Controlled assembly of rotaxane translational isomers using dual molecular pumps

Abstract

The ability to control the relative motion between different components of molecules with precision is a cornerstone of synthetic nanotechnology. Mechanically interlocked molecules such as rotaxanes offer a platform for exploring this control by means of the positional manipulation of their components. Here, we demonstrate the use of a molecular dual pump to achieve the assembly of translational isomers with high efficiency and accuracy. By harnessing pumping cycles, rings can be guided selectively along a molecular axle, resulting in two sets of distinct translational isomers of [2]- and [3]rotaxanes. These isomers, produced in high yields, are characterized by mass spectrometry in addition to one- and two-dimensional nuclear magnetic resonance spectroscopy, which collectively reveal the location of the rings in the rotaxanes. Nuclear Overhauser effect spectroscopy confirms the spatial localization of rings, while diffusion ordered spectroscopy measurements quantifies the differences in hydrodynamic properties between the rotaxanes. This research supports the status of molecular pumps as a robust tool for precise nanoscale assembly, while advancing the practice of molecular machinery at the frontiers of synthetic nanotechnology.

Fig. 1. Graphical depiction of the design, and approximate conceptual energy diagrams detailing operation of the dual pump DP•6PF₆ through redox cycling.

DP•6PF₆ comprises two pumping cassettes, composed of a 2,6-dimethyl pyridinium (PY⁺) Coulombic barrier, viologen (BIPY²⁺) recognition sight, and an isopropylphenyl (IPP) steric speed bump, serviced by collecting chains 1 and 2. Initially, the cationic DP•6PF₆ and CBPQT•4PF₆ are repelled. Once reduced, the decreased charge of CBPQT^2(•+) allows rings from solution to thread over the PY⁺ barrier onto the first recognition site to form a trisradical tricationic complex. Oxidation removes the radical stabilization, and Coulombic repulsion from the PY⁺ unit prevents dethreading of the CBPQT⁴⁺, so the ring is compelled to move to the right giving the [2]rotaxane isomer with a ring located on the central collecting chain (R1•10PF₆). Reduction of this [2]rotaxane in the presence of free CBPQT•4PF₆ results in the acquisition of an additional ring from solution, as the steric bulk of the IPP unit prevents return of the already threaded ring to the first recognition site. Subsequent oxidation, and electrostatic repulsion of the PY⁺ barriers results in both rings moving to the right, yielding the [3]rotaxane isomer (R3•14PF₆) with individual CBPQT⁴⁺ rings located on both the central and terminal collecting chains.

Fig. 2. Synthesis of the dual pump DP•6PF₆. The azide S1•2PF₆ and the bromide S2 were dissolved in DMF and heated to 40 °C for 4 h under microwave irradiation to afford S3•3PF₆ in 51% yield.

The azide S3•3PF₆ was subjected to a copper-catalyzed click reaction in DMF with the propargyl ether^, S4•3PF₆ in the presence of tris[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]amine (TBTA). After workup the dual pump DP⁶⁺ was isolated as a yellow solid in 71% yield as the PF₆⁻ salt.

Fig. 3. Assigned and color-coded ¹H NMR (600 MHz, CD₃CN, 298 K) spectrum and labeled structural formula of DP•6PF₆.

The aromatic region is enlarged to clarify the peak assignments.

Fig. 4. Graphic depiction of the preparation of [2]rotaxane and [3]rotaxane translational isomers using the dual pump.

Pumping cycles were performed in acetonitrile (MeCN) solutions under an Argon atmosphere and entail reduction using cobaltocene (CoCp₂) at room temperature to thread rings onto the recognition site, followed by oxidation with AgPF₆ at 50 °C to allow the CBPQT⁴⁺ rings to overcome the IPP barriers. Cycling of DP•6PF₆ in the presence of CBPQT•4PF₆ yields the M[2]rotaxane R1•10PF₆, which, when redox cycled in the absence of free rings is converted to the complimentary T[2]rotaxane translational isomer R2•10PF₆. Redox cycling either [2]rotaxane in the presence of CBPQT•4PF₆ results in the MT[3]rotaxane R3•14PF₆, which can in turn be cycled to yield the TT[3]rotaxane translational isomer R4•14PF₆.

Fig. 5. ¹H NMR of the rotaxane translational isomers.

Comparison of the ¹H NMR spectra of (a) DP•6PF₆ and its rotaxane translational isomers, (b) R1•10PF₆, (c) R2•10PF₆, (d) R3•14PF₆, and e R4•14PF₆. Spectra were recorded in CD₃CN at 298 K and a field strength of 600 MHz. Key shifts demonstrating the mechanically interlocked nature of these compounds, and the changes between pumping cycles, are labeled. In particular, the presence of a CBPQT⁴⁺ ring on the central collecting chain, as in R1•10PF₆ and R3•14PF₆, is demonstrated by the upfield shift of H-16 of the linker and H-17 of the triazole unit from the aromatic region to 3.5–4.5 ppm. Rings on the terminal chain; as in R2•10PF₆, R3•14PF₆, and R4•14PF₆; are evidenced by the upfield shifting of the H-42 to H-49 alkane resonances. The additional ring density of R4•14PF₆ results in upfield shifting of H-35 of the second IPP unit.

Fig. 6. DOSY NMR (600 MHz, CD₃CN, 298 K) spectra of DP•6PF₆, R1•10PF₆, R2•10PF₆, R3•14PF₆, and R4•14PF₆, labeled with their diffusion constants.

A trend of decreasing diffusion constant with increasing rings, and particularly their presence on the terminal chain is evident.

Fig. 7. Partial ¹H-¹H NOESY spectra (600 MHz, CD₃CN, 298 K) of the [2]rotaxane translational isomers R1•10PF₆ and R2•10PF_6, which have been made with the dual pump.

Peaks of interest are labelled on the projected 1D spectra. Key crosspeaks between the CBPQT⁴⁺ rings with the central collecting chain (H-15 to H-20) in the case of R1•10PF₆, and the terminal collecting chain (H-40 to H-51 and H-53) for R2•10PF₆ are indicated in boxes. These crosspeaks demonstrate the threading and location of the rings in these [2]rotaxane translational isomers.

Fig. 8. ¹H–¹H NOESY spectra of the [3]rotaxanes.

Partial ¹H-¹H NOESY spectra (600 MHz, CD₃CN, 298 K) of the [3]rotaxane translational isomers (a) R3•10PF₆, and (b) R4•14PF₆. Key peaks on the 1D projections are annotated in the complete spectra given in the Supplementary Information. The graphical depictions are labeled to present the subscripts denoting the different CBPQT⁴⁺ rings. a Subscript M denotes the ring on the middle chain, T the terminal chain. Crosspeaks between CBPQT⁴⁺ and both the central (H-15 to H-20) and terminal (H-41 to H-50) collecting chains indicate that the rings are located in distinct regions of the DP⁶⁺ pump. b Subscript IPP denotes the ring closest to the IPP, and S the ring closest the stopper. Crosspeaks between CBPQT⁴⁺_IPP with H-35 and H-37 of the second IPP unit, and the H-38 to H-41 alkane protons reveal that this ring is located on the first half of the terminal collecting chain. Crosspeaks between CBPQT⁴⁺_S with the H-46, H-47, H-50, H-51, and H-53 resonances indicate that this ring is positioned on the second half of the terminal collecting chain.