, facile single-monomer addition to the growing polymer chain end in conventional polymerization processes has been a strongly pursued target for the flexible design of polymer sequences. Toward this goal, a proof-of-concept study based on atom transfer radical polymerization (ATRP) of vinyl monomers has been conducted, where the reactivity of the growing polymer chain end was controlled by the chemical transformation of the side group at the chain end to allow the single-monomer addition (Scheme 2.12) [16].

2.2 More-Than-Three Component Systems For the precise control of sequences composed of more than three types of monomeric unit, one of the most solid strategies proposed so far would be sequence elongation through the stepwise coupling of monomeric components in a desired order. Since this strategy inevitably requires multiple repetitions of purification of products, the ease of removing impurities, i.e., byproducts, unreacted monomers, and other unnecessary chemicals, from the reaction mixture is the key factor that determines its practical utility. There have been several strategies developed that allow the facile purification of the sequences produced; however, the use of the combination of two different phases, such as solid and solution during the synthetic processes, has been the most frequently adopted strategy owing to its theoretically wide applicability. This section also includes other synthetic strategies that are effective with more specific chemical species or conditions.

2.2.1

Periodic Sequences

Multiply repeating short sequences are found in several biopolymers. Examples of such sequences include telomeric repeats in DNA and heptapeptidic tandem repeats in

2.2 More-Than-Three Component Systems S N (CH2)3

O P O O

H N

15 O

O O N

N O

N O

S

O

O O P O

N H N (CH2)2 N H

5

4

Duplex

Oxidative

Formation

Coupling

Duplex

Oxidative

Formation

Coupling

Scheme 2.10 Preorganization of two types of π-conjugated monomer mediated by DNA duplex formation to construct their oligomeric sequences in a flexibly designable manner

16

2 Synthetic Strategies of Molecular Sequences Linked …

M2 M1

M1

M1

M1

M1

M1

M1

M1

M1

M2

M2 M2 M2 M2 M1

M1

Scheme 2.11 Preorganization of two types of coordination site mediated by DNA duplex formation for their site-specific metallation with two types of metal ion to achieve the sequentialization of two metal complexes in a flexibly designable manner

Br n O O O O

Br

OH Cu/CuBr2 /Me6TREN

O O O O

Br TEMPO

n OH

NaOCl/KBr

n O O O O O O H

OH Br n EDC/DMAP

O O O O O O

OH Cu/CuBr2 /Me6TREN

Br n O O O O O O

OH

Scheme 2.12 Single-monomer addition to the growing polymer chain end achieved in atom transfer radical polymerization of vinyl monomers as a proof of concept

RNA polymerase II. If the target synthetic sequence has the same structural feature as these sequences in nature, polymerization of the corresponding short sequence may be the most straightforward approach. On the basis of this idea, linear or cyclic organic short sequences were finely prepared to be converted into their polymeric forms containing an ABC (6), AABC (7), ABCD (8), or ABCDE (9) sequence in the polymer main chain. For example, sequence-regulated copolymers composed of three common vinyl monomers, i.e., vinyl chloride, styrene, and acrylate, were obtained by the metal-catalyzed step-growth radical polymerization of the corresponding linear oligomers prepared by efficient two- or three-step coupling reactions (Scheme 2.13) [17]. Another type of polymerization technique used for this approach is ring-opening metathesis polymerization (ROMP), which was combined with the synthesis of multiply substituted cyclooctenes (Scheme 2.14a) [18] or macrolactams (Scheme 2.14b) [19].

2.2 More-Than-Three Component Systems

17 Cl

Cl +

+

CO2R

CuCl PMDETA Cl

Cl

CO2R

or

n CO2R

or

CO2R CO2R

n CO2R CO2R

Cl

6

7-1

Scheme 2.13 Metal-catalyzed step-growth radical polymerization of pre-prepared short sequences obtained from three types of vinyl monomer to afford ABC (6) or AABC (7-1) periodic sequence

a)

R1

SO2

R3

R1

Grubbs Cat. G2

R3

R1

NH 2NH 2

R2

n

n

R2

R3

R2 7-2

b)

O O

HN O S N

O

O O

O O

O

G3

O O

O

H N

O

O

O O S N O

O

n

8

H N

O O

O S O

O

O

G3

N O

O

O

O O

O O

O

O O

H N

O

O O S N O

n

O O 9

Scheme 2.14 Ring-opening metathesis polymerizations of cyclic short sequences to afford AABC (7-2), ABCD (8), or ABCDE (9) periodic sequence

2.2.2

Flexibly Designable Discrete Sequences

Elongation of surface-immobilized molecular sequences is one of the synthetic methods for molecular sequences with the longest histories of use. This method

18

2 Synthetic Strategies of Molecular Sequences Linked …

was initially developed by Merriefield for the artificial preparation of natural molecular sequences such as peptides, where the growing peptide chains are kept linking covalently with the surface of functionalized polymeric resins during the sequential coupling of all the necessary amino-acids one by one at the chain end to construct the target sequences (Scheme 2.15) [20]. By taking advantage of the immobilization of growing sequences on the resin, one can remove all the other chemicals dissolved in the reaction media in each synthetic step simply by washing the resin with appropriate solvents. Therefore, this method requires only a single thorough purification step, i.e., only after the cleavage of the crude products from the resin, throughout the entire synthetic processes consisting of 20–30 or even as many as 100 steps. Because the entire protocol of solid-phase synthesis is composed of multiply repeating combinations of some simple experimental operations, such as addition and draining of the solvents with or without other chemicals, as well as the agitation of the resins in these media, it was not difficult to achieve automation of the protocol, enabling the parallel yet selective production of many different sequences at the same time. Such remarkable developments of the solid-phase synthesis techniques for the production of natural molecular sequences led to its applications to the preparation of analogous sequences partly containing or fully composed of non-natural monomers including ß-amino acids (10) [21], peptoid monomers (11) [22], peptide nucleic acid (PNA) monomers (12) [23], and even metallated amino-acid derivatives (13) (Fig. 2.2) [24]. One may also need to take note, however, of the disadvantage of this method, especially when considering its application. Since the coupling reaction of a monomer with the growing end of the immobilized sequence generally takes place at the inner space of the cross-linked polymeric resin, its reactivity is clearly lower than that of the same reaction in a homogeneous solution, requiring a largely excessive amount of the monomer to be fed into the reaction mixture to achieve the nearly quantitative coupling yield. This means that a major portion of the monomers consumed in the solid-phase synthesis must be discarded at the end. Not only from the viewpoint of SDGs but also from that of using a wider range of monomeric components whose large-scale supply is not very easy to procure, the issue of low coupling efficiency needs to be addressed by an appropriate modification of the synthetic protocols, e.g., the microwave irradiation of reaction mixtures, which was found to work in several occasions [25].

Scheme 2.15 Schematic representation of solid-phase polypeptide synthesis

2.2 More-Than-Three Component Systems

19 Base

R2 O R1 10

O

O

R

H 3N +

H 2N +

O

H 3N +

N

Metal Complex

O O

O

H 3N + O

O 11

12

13

Fig. 2.2 Molecular structures of ß-amino acids (10), peptoid monomers (11), peptide nucleic acid monomers (12), and metallated amino-acid derivatives (13)

As an example of the synthesis of non-natural sequences, a series of mononuclear metal complexes having a 9-fluorenylmethyloxycarbonyl (Fmoc)-protected amino acid moiety were sequentially coupled to give multimetallic peptidic arrays by using the protocols of solid-phase polypeptide synthesis with appropriate modifications (Scheme 2.16). The Pt(II), Rh(III), or Ru(II) complex moiety adopted in that work (Fig. 2.3) was designed to be sufficiently kinetically stable under the synthetic conditions used so that neither the randomization of the targeted metal sequence nor the partial leaching of the metal centers took place during the synthesis [24, 26]. That method enabled the preparation of three heterotrimetallic arrays having isomeric metal sequences, which were found to exhibit sequence-specific gelation behavior (Fig. 2.4) [27]. Later, this approach was further modularized to synthesize various longer and/or branched metal sequences by combining the solid-phase synthesis of shorter sequences with their chemoselective ligation at the following step (Scheme 2.17) [28]. Because of the presence of eight metal ions, the total molecular weight of one of the resultant arrays exceeds over 8000, which is comparable to those of small proteins such as ubiquitin. More importantly, that array shares the same level of structural integrity, in terms of its precisely determined sequence, as the protein. Although metal sequences composed of lanthanoid complexes have been synthetically challenging targets owing to their kinetic lability, judicious choice of the ligand structure based on cryptate enabled the successful construction of a heterometallic sequence composed of up to three types of emissive lanthanoid complex (Fig. 2.5) [29]. In all these works, the conventional protection/deprotection chemistry of the Fmoc-protecting group for the selective coupling of the sequence terminal and monomer was adopted [30]. There could be another method, however, that enables their controlled coupling. Recently, the electrosynthesis of sequences of metal complexes has been reported, in which each metal complex monomer was designed to possess two different electroactive organic functionalities that work in the electrochemical homocoupling reactions (Scheme 2.18) [31]. Since the directions of the applied voltages necessary to activate these two functionalities are opposite, stepwise coupling of metal complex monomers with the sequence terminal immobilized on the electrode surface was achieved in a controlled manner by applying positive and negative voltages alternatingly. If two types of efficient reaction, both of which are promoted by the same catalyst, can be adopted for the step-by-step growth of a sequence, it is possible to

20

2 Synthetic Strategies of Molecular Sequences Linked …

Scheme 2.16 Schematic representation of the solid-phase synthesis of multimetallic peptidic arrays

achieve a solution-phase one-pot synthesis of molecular sequences with the suppression of monomer consumption. A representative example is found in the sequencecontrolled synthesis of oligosiloxanes [32]. The synthetic protocol reported in the work is composed of the alternating repetitions of B(C6 F5 )3 -catalyzed (1) dehydrocarbonative cross-coupling of alkoxysilanes with hydrosilanes and (2) hydrosilylation of carbonyl compounds such as acetone, where the sequence in the resultant oligosiloxanes can be controlled simply by the addition of hydrosilane monomers in a specific order (Scheme 2.19). Owing to the highly orthogonal nature of these two reactions, not only linear but also branched or cyclic oligosiloxane sequences were successfully constructed from more than three types of Si-containing monomer. The advances of synthetic technology in the fields of organic and organometallic chemistries have made the construction of molecular sequences manageable even with the multiple repetitions of conventional reaction–isolation procedures. Although cyclic structures are topologically different from linear structures, a cyclic array can be regarded as the endless analogue of the corresponding linear sequences. In fact, peptidic macrocycles are an important class of cyclic biosequences that often exhibit significant activities toward biosystems similarly to linear analogues [33]. Recently, the concept of molecular sequences has been introduced even into purely synthetic macrocycles. As a representative example, three different carbazole units were linked by the stepwise click reaction to afford a shape-persistent macrocycle, whose carbazole sequence–self-assembly relationship was thoroughly investigated by taking advantage of the rigidity of cyclic structures (Fig. 2.6) [34]. Not only pure organic components but also metal-containing units were site-specifically linked to afford multinuclear heterometallic structures. One of the examples of the most elaborated structures in terms of the variety of metal elements in a single molecule

2.2 More-Than-Three Component Systems

21

Fig. 2.3 Molecular structure of a Pt(II), Rh(III), and Ru(II) metallated peptidic sequence prepared by the solid-phase synthesis approach

2CF3CO2

Cl Cl

N

N

N

N

O

O

O

O

H N

N H

Pt + Cl

N CF3CO2

N N

Pt + Cl

O

O

N N

NH 2

N H

O

O

N N

O

H N

N H

O

O

CF3CO2

N N

N

O

Fmoc

Cl

Rh

N

N

H N

Cl

N Ru 2+

Rh N

Cl

N Cl

N CF3CO2

N

Pt + Cl

is composed of seven different metal complexes, e.g., complexes of Cu(I), Fe(II), Os(II), Pt(II), Re(I), Ru(II), and Ti(IV), which are linked in a specific order to afford a branched metal sequence (Fig. 2.7) [35]. Its successful synthesis clearly shows that highly complexed yet well-defined structures could be accessible by adopting the conventional synthetic strategies in organometallic chemistry.

2.2.3

Flexibly Designable Polymer Sequences

To address the general issue of low reactivity in solid-phase synthesis (see Sect. 2.2.2), linear polymer-based soluble supports instead of cross-linked insoluble resins were sometimes used as the scaffolds for the preparation of sequences because they make

22

2 Synthetic Strategies of Molecular Sequences Linked …

N

Cl

N

N N

N

O

N H

H N O

Cl

OC CO N Re CO N

OC CO N Re CO N

OC CO N Re CO N

O N H

H N O

O

O O

Fmoc

Cl

O NH

O N H

H N O

O O NH 2

Fmoc

N H

H N O

N H

H N O

O

O N H

H N O

O

O

NH

O

N

N

Cl

N

N

N

N

N

N

N

Ru 2+ 2Cl

Pt + Cl

N

N

N

N

N

Ru 2+ 2Cl

Pt + Cl

N

Cl N

N

Ru 2+ 2Cl

N

N

N

Cl N

N

Pt + Cl

NH

O NH 2

Fmoc

N H

H N O

O N H

H N O

O N H

H N

O NH 2

O

Fig. 2.4 Heterotrimetallic peptides with isomeric metal sequences exhibiting sequence-specific gelation behavior

Scheme 2.17 Schematic representation of the modular approach for the synthesis of longer and/or branched metal sequences, where two shorter sequences prepared by solid-phase synthesis protocols were linked by solution-phase chemoselective ligation

2.2 More-Than-Three Component Systems

N

23

N

N

N

N

N

N

N

N

Eu 3+

N

Tb3+

N

O O N+ N+

N N N

O O N+ N+

O

HN S

H 3N + O

HN

N H

S

HN

O

*

N

NH

HN

S

H N

Sm3+

O NH

NH

N N

O O N+ N+

O

HN

NH

N

H N

*

O

O N H

H N

O O

O

Fig. 2.5 Molecular structure of a heterotrimetallic peptide sequence bearing three emissive lanthanoid complexes. The carbon and nitrogen atoms marked with * represent isotopically labeled 13 C and 15 N, respectively

the facile purification of the products possible by simple precipitation, and the easy access of the substrates to a growing sequence can be expected by operating the reactions in solution [36]. Although these polymer supports used in the conventional protocols are discarded at the end of the synthesis after the cleavage of the products from them, they also have potential use as components of sequences if they are designed to have well-defined structures. On the basis of this idea, linear polystyrenes with a highly narrow molecular weight distribution (M w /M n ≈ 1.13) were prepared by the ATRP technique as the soluble supports for the following alternating couplings of two bifunctional monomers [37]. A detailed characterization of the final products compared with the reference compounds proved that this approach indeed works for the construction of sequence-defined, ternary component polymers (Scheme 2.20). Another type of soluble scaffold used for the synthesis of artificial sequences is a template. On the basis of the mechanism of replication, transcription, or translation of genetic codes in biological systems, the selective preparation of synthetic sequences has been attempted using DNA-based templates. While the pioneering works on this subject frequently produced a low efficiency in terms of product yield as well as sequence selectivity, the judicious choice of the type of coupling reaction such as reductive amination between the building blocks of DNA sequences enabled the efficient and sequence-specific DNA-templated synthesis of PNAs, as shown by the detailed product analysis by electrophoresis (Scheme 2.21) [38]. In that research work, DNA sequences containing a 5' -amine-terminated hairpin motif were used as covalent templates, which were enzymatically digested after the formation of targeted PNA sequences. The last treatment eliminated the issue generally encountered in

24

2 Synthetic Strategies of Molecular Sequences Linked …

N

N N

N

M 2+ N

N N

N N

N N

N

N

N

N

N

N

N

N

N

N

N

N

N

N N

N N

N

N M 2+

N

N M 2+

N N

N

O

P

Electrode

O

Electrochemical Oxidation

N

N M 2+

N

N

M 2+ N N

N

P

N

M 2+ N

N N

O O

N N

N

N O

O

N

N

N

N O

N

N

N N M 2+

N

N

N

N

N

M 2+

M 2+

O

P

O

Electrochemical Reduction

M 2+, M 2+, M 2+, M 2+ = Fe 2+, Ru 2+, Os2+

Scheme 2.18 Electrosynthesis of sequences of metal complexes

template synthesis, in which the dissociation of the template and product is not smooth if the template is used for thermodynamic control. One of the key points to achieve the controlled synthesis of molecular sequences is to selectively allow the bond-forming reaction between the sequence terminal and the preferred monomer by suppressing other reactions between nonpreferable pairs. In particular, if the reaction is conducted in an ordinary homogeneous solution, a

2.2 More-Than-Three Component Systems

25 SiMe3

Me 3Si

Et 2SiH2

O

PhSiH3

O

SiEt 2

O

Et 2 O Ph Si Si O O H

Me 3Si

SiMe3 O

Ph

O

Et 2SiH2

SiEt 2 Me 3Si

Et 2 O Ph Et 2 Si Si Si O O H O

Scheme 2.19 One-pot synthesis of sequence-regulated oligosiloxanes through alternating repetitions of B(C6 F5 )3 -catalyzed cross-coupling and hydrosilylation reactions R1

Fig. 2.6 Molecular structures of shape-persistent macrocycles featured by the presence of controlled carbazole sequence

N

N

N N

N

N N

R3

N

N

R2

N N N

+ N Ph 2 P Ru P Ph 2

Fe

N

SiMe3

Cu

SiMe3

Ti Me 3Si SiMe3

PPh 3 tBu

Pt PPh 3 N

tBu

N Re CO

Ph 3P

OC CO

Os PPh 3

Fig. 2.7 Molecular structure of a branched metal sequence composed of seven different metal complexes O

O N3 OH

H 2N

O 3

N

N3

n

n CuBr, dNbpy

NHS, DCC

N N

N H

O 3 m

xm

Scheme 2.20 Liquid-phase synthesis of sequence-ordered ternary component copolymers using a soluble and well-defined polymer scaffold

26

2 Synthetic Strategies of Molecular Sequences Linked …

H

H N

N O

O

O N

H N

N

O

O N

O NH

H N

N O

N

O

NH 2

T

C

O

N

N

O

N N

N

NH 2

N O

NH

N

NH 2

TCAG

NH 2

N

TCAG

TCAG

(AGTC)4

O

A

TCAG

NH 2

G

Scheme 2.21 Synthesis of a peptide nucleic acid sequence using a DNA template

technique that fulfills the above requirement should be developed. As described in Sect. 2.1.2, the judicious choice of a particular combination of two monomers enables their alternating copolymerization. Although it is not easy to flexibly design alternatingly copolymerizable ternary monomer systems [39], the corresponding binary monomer combination can be expanded to prepare polymers having a controlled monomer sequence distribution composed of more than three components [5]. In the ATRP-based copolymerization of styrene and a series of N-substituted maleimides, four types of the latter comonomer were sequentially added to the reaction mixture (Scheme 2.22). Although the resultant copolymers did not have perfectly determined sequences at the molecular level, they possessed the controlled distribution of four different N-substituents along the main chain since each maleimide monomer was fed to participate in the polymerization after the incorporation of most of the preadded maleimide monomers into the polymer chains, as confirmed by 1 H NMR spectroscopy. Although it is not a typical example with a linear distribution, the site-specific complexation of four types of metal ion into a dendritic polyphenylazomethine afforded the radial sequence of Fe3+ , Ga3+ , V3+ , and Sn2+ from the core to the periphery of the dendrimer (Scheme 2.23), as supported by the successive observation of four isosbestic points in their UV–Vis spectroscopic titration profiles [40]. The observed site-specific metallation was ascribed to the basicity gradient of the constituent imines of the dendrimer, where the two most-electron-rich imines at the core provide the most affinitive sites for the metal ions. By adding metal ions of proper R2

R1 O

N

O

O

N

R3 O

O

N

R4 O

O

N

O

conv. ~ 1/4

conv. ~ 2/4

conv. ~ 3/4

conv. ~ 1

N

O O

n1

N

R4

R3

R2

R1 O

O O

n2

N

O O

n3

N

O

n4

4

Scheme 2.22 Controlled copolymerization of styrene and four types of N-substituted maleimide to afford alternating styrene–maleimide sequences having the gradient of these N-substituents

2.2 More-Than-Three Component Systems

N

N

N

27

N

N

N

N

N

N

N

N

N

1) Fe 3+ 2) Ga3+ N

N N

N

N

3) V3+

N

N

N

N

N

N N N

N

N

N N

N

N

N

N

N

N

N N

N

N

N

N

N

N

N

N N

N

4) Sn2+

N

N

N N

N

N N

N

N

N

N

N

N

Scheme 2.23 Stepwise metallation of a dendritic polyimine with four types of metal ion from the core to the periphery

stoichiometries with respect to the expected coordination sites of the dendrimer irrespective of the order of their addition, a unique radial distribution of four types of metal ion was spontaneously obtained according to the thermodynamic demand. The next challenge for this approach would be the realization of less symmetric metallation patterns that may require the preparation of organic scaffolds with lower symmetry such as Janus-type dendrimers. It might sound contradictory to discuss molecular sequences composed of metals as there is no concept of molecules in the corresponding field of materials science. Instead of the bottom-up approaches usually adopted for the preparation of synthetic molecular sequences, a membrane-based template synthesis approach [41] was applied to the fabrication of the 1D multimetal nanocomposites encoded in stripes of each metal (Scheme 2.24) [42]. Although currently the minimum diameters of these so-called “nanobarcodes” are still more than one order of magnitude larger than the typical scale for the molecular sequences, the pore diameter of the template materials used for the synthesis of these nanobarcodes has been reduced to as small as 5 nm, indicating the future potential of the further miniaturization of these materials down to the scale comparable to molecular sequences.

28

2 Synthetic Strategies of Molecular Sequences Linked … Porous Alumina

1) M1n+ reduction 2) M 2m+ reduction 3) M 3l+ reduction

Electrode

Scheme 2.24 Stepwise electrochemical reduction of multiple types of metal ion using porous aluminum membranes as the templates to afford multimetallic nanobarcodes

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29

14. Chen W, Schuster GB (2013) Precise sequence control in linear and cyclic copolymers of 2,5bis(2-thienyl)pyrrole and aniline by DNA-programmed assembly. J Am Chem Soc 135:4438– 4449 15. Tanaka K, Clever GH, Takezawa Y, Yamada Y, Kaul C, Shionoya M, Carell T (2006) Programmable self-assembly of metal ions inside artificial DNA duplexes. Nat Nanotechnol 1:190–194 16. Tong X, Guo B-H, Huang Y (2011) Toward the synthesis of sequence-controlled vinyl copolymers. Chem Commun 47:1455–1457 17. Satoh K, Ozawa S, Mizutani M, Nagai K, Kamigaito M (2010) Sequence-regulated vinyl copolymers by metal-catalysed step-growth radical polymerization. Nat Commun 1:6 18. Zhang J, Matta ME, Hillmyer MA (2012) Synthesis of sequence-specific vinyl copolymers by regioselective ROMP of multiply substituted cyclooctenes. ACS Macro Lett 1:1383–1387 19. Gutekunst WR, Hawker CJ (2015) A general approach to sequence-controlled polymers using macrocyclic ring opening metathesis polymerization. J Am Chem Soc 137:8038–8041 20. Merrifield RB (1963) Solid phase peptide synthesis. I. The synthesis of a tetrapeptide. J Am Chem Soc 85:2149–2154 21. Seebach D, Overhand M, Kühnle FNM, Martinoni B, Oberer L, Hommel U, Widmer H (1996) β-Peptides: synthesis by Arndt-Eistert homologation with concomitant peptide coupling. Structure determination by NMR and CD spectroscopy and by X-ray crystallography. Helical secondary structure of a β-hexapeptide in solution and its stability towards pepsin. Helv Chim Acta 79:913–941 22. Simon RJ, Kania RS, Zuckermann RN, Huebner VD, Jewell DA, Banville S, Ng S, Wang L, Rosenberg S, Marlowe CK, Spellmeyer DC, Tan R, Frankel AD, Santi DV, Cohen FE, Bartlett PA (1992) Peptoids: a modular approach to drug discovery. Proc Natl Acad Sci USA 89:9367–9371 23. Nielsen PE, Egholm M, Berg RH, Buchardt O (1991) Sequence-selective recognition of DNA by strand displacement with a thymine-substituted polyamide. Science 254:1497–1500 24. Vairaprakash P, Ueki H, Tashiro K, Yaghi OM (2011) Synthesis of metal–organic complex arrays. J Am Chem Soc 133:759–761 25. Pedersen SL, Tofteng AP, Malik L, Jensen KJ (2012) Microwave heating in solid-phase peptide synthesis. Chem Soc Rev 41:1826–1844 26. Bose P, Sukul PK, Yaghi OM, Tashiro K (2016) Synthesis of a water-soluble metal–organic complex arrays. JoVE 116:54513. https://www.youtube.com/watch?v=LO97zgXdD2A 27. Fracaroli AM, Tashiro K, Yaghi OM (2012) Isomers of metal–organic complex arrays. Inorg Chem 51:6437–6439 28. Sajna KV, Fracaroli AM, Yaghi OM, Tashiro K (2015) Modular synthesis of metal–organic complex arrays containing precisely designed metal sequences. Inorg Chem 54:1197–1199 29. Kreidt E, Leis W, Seitz M (2020) Direct solid-phase synthesis of molecular heterooligonuclear lanthanoid-complexes. Nat Commun 11:1346 30. Carpino LA, Han GY (1970) The 9-fluorenylmethoxycarbonyl function, a new base-sensitive amino-protecting group. J Am Chem Soc 92:5748–5749 31. Zhang J, Wang J, Wei C, Wang Y, Xie G, Li Y, Li M (2020) Rapidly sequence-controlled electrosynthesis of organometallic polymers. Nat Commun 11:2530 32. Matsumoto K, Oba Y, Nakajima Y, Shimada S, Sato K (2018) One-pot sequence-controlled synthesis of oligosiloxanes. Angew Chem Int Ed 57:4637–4641 33. de Veer SJ, White AM, Craik DJ (2021) Sunflower trypsin inhibitor-1 (SFTI-1): sowing seeds in the fields of chemistry and biology. Angew Chem Int Ed 60:8050–8071 34. Dobscha JR, Castillo HD, Li Y, Fadler RE, Taylor RD, Brown AA, Trainor CQ, Tait SL, Flood AH (2019) Sequence-defined macrocycles for understanding and controlling the build-up of hierarchical order in self-assembled 2D arrays. J Am Chem Soc 141:17588–17600 35. Packheiser R, Ecorchard P, Rüffer T, Lang H (2008) Heteromultimetallic transition metal complexes based on unsymmetrical platinum(II) bis-acetylides. Organometallics 27:3534– 3546

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36. Ojeda R, de Paz J-L, Martín-Lomas M (2003) Synthesis of heparin-like oligosaccharides on a soluble polymer support. Chem Commun 2486–2487 37. Pfeifer S, Zarafshani Z, Badi N, Lutz J-F (2009) Liquid-phase synthesis of block copolymers containing sequence-ordered segments. J Am Chem Soc 131:9195–9197 38. Rosenbaum DM, Liu DR (2003) Efficient and sequence-specific DNA-templated polymerization of peptide nucleic acid aldehydes. J Am Chem Soc 125:13924–13925 39. Saegusa T, Kobayashi S, Kimura Y (1977) Polymerization via zwitterion. 12. Novel 1:1:1 alternating terpolymerizations of 2-phenyl-l,3,2-dioxaphospholane, electron deficient vinyl monomers of acrylonitrile and acrylate, and carbon dioxide. Macromolecules 10:68–72 40. Takanashi K, Fujii A, Nakajima R, Chiba H, Higuchi M, Einaga Y, Yamamoto K (2007) Heterometal assembly in dendritic polyphenylazomethines. Bull Chem Soc Jpn 80:1563–1572 41. Martin CR (1994) Nanomaterials: a membrane-based synthetic approach. Science 266:1961– 1966 42. Nicewarner-Peña SR, Freeman RG, Reiss BD, He L, Peña DJ, Walton ID, Cromer R, Keating CD, Natan MJ (2001) Submicrometer metallic barcodes. Science 294:137–141

Chapter 3

Synthetic Strategies of Molecular Sequences Linked with Dynamic Bonds

The degree of difficulty to construct a sequence with dynamic bonds is largely dependent on whether the targeted sequence is thermodynamically most stable or not. If it is most stable, all the necessary steps are just to mix the required monomeric components and leave the mixture under conditions that allow it to reach its thermodynamic equilibrium, enabling the preparation of the targeted sequence more easily than the sequence linked with static bonds. In contrast, if the target sequence is not thermodynamically stable, its preparation becomes much more challenging and requires more sophisticated protocols to control the sequence formation of the components kinetically. One of the basic strategies to kinetically control sequence formation is the switching of the nature of the linking bond, i.e., from being dynamic to static and vice versa, in a chemical or physical manner. Accordingly, these sequences are often prepared in not only homogeneous solutions but also less dynamic phases such as crystals, liquid crystals, and gels. Another approach is based on the simultaneous use of dynamic and static bonds for the sequence formation, which can lower the difficulty in the synthesis of target sequences by decreasing the number of dynamic bonds necessary in a single sequence. Indeed, this approach was found to work effectively for the construction of several block sequences, allowing the construction of relatively complicated structures, which is not possible by sequencing via either purely static or dynamic bonds. It should also be mentioned that the dynamic linkage bonds in a sequence are an attractive feature for making that sequence stimuli-responsive, since the mixing of monomeric components under equilibrium conditions often affords the library of multiple types of sequence, whose individual content can be altered by adding physical or chemical perturbations. Although currently, there are no generally applicable directions for the flexible design of dynamically linked sequences, as compared with the solid-phase synthesis concept for the statically linked sequences, it will not be surprising if they will be established in the near future, considering the rapid growth of related research fields.

© National Institute for Materials Science, Japan 2023 K. Tashiro, Synthetic Molecular Sequences in Materials Science, NIMS Monographs, https://doi.org/10.1007/978-4-431-56933-6_3

31

32

3 Synthetic Strategies of Molecular Sequences Linked …

3.1 Binary Component Systems Majority of the examples of molecular sequences linked with dynamic bonds so far, in contrast with those linked with static bonds, are composed of only two different components, partly owing to the shorter research history for this type of construction. On the other hand, the choices for dynamic bonds are more diverse than those for static bonds, allowing for larger structural variations of monomeric components. Driving forces to form a dynamic bond include donor–acceptor, hydrogen-bonding, metal–metal, and van der Waals interactions together with relatively weak metal coordination.

3.1.1 Coexisting Homosequences The preparation of two different coexisting homosequences can be tricky when both of these homosequences are formed through dynamic bonds, since the simple mixing of solutions of these sequences, for instance, can produce mixed sequences through the intersequence exchange of monomeric components. Therefore, it is important to find a smart way to prepare coexisting homosequences uncontaminated with the mixed sequences. To realize this, the self-sorting phenomenon has been a longterm research subject, in which a chemically programmed homoselective sequence formation has been achieved recently on the basis of small-molecule organic gelators (Fig. 3.1) [1]. A mixture of similar dipeptide derivatives bearing either of two types of naphthalene moiety in an aqueous medium was subjected to gelation by gradually lowering the pH of the medium. Traces of its gelation behavior obtained by 1 H NMR spectroscopy demonstrated that one of the gelators having the higher pKa (14) selectively became invisible first owing to the preferential formation of the hydrogel via its supramolecular 1D fibrillation, which was followed by the fiber formation of the other gelator (15) when the pH was lowered sufficiently. X-ray diffractometry (XRD) of the resultant gels also supported the coexistence of two single-component gels, although the presence of block-like structures (see Sect. 3.1.2) could not be completely ruled out. Spontaneous resolution of enantiomers is also a type of self-sorting phenomenon, which requires more severe conditions than the self-sorting of two chemically different species for its realization because the chemical and physical properties of Fig. 3.1 Molecular structures of small-molecule organic gelators whose mixtures exhibited self-sorting gelation behavior under gradually decreasing pH of the medium

O O

N H

Br

H N

N H

OH

14

OH

15

O

O O

O

H N O

O

3.1 Binary Component Systems Fig. 3.2 Molecular structures of a pair of enantiomers whose mixtures undergo spontaneous resolution of these enantiomers to afford homochiral supramolecular polymers

33 C18H 37O

NH C18H 37O

HN

NH O

O

O HN

OC18H 37

NH O

OC18H 37

NH

C18H 37O HN

NH O

OC18H 37

O

O

OC18H 37

C18H 37O

O

enantiomers are identical except for their stereochemical aspect. A xylylene-bridged bis(cyclic dipeptide) with four stereocenters in total (Fig. 3.2) was found to form homochiral supramolecular polymers when a pair of its enantiomers coexisted in nonpolar organic solvents such as CHCl3 , which was demonstrated by comparing the theoretical and observed absorption/CD responses of the nonstoichiometric mixtures of its enantiomers in size-exclusion chromatography [2]. Another type of coexisting homosequences can be obtained through the controlled self-assembly of A–B dyads resulting in the homo-segregations of A and B parts in the assembly (Scheme 3.1). Representative examples are supramolecular heterojunctions obtained from donor–acceptor (D–A) dyad molecules, which are described in detail in Sect. 4.2. It is important that the coexisting homosequences as obtained through this approach are always closely oriented to each other, thereby advantageous for the construction of heterojunctions. Similar type of proximally located coexisting homosequences are also preparable through the controlled folding of polymers having alternating sequences. Temperature-controlled cooling of a solution of copolymers composed of alternatingly linked oligo(ethylene glycol) (OEG) and phenyl-capped bithiophene (Ph2TPh) (Scheme 3.2) was found to afford OEG–Ph2TPh–OEG triple layer [3].

A

B

Scheme 3.1 Controlled self-assembly of an A–B dyad to afford closely located coexisting homosequences

34

O

3 Synthetic Strategies of Molecular Sequences Linked … S

O 4

O

S

N N N

O NN N O NN N O NN N O NN N O

O

O

O

O

O O O O O O O

O

O

O

O

O O O O

S

O O O O O

O O O O O O

O

O

S

O

4 N

O

S

S S S S S S S S S S S S S S

S

4

O

O

4

N N

O

S

S

O

O

O

4

O

O

O

S

S

O

O

O

4

O

O

O

O O O O O O

O O O O O O

n

O

O

O

O

O

O

O

O

O

O

O

O

O

O

O

O

O

O

O

N NN O N NN O N NN O N NN O

Scheme 3.2 Controlled folding of alternating sequences of oligo(ethylene glycol) (OEG) and phenyl-capped bithiophene (Ph2TPh) to afford OEG–Ph2TPh–OEG triple layer

3.1.2 Block Sequences The successful construction of supramolecular block sequences was achieved by the two-step controlled self-assembly of two types of hexa-peri-hexabenzocoronene derivative that afforded semiconducting nanotubes with a heterojunction structure [4]. Since the monomeric components used are a pair of electron-rich (16) and electron-deficient (17) π-conjugated molecules, they prefer the heterotropic π-stacking interaction to form alternating sequences during their single-step coassembly. To prevent their alternating supramolecular polymerization, one of the monomers bearing two bipyridine ligand moieties for the post-metallation was initially formed into a single-component nanotubular structure, whose surface was then metallated with Cu2+ to immobilize the homosequence structure, which was finally used as the seed to trigger the self-assembly of the other monomer from the ends of the pre-prepared nanotubes (Scheme 3.3). Several microscopy techniques including elemental mapping using transmission electron microscopy (TEM) demonstrated the formation of a block sequence composed of two different nanotubular domains. Although the production of nanotubes composed of three domains was also expected, such triblock sequences were found to be much less abundant than the diblock sequences. While most of the supramolecular block sequences reported

3.1 Binary Component Systems

35 O

O

O

O

O

O

N

N

N

N

O

O

F

F

F

H 25C12 Cu2+

O

O

O

F

O

O

O

Self-assembly

C12H 25 17

Self-assembly

O

O

H 25C12

C12H 25 16

Scheme 3.3 Two-step controlled self-assembly of π-electron-rich (16) and π-electron-deficient (17) hexa-peri-hexabenzocoronene derivatives to afford semiconducting nanotubes with a heterojunction structure

so far were prepared by the kinetic control approach as described above, the possibility to obtain them under thermodynamic control by directly mixing two types of preassembled homopolymer has recently been investigated (Scheme 3.4) [5]. Detailed spectroscopic and microscopic characterizations suggested the production of block sequences as a result of the interpolymer exchange of short block domains. However, the precise control of the position of these domains in a single polymer has not yet been achieved. To mimic the secondary-structure-forming capability of proteins by controlling the primary structure in fully synthetic molecular sequences, a hybrid approach that employs both static and dynamic bonds for the construction of entire sequences was reported [6, 7]. Each homosequence segment forming a particular secondary structure such as a coil, helix, or sheet was prepared as the covalently linked synthetic homopolymer, whose chain ends were functionalized with structural motifs to achieve highly selective interblock connections via hydrogen-bonding interactions or metal coordination. This design strategy allowed access to diverse supramolecular multiblock copolymer sequences such as the A–B–B' –A type that actually formed complexed secondary structures (Fig. 3.3).

36

3 Synthetic Strategies of Molecular Sequences Linked … O

O

O H N

O

H N

O

R

R N H O

R

N N

R HN

N

+ O

N O

R

NH

R N H O

N

R HN

O O

R

R N H O

NH

R N H O

R=

R N H O

R N H N N N O N R N H N N N O N R N H N N N O N R N H N N N O N R N H N N N O N R N H N N N N

R N H

O

O

O

R N H O

R N H N O

N R H O

N R H O

R N H O

N R H O

R N H O

R N H O

R N H N O

N R H O

R N H O

R N H N O

N R H O

R N H O

R N H N N O N R N H N N N O N R N H N O

N R H O

R N H O

N

N R H

R N H

R N H O

R N H O R N H

N

R N H N N N

N R H O

R N H O

R N H N O

N R H O

N R H O

R N H O

R N H N O

N R H O

N R H O

R N H O

R N H N O

N R H O

N R H O

R N H O

R N H N O

N R H O

N R H O

R N H O

R N H N

N R H O

N R H

R N H

O

+

O

N R H

O R N H N O

R N H N N N O N R N H N N N O N R N H N O

O

Copolymerization

O

R N H N O

O

,

R N H O

N

R N H N N N

Interpolymer Block Exchange

N R H O N R H O

, ...

N R H O N R H O N R H

Scheme 3.4 Binary component supramolecular block sequences obtained under thermodynamic control

3.1.3 Alternating Sequences The most straightforward approach to the construction of alternating sequences linked with dynamic bonds would be the introduction of two heteroselective functionalities into monomeric components to spontaneously form the target sequence under thermodynamic control. Since many types of supramolecular bonding interaction are intrinsically heteroselective, a wide range of structural candidates for heteroselective functionalities have been found or designed over the past two decades, resulting in the rapid growth of related research fields. As a representative example, macromonomers bearing either of the complementary quadruple hydrogen-bonding motifs based on 2ureido-4[1H]-pyrimidinone (18) or 2,7-diamido-1,8-naphthyridine (19) at both chain ends were designed to form a viscous solution of supramolecular polymers composed of alternating sequences of these macromonomers (Fig. 3.4) [8]. Two orthogonal types of interaction were also employed for the formation of supramolecular alternating copolymers, where a hydrogen-bonded Zn(II) porphyrin hexamer (20) and

3.1 Binary Component Systems

O S

37

NH

NC HN

CN m

S

O

N

O

O (CH2)11

O

O

O

N

O

O N

N

O

N

N N

N

O

N

O N

O

N

O O

O

N

O N

N

O (CH2)11 O N

O

N

S

S m

O O

O

O

O O C8H17O OC 8H17

n OC 8H17 C8H17O n O Ph S

N Pd + SPh

O

O

Fig. 3.3 Molecular structure of a supramolecularly linked block sequence composed of purely synthetic homopolymers each of which forms a particular secondary structure

a pyridine hexadentate linker (21) coassembled to afford their alternatingly linked copolymers via the multivalent coordination of pyridyl moieties to the zinc centers (Scheme 3.5) [9]. Assemblies in the solid state provide a good opportunity for weak interactions, which are too dynamic in solutions, to work for the realization of alternating sequences of two molecular components. The donor–acceptor π-electronic interaction operating between electron-rich and electron-deficient π-conjugated systems

38

3 Synthetic Strategies of Molecular Sequences Linked …

O

O O O

H N

H N N

H

O N 9

6 n

N H O

N H N

N N 9 H

N H N

N H O

9

6 n 19

O

9 N H O

N

N

H N

H N N

H

O

O

N H O

N H O

N 9

6 n

N

N

H N

H N

N H

O 9

6 n

9 N H

N

N

N H

O

O

N N 9 H

m 18

Fig. 3.4 Molecular structure of alternatingly hydrogen-bonded macromonomers bearing complementary quadruple hydrogen-bonding motifs

often plays the decisive role in the alternate stacking of these moieties in their cocrystals, which was utilized for the following photo- (Scheme 2.5) [8, 9] or pressureinduced (Scheme 3.6) [10] solid-state polymerization to afford the corresponding covalently linked sequences. Another type of weak bonding interaction is the metal– metal interaction that is operating between homo- and heterometallic centers. In particular, the bonds between d8 and/or d10 metal centers often retain their dynamic nature even in the solid state, in which, upon subtle structural changes of their assemblies triggered by external stimuli, the bonding mode of the metal centers is switched among non-bonded, dimeric, and polymeric states, inducing the change in their photophysical [11] or photochemical properties (Scheme 3.7) [12]. One of the rational ideas for the design of alternating sequences of two different metal centers is to use the combination of oppositely charged metal complexes so that they are expected to be arranged alternatingly owing to their electrostatic interactions (Fig. 3.5a) [13]. Although such a charge compensation has been proven by single X-ray crystallography to be actually meaningful, it is not always necessary because even cationic metal complexes of Au(III) and Ag(I), for instance, could form their alternating sequences in the presence of suitable multidentate ligands (Fig. 3.5b) [14]. It is known that more than 90% of crystalline assemblies of chiral compounds are racemic compounds whose single crystals are composed of a stoichiometric mixture of both enantiomers [15]. In contrast, the formation of homochiral assemblies has been claimed to be the dominant event in the case of supramolecular polymerization of chiral compounds in solution when their enantiomers coexist [16], suggesting some difficulty in obtaining alternating sequences of a pair of enantiomers (Scheme 3.8) under these conditions. However, a recent study using a perylene bisimide bearing two chiral amide substituents revealed that its solution-phase self-assembly under kinetic or thermodynamic control selectively afforded homo- or heterochiral 1D supramolecular polymers, the latter of which was composed of alternatingly stacked homodimers of both of the enantiomers (Scheme 3.9) [17]. Host–guest chemistry has also contributed to the construction of molecular sequences with dynamic bonds, affording both discrete and polymeric forms. An example of the discrete form was prepared by using the 2,4,6-tri(4-pyridyl)-1,3,5triazine (A) end-capped, organic-pillared coordination cage system as the cavitysize-tunable host, whose complexation with flat π-conjugated molecules such as

3.1 Binary Component Systems

39

tBu

tBu

tBu tBu

Zn N

N

tBu

tBu

tBu

tBu

tBu

N N

tBu N

tBu

N

O

H

H

N

N

H

H

O

N

N Et

N

N

H

H

N N Zn N N

N

NEt

Zn

tBu

NEt H N N

EtN

Et N N

O

N

N

N

tBu O

O

tBu

H

N

H

H

H N

N H O

N

H

N

N

N

tBu

O

O

N

tBu

O

O

O

O

N

N

N

N

N

Zn

O

tBu

O N

N tBu

O

O N

N

N N

N H O

N H N

N H EtN

N N H N

O H N

tBu tBu

tBu

tBu

tBu

N N N Zn N

tBu

N

N

tBu

N

tBu tBu

tBu

tBu tBu

tBu

N N

tBu

Zn

tBu

N N

tBu tBu

tBu Zn

N

N

Zn

Zn

N

N Zn

Zn

N

N

Zn 20

21

N

Zn

N

Zn

N

N

Zn

Zn

Zn Zn N

Zn

N

N

N Zn

N

Zn N

Zn N N

Zn

N

Zn N Zn

Zn N

Zn

Scheme 3.5 Schematic representation of alternatingly linked supramolecular sequences composed of hydrogen-bonded Zn(II) porphyrin hexamer 20 and pyridine hexadentate linker 21

40

3 Synthetic Strategies of Molecular Sequences Linked …

Scheme 3.6 Pressure-induced polymerization of alternatingly stacked π-electron-rich and π-electron-deficient molecules in their cocrystals

OH

OH F

F

F

F

F

F

F

F

F

F

F

F

HO

F

F

F

F

F

F

F

F

F

F

F

HO

F

F

High Pressure

OH

HO

F

OH

HO

F

F

OH

OH

F

HO

F

HO

Scheme 3.7 Schematic representation of the crystalline assemblies of a Pt(II) terpyridine complex that switches its photochemical reactivity upon changing the mode of Pt–Pt interaction Fig. 3.5 Crystal and the corresponding partial molecular structures of metal–metal bonded alternating sequences of a Ag(I)/Au(I) and b Ag(I)/Au(III) metal complexes

a)

S

N N

N C6F 5

Ag(I)

Au(I) F 5C6

b) N N Ag(I)

N

Au(III)

N

3.1 Binary Component Systems

41

O

O O NH O

HN

O

O S

S

S

S

HN

O

O

HN

O NH

O

HN

S

S

S

S

O

NH O

NH

O

O O

O

R R

NH

O

R

N H

O

R

NH

O

NH

O S S

H R N O

H S R N S O

O N R S H

H RN

S S O

S

H S R N R N H O S

O

S

O

H N

S S

O S N R S H

O NR H

S HN R

O HN R

O HN

R n

O

R

Scheme 3.8 Heterochiral-selective supramolecular polymerization of a pair of enantiomers (blue and red) to afford their alternating sequences. The hydrogen-bonded heterochiral dimer polymerizes by forming stacked thiophene amide pairs between the dimers

(A) as well as coronene (B) resulted in the formation of their alternating [ABA (22) and ABABA (24)] or other [ABBA (23)] sequences depending on the length of the rigid organic pillars (Fig. 3.6) [18]. As a flexible host molecule exhibiting guest accommodations in an induced-fit manner, a series of cyclodimeric metalloporphyrin hosts were found to include various fullerenes to form ABA-type sequences composed of two types of π-conjugated molecule [19]. When a combination of paramagnetic Cu(II) porphyrin and endohedral metallofullerene La@C82 were used as the components of the sequence, the spins on the host and guest were ferromagnetically coupled to give a three-spin sequence with the quartet ground state S = 3/2 (25), as determined by 2D ESR spectroscopy (Scheme 3.10) [20]. The spin–spin interaction in the spin sequence was switched into a ferrimagnetic one

42

3 Synthetic Strategies of Molecular Sequences Linked …

C12H 25O

OC12H 25

O

O

C12H 25O C12H 25O

OC12H 25 O

O

NH N

N

O

O

O

O

OC12H 25

Kinetic Control

R

R

R

O N H O N H O N H

O N O O N O O N O O N O

O N O O N O O N O O N O

H N O H N O H N O H N O

C12H 25O

R

O N H

R

O N H

R

R R R R R

+ R R

R

O N H

R

O N H

R

O N H

O N O O N O O N O O N O

O N O O N O O N O O N O

O

O

OC12H 25

Thermodynamic Control

R

O N H

N

OC12H 25

C12H 25O C12H 25O

N HN

NH

O N H

O

O

HN

R

OC12H 25

H N O

R

R

H N O

R

R

H N O

R

H N O

R

O N H O N H O N H O N H O N H O N H

O N O O N O O N O O N O O N O O N O O N O O N O

O N O O N O O N O O N O O N O O N O O N O O N O

H N O

R

H N O

R

H N O

R

H N O

R

H N O

R

H N O

R

H N O

R

H N O

R

Scheme 3.9 Selective formation of coexisting homosequences or alternating homodimer sequences of a pair of enantiomers from their racemic mixtures, directed by kinetic or thermodynamic control, respectively

when the orientation of the included La@C82 with respect to the Cu(II) porphyrin moieties was forcibly altered by the additional intracomplex cross-linkages between the two Cu(II) porphyrin moieties (26). Host molecules for fullerenes functioned in the formation of not only discrete but also polymeric alternating sequences, where, for example, a covalently linked dimeric form of hexakiscalix[5]arene (27) afforded the linear polymers upon complexation with fullerene dimers (28, 29) (Fig. 3.7) [21].

3.2 More-Than-Three Component Systems

43 N

Pd 2+

N

Pt 2+ N N

N N

Pt 2+ N

N

N

N N

N

N

N

N Pt 2+ N

N

Pt 2+ N

N N

N Pd 2+

N

N Pd 2+

N

N N

Pd 2+N

N N

Pd 2+N

N

N

N N

22

N N Pt 2+

N Pd 2+N

N

N N

N N Pd 2+

23

N Pd 2+N

N

N N

N N Pd 2+

24

Fig. 3.6 Molecular structures of discrete ABA (22), ABBA (23), and ABABA (24) sequences designed using host–guest chemistry

Although it would require a more sophisticated structural design, a polymeric alternating sequence was also obtained from a combination of heteroditopic A–B- and C–D-type monomers through the selective A/D and B/C host–guest complexations, where hydrogen-bonding and donor–acceptor π-electronic interactions were mainly operative, respectively (Scheme 3.11) [22]. This approach can be expanded to the construction of repeating sequences composed of more than three components by the judicious choice of host and guest moieties with the highly selective complexation behavior (see Sect. 3.2.2). Although it was not a sequence expected to be formed, mixtures of cationic Ir(III) and anionic Fe(II) complexes in various ratios, in the presence of cucurbit[8]uril, were found to afford repetitive Ir–Fe–Ir sequences selectively in aqueous media, where the cucurbit[8]uril unit linked two metal complexes through the inclusion of their hydrophobic organic substituents (Scheme 3.12) [23]. The selective formation of (Ir–Fe–Ir)n sequences was ascribed for the electrostatic interaction between Ir and Fe complexes as well as the net charges on the resultant sequences that is crucial for their dissolution.

3.2 More-Than-Three Component Systems The sequencing of more than three types of component via dynamic bonds is the least explored and currently most challenging research subject among works on the synthesis of molecular sequences. A sophisticated structural design of multiple monomeric components is generally required to achieve their specific sequence formation.

44

3 Synthetic Strategies of Molecular Sequences Linked …

H 25C12O

O

N N Cu N N

C12H 25O

OC12H 25

O

N N Cu N N

O

OC12H 25

O

O

O O

O

O H 25C12O

H 25C12O

N N Cu N N

O O

O

O

OC12H 25 O

N N Cu N N

O

S = 3/2

25

O OC12H 25

S = 1/2

26

Grubbs Cat. G1

Scheme 3.10 Schematic representation of the switching of a ferromagnetically coupled three-spin sequence composed of a paramagnetic host and a guest (25) into a ferrimagnetic one (26) by altering the host–guest geometry OH HO HO HO OH

OH OH OH OH OH O HN

OC12H 25

O

OC12H 25

NH

N

N

HN O

NH

C12H 25O

C12H 25O

O

OH HO OH HO HO

OH OH OH OH OH 27

C12H 25O

OC12H 25 OC12H 25

OC12H 25

O

O O

O

O

O

O

O

O

C12H 25O

O C12H 25O C12H 25O

OC12H 25

28

29

Fig. 3.7 Molecular structures of dimeric forms of hexakiscalix[5]arene (27) and fullerenes (28, 29) whose host–guest complexation affords their alternating sequences O O

O

O

O

O

O

O

O

O

5

N+

N+

O

O

O

O

O

O

O

O O

O

O O

10

O

O

C

D

O O

N+ H H

O

+

B

O

O

O O

A

O

5

O O

O

O

N+ O

O

O

O

N+ O

O

O 10 O O

O O N+ OH HO

O

O

O

5

N+

N+

O n

Scheme 3.11 Heteroditopic A–B- and C–D-type monomers that afford their alternating sequences through the selective A/D and B/C host–guest complexations

3.2 More-Than-Three Component Systems

45

O O

O O

HN O NH O

N

N

F N F

F

N Fe 2+ N N

N N

+ F

+

N

N

O

Ir 3+ N N

NH O O

HN

O

O O

O O

O O

HN O

N N N

N

NH O

Ir 3+ N N

N

N

F N

N F

F

N Fe 2+ N N

N

Ir 3+ N N N

F

N

O NH

O O

n

HN

O

O O

O N

N

H

H

N

N 8 O

Scheme 3.12 Cucurbit[8]uril-mediated selective formation of repetitive Ir–Fe–Ir sequences

3.2.1 Discrete Sequences Sequentially aligned multiple electron/energy donor and acceptor moieties have attracted the attention of researchers as models of natural photosynthetic systems [24, 25] to gain insights on the efficient energy conversion of sunlight. Although most of these donor–acceptor oligoarrays were constructed purely via static bond linkages, some of them were constructed partly or completely through the controlled

46

3 Synthetic Strategies of Molecular Sequences Linked …

assembly of their components in a supramolecular manner. A triad composed of boron dipyrrin, zinc porphyrin, and fullerene was prepared by the coordination of imidazolyl functionality located at the fullerene moiety to the Zn(II) metal center of the covalent boron dipyrrin–zinc porphyrin dyad, where the boron dipyrrin, zinc porphyrin, and fullerene were found to work as the light energy antenna, energy acceptor/electron donor, and electron acceptor, respectively (Fig. 3.8) [26]. Another incentive to form discrete molecular sequences via dynamic bonds can be found in the field of molecular machinery, as it is crucial for the construction of molecular machines to achieve the supramolecular sequentialization of multiple modules, each of which is responsive to a particular mechanical function. To achieve longdistance mechanical communication, separately synthesized signaling (30), bridging (31), and scissoring (32) modules were sequentially linked by the coordination of pyridyl moieties in the signaling and scissoring modules to the Zn(II) metal centers of the bridging module (Fig. 3.9) [27]. The bridging module was designed nonsymmetrically to realize its selective binding to one unit each of signaling and scissoring modules. CD spectroscopy revealed that the scissoring module exhibited a rotational conformational change in response to the photo-isomerization of the signaling module that caused an angular motion of the bridging module. N

Fig. 3.8 Molecular structures of a triad sequence composed of a light energy antenna (A), energy acceptor/electron donor (B), and electron acceptor (C) linked via covalent as well as coordination bonds

N N N Zn N N

N

N F B

O

O

N

F

A

Ar N N Zn N N NAr

B

C

Ar NH N N HN

Ar N N N Zn N N

Ar Fe

Ar

Ar

S S

Ar N

N

N N Zn N N Ar

30

N

N N NZn N

Ar

N H

HN N

Ar

Ar 31

32

Fig. 3.9 Molecular structures of sequentially linked signaling (30), bridging (31), and scissoring (32) modules for long-distance mechanical communication

3.2 More-Than-Three Component Systems Cl

Cl

CF3CO2 Pt + N N N

Re(CO) 3 N N N

O

O

H N

O O

O

47

O

H N

N H

O

Amyloid-like

O N H

OH O

O

50 nm N N Cl

Rh Cl

N Cl

N

N N Re(CO) 3 Cl

Scheme 3.13 Amyloid-like nanofibrillation of a heterometallic tetrad that affords homosequences of three types of metal complex

3.2.2 Polymer Sequences A discrete Rh(III)–Pt(II)–Re(I)–Re(I) metal sequence constructed on a peptide backbone was found to afford fibrous assemblies, which is regarded as a formation of coexisting homosequences [28]. Since this tetrad metal sequence had the parallel ß-sheet orientation in these fibers, as confirmed by IR spectroscopy and XRD, there must be segregated 1D homosequences of Rh(III), Pt(II), and Re(I) metal centers in the assemblies (Scheme 3.13). ß-Sheet formation was also used as a driving force for the surfacegrafted supramolecular polymerization of peptide-tagged C 3 -symmetric motifs (Scheme 3.14) [29]. One of the motifs bearing a thioether functionality at each peptide terminal (33) was used as the initiator for the polymerization from the gold surface. Since the other two possess positively (34) or negatively (35) charged side residues, they were alternately stacked one by one from the cationic initiator motif on the surface as a conceptual merging of layer-by-layer deposition affording 2D nanostructures [30] and surface-grafted polymerization affording 1D objects. With the capability of a Pt(II) center in a square-planar geometry to form bonds with other metal centers, repeating sequences of Pt(II)–Cu(II)–Pt(II)–Rh(II)–Rh(II) were constructed in the crystalline phase [31]. The sequence was prepared by simply mixing the corresponding Rh-dimer and heterotrinuclear Pt(II)–Cu(II)–Pt(II) complex, the latter of which was obtained from a monomeric Pt(II) complex and inorganic Cu(II) salt (Scheme 3.15). The simplicity of the adopted protocols enables the construction of other similar sequences such as Pt(II)–Co(II)–Pt(II)–Rh(II)–Rh(II), in which an intrasequence antiferromagnetic interaction was observed between Co(II) centers through multiple metal–metal bonds [32]. Three types of heteroditopic monomer (A–B, C–D, and E–F; Fig. 3.10) were designed to realize their supramolecular repetitive sequentialization [33]. The key

48

3 Synthetic Strategies of Molecular Sequences Linked … 33: X = S, R = (CH2)4NH3+

X O

HN R

34: X = O, R = (CH2)4NH3+

NH O O

HN R

35: X = O, R = (CH2)2CO2

NH O O

HN

NH

O

O

N H

H N O

O

R N H

H N O

O

R N H

H N

X

O

O

HN O NH O

HN O

O NH

HN

O

O

O

O NH

O

X

Scheme 3.14 Surface-grafted supramolecular polymerization of peptide-based monomers

Cu(II)

Pt

Rh 2(O2CCH3)4

Pt

Cu Pt

Pt

Cu Pt

Rh Rh n

Scheme 3.15 Preparation of a periodic sequence of bonded metal centers as a form of crystal

to achieve their sequence-controlled polymerization is the use of three types of orthogonal host–guest interaction, i.e. those operative between biscalix[5]arene–C60 (B–C), bis(acetamidopyridinyl)isophthalamide–barbiturate (D–E), and bisporhyrin– trinitrofluorenone (TNF) (F–A). SEM, 1 H NMR spectroscopy, and ESI–MS on 1:1:1 mixtures of these three monomers with and without the competitive guests such as C60 , barbiturate, and TNF supported the formation of expected repetitive sequences of these three monomers.

3.2 More-Than-Three Component Systems

49 OH OH OH OH OH

O

O

O

O2N

C12H 25O O

NO 2 NO 2

NH

N (CH2)6 O NN

N OC12H 25

A

NH O OH OH OH OH OH

B

O NH O

O

O O (CH2)12 O

C11H 23

N NH

C12H 25O N (CH2)6 O NN OC12H 25

C

NH O

N

NH O

C11H 23

D

Ph N HN NH N

O O

C12H 25O

HN

NH

HN O

Ph

N

N

O

Ph

OC12H 25

Ph

NH O

N HN NH N

E

Ph

Ph

F Fig. 3.10 Molecular structures of three heteroditopic monomers whose 1:1:1 mixtures afford supramolecular repetitive sequences of host–guest complexes B–C, D–E, and F–A via the selective complexations between these pairs

Although the dynamic nature of the bonds that link the components of sequences generally makes it difficult to precisely control sequence formation, this characteristic is advantageous for making a sequence stimuli-responsive. Copolymers composed of three types of pegylated benzene-1,3,5-tricarboxamide were prepared in aqueous media, two of which were cationic and labeled with either pair of fluorescent cyanine dyes used for the Förster resonance energy transfer (FRET)-based evaluation of their spatial distribution in the copolymers (36, 37), whereas the remaining one was neutral

50

3 Synthetic Strategies of Molecular Sequences Linked …

36: R = O

R

O 12

O3

NH 3+

O

X=

12

H N

O3

H N

N

N+

O HN

O

N+

O

R NH

37: R = X

O 12

O3

NH 3+

O

X=

12

H N

O3

O N

38: R = X =

H R N

H R N

O O H H N R R N O H R N

O H R N

H N O H N

H N

O O H H N R R N

O H N

O O H H N R R N

O H N

H R N O

O H R N O

O 12

O H N

O O H H R N R N

O

O

12

O

12

O3

O3

O3

O 12

O 12

O3

O3

O3

H R N

OH

HO O H H N R R N

H N

O H R N

O

N+

O H R N

O3

O

OH

O H N

O O H H N R R N

O H N

Low FRET

OH

H N

O

O H R N

H R N O

O

O

12

O

12

O

12

O O H H N R R N

N

36 + 37 + 38

O H N

H N

N+ 12

O H N

OH

O

O

H N

O O H H R N R N

O H N

O3

H R N

N 12

12

OH

OH

O O

O

O3

O3

O3

OH

OH

H N

O

H N

O

O

N+ NN+

O 12

O3

N O 12

O

12

O3

O3

OH

High FRET

OH

O H N

O 12

O3

OH

O

36 + 37 + 38 + DNA

Scheme 3.16 Dynamic polymer sequences that change in response to the binding of DNA polyanion

and unlabeled (38) (Scheme 3.16) [34]. Upon the addition of single-stranded DNA as a polyanion, the FRET ratio increased owing to the clustering of cationic components induced by DNA binding, making the visualization of the stimuli-responsive nature of the sequence in the copolymers possible.

References 1. Morris KL, Chen L, Raeburn J, Sellick OR, Cotanda P, Paul A, Griffiths PC, King SM, O’Reilly RK, Serpell LC, Adams DJ (2013) Chemically programmed self-sorting of gelator networks. Nat Commun 4:1480 2. Ishida Y, Aida T (2002) Homochiral supramolecular polymerization of an “S”-shaped chiral monomer: translation of optical purity into molecular weight distribution. J Am Chem Soc 124:14017–14019 3. Zheng YJ, Zhou HX, Liu DA, Floudas G, Wagner M, Koynov K, Mezger M, Butt HJ, Ikeda T (2013) Supramolecular thiophene nanosheets. Angew Chem Int Ed 52:4845–4848

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4. Zhang W, Jin W, Fukushima T, Saeki A, Seki S, Aida T (2011) Supramolecular linear heterojunction composed of graphite-like semiconducting nanotubular segments. Science 334:340–343 5. Adelizzi B, Aloi A, Markvoort AJ, Ten Eikelder HMM, Voets IK, Palmans ARA, Meijer EW (2018) Supramolecular block copolymers under thermodynamic control. J Am Chem Soc 140:7168–7175 6. Elacqua E, Croom A, Manning KB, Pomarico SK, Lye D, Young L, Weck M (2016) Supramolecular diblock copolymers featuring well-defined telechelic building blocks. Angew Chem Int Ed 55:15873–15878 7. Elacqua E, Manning KB, Lye DS, Pomarico SK, Morgia F, Weck M (2017) Supramolecular multiblock copolymers featuring complex secondary structures. J Am Chem Soc 139:12240– 12250 8. Scherman OA, Ligthart GBWL, Ohkawa H, Sijbesma RP, Meijer EW (2006) Olefin metathesis and quadruple hydrogen bonding: a powerful combination in multistep supramolecular synthesis. Proc Natl Acad Sci USA 103:11850–11855 9. Chen S-G, Yu Y, Zhao X, Ma Y, Jiang X-K, Li Z-T (2011) Highly stable chiral (A)6 –B supramolecular copolymers: a multivalency-based self-assembly process. J Am Chem Soc 133:11124–11127 10. Gerthoffer MC, Wu S, Chen B, Wang T, Huss S, Oburn SM, Crespi VH, Badding JV, Elacqua E (2020) ‘Sacrificial’ supramolecular assembly and pressureinduced polymerization: toward sequence-defined functionalized nanothreads. Chem Sci 11:11419–11424 11. Bryant MJ, Skelton JM, Hatcher LE, Stubbs C, Madrid E, Pallipurath AR, Thomas LH, Woodall CH, Christensen J, Fuertes S, Robinson TP, Beavers CM, Teat SJ, Warren MR, PradauxCaggiano F, Walsh A, Marken F, Carbery DR, Parker SC, McKeown NB, Malpass-Evans R, Carta M, Raithby PR (2017) A rapidly-reversible absorptive and emissive vapochromic Pt(II) pincer-based chemical sensor. Nat Commun 8:1800 12. Tashiro K, Ohtsu H, Kawano M, Kojima T, Kato T (2018) Platinum(II) terpyridine complex that switches its photochemical reactivity in response to its chromic behavior in the crystalline state. Inorg Chem 57:13079–13082 13. López-de-Luzuriaga JM, Mahmoudi G, Monge M, Olmos ME, Rodríguez-Castillo M, Villar M, Zubkov FI, Kvyatkovskaya EA (2020) Zigzag vs helicoidal gold–silver 1D chains: influence of subtle interactions in the spatial arrangement of supramolecular systems. Inorg Chem 59:9443– 9451 14. Catalano VJ, Malwitz MA, Etogo AO (2004) Pyridine substituted N-heterocyclic carbene ligands as supports for Au(I)-Ag(I) interactions: formation of a chiral coordination polymer. Inorg Chem 43:5714–5724 15. Jacques J, Collet A, Wilen SH (1994) Enantiomers, racemates, and resolutions. Krieger Publishing Company, United States 16. Ueda M, Aoki T, Akiyama T, Nakamuro T, Yamashita K, Yanagisawa H, Nureki O, Kikkawa M, Nakamura E, Aida T, Itoh Y (2021) Alternating heterochiral supramolecular copolymerization. J Am Chem Soc 143:5121–5126 17. Wehner M, Röhr MIS, Stepanenko V, Würthner F (2020) Control of self-assembly pathways toward conglomerate and racemic supramolecular polymers. Nat Commun 11:5460 18. Yoshizawa M, Nakagawa J, Kumazawa K, Nagao M, Kawano M, Ozeki T, Fujita M (2005) Discrete stacking of large aromatic molecules within organic-pillared coordination cages. Angew Chem Int Ed 44:1810–1813 19. Tashiro K, Aida T (2007) Metalloporphyrin hosts for supramolecular chemistry of fullerenes. Chem Soc Rev 36:189–197 20. Hajjaj F, Tashiro K, Nikawa H, Mizorogi N, Akasaka T, Nagase S, Furukawa K, Kato T, Aida T (2011) Ferromagnetic spin coupling between endohedral metallofullerene La@C82 and a cyclodimeric copper porphyrin upon inclusion. J Am Chem Soc 133:9290–9292 21. Hirao T, Tosaka M, Yamago S, Haino T (2014) Supramolecular fullerene polymers and networks directed by molecular recognition between calix[5]arene and C60 . Chem Eur J 20:16138–16146

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22. Wang F, Han C, He C, Zhou Q, Zhang J, Wang C, Li N, Huang F (2008) Self-sorting organization of two heteroditopic monomers to supramolecular alternating copolymers. J Am Chem Soc 130:11254–11255 23. Raeisi M, Kotturi K, del Valle I, Schulz J, Dornblut P, Masson E (2018) Sequence-specific self-assembly of positive and negative monomers with cucurbit[8]uril linkers. J Am Chem Soc 140:3371–3377 24. Deisenhofer J, Epp O, Miki K, Huber R, Michel H (1985) Structure of the protein subunits in the photosynthetic reaction centre of Rhodopseudomonas viridis at 3Å resolution. Nature 318:618–624 25. McDermott G, Prince SM, Freer AA, Hawthornthwaite-Lawless AM, Papiz MZ, Cogdell RJ, Isaacs NW (1995) Crystal structure of an integral membrane light-harvesting complex from photosynthetic bacteria. Nature 374:517–521 26. D’Souza F, Smith PM, Zandler ME, McCarty AL, Ito M, Araki Y, Ito O (2004) Energy transfer followed by electron transfer in a supramolecular triad composed of boron dipyrrin, zinc porphyrin, and fullerene: a model for the photosynthetic antenna-reaction center complex. J Am Chem Soc 126:7898–7907 27. Kai H, Nara S, Kinbara K, Aida T (2008) Toward long-distance mechanical communication: studies on a ternary complex interconnected by a bridging rotary module. J Am Chem Soc 130:6725–6727 28. Rajmohan R, Vrla G, Ueki H, Sajna K, Takei T, Ohtsu H, Kawano M, Vairaprakash P, Tashiro K (2020) Amyloid-like nanofibrillation of metal-organic complex arrays ruled by their precisely designed metal sequences. Chem Asian J 15:766–769 29. Frisch H, Fritz E-C, Stricker F, Schmüser L, Spitzer D, Weidner T, Ravoo BJ, Besenius P (2016) Kinetically controlled sequential growth of surface-grafted chiral supramolecular copolymers. Angew Chem Int Ed 55:7242–7246 30. Lvov Y, Ariga K, Ichinose I, Kunitake T (1995) Assembly of multicomponent protein films by means of electrostatic layer-by-layer adsorption. J Am Chem Soc 117:6117–6123 31. Uemura K, Ebihara M (2013) Paramagnetic one-dimensional chains comprised of trinuclear Pt– Cu–Pt and paddlewheel dirhodium complexes with metal–metal bonds. Inorg Chem 59:1692– 1701 32. Uemura K, Miyake R (2020) Paramagnetic one-dimensional chain complex consisting of three kinds of metallic species showing magnetic interaction through metal–metal bonds. Inorg Chem 52:5535–5550 33. Hirao T, Kudo H, Amimoto T, Haino T (2017) Sequence-controlled supramolecular terpolymerization directed by specific molecular recognitions. Nat Commun 8:634 34. Albertazzi L, Martinez-Veracoechea FJ, Leenders CMA, Voets IK, Frenkel D, Meijer EW (2013) Spatiotemporal control and superselectivity in supramolecular polymers using multivalency. Proc Natl Acad Sci USA 110:12203–12208

Chapter 4

Outcomes from Synthetic Molecular Sequences in Materials Science

Although it is basically regarded to be in a preliminary stage, outcomes from synthetic molecular sequences have already been observed in both polymeric and discrete systems, encouraging researchers to meet greater challenges. In this chapter, examples of the outcomes obtained from the structural features of sequences are divided into five groups on the basis of the type of sequence.

4.1 Discrete Sequences Amphiphiles generally contain both hydrophobic and hydrophilic parts in their molecular structure. For the surface functionalization of their self-assembled forms such as micelles and vesicles, mannose moieties were covalently attached to the hydrophilic terminal of rod–coil amphiphiles composed of oligo-ethylene glycol and aromatic moieties to afford three-component discrete sequences (Fig. 4.1) [1]. Because of the multivalent interactions between their nanofibrous coassemblies and E. coli that expresses the mannose-binding adhesion protein at the cell surface, the mannose-decorated nanofibers induced E. coli cell agglutination, by which their proliferation was found to be suppressed effectively. Advances in scanning tunneling microscopy (STM) techniques over the past decades enabled the evaluation of charge transport properties in single molecules, which provides new insights into the molecular structure–bulk charge transport capability relationship. A series of sequence-defined π-conjugated oligomers composed of multiple types of aromatic building block, including oxazole, imidazole, pyrrole, and/or substituted and nonsubstituted benzene, were prepared by the iterative coupling of a universal monomer that is transformable into these three heteroaromatics [2]. The single-molecule conductance of these sequences was evaluated by using a scanning tunneling microscope-break junction technique. As a result, it was found that sequences containing the imidazole or pyrrole moiety at specific positions exhibited unambiguously larger conductance values than the other sequences because © National Institute for Materials Science, Japan 2023 K. Tashiro, Synthetic Molecular Sequences in Materials Science, NIMS Monographs, https://doi.org/10.1007/978-4-431-56933-6_4

53

54

4 Outcomes from Synthetic Molecular Sequences in Materials Science H O O

H O H O O H

H O O

H O H O O H

O O

N N N

HN

N N N

HN

O

O

O

O

O

N N N

HN

O

O

O

N N N

HN

O

O

O

O

O

O

O

H O O

H O H O O H

O

O

O

O

H O O

H O H O O H

O

O

O

O

O

Fig. 4.1 Molecular structures of mannose-bearing amphiphiles whose coassemblies suppress E. coli proliferation through the induction of cell agglutination of that bacteria

they made the gold electrodes come in closer contact with the oligomer backbone (Fig. 4.2). Another example of the functions/properties that strongly correlated with the precise control of discrete static sequences can be seen in the synthetic foldamers [3]. They have been designed to possess particular sequences that mimic the wellprogrammed 3D structure formation capability of natural sequences such as proteins and DNA [4]. Later, these foldamers were used as host molecules with a precise molecular recognition capability. A synthetic helical aromatic oligoamide foldamer host that strongly prefers the tartaric acid guest over a structurally similar malic acid guest was subjected to the iterative mutation of its sequence, where multiple cycles of single-sequence mutation–guest binding enabled to reach a new sequence exhibiting reversed preferences to the two acid guests (Fig. 4.3) [5]. Mutation of sequence 39 into 40 decreased the number of H-bond between the foldamer and tartaric acid (Fig. 4.4a), lowering their binding constant. In contrast, the same mutation did not alter the number of H-bond with malic acid that lacks one OH functionality of tartaric acid (Fig. 4.4b), while the accompanied dessymmetrization of the foldamer cavity allowed its better fit to the less symmetric molecular shape of malic acid, enlarging the binding constant of the foldamer and malic acid.

4.2 Coexisting Homosequences One of the nanostructures for the efficient conversion of light energy into electrical energy is composed of closely oriented homosequences of the electron donor and

4.2 Coexisting Homosequences

55

Fig. 4.2 Scanning tunneling microscope-break junction technique that uncovered the relatively large single-molecule conductance of π-conjugated oligomers with particular sequences

Fig. 4.3 Helical aromatic oligoamide foldamer sequence (39) and its mutated analogue (40) exhibiting reversed preferences toward two structurally similar guests

56

4 Outcomes from Synthetic Molecular Sequences in Materials Science

Fig. 4.4 Host–gues interactions of a NNpyr-pyz-pyrNN–tartaric acid and b NNpyr-pyzpyrNNQF –malic acid

acceptor, which is suitable for fulfilling the two important requisites, i.e., efficient photoinduced charge carrier production and rapid conduction of the generated charge carriers [6]. Controlled self-assembly of donor–acceptor (D–A) dyads or analogous oligo-ads in the construction of such supramolecular heterojunctions has been a hot research subject [7], where the key issue is to achieve the homosegregation of donor and acceptor moieties by overcoming heteroselective D–A interactions. A rational idea to address this issue would be the use of homoselective bonding interactions to prevent D–A alternation. Along this line, self-assembly of an organoplatinum(II) complex–fullerene dyad was attempted with an expectation of the operation of Pt– Pt interactions, which actually afforded the segregated and alternatingly layered platinum(II) complex donor and fullerene acceptor (Scheme 4.1) [8]. An exfoliated analogue of the multilayers, which was obtained by the coassembly of that dyad with the same organoplatinum(II) complex lacking the fullerene moiety, exhibited a clear photoconductive response with the ambipolar charge-transporting behavior, as shown using a field-effect transistor setup. Another issue is the morphological control of the resultant assemblies, as exemplified for a porphyrin–fullerene dyad having one stereogenic center (Fig. 4.5) [9]. The self-assembling behavior of this particular dyad was found to be dependent on its optical purity, where its enantiomerically pure form afforded bundles of very long nanofibers containing homosequences of the donor and acceptor, whereas its racemic mixture formed submicron-sized spheres composed of intermolecularly stacked D–A moieties. Owing to the differences in the morphology of the assemblies as well as the supramolecular sequences of the donor and acceptor in them, the former exhibited ambipolar charge transport characteristics with electron and hole mobilities of up to 0.14 and 0.10 cm2 V–1 s–1 , respectively, while the latter showed only a small hole mobility of ~10–4 cm2 V–1 s–1 , as evaluated from their time-of-flight (TOF) profiles of transient photocurrents. These works were conducted through sequence control at two different stages, namely, (1) design of short discrete sequences linked with static bonds and (2) their controlled self-assembly to afford

4.2 Coexisting Homosequences

57

coexisting homosequences linked with dynamic bonds, suggesting one of the future directions for materials science based on synthetic molecular sequences. If the formation of homochiral sequences of enantiomers is self-promoted, macroscopic chiral symmetry breaking can take place in a racemic mixture of the enantiomers by amplifying the initially produced small stochastic fluctuations in chirality. Although almost all of the known examples are related with crystallization [10], the occurrence of macroscopic chiral symmetry breaking has been observed in gelation

Scheme 4.1 Donor–acceptor dyad composed of an organoplatinum(II) complex and fullerene, whose self-assembly afforded segregated and alternatingly layered platinum(II) complex donor and fullerene acceptor

Fig. 4.5 Effects of the optical purity of a chiral donor–acceptor dyad on the morphology and charge transport properties of its assembly

58

4 Outcomes from Synthetic Molecular Sequences in Materials Science

H N

O

O

O O

O

H N

O

O O

O HN

L-Form

O NH

D-Form

Fig. 4.6 Molecular structures of a pair of enantiomers whose racemic mixture affords a non-racemic gel as the result of macroscopic chiral symmetry breaking

very recently, where the partial gelation of a racemic mixture of π-decorated glutamate (Fig. 4.6) afforded a gel enriched in either of the L- or D-form of the gelator [11]. Since the gelation-mediated macroscopic chiral symmetry breaking was observed for a racemic compound that cannot afford conglomerate crystal, it would provide a new solution to address the issue of narrow applicability of preferential crystallization for the resolution of enantiomers [12].

4.3 Block Sequences Polymer sequence–physical property relationship would be a good example of a research subject to understand the significance of sequence control at the molecular level for the engineering of materials with specific functions or properties. As one of the most well-known examples of block polymers, the SBS block sequence was established to make the resultant polymer suitable for synthetic rubbers. In this sequence, the polystyrene segments serve as the hard physical cross-linkers to give the material mechanical durability, whereas polybutadiene is the soft segment that provides elasticity to the polymer (Fig. 4.7). Similar strategies using micro- or nanoscale phase separation of the segments of a block sequence were also adopted for the preparation of nano-porous membranes or photovoltaic materials. The former can be seen in the temperature-controlled annealing of a film of an amphiphilic block copolymer, in which the hexagonally arranged cylindrical domains of hydrophilic poly(ethylene oxide) (PEO) segments were spontaneously formed in the hydrophobic and liquid crystalline polymethacrylate-based matrix (Scheme 4.2) [13]. The resultant phase-separated film played a role as the template for the fabrication of nanoporous membranes [14]. On the other hand, copolymers composed of electron donor and acceptor segments were designed to construct the nanostructured D–A heterojunctions for the fabrication of highly efficient photovoltaic devices (Fig. 4.8) [15].

4.3 Block Sequences

59

A metallic analogue of the block copolymers, although its diameter is over 100 nm, was found to behave as a chemically fueled catalytic nanomotor [16]. When a Pt–Au block nanorod was put into an aqueous H2 O2 solution, the Pt and Au ends catalyzed the oxidation and reduction of H2 O2 , respectively (Fig. 4.9), producing a gradient of proton concentration along the long axis of the nanorod. It is claimed that a local electronic field caused by this proton gradient drove the negatively charged nanorod toward the Pt end, as observed in experiments. Polyrotaxane is a new type of polymer composed of one axis polymer mechanically interlocked with multiple rings [17]. Since the rings are generally mobile along Fig. 4.7 Microphase separation of polystyrene (red)–polybutadiene (blue)–polystyrene block copolymers

O

Br m O

O n O

O

O

O

O

O

O m

N

C4H 9 O

O n Br

O

O O

m

N

N

O(CH2)11

Br

O

O

O C4H 9

N

N

C4H 9 O

O

N

N

Br m O

O n

O

n

(CH2)11O

N

O

Br m O

O C4H 9

O(CH2)11

O

O

N

N

O(CH2)11

C4H 9

O n

(CH2)11O

N

O

(CH2)11O

(CH2)11O

C4H 9

N N

Br m O

n

N

C4H 9 O

Br

O O

O

n

m

Scheme 4.2 Spontaneous formation of hexagonally arranged cylindrical domains of hydrophilic poly(ethylene oxide) segments in the hydrophobic and liquid crystalline polymethacrylate-based matrix by temperature-controlled annealing of amphiphilic block copolymer film

60

4 Outcomes from Synthetic Molecular Sequences in Materials Science (OCH2CH2)3OCH 3

n

O

N

OO

m

N

O N

D=

N

D

N Zn

X

(OCH2CH2)3OCH 3

N A = H 3C

N

A

Y

(OCH2CH2)3OCH 3 X=

Y=

(OCH2CH2)3O

(OCH2CH2)3O O(CH 2)6O

O(CH 2)6O

O(CH 2)12O

Fig. 4.8 Donor–acceptor block copolymers that spontaneously form heterojunctions by the segregations of donor and acceptor segments

2H+ + 2e + H2O2

H2O2

Pt

2H+ + 2e + O2

Au

2H2O

Fig. 4.9 Pt–Au block nanorod as a chemically fueled nanomotor that catalyzes the oxidation and reduction of H2 O2 at the Pt and Au ends, respectively

the axis polymer, polyrotaxane can be an interesting structural motif for achieving the switching of block sequences between, e.g., ABA and BAB, by controlling the location of the rings. When polyrotaxane was prepared from a PEO–poly(propylene oxide) (PPO)–PEO axis and ß-cyclodextrin (ß-CD) rings, the location of ß-CD was controlled by the chemical modification of OH functionalities of ß-CD with hydrophilic hydroxypropyl or the subsequent capping with hydrophobic trimethylsilyloxypropyl groups. Small- and wide-angle X-ray scattering (SWAXS) studies on the self-assembed structure of these polyrotaxaes revealed that hydrophilic or hydrophobic ß-CD moieties were found to locate at the central PPO (PPO@ßCD) or terminal PEO (PEO@ß-CD) segments, respectively (Scheme 4.3) [18]. The mechanical properties of the resultant polymeric materials were quite different, as PPO@ß-CD and PEO@ß-CD became fluidic and elastic, respectively, above their glass transition temperatures. SWAXS measurements of these materials revealed that the ß-CD parts of multiple rotaxane molecules self-assembled to form a crystalline hard domain, whereas the axis segments uncovered with ß-CD served as a soft domain. The elasticity observed for PEO@ß-CD was explained by analogy with the elasticity of SBS rubber, where crystalline ß-CDs play the role of hard physical cross-linkers similarly to the polystyrene segments in SBS rubber.

4.4 Alternating Sequences

61 O

HO

O

O

29

75

O

O

O

OH 75

(CH2)6

H 2N

N H

CPh3

O

Ph 3C

H N

O

H N

(CH2)6

O

O

29

75

O

O

O

N H

75

(CH2)6

N H

CPh3

7 PPO@ -CD SiMe3 N N

Ph 3C

H N

O

H N

(CH2)6

O

O

O

29

75

O

O

3

N H

75

(CH2)6

N H

CPh3

3

PEO@ -CD

OR O OR OR

7

R =H

R = CH2CH(CH3)OH

R = CH2CH(CH3)OSi(CH3)3

Scheme 4.3 Polyrotaxane as a block sequence switchable by controlling the position of the ring parts

4.4 Alternating Sequences Not only blocks but also alternating sequences in organic polymers contribute to achieving intriguing functions. Polymeric alternating sequences composed of an electron acceptor (fullerene or perylene bisimide) and zwitterionic moieties were found to become an excellent cathode interlayer material for organic photovoltaics [19]. Since the electron acceptor and zwitterionic moieties in the polymers are well compatible

62

4 Outcomes from Synthetic Molecular Sequences in Materials Science

SO3 O

O

N+

N+

n SO3

N

Fig. 4.10 Alternating sequences of fullerene and zwitterionic moieties that work as the cathode interlayer material, significantly improving the performance of organic photovoltaics

with organic n-type semiconductors and metal electrode surfaces in photovoltaics, respectively, integration of this material containing fullerene moieties (Fig. 4.10) into a setup improved the power conversion efficiency of the devices from 2.75 to 10.74%. Another sequence-dependent property reported is the adhesion property of the materials based on dynamic polymers. A 1:1 mixture of a π-conjugated macrocycle and a phenylene-bridged diphosphate afforded supramolecular alternating sequences of hydrogen-bonded phosphate–phosphate dimers, wrapped and unwrapped with two molecules of a macrocycle (41) (Scheme 4.4), which exhibited a similar adhesion strength to commercial white glues [20]. In contrast, when the macrocycle/diphosphate ratio was changed to 2, all the phosphate–phosphate dimers were wrapped and stabilized with two molecules of that π-conjugated macrocycle (42), where the adhesion property of the resultant homosequence became as excellent as that of superglues.

4.5 Networked Sequences Although the concept of sequences is generally associated with 1D nanostructures, molecular sequences in 3D networks have also become research subjects. A series of nano-porous metal–organic frameworks (MOFs) sharing common crystalline lattice parameters were prepared using different combinations of differently substituted organic linkers (Fig. 4.11) [20]. This multivariate approach demonstrated that MOFs composed of three different organic linkers were superior to their analogous MOFs with less variable linkers in terms of H2 storage capacity or the selective uptake capacity for CO2 over CO, exemplifying the scientific maxim “more is different” [21]. On the basis of the results obtained using the rotational-echo doublet resonance NMR technique to measure the distances between atoms, with the help of molecular

4.5 Networked Sequences

63 OR

RO

CN CN

OR

NC CN

OR

OR

NC RO

RO CN

RO O H O

O

CN

RO

O O

O H

O O

P O

R = (CH2CH2O) 3CH 3

O P

O

H O

O

O

O P

H O

O

O H

O O H O O OR P NCP O O H O O

NC

P O

CN

CN

P

O

OR O

O H P

O

CN

CN

O

NC

NC RO

RO

n

RO

RO

41 OR

RO

CN CN

OR

NC

OR

OR

CN

RO CN

RO

NC RO

CN CN

CN RO

NC

O O H O O OR P NCP O O H O O CN

CN NC RO

OR

NC

RO

RO

RO

m

42

Scheme 4.4 Switching of an alternating sequence (41; macrocycle:diphosphate = 1:1) to a homosequence (42; macrocycle:diphosphate = 2:1) by the stoichiometric control of their components accompanied by the significant enhancement of the adhesive property

simulations, the distribution pattern of each organic linker in its mixtures in MOFs was later classified into either small cluster forming, random, or alternating [22].

64

4 Outcomes from Synthetic Molecular Sequences in Materials Science

Fig. 4.11 Molecular structures of organic linkers used for the construction of multivariate metal–organic frameworks

Zn

Zn

O

O R2

R1 O

O

Zn

Zn

R 1 = R 2 = H, Cl, CH 3, OCH 2Ph,

R 1 = NH 2, Br, NO 2,

O

, R2 = H

References 1. Lee D-W, Kim T, Park I-S, Huang Z, Lee M (2012) Multivalent nanofibers of a controlled length: regulation of bacterial cell agglutination. J Am Chem Soc 134:14722–14725 2. Yu H, Li S, Schwieter KE, Liu Y, Sun B, Moore JS (2020) Charge transport in sequence-defined conjugated oligomers. J Am Chem Soc 142:4852–4861 3. Lokey RS, Iverson BL (1995) Synthetic molecules that fold into a pleated secondary structure in solution. Nature 375:303–305 4. Selkoe DJ (2003) Folding proteins in fatal ways. Nature 426:900–904 5. Lautrette G, Wicher B, Kauffmann B, Ferrand Y, Huc I (2016) Iterative evolution of an abiotic foldamer sequence for the recognition of guest molecules with atomic precision. J Am Chem Soc 138:10314–10322 6. Madhu M, Ramakrishnan R, Vijay V, Hariharan M (2021) Free charge carriers in homo-sorted π-stacks of donor–acceptor conjugates. Chem Rev 121:8234–8284 7. Würthner F, Chen Z, Hoeben FJM, Osswald P, You C-C, Jonkheijm P, van Herrikhuyzen J, Schenning APHJ, van der Schoot PPAM, Meijer EW, Beckers EHA, Meskers SCJ, Janssen RAJ (2004) Supramolecular p–n-heterojunctions by co-self-organization of oligo(p-phenylene vinylene) and perylene bisimide dyes. J Am Chem Soc 126:10611–10618 8. Sato S, Takei T, Matsushita Y, Yasuda T, Kojima T, Kawano M, Ohnuma M, Tashiro K (2015) Coassembly-directed fabrication of an exfoliated form of alternating multilayers composed of a self-assembled organoplatinum(II) complex–fullerene dyad. Inorg Chem 54:11581–11583 9. Hizume Y, Tashiro K, Charvet R, Yamamoto Y, Saeki A, Seki S, Aida T (2010) Chiroselective assembly of a chiral porphyrin-fullerene dyad: photoconductive nanofiber with a top-class ambipolar charge-carrier mobility. J Am Chem Soc 132:6628–6629 10. An G, Yan P, Sun J, Li Y, Yao X, Li G (2015) The racemate-to-homochiral approach to crystal engineering via chiral symmetry breaking. Cryst Eng Comm 17:4421–4433 11. Tashiro K, Takei T, Fracaroli AM, Ohtsu H, Kawano M, Hashizume D (2022) Gelation of a π-decorated glutamate as a homochiral selective self-assembly to emerge macroscopic chiral symmetry breaking. Chem Asian J e202200230 12. Coquerel G (2007) Preferential crystallization. Top Curr Chem 269:1–51

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13. Tian Y, Watanabe K, Kong X, Abe J, Iyoda T (2002) Synthesis, nanostructures, and functionality of amphiphilic liquid crystalline block copolymers with azobenzene moieties. Macromolecules 35:3739–3747 14. Chen A, Komura M, Kamata K, Iyoda T (2008) Highly ordered arrays of mesoporous silica nanorods with tunable aspect ratios from block copolymer thin films. Adv Mater 20:763–767 15. Sommer M, Huettner S, Thelakkat M (2010) Donor–acceptor block copolymers for photovoltaic applications. J Mater Chem 20:10788–10797 16. Ren L, Wang W, Mallouk TE (2018) Two forces are better than one: combining chemical and acoustic propulsion for enhanced micromotor functionality. Acc Chem Res 51:1948–1956 17. Lipatova TE, Kosyanchuk LF, Shilov VV (1985) Complex formation between cyclic urethane and zinc chloride: its effect on polyrotaxane synthesis. J Macromol Sci A 22:361–372 18. Uenuma S, Maeda R, Kato K, Mayumi K, Yokoyama H, Ito K (2019) Drastic change of mechanical properties of polyrotaxane bulk: ABA−BAB sequence change depending on ring position. ACS Macro Lett 8:140–144 19. Liu Y, Sheri M, Cole MD, Emrick T, Russell TP (2018) Combining fullerenes and zwitterions in non-conjugated polymer interlayers to raise solar cell efficiency. Angew Chem Int Ed 57:9675– 9678 20. Deng H, Doonan CJ, Furukawa H, Ferreira RB, Towne J, Knobler CB, Wang B, Yaghi OM (2010) Multiple functional groups of varying ratios in metal-organic frameworks. Science 327:846–850 21. Anderson PW (1972) More is different. Science 177:393–396 22. Kong X, Deng H, Yan F, Kim J, Swisher JA, Smit B, Yaghi OM, Reimer JA (2013) Mapping of functional groups in metal-organic frameworks. Science 341:882–885

Chapter 5

Future Perspectives: Sequence-Based Point of View in Materials Science

From the examples of synthetic molecular sequences described in Chaps. 2–4, it will be noticed that they are roughly divided into two different types: (1) relatively long but less precisely determined sequences mainly studied in the field of polymer science and (2) short discrete sequences handled in synthetic or other chemistry fields. These facts clearly tell that presently there is no satisfactory synthetic method to perfectly control every structural parameter of a molecular sequence, where one or more parameters have to be sacrificed to control other parameters. A valuable future innovation that addresses the current issues can be the development of methods to effectively exclude the wrong sequences from the target during the processes of synthesis. Moreover, as described in Chap. 1, the huge structural diversity of molecular sequences strongly requires efficient protocols of mutation–evaluation cycles to maximize their structural advantages, thereby making the development of sophisticated protocols highly impactful. Regarding the future targets of sequences, their selected examples that are expected to bring particular outcomes are (1) those composed of multiple catalytic sites arrayed into a proper sequence to work for tandem-type reactions similarly to fatty acid synthase working in various living things [1], (2) molecular machinery systems constructed via supramolecular sequence formation of multiple components in a specific order to behave as robotics in the nanoscale world [2], and (3) sequences far from naturally existing ones but exhibit unique bioactivity through their interplay with biosequences [3]. Moreover, there are conceptually novel types of sequence whose realization is fundamentally attractive but not yet achieved. One of such “exotic” sequences is that having the feature of the Fibonacci sequence, which apparently appears random but is actually under the control of particular regulation [4]. Since this type of specifically regulated but non-periodic structures is a less explored but possibly fruitful research target, as is the case of quasicrystals having similar structural features [5], the successful synthesis of such sequences will trigger the start of a new scientific field that produces many unexpected outcomes.

© National Institute for Materials Science, Japan 2023 K. Tashiro, Synthetic Molecular Sequences in Materials Science, NIMS Monographs, https://doi.org/10.1007/978-4-431-56933-6_5

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