Electrochemical switching in mechanically interlocked molecules (MIMs)

Abstract

Mechanically interlocked molecules (MIMs) which include rotaxanes and catenanes are formed by the mechanical linking of two or more components and have significant potential in the construction of molecular machinery owing to their intercomponent dynamics. Synthesis of these mechanically bonded interlocked molecules is delicate due to the inherent entropy constraints required to preorganize structural units for interlocking. However, if accomplished, it offers the advantage of stimuli-responsive behaviour and the control of the rotation/movement of components at the macroscopic level. Currently, synthetic MIMs are transitioning from creating basic architectures to complex architectures with potential functional systems for real-world applications. Switching occurs in different ways in these MIMs, such as chemical (pH, solvent polarity, and guest-induced switching), and electrochemical switching (redox switching). This review looks at some of the most recent studies on electrochemical switching that shows prevalent interest in MIMs among scientists seeking to create functional molecular machines that outperform their natural analogs or possess unique features.

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Ayush Bhadani

Ayush Bhadani is presently pursuing his Integrated Master's program in Chemistry at the National Institute of Science Education and Research (NISER) in Bhubaneswar, India. As part of his M.Sc. research, he is concentrating on supramolecular chemistry, specifically in synthesizing water-soluble and light-responsive coordination cages using Pd(II) metal.

Murugavel Kathiresan

Dr Murugavel Kathiresan graduated from the University of Madras with both Bachelor's (2004) as well as Master's degrees (2006), and received his Ph.D. from the University of Osnabrück, Germany, in 2010 under the guidance of Prof. Lorenz Walder. He then moved to the University of Basel, Switzerland, to conduct his postdoctoral research with Prof. Marcel Mayor. He was awarded the DST-INSPIRE Faculty Award in December 2013. From March 2014 to April 2017, he worked as a DST-INSPIRE faculty, since April 2017, he has been working as a Scientist and currently, he is a Senior Scientist at the Electro Organic & Materials Electrochemistry Division, CSIR-Central Electro Chemical Research Institute, Karaikudi, India. His current research interests include viologen-based supramolecular chemistry, along with the investigation of their applications towards photophysical applications, electro-organic synthesis, electrochemical CO2 reduction and conversion to useful organics, metal–organic frameworks, and porous organic polymers for sensing and energy-related applications.

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Introduction

The term Supramolecular chemistry was initially coined by Nobel laureate Prof. J. M. Lehn in the 1970s, who defined Supramolecular chemistry as “chemistry beyond the molecules”.¹ Supramolecular chemistry has become a multi/inter-disciplinary field of research with its arms touching the significant branches of science like organic, inorganic, materials, analytical, biological, and environmental chemistry.² Its significance can be inferred by the two Nobel prizes given in this subject in 1987 (Donald J. Cram, Jean-Marie Lehn, and Charles J. Pedersen) & 2016 (Jean-Pierre Sauvage, Sir J. Fraser Stoddart, and Bernard L. Feringa) for their works on the advancement of host–guest systems which lead to elementary comprehension of the concepts of intermolecular forces/non-covalent interactions and later for the development of miniaturized nanomachines using the concepts of supramolecular chemistry respectively.³ These multicomponent structures, which depend on reversible non-covalent interactions for existence, can associate and dissociate in response to external stimuli.⁴ Non-covalent interactions comprise electrostatic interactions, pi–pi interactions, hydrogen bonding, metal coordination, charge-transfer complexes, hydrophobic forces, and van der Waals forces (Fig. 1).^5–11 These non-covalent interactions are highly selective with structure specificity.

Fig. 1 Cartoon representation of non-covalent interactions.

The concept of intermolecular forces was first put forth by Johannes Diderik van der Waals in 1873. However, it was Hermann Emil Fischer who laid the philosophical groundwork for supramolecular chemistry. Fischer proposed the “lock and key” model of host–guest chemistry and molecular recognition in 1894, which describes the interactions between enzymes and their substrates.¹² Non-covalent bonds were gradually identified in greater detail at the start of the twentieth century after Latimer and Rodebush's description of the hydrogen bond in 1920.¹³ These concepts resulted in the understanding of biological processes and protein structure, of which a significant discovery is the double helix structure of DNA, two distinct strands of nucleotides coupled through hydrogen bonds. Based on these understandings, chemists began studying artificial structures based on non-covalent interactions, like micelles and microemulsions in parallel. Further, these concepts were successfully applied to synthetic systems and the advancement came in 1960s with the synthesis of artificial supermolecule, Crown ether that can selectively bind to K⁺ ions.¹⁴ Meanwhile, Prof. Cram and Prof. Lehn's group reported the preparation and complexation of spherands and cryptands respectively.^15,16 After these reports, there was a rapid expansion in the field of supramolecular chemistry where new concepts such as interlocked molecules beyond host–guest recognition started to emerge.^17–21

Recently, the development of new materials and technologies with applications in energy storage,^22,23 catalysis,^24,25 sensing,^26,27 and more has shown a great deal of interest in supramolecular. Recent research has demonstrated that electrochemical formation of supramolecular polymers allows precise control over their structures, properties, and responsiveness to external stimuli.^28–30 Additionally, supramolecular assemblies with electroactive components have drawn lot of attention due to their potential use in energy storage and electronic devices. Researchers have improved charge transport,^31–33 electrochromic behavior,^34–36 and electrocatalytic activity by integrating redox-active molecules or metal complexes into supramolecular structures.^37–40 The creation of next-generation electrical and energy conversion devices is possible with the help of these electroactive supramolecular structures. Advanced electrode materials for energy storage devices like batteries and supercapacitors have been created using supramolecular chemistry to improve the electrode materials’ stability and electrochemical performance.^41,42 For instance, ion transport kinetics,^43,44 energy density,^45,46 and cycle life can all be enhanced by functionalizing electrode surfaces with supramolecular host–guest systems.⁴⁷

Overall, integrating supramolecular chemistry with electrochemistry has opened up exciting avenues for designing and developing functional materials, devices, and sensing platforms. These advancements hold promise for addressing critical challenges in energy storage, catalysis, sensing, and other fields. They might stimulate the emergence of sustainable and more effective technologies. The focus of this review is to give an overview about electrochemically switchable supramolecular systems. An in-depth discussion on the host–guest interactions in systems such as catenanes, rotaxanes are discussed in detail.

Mechanically interlocked molecules

Mechanically interlocked molecules (MIMs) are molecules that are bound together by mechanical bonds. Rotaxanes, borromean rings, catenanes, and molecular knots are few examples of mechanically interlocked molecular architectures. The synthesis of such intertwined architectures has become more successful with the integration of supramolecular chemistry with conventional covalent synthesis; nonetheless, mechanically interlocked molecular architectures differ from covalently bound molecules and supramolecular assemblies in several aspects. A mechanical bond is the connection that develops between the components of molecules that are mechanically interlocked. Non-covalent interactions are stronger in a mechanically interlocked molecular architecture than they are in a non-mechanically connected one. When exposed to different environmental stimuli such as redox potentials, pH, temperature, solvent nature, etc., MIMs respond, i.e., they move in a variety of ways. Typically, the mechanical motions are driven by reversible non-covalent interactions that are promoted by external stimuli. Recently, MIMs were incorporated into solid-state platforms such as metal organic frameworks and covalent organic frameworks and their applications in optoelectronics, water desalination, and drug delivery were highlighted.⁴⁸ Furthermore, Stoddart and co-workers reported the production of poly[n]rotaxanes with progressively greater energies by using artificial molecular pumps to provide rings in pairs through cyclical redox-driven processes, all while following the principles of supramolecular chemistry.⁴⁹ In a recent review, Stoddart and co-workers has summarized the nature of interactions, synthesis, mechanochemistry and the use of these MIMs in various fields.⁵⁰

Rotaxanes

Rotaxanes are class of mechanically interlocked molecules (MIMs), having unique molecular architecture where macrocycle has been attached onto a linear molecular axle with bulky stoppers at each end. This structure imparts specific properties to rotaxanes, including low bond dissociation energy and susceptibility to external stimuli, like changing pH, vibrations, emitting light energy, removal/addition of electrons, and, etc.^51–54 Rotaxanes typically use redox-active groups incorporated into the thread or the macrocycle as the mechanism for electrochemical switching. When an electric potential is applied, these redox-active groups can experience reversible redox reactions that alter their oxidation state and charge. A switchable molecule must exhibit different levels of affinities for a second species in its reduced and oxidized states. As a result, the combination between the receptor and a guest species is thermodynamically stable depending on its oxidation state. In such a system, the differential interaction is often entirely electrostatic. It is necessary for the receptor, the guest, or both to be redox active. A guest or an electrochemically switchable receptor must meet similar conditions. Such a system requires a redox-active component that interacts strongly with the binding element and displays reversible heterogeneous electron transfer kinetics.⁵⁵ The rotaxane group must exhibit a redox active group, like ferrocene,^56,57 or viologen units,^58,59 that have different binding stabilities upon electrical stimuli or reduction/oxidized form. These groups can accept/donate electrons providing a redox active system. However, due to attractive interactions or steric effects, the ring often occupies a preferred binding position (station) on the thread without an applied electric potential. The system is stable in this arrangement because the redox-active groups are in a specific oxidation state. The rotaxane system undergoes a redox reaction when an electric potential is applied. By absorbing electrons from an external electrode, the redox-active group, for instance, can be reduced if it is initially oxidized. On the other hand, if the group is initially reduced, it can oxidize by giving electrons to the electrode. The redox reaction changes the redox-active groups’ charge distribution and electronic facets. This shift in charge or electrical state might cause the ring and thread's captivating interactions to become weaker or more robust. Consequently, depending upon the oxidation state of the redox-active groups, the ring can be pushed to a different binding site (station) along the thread. The redox-active groups return to their initial oxidation state when the supplied electric potential is removed, stabilizing the ring's new position on the thread. Until applying a different electric potential, this new condition is stable.

Electrochemical switching of MIMs

Rotaxanes and catenanes are types of mechanically interlocked molecular architectures (Fig. 2). In case of rotaxane and catenane they thread one molecular component through another, resulting in unique properties and functionalities. Rotaxanes consist of a linear molecular component called an “axle” or “thread” threaded through a macrocyclic element referred to as a “ring” or “wheel”.

Fig. 2 Cartoon depicting rotaxanes (left), catenanes (right).

The axle and ring are held together by noncovalent interactions including hydrogen bonding and coordination interactions. Crucially, the large stoppers or groups at the edges of the axle on rotaxanes which prevents the ring from dissociating. The threaded ring can move along the axle but cannot be completely detached.^60,61 While, catenanes comprise two or more interlocked macrocycles, called rings or cycles, akin to the methodology employed in crafting other mechanically connected molecular structures like interlocked rings (catenanes) and rings threaded onto molecular axles (rotaxanes)^62,63 Unlike rotaxanes, catenanes do not have a linear component threaded through a macrocycle; instead, they consist of two or more rings linked together topologically (Fig. 2). The interlocking can occur in various ways, such as a simple ring threading through another or two rings intertwining. Catenanes typically do not have stoppers or groups to prevent dissociation between the rings.^64,65

Mechanism for electrochemical switching in rotaxanes

The driving force for the electrochemical switching in rotaxanes is the change in Gibbs free energy (ΔG) associated with the redox reactions of the electroactive groups. The Gibbs free energy change can be related to the potential difference (ΔV) applied across the system using the equation:

ΔG = −nFΔV

where n is the number of electrons transferred in the redox reaction, and F is the Faraday constant.

The position of the ring on the thread is determined by the binding energies between the ring and different binding sites (stations) along the thread. Denoting the binding energy at a particular station as E_i, where i represents the station index. The probability of finding the ring at a specific station depends on the relative binding energies. According to the Boltzmann distribution, the probability (P_i) of the ring being at station i is given by:

where k is the Boltzmann constant, and T is the temperature.

The redox-active groups in the rotaxane undergo reversible redox reactions, changing their oxidation state and charge. The redox reactions are driven by the applied potential difference (ΔV) and are described by the Nernst equation:

where E_i is the potential at station i, E^o_i is the standard potential at that station, [Ox] and [Rd] are the concentrations of the oxidized and reduced forms of the redox-active group, R is the gas constant, and [Ox]/[Rd] represents the ratio of the oxidized and reduced species concentrations.

The minimum free energy state determines the equilibrium position of the ring on the thread. At equilibrium, the sum of the free energy contributions from the binding energies (E_i) and the redox reactions (ΔG) is minimized.

here, the probability-weighted sum of the binding energies and the free energy change associated with the redox reaction is minimized.

The equilibrium position of the ring can be calculated by numerically solving the optimization problem. This involves iterating through different potential values (ΔV) and calculating the probabilities (P_i) and the corresponding free energy contributions. The potential that minimizes the free energy is the equilibrium potential, and the corresponding probabilities give the equilibrium distribution of the ring along the thread.

By manipulating the potential difference applied across the rotaxane system, one can control the redox reactions, which affect the binding energies and the equilibrium distribution of the ring. This enables the electrochemical switching of the ring's position in the rotaxane. The mathematical model described here provides a simplified framework for understanding the principals involved in the electrochemical switching mechanism. Still, existing systems can involve additional factors, such as solvent effects and non-ideal behaviour, which may require more rigours mathematical descriptions.

Recently, extensive work has been done on interlocked molecules under the umbrella of the Ratchet mechanism, especially by Leigh,^66,67 and Stoddart,^68–70 Credi,^71–73 and others.^74–77 For example, in two independent studies Stoddart and coworkers, show electrochemical switching through ratchet mechanism.^78,79 Herein, they showed the synthesis (Fig. 3a), and functioning of a linear molecular pump, crafted as an intermediate [2]rotaxane. It is formed through the controlled threading (under redox/thermal influence) and unthreading (also under redox/thermal control) of a CBPQT⁴⁺ ring along a molecular dual pump (MDP⁶⁺) dumbbell. The action of this dual pump uses an energy ratchet mechanism, achieved by adjusting noncovalent interactions and leveraging redox switching properties in both components. Initially, CBPQT⁴⁺ and MDP⁶⁺ exhibit strong repulsion, which is transformed into strong attraction upon reduction of BIPY²⁺ units to BIPY⁺˙ units, facilitating the development of stable trisradical tricationic complexes (stage II, Fig. 3b). Subsequent oxidation separates these complexes due to coulombic repulsion. One CBPQT⁴⁺ ring undergoes rearrangement to form a stable [2]rotaxane, while the second simply unthreads (Stage – III, Fig. 3b). A second reduction prompts the remaining [2]rotaxane to form a complex with the terminal BIPY⁺˙ unit. (Stage – IV, Fig. 3b) Upon oxidation, the CBPQT⁴⁺ ring is expelled in the same direction it entered, resetting the energy ratchet. Redox chemistry regulates this, causing the potential energy wells and coulombic barriers to vary. This process facilitates the gradual, unidirectional capture and release of a ring by coordinating two redox cycles and one rearrangement.

Fig. 3 Stoddart's artificial molecular dual pump. Reproduced with permission from ref. 79, Copyright 2019, American Chemical Society.

In further study, they synthesized [2]rotaxanes using they synthesised the similar ring (Fig. 4a). They demonstrated the corresponding energy profiles as well as the unidirectional transit of a ring onto, along, and finally off the dumbbell (Fig. 4b). Initially, in Stage I, steric interactions with the PcS and strong coulombic repulsions with PY⁺ cause difficulties for the positively charged ring when it tries to thread onto the dumbbell. Subsequently, in Stage II, the coulombic barrier is lowered by a negative potential reduction of −700 mV, which makes it easier for a stable triradical tricationic complex to form. In Stage III, the ring's escape into the bulk solution is impeded by oxidation by a positive potential of +700 mV, which also decreases the ring's contact with the recognition site and reinstates the coulombic barrier from PY⁺. As a result, the ring must traverse over the IPP steric barrier in order to join the collecting chain. Ultimately, photocleavage of the stopper PcS is caused by UV irradiation in Stage IV, allowing the ring to reenter the bulk solution.

Fig. 4 Stoddart's artificial molecular pump. (a) [2]rotaxane and interlocked ring CBPQT⁴⁺, (b) ratchet mechanism for shuttling of AMPs (the green and red curved arrows in energy profile diagram represent kinetically favoured and disfavoured transitions, respectively). Reproduced with permission from ref. 78, Copyright 2020, American Chemical Society.

Redox-switching in rotaxanes

The electrochemical switching of rotaxanes changes oxidation states of the molecules due to reversible redox reactions.^80,81 In the presence of electrochemical stimuli, these macrocycles bear large conformational changes and result in a substantial difference in the amplitude of molecular motion (Fig. 5).⁸² Moreover, electrochemical changes offer an excellent description of the oxidation state of the central metal atoms,⁸³ diffusion constants,⁸⁴ orbital energies,⁸⁵ and electrochemical mechanisms.⁸⁶ The electrochemical switching in rotaxanes relies on incorporating redox-active components into the structure. Typically, one or both components—the axle or the ring—contain redox-active units, such as metal centers or organic moieties that are capable of undergoing redox reactions.⁸⁷ These redox-active units can exist in different oxidation states, which enables the control of the rotaxane's overall electronic condition.⁸⁸ Electroanalytical techniques, such as widely used cyclic voltammetry (CV), can measure the variation in the number of isomers in various redox states and convey qualitative evidence for co-conformational alterations via altered half-wave (E_1/2) or peak (E_p) potentials.^89,90 Further information such as shift in peak potentials, reversibility of the system, diffusion coefficients of the complex, association constants, etc. can also be determined.

Fig. 5 Electrochemical switching of rotaxane. Reproduced with permission from ref. 91, Copyright 2003, American Chemical Society.

Pioneering work led by Stoddart,^92,93 Sauvage,⁹⁴ and Leigh,^95,96 established the effectiveness of electrochemical switching in rotaxanes. For instance, Stoddart and Wasielewski reported the electroswitching of bistable[2]rotaxane in the ground and excited state electronic configuration of BODIPY⁵³ (Fig. 6).

Fig. 6 Redox actuation of a bistable BODIPY rotor [2]. Reproduced with permission from ref. 53, Copyright 2020, American Chemical Society.

In this report, they showed that the oxidation of tetrathiafulvalene (TTF) (neutral molecule) to its dicationic state TTF²⁺, which drives the cyclobis(paraquat-p-phenylene) (CBPQT⁴⁺) towards the BODIPY rotor that substantially increases the quantum yield of BODIPY. Fluorescence becomes more intense due to its high nonradiative rate constant and larger energy barrier caused by its excited-state rotation. After introducing the oxidizing agent Fe(ClO₄)₃ (6.25 M), the inherent charge-transfer peak for the TTF unit in the CBPQT⁴⁺ at 843 nm vanished (Fig. 7a). In contrast, two new absorption bands indicative of the mono-oxidized form of TTF emerged at 450 and 600 nm (Fig. 7b). Additional oxidant addition (up to 2 mol equiv.) caused the mono-oxidized TTF absorbance to vanish and was replaced by an absorption band at 375 nm that indicated the presence of TTF²⁺ dication (Fig. 7c). Later on, the addition of Zn powder (reducing agent) restores all initial absorption bands (Fig. 7d). This restoring of absorption of bands after reduction confirms redox switching where the control unit was CBPQT⁴⁺ and BODIPY act as the functional unit.

Fig. 7 UV/Vis absorption spectra of Stoddart bistable BODIPY rotor [2]. Reproduced with permission from ref. 53, Copyright 2020, American Chemical Society.

A dumbbell-shaped guest system and rotaxane based macrocyclic host were developed to provide a straightforward and adaptable method for expanding electron catalysis to aid in molecular recognition.⁹⁷ The guest D⁺⁽˙⁺⁾ has three components, a 2,6-diisopropylphenyl group on one side of the dumbbell that imparts steric hindrance and prevents the ring from threading, a 2,6-dimethylpyridinium (PY⁺) cation on the other side, that functions as a switchable energy barrier in conjunction with a positively charged BIPY˙⁺ unit and a BIPY˙⁺ unit in the middle of the dumbbell that binds R²⁽˙⁺⁾ to form a trisradical complex via radical–radical interactions. Initial studies indicate that significant coulombic repulsion causes R²⁽˙⁺⁾ to cross over the PY⁺ terminal of D⁺⁽˙⁺⁾ very slowly. The energy barrier arising from this repulsive interaction can be modified (Fig. 8a), depending on the charges on the host and guest, by modifying the redox states of the bipyridinium units.

Fig. 8 (a) Structure of the host–guest system consisting of a macrocyclic host and a dumbbell-shaped guest. Each BIPY unit in the system has three redox states, dicationic, radical cationic state and neutral state mentioned in different colors. The variable redox states of viologen is responsible for electron catalysis. (b) The conceptual system for molecular recognition process aided by electrons. The first step involves injecting an electron, second step involves the reduction of one BIPY˙⁺ unit in R²⁽˙⁺⁾ or one BIPY˙⁺ unit in D⁺⁽˙⁺⁾ to a radical state. Third step involves the quick creation of a crucial intermediate, a [D⊂R]⁺²⁽˙⁺⁾ bisradical complex, which is promoted by a reduction in the coulombic repulsion involving the host and guest molecules and the last step involves the oxidation of [D⊂R]⁺²⁽˙⁺⁾ bisradical complex by release of an electron to complete the catalytic cycle and resulting in a [D⊂R]⁺³⁽˙⁺⁾ trisradical complex as the end product. Reproduced with permission from ref. 97, Copyright 2022, Springer Nature.

In 2023, Gu et al. reported on a tristable [3]rotaxane with redox and photo switchable properties. It was composed of two CBPQT⁴⁺ macrocycles arranged in a dumbbell shape, with a dioxynaphthalene (DNP) unit between the redox-active tetrathiofulvalene (TTF) and photoactive azobenzene (AB) units.⁹⁸ The movement of the CBPQT⁴⁺ wheels within the [3]rotaxane, labelled as R1, could be initiated by both UV/Vis light exposure and manipulation of the redox states of the TTF unit (Fig. 9).

Fig. 9 Gu et al., redox triggered tristable [3]rotaxane(R1). Reproduced with permission from ref. 98, Copyright 2023, Royal Society of Chemistry.

The two CBPQT⁴⁺ wheels in R1 predominantly occupied positions adjacent to the TTF and terminal E-AB units, respectively, before they were exposed to light. When exposed to UV (365 nm)/Vis (525 nm) light, the Z/E photoisomerization of the AB unit-initiated movement, prompting one CBPQT⁴⁺ wheel (A) to hop across the AB and DNP units (Fig. 10a). Furthermore, the redox state of the TTF unit within R1E may be switched between its dicationic and neutral forms by sequentially adding oxidising and reducing chemicals without exposure to light. The other CBPQT⁴⁺ wheel was propelled by this manipulation to alternate between the TTF and DNP units. In order to better understand the redox-driven shuttling of the CBPQT⁴⁺(B) wheel in R1, extensive UV-vis absorption and ¹H NMR spectroscopic investigations were used to assess the orthogonal controllability of the CBPQT⁴⁺ wheel shuttling process of R1. The greatly elevated absorption broad band at 540 nm indicates that the neutral TTF unit might be oxidized to a positively charged dicationic TTF²⁺ unit when the oxidizing agent was added to the PSSE (>525 nm) mixed solution of R1 (Fig. 10b). The CT band of the TTF⊂CBPQT⁴⁺(B) complex at 810 nm completely vanished upon oxidation, indicating that the production of TTF²⁺ may cause the initial TTF-encapsulated CBPQT⁴⁺(B) wheel to shift to the middle DNP unit, resulting in production of the [3]rotaxane R1E¹⁰⁺, in which the CBPQT⁴⁺ wheels encapsulates both the E-AB and DNP units. The transition from R1E⁸⁺ to R1E¹⁰⁺ caused by oxidation was also confirmed by the recorded ¹H NMR spectra.

Fig. 10 UV/Vis absorption spectra of Gu et al., tristable [3]rotaxane (R1). Reproduced with permission from ref. 98, Copyright 2023, Royal Society of Chemistry.

Stimuli triggered guest binding/release

The complex synthetic methods used by MIMs, such as active/passive metal template,^99–101 stacking interaction,^85,102,103 halogen/hydrogen bonding,^104,105 or other hydrophobic interactions,^106–108 have also come to light. Functional metal templates and donor–acceptor techniques have been appropriately advanced in this area over the past few years by Leigh et al.,^99,109,110 Goldup et al.,^101,111,112 Stoddart et al.,^113–115 and others.^59,116–121 Tetrathiafulvalene (TTF), 1,5-dioxynaphthalene (DNP), bipyridine, pyridine, viologen, cyclobis-paraquat-p-phenylene (CBPQT⁴⁺), and crown ether derivatives (Fig. 11) are exemplary examples of unique ligands that are preferred critical elements in these systems and aid in developing the dynamic features in the interlocked structures.^69,122–125

Fig. 11 Redox-active units responsible for switching.

Nandi et al. reported a metal templated synthesis of redox-active rotaxane (Fig. 12).⁵⁹ By using PhenMC's phenanthroline motif, which has anion binding capabilities as demonstrated by NMR titration and electrochemical techniques. They reported the active metal binding synthesis of RTXN1, a novel redox-active rotaxane. Further, a “π–π” stacking interaction between Phen MC and an alkyne-terminated axle having viologen was used to synthesize RTXN2 rotaxane with multiple redox centers.

Fig. 12 Nandi's redox-active rotaxane (reproduced with permission from ref. 59, Copyright 2020, Wiley VCH).

Stimuli induced controlled conformation changes

Rotaxanes, a significant class of MIMs, have become crucial contenders for building artificial molecular machines as well as electronic devices because of their switching and shuttling characteristics.^79,126,127 In response to external stimuli, the macrocyclic component of rotaxane can alter conformation around the axle component.^128–130

Dumartin et al. reported a branched “tail” of the molecular shuttle which is connected to electrochemical hysteresis that opens and closes like a zipper.¹³¹ The MSⁿ⁺ cyclophane is shuttled between two recognition sites in this ring-to-ring based [2]rotaxane, where one recognition site (Zip-R⁴⁽⁺˙⁾) stabilizes via radical-pairing in the reduced state. Conversely, donor/acceptor interactions maintain Zip-R⁸⁺ in its oxidized state as an alternative (Fig. 13).

Fig. 13 Dumartin's zipper – [2]rotaxane switching: electrochemically driven actuation of the molecular zipper (Zip-R⁴⁽⁺˙⁾/Zip-R⁸⁺). (Reproduced with permission from ref. 131, Copyright 2019, American Chemical Society).

Methods such as UV-Vis-NIR and ¹H NMR spectroscopy were used to investigate the interconversion of Zip-R⁸⁺ and Zip-R⁴⁽⁺˙⁾. Zinc dust was used to reduce Zip-R⁸⁺ in acetonitrile (MeCN), producing Zip-R⁴⁽⁺˙⁾ which has a distinctive near-infrared (NIR) band with a centre wavelength of 958 nm that confirms the existence of bipyridinium radical-pairing. Two oxidation waves are seen when Zip-R⁴⁽⁺˙⁾ was oxidised to Zip-R⁸⁺ at 100 mV s⁻¹ scan rate, demonstrating the existence of slow dynamic processes (Fig. 14). The redox behaviour of the dumbbell component displays a distinct reversible redox wave across a range of scan rates, demonstrating its stability. In contrast, the dynamics of the mechanically interlinked parts impact how the oxidation peaks in Zip-R⁸⁺ divide. Regardless of the scan rate, Zip-R⁸⁺ exhibits a distinct reduction wave which becomes broader and shifts to more negative potentials as the scan rate increases. Lower scan rate result in a sharper, more positive reduction wave, which indicates that the radical state has stabilized during the creation of the ring-in-ring recognition motif. The reduction process starts with the innermost cyclophane, leading to the intermediary Zip-R⁽⁶⁺⁾⁽²˙⁾D.

Fig. 14 (a) UV–vis–NIR spectra and (b) CV of the Zip-R·8PF₆ (0.035 and 0.03 mM in MeCN and 0.1 M tetrabutylammonium hexafluorophosphate/MeCN respectively) at RT. (Reproduced with permission from ref. 131, Copyright 2019, American Chemical Society).

In Zip-R⁽⁶⁺⁾⁽²˙⁾D, MS⁴⁺ is in an electron-rich environment that stabilizes its reduction while requiring more negative potentials than free cyclophane. Moreover, the reduction wave shifts in favour of positive potentials at slower scan rates as they instantly transition into the more stable Zip-R⁴⁽⁺˙⁾A state. Due to the restricted interaction between the Zip-R⁽⁶⁺⁾⁽²˙⁾D and Zip-R⁴⁽⁺˙⁾D cyclophanes, rapid scan rates result in a more negative and significant reduction wave, which corresponds to the thorough decrease of the metastable co-conformation of Zip-R⁴⁽⁺˙⁾D. At intermediate scan rates, two distinct oxidation waves can be seen. As the scan rate increases, the first obvious oxidation wave at −0.55 V becomes less prominent; nevertheless, at scan rates lower than 1000 mV s⁻¹, another oxidation wave at a more negative potential (−0.65 V) becomes dominant. At lower scan speeds, the more positive oxidation wave is associated with the electronically stabilised fully developed ground-state co-conformationZip-R⁴⁽⁺˙⁾A. Further, the metastable co-conformation Zip-R⁴⁽⁺˙⁾D, which is capable of swiftly transitioning into the ground-state co-conformation, is reached by the negative oxidation wave. At slow scan rates, the transformation between Zip-R⁸⁺ and Zip-R⁴⁽⁺˙⁾ can be observed as quasi-reversible.

Recently, a novel type of rotaxane known as daisy chain rotaxane has gained significant attention for its role in developing molecular machines. “Daisy chain rotaxanes” refers to a specific type of rotaxane structure where several macrocycles are threaded onto a single axle, akin to a daisy chain. Each macrocycle is linked to the next in a linear arrangement, resembling the petals of a daisy connected in a chain.¹³² These structures are of interest to supramolecular chemistry and nanotechnology owing to their special characteristics and potential applications in molecular machines, materials, and drug delivery systems.^133,134 In 2023, Stoddart and colleagues published findings on the template-directed synthesis of redox-active [c3]daisy chain rotaxanes. They describe the design (depicted in Fig. 15A) and synthesis of two such rotaxanes, named [c3]DC2·18PF⁶⁻ and [c3]DC12·18PF₆, employing a combination of radical and anion templation. The arrangement of the self-complementary monomers, along with templation by PF⁶⁻ counterions, has resulted in the highly efficient formation of [c3]DC2·18PF⁶⁻ and [c3]DC12·18PF⁶⁻ with yields approaching full conversion. The mechanically interlinked structure and self-aggregation of [c3]DC12⁹⁽˙⁺⁾—a nonaradical nonacationic variant—exhibit significantly improved air stability. Additionally, by employing an electrochemical stimulus, the geometry of the macrocycle, which is formed from [c3]DC12¹⁸⁺ in solution, can be easily and reversibly changed between its reduced trisarm-shaped [c3]DC12⁹⁽˙⁺⁾ and oxidized cyclic [c3]DC12¹⁸⁺ states (Fig. 15B).

Fig. 15 Stoddart's redox switchable [c3]daisy chain rotaxanes. Reproduced with permission from ref. 135, Copyright 2021, Elsevier.

¹H NMR spectroscopy reveals that the mCBPQT⁴⁺ rings within [c3]DC12·18PF₆ encircle the triazoles near the stoppers, forming a macrocycle-like co-conformation (Fig. 16b). The solution of [c3]DC12¹⁸⁺ turns from colorless to deep purple after reduction with Zn dust in MeCN and a distinctive absorption at 1070 nm is visible in the Vis/NIR spectrum. According to these findings, [c3]DC12¹⁸⁺ is reduced to [c3] DC12⁹⁽˙⁺⁾, a nonaradical nonacationic state, and the mCBPQT²⁽˙⁺⁾ rings are moving to interact with the in-chain BIPY˙⁺ units (Fig. 16c). The ¹H NMR spectrum of [c3]DC12⁹⁽˙⁺⁾ indicates that the protons on the nine BIPY˙⁺ units and near the BIPY˙⁺ units are affected by the paramagnetic properties of the BIPY˙⁺ radicals. However, because of their distance from the BIPY˙⁺ radicals protons on the stoppers, triazoles, and portions of the oligomethylene chains remain detectable. Thus, the ¹H NMR spectrum confirms the positioning of the mCBPQT⁴⁽˙⁺⁾ rings on the BIPY˙⁺ units, supporting the three-arm star-shaped geometry of [c3]DC12⁹⁽˙⁺⁾. Compared to chemical redox processes, electrochemical stimulation provides a cleaner and more convenient way to move across cyclic and trisarm-shaped states. Their Vis/NIR spectra show that when different potentials are applied to a MeCN solution of [c3]DC12·18PF₆ using controlled potential electrolysis (CPE), the solution's color reversibly switches between colorless and deep purple, indicating the presence of [c3]DC12¹⁸⁺ and [c3]DC12⁹⁽˙⁺⁾, respectively. Demonstrates good chemical stability of the [c3]DC system is demonstrated by the CPE switching process as evidenced by repeated cycles with no discernible alterations in the Vis/NIR spectra (Fig. 16d).

Fig. 16 (A) Electrochemical switching between [c3]DC12¹⁸⁺ and [c3]DC12⁹⁽˙⁺⁾. (B) ¹H NMR spectra, (C) Vis/NIR absorption spectra, (D) reversible switching cycle. Reproduced with permission from ref. 135, Copyright 2021, Elsevier.

Kinetics of rotaxane redox switching

Rotaxane macrocycle can go amid several stations built in a dumbbell ‘track’. An external stimulus must be given to initiate this shuttling process, given that it alters the stations’ based on the affinities and provides the macrocycle with a push to move and produce a newly stable translational isomer. Controlling the kinetics of the system is crucial for effectively utilizing this motion.

Andersen et al. reported the kinetics of switching of CBPQT⁴⁺ by changing ionic environment of rotaxane from central TTF unit to peripheral oxyphenylene unit of macrocycle.¹³⁶ UV-Vis-NIR were used to investigate the kinetics of electrochemical switching of CBPQT⁴⁺. Initially the macrocycle (4PF₆) mainly exists in the “unswitched” form, where CBPQT⁴⁺ surrounds the central TTF station (Fig. 17). Introducing a one equivalent of Fe(ClO₄)₃ allows for investigating the switching process's kinetics in the oxidized [2]rotaxane, where CBPQT⁴⁺ moves between the stations. The presence of 0.1 M Fe(ClO₄)₃ solution significantly enhances the rate constant in connection with the switching process as compared to the absence of the salt. Moreover, the TTF unit's oxidation rate displayed a significant increase. Different PF₆⁻ salts with varying ammonium cations (n-Bu₄N⁺, Et₄N⁺, Me₄N⁺, and NH₄⁺) amplified the switching rate by the order of 1.5 to 1.8.

Fig. 17 Effect of adding Fe(ClO₄)₃ salt while shuttling of rotaxane. The mono-oxidised rotaxane 1^5+/1˙ is produced first. Second, switching 1^5+/1˙ produces the switched form of [2]rotaxane S1^5+/1˙, which disproportionately produces the initial, ground state rotaxane 1⁴⁺ and the doubly-oxidised switched molecule S1⁶⁺. RDS = rate determining step (reproduced with permission from ref. 136, Copyright 2019, Royal Society of Chemistry).

The most pronounced enhancement was observed with the most significant cation, n-Bu₄N⁺. However, the resulting rate constants were closely clustered, indicating that the size of the cation has minimal impact on the kinetics, if any. When comparing n-Bu₄N·PF₆ to n-Bu₄N·ClO₄, the rate constant increased significantly when the smaller ClO₄⁻ anion was used, approximately 3.5-fold higher. These observations are explained by changes in the ion-pair equilibrium caused by the presence of salts, which influence the binding potential of CBPQT⁴⁺ onto the stations in the dumbbell. Additionally, the salts assist in stabilizing the transition state as CBPQT⁴⁺ overcomes the significant thioethyl (Set) barrier. Adding salts offers a convenient approach to enhance the transitioning rates in CBPQT⁴⁺ based electroactive molecular shuttles.

Chemical/redox switching in catenanes

A member of mechanically interlocked molecules (MIMs) known as catenanes is made up of two or more macrocycles (rings) that are woven through one another and are unable to be separated without breaching a covalent interaction. The word “catenane” is derived from the Latin word “catena”, which means chain, and it refers to their interconnected character.¹³⁷ Despite having different topologies, catenanes and rotaxanes can be considered molecular siblings since they can be made from a pseudorotaxane, a supramolecular species in which one or more macrocycles ring a thread.¹³⁸ The most stable species in solution are usually produced by noncovalent bonding interactions that induce thermodynamic threading of a linear component through the macrocycle (Fig. 18).^139–142

Fig. 18 Cartoon representation of different catenanes.

As contenders for the development of molecular switches, machines, and memory devices, bistable catenanes represent a family of functional molecules that is very intriguing.^143,144 The propensity of these molecules’ parts to undergo specific and reversing large-amplitude motions (of one component with respect to another) without affecting their mechanically interlocked structure makes them appropriate for the fabrication of artificial nanodevices. Numerous reports concerning the chemical, electro/photochemical induced molecular shuttles have been published, and this behavior has been extensively investigated using numerous techniques.^145–147 Catenanes are at the forefront of this field to construct artificial molecular machines and take advantage of the dynamics of interlocked structures in polymers, metal/covalent–organic frameworks (M/COFs), and other materials.^148–152 Their research has resulted in significant advancements that have significance for various scientific fields, from biology to soft matter physics, as well as supramolecular chemistry.¹⁵³

Like rotaxanes, catenanes have a naming system where the term is preceded by square brackets denoting the number of macrocycles that make up a catenane. So a molecule made of n macrocycles is called a [n]catenane.¹⁵⁴ (Fig. 11) Catenanes’ interlocked design can be functionally utilized in several ways. Catenanes are appealing candidates for use in molecular machines due to the dynamics of the substantial amplitude motions that their components can undergo.¹⁵⁵ A rotary motor can be built based on the 360° rotation of one ring about the other or the change in the relative placement of the rings, which can be utilized as a switch. This characteristic can be exploited to bind substrates precisely because the cavity created by interlocking rings can be employed to hold functional groups in precise places in 3D space.^{143,147,156–159}

Mechanism of redox switching in catenanes

The ability of catenane structures to undergo reversible conformational changes or switch between several states in response to a chemical/electrochemical stimulus is called stimuli-responsive switching in catenanes (Fig. 19). This behavior is made possible by including redox-active units in the catenane's macrocycles, which enable electron transfer during the electrochemical reaction.

Fig. 19 Cartoon representation of catenane switching in presence of external stimuli.

This electrochemical switching in catenanes can occur in following steps: (1) presence of redox active functional groups in catenanes. Switchable catenanes often contain redox-active groups within their macrocycles, such as metal centers or organic moieties. These redox-active units can undergo reversible oxidation and reduction reactions chemically or electrochemically, leading to changes in their electronic state and overall conformation of the catenane. (2) Activation of redox groups: an electrical potential is applied to the catenane system (e.g., through cyclic voltammetry or other electrochemical techniques), and the redox-active groups within the macrocycles can accept or donate electrons, depending on the applied potential. This electron transfer process induces a change in the redox state of the catenane, which in turn alters the interactions between the interlocked macrocycles. (3) Changes in the redox state of the catenane can cause conformational switching, which causes the threaded macrocycles to move about one another. Depending on the design of the catenane and the specific redox-active groups, this movement may involve switching between different binding sites or adopting different spatial arrangements. (4) Reversibility of catenanes: electrochemical switching in catenanes is typically reversible. Once the electrical potential is removed or changed, the redox-active groups can undergo the reverse electron transfer process, leading the catenane to return to its initial state or adopt a different conformation. In cases, where the switching is carried out chemically using oxidant or reductant, the reverse reaction can bring down the catenane to its original state.

Due to the possibility of using redox-switchable catenanes in molecular machines, sensors, and other responsive nanoscale systems, they have attracted a lot of attention. The ability to control their conformation and properties through chemical/electrochemical stimuli opens up new possibilities for dynamic and adaptive materials at the molecular level. However, it's essential to note that the design and specific behavior of redox-switchable catenanes can vary significantly depending on the choice of redox-active groups and the overall structure of the interlocked molecules.

Recent catenanes redox/electrochemical switches and their different applications

Switching between binding sites

Catenanes with multiple binding sites can exhibit redox-chemical switching between different binding states. By controlling the redox potential, the catenane can be switched between states where specific sites are accessible or blocked, affecting its binding properties. The ability of these interconnected molecules to exhibit reversible conformational changes in response to variations in the oxidation state of redox-active units within the catenane structure is referred to as “redox-driven conformational switching” in catenanes.¹⁵³ Redox-active groups, which can accept or donate electrons, are included in the catenane's macrocycles to facilitate this behavior. Recently, Stoddart and co-workers demonstrated an artificial molecular rotor made of [3]catenane and 2 cyclobis(paraquat-p-phenylene) (CBPQT⁴⁺) rings that rotate in a single direction around a 50-membered loop while being impacted by an electric field in solution¹²² (Fig. 20a). The two rings’ single-directional circumrotation during this switching does not necessitate the breakage of any covalent bonds. It takes only a few minutes to complete two redox cycles that need the single-directional circumrotation of both the tiny rings across 360° about the loop (Fig. 20b). In an oxidizing environment, the two CBPQT⁴⁺ rings surround the loop. One of the rings occupy the well formed by the BPM unit, necessitating the other ring to cross the IPP unit. Two mechanically interlocked CBPQT⁴⁺/²⁽⁺˙⁾ rings, a switchable barrier connected to the PY⁺ unit, two switchable viologen (V²⁺/⁺˙) recognition sites, and a steric hindrance (IPP) are essential for the production of unidirectional motion (Fig. 20c) of the two rings with regard to the loop. The BPM unit is surrounded by [CBPQT-B]⁴⁺ because of repulsive coulombic forces, whereas the T unit is originally surrounded by [CBPQT-A]⁴⁺. Reduction occurs when six electrons are added to the [3]catenane (Fig. 20c, step 1), changing the CBPQT⁴⁺ rings into CBPQT²⁽⁺˙⁾ and the V²⁺ units to V⁺˙. An increase in attractive radical–radical interactions is accompanied by a decrease in coulombic interactions (Fig. 20c, II). On the other hand, for a CBPQT²⁽⁺˙⁾ ring, the barrier to cross the IPP unit is significantly greater than the barrier to cross the PY⁺ unit. Therefore, [CBPQT-A]²⁽⁺˙⁾ traverses the PY⁺ unit before continuing clockwise to V⁺˙, and [CBPQT-B]²⁽⁺˙⁾ moves concurrently to occupy the V⁺˙ unit that is adjacent to the IPP unit. The stable [3]CMM⁷⁺⁶˙ form in this overall reduced state is the one in which the V⁺˙ binding sites are encircled by both CBPQT²⁽⁺˙⁾ rings. The [CBPQT-A]⁴⁺ ring is installed on the BPM unit and the [CBPQT-B]⁴⁺ ring is installed on the T unit by a biased Brownian motion (Fig. 20c, III) that results from further oxidation (Fig. 20c, step 2). Overall, a single redox cycle initiates the 180° unidirectional rotation and positional exchange (Fig. 20c, I′) amongst the two CBPQT⁴⁺ rings. The rings complete a 360° clockwise circumrotation across the loop and return to their original starting places after a second redox cycle (Fig. 20c, steps 3 and 4). It takes only a few minutes to complete two redox cycles for the two tiny rings to circumrotate 360° in relation to the loop in a unidirectional manner. Additionally, by chemically modifying one of the two tiny rings, the co-constitution of the [3]catenane permits adherence to the electrode surface, facilitating spatially directed rotation for a fixed frame of reference and the conversion of electrical energy into mechanical energy at a surface. On the other hand, redox control of the two-dimensional potential energy landscape of [3]catenane drives the energy ratchet mechanism of electric molecular motors. The design of the loop fundamentally modifies the energy landscape in a way that allows the redox potential to oscillate externally, providing the energy required to achieve unidirectionality and harness the molecular system's Brownian motion.

Fig. 20 (a) Graphical depictions of the oxidised state of the [3]catenane molecular motor [3]CMM¹³⁺, together with important structural components. The terms CBPQT⁴⁺, CBPQT²⁽⁺˙⁾, V²⁺, V⁺˙, BPM, IPP, T, and PY⁺ refer to the cyclobis (paraquat-p-phenylene) rings, the bisradical dicationic states of cyclobis (paraquat-p-phenylene), the viologens, the radical cationic states of the viologens, the bis(4-methylenephenyl)methane, the isopropylphenylene, the triazole, and the 2,6-dimethypyridinium units, respectively, (b) graphical depictions of the reduced state of the [3]catenane molecular motor [3]CMM⁷⁺⁶˙, CBPQT²⁽⁺˙⁾ rings and the V⁺˙ units interact through radical-pairing, (c) redox operation of [3]CMM^13+/7+6˙. Reproduced with permission from ref. 122, Copyright 2023, Springer Nature.

Because of its complex synthetic process and the few interactions, such as van der Waals forces among the cycloalkane as well as the ring, which lead to the statistical synthesis of catenanes during the cyclization stage, switching in higher catenanes is always tricky.¹⁶⁰ A recent example was provided by Stoddart and coworkers, who reported the successful synthesis of two catenanes: a tetracosacationic radial [5]catenane, which comprises four mechanically interlocked 4⁺ charged rings around an 8⁺ charged ring and can contain up to 24 positive charges, and a dodecacationic [3]catenane, which is consisting of three mechanically interlocked 4⁺ charged rings regardless of their common coulombic attraction (Fig. 21).¹⁶¹

Fig. 21 Stoddart's dodecationic [3]catenane (reproduced with permission from ref. 161, Copyright 2018, Elsevier).

Template-directed methods are typically required for mechanical bond formation to reconcile the entropy loss from the interlocking of mechanical bonds and the enthalpic gains from the molecular templation. However, under reducing conditions to a fundamentally based template negated during oxidation, [n]catenanes are formed, both are enthalpically and entropically demanding. Additionally, this catenane can switch chemically or electrochemically into two stable states: dodecacationic as well as hexaradical hexacationic. These two redox states, which were demonstrated to have two distinct geometries in their solid states by X-ray diffraction, enabled for the formation of excellent single crystals. The two exterior cyclophanes’ circumrotation from surrounding the triazole linkers to include the BIPY⁽˙⁺⁾ units after being reduced from CBPQT⁴⁺ to CBPQT²⁽˙⁺⁾ led to these geometries. As evidenced by CV and UV-vis-NIR spectroscopy, the molecular switch is reversible in action and can be switched for a minimum of five times in solution (Fig. 22b and c).

Fig. 22 (a) Stoddart's dodecationic [3]catenane, (b) cyclic voltammogram of [3]C·12PF₆ (0.1 M TBAPF₆/MeCN), (c) UV-vis-NIR spectra of [3]C¹²⁺ (blue) and [3]C⁶⁽˙⁺⁾ (purple) are depicted. Insets show absorption intensities of [3]C¹²⁺ (blue dots) and [3]C⁶⁽˙⁺⁾ (purple dots) at 1162 nm wavelength, indicating reversible switching between the two states across five cycles using Zn dust and NOPF₆ as reducing and oxidizing agents, accompanied by photographs of the solutions (reproduced with permission from ref. 161, Copyright 2018, Elsevier).

Radical pairing interactions between viologen units in catenanes have played a significant role in synthesizing different derivatives of catenanes. Moreover, sometimes it also acts as a procrastinator in stabilizing the co-conformation derivatives.^162,163 A similar approach has been used by Wang et al., where they reported an oxime condensation product, octa cationic homo-catenane, that possesses redox induced switching (Fig. 23).¹⁶⁴

Fig. 23 Wang's Oxime product catenane (reproduced with permission from ref. 164, Copyright 2020, Wiley-VCH).

The switching behavior was established through UV/Vis/NIR and NMR spectroscopy. In UV/Vis/NIR spectra, they found a broad peak centered at 1100 nm, establishing the presence of (BIPY⁺˙)₂ after the addition of Zn dust (Fig. 24). This confirms the switching from phenylene units to BIPY units upon reduction. The findings were supported by ¹H NMR, where a broadening of the baseline after adding Zn dust was noted. The [2]catenane is found in an oxidised state in a co-conformation where one of its two macrocycles encircles a phenyl unit of another, preventing coulombic repulsion between the components of BIPY²⁺. The [2]catenane moves mechanically after reduction, causing another co-formation in which the interactions between its two BIPY⁺˙ radical cations have radical pairing interactions.

Fig. 24 UV/Vis (left) and ¹H NMR spectra (right) Wang's catenane switching (reproduced with permission from ref. 164, Copyright 2020, Wiley-VCH).

Conclusion and future prospects

The emergence of a new form of covalent and non-covalent bonding in multifunctional architectures opens the most significant window of opportunity for chemical sciences. This also applies to the mechanical bond. Some of the most complex structures and fascinating synthetic molecular devices have been created because of the chemistry of “small” mechanically linked molecules.^165–169 The use of the mechanical bond in materials research has just recently begun to take off.¹⁷⁰ However, chemists have tried these mechanically interlocked molecules, i.e., rotaxanes and catenanes for applications such as nanomotors, etc. where precise molecular level control has been achieved. In its most comprehensive scope of applications, they began to endow such molecules as making molecular machines,^171–174 molecular sensors,^175–179 molecular electronics,^180–183 drug delivery,^184–186 molecular switches,^{164,187–189} and, catalysis.^{176,190–192}

The molecular switching discussed herein has different binding sites responsible for shuttling/switching when an external stimulus is applied. This review covered recent progress in molecular switching of rotaxanes and catenanes. Herein, we demonstrated how different binding sites in rotaxanes, such as Tetrathiafulvalene (TTF), 1,5-dioxynaphthalene (DNP), bipyridine, pyridine, viologen, and cyclobis-paraquat-p-phenylene (CBPQT⁴⁺), etc., activated in the presence of different external stimuli like, electric current applied, pH change, addition of acid/base, solvent polarity changes, guest induced, or, addition/removal of electrons from these units. On the contrary, catenanes have different binding sites, like CBPQT⁴⁺, DNP, NDI, BIPY, etc., responsible for switching. These binding sites get activated by external stimuli like reduction/oxidation, pH change, acid/base addition, cation/anion addition, or change in solvent polarity. These switching will further result in co-conformational changes of these mechanically interlocked molecules, and come its initial conformation when stimuli are removed. This reversible conformational change is the procrastinator in comprehending its most comprehensive applications.

Future research on mechanically interlocked molecules may focus on biological, environmental, and medical applications. We believe that there is a need of novel synthetic strategy which reduce the synthetic complexity like reducing multistep synthetic processes, making their preparation labour-intensive and time-consuming and improving yield of product. There is also a need of improving solvent and environment influence such as solvent polarity, temperature, and pH of reaction mixture during the synthesis. However, rotaxanes and catenanes can sometimes be trapped kinetically in one conformation because of energy barriers hindering the transition to other states. Overcoming these barriers to achieve controlled switching is still needed, especially for complex systems that significantly improve its widest applications. In some cases, multiple regioisomers (different positional/region isomers) of rotaxanes and catenanes can be formed during synthesis. These isomers can have various switching properties and stabilities, complicating the isolation and characterization of the desired product can lead to significant applications. On the laboratory scale, significant progress has been accomplished with the design and synthesis of rotaxanes and catenanes. However, larger-scale applications for mechanically interlocked molecules are still a proof of concept. Perhaps, incorporating rotaxanes and catenanes into functional devices or applications can be complex and working on these issues is highly appreciated. Last but not the least, rotaxanes and catenanes form multiple regioisomers (different positional isomers) during synthesis, and these isomers can have other switching properties and stabilities, complicating the isolation and characterization. Despite these difficulties, continued research is concentrated on finding solutions and creating plans to utilize the special switching abilities of rotaxanes and catenanes for various applications.

Conflicts of interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

The authors thank Director and support staff of CSIR-CECRI for their constant encouragement and support. CECRI manuscript number: CECRI/PESVC/Pubs/2024-024.

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