In supramolecular chemistry,[1] host–guest chemistry describes complexes that are composed of two or more molecules or ions that are held together in unique structural relationships by forces other than those of full covalent bonds. Host–guest chemistry encompasses the idea of molecular recognition and interactions through non-covalent bonding. Non-covalent bonding is critical in maintaining the 3D structure of large molecules, such as proteins and is involved in many biological processes in which large molecules bind specifically but transiently to one another.
Although non-covalent interactions could be roughly divided into those with more electrostatic or dispersive contributions, there are few commonly mentioned types of non-covalent interactions: ionic bonding, hydrogen bonding, van der Waals forces and hydrophobic interactions.[2]
Host-guest interaction has raised dramatical attention since it was discovered. It is an important field, because many biological processes require the host-guest interaction, and it can be useful in some material designs. There are several typical host molecules, such as, cyclodextrin, crown ether, et al.
Although van der Waals postulated the intermolecular interaction in 1873, in 1894, Fischer built a philosophical root for supramolecular chemistry. He pointed out that enzyme-protein interactions behave in a "lock-and-key" manner. This interaction is the foundation to host-guest chemistry. With the deeper understanding of the non-covalent interactions, for example, the clear elucidation of DNA structure, chemists started to emphasize the importance of non-covalent interactions. In 1967, Charles J. Pedersen discovered crown ethers, which are ring-like structures capable of chelating certain metal ions. Then, in 1969, Jean-Marie Lehn discovered a class of molecules similar to crown ethers, called cryptands. After that, Donald J. Cram synthesized many variations to crown ethers, on top of separate molecules capable of selective interaction with certain chemicals. The three scientists were awarded the Nobel Prize in Chemistry in 1987 for "development and use of molecules with structure-specific interactions of high selectivity”.[3] In 2016, Bernard L. Feringa, Sir J. Fraser Stoddart, and Jean-Pierre Sauvage were awarded the Nobel Prize in Chemistry, "for the design and synthesis of molecular machines".[4]
Supramolecular chemistry refers to the chemical systems that contains discrete number chemical components. The strengths of the systems vary from the intermolecular forces to covalent bindings. The researchers mentioned above created and enlarged the area of host-guest interaction, one of the most important concepts of the supramolecular chemistry fields. There are two significant components in the host-guest interaction. One is the "host molecules", which usually have "pore-like" structure that is able to capture some other molecules. The other one is the "guest molecules", which are generally smaller than the host molecules, and capable of binding the host molecules. The driving forces of the interaction might vary in different cases, such as hydrophobic effect, chelate effect, van der Waals force, et al.[5] Different bindings will provide variant properties for the materials, i.e., stimuli-responsiveness, self-healing, matrix rigidification. As a consequence, the host-guest interaction can be applied for self-healing materials, stimuli-responsive materials, room-temperature phosphorescence (RTP), improvement of mechanical properties, et al. The sizes of the host and guest molecules play an essential role in the interactions, and some typical examples of the host interactions will be discussed as follows.[5] [6] [7]
Host–guest chemistry is a branch of supramolecular chemistry in which a host molecule binds a so-called guest molecule or ion. The two components of the complex interact by non-covalent forces, most commonly by hydrogen-bonding. Binding between host and guest can be highly selective, in which case the interaction is called molecular recognition. Often, a dynamic equilibrium exist between the unbound and the bound states:
H+G\rightleftharpoons HG
H ="host", G ="guest", HG ="host–guest complex"
The "host" component is often the larger molecule, and it encloses the smaller, "guest", molecule. In biological systems, the analogous terms of host and guest are commonly referred to as enzyme and substrate respectively.[8]
Crown ethers are ring-like structures composed of several units of ethylene glycol. Because the radius of their pores are similar to that of alkali metal ions, crown ethers are well known for their ability to bind metallic ions. For example, 12-crown-4, 15-crown-5, 18-crown-6, 21-crown-7, and 24-crown-8 interact with potassium, sodium, ammonium, and calcium ions, respectively.[5] Among the aforementioned crown ethers, all the ions have the strongest binding affinity with 18-crown-6 because the size of 18-crown-6 most closely matches that of the ions. Besides ionic species, crown ethers can also bind to neutral molecules, e.g., 1, 2, 3- triazole. Crown ethers can also be threaded with long, linear molecules and/or polymers, giving rise to supramolecular structures called rotaxanes. Given that the crown ethers are not bound to the chains, they can move up and down the threading molecule.[7]
Cyclodextrin (CD) is composed of several glucose units and connects by ether bonds. There are three kinds of CDs, α-CD (6 units), β-CD (7 units), and γ-CD (8 units). The heights of the structure are all around 8 Å, while the cavity sizes of them are different, around 5, 6, and 8 Å, respectively. By comparing the size of the guest molecule and the CD, the binding behavior can be predicted. For instance, if the guest molecule is larger than the CD, it can be assumed that the binding will not occur. Typically, the α-CD can thread onto one PEG chain, while γ-CD can thread onto 2 PEG chains. β-CD can bind with thiophene-based molecule.[5]
The structure of cryptophanes contain 6 phenyl rings, mainly connected in 4 ways . Due to the phenyl groups and aliphatic chains, the cages inside cryptophanes are highly hydrophobic, suggesting the capability of capturing non-polar molecules. Based on this, cryptophanes can be employed to capture xenon in aqueous solution, which could be helpful in biological studies.[5]
One of the classic structures of resorcinarenes and pyrogallolarenes is shown below. Because of the phenol group, some hydrogen bonds are foromed among the molecules. Sometimes, the binding ratio of the host and guest could reach 2 : 1.[5]
Cucurbit[n]urils have similar size of γ-CD, which also behave similarly (e.g., 1 cucurbit[n]uril can thread onto 2 PEG chains).
The thermodynamics of the host and guest interaction can be assessed by NMR spectroscopy, UV/visible spectroscopy, and isothermal titration calorimetry.[9] Quantitative analysis of binding constant values provides useful thermodynamic information.[8]
\ominus | |
K | |
a |
\ominus | |
K | |
a |
=
\{HG\ | |
[HG]
[H]
[G]
\Gamma
In practice the equilibrium constant is usually defined in terms of concentrations.
Ka=
[HG] | |
[H][G] |
KA
\DeltaG\ominus
\DeltaG\ominus=-RTln{K}
\Gamma
\Gamma
A Large
Ka
See main article: Determination of equilibrium constants.
When the host and guest molecules combine to form a single complex, the equilibrium is represented as
H+G\leftrightharpoonsHG
K= | [HG] |
[H][G] |
TH=[H]+K[H][G]
TG=[G]+K[H][G]
TG
TH
[H]=TH-TG+[G]
[HG]=K[H][G]
calc | |
X | |
i |
obs | |
X | |
i |
U=\sumi=1,np
obs | |
(X | |
i |
2 | |
-X | |
i) |
This procedure is applicable to 1:1 adducts.
With nuclear magnetic resonance (NMR) spectra the observed chemical shift value,, arising from a given atom contained in a reagent molecule and one or more complexes of that reagent, will be the concentration-weighted average of all shifts of those chemical species. Chemical exchange is assumed to be rapid on the NMR time-scale. terms of mole fractions,
\bar\delta=\sumxi\deltai
\deltai
xi
xi=
ci | |
\sumjcj |
It is assumed that the absorbance of each species is proportional to the concentration of that species, according to the Beer–Lambert law.
Aλ=
N | |
\ell\sum | |
i=1 |
\varepsiloni,λci
where λ is a wavelength,
\ell
\varepsiloni,λ
The treatment of this type of data is similar to the treatment of absorbance data. In fact the equation defining the relation between fluorescent intensity and species' concentrations is very similar.
Iλ=
N | |
\sum | |
i=1 |
\varphii,λci
\varphii,λ
The heat evolved when an aliquot of host solution is added to a solution containing the guest is the sum of contributions from each reaction
Qj=\sum
N | |
i=1 |
\Delta
\ominus | |
H | |
i |
x \deltani,j
Qj
\Delta
\ominus | |
H | |
i |
\deltani,j
\deltan
Isothermal titration calorimetry is commonly used to determine the values of both an equilibrium constant and the corresponding standard reaction enthalpy. The manufactures of ITC instruments supply some software with which these quantities may be obtained from experimental data values.
For each equilibrium involving a host, H, and a guest G
pH+qG\leftrightharpoonsHpGq
\betapq
\betapq=
[HpGq] | |
[H]p[G]q |
[H]
[G]
TH=[H]+\sump\betapq[H]p[G]q
TG=[G]+\sumq\betapq[H]p[G]q
[HpGq]=\betapq[H]p[G]q
The binding process is reversible, indicating that the associate constant (ka) is not far larger than disassociate constant (kd). Combing the rate of the reaction, ka, kd, concentration, and time, the relation of the free guest molecule and time can be calculated.[10] By calculating the integration of UV spectrum or NMR,[11] the concentration as a function of time curve can be obtained.
In cooperativity, the initial ligand binding affects the host's affinity for subsequent ligands. In positive cooperativity, the first binding event enhances the affinity of the host for another ligand. Examples of positive and negative cooperativity are hemoglobin and aspartate receptor, respectively.[12] The thermodynamic properties of cooperativity have been studied in order to define mathematical parameters that distinguish positive or negative cooperativity. The traditional Gibbs free energy equation states:
\DeltaG=\DeltaH-T\DeltaS
\Delta
\circ | |
G | |
S |
=\Delta
\circ | |
G | |
A |
+\Delta
\circ | |
G | |
B |
-\Delta
\circ | |
G | |
AB |
\Delta
\circ | |
H | |
S |
=\Delta
\circ | |
H | |
A |
+\Delta
\circ | |
H | |
B |
-\Delta
\circ | |
H | |
AB |
T\Delta
\circ | |
G | |
S |
=T\Delta
\circ | |
H | |
A |
+T\Delta
\circ | |
H | |
B |
-T\Delta
\circ | |
S | |
AB |
\Delta
\circ | |
G | |
A |
\Delta
\circ | |
G | |
B |
\Delta
\circ | |
G | |
S |
\Delta
\circ | |
G | |
AB |
It is considered that if
\Delta
\circ | |
G | |
S |
\Delta
\circ | |
G | |
A |
\Delta
\circ | |
G | |
B |
\Delta
\circ | |
G | |
S |
Because of the non-covalent host-guest interaction, the polymer backbone can have enough flexibility to diffuse. If a crack exists in the materials, after compressing the two materials around the crack, because of the fast exchange of the host-guest molecular structure, the crack will rejoin again revealing good self-healing properties. Harada et al reported a self-healing hydrogel constructed by vinyl-group-modified cyclodextrin and adamantane.[16] Another strategy is to use the interaction between the polymer backbone and host molecule (host molecule threading onto the polymer). If the threading process is fast enough, self-healing can also be achieved.
Generally, it is not easy to achieve pure organic phosphorescence, partly because of the instability of the triplet state (easily be quenched by moisture, oxygen, etc). Host-guest structures can provide a rigid matrix, which protects the triplet state from being quenched. In this circumstance, α-CD and CB could be used,[17] [18] in which the phosphor is served as a guest to interact with the host. For example, 4-phenylpyridium derivatives interacted with CB, and copolymerize with acrylamide. The resulting polymer yielded ~2 s of phosphorescence lifetime. Additionally, Zhu et al used crown ether and potassium ion to modify the polymer, and enhance the emission of phosphorescence.[19]
Some guest molecules are charged compounds, which might be oxidized or reduced by certain chemicals. This type of guest molecule can present redox responsiveness. Some host molecules (i.e., α-CD) or guest molecules (i.e., tetra ammonium ion) are pH-sensitive, different pH can result in different species, which significantly influences the binding behavior, giving the material pH responsive properties. Some guest molecules may change their configurations under different lights, which makes the material photo-responsive.[20] Cai et al employed a halogen bond to prepare a host-guest system, and the materials are heat- and mechano-responsive with long persistent emission.[21]
An encryption system constructed by pillar[5]arene, spiropyran and pentanenitrile (free state and grafted to polymer) was constructed by Wang et al. After UV irradiation, spiropyran would transform into merocyanine. When the visible light was shined on the material, the merocyanine close to the pillar[5]arene-free pentanenitrile complex had faster transformation to spiropyran; on the contrary, the one close to pillar[5]arene-grafted pentanenitrile complex has much slower transformation rate. This spiropyran-merocyanine transformation can be used for message encryption.[22] Another strategy is based on the metallacages and polycyclic aromatic hydrocarbons.[23] Because of the fluorescnece emission differences between the complex and the cages, the information could be encrypted.
Although some host-guest interactions are not strong, increasing the amount of the host-guest interaction can improve the mechanical properties of the materials. As an example, threading the host molecules onto the polymer is one of the commonly used strategies for increasing the mechanical properties of the polymer. It takes time for the host molecules to de-thread from the polymer, which can be a way of energy dissipation.[16] [24] [25] Another method is to use the slow exchange host-guest interaction. Though the slow exchange improves the mechanical properties, simultaneously, self-healing properties will be sacrificed.[26]
Traditionally, chemical sensing has been approached with a system that contains a covalently bound indicator to a receptor though a linker. Once the analyte binds, the indicator changes color or fluoresces. This technique is called the indicator-spacer-receptor approach (ISR).[27] In contrast to ISR, indicator-displacement assay (IDA) utilizes a non-covalent interaction between a receptor (the host), indicator, and an analyte (the guest). Similar to ISR, IDA also utilizes colorimetric (C-IDA) and fluorescence (F-IDA) indicators. In an IDA assay, a receptor is incubated with the indicator. When the analyte is added to the mixture, the indicator is released to the environment. Once the indicator is released it either changes color (C-IDA) or fluoresces (F-IDA).[28]
IDA offers several advantages versus the traditional ISR chemical sensing approach. First, it does not require the indicator to be covalently bound to the receptor. Secondly, since there is no covalent bond, various indicators can be used with the same receptor. Lastly, the media in which the assay may be used is diverse.[29]
Chemical sensing techniques such as C-IDA have biological implications. For example, protamine is a coagulant that is routinely administered after cardiopulmonary surgery that counter acts the anti-coagulant activity of herapin. In order to quantify the protamine in plasma samples, a colorimetric displacement assay is used. Azure A dye is blue when it is unbound, but when it is bound to herapin, it shows a purple color. The binding between Azure A and heparin is weak and reversible. This allows protamine to displace Azure A. Once the dye is liberated it displays a purple color. The degree to which the dye is displaced is proportional to the amount of protamine in the plasma.[30]
F-IDA has been used by Kwalczykowski and co-workers to monitor the activities of helicase in E.coli. In this study they used thiazole orange as the indicator. The helicase unwinds the dsDNA to make ssDNA. The fluorescence intensity of thiazole orange has a greater affinity for dsDNA than ssDNA and its fluorescence intensity increases when it is bound to dsDNA than when it is unbound.[31] [32]
A crystalline solid has been traditionally viewed as a static entity where the movements of its atomic components are limited to its vibrational equilibrium. As seen by the transformation of graphite to diamond, solid to solid transformation can occur under physical or chemical pressure. It has been proposed that the transformation from one crystal arrangement to another occurs in a cooperative manner.[33] [34] Most of these studies have been focused in studying an organic or metal-organic framework.[35] [36] In addition to studies of macromolecular crystalline transformation, there are also studies of single-crystal molecules that can change their conformation in the presence of organic solvents. An organometallic complex has been shown to morph into various orientations depending on whether it is exposed to solvent vapors or not.[37]
Host guest systems have been utilized to remove hazardous materials from the environment. They can be made in different sizes and different shapes to trap a variety of chemical guests. One application is the ability of p-tert-butycalix[4]arene to trap a cesium ion. Cesium-137 is radioactive and there is a need to remove it from nuclear waste in an efficient manner. Host–guest chemistry has also been used to remove carcinogenic aromatic amines, and their N-nitroso derivatives from water. These waste materials are used in many industrial processes and found in a variety of products such as: pesticides, drugs, and cosmetics.[38] [39]