**2.1 General aspects**

One of the key roles of solvents which are dominant in supramolecular chemistry is their role in supramolecular recognition. This is essential for systems consisting of a host (Ho) and a guest (G) (**Figure 1**). In solution solvent molecules can interact with Ho and G molecules through various types of noncovalent weak interactions, and this process readily affects the mutual interactions between the Ho and G counterparts. Consequently, the thermodynamics of their binding can be significantly altered simply by changing solvents. The most dominant interactions in Ho-G-S system (where S is a solvent) can be electrostatic (i.e., ion-ion, ion-dipole, dipole-dipole, or dipole-induced dipole interactions), H-bonding, van der Waals, or π-π interactions. Inevitably, the type of developed interactions is influenced by the physicochemical properties of the Ho, G, and S molecules [9].

#### **Figure 1.**

*Illustration of the equilibrium of the binding between a solvated Ho (blue) and a solvated G (orange) molecule involving the release of solvent molecules (red).*

**209**

**Figure 2.**

*and coworkers [11].*

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

), enthalpy (Δ*H*<sup>ο</sup>

−T. Δ*S*<sup>o</sup>

described equilibrium by affecting the terms Δ*H*<sup>ο</sup>

= Δ*H*<sup>ο</sup>

aromatic solvent like benzene.

energy (Δ*G*<sup>o</sup>

*RT* ln*Ka* = Δ*G*<sup>o</sup>

From a thermodynamic perspective, the simple equilibrium of **Figure 1** is described by the equilibrium (association) constant which is connected to the thermodynamic activities of the Ho, G, and (Ho-G) species, i.e., *Ka* = *a*[Ho-G]/*a*[Ho]. *a*[G]. The association constant is in turn related to the changes in standard Gibbs free

), and entropy (Δ*S*<sup>o</sup>

and temperature, respectively. Solvents are capable of influencing the above-

to Supramolecular Complexation (SC), a general classification of solvents is based on their aptitude to undertake to self-organization. Self-organized (structured) solvents are in general relatively polar solvents, e.g., water, alcohols, amides, etc., whereas the nonstructured are generally less polar, e.g., hydrocarbons, haloalkanes, etc. One might assume that the importance of nonstructured solvents would be minor in supramolecular complexation due to the weaker interaction with the Ho and G molecules; the situation however is much different. Of course highly structured/polar solvents like water exhibit major effects on the complexation of Ho and G. Surprisingly though, dramatic differences in the stabilization of a (Ho-G) complex can be observed when shifting from a haloalkane like chloroform to an

The tremendous impact of solvent polarity on the supramolecular assembling is easily manifested through the following example by Nishimura and coworkers [11]. In their work by employing dynamic covalent chemistry, they managed to develop a complementary capsule-guest supramolecular system (**Figure 2**) behaving very

Specifically, the thermodynamics of the supramolecular recognition were different in these two solvents with *Ka* values differing by three orders of magnitude (Ka(C6D6)/Ka(CDCl3) = 1150). It was also found that the supramolecular recognition effect was in both solvent cases enthalpy driven. Yet, *ΔΗ*(kcal/mol) was determined to be −18.6 in deuterated benzene and −2.7 in deuterated chloroform which corresponds to a significant thermodynamic solvent effect. Interestingly, Kang and Rebek some years earlier designed and synthesized a dimeric supramolecular guest corresponding to various carboxylic acids such as 1-adamantanecarboxylic acid [12]. Working in the same two deuterated solvents, they discovered a reversed solvent effect (compared to that of Nishimura and coworkers). The supramolecular recognition effect in that case was found to be entropically favored with however two orders of magnitude difference in *Ka*: (*Ka*(CDCl3)/*Ka*(C6D6) = 243). Through these stimulating examples, it is easily made understood that solvents have a drastic effect

*Supramolecular assembly exploiting dynamic covalent chemistry. Reprinted with permission from Nishimura* 

differently in two deuterated solvents of interest: CDCl3 and C6D6.

on supramolecular binding/recognition effects [9].

) upon binding of G to Ho, i.e.,

[9, 10]. When it comes

, where R and *T* correspond to the ideal gas constant

and Δ*S*<sup>o</sup>

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

*Solvents, Ionic Liquids and Solvent Effects*

**2. Supramolecular recognition**

*involving the release of solvent molecules (red).*

**2.1 General aspects**

molecular-engineered compounds, whereby complexes are formed from small molecular building blocks held together by reversible intermolecular noncovalent interactions such as van der Waals interactions, hydrogen bonding, electrostatic, π-π stacking, and hydrophobic interactions. Their design, control, and function compose new relevant interdisciplinary key enabling areas (KEA) of science and technology. In all these solvents and solvation are demonstrating a fundamentally important role. Ordinarily, solvents are categorized into two main categories cited as polar and nonpolar, whereby their efficacy is often characterized by their dielectric constants. Solvents with a dielectric constant of less than 15 are usually regarded to be nonpolar. Nonpolar solvents contain bonds between atoms with similar electronegativities, such as carbon and hydrogen. Polar solvents have large dipole moments and they comprise bonds between atoms with very different electronegativities, such as oxygen and hydrogen. The aforementioned solvents are additionally divided into polar aprotic and polar protic. The solvation efficacy in a predefined medium pays a key role in thermodynamics and kinetics especially in supramolecular host-guest interactions. This is profoundly correlated to changes in solubility, stability constant, reactivity, redox potential, and some spectral parameters. Host-guest association behaviors can essentially be controlled only by applying diverse solvent system, thus altering by demand their solvation properties. Hence, the solvation environment plays a dynamic role for supramolecular solutes, being able thus to affect the thermodynamics of complex systems. In general, the interactions involved in supramolecular systems are quite weaker than covalent bonds, and thus they can be highly controlled and reversible. Acknowledging the importance of the above, this chapter

discusses the impact of solvents in various types of supramolecular systems.

One of the key roles of solvents which are dominant in supramolecular chem-

*Illustration of the equilibrium of the binding between a solvated Ho (blue) and a solvated G (orange) molecule* 

istry is their role in supramolecular recognition. This is essential for systems consisting of a host (Ho) and a guest (G) (**Figure 1**). In solution solvent molecules can interact with Ho and G molecules through various types of noncovalent weak interactions, and this process readily affects the mutual interactions between the Ho and G counterparts. Consequently, the thermodynamics of their binding can be significantly altered simply by changing solvents. The most dominant interactions in Ho-G-S system (where S is a solvent) can be electrostatic (i.e., ion-ion, ion-dipole, dipole-dipole, or dipole-induced dipole interactions), H-bonding, van der Waals, or π-π interactions. Inevitably, the type of developed interactions is influenced by the

physicochemical properties of the Ho, G, and S molecules [9].

**208**

**Figure 1.**

From a thermodynamic perspective, the simple equilibrium of **Figure 1** is described by the equilibrium (association) constant which is connected to the thermodynamic activities of the Ho, G, and (Ho-G) species, i.e., *Ka* = *a*[Ho-G]/*a*[Ho]. *a*[G]. The association constant is in turn related to the changes in standard Gibbs free energy (Δ*G*<sup>o</sup> ), enthalpy (Δ*H*<sup>ο</sup> ), and entropy (Δ*S*<sup>o</sup> ) upon binding of G to Ho, i.e., *RT* ln*Ka* = Δ*G*<sup>o</sup> = Δ*H*<sup>ο</sup> −T. Δ*S*<sup>o</sup> , where R and *T* correspond to the ideal gas constant and temperature, respectively. Solvents are capable of influencing the abovedescribed equilibrium by affecting the terms Δ*H*<sup>ο</sup> and Δ*S*<sup>o</sup> [9, 10]. When it comes to Supramolecular Complexation (SC), a general classification of solvents is based on their aptitude to undertake to self-organization. Self-organized (structured) solvents are in general relatively polar solvents, e.g., water, alcohols, amides, etc., whereas the nonstructured are generally less polar, e.g., hydrocarbons, haloalkanes, etc. One might assume that the importance of nonstructured solvents would be minor in supramolecular complexation due to the weaker interaction with the Ho and G molecules; the situation however is much different. Of course highly structured/polar solvents like water exhibit major effects on the complexation of Ho and G. Surprisingly though, dramatic differences in the stabilization of a (Ho-G) complex can be observed when shifting from a haloalkane like chloroform to an aromatic solvent like benzene.

The tremendous impact of solvent polarity on the supramolecular assembling is easily manifested through the following example by Nishimura and coworkers [11]. In their work by employing dynamic covalent chemistry, they managed to develop a complementary capsule-guest supramolecular system (**Figure 2**) behaving very differently in two deuterated solvents of interest: CDCl3 and C6D6.

Specifically, the thermodynamics of the supramolecular recognition were different in these two solvents with *Ka* values differing by three orders of magnitude (Ka(C6D6)/Ka(CDCl3) = 1150). It was also found that the supramolecular recognition effect was in both solvent cases enthalpy driven. Yet, *ΔΗ*(kcal/mol) was determined to be −18.6 in deuterated benzene and −2.7 in deuterated chloroform which corresponds to a significant thermodynamic solvent effect. Interestingly, Kang and Rebek some years earlier designed and synthesized a dimeric supramolecular guest corresponding to various carboxylic acids such as 1-adamantanecarboxylic acid [12]. Working in the same two deuterated solvents, they discovered a reversed solvent effect (compared to that of Nishimura and coworkers). The supramolecular recognition effect in that case was found to be entropically favored with however two orders of magnitude difference in *Ka*: (*Ka*(CDCl3)/*Ka*(C6D6) = 243). Through these stimulating examples, it is easily made understood that solvents have a drastic effect on supramolecular binding/recognition effects [9].

#### **Figure 2.**

*Supramolecular assembly exploiting dynamic covalent chemistry. Reprinted with permission from Nishimura and coworkers [11].*

Large solvent effects are also encountered in supramolecular complexation (SC) involving ionic and neutral, e.g., hydrophobic, entities. These effects are largely dependent of the nature of the target guest molecule for a given host molecule. Noteworthy, ionic and neutral SC often exhibits opposite solvent polarity dependencies. Two characteristic such examples are the SC of aromatic hydrophobic molecules by a cyclophanes and that of potassium ions by the crown ether 18-crown-6. For instance, Smithrud and Diederich observed five orders of magnitude higher association constant in water compared to the solvent carbon disulfide for a cyclophane/ pyrene SC system [13]. The hydrophobic 3D cyclophane developed by Smithrud and Diederich involved a large cavity accessible to solvent molecules, and the huge *Ka* determined in water was attributed to the solvophobic effect. In simple words pyrene prefers to be encapsulated in the hydrophobic cavity of the cyclophane instead of interacting with water. The effect becomes less and less important as one moves from water to apolar solvents [13]. The opposite effect is observed for the SC of potassium ions by ether 18-crown-6 [14]. In that case the association constant becomes larger in solvents of lower polarity, e.g., log*Ka* (H2O) = 2.0, whereas logKa (acetone) = 6.0 [14]. Interestingly, the log*Ka* exhibits a linear dependence to the surface tension of the medium as well as to other parameters/properties of solvents [15, 16].

The above-described examples are fundamental for the development of complex supramolecular systems with possibilities of external control and the design of molecular machines. Focus of the next section is the effect of solvents on some characteristic molecular machines and switches.
