Chiral Nanotubes.

nanomaterials Review

Chiral Nanotubes Andrea Nitti 1,† , Aurora Pacini 1,2,† and Dario Pasini 1,2, * 1 2

* †

Department of Chemistry, University of Pavia, Viale Taramelli, 12-27100 Pavia, Italy; [email protected] (A.N.); [email protected] (A.P.) INSTM Research Unit, University of Pavia, Viale Taramelli, 12-27100 Pavia, Italy Correspondence: [email protected]; Tel.: +39-038-298-7835 These authors contributed equally to this work.

Academic Editors: Ashraf Ghanem and Yizhak Mastai Received: 7 June 2017; Accepted: 28 June 2017; Published: 4 July 2017

Abstract: Organic nanotubes, as assembled nanospaces, in which to carry out host–guest chemistry, reversible binding of smaller species for transport, sensing, storage or chemical transformation purposes, are currently attracting substantial interest, both as biological ion channel mimics, or for addressing tailored material properties. Nature’s materials and machinery are universally asymmetric, and, for chemical entities, controlled asymmetry comes from chirality. Together with carbon nanotubes, conformationally stable molecular building blocks and macrocycles have been used for the realization of organic nanotubes, by means of their assembly in the third dimension. In both cases, chiral properties have started to be fully exploited to date. In this paper, we review recent exciting developments in the synthesis and assembly of chiral nanotubes, and of their functional properties. This review will include examples of either molecule-based or macrocycle-based systems, and will try and rationalize the supramolecular interactions at play for the three-dimensional (3D) assembly of the nanoscale architectures. Keywords: chirality; nanotubes; three-dimensional (3D) assembly; supramolecular polymers; anisotropic materials

1. Introduction The organization of small molecules, macrocycles and polymers into tubes with hollow cavities is a key structural feature of living systems, as exemplified by cytoplasmic microtubules [1]. The term tubule refers to a small tube or canal and it is ubiquitous in biological and medical dictionaries. In general, tubes can be grouped into two principal categories, depending on tube diameter: (a) nanoscale tubes (nanotubes); and (b) microscale tubes (microtubes or tubules). Nanotubes (NTs), which present a diameter in the range several to 100 nanometers and a length-to-diameter ratio that can be greater than 106 , have potential for technological applications starting from medicine and biology, and passing through electronics, optics and sensing. Depending on their nature, they can be classified as inorganic NTs [2], organic NTs and hybrid NTs (Figure 1). Hybrid NTs are essentially formed by complementary organic and inorganic structures, and they have been recently reviewed [3]. The prototypical organic NT are carbon NT, and in particular single-walled carbon NTs (SWCNTs), which are cylindrical molecular structures, often considered as rolled-up graphene sheets. Depending on the angles with which the graphene sheet rolls up, SWCNTs can have different chirality and handedness. Their typical industrially adopted synthesis include arc discharge, laser ablation, and chemical vapor deposition techniques [4–6], but they invariably lead to a mixture of nanotubes with a broad distribution in diameter and chirality. The unique electronic and optical properties of SWCNTs, such as high surface area, high current capacity, and mechanical and chemical properties, can be significantly influenced by their dimensions and three-dimensional (3D) structure. Obtaining

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form, is a major challenge applications, and has gained research homogeneous SWCNTs, i.e., for the their same large-scale diameter and the same enantiomeric form,considerable is a major challenge attention [7–9]. for their large-scale applications, and has gained considerable research attention [7–9].

Figure 1. Classification of tubular objects, and a schematic representation of a biological tubule Figure 1. Classification tubular objects, and NT a schematic of a biological tubule (micrometer scale), and ofofa single-walled carbon (SWCNT)representation (nanometer scale). (micrometer scale), and of a single-walled carbon NT (SWCNT) (nanometer scale).

Chirality plays an important role in the materials field, influencing optical, magnetic and electrical Chirality plays an important role in the materials field, influencing optical, magnetic and properties such as magnetochiral circular dichroism, magnetic skyrmions in chiral magnetics and electrical properties such as magnetochiral circular dichroism, magnetic skyrmions in chiral nonreciprocal carrier transport in chiral conductors [10–12]. Controlling the chirality of tubular magnetics and nonreciprocal carrier transport in chiral conductors [10–12]. Controlling the chirality nanosystems will be essential to increase their potential for targeted applications. of tubular nanosystems will be essential to increase their potential for targeted applications. The self-organization of organic molecules in 3D structures is a parallel, and increasingly The self-organization of organic molecules in 3D structures is a parallel, and increasingly popular way to achieve organic NTs. Inspired by biological systems, numerous efforts have been popular way to achieve organic NTs. Inspired by biological systems, numerous efforts have been devoted to the design of synthetic building blocks that can form such hollow nanostructures through devoted to the design of synthetic building blocks that can form such hollow nanostructures through orchestrated interplay of various noncovalent interactions, using well-established principles of crystal orchestrated interplay of various noncovalent interactions, using well-established principles of engineering and supramolecular chemistry. Their development has already opened a broad spectrum crystal engineering and supramolecular chemistry. Their development has already opened a broad of opportunities and potential for applications in sensing, optics, organic electronics, and catalysis, spectrum of opportunities and potential for applications in sensing, optics, organic electronics, and as well as in biology and medicine [13–16]. catalysis, as well as in biology and medicine [13–16]. Since the field described in the introduction is indeed too ample and varied to be described into Since the field described in the introduction is indeed too ample and varied to be described into a single short review, we will exclude research related to chiral SWCNTs. Their selective synthesis a single short review, we will exclude research related to chiral SWCNTs. Their selective synthesis has been recently reviewed [17], and supramolecular approaches to their enantiomeric resolution has been recently reviewed [17], and supramolecular approaches to their enantiomeric resolution have appeared [18]. Oligomers and polymers can self-organize in appropriate solvents to give folded have appeared [18]. Oligomers and polymers can self-organize in appropriate solvents to give structures (foldamers), with an interior cavity. In this case, the length of the nanotube is dictated by folded structures (foldamers), with an interior cavity. In this case, the length of the nanotube is the dimension of the unfolded oligomer-polymer precursor. This elegant approach is too ample to be dictated by the dimension of the unfolded oligomer-polymer precursor. This elegant approach is too discussed here, and several thorough and authoritative reviews have already appeared [19–26]. This ample to be discussed here, and several thorough and authoritative reviews have already appeared review will focus on progress in research on chiral NTs architectures based on small molecules (cyclic [19–26]. This review will focus on progress in research on chiral NTs architectures based on small or acyclic in their initial nature), their functional properties and applications. molecules (cyclic or acyclic in their initial nature), their functional properties and applications. 2. Discussion 2. Discussion This review is centered on chiral NTs, and will deal with organic NTs obtained by the assembly of This review is centered on chiral NTs, and will deal with organic NTs obtained by the assembly chiral molecules. Chiral synthetic nanotubes have been targeted essentially by two complementary of chiral molecules. Chiral synthetic nanotubes have been targeted essentially by two strategies: (a) stacking of covalent cyclic molecules; or (b) 3D self-assembly of smaller building complementary strategies: (a) stacking of covalent cyclic molecules; or (b) 3D self-assembly of blocks. Preformed covalent chiral macrocycles can offer advantages in terms of the tuning of the smaller building blocks. Preformed covalent chiral macrocycles can offer advantages in terms of the cavity magnitude; furthermore, the direct introduction of chirality elements into the cyclic skeleton tuning of the cavity magnitude; furthermore, the direct introduction of chirality elements into the cyclic skeleton of the macrocycles can lead to high control of the resulting helicity and directionality

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of the macrocycles can lead to high control of the resulting helicity and directionality during the nanotube assembly. On the other end NTs formed from self-assembly of small building blocks can offer advantages in their easy and scalable synthesis. The aggregation of organic building blocks and macrocycles into the third dimension of space, to form organic nanotubes, occurs through the implementation of various noncovalent interactions, such as hydrogen bonds, π–π stacking interactions, metal mediated interactions, and multiple interactions. Although the interplay between these noncovalent forces is often in place, we have classified them separately in different subchapters. In general, the most used techniques to characterize chiral nanotubes are: (i) Scanning Electron (SEM) and Atomic Force (AFM) microscopies; and (ii) Circular Dichroism (CD) spectroscopy. The first ones are imaging techniques, useful to verify the formation and the relative morphology of the nanotubular structures: both are able to achieve resolution in the order of nanometers and mainly, the samples are prepared by solution casting onto appropriate surfaces. CD spectroscopy usually allows the gathering of fundamental information on the supramolecular structures formed and to check the chirality of the tubular superstructures, by examining the absorption bands of optically active chiral molecules and ensembles; most measurements are reported in degrees of ellipticity. 2.1. Hydrogen Bonds In recent years, the construction of hydrogen-bonded tubular assemblies of peptide macrocycles has become an important area of research for the realization of biomimetic materials with useful applications both as models for biological channels and as materials with novel electronic and photonic properties [13,16,27–30]. In general, cyclic-(D,L)-α-peptides, β- and γ-peptides and peptide hybrids constitute a class of flat ring-shaped molecules forming β-sheet-like assemblies, through the intermolecular association of amide hydrogen bonding units present in the cyclic backbone. The internal diameter of the tubular structures can be varied by changing the size of cyclopeptides, making these molecules very interesting. The first example of organic NT originated by a cyclic-(D,L)-α-peptide, able to form hollow tubular structures through antiparallel β-sheet hydrogen bonding, was reported in 1993 by Ghadiri et al. [31]. The cyclo[-(L-Gln-D-Ala-L-Glu-D-Ala)2 -] presents an alternating D and L arrangement of amino acid residues within the cyclopeptide backbone, forming a cyclic structure with an overall C2 symmetry in enantiomerically pure form, given that enantiopure amino acid building blocks are used in the solid phase synthesis of the starting linear peptide, which is subsequently cyclized. The described net molecular chirality translates therefore to form homochiral nanotubes, which were not however further characterized from the point of view of their chiroptical properties. The assembly of conformationally flat cyclic peptides approach has been later thoroughly developed by Granja et al., with recently reported and elegant examples [32,33]. Although several of the enantiopure structures proposed lose even the low C2 symmetry of the prototypical system developed by Ghadiri, the chirality properties of the resulting chiral nanotubes have not been exploited to date. One of the most intriguing nanotubular system developed with cyclic peptides have been recently reported by Danial, Catrouillet et al. They combined self-assembling cyclic peptides with a pH-responsive polymer [34,35], creating pH-sensitive materials which can be used in pharmaceutical applications, such as drug delivery agents or membrane channels. The new structure is composed by a polymer, poly(dimethylamino ethyl methacrylate) (pDMAEMA), conjugated to a cyclopeptide (structure 1 in Figure 2). The cyclic peptide consists of alternating D- and L-amino acids with the sequence L-Lys-D-Leu-L-Trp-D-Leu-L-Lys-D-Leu-L-Trp-D-Leu, modified with two diametrically opposed pendant chains that are attached to the free amine groups of the lysine residues, and polymer chains are grown from the modified CP via the reversible addition-fragmentation chain transfer (RAFT) process. The system can be seen as intrinsically formed by diastereoisomers, since the statistically unequal length of polymer chains on the two diametrically opposite lysine residues breaks the local molecular C2 symmetry.

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Figure 2. Molecular structure of the cyclopeptide-polymer conjugate 1 and illustration of pH Figure 2. Molecular structureofofNTs. thePartially cyclopeptide-polymer and Ref. illustration of pH responsiveness in the formation reproduced withconjugate permission1 from [35] (Copyright responsiveness in the formation of NTs. Partially reproduced with permission from Ref. [35] American Chemical Society, 2016). (Copyright American Chemical Society, 2016).

The self-assembly process could be studied in aqueous solution using Small-Angle Neutron The self-assembly process could be studied in aqueous solution using Small-Angle Neutron Scattering (SANS), in order to monitor the effect of protonation on the morphology and the size Scattering (SANS), in order to monitor the effect of protonation on the morphology and the size of of the aggregates and controlled by variation of pH; the assembly was fully reversible. Due to the the aggregates and controlled by variation of pH; the assembly was fully reversible. Due to the basic basic tertiary amine groups on the polymer, pH = 9 is recorded when the (CP)-polymer conjugate is tertiary amine groups on the polymer, pH = 9 is recorded when the (CP)-polymer conjugate is solubilized in D2 O, leading to NTs with a number of aggregation of 15. When the solution is acidified solubilized in D2O, leading to NTs with a number of aggregation of 15. When the solution is by addition of small amounts of DCl, a decrease in the number of aggregation, to 8 at pH 8, 5 at pH 7, acidified by addition of small amounts of DCl, a decrease in the number of aggregation, to 8 at pH 8, and finally 1 at pH 2, is observed. In acidic conditions, the conjugates become highly charged, causing 5 at pH 7, and finally 1 at pH 2, is observed. In acidic conditions, the conjugates become highly an electrostatic repulsion between them, due to the protonation of the tertiary amine groups on the charged, causing an electrostatic repulsion between them, due to the protonation of the tertiary polymer, disrupting the self-assembly. To demonstrate the reversibility of the self-assembly process, amine groups on the polymer, disrupting the self-assembly. To demonstrate the reversibility of the the addition of NaOD restored the number of aggregation to 13 at pH 9.7. self-assembly process, the addition of NaOD restored the number of aggregation to 13 at pH 9.7. More recently, a chiral 1,4-linked triazole/amide based peptidomimetic macrocycle has been More recently, a chiral 1,4-linked triazole/amide based peptidomimetic macrocycle has been reported by Ghorai et al. [36]. The synthesis of the molecular cyclic structure is based on the reported by Ghorai et al. [36]. The synthesis of the molecular cyclic structure is based on the Cu-catalyzed Cu-catalyzed alkyne-azide alkyne-azide cycloaddition cycloaddition (CuAAC) (CuAAC) reaction reaction between between alkyne alkyne and and azide azide moieties moieties of of precursors, composed of cis-furanoid sugars and β-alanines as amino acids. Two regioisomeric chiral precursors, composed of cis-furanoid sugars and β-alanines as amino acids. Two regioisomeric products 2a,b (Figure 3) were separately obtained.obtained. The CuAAC can chiral products 2a,b (Figure 3) were separately Thereaction CuAACgenerates reaction triazoles, generateswhich triazoles, be considered amide bond inanalogues, terms of planarity wellpolarity, as hydrogen bond which can be as considered as analogues, amide bond in termsand of polarity, planarityasand as well as donating and accepting ability. Nuclear Magnetic Resonance (NMR) and molecular modeling studies hydrogen bond donating and accepting ability. Nuclear Magnetic Resonance (NMR) and molecular established that the conformation of the novel peptidomimetic macrocycle, essentially planar, is similar modeling studies established that the conformation of the novel peptidomimetic macrocycle, to that of (D,L)-α-amino acid based achiral cyclic peptides. The mode of self-assembly is however essentially planar, is similar to that of (D,L)-α-amino acid based achiral cyclic peptides. The mode of different from previous cases; in fact, from the formation a well-defined tubular chiral nanostructure has self-assembly is however different previousofcases; in fact, the formation of a well-defined occurred, involving amide NHhas andoccurred, triazole N2/N3 as well as by stacking via amide NHasand tubular chiral nanostructure involving amide NHparallel and triazole N2/N3 as well by amide carbonyl oxygen H–bonding. parallel stacking via amide NH and amide carbonyl oxygen H–bonding.

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H N N N

N O

5.5 D

O

O

N N N

O O

O

O

O O

O

O O

N N N

2a

O

O NH

HN

O

O

O

O

3.7 D

N N N

O

O O O

NH

NH

O O O

O O

N N N

O

O

2b

Figure 3. Comparison between triazole and amide functionalities, and diastereoisomeric rotamers of Figure 3. Comparison between triazole and amide functionalities, and diastereoisomeric rotamers of macrocycle 2. For the comparison between dipole moments, see Ref. [37]. macrocycle 2. For the comparison between dipole moments, see Ref. [37].

The concept of directionality in the assembly of enantiopure cyclic peptides have been pushed forward and addressed, with the the synthesis synthesis of of macrocyclic macrocyclic urea/amide urea/amide hybrids, by Hennig et al. The as functional, anion-selective membrane transporters in lipid bilayer membranes. derived NTs NTsfunction function as functional, anion-selective membrane transporters in lipid bilayer The authors describe derivatives with varying side chains (aliphatic and aromatic) and were able to membranes. The authors describe derivatives with varying side chains (aliphatic and aromatic) and engineer conformations with parallel and antiparallel carbonyl dipoles: “antiparallel” macrocycles were able to engineerboth conformations both with parallel and antiparallel carbonyl dipoles: that self-assemble into “antiparallel” NTs, similar the above described cyclic peptides; anddescribed “parallel” “antiparallel” macrocycles that self-assemble intoto“antiparallel” NTs, similar to the above macrocycles thatand self-assemble “parallel”that oriented NTs, in which the overall nanostructure itself cyclic peptides; “parallel” into macrocycles self-assemble into “parallel” oriented NTs, iniswhich intrinsically chiral with strong macrodipoles. The overall unusual parallel NTsunusual call for the overall nanostructure is itself intrinsically chiral with strongcharacteristics macrodipoles.ofThe overall a new transportofmechanism, where interactions account for voltage sensitivity characteristics parallel NTs call macrodipole-potential for a new transport mechanism, where macrodipole-potential and anion-macrodipole account for selectivity [38]. interactions account for anion interactions account forinteractions voltage sensitivity andanion anion-macrodipole Peptides, selectivity [38]. as short as dipeptides, contain all the molecular information needed to form well-ordered nanoscale.contain Dipeptides have been demonstrated be able to to grow Peptides,structures as short at asthe dipeptides, all the molecular informationtoneeded form supramolecular (chiral) NTs. Furthermore, they have been templates for the internal well-ordered structures at the nanoscale. Dipeptides haveused beenasdemonstrated to be able togrowth grow of metallic nanowires byNTs. Reches et al. [39]. they The same have recently reviewed the significant supramolecular (chiral) Furthermore, have authors been used as templates for the internal growth advancements in the field of peptide nanostructures in the last few years [40]. Other more complex of metallic nanowires by Reches et al. [39]. The same authors have recently reviewed the significant peptide architectures have of been elegantly shown to form (chiral) NTs, but [40]. the chirality has not been advancements in the field peptide nanostructures in the last few years Other more complex specifically addressedhave [41,42]. peptide architectures been elegantly shown to form (chiral) NTs, but the chirality has not been In an approach has some analogy with the cyclic peptides, Gattusoet al. have published specifically addressedthat [41,42]. the synthesis of largethat cyclic which assemble in theGattusoet solid stateal.tohave formpublished nanotubular In an approach hasoligosaccharides some analogy with the cyclic peptides, the structures [43,44]. The authors have established a synthetic protocol for the high-yielding cyclization of synthesis of large cyclic oligosaccharides which assemble in the solid state to form nanotubular a series of suitably protected disaccharide precursors, containing bothfor a glycosyl donor andcyclization a glycosyl structures [43,44]. The authors have established a synthetic protocol the high-yielding acceptor. cyclization in diluted conditions in the presence ofboth TrClO as the catalyst, and of a series After of suitably protected disaccharide precursors, containing a 4glycosyl donor and a deprotection, a series of cyclic oligosaccharides have been obtained and characterized. In particular, glycosyl acceptor. After cyclization in diluted conditions in the presence of TrClO4 as the catalyst, cyclicdeprotection, oligosaccharidic octamers or decamers obtained by L-mannopyranose and a series of cyclic oligosaccharides have been obtained and andD-mannopyranose characterized. In containing monomers (MM), or L-rhamnopyranose and D-rhamnopyranose containing monomers particular, cyclic oligosaccharidic octamers or decamers obtained by L-mannopyranose and (RR), are achiral, since they possess S8 or S10 molecular X-ray crystallographic investigation D-mannopyranose containing monomers (MM), or symmetry. L-rhamnopyranose and D-rhamnopyranose demonstrates the presence of the molecular cyclic achiral octasaccharide containing monomers (RR), are described achiral, since they symmetry, possess S8 and or Sthe 10 molecular symmetry. X-ray and decasaccharide belonging to the RR series revealed infinite stacks to form nanotubes ranging crystallographic investigation demonstrates the presence of the described molecular symmetry,from and the cyclic achiral octasaccharide and decasaccharide belonging to the RR series revealed infinite stacks to form nanotubes ranging from 1 nm for the cyclic octasaccharide to 1.3 nm for the cyclic


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decasaccharide in octasaccharide diameter. Nanotubular aredecasaccharide held together in bydiameter. loose vanNanotubular der Waals 1 nm for the cyclic to 1.3 nmstructures for the cyclic contacts. structures are held together by loose van der Waals contacts. A A very very interesting interesting approach approach to to create create chiral chiral NTs NTs is is the the guest-assisted guest-assisted assembly assembly of of macrocycles. macrocycles. Liu Liu et et al. al. reported reported the the specific specific assembly assembly of of supramolecular supramolecular NTs, NTs, starting starting from from a pair of enantiomeric enantiomeric rigid rigid triangular triangular naphthalenediimide-based naphthalenediimide-based macrocycles macrocycles with with tubular tubular cavities, cavities, namely namely (RRRRRR)(RRRRRR)and and (SSSSSS)-NDI-Δ (SSSSSS)-NDI-∆ (R-Δ (R-∆ and and S-Δ, S-∆, respectively), respectively), used used as as hosts, hosts, and and aa class class of solvents, solvents, namely namely 1,2-dihalohydrocarbons, 1,2-dihalohydrocarbons, used used as as guests guests [45]. The The macrocycles macrocycles 3a,b 3a,b (Figure (Figure 4) 4) were were synthesized synthesized combining combining three three naphthalenediimides naphthalenediimides (NDIs) (NDIs) with with three three (RR)- or (SS)-trans-1,2-cyclohexanediamine (SS)-trans-1,2-cyclohexanediamine units units as as linkers.

Figure 4. macrocycles 3a,b3a,b (top(top left). left). Schematic view of the [C–H ···O] interactions between Figure 4. R-∆ R-Δand andS-∆ S-Δ macrocycles Schematic view of the [C–H···O] interactions the NDI units (top right): (A) bottom: top view showing that the coaxial DBA chain is stabilized through between the NDI units (top right): (A) bottom: top view showing that the coaxial DBA chain is latitudinal [Br ···π] interactions; (B) bottom schematicand illustration of nanotubular structure. Partially stabilized through latitudinaland [Br···π] interactions; (B) bottom schematic illustration of reproduced with permission fromreproduced Ref. [45] (Copyright American Chemical Society, 2014). American nanotubular structure. Partially with permission from Ref. [45] (Copyright Chemical Society, 2014).

Solvents including 1,2-dihalo-ethanes and -ethenes (DXEs) are necessary to create host-based Solvents including and -ethenes are necessary to create host-based tubular structures, as a 1,2-dihalo-ethanes result of a cooperation between(DXEs) the [halogen ···halogen] interactions and tubular structures, as a result of a cooperation between the [halogen···halogen] interactions and the the weak hydrogen bonds among NDI-∆ units, since the latter are not sufficient to hold them weak hydrogen bonds among NDI-Δ units, since theThe latter are notdemonstrated sufficient to hold them together on in together in a columnar manner to produce NTs. authors that, depending athe columnar manner to produce NTs. The authors demonstrated that, depending on the solvent, solvent, different supramolecular structures can be formed. Using the R-∆ macrocycle and different supramolecular structures can immediately be formed.formed, Usingprobably the R-Δ macrocycle and (E)-1,2-dichloroethene ((E)-DCE), an organogel due to the electron-rich (E)-1,2-dichloroethene ((E)-DCE), an organogel formed, probably due revealed to the C=C double bond and its anti-conformation. The gel immediately presented a composition of nanofibers, electron-rich C=C microscopies. double bond X-ray and its anti-conformation. The gel presented a composition of by SEM and AFM diffraction (XRD) analysis showed the formation of tubular nanofibers, revealed by SEM and AFM microscopies. X-ray diffraction (XRD) showed and the nanostructures. Single-crystal X-ray superstructure of DBA&R-∆, composed byanalysis R-∆ macrocycle formation of tubular nanostructures. Single-crystal X-ray superstructure of DBA&R-Δ, composed by BrCH2 CH2 Br (DBA), presented a nonhelical tubular structure, showing the coaxial stacking of two R-Δ macrocycle and BrCH 2 CH 2 Br (DBA), presented a nonhelical tubular structure, showing the R-∆ molecules a and b involving three pairs of [C–H···O] interactions between the NDI units, with a coaxial stackingrotation of two R-Δ molecules a and b4).involving pairs of [C–H···O] interactions between perpendicular angle of 60◦ (Figure The R-∆ three ab pairs constitute a pattern which supports the NDI units, with a perpendicular rotation angle of 60° (Figure 4). The R-Δ ab pairs constitute a a hexagonal channel, perfectly filled and stabilized by a [Br···Br]-bonded DBA chain, with latitudinal pattern supports a hexagonal channel, filledmolecules and stabilized a [Br···Br]-bonded [Br···π] which interactions between the Br atoms of the perfectly bridging DBA and thebyNDI planes of R-∆ ab DBA with latitudinal [Br···π] interactions between the Br bridging DBA pairs. chain, The DBA chain is composed of two kinds of DBA molecules, thatatoms adopt of antithe conformations and molecules and the NDI planes of R-Δ ab pairs. The DBA chain is composed of two kinds of DBA are arranged in an alternating manner linked by longitudinal [Br···Br] bonding interactions (Figure 4). molecules, that adopt anti conformations and are arranged in an alternating manner linked by longitudinal [Br···Br] bonding interactions (Figure 4). The same mechanism is observed for the single-crystals X-ray superstructures composed by R-Δ macrocycle and ClCH2CH2I (CIA).


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The same mechanism is observed for the single-crystals X-ray superstructures composed by R-∆ In contrast with DBA&R-Δ, the R-Δ macrocycle and ClCH2CH2Cl (DCA) formed a tetrameric, macrocycle and ClCH 2 CH2 I (CIA). single-handed (P)-helical nanotubular structure, showing the coaxial stacking of four R-Δ molecules In contrast with DBA&R-∆, the R-∆ macrocycle and ClCH 2 CH2 Cl (DCA) formed a tetrameric, a, b, a’ and b’ involving nine interfacial pairs of [C–H···O] interactions, a counterclockwise single-handed (P)-helical nanotubular structure, showing the coaxial stackingwith of four R-∆ molecules a, rotation angle of +62.7°, thanpairs 60°. of The axes of interactions, the tetramerwith do not overlap completely but b, a’ and b’ involving nine rather interfacial [C–H ···O] a counterclockwise rotation ◦ ◦ exhibit net counterclockwise rotation angles of +5.4°. The enantiomeric DCA&S-Δ showed the angle of +62.7 , rather than 60 . The axes of the tetramer do not overlap completely but exhibit net ◦ single-handed (M)-helical between DBA&R-Δ DCA&R-Δ is shown in counterclockwise rotationstructure. angles of The +5.4comparison . The enantiomeric DCA&S-∆ and showed the single-handed Figure 5. (M)-helical structure. The comparison between DBA&R-∆ and DCA&R-∆ is shown in Figure 5.

Comparison of single-crystal superstructures: nonhelical tetrameric unit of Figure 5.5.Comparison of single-crystal X-rayX-ray superstructures: nonhelical tetrameric unit of DBA&R-∆ DBA&R-Δ (on left) and (P)-helical tetrameric DCA&R-Δ (on right). Reproduced with permission (on left) and (P)-helical tetrameric DCA&R-∆ (on right). Reproduced with permission from Ref. [45] from Ref. [45] (Copyright American Chemical (Copyright American Chemical Society, 2014). Society, 2014).

Ponnuswamy et al. reported a class of amino acid functionalized NDIs, able to aggregate into Ponnuswamy et al. reported a class of amino acid functionalized NDIs, able to aggregate into hydrogen-bonded helical NTs. They could investigate NDI aggregates in solution using S-trityl hydrogen-bonded helical NTs. They could investigate NDI aggregates in solution using S-trityl protected, cysteine functionalized NDIs 4a–c (Figure 6), due to their good solubility in chlorinated protected, cysteine functionalized NDIs 4a–c (Figure 6), due to their good solubility in chlorinated solvents [46]. solvents [46].

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Schematic representation of the equilibria between anti Figure 6. 6. Amino Aminoacid acidfunctionalized functionalizedNDIs NDIs4a–c. 4a–c. Schematic representation of the equilibria between and syn of theof NDI (on top)(on and possible NDI aggregates (above). Partially anti andconformations syn conformations themonomer NDI monomer top) and possible NDI aggregates (above). reproduced with permission from Ref.from [46] (© American ChemicalChemical Society). Society). Partially reproduced with permission Ref. [46] (© American

The self-assemblyofofthe the NDI monomers occur via π-stacking and hydrogen In The self-assembly NDI monomers can can occur via π-stacking and hydrogen bonds. bonds. In aprotic aprotic solvents of medium polarity, such as CHCl 3, the formation of π-stacked polymers is solvents of medium polarity, such as CHCl3 , the formation of π-stacked polymers is unfavorable, due unfavorable, to the electron character of the and theofsteric hindrance to the electrondue deficient characterdeficient of the NDI aromatic coreNDI andaromatic the stericcore hindrance the amino acid of the amino acid side chains. Considering the two possible anti or syn conformations which be side chains. Considering the two possible anti or syn conformations which can be engaged can by the engaged by the side chains of the NDI monomers, supramolecular polymers via hydrogen bonds side chains of the NDI monomers, supramolecular polymers via hydrogen bonds formation can be formation canNDI be conformers formed. Both NDI conformers can self-assemble viaproduce COOHrandom dimerization to formed. Both can self-assemble via COOH dimerization to polymers, produce random polymers, but only the poly-sin-NDI is able to form supramolecular NTs (Figure 6). but only the poly-sin-NDI is able to form supramolecular NTs (Figure 6). The The supramolecular supramolecular polymerization polymerization of of these these NDI NDI helical helical NTs NTs occurs occurs via via aa non-cooperative, non-cooperative, isodesmic process, in which the addition of each monomer to the growing chain is governed by a isodesmic process, in which the addition of each monomer to the growing chain is governed by a single single equilibrium association constant. In order to investigate the thermodynamics of the formation equilibrium association constant. In order to investigate the thermodynamics of the formation of the of the NTs, temperatureand concentration-dependent proton NMR (NMR) were experiments were NTs, temperatureand concentration-dependent proton NMR (NMR) experiments performed on performed on NDIs 4a–c in CHCl 3 or 1,1,2,2-tetrachloroethane (TCE): 4b cannot form hydrogen NDIs 4a–c in CHCl3 or 1,1,2,2-tetrachloroethane (TCE): 4b cannot form hydrogen bonds and 4c can only bonds 4c can only form a hydrogen-bonded while the monomer 4a demonstrated a form a and hydrogen-bonded dimer, while the monomerdimer, 4a demonstrated a highly dependence on both 1 H-NMR spectra hydrogen-bonded revealed that, in a highly dependence on both concentration and spectra temperature. Thethat, concentration and temperature. The 1 H-NMR revealed in a random random hydrogen-bonded polymer, the NDI aromatic protons show a symmetric environment, polymer, the NDI aromatic protons show a symmetric environment, appearing as a broad singlet; appearing broad contrarily, in the NT, at lowerof temperatures, a splitting of peaks the NDI peak contrarily, as inathe NT,singlet; at lower temperatures, a splitting the NDI peak into two can be into two peaks can be observed, supporting the formation of a well-defined hydrogen-bonded observed, supporting the formation of a well-defined hydrogen-bonded supramolecular structure supramolecular structure with two for7).the NDI protons (Figure 7). with two different environments fordifferent the NDI environments protons (Figure


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Figure7.7.11H-NMR H-NMRspectrum spectrumof ofthe theNDI NDIprotons protonsof ofaasolution solutionof of4a 4ain inTCE, TCE, at at different differenttemperatures. temperatures. Figure Partiallyreproduced reproducedwith withpermission permissionfrom fromRef. Ref.[46] [46](Copyright (CopyrightAmerican AmericanChemical ChemicalSociety, Society,2012). 2012). Partially

H-NMR experiments recorded at different temperatures and concentrations of 4a in CHCl3 1 H-NMR experiments recorded at different temperatures and concentrations of 4a in CHCl3 1

suggested that the formation of the NT is enthalpy driven and entropically disfavoured, because of suggested that the formation of the NT is enthalpy driven and entropically disfavoured, because of the restriction of the conformational freedom due to the hydrogen bonds between NDI monomers. the restriction of the conformational freedom due to the hydrogen bonds between NDI monomers. Furthermore, the degree of polymerization showed a greater number for a solution of 4a in TCE at Furthermore, the degree of polymerization showed a greater number for a solution of 4a in TCE at 273 K, 273 K, respect to 300 K, revealing the presence of NTs up to 9 helical turns, corresponding to 28 respect to 300 K, revealing the presence of NTs up to 9 helical turns, corresponding to 28 aggregated aggregated NDI monomers. Association studies could also be performed using NDI monomers. Association studies could also be performed using concentration-dependent circular concentration-dependent circular dichroism (CD) spectroscopy. The solvation and the introduction dichroism (CD) spectroscopy. The solvation and the introduction of guests can change the stability of of guests can change the stability of the NTs: the addition of a noncompetitive solvent, such as the NTs: the addition of a noncompetitive solvent, such as cyclohexane [47], to a solution of 4a in TCE cyclohexane [47], to a solution of 4a in TCE showed an increase of the strength of hydrogen bonds in showed an increase of the strength of hydrogen bonds in the NDI NT; the encapsulation of C60 in the the NDI NT; the encapsulation of C60 in the tubular structure (Figure 6) allows its stabilization, due tubular structure (Figure 6) allows its stabilization, due to the good match between the solvophobic to the good match between the solvophobic surface of guest and the inner walls of the host NT, surface of guest and the inner walls of the host NT, increasing degree of polymerization. In addition increasing degree of polymerization. In addition to C60, NDI NTs can also act as receptors for to C60 , NDI NTs can also act as receptors for ammonium ions in a solution of CHCl3 : an interesting ammonium ions in a solution of CHCl3: an interesting competition experiment with C60 and competition experiment with C60 and ammonium ions revealed the formation of mixed complexes, ammonium ions revealed the formation of mixed complexes, with both guest molecules present in with both guest molecules present in the cavity of NT. the cavity of NT. As control experiments, the authors modified the side chains of the NDI monomers, introducing As control experiments, the authors modified the side chains of the NDI monomers, ε-NHBoc protected lysine 5 and isoleucine 6 functionalized NDIs, and N-desymmetrized NDIs, introducing ε-NHBoc protected lysine 5 and isoleucine 6 functionalized NDIs, and whereby 7 and 8, with a S-trityl protected cysteine on one side and respectively, ε-NHBoc protected N-desymmetrized NDIs, whereby 7 and 8, with a S-trityl protected cysteine on one side and lysine or ε-NH-thiourea lysine, on the other. The association constants and CD studies revealed respectively, ε-NHBoc protected lysine or ε-NH-thiourea lysine, on the other. The association a formation of less stable NTs of molecules 5 and 6, compared to 4a, due to: (i) solvophobic effects; constants and CD studies revealed a formation of less stable NTs of molecules 5 and 6, compared to (ii) competition for COOH groups to form hydrogen-bonded dimers with amide groups present in the 4a, due to: (i) solvophobic effects; (ii) competition for COOH groups to form hydrogen-bonded Boc side chain of 5; and (iii) the higher steric repulsion caused by the β-substituent in 6. Furthermore, dimers with amide groups present in the Boc side chain of 5; and (iii) the higher steric repulsion in the case of compound 8 compared to 7, thiourea gives an additional stabilization of the helical caused by the β-substituent in 6. Furthermore, in the case of compound 8 compared to 7, thiourea NT through non-covalent hydrogen-bonded cross-linking; however, the presence of the thiourea gives an additional stabilization of the helical NT through non-covalent hydrogen-bonded compensates the loss of the trityl group, which has a stabilizing effect via solvophobic interaction, cross-linking; however, the presence of the thiourea compensates the loss of the trityl group, which revealing the same stability of the NTs of 8 and 4a. has a stabilizing effect via solvophobic interaction, revealing the same stability of the NTs of 8 and Another recent example of guest-assisted host assembly of small molecules was reported by Shi 4a. et al., in which a stimuli-responsive H-bonding monomer changes its aggregation mode in response to Another recent example of guest-assisted host assembly of small molecules was reported by Shi different solvents or in the absence and presence of C60 and C70 guests [48]. et al., in which a stimuli-responsive H-bonding monomer changes its aggregation mode in response The novel enantiopure bicyclic compound 9 (Figure 8) presents a bicyclo[3.3.1]nonane (BCN) to different solvents or in the absence and presence of C60 and C70 guests [48]. core symmetrically fused with two N-methyl pyrrolopyrimidin-4-one moieties, bearing unsubstituted


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ureas. The intra-cyclic H-bonding site (marked as blue in Figure 8) might be expected to be used for the connection of the monomers into a cyclic tetramer while the terminal urea units (marked as red in Figure 8) might be the sites to link of the resulting noncovalent macrocycle into a 2H-bonded polymeric tube. 1 H-NMR and gel permeation chromatography (GPC) analysis showed that the monomeric compound exists as a single H-bonded tetrameric cyclic aggregate (Figure 8A) in CHCl3 , with a polydispersity index of 1.02. A possible reason for the formation of the tetramer is due to the weak H-bonds between terminal urea units, in contrast to the strong intra-cyclic H-bonds. Thus, in order to increase the strength of the H-bonds, 1 H-NMR experiments were performed in aromatic solvent, such as toluene and benzene, revealing the formation of high molecular-weight aggregates, composed by 15–20 cyclic tetrameric units in the chain (Figure 8B); GPC analysis detected a bimodal distribution, probably due to a mixture of oligomers and cyclic tetramers, which disappeared during ageing, displaying a single peak corresponding to the supramolecular polymer. The formation of the polymeric tubular structures was also detected with the addition of a C70 guest to a solution of the monomer 9 in CDCl3 (Figure 8C): this mechanism is unknown but ultraviolet-visible studies showed that2017, the 7, guest Nanomaterials 167 is incorporated into the cavity of the tube, since the absorption band of C 1070ofis23 shifted bathochromically.

Figure 8. Monomer 9 with two orthogonal 2H-bonding sites (marked as red and blue). Molecular models 94 and the corresponding polymeric tube, represented 98 . Schematic Figureof8.2H-bonded Monomer 9tetramer with two orthogonal 2H-bonding sites (marked as red and as blue). Molecular representation of: (A) tetrameric cyclic aggregate in CDCl ; (B) nanotubular structure in toluene-d polymeric tube, represented as 98 ;8. models of 2H-bonded tetramer 94 and the corresponding 3 and (C) nanotubular structure Partially reproduced with permission fromin 3; (B) nanotubular structure Schematic representation of: in (A)CDCl tetrameric cyclic aggregate in CDCl 3 with C 70 as guest. Ref. [48] (Copyright Publishing Group, toluene-d 8; and (C)Nature nanotubular structure in2017). CDCl3 with C70 as guest. Partially reproduced with permission from Ref. [48] (Copyright Nature Publishing Group, 2017).

The addition of a C60 guest to a solution of the monomer 9 in CDCl3 , in contrast to the polymeric The novel enantiopure compound 9 (Figureof 8) apresents a bicyclo[3.3.1]nonane (BCN) aggregates formed with C70 ,bicyclic highlighted the formation well-defined inclusion complex, in core symmetrically fused with two N-methyl pyrrolopyrimidin-4-one moieties, bearing which two different conformers were present: one conformer has an intramolecular H-bond between ureas. The intra-cyclic H-bonding siteC=O (marked as blue in the Figure 8) conformer might be expected aunsubstituted N–H proton of the isocytosine and one of the urea groups while other has an to be used for the connection of the monomers into a cyclic tetramer while the terminal urea units intramolecular H-bond between a urea N–H donor and an isocytosine acceptor. In order to demonstrate (marked as red in Figure 8) might be the sites to link of the resulting noncovalent macrocycle into the role of C60 as a selective switch in a multicomponent supramolecular system, a second bicyclica 2H-bonded polymeric tube. 1H-NMR and gel permeation chromatography (GPC) analysis showed that the monomeric compound exists as a single H-bonded tetrameric cyclic aggregate (Figure 8A) in CHCl3, with a polydispersity index of 1.02. A possible reason for the formation of the tetramer is due to the weak H-bonds between terminal urea units, in contrast to the strong intra-cyclic H-bonds. Thus, in order to increase the strength of the H-bonds, 1H-NMR experiments were performed in


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demonstrate the role of C60 as a selective switch in a multicomponent supramolecular system, a second bicyclic compound was considered (Figure 9). Compound 10 formsaggregate a cyclic tetrameric compound 10 was considered10(Figure 9). Compound 10 forms a cyclic tetrameric in CDCl3 , aggregate 3, which does not interact with C60 guest. In the presence of both 9 and 10 (1:1 which does in notCDCl interact with C60 guest. In the presence of both 9 and 10 (1:1 mixture) in CDCl3 solution, 1 1mixture) in CDCl3 solution, revealed that no exchange of monomers between H-NMR experiments revealedH-NMR that no experiments exchange of monomers between two tetramers 94 and 10 4 took two tetramers 9 4 and 104 took place (Figure 9A). The addition of a C60 guest to the solution resulted in place (Figure 9A). The addition of a C60 guest to the solution resulted in the selective formation of selective formation a capsule-like complex C60@94, leaving 104 intact (Figure 9B). The athe capsule-like insertion of complex C60 @94 ,insertion leaving 10 4 intact (Figure 9B). The replacement of CDCl3 replacement of CDCl 3 with toluene-d8 created the rearrangement of the complex C60@94 into the with toluene-d8 created the rearrangement of the complex C60 @94 into the tubular polymer 9n with the tubular polymer 9n with of C6010 into the cavity of the tetramer 104: this contemporary insertion of the C60 contemporary into the cavity insertion of the tetramer 4 : this process has been demonstrated process has been demonstrated to be reversible (Figure 9C). to be reversible (Figure 9C).

Figure 9. Monomer 10; schematic representation of: (A) tetrameric cyclic aggregates in CDCl3 ; (B) capsule-like insertion complex C60 @94 and tetramer 104 , in CDCl3 ; and (C) capsule-like insertion Figure 9. Monomer 10; schematic representation of: (A) tetrameric cyclic aggregates in CDCl3; (B) complex C60 @104 and nanotubular structure 9n , in toluene-d8 . Partially reproduced with permission capsule-like insertion complex C60@94 and tetramer 104, in CDCl3; and (C) capsule-like insertion from Ref. [48] Copyright Nature Publishing Group, 2017). complex C60@104 and nanotubular structure 9n, in toluene-d8. Partially reproduced with permission from Ref. [48] Copyright Nature Publishing Group, 2017).

2.2. π–π Stacking Interactions

2.2. π–π Interactions The Stacking π–π stacking of aromatic compounds is a type of noncovalent interaction widely used in supramolecular chemistry for construction of nano objects. π–π Stacking was first thoroughly The π–π stacking of aromatic compounds is a type of noncovalent interaction widely used in examined by Sanders and Hunter in the early 1990s [49]. supramolecular chemistry for construction of nano objects. π–π Stacking was first thoroughly Huang et al. in a recent approach [50] build on previous achievements dealing with NTs obtained examined by Sanders and Hunter in the early 1990s [49]. through π–π stacking interaction between covalent macrocycles, by assembling noncovalent aromatic Huang et al. in a recent approach [50] build on previous achievements dealing with NTs macrocycles (11, 12a or 12b) in which adjacent aromatic segments interact with one another by π–π obtained through π–π stacking interaction between covalent macrocycles, by assembling stacking interactions, defining the macrocyclic structure. The noncovalent macrocycles spontaneously noncovalent aromatic macrocycles (11, 12a or 12b) in which adjacent aromatic segments interact stack on top of each other in diluted aqueous solution to form a tubular structure with a hydrophobic with one another by π–π stacking interactions, defining the macrocyclic structure. The noncovalent interior. The self-assembling molecules that form this aggregate consist of a bent-shaped aromatic macrocycles spontaneously stack on top of each other in diluted aqueous solution to form a tubular segment with an internal angle of 120◦ and with aldehyde moiety as the terminal group. The chirality structure with a hydrophobic interior. The self-assembling molecules that form this aggregate of the correspondent NTs is guaranteed by the design of the hydrophilic oligoether dendron grafted at consist of a bent-shaped aromatic segment with an internal angle of 120° and with aldehyde moiety its apex, in which the side chains possess chiral centers of the (S) configuration (compounds 11 and as the terminal group. The chirality of the correspondent NTs is guaranteed by the design of the 12a) or the (R) configuration (compound 12b) (Figure 10). hydrophilic oligoether dendron grafted at its apex, in which the side chains possess chiral centers of the (S) configuration (compounds 11 and 12a) or the (R) configuration (compound 12b) (Figure 10).


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Figure 10. (A) Building blocks used in self-assembly of noncovalent NTs; (B) NTs section formed from 12a with reversible dilatation-contraction in function of thermal response; and (C) stimuli response on NTs in function of the temperature in sensing of C60 . Reproduced with permission from Ref. [50] (Copyright the American Association for the Advancement of Science, 2012).

The molecular weight of the primary aggregate, obtained by vapor pressure osmometry (VPO) measurements, resulted to be six times as large as that of the single building blocks indicating, together with inspection of Corey-Pauling-Koltun (CPK) models, that a single noncovalent macrocycle precursor of NTs is formed via fully overlapped packing arrangement of six unit of building blocks (Figure 10B). In NTs formed by self-assembly of 11, TEM measurements showed elongated object with an external diameter of 7 nm and a hollow interior with a diameter 3 nm. H-type stacking occurs between the aromatic segments of monomeric 11 units, as observed by Ultraviolet-Visible (UV-Vis) and fluorescence spectroscopies. CD spectra in aqueous solution showed a significant Cotton effect, indicating that the tubes adopt a one-handed helical structure. Changing building blocks to 12a and 12b afforded important structural modifications in the correspondent NTs: the increment of external and internal cavity diameter observed by TEM imaging, and a J-type stacking of the aromatic segments, suggest an expansion of the noncovalent macrocycles. The introduction of a pyridine unit on the concave side of Figure 10. (A) Building blocks used in self-assembly of noncovalent NTs; section formed the apex of the bent shaped aromatic segment induce adjacent molecules to slide(B) intoNTs a looser packing fromarrangement 12a with reversible dilatation-contraction in function of thermal (C) stimuli because pyridine is well-known to form water clusters throughresponse; hydrogen and bonding. and very aspect of NTsofisC their capability of with dynamic motion infrom responseThe on innovative NTs in function of interesting the temperature in these sensing 60. Reproduced permission response to external stimuli. The hollow tubes with oligoether dendritic exterior and pyridine interior Ref. [50] (Copyright the American Association for the Advancement of Science, 2012). exhibit thermoresponsive behavior due to thermally regulated dehydration capability of the ethylene oxide chains and the pyridine moieties. The reversible expansion-contraction motion of cavities of the The molecular weight of the primary aggregate, obtained by vapor pressure osmometry (VPO) NTs obtained from 12a or 12b, corresponding respectively to the hydrated and dehydrated forms, can measurements, resulted tobybemodifying six times large asofthat of the solution single from building blocks indicating, be activated thermally the as temperature the aqueous room temperature ◦ togethertowith inspection Corey-Pauling-Koltun (CPK)canmodels, that abysingle noncovalent 60 C and vice versa.ofThe dynamic motion of the tubules be accompanied variations of encapsulated hydrophobic molecules The NTs can take up arrangement C60 molecules through macrocycle precursor of NTs guest is formed via(Figure fully 10C). overlapped packing of six unit of hydrophobic interactions during assembly. Authors have observed that upon addition of C60 to showed building blocks (Figure 10B). In NTs formed by self-assembly of 11, TEM measurements a solution of 12a, the fluorescence intensity was considerably suppressed up to a maximum of 0.8 elongated object with an external diameter of 7 nm and a hollow interior with a diameter 3 nm. equivalent of C60 , indicating that C60 was effectively encapsulated within the hydrophobic interior of H-type stacking between ofa portion monomeric 11 guest units,population as observed by the tubulesoccurs at maximum value the of 0.8aromatic equivalent.segments On heating, of the C 60 Ultraviolet-Visible (UV-Vis) andinterior fluorescence spectroscopies. CDThespectra in and aqueous was released from the tubular due to the shrinkage of the tubes. absorbance solution solution immediately recover to those of the contracted statetubes upon adopt subsequent heating, indicating that showed color a significant Cotton effect, indicating that the a one-handed helical structure. the breathing motion of the tubes leads to a reversible switch between tight and loose packing of the Changing building blocks to 12a and 12b afforded important structural modifications in the C60 moieties.

correspondent NTs: the increment of external and internal cavity diameter observed by TEM imaging, and a J-type stacking of the aromatic segments, suggest an expansion of the noncovalent macrocycles. The introduction of a pyridine unit on the concave side of the apex of the bent shaped aromatic segment induce adjacent molecules to slide into a looser packing arrangement because pyridine is well-known to form water clusters through hydrogen bonding. The innovative and very interesting aspect of these NTs is their capability of dynamic motion in

heating, indicating that the breathing motion of the tubes leads to a reversible switch between tight and loose packing of the C60 moieties. CD-active NTs via π–π stacking interaction can be achieved by supercoiling of nanohelices as described by Ma, Peng et al. [51,52] using a family perylene diimide (PDI) molecules as building Nanomaterials of 23 blocks. The NTs 2017, have7, 167 tunable diameters and wall thicknesses via simple molecular13engineering, from two new classes of asymmetric PDIs compounds. The molecular design developed includes a CD-active via π–π stackingthe interaction canatoms be achieved by supercoiling of nanohelices perylene diimide coreNTs linked through nitrogen to a linear C12 chain and, by anasethylene described by Ma, Peng et al. [51,52] using a family perylene diimide (PDI) molecules as building blocks. studies bridge, to a bulky, branched m- or p-substituted alkoxyphenyl moiety (Figure 11). Design The NTs have tunable diameters and wall thicknesses via simple molecular engineering, from two conducted have suggested the crucial rule of the ethylene linkage to provide the necessary flexibility new classes of asymmetric PDIs compounds. The molecular design developed includes a perylene requireddiimide for the of the thenitrogen nanotubular Molecules 13a–c form bilayer-walled coreformation linked through atoms to astructure. linear C12 chain and, by an ethylene bridge, to a nanotubes, whereas molecules 14a–c form monolayer-walled NTs featuring an alternative geometry bulky, branched m- or p-substituted alkoxyphenyl moiety (Figure 11). Design studies conducted have suggested crucial the rule of the ethyleneoflinkage to provide the necessary required for the of the side chainsthewithin π-stacking the PDI molecules (Figureflexibility 11). More interestingly, the of the nanotubular Molecules 13a–c formthe bilayer-walled diameterformation of the bilayer NT dilatesstructure. or contracts by changing size of the nanotubes, branchedwhereas substituents at molecules 14a–c form monolayer-walled NTs featuring an alternative geometry of the side chains the meta-position of the phenyl moiety of 13. In fact, nanotubes obtained from 13c exhibit a uniform within the π-stacking of the PDI molecules (Figure 11). More interestingly, the diameter of the bilayer external NT diameter ≈25 nm, thesize nanotubes obtained from 13a and 13b showofuniform dilates orofcontracts by whereas changing the of the branched substituents at the meta-position external the diameters of ≈17ofand ≈14 nm, respectively. This ability to change the external externaldiameter diameter with phenyl moiety 13. In fact, nanotubes obtained from 13c exhibit a uniform of ≈ 25 nm, whereas the nanotubes obtained from 13a and 13b show uniform external diameters the size of the branched substituents is not observed in monolayer-walled NTs formed by 14a–c. The of ≈17 and ≈14 nm, respectively. ability toto change the external with the size of thepure (R)use of racemic compounds 13a–c and This 14a–c leads CD silent NTs, diameter but when enantiomeric branched substituents is not observed in monolayer-walled NTs formed by 14a–c. The use of racemic or (S)-13a were used, a CD signal in the range of 460–660 nm is observed, indicative of the formation compounds 13a–c and 14a–c leads to CD silent NTs, but when enantiomeric pure (R)- or (S)-13a were of single-handed All high fluorescence quantum yields exceeding 43% due to used, a CD NTs. signal in theNTs rangeexhibited of 460–660 nm is observed, indicative of the formation of single-handed their perylene with the monolayer-walled NTs being the photostable. NTs. Allmoieties, NTs exhibited high fluorescence quantum yields exceeding 43%less due to their peryleneBecause moieties, of their with theofmonolayer-walled NTs beinginterior the less photostable. Becauserobust of their combination of tunable combination tunable diameter, nanoporosity, photostability, and high diameter, interior nanoporosity, robust photostability, and high fluorescence, these bilayer-walled NTs fluorescence, these bilayer-walled NTs are ideal for applications as fluorescent sensors. are ideal for applications as fluorescent sensors.

Figure 11. PDI-based building blocks for construction of chiral NTs. Partially reproduced with

Figure 11. PDI-based building blocks for construction of chiral NTs. Partially reproduced with permission from Ref. [52] (Copyright Wiley-VCH, 2016). permission from Ref. [52] (Copyright Wiley-VCH, 2016). Van Dijken et al. [53] have reported the synthesis of enantiomerically pure supercoiled helical

VanNTs Dijken et al. [53]doping have reported synthesis ofofenantiomerically in water simply the achiral the tubular structure amphiphile 15a withpure smallsupercoiled amounts of helical a closely relateddoping enantiopure 15b. Onlystructure small amounts of enantiomerically pure small compound is NTs in water simply the analogue achiral tubular of amphiphile 15a with amounts of a required to control CD-response and, more importantly, the morphology of the chiral NTs (Figure 12). The structures of amphiphiles 15a and 15b contain a photosensitive overcrowded alkene unit that links two hydrophilic oligo-ethylene glycol headgroups with two hydrophobic alkyl tails. The capability of photoisomerization of the bis-thioxanthylidene core when exposed to light provides a facile NTs

closely related enantiopure analogue 15b. Only small amounts of enantiomerically pure compound is required to control CD-response and, more importantly, the morphology of the chiral NTs (Figure 12). The structures of amphiphiles 15a and 15b contain a photosensitive overcrowded alkene unit that links two oligo-ethylene glycol headgroups with two hydrophobic alkyl tails. The Nanomaterials 2017,hydrophilic 7, 167 14 of 23 capability of photoisomerization of the bis-thioxanthylidene core when exposed to light provides a facile NTs disassembly methodology, and the oligo-ethylene glycol units facilitate its solubility in disassembly methodology,alkyl and the oligo-ethylene glycol facilitate its solubility The water. The hydrophobic chains are positioned at units the core structure in orderintowater. maximize hydrophobic alkyl chains are positioned at the core structure in order to maximize interaction and interaction and to facilitate supramolecular assembly. Chiral information in compound 15b is to facilitate assembly. Chiral information compound 15b is brought by two brought by supramolecular two stereocenters in the hydrophobic chains.inDistinct differences in morphology stereocenters in the hydrophobic chains. Distinct differences in morphology between the NTs of between the NTs of pure achiral 15a and chiral 15b were observed by cryo-TEM. NTs of 15a (Figure pure achiral 15a and chiral 15b were observed by cryo-TEM. NTs of 15a (Figure 12a) are typically 12a) are typically longer than a micrometer, very straight and generally isolated amongst them, longer than a micrometer, very 12e) straight generally isolated them, tubes of 15b while the tubes of 15b (Figure are and shorter (typically only amongst ≈300 nm), and while tend tothe aggregate. CD (Figure 12e) are shorter (typically only ≈ 300 nm), and tend to aggregate. CD response of chiral NTs response of chiral NTs formed from 15b exhibits Cotton effect, whereas as expected NTs formed formed 15bsilent. exhibits Cotton effect, whereas as15a expected NTs formed from 15a are CDstudied silent. from 15afrom are CD Having confirmed that both and 15b form NTs, the author have Having confirmed that both 15a and 15b form NTs, the author have studied the effect of doping the the effect of doping the achiral NTs, with fixed amount of 15b, performing sergeant-soldiers achiral NTs, with fixed amount of 15b, performing sergeant-soldiers experiments. The mixed NTs experiments. The mixed NTs formation was not inhibited at any ratio of the amphiphile 15a:15b. formation at any of the any amphiphile 15a:15b. with lessimaging than 25%the of NTs 15b NTs with was less not thaninhibited 25% of 15b doratio not show CD signal and inNTs Cryo-TEM do not show any CD signal and in Cryo-TEM imaging the NTs appeared with morphology detected appeared with morphology detected for achiral NTs of 15a (Figure 12b). With a ratio of amphiphile for achiral NTs of 25–50% 15a (Figure 12b).a With a ratiowas of amphiphile 15a:15b betweenimaging 25–50% showed of 15b a that CD 15a:15b between of 15b CD signal recorded, and Cryo-TEM signal wasNTs recorded, and Cryo-TEM that NTs are micrometers longmajor and mixtures are micrometers long imaging and withshowed tendency tomixtures be straight until 15b became the with tendency to be straight until 15b became the major component (>50%) (Figure 12c). When thea component (>50%) (Figure 12c). When the fraction of 15b is over 50%, CD signal intensity tends to fraction 15b is over 50%, CD signal intensity tends tomorphology a plateau and the plateau of and Cryo-TEM imaging showed the typical of Cryo-TEM chiral NTsimaging (Figure showed 12d). These typical morphology of chiral NTs (Figure 12d). These results show that chirality is a distinctive factor results show that chirality is a distinctive factor in controlling the length of individual self-assembled in controlling the length individual self-assembled NTs, the aggregation of NTs and the chirality of NTs, the aggregation of of NTs and the chirality of the assembly. the assembly.

Figure 12. Top: Structure of amphiphile 15a and 15b. Bottom: Schematic model for the observed Figure 12.ofTop: 15b. Bottom: Schematic the 15a; observed behavior NTs Structure consistingofofamphiphile 15a and 15b15a as and a function of the amount of model 15b: (a)for pure long, behavior of NTs consisting of 15a and 15b as a function of the amount of 15b: (a) pure 15a; long, isolated achiral nanotubes; (b) 50% 15b; short, bundled chiral nanotubes; pure 15b; Royal short, bundled chiral nanotubes; nanotubes. (d) Partially reproduced with permission from Ref.and [53](e)(Copyright bundledofchiral nanotubes. Society Chemistry, 2017). Partially reproduced with permission from Ref. [53] (Copyright Royal Society of Chemistry, 2017).


2.3. Metal-Organic Interactions Nanomaterials 2017, 7, 167

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Metal-organic interactions have been attracting considerable attention from chemists and material2.3. scientists in the formation of 3D metal-organic frameworks (MOFs) due to their great Metal-Organic Interactions potential in the areas of gas adsorption and energy storage. Elements of chirality have already been Metal-organic interactions have been attracting considerable attention from chemists and material introduced into in MOFs [54–59].ofIn3Dthe assembly of chiral NTs, it isdue especially important scientists the formation metal-organic frameworks (MOFs) to their great potentialtoincarefully choose organic and metal search crystallization conditions, including guest molecules, the areasligands of gas adsorption andions, energy storage. Elements of chirality have already been introduced intoappropriate MOFs [54–59]. In the assembly of chiral NTs, it is especially important to carefully choose and adopt synthesis strategies. organic ligands and metal ions, search crystallization conditions, including guest molecules, andwhich adopt can be Fukino et al. [60] reported the noncovalent synthesis of large-diameter NTs, appropriate synthesis strategies. preferentially “cut” into its building blocks. A key for the success in cutting the NTs is the Fukino et al. [60] reported the noncovalent synthesis of large-diameter NTs, which can be redox-active ferrocene motif used in metal-ligating 16 and 17 (Figure 13). preferentially “cut” into its building blocks. A key forunits the success in cutting the NTs is the redox-active ferrocene motif used in metal-ligating units 16 and 17 (Figure 13).

Figure 13. (A) Building blocks used for construction of NTs; and (B) schematic illustration of possible

Figure 13. (A) Building blocks used for construction of NTs; and (B) schematic illustration of possible noncovalent structure upon complexation with Ag(I). Partially reproduced with permission from noncovalent structure upon complexation with Partially of reproduced with permission from Ref. [60] (Copyright the American Association forAg(I). the Advancement Science, 2014). Ref. [60] (Copyright the American Association for the Advancement of Science, 2014). The tetratopic ligands carry a metal-coordinating 4-pyridyl group at each terminus of the four arms. Triethylene (TEG) side chains are introduced to enhance solubility of the Thearomatic tetratopic ligands carryglycol a metal-coordinating 4-pyridyl group at each terminus of the four ligands and to provide better dispersibilities of assembled products in common organic solvents. aromatic arms. Triethylene glycol (TEG) side chains are introduced to enhance solubility of the As a metal ion source, AgBF4 was chosen because of its well established capability of coordination ligands and to provide better dispersibilities of assembled products in common organic solvents. As with pyridine derivatives. NTs obtained in MeCN were 50 nm to 2 µm long and show a uniform a metal ion source, AgBF 4 was chosen because of its well established capability of coordination with diameter of 7.5 nm and 14.3 nm respectively for 16 and 17 (Figure 14A,B). Taking into account the pyridinebent derivatives. NTs obtained in MeCN were 50 nmfor to the 2 μm long andofshow a uniform angle of 16 and 17 (144◦ ), these NTs diameter allows construction a molecular modeldiameter ◦ with a decagonal section (vertex angle; composed of 10 bent-shaped ligands and 20 Ag(I) of 7.5 nm and 14.3 nm cross respectively for 16 and144 17 )(Figure 14A,B). Taking into account the bent angle ions. The intrinsically achiral structure of building blocks did not lead to formation of chiral NT. of 16 and 17 (144°), these NTs diameter allows for the construction of a molecular model with a However, a closer examination of the 2D X-ray diffraction (2D XRD) image of the magnetically decagonal cross section (vertex angle; 144°) composed of 10 bent-shaped ligands and 20 Ag(I) ions. oriented NTs indicated that a small helical twist may exist in the stacking geometry. If this helical twist The intrinsically achiral bestructure blocks did lead to formation of chiral NT. can unidirectionally developed of overbuilding the entire nanotube, NTs not would be optically active.

However, a closer examination of the 2D X-ray diffraction (2D XRD) image of the magnetically oriented NTs indicated that a small helical twist may exist in the stacking geometry. If this helical twist can unidirectionally be developed over the entire nanotube, NTs would be optically active.


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Figure 14. TEM micrographs of air-dried MeCN/water dispersions of: (A) 16; (B) 17; (C) CD active NT Figure 14. TEM micrographs of air-dried MeCN/water dispersions of: (A) 16; (B) 17; (C) CD active formed by 16 in presence of (+/−)-MS; and (D) CD spectrum of NTs obtained using (+)-MS (red line) NT formed by 16 in presence of (+/−)-MS; and (D) CD spectrum of NTs obtained using (+)-MS (red and (−)-MS (blue line). Partially reproduced with permission from Ref. [60] (Copyright the American line) and (−)-MS (blue line). Partially reproduced with permission from Ref. [60] (Copyright the Association for the Advancement of Science, 2014) and [61] (Copyright the American Chemical Society, American Association for the Advancement of Science, 2014) and [61] (Copyright the American 2015). Chemical Society, 2015).

As Asdescribed describedby bythe thesame sameauthors authors[61], [61],when whenthe thecoassembly coassemblywas wascarried carriedout outin inthe thepresence presenceofof (+)or ( − )-menthylsulfate (MS* − ), the resultant NTs indeed displayed an optical activity (+)- or (−)-menthylsulfate (MS*−), the resultant NTs indeed displayed an optical activityexhibiting exhibiting Cotton Cottoneffects effectsatat325 325nm nmand and343 343nm nmininits itsCD CDspectrum spectrum(Figure (Figure14C,D). 14C,D). Caricato the metal-organic metal-organic induced induced nanoscale nanoscale organization organizationofofa Caricato et et al. al. [62] [62] recently recently reported reported the aBINOL-based BINOL-basedmacrocycle. macrocycle.This This report continues a series of contributions from the same group, report continues a series of contributions from the same group, on on chiral nanostructuring and chiroptical sensing [63–72]. The innovation in the design resides in chiral nanostructuring and chiroptical sensing [63–72]. The innovation in the design resides in the the incorporation a robust,chromophoric chromophoricsource sourceofofaxial axial chirality chirality into into aa cyclic, incorporation of of a robust, cyclic, shape shapepersistent persistent covalent framework (Figure 15A). The homochiral macrocycle (RR)-18 possesses an overall molecular covalent framework (Figure 15A). The homochiral macrocycle (RR)-18 possesses an overall Dmolecular multivalency is introducedisinto the covalent means of four suitably 2 symmetry, D2 and symmetry, and multivalency introduced into framework the covalentbyframework by means of 2+ , coordination of the pyridine moieties occurs positioned pyridine moieties. Upon addition of Pd 2+ four suitably positioned pyridine moieties. Upon addition of Pd , coordination of the pyridine both intra- occurs and intermolecularly, to afford chiral orderedtomono andchiral dimeric macrocycles multimeric moieties both intra- and intermolecularly, afford ordered monoorand dimeric aggregates depending on theaggregates solvents and conditions The metal event takesThe place in macrocycles or multimeric depending on used. the solvents andbinding conditions used. metal combination with a significant macrocyclic conformational rearrangement detected by CD spectroscopy binding event takes place in combination with a significant macrocyclic conformational 2+ (Figure 15C). When in combination with a third component (C60 ), in thecombination macrocycle-Pd rearrangement detected by CD spectroscopy (Figure 15C). When with hybrid a third undergoes surface-confined nanostructuring into chiral NTs, with extremely high aspect ratio 2+ component (C60), the macrocycle-Pd hybrid undergoes surface-confined nanostructuring into(cross chiral section of ca. 1 nm, Figure NTs, with extremely high 15D). aspect ratio (cross section of ca. 1 nm, Figure 15D). Zhou et al. [73] designed low-molecular-weight organogelator 19 containing a benzimidazole moiety linked an amphiphilic L-glutamic amide, able to form chiral nanotubes in polar solvents (DMF and acetone) (Figure 16). The enantiopure amphiphilic glutamide part was used as the gelator moiety, while the heteroaromatic benzimidazole moiety was introduced for π–π stacking, H-bonding and metal coordination. NTs were obtained in gel phase, confirmed by TEM characterization and shown in Figure 16A (hollow outer diameter of 85–100 nm, hollow inner diameter 34–40 nm, wall thickness of 25–30 nm), with CD spectroscopy showing a Cotton effect in DMF and acetone in the chromophore


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region. The well-known capability of benzimidazole to coordinate lanthanide ions was used by the authors to promote the formations of 3D tubular motif (Figure 16B). The authors have observed, upon addition of Eu(NO3 )3 and Tb(NO3 )3 , the formation of tuber flower structures, whose outer diameter ranged from 50 to 80 nm as measured from SEM, which were hierarchically constructed by a large Nanomaterials 2017, 7, 167 17 of 23 number of NTs.

Figure 15. (A) Cartoon representation of the design; (B) chemical structure of the D2 symmetrical macrocycle (RR)-18; (C) CD spectra of the macrocycle, and of the aggregates in MeCN solutions upon addition of two equivalents of the bidentate Pd2+; and (D) AFM images of fibers formed by (RR)-18, C60 and PdCl2(MeCN)2, with cross section of ca. 1 nm. Partially reproduced with permission from Ref. [62] (Copyright Royal Society of Chemistry, 2015).

Zhou et al. [73] designed low-molecular-weight organogelator 19 containing a benzimidazole moiety linked an amphiphilic L-glutamic amide, able to form chiral nanotubes in polar solvents (DMF and acetone) (Figure 16). The enantiopure amphiphilic glutamide part was used as the gelator moiety, while the heteroaromatic benzimidazole moiety was introduced for π–π stacking, H-bonding and metal coordination. NTs were obtained in gel phase, confirmed by TEM characterization and shown in Figure 16A (hollow outer diameter of 85–100 nm, hollow inner diameter 34–40 nm, wall thickness of 25–30 nm), with(B) CD spectroscopy showing Cotton effect in Figure 15. (A) (A) Cartoon representation of the the design; (B) chemical structure ofthe theDD2a2symmetrical symmetrical Figure 15. Cartoon representation of design; chemical structure of DMFmacrocycle and acetone in (C) the chromophore Theand well-known capability of solutions benzimidazole macrocycle (RR)-18; (C)CD CD spectraof ofthe theregion. macrocycle, and ofthe theaggregates aggregates inMeCN MeCN solutions upon to (RR)-18; spectra macrocycle, of in upon 2+; and 2+ (D) AFM images of fibers formed by (RR)-18, addition of two equivalents of the bidentate Pd coordinate lanthanide ions was used by the authors to promote the formations of 3D tubular addition of two equivalents of the bidentate Pd ; and (D) AFM images of fibers formed by (RR)-18,motif C6016B). andPdCl PdCl2authors 2(MeCN) (MeCN)22have ,, with withobserved, cross section section of ca. ca. nm. Partially Partially reproduced with permission permission from of (Figure The upon addition of Eu(NO 3)3 and Tb(NO 3)3, the formation C60 and cross of 11 nm. reproduced with from Ref. [62] (Copyright Royal Society of Chemistry, 2015). tuberRef. flower structures, whose outer diameter 2015). ranged from 50 to 80 nm as measured from SEM, [62] (Copyright Royal Society of Chemistry, which were hierarchically constructed by a large number of NTs. Zhou et al. [73] designed low-molecular-weight organogelator 19 containing a benzimidazole moiety linked an amphiphilic L-glutamic amide, able to form chiral nanotubes in polar solvents (DMF and acetone) (Figure 16). The enantiopure amphiphilic glutamide part was used as the gelator moiety, while the heteroaromatic benzimidazole moiety was introduced for π–π stacking, H-bonding and metal coordination. NTs were obtained in gel phase, confirmed by TEM characterization and shown in Figure 16A (hollow outer diameter of 85–100 nm, hollow inner diameter 34–40 nm, wall thickness of 25–30 nm), with CD spectroscopy showing a Cotton effect in DMF and acetone in the chromophore region. The well-known capability of benzimidazole to coordinate lanthanide ions was used by the authors to promote the formations of 3D tubular motif (Figure 16B). The authors have observed, upon addition of Eu(NO3)3 and Tb(NO3)3, the formation of tuber flower structures, whose outer diameter ranged from 50 to 80 nm as measured from SEM, which were hierarchically constructed by a large number of NTs.

Figure 16. 16. Molecular Molecular structure structure of of 19 19 and and fabrication fabrication of of hierarchical hierarchical chiral chiral nanostructures, nanostructures, which which was was Figure based on on the the self-assembly self-assembly of of 33 and and regulated regulated by by solvents solvents and and metal metal ions: ions: (A) (A) nanotubes nanotubes (scale (scale bar bar == based 100 nm); nm); and and (B) (B) flower-like flower-like structures structures (scale (scale bar bar == 11 µm). μm). Partially Partially reproduced reproduced with with permission permission from from 100 [73] (Copyright (Copyright Wiley-VCH, Wiley-VCH, 2016). 2016). Ref. [73]

2.4. Multiple Interactions Nanotubes can be also formed by multiple interactions, such as the cooperation of multiple hydrogen bonding and π–π stacking interactions. Tubular structures made by self-assembly from

Figure 16. Molecular structure of 19 and fabrication of hierarchical chiral nanostructures, which was based on the self-assembly of 3 and regulated by solvents and metal ions: (A) nanotubes (scale bar =


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2.4. Multiple Interactions Nanotubes Nanomaterials 2017, 7,can 167

be also formed by multiple interactions, such as the cooperation of multiple 18 of 23 hydrogen bonding and π–π stacking interactions. Tubular structures made by self-assembly from rigid macrocycles containing oligo-(phenylene ethynylene) backbones have been pioneered by the rigid macrocycles containing oligo-(phenylene ethynylene) backbones have been pioneered groups led by Moore et al., Schlüter et al. [74–79], and the assembly made to order essentiallyby bythe π– groups led by Moore et al., Schlüter et al. [74–79], and the assembly made to order essentially by π–π π stacking between the large cyclic aromatic surfaces. A new class of hexakis(m-phenylene stacking between the largehas cyclic aromatic surfaces. A new hexakis(m-phenylene ethynylene) ethynylene) macrocycles been recently reported by class Zhouofet al. [80]. The stability of such macrocycles has been recently reported by Zhou et al. [80]. The stability of such nanotubes is connected nanotubes is connected to the presence of multiple hydrogen-bonding side chains further to π–π to the presence of multiple hydrogen-bonding side chains further to π–π stacking involving the stacking involving the backbones. The modulation of the stacking strength of the helical nanotubular backbones. modulation of the stacking of the helical nanotubular assemblies The depends on the presence ofstrength different functional groups in assemblies the inner depends cavities on of the presence of different functional groups in the inner cavities of macrocycles [81]. Compounds 20a–l macrocycles [81]. Compounds 20a–l (Figure 17) were prepared following a convergent synthetic (Figure 17)that were prepared following a Sonogashira convergent synthetic that involves Pd-catalyzed sequence involves a Pd-catalyzed couplingsequence of monomeric buildingablocks to give Sonogashira coupling of monomeric building blocks to give trimeric precursors, which are trimeric precursors, which are recombined in a ring-closure reaction to give macrocycles.recombined in a ring-closure reaction to give macrocycles.

Figure 17. Structures of m-PE macrocycles 20a–l (top left), QMD simulation of a helical stack of the Figure 17. Structures of m-PE macrocycles 20a–l (top left), QMD simulation of a helical stack of the macrocycles (top right), and variable-temperature CD spectra of 20i and 20k measured in CCl4 (10 µM) macrocycles (top right), and variable-temperature CD spectra of 20i and 20k measured in CCl4 (10 (bottom). Partially reproduced with permission from Ref. [80] (Copyright Nature Publishing Group, μM) (bottom). Partially reproduced with permission from Ref. [80] (Copyright Nature Publishing 2012) and [81] (Copyright the American Chemical Society, 2016). Group, 2012) and [81] (Copyright the American Chemical Society, 2016).

The groups influence influence the the stacking stacking propensity propensity of of the the resultant resultant macrocycles: macrocycles: The internal internal functional functional groups electron-withdrawing groups decrease the electron density of the backbone and increase electron-withdrawing groups decrease the electron density of the backbone and increase the the π–π π–π stacking, groups enhance A study study stacking, while while electron-donating electron-donating groups enhance electron electron density density decreasing decreasing the the stacking. stacking. A was performed by by comparing comparingcompounds compounds20g, 20g,20i, 20i,and and20k, 20k,which which contain two functional groups was performed contain two functional groups in in their cavity, and 20c, with six fluorine atoms in its cavity, with 20a. The 1 H-NMR signals of these macrocycles are broadened in spectra recorded in CDCl3 , indicating that these molecules undergo


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decreased motion due to aggregation in this solvent. The stacking propensities of the macrocycles were assessed by comparing absorption spectra measured in different solvents: in CCl4 the five compounds adopt the same helical tubular assembly but show different stacking strength, and the aggregation of the macrocycles is interrupted in high polarity solvents. The helical stacking of the macrocycles is also confirmed by CD spectra in CCl4 , obtained at different temperatures, where induced CD activity could be seen in the UV-Vis bands of the chromophoric backbone, with maxima between 295 nm and 350 nm and minima around 275 nm (Figure 17), indicating an effective translation of the chirality from the amino acidic side chains into the supramolecular structure as a whole. The temperature-dependent nature of the CD traces is fully in line with a supramolecular system assembled under thermodynamic control. 3. Conclusions We have reviewed most recent, prominent examples of organic NTs, in which chirality is expressed in various forms. Many different molecular shapes and forms have been used for the construction of the described structures. We have focused on nanostructures assembled using weak noncovalent interactions; it is note worthy, however, to see that some of the proposed structures are stable in polar solvents, such as in water in physiological conditions. It is somehow surprising to notice that, on most occasions, chiral properties have not been fully developed and translated into new materials properties. We think, therefore, it is safe to say to the many researchers involved that the future is bright in this field of research, and that exciting new properties will be reported in the near future. Acknowledgments: DP acknowledges support from MIUR (Programs of National Relevant Interest PRIN grant 2009-A5Y3N9) and, in part, from INSTM-Regione Lombardia (2010–2012, 2013–2015 and 2016–2018) and from industrial contracts (ENI, IVM, and MARBO). Support from the University of Pavia (Postdoctoral Fellowship to AN) is gratefully acknowledged. Author Contributions: A.N., A.P. and D.P. analyzed the data and wrote the paper. Conflicts of Interest: The authors declare no conflict of interest.

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Dispersing carbon nanotubes by chiral network surfactants.

Self-assembly of π-conjugated gelators into emissive chiral nanotubes: emission enhancement and chiral detection.

A new synthesis strategy for chiral CdS nanotubes based on a homochiral MOF template.

Highly fluorescent one-handed nanotubes assembled from a chiral asymmetric perylene diimide.

Mechanical properties of chiral and achiral silicon carbide nanotubes under oxygen chemisorption.

Chiral rhodium complexes covalently anchored on carbon nanotubes for enantioselective hydrogenation.

Photoreactivity of unfunctionalized single-wall carbon nanotubes involving hydroxyl radical: chiral dependency and surface coating effect.

Evaluation of ionic liquids-coated carbon nanotubes modified chiral separation system with chondroitin sulfate E as chiral selector in capillary electrophoresis.

Chiral plasmonics.

Inherently chiral electrodes: the tool for chiral voltammetry.

Peptide nanotubes.

Lysine-based chiral vesicles.

Chiral methyl-branched pheromones.

Spintronics: Chiral damping.

Chiral separations 2013. Preface.

Cucurbituril: chiral applications.

3D plasmonic chiral colloids.

Gold(I)-alkanethiolate nanotubes.

Nanotubes in biological applications.

Water-soluble chiral metallopeptoids.

Coordinating chiral ionic liquids.

Superenantioselective chiral surface explosions.

Transparent conducting oxide nanotubes.

Hemotoxicity of carbon nanotubes.