Construction of molecular nanotubes with precise length, diameter and chirality

Molecular nanotubes are nanoscale organic materials with tubular architecture, that show potential applications in molecular recognition/separation, cross-membrane transportation, catalysis in confined spaces, and nanoelectronics [1].However, the precise construction of molecular nanotubes with well-defined cavity sizes and shapes is non-trivial.The bottom-up fabrication of discrete nanotubes with uniform lengths/diameters and one handedness from small-molecular building blocks is a highly desirable approach [2].A straightforward way to achieve this is to use ringshaped macrocyclic molecules that stack on top of each other along an axis, resulting in extended cavities.However, implementing this strategy at the molecular level remains a significant challenge.Three key attributes are required: First, macrocyclic precursors with appropriate shape, symmetry and chemical composition need to be easily accessible through chemical synthesis; second,an efficient approach is needed to ‘stitch’these macrocycles together with stable linkages; third, full characterization of the obtained molecular nanotube should not be too laborious.

Andrew C.-H.Sue and co-workers from Xiamen University have recently achieved the goal of precisely constructing molecular nanotubes.At first, they developed highly efficient strategies for synthesizing rim-differentiated pillar[n]arenes and tiara[n]arenes[3-5].This allowed the assembly of twisted pentagonal prisms by stacking two such pillar[5]arenes through non-covalent metal coordination [6].Recently, they have taken another big step towards successfully constructing discrete covalent organic nanotubes using a similar design strategy (Fig.1a) [7].As shown in Fig.1b,a pair of covalent organic pillars (COP-1) were synthesized by condensing the pentaaldehyde pillar[5]arenep-formyl-T[5] andpphenylenediamine under reflux in CHCl3for 8 h.Thanks to the reversible nature of the dynamic imine bonds, the targeted [2+5]COP-1 was exclusively formed with a quantitative yield.With the product in hand, the authors thoroughly investigated the structure,stereochemistry and the host-guest behaviors of the nanotubes.

A racemic sample of COP-1 can be resolved into two enantiopure isomers (M)-COP-1 and (P)-COP-1 by employing a preparative HPLC instrument with a chiral column.The enantiomers exhibit mirror-image spectra in electronic circular dichroism (ECD).The chirality of the nanotubes originates from the inherently chiralp-formyl-T[5] precursor.The first fraction of COP-1 separated by HPLC exhibited a positive Cotton effect around 385 nm, which was crystallized for X-ray analysis (Fig.2).The result confirmed the [2+5] nanotubular architecture and was assigned as the lefthanded helical (M)-COP-1.This enantiopure molecular nanotube has a length of 2 nm, a diameter of 4.7 ?A, and an interior volume of approximately 440 ?A3.

Fig.1.(a) Schematic illustration of the molecular design of COPs.(b) Synthetic scheme of COP-1 involving [2+5] imine condensation of p-formyl-T[5] macrocycles and p-phenylenediamine linkers.Reproduced with permission [7].Copyright 2023,Nature Publishing Group.

The size and shape of COP-1 indicated that this 2 nmlong nanotube could potentially encapsulate linear guests.Accordingly, the authors investigated the host-guest behavior of COP-1 by1H NMR towards assortedn-alkane derivatives.However, no strong complexations between COP-1 andn-alkanes were observed, presumably due to the lack of energetically favoured interactions between them.Therefore,α,ω-dibromoalkanes andα,ω-alkanediols were selected as guest candidates.The binding capacity of COP-1 for these guests is strongly length-dependent.Large upfield-shifts of proton signals of the guests (Br(CH2)nBr(n≥10) or HO(CH2)nOH (n≥12)) to minus ppm values were observed when mixed with COP-1, indicative of the host-guest complexation.X-ray crystal structures of the [Br(CH2)10Br?(M)-COP-1]and [HO(CH2)12OH?(M)-COP-1] were obtained (Fig.3), and further confirmed the threading of these long linear guests into the COP-1 nanotube.

Fig.2.X-ray crystal structure of (M)-COP-1: (a) Fused stick/Corey-Pauling-Koltun(CPK) representation, (b) side view featuring the length and volume of the inner 1D channel.Reproduced with permission [7].Copyright 2023, Nature Publishing Group.

Fig.3.X-ray crystal structures of (a) [Br(CH2)10Br?(M)-COP-1] and (b)[HO(CH2)12OH?(M)-COP-1] inclusion complexes.Reproduced with permission[7].Copyright 2023, Nature Publishing Group.

In summary, Andrew C.-H.Sue and co-workers have successfully and precisely constructed a class of single-molecule nanotubes by linking two rim-differentiated macrocycles with dynamic covalent imine bonds.Solid-state structure showed that the nanotube contains a 2-nm-long and 4.7-?A-wide 1D channel with an interior volume of ～440 ?A3.They further investigated the hostguest studies of the nanotube, which shows specific recognition of linear guest molecules with complimentary length and electronic properties.The design of this work is genius, especially the use of rim-differentiated macrocycles as the main ring motif to build this concise and beautiful nanotubes.However, the work of genius does not happen overnight.Andrew C.-H.Sue’s team has put in a lot of efforts in this direction and has made important progress one after another, including their previously reported tiara[5]arenes and metal-organic pillars as mentioned above.The development of potential applications for such nanotubes is far from over.For example, such nanotubes may have potential applications in the separation of enantiomeric guests due to their chirality.Furthermore,owing to their ease of modification and derivatization, the development of water-soluble nanotubes is another interesting research direction.We believe that they will bring us more exciting surprises in the near future.On the other hand, the fabrication ofCOP-1opens a new window for the design and synthesis of deep-cavity molecular hosts.This work has also stimulated research ideas in the field.There is reason to believe that more molecular nanotubes with different functions will be constructed.

Qiaona Zhang, Hongwei Qian, Tangxin Xiao?School of Petrochemical Engineering,Changzhou University,Changzhou 213164,China

Robert B.P.Elmes?Department of Chemistry,Maynooth University,National University of Ireland,Maynooth,Co.Kildare,Ireland

Leyong Wang?State Key Laboratory of Analytical Chemistry for Life Science,Jiangsu Key Laboratory of Advanced Organic Materials,School of Chemistry and Chemical Engineering,Nanjing University,Nanjing 210023,China

?Corresponding authors.E-mail addresses: xiaotangxin@cczu.edu.cn (T.Xiao),robert.elmes@mu.ie (R.B.P.Elmes), lywang@nju.edu.cn (L.Wang)Available online 22 March 2023