**3.2 Molecular shuttles**

Interlocking a part of a linear molecule of a rotaxane into the cavity of a macrocycle molecule is associated with a series of complex interaction phenomena. An important function that many of the aforementioned systems can undergo is that of molecular shuttling. This often happens when a macrocycle trapped onto a linear component (axle) is capable of moving reversibly between two or more Regions on the axle (often called stations), in response to external stimuli (e.g., electrochemical stimuli, irradiation, heating/cooling, and/or solvent polarity changes) [21].

As already mentioned the main forces that hold these supramolecular structures together are relatively weak, and therefore the systems can undergo the described shuttling movement under mild external changes in a fully controlled manner [21]. Across all the potential driving forces, all the kind of energy inputs, and all aforementioned parameters, it is noteworthy that a simple change in solvent polarity can be harvested in order to induce a controllable molecular machine function (**Figure 4**). In this section the stimulating role of solvents on the function of interlocked systems is reviewed.

One of the key/pioneering contributions in the field of solvent effects on the (multi)functional behavior of rotaxanes has been made by Leigh and coworkers. By applying chemistry similar to that occurring in natural systems and specifically

**Figure 4.** *Schematic illustration of controllable switching of [2]rotaxanes through external stimuli.*

in peptides, they managed to synthesize the rotaxanes of **Figure 5A** [22]. In both cases of rotaxanes of **Figure 5A**, the linear component consists of a glycylglycine chain and two diphenylmethane end groups (stoppers). The stabilization of these [2]rotaxanes is achieved through the development of hydrogens bonds between amide hydrogen of the macrocycle molecule with the carbonyl groups of the linear compound and vice versa. The resulted bonds are very stable when the rotaxanes are dissolved in non polar solvents such as CHCl3. However, when they are dissolved in polar solvents such as DMSO which can specifically interact with parts of these molecules, these bonds become unstable, and this results to a different molecular configuration for each of the two [2]rotaxanes. This solvent-driven feature is essential for triggering the switching ability of this supramolecular complex, thus functioning as a molecular machine, and has been a stimulating example for a number of later scientific works.

In 2003 Da Ros et al. published a [2]rotaxane which performs a solvent-induced shuttling movement as shown in **Figure 5B** [23]. This [2]rotaxane consists of fullerene C60 group behaving as both a stoppering unit and a photoactive group. The amphiphilic nature of the rotaxane thread was used to shuttle the macrocycle from close to the fullerene spheroid (in nonpolar solvents) to far away (in polar solvents). The rotaxane is based on hydrogen bond-directed assembly of a benzylic amide macrocycle around a dipeptide thread, solvent-switchable molecular shuttles in a similar fashion to the work by Leigh et al. [22]. In nonpolar solvents, e.g., CH2Cl2 or CHCl3, the macrocycle forms hydrogen bonds with the peptide residue. In polar aprotic solvents such as DMSO, the hydrogen bonding between the macrocycle >NH group and the peptide carbonyl group is disrupted by the competing solvent interactions, and thus the macrocycle selectively stops over the alkyl chain [23].

In 2005 Gschwind and coworkers published a series of [2]rotaxanes, containing a phenol-involving linear part, amide-involving macrocycles, and triphenylmethane-stoppering units [24]. The dumbbell molecule 1 of **Figure 6** offers three diamide stations to the macrocyclic molecule in the protonated form of the [2] rotaxane. It was found that electrostatic interactions can modulate exceptionally well the speed of the mechanical motion between a fast- and a slow-motion state as a response to a reversible external solvent-provided stimulus. The electrostatic interactions in these rotaxanes are controllably regulated through solvent effects

#### **Figure 5.**

*(A) The two rotaxanes by Leigh et al. [22] and (B) the solvent-switchable [2]rotaxane containing C60 stoppering unit by Da Ros et al. Reprinted with permission from Da Ros et al. [23].*

**213**

**Figure 7.**

*Solvent Effects in Supramolecular Systems DOI: http://dx.doi.org/10.5772/intechopen.86981*

switching function.

**Figure 6.**

**4.1 Generalities**

higher free energy barrier in the case of water.

**4. Solvatochromic supramolecular systems**

*in (A). Reprinted with permission from Gschwind and coworkers [24].*

induced by altering the proportion of polar solvent in a binary solvent mixture. For example, when different amounts of DMSO are added to dichloromethane, solvent-driven shuttling modifications occur (**Figure 6C**). It was further found that the molecular wheel shuttling in deprotonated rotaxanes is hindered by the counter-cation held through electrostatic forces close to the anion at the axlecenter region. Thus, the shuttling speed can easily be regulated by addition of acids and bases enabling a fast- and a slow-motion mode parallel to the on-off

*(A) Various [2] rotaxanes by Gschwind and coworkers [24]. (B) Interactions in a [2]rotaxane. (C) Cartoon representation illustrating the dynamic processes in the acid-/base-regulated switching of [2]rotaxanes depicted* 

Cai and coworkers have a long-standing interest in the effects of solvents in the shuttling movements in mechanically interlocked compounds [25–27]. In 2012 they reported a [2]rotaxane molecular shuttle controlled by solvent. The rotaxane involved α-cyclodextrin (α-CD), dodecamethylene, and bipyridinium moieties as shown in **Figure 7** [26]. Cai et al. discovered that the molecular shuttling in this [2]rotaxane can be driven by both solvent and temperature changes. They indeed demonstrated the shuttling process of α-CD along the linear thread in solvents of different polarities such as DMSO and H2O. The energy barrier in water was shown to be 4.0 kcal/mol higher than in DMSO. Water interacts favorably with the bipyridinium moieties, however, negligibly with the alkyl chain, and this yields to a

Solvatochromism is a well-studied phenomenon occurring in many diverse systems. It is described as the change in color (*χρώμα*, Greek word for color) induced by solvents. In a broader context, the term solvatochromism covers changes in the electronic (UV-Vis), FTIR, Raman, or EPR spectra induced by solvents [28]. A

*Solvent-induced shuttle movement in a [2]rotaxane. Reprinted with permission from Cai and coworkers [26].*

*Solvent Effects in Supramolecular Systems DOI: http://dx.doi.org/10.5772/intechopen.86981*

**Figure 6.**

*Solvents, Ionic Liquids and Solvent Effects*

number of later scientific works.

in peptides, they managed to synthesize the rotaxanes of **Figure 5A** [22]. In both cases of rotaxanes of **Figure 5A**, the linear component consists of a glycylglycine chain and two diphenylmethane end groups (stoppers). The stabilization of these [2]rotaxanes is achieved through the development of hydrogens bonds between amide hydrogen of the macrocycle molecule with the carbonyl groups of the linear compound and vice versa. The resulted bonds are very stable when the rotaxanes are dissolved in non polar solvents such as CHCl3. However, when they are dissolved in polar solvents such as DMSO which can specifically interact with parts of these molecules, these bonds become unstable, and this results to a different molecular configuration for each of the two [2]rotaxanes. This solvent-driven feature is essential for triggering the switching ability of this supramolecular complex, thus functioning as a molecular machine, and has been a stimulating example for a

In 2003 Da Ros et al. published a [2]rotaxane which performs a solvent-induced shuttling movement as shown in **Figure 5B** [23]. This [2]rotaxane consists of fullerene C60 group behaving as both a stoppering unit and a photoactive group. The amphiphilic nature of the rotaxane thread was used to shuttle the macrocycle from close to the fullerene spheroid (in nonpolar solvents) to far away (in polar solvents). The rotaxane is based on hydrogen bond-directed assembly of a benzylic amide macrocycle around a dipeptide thread, solvent-switchable molecular shuttles in a similar fashion to the work by Leigh et al. [22]. In nonpolar solvents, e.g., CH2Cl2 or CHCl3, the macrocycle forms hydrogen bonds with the peptide residue. In polar aprotic solvents such as DMSO, the hydrogen bonding between the macrocycle >NH group and the peptide carbonyl group is disrupted by the competing solvent interactions, and thus the macrocycle selectively stops over the alkyl chain [23]. In 2005 Gschwind and coworkers published a series of [2]rotaxanes, containing a phenol-involving linear part, amide-involving macrocycles, and triphenylmethane-stoppering units [24]. The dumbbell molecule 1 of **Figure 6** offers three diamide stations to the macrocyclic molecule in the protonated form of the [2] rotaxane. It was found that electrostatic interactions can modulate exceptionally well the speed of the mechanical motion between a fast- and a slow-motion state as a response to a reversible external solvent-provided stimulus. The electrostatic interactions in these rotaxanes are controllably regulated through solvent effects

*(A) The two rotaxanes by Leigh et al. [22] and (B) the solvent-switchable [2]rotaxane containing C60*

*stoppering unit by Da Ros et al. Reprinted with permission from Da Ros et al. [23].*

**212**

**Figure 5.**

*(A) Various [2] rotaxanes by Gschwind and coworkers [24]. (B) Interactions in a [2]rotaxane. (C) Cartoon representation illustrating the dynamic processes in the acid-/base-regulated switching of [2]rotaxanes depicted in (A). Reprinted with permission from Gschwind and coworkers [24].*

induced by altering the proportion of polar solvent in a binary solvent mixture. For example, when different amounts of DMSO are added to dichloromethane, solvent-driven shuttling modifications occur (**Figure 6C**). It was further found that the molecular wheel shuttling in deprotonated rotaxanes is hindered by the counter-cation held through electrostatic forces close to the anion at the axlecenter region. Thus, the shuttling speed can easily be regulated by addition of acids and bases enabling a fast- and a slow-motion mode parallel to the on-off switching function.

Cai and coworkers have a long-standing interest in the effects of solvents in the shuttling movements in mechanically interlocked compounds [25–27]. In 2012 they reported a [2]rotaxane molecular shuttle controlled by solvent. The rotaxane involved α-cyclodextrin (α-CD), dodecamethylene, and bipyridinium moieties as shown in **Figure 7** [26]. Cai et al. discovered that the molecular shuttling in this [2]rotaxane can be driven by both solvent and temperature changes. They indeed demonstrated the shuttling process of α-CD along the linear thread in solvents of different polarities such as DMSO and H2O. The energy barrier in water was shown to be 4.0 kcal/mol higher than in DMSO. Water interacts favorably with the bipyridinium moieties, however, negligibly with the alkyl chain, and this yields to a higher free energy barrier in the case of water.
