In
supramolecular chemistry
Supramolecular chemistry refers to the branch of chemistry concerning Chemical species, chemical systems composed of a integer, discrete number of molecules. The strength of the forces responsible for spatial organization of the system range from w ...
, host–guest chemistry describes
complexes that are composed of two or more
molecule
A molecule is a group of two or more atoms that are held together by Force, attractive forces known as chemical bonds; depending on context, the term may or may not include ions that satisfy this criterion. In quantum physics, organic chemi ...
s or
ion
An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by convent ...
s that are held together in unique structural relationships by forces other than those of full
covalent bond
A covalent bond is a chemical bond that involves the sharing of electrons to form electron pairs between atoms. These electron pairs are known as shared pairs or bonding pairs. The stable balance of attractive and repulsive forces between atom ...
s. 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
Ionic bonding is a type of chemical bonding that involves the Coulomb's law, electrostatic attraction between oppositely charged ions, or between two atoms with sharply different electronegativities, and is the primary interaction occurring in io ...
,
hydrogen bond
In chemistry, a hydrogen bond (H-bond) is a specific type of molecular interaction that exhibits partial covalent character and cannot be described as a purely electrostatic force. It occurs when a hydrogen (H) atom, Covalent bond, covalently b ...
ing,
van der Waals forces
In molecular physics and chemistry, the van der Waals force (sometimes van der Waals' force) is a distance-dependent interaction between atoms or molecules. Unlike ionic or covalent bonds, these attractions do not result from a chemical ele ...
and
hydrophobic interactions
The hydrophobic effect is the observed tendency of nonpolar substances to aggregate in an aqueous solution and to be excluded by water. The word hydrophobic literally means "water-fearing", and it describes the segregation of water and nonpolar ...
.
Host-guest interaction has raised significant 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''.

"Host molecules" usually have "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 might 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
Supramolecular chemistry refers to the branch of chemistry concerning Chemical species, chemical systems composed of a integer, discrete number of molecules. The strength of the forces responsible for spatial organization of the system range from w ...
. Often, a
dynamic equilibrium
In chemistry, a dynamic equilibrium exists once a reversible reaction occurs. Substances initially transition between the reactants and products at different rates until the forward and backward reaction rates eventually equalize, meaning the ...
exists between the unbound and the bound states:
:
: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
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
and
substrate
Substrate may refer to:
Physical layers
*Substrate (biology), the natural environment in which an organism lives, or the surface or medium on which an organism grows or is attached
** Substrate (aquatic environment), the earthy material that exi ...
respectively.
Inclusion and clathrate compounds
Closely related to host–guest chemistry are inclusion compounds (also known as an inclusion complexes). Here, a
chemical complex in which one
chemical compound
A chemical compound is a chemical substance composed of many identical molecules (or molecular entities) containing atoms from more than one chemical element held together by chemical bonds. A molecule consisting of atoms of only one element ...
(the "host") has a cavity into which a "guest" compound can be accommodated. The interaction between the host and guest involves purely
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.
Yet another related class of compounds are
clathrate
A clathrate is a chemical substance consisting of a lattice (group), lattice that traps or contains molecules. The word ''clathrate'' is derived from the Latin language, Latin (), meaning 'with bars, Crystal structure, latticed'. Most clathrate ...
s, which often consist of a
lattice that traps or contains molecules.
[Atwood, J. L. (2012) "Inclusion Compounds" in ''Ullmann's Encyclopedia of Industrial Chemistry''. Wiley-VCH, Weinheim. ] The word ''clathrate'' is derived from the
Latin
Latin ( or ) is a classical language belonging to the Italic languages, Italic branch of the Indo-European languages. Latin was originally spoken by the Latins (Italic tribe), Latins in Latium (now known as Lazio), the lower Tiber area aroun ...
(), 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 (and host-guest chemistry in general) is that the guest behaves differently from the way it would when in solution. Guest molecules that would react by bimolecular pathways are often stabilized because they cannot combine with other reactants. The spectroscopic signatures of trapped guests are of fundamental interest. Compounds normally highly unstable in solution have been isolated at room temperature when molecularly encapsulated. Examples include
cyclobutadiene
Cyclobutadiene is an organic compound with the formula . It is very reactive owing to its tendency to dimerize. Although the parent compound has not been isolated, some substituted derivatives are robust and a single molecule of cyclobutadiene is ...
,
aryne
In organic chemistry, arynes and benzynes are a class of highly Reactivity (chemistry), reactive chemical Chemical species, species derived from an aromatic ring by removal of two substituents. Arynes are examples of didehydroarenes (1,2-didehydro ...
s or cycloheptatetraene. Large metalla-assemblies, known as
metallaprism Coordination cages are three-dimensional ordered structures in solution that act as hosts in host–guest chemistry. They are self-assembled in solution from organometallic precursors, and often rely solely on noncovalent interactions rather than co ...
s, 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 (abbreviated A-CO-B) 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 (isomers of A-CO-B).
Macrocyclic hosts
Organic hosts are occasionally called cavitands. The original definition proposed by
Cram
Cram may refer to:
* Cram (surname), a surname, and list of notable persons having the surname
* Cram.com, a website for creating and sharing flashcards
* ''Cram'' (Australian game show), a television show
* ''Cram'' (game show), a TV game show ...
includes many classes of molecules:
cyclodextrins
Cyclodextrins are a family of cyclic oligosaccharides, consisting of a macrocyclic ring of glucose subunits joined by α-1,4 glycosidic bonds. Cyclodextrins are produced from starch by enzymatic conversion. They are used in food, pharmaceuti ...
,
calixarene
A calixarene is a macrocycle or cyclic oligomer based on a methylene-linked phenols. With hydrophobic cavities that can hold smaller molecules or ions, calixarenes belong to the class of cavitands known in host–guest chemistry.
Nomenclature
...
s,
pillararenes and
cucurbituril
In host–guest chemistry, 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 ...
s.
Calixarenes
Calixarene
A calixarene is a macrocycle or cyclic oligomer based on a methylene-linked phenols. With hydrophobic cavities that can hold smaller molecules or ions, calixarenes belong to the class of cavitands known in host–guest chemistry.
Nomenclature
...
s and related formaldehyde-arene condensates (
resorcinarenes and
pyrogallolarenes) form a class of hosts that form inclusion compounds.
A related family of formaldehyde-derived oligomeric rings are
pillararenes (pillered arenes). One famous illustration of the stabilizing effect of host-guest complexation is the stabilization of
cyclobutadiene
Cyclobutadiene is an organic compound with the formula . It is very reactive owing to its tendency to dimerize. Although the parent compound has not been isolated, some substituted derivatives are robust and a single molecule of cyclobutadiene is ...
by such an organic host.
Cyclodextrins and cucurbiturils
Cyclodextrin
Cyclodextrins are a family of cyclic oligosaccharides, consisting of a macrocycle, macrocyclic ring of glucose subunits joined by α-1,4 glycosidic bonds. Cyclodextrins are produced from starch by enzyme, enzymatic conversion. They are used in ...
s (CDs) are tubular molecules composed of several glucose units connected by ether bonds. The three kinds of CDs, α-CD (6 units), β-CD (7 units), and γ-CD (8 units) 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 2 PEG chains. β-CD can bind with thiophene-based molecule.
Cyclodextrins are well established hosts for the formation of inclusion compounds. Illustrative is the case of
ferrocene
Ferrocene is an organometallic chemistry, organometallic compound with the formula . The molecule is a Cyclopentadienyl complex, complex consisting of two Cyclopentadienyl anion, cyclopentadienyl rings sandwiching a central iron atom. It is an o ...
which is inserted into the cyclodextrin at 100 °C under hydrothermal conditions.
Cucurbituril
In host–guest chemistry, 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 ...
s are
macrocyclic molecules made of
glycoluril ()
monomer
A monomer ( ; ''mono-'', "one" + '' -mer'', "part") is a molecule that can react together with other monomer molecules to form a larger polymer chain or two- or three-dimensional network in a process called polymerization.
Classification
Chemis ...
s linked by
methylene bridge
In chemistry, a methylene bridge is part of a molecule with formula . The carbon atom is connected by single bonds to two other distinct atoms in the rest of the molecule. A methylene bridge is often called a methylene group or simply methylene, ...
s (). The oxygen atoms are located along the edges of the band and are tilted inwards, forming a partly enclosed cavity (
cavitand). Cucurbit
rils have similar size of γ-CD, which also behave similarly (''e.g.'', 1 cucurbit
ril can thread onto 2 PEG chains).
Cryptophanes

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.
Crown ethers and cryptands
Crown ether
In organic chemistry, crown ethers are cyclic chemical compounds that consist of a ring containing several ether groups (). The most common crown ethers are cyclic oligomers of ethylene oxide, the repeating unit being ethyleneoxy, i.e., . Impor ...
s bind cations. Small crown ethers, e.g.
12-crown-4 bind well to small ions such as Li+ and large crowns, such as 24-crown-8 bind better to larger ions.
Beyond binding ionic guests, 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, giving rise to supramolecular structures called
rotaxane
A rotaxane () is a mechanically interlocked molecular architecture consisting of a dumbbell-shaped molecule which is threaded through a macrocycle (see graphical representation). The two components of a rotaxane are kinetically trapped since ...
s. 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 (and the corresponding complexes of
Cryptand
In chemistry, cryptands are a family of synthetic, bicyclic and polycyclic, multidentate ligands for a variety of cations. The Nobel Prize for Chemistry in 1987 was given to Donald J. Cram, Jean-Marie Lehn, and Charles J. Pedersen for ...
s) are not considered to be inclusion complexes since the guest is bound by forces stronger than van der Waals bonding.
Polymeric hosts
Zeolite
Zeolites are a group of several microporous, crystalline aluminosilicate minerals commonly used as commercial adsorbents and catalysts. They mainly consist of silicon, aluminium, oxygen, and have the general formula ・y where is either a meta ...
s have open framework structures with cavities in which guest species can reside.
Aluminosilicate
Aluminosilicate refers to materials containing anionic Si-O-Al linkages. Commonly, the associate cations are sodium (Na+), potassium (K+) and protons (H+). Such materials occur as minerals, coal combustion products and as synthetic materials, of ...
s being their composition, zeolites are rigid. Many structures are known, some of which are considerably useful as catalysts and for separations.
[
Silica clathrasil are compounds structurally similar to clathrate hydrates with a SiO2 framework and can be found in a range of marine sediment.
Clathrate compounds with formula ''A''8''B''16''X''30, where ''A'' is an ]alkaline earth metal
The alkaline earth metals are six chemical elements in group (periodic table), group 2 of the periodic table. They are beryllium (Be), magnesium (Mg), calcium (Ca), strontium (Sr), barium (Ba), and radium (Ra).. The elements have very similar p ...
, ''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
The thermal conductivity of a material is a measure of its ability to heat conduction, conduct heat. It is commonly denoted by k, \lambda, or \kappa and is measured in W·m−1·K−1.
Heat transfer occurs at a lower rate in materials of low ...
and high electrical conductivity is desired to produce the Seebeck Effect
The thermoelectric effect is the direct conversion of temperature differences to electric voltage and vice versa via a thermocouple. A thermoelectric device creates a voltage when there is a different temperature on each side. Conversely, when ...
. 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 In inorganic chemistry, Hofmann clathrates refers to materials with the formula Ni(CN)2(NH3)(C6H6). These materials are a type of coordination polymer that have properties of inclusion compounds. They have attracted attention because they can be ...
are coordination polymer
Coordination may refer to:
* Coordination (linguistics), a compound grammatical construction
* Coordination complex, consisting of a central atom or ion and a surrounding array of bound molecules or ions
** A chemical reaction to form a coordinat ...
s with the formula Ni(CN)4·Ni(NH3)2(arene). These materials crystallize with small aromatic guests (benzene, certain xylenes), and this selectivity has been exploited commercially for the separation of these hydrocarbons.[ Metal organic frameworks (MOFs) form clathrates.
]
Urea
Urea, also called carbamide (because it is a diamide of carbonic acid), is an organic compound with chemical formula . This amide has two Amine, amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest am ...
, a small molecule with the formula , has the peculiar property of crystallizing in open but rigid networks. The cost of efficient molecular packing is compensated by hydroge-bonding. Ribbons of hydrogen-bonded urea molecules form tunnel-like host into which many organic guests bind. Urea-clathrates have been well investigated for separations. Beyond urea, several other organic molecules form clathrates: thiourea
Thiourea () is an organosulfur compound with the formula and the structure . It is structurally similar to urea (), with the oxygen atom replaced by sulfur atom (as implied by the '' thio-'' prefix). The properties of urea and thiourea differ s ...
, hydroquinone
Hydroquinone, also known as benzene-1,4-diol or quinol, is an aromatic organic compound that is a type of phenol, a derivative of benzene, having the chemical formula C6H4(OH)2. It has two hydroxyl groups bonded to a benzene ring in a ''para' ...
, 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 (all activity coefficients are assumed to have a numerical values of 1).
The mass-balance equations, at any data point,
:
See also
* Cryptophane
Further reading
*
*
*
*
*
References
{{DEFAULTSORT:Host-guest chemistry
Supramolecular chemistry
Equilibrium chemistry