Host–guest chemistry

In supramolecular chemistry, 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.
Host–guest interaction has raised significant attention since it was discovered. Many biological processes and material designs require the host–guest interaction. There are several typical host molecules, such as, cyclodextrin, crown ether, et al..
"Host molecules" usually have a "pore-like" structure that is able to capture a "guest molecule." Although called molecules, hosts and guests are often ions. The driving forces of the interaction vary, such as hydrophobic effect and van der Waals forces.
Binding between host and guest can be highly selective, in which case the interaction is called molecular recognition. Often, a dynamic equilibrium exists between the unbound and the bound states:
The "host" component is often the larger molecule, and it encloses the smaller, "guest" molecule. In biological systems, the terms of host and guest are commonly referred to as enzyme and substrate respectively.

Inclusion and clathrate compounds

Closely related to host–guest chemistry are inclusion compounds. Here, a chemical complex in which one chemical compound has a cavity into which a "guest" compound can be accommodated. The interaction between the host and guest involves van der Waals bonding. The definition of inclusion compounds is very broad, extending to channels formed between molecules in a crystal lattice in which guest molecules can fit.
Another related class of compounds are clathrates, which often consist of a lattice that traps or contains molecules. The word clathrate is derived from the Latin , meaning 'with bars, latticed'.

Molecular encapsulation

Molecular encapsulation concerns the confinement of a guest within a larger host. In some cases, true host–guest reversibility is observed. In other cases, the encapsulated guest cannot escape.
An important implication of encapsulation is that the guest behaves differently than when in solution. Guest molecules that would react by bimolecular pathways are often stabilized because they cannot combine with other reactants. Compounds, like cyclobutadiene, arynes or cycloheptatetraene, that are normally highly unstable in solution have been isolated at room temperature when molecularly encapsulated. Large metalla-assemblies, known as metallaprisms, contain a conformationally flexible cavity that allows them to host a variety of guest molecules. These assemblies have shown promise as agents of drug delivery to cancer cells.
Encapsulation can control reactivity. For instance, excited state reactivity of free 1-phenyl-3-tolyl-2-proponanone yields products A-A, B-B, and AB, which result from decarbonylation followed by random recombination of radicals A• and B•. Whereas, the same substrate upon encapsulation reacts to yield the controlled recombination product A-B, and rearranged products.

Macrocyclic hosts

Organic hosts are occasionally called cavitands. The original definition proposed by Cram includes many classes of molecules: cyclodextrins, calixarenes, pillararenes and cucurbiturils.

Calixarenes

s and related formaldehyde-arene condensates form a class of hosts that form inclusion compounds. Pillararenes are a related family of formaldehyde-derived oligomeric rings. One famous illustration of the stabilizing effect of host–guest complexation is the stabilization of cyclobutadiene by such an organic host.

Cyclodextrins and cucurbiturils

s are tubular molecules composed of several glucose units connected by ether bonds. The three kinds of CDs--α-CD, β-CD, and γ-CD --differ in their cavity sizes: 5, 6, and 8 Å, respectively. α-CD can thread onto one PEG chain, while γ-CD can thread onto two PEG chains. β-CD can bind with thiophene-based molecules. Cyclodextrins are well established hosts for the formation of inclusion compounds. An example is when ferrocene is inserted into the cyclodextrin at 100°C under hydrothermal conditions.
Cucurbiturils are macrocyclic molecules made of glycoluril monomers, linked by methylene bridges. The oxygen atoms are located along the edges of the band and are tilted inwards, forming a partly enclosed cavity. Cucurbiturils have similar size of γ-CD, which also behave similarly.

Cryptophanes

The structure of cryptophanes contain six phenyl rings, mainly connected in four 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 to help biological studies.

Crown ethers and cryptands

s bind cations. Small crown ethers, e.g. 12-crown-4, bind well to small ions such as Li+. Large crowns, such as 24-crown-8, bind better to larger ions. Crown ethers also bind to some neutral molecules, e.g., 1, 2, 3- triazole. Crown ethers can also be threaded with slender linear molecules and/or polymers, creating supramolecular structures called rotaxanes. Given that the crown ethers are not bound to the chains, they can move up and down the threading molecule. Crown ether complexes of metal cations are not considered to be inclusion complexes, since the guest is bound by forces stronger than van der Waals bonding.

Chiral capsules

Molecular capsules have been developed with a chiral interiors. This capsule is made of two halves, like a plastic easter egg. Salt bridge interactions between the two halves cause them to self-assemble in solution. They are stable even when heated to 60 °C.

Polymeric hosts

s have open framework structures with cavities where guest species can reside. Zeolites are rigid due to Aluminosilicates being their composition. Many structures are known, some of which are used as catalysts and for separations.
Silica clathrasil are compounds that are structurally similar to clathrate hydrates with a SiO₂ framework and can be found in a range of marine sediments.
Clathrate compounds, with formula A₈B₁₆X₃₀, where A is an alkaline earth metal, B is a group III element, and X is an element from group IV, have been explored for thermoelectric devices. Thermoelectric materials follow a design strategy called the phonon glass electron crystal concept. Low thermal conductivity and high electrical conductivity is desired to produce the Seebeck Effect. When the guest and host framework are appropriately tuned, clathrates can exhibit low thermal conductivity, i.e., phonon glass behavior, while electrical conductivity through the host framework is undisturbed, allowing clathrates to exhibit electron crystal.
Hofmann clathrates are coordination polymers, with the formula Ni₄·Ni₂. These materials crystallize with small aromatic guests, and this selectivity has been commercially exploited for the separation of these hydrocarbons. Metal organic frameworks form clathrates.
Urea, a small molecule with the formula, has the property of crystallizing in open but rigid networks. The cost of efficient molecular packing is compensated by hydrogen-bonding. Ribbons of hydrogen-bonded urea molecules form a tunnel-like host into which many organic guests bind. Urea-clathrates have been well investigated for separations. Several other organic molecules form clathrates: thiourea, hydroquinone, and Dianin's compound.

Thermodynamics of host–guest interactions

When the host and guest molecules combine to form a single complex, the equilibrium is represented as
and the equilibrium constant, K, is defined as
where denotes the concentration of a chemical species X.
The mass-balance equations, at any data point,
where and represent the total concentrations, of host and guest, can be reduced to a single quadratic equation in, say, and so can be solved analytically for any given value of K. The concentrations and can then derived.
The next step in the calculation is to calculate the value,, of a quantity corresponding to the quantity observed. Then, a sum of squares, U, over all data points, np, can be defined as
and this can be minimized with respect to the stability constant value, K, and a parameter such as the chemical shift of the species HG or its molar absorbency. This procedure is applicable to 1:1 adducts.

Experimental techniques

With nuclear magnetic resonance 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.
Using UV-vis spectroscopy, the absorbance of each species is proportional to the concentration of that species, according to the Beer–Lambert law.
Where λ is a wavelength, is the optical path length of the cuvette which contains the solution of the N compounds,
is the molar absorbance of the ith chemical species at the wavelength λ, and c_i is its concentration. When the concentrations have been calculated and absorbance has been measured for samples with various concentrations of host and guest, the Beer–Lambert law provides a set of equations, at a given wavelength, that can be solved by a linear least-squares process for the unknown extinction coefficient values at that wavelength.
Host–guest structures can be probed by their luminescence. A rigid matrix protects emitters from being quenched, extending the lifetime of phosphorescence. In this circumstance, α-CD and CB can be used, in which the phosphor serves as a guest to interact with the host. For example, when 4-phenylpyridium derivatives interacted with CB, and copolymerized with acrylamide, the resulting polymer yielded ~2 s of phosphorescence lifetime. Additionally, Zhu et al. used crown ether and potassium ions to modify the polymer and enhance the emission of phosphorescence.
Another technique for evaluating host–guest interactions is calorimetry.