Nanotubes, with their confined one-dimensional (1D) interior space, hold immense potential across various applications, including molecular recognition and storage, catalysis, artificial channels for transmembrane transport, and nanoelectronics. While carbon nanotubes are the most well-known, polymeric nanotubes lack the structural precision needed for complex applications. Atomically precise synthesis of discrete nanotubes with uniform length, diameter, and chirality is crucial for fully exploiting their anisotropic 1D nanochannels. Although significant progress has been made in synthesizing macrocycles and carbon nanobelts, single-molecule nanotubes with length/diameter ratios exceeding unity remain rare. A common approach involves stacking ring-shaped building blocks to extend cavity space axially. This research aims to address this challenge by creating a precise, discrete molecular nanotube with a well-defined structure, opening possibilities for studying chemical reactions and transport in confined spaces, as well as fabricating molecular devices and nanoporous materials.

The authors reviewed existing literature on nanotubes, highlighting the limitations of polymeric nanotubes due to their lack of structural precision. They discussed various macrocyclic compounds (cyclodextrins, cyclotriveratrylenes, resorcinarenes, and calixarenes) used to create single open-ended cavitands and oligomeric tubular capsules. The review also emphasized the scarcity of single-molecule nanotubes with high length/diameter ratios and the importance of precise synthesis methods for creating such structures. Existing work on macrocycles, carbon nanobelts, and other attempts to create discrete nanotubes are referenced, emphasizing the novelty of this achievement in creating a precise, well-defined nanotube.

COP-1 was synthesized via a [2+5] imine condensation reaction involving two penta-aldehyde macrocycles and five phenylenediamine linkers. The reaction was performed in CHCl3 under reflux for 8 hours, yielding a quantitative NMR yield. The crude product was purified by washing with EtOAc and MeOH. Chiral resolution was achieved using HPLC with a Daicel CHIRALPAK IE semi-preparative column and a CHCl3/MeOH mobile phase. The resolved enantiomers were characterized using NMR spectroscopy, isothermal titration calorimetry (ITC), and X-ray crystallography. X-ray crystallographic data were collected using XtaLAB Synergy diffractometers with Cu Kα radiation. Data were reduced using CrysAlisPro software and structures were solved and refined using ShelXT, ShelXL, and Olex2. Electrostatic potential maps were calculated using density functional theory (DFT) with the Gaussian 16 suite of programs, employing the B3LYP functional with Grimme's dispersion correction and 6-31G(d) basis sets. ITC measurements were conducted using a low-volume Affinity ITC instrument, with data fitting performed using NanoAnalyze. Host-guest interactions were investigated by NMR spectroscopy and HRMS in CDCl3 and CHCl3.

The synthesis resulted in a pair of enantiomeric COP-1 nanotubes, successfully resolved and characterized. X-ray crystallography confirmed the [2+5] nanotubular structure, a hollow twisted pentagonal prism with a length of 2 nm, a diameter of 4.7 Å, and an internal volume of ~440 ų. The inner channel accommodates four CH2Cl2 solvent molecules. NMR spectroscopy revealed a length-dependent binding affinity for α,ω-disubstituted n-alkanes, with critical chain lengths (n≥10 for dibromoalkanes and n≥12 for alkanediols). High-field 1H NMR signals for encapsulated guests confirmed strong binding for those exceeding the critical length. ITC measurements quantified binding constants (Ka), revealing strong affinities (Ka > 10⁵ M⁻¹) for guests meeting the length requirement. Shorter guests exhibited significantly weaker binding (Ka values dropping one to two orders of magnitude), attributed to unfavorable entropic changes. X-ray crystallography of inclusion complexes showed that longer guests adopted relaxed anti-periplanar conformations, while a shorter guest (1,9-dibromononane) displayed an energetically unfavorable gauche conformation, compensated by a C-Br π interaction. This demonstrates size-selective binding and conformational adaptation of guests within the nanotube's confines.

The successful synthesis and characterization of COP-1 demonstrates a significant advance in the creation of structurally precise molecular nanotubes. The strong length-dependent binding affinity and conformational adaptation of guest molecules highlight the importance of host-guest complementarity. The observed critical lengths for different guest types underscore the influence of both size and electronic properties on binding. The significantly stronger binding ability of COP-1 compared to individual macrocycles emphasizes the advantages of the pre-organized tubular structure and extended surface area. These results contribute to fundamental understanding of host-guest chemistry and open new avenues for designing highly selective molecular recognition systems and functional nanomaterials.

This study successfully synthesized structurally precise single-molecule nanotubes (COP-1) through dimerization of rim-differentiated macrocycles. The use of reversible imine bonds enabled efficient formation of extended nanotubular structures. COP-1, with its 2-nm-long and 4.7-Å-wide channel, demonstrated size- and electronic property-selective recognition of guest molecules. The design strategy is applicable to a broader range of nanorings and nanobelts, paving the way for syntheses of discrete molecular nanotubes with diverse functionalities for applications in catalysis, biointerfaces, and molecular nanotechnologies.

The study focuses on a specific type of nanotube (COP-1) and a limited range of guest molecules. Further studies are needed to explore the generality of the findings with other types of nanotubes and a wider variety of guest molecules. The study predominantly uses organic solvents; investigations in aqueous solutions could offer valuable insights into biological applications.