Pillar[5]arene Based [1]rotaxane Systems With Redox-Responsive Host-Guest Property: Design, Synthesis and the Key Role of Chain Length

Pillar[n]arenes are a new type of macrocyclic compounds, which were first reported in 2008 by Ogoshi. They not only have cylindrical, symmetrical, and rigid structures, but also have many advantages, including easy functionalization and rich host-guest properties. On the other hand, mechanically interlocked molecules (MIMs) exist extensively in nature which have been artificially synthesized and widely applied in the fields of nanotechnology and biology. Although pillar[5]arene-based MIMs have been investigated much over recent years, pillar[5]arene-based [1]rotaxanes are very limited. In this report, we synthesized a series of amide-linked pillar[5]arene-based [1]rotaxanes with ferrocene unit as the stopper. Under the catalysis of HOBT/EDCL, the mono-amido-functionalized pillar[5]arenes were amidated with ferrocene carboxylic acid to constructed ferrocene-based [1]rotaxanes, respectively. The structure of the [1]rotaxanes were characterized by 1H NMR, 13C NMR, 2D NMR, mass spectroscopy, and single-crystal X-ray structural determination. In the experiment, the monofunctionalized pillar[5]arene was synthesized with a self-inclusion property, which allows for forming a pseudo-rotaxane. The key role is the length of the imine chain in this process. The formation of a rotaxane was realized through amidation of ferrocene dicarboxylic acid, which acted as a plug. In addition, due to the ferrocene units, the pillar[5]arene-based [1]rotaxanes perform electrochemically reversible property. Based on this nature, we hope these pillar[5]arene-based [1]rotaxanes can be applied in battery devices in the future.


INTRODUCTION
Mechanically interlocked molecules (MIMs) are a type of "star" molecule due to their beautiful and interesting architectures and wide applications in the area of biology and nanoscience (Bissell et al., 1994;Brouwer et al., 2001;Zhu and Chen, 2005;Crowley et al., 2009;Yonath, 2010;Zhang et al., 2011;Li et al., 2014;Wang et al., 2015Wang et al., , 2018. Among various MIMs, rotaxanes, which have dumbbell-like structures with a wheel sliding along an axle, have attracted great interest due to their wide application in preparation of artificial molecular machines (Green et al., 2007;Lewandowski et al., 2013;Zhang et al., 2013).

MATERIALS
All reactions were performed in atmosphere unless noted. All reagents were commercially available and used as supplied without further purification. NMR spectra were collected on either a Bruker AVIII-400 MHz spectrometer or a Bruker AV-600 MHz spectrometer with internal standard tetramethylsilane (TMS) and signals as internal references, and the chemical shifts (δ) were expressed in ppm. High-resolution Mass (ESI) spectra were obtained with a Bruker Micro-TOF spectrometer. X-ray data were collected on a Bruker Smart APEX-2 CCD diffractometer.

RESULTS AND DISSCUSSION 1 H NMR Investigation
The 1 H NMR spectra of AM 3 and P[5] 4 PR were taken into consideration first. As shown in Figure 1B, the chemical shift of four groups of peaks shift below 0 ppm field, indicating that the alkyl chain penetrated into the cavity of pillar[5]arene to form either pseudo[1] rotaxane or [c2]daisy chain (Du et al., 2017). Then P[5] 4 R was prepared from P[5] 4 PR reacted with ferrocenecarboxylic acid as the stopper. 1 H NMR spectra of monomer M 3 and [1] rotaxane P[5] 4 R in CDCl 3 at 293 K are shown in Figure 1 (spectra c and e). Compared with M 3 , we found that the signals of protons on the alkyl chain attaching onto the pillar[5]arene platform shifted upfield obviously due to the shielding effect ( Figure 1C). Then we used a polar solvent, DMSO-d 6 , for 1 H NMR investigations to confirm the formation of [1] rotaxane. In DMSO-d 6 , we also found that the signals of protons on the alkyl chains upfield were below 0 ppm due to the shielding effect (Figure 1D), which indicated the formation of a mechanically interlocked structure (Dong et al., 2014). The 1 H NMR of P[5] 2 R, P[5] 4 R, P[5] 6 R, P[5] 8 R all showed several groups of protons on the alkyl chains upfield obviously (Figures S8, S12, S16, S20), and the formation of [1] rotaxanes was also confirmed. However, the 1 H NMR of P[5] 0 R and P[5] 1 R showed no signal below 0 ppm, indicating the sidechain stayed outside of the cavity of the pillar[5]arene platform (Figures S1, S5). The reason for this phenomenon is due to the relatively short length of the axle (only two or three CH 2 groups) of P[5] 0 R, and P[5] 1 R, which was not able to allow the large ferrocene group to connect it from the cavity. Thus, the aminogroup of the side-chain of P[5] 0 PR (or P[5] 1 PR) stayed outside of the cavity and was then reacted with ferrocene-carboxylic acid to obtain free form P[5] 0 R (or P[5] 1 R). Furthermore, the temperature-dependent 1 H NMR of P[5]4R showed that the peaks became broad as the temperature increased, indicating the chain in the cavity (Figures S15, S19, S26).

2D NOESY Studies
The formation of [1]rotaxane was then confirmed by 2D Nuclear Overhauser Effect Spectroscopy (NOESY). Here we also take P[5] 4 R as the model compound. As shown in Figure 2, the hydrogens of the alkyl chain on P[5] 4 R were close to the pillar[5]arene platform because H 1−4 showed strong correlation with H a and H b , indicating that the alkyl chain was in close proximity to the cavity. The -NH-group H c is close to H 1−2 while H d is close to H 3−4 . Furthermore, ArH-3 from the ferrocene group showed space correction to the hydrogen-OCH 3 and -OCH 2 -on the pillar[5]arene platform (Data Sheets 1-4).

Single Crystal Structures
The direct evidence for the formation of [1] rotaxanes only when the length of axle longer than three CH 2 groups is from single crystal investigation. As shown in Figure 3A and Figure S4, the whole side chain of P[5] 0 R stayed outside of the cavity of pillar[5]arene. It should be pointed that we observed hydrogen bonding between the hydrogen atom of the amine group and the oxygen atom of carbonyl group (Figure 3A, pink dash line). However, for P[5] 2 R, we can clearly see that the alkyl chain penetrated into the cavity of pillar[5]arene to form a [1] rotaxane ( Figure 3B and Figure S11). The C-H···π interactions and C-H···O interactions were the driving forces for the formation of [1] rotaxane.

Cyclic Voltammetry Investigation
With the [1]rotaxanes in hand, we then investigated their reversible redox property by electrochemistry methods. Take P[5] 4 R as an example, in cyclic voltammetry (CV) experiment (Figure 4), the cyclic voltammogram was quasi-reversible with nearly equal i pa and i pc , in which the potential difference E p was around 0.090 V. Compared with ferrocene, P[5] 4 R has a larger half wave potential (E 1/2 = 612 mV). Further study showed that the free state P[5] 0 R has the similar redox property with P[5] 4 R due to the same ferrocene unit ( Figure S25).

CONCLUSIONS
In this paper, we synthesized a series of amide-linked pillar[5]arene-based [1]rotaxanes with ferrocene unit as the stopper. Under the catalysis of HOBT/EDCL, the monoamido-functionalized pillar[5]arenes were amidated with ferrocene carboxylic acid, to constructed ferrocene-based [1]rotaxanes, respectively. The structure of the [1]rotaxanes were characterized by 1 H NMR, 13 C NMR, 2D NMR, mass spectroscopy and single-crystal X-ray structural determination. In the formation of [1]rotaxane, the key role is the length of the alkyl chain in this process, and only when the number of C on the alkyl chain is larger than three can the formation of [1]rotaxane occur. In addition, due to the ferrocene units, the pillar[5]arenebased [1]rotaxanes display electrochemically reversible properties. Based on this nature, we hope these pillar[5]arenebased [1]rotaxanes can be applied in battery devices in future.

DATA AVAILABILITY
The raw data supporting the conclusions of this manuscript will be made available by the authors, without undue reservation, to any qualified researcher.

AUTHOR CONTRIBUTIONS
RZ prepared all the pillar[5]arene-based [1]rotaxanes. CW and RL prepared the monomer M 3 . TC and CY analyzed the data. YY analyzed the data and wrote the paper.