{{Short description|Supramolecular structures held together other than by covalent bonds}} {{copy edit|date=April 2025}} In supramolecular chemistry,<ref>{{cite book|last1=Steed|first1=Jonathan W.|last2=Atwood|first2=Jerry L.|title=Supramolecular Chemistry|date=2009|publisher=Wiley|isbn=978-0-470-51234-0|page=1002|edition=2nd.}}</ref> '''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 therefore encompasses the idea of molecular recognition and interactions through non-covalent bonding, which is critical in maintaining the three-dimensional 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 a few commonly mentioned types of non-covalent interactions: ionic bonding, hydrogen bonding, van der Waals forces and hydrophobic interactions.<ref name="Molecularcellbiology">{{cite book | title = Molecular Cell Biology | year = 2008 | isbn = 978-0-7167-7601-7 | author1 = Lodish, H.|author2 = Berk, A.| author3 = Kaiser, C.| publisher = Macmillan }}</ref>

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 and crown ether.

[[File:Cucurbit-6-uril ActaCrystallB-Stru 1984 382.jpg|thumbnail|200px|Crystal structure of a host–guest complex with a p-xylylenediammonium bound within a cucurbituril <ref>{{cite journal |last= Freeman |first= Wade A. |journal= Acta Crystallographica B |year= 1984 |pages= 382–387 |title= Structures of the ''p''-xylylenediammonium chloride and calcium hydrogensulfate adducts of the cavitand 'cucurbituril', C<sub>36</sub>H<sub>36</sub>N<sub>24</sub>O<sub>12</sub> |doi= 10.1107/S0108768184002354 |volume=40|issue= 4 |bibcode= 1984AcCrB..40..382F }}</ref>]]

[[File:Encapsulating Assembly ChemEurJ 1996 v2 p989.jpg|thumbnail|200px|A guest N<sub>2</sub> is bound within a host hydrogen-bonded capsule <ref>{{cite journal| last1=Valdés| first1=Carlos| last2=Toledo| first2=Leticia M.| last3=Spitz|first3=Urs|last4=Rebek|first4=Julius |title=Structure and Selectivity of a Small Dimeric Encapsulating Assembly |journal=Chem. Eur. J. |year=1996 |volume=2 | issue=8|pages=989–991 |doi=10.1002/chem.19960020814}}</ref>]]

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.<ref name=":05">{{Cite book |title=Comprehensive supramolecular chemistry II |date=2017 |others=J. L. Atwood, George W. Gokel, Leonard J. Barbour |isbn=978-0-12-803199-5 |location=Amsterdam, Netherlands |oclc=992802408}}</ref><ref>{{Cite journal |last=Stoddart |first=J. F. |date=1988 |title=Chapter 12. Host–guest chemistry |url=http://xlink.rsc.org/?DOI=OC9888500353 |journal=Annu. Rep. Prog. Chem., Sect. B: Org. Chem. |language=en |volume=85 |pages=353–386 |doi=10.1039/OC9888500353 |issn=0069-3030|url-access=subscription }}</ref><ref>{{Citation |last=Harada |first=Akira |title=Supramolecular Polymers (Host–Guest Interactions) |date=2013 |url=http://link.springer.com/10.1007/978-3-642-36199-9_54-1 |encyclopedia=Encyclopedia of Polymeric Nanomaterials |pages=1–5 |editor-last=Kobayashi |editor-first=Shiro |access-date=2023-02-15 |place=Berlin, Heidelberg |publisher=Springer Berlin Heidelberg |language=en |doi=10.1007/978-3-642-36199-9_54-1 |isbn=978-3-642-36199-9 |editor2-last=Müllen |editor2-first=Klaus|url-access=subscription }}</ref><ref name=":12">{{Cite journal |last1=Seale |first1=James S. W. |last2=Feng |first2=Yuanning |last3=Feng |first3=Liang |last4=Astumian |first4=R. Dean |last5=Stoddart |first5=J. Fraser |date=2022 |title=Polyrotaxanes and the pump paradigm |url=http://xlink.rsc.org/?DOI=D2CS00194B |journal=Chemical Society Reviews |language=en |volume=51 |issue=20 |pages=8450–8475 |doi=10.1039/D2CS00194B |pmid=36189715 |s2cid=252682455 |issn=0306-0012|url-access=subscription }}</ref>

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 stating:

<math display="block">H + G\ \rightleftharpoons\ HG</math>

where <math>H</math> denotes "host", <math>G</math> denotes "guest", and <math>HG</math> denotes "host–guest complex".

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.<ref name="textbook">{{cite book |last1=Anslyn |first1=Eric V. |title=Modern Physical Organic Chemistry |last2=Dougherty |first2=Dennis A. |publisher=MacMillan |year=2005 |isbn=978-1-891389-31-3}}</ref>

==Inclusion and clathrate compounds== [[File:Cd(CN)2CCl4.jpg|thumb|Cd(CN)<sub>2</sub>·CCl<sub>4</sub>: Cadmium cyanide clathrate framework (in blue) containing carbon tetrachloride (C atoms in gray and disordered Cl positions in green)]] Closely related to host–guest chemistry are inclusion compounds (also known as an inclusion complexes). Here, a chemical complex in which one chemical compound (the "host") 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. {{Quote box | title = IUPAC definition | quote = The IUPAC Gold Book defines an inclusion compound as a complex in which a host forms a cavity or lattice of channels that accommodates a guest species; the association is non-covalent and generally driven by van der Waals forces.<ref>{{cite web |title=inclusion compound (inclusion complex) |url=https://goldbook.iupac.org/html/I/I02998.html |website=IUPAC Gold Book |publisher=International Union of Pure and Applied Chemistry |access-date=20 May 2025}}</ref> | align = left | width = 30% }}

Another related class of compounds are clathrates, which often consist of a lattice that traps or contains molecules.<ref name=Ullmann>Atwood, J. L. (2012) "Inclusion Compounds" in ''Ullmann's Encyclopedia of Industrial Chemistry''. Wiley-VCH, Weinheim. {{doi| 10.1002/14356007.a14_119}}</ref> The word ''clathrate'' is derived from the Latin {{wikt-lang|la|clathratus}} ({{lang|la|clatratus}}), meaning 'with bars, latticed'.<ref>[http://lysy2.archives.nd.edu/cgi-bin/WORDS.EXE?clathrate Latin dictionary] {{webarchive|url=https://web.archive.org/web/20120414202654/http://lysy2.archives.nd.edu/cgi-bin/WORDS.EXE?clathrate |date=2012-04-14 }}</ref>

==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.<ref>{{cite book|title=The Encapsulation Phenomenon Synthesis, Reactivity and Applications of Caged Ions and Molecules|author= Yan Voloshin, Irina Belaya, Roland Krämer|year=2016|publisher=Springer|isbn=978-3-319-27738-7}}</ref> [[File:Nitrobenzene bound within hemicarcerand from Chemical Communications (1997).jpg|thumbnail|200px|Molecular encapsulation of a nitrobenzene bound within a hemicarcerand<ref>{{cite journal | journal = Chem. Commun. | year = 1997 | pages = 1303–1304 | title = Dissymmetric new hemicarcerands containing four bridges of different lengths |author1=Juyoung Yoon |author2=Carolyn B. Knobler |author3=Emily F. Maverick |author4=Donald J. Cram | doi = 10.1039/a701187c | issue = 14}}</ref>]]

An important implication of encapsulation (and host–guest chemistry in general) 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,<ref>Cram, D. J.; Tanner, M. E.; Thomas, R., ''The Taming of Cyclobutadiene'' Angewandte Chemie International Edition Volume 30, Issue 8, Pages 1024 - 1027 '''1991'''</ref> arynes or cycloheptatetraene, that are normally highly unstable in solution have been isolated at room temperature when molecularly encapsulated.<ref>{{cite journal |author=Dorothea Fiedler, Robert G. Bergman, Kenneth N. Raymond |year=2006 |title=Stabilization of Reactive Organometallic Intermediates Inside a Self-Assembled Nanoscale Host |journal=Angewandte Chemie International Edition |volume=45 |issue=5 |pages=745–748 |doi=10.1002/anie.200501938 |pmid=16370008}}</ref><ref>{{cite journal |author1=Fraser Hof |author2=Stephen L. Craig |author3=Colin Nuckolls |author4=Julius Rebek Jr. |date=May 3, 2002 |title=Molecular Encapsulation |journal=Angewandte Chemie International Edition |volume=41 |issue=9 |pages=1488–1508 |doi=10.1002/1521-3773(20020503)41:9<1488::AID-ANIE1488>3.0.CO;2-G |pmid=19750648}}</ref> 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 (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).<ref>{{Cite journal|last=Kaanumalle|first=Lakshmi S|date=Oct 20, 2004|title=Controlling Photochemistry with Distinct Hydrophobic Nanoenvironments.|url=https://pubs.acs.org/doi/10.1021/ja0450197|journal=J. Am. Chem. Soc. |volume=126|issue=44|pages=14366–14367|doi=10.1021/la203419y|pmid=15521751|url-access=subscription}}</ref>

== Macrocyclic hosts == Organic hosts are occasionally called cavitands. The original definition proposed by Cram includes many classes of molecules: cyclodextrins, calixarenes, pillararenes and cucurbiturils.<ref>{{cite book |last1=Cai |first1=X. |last2=Gibb |first2=B. C. |editor1-last=Atwood |editor1-first=Jerry |title=Comprehensive Supramolecular Chemistry II |date=2017 |publisher=Elsevier |isbn=978-0-12-803199-5 |pages=75–82 |chapter-url=https://www.sciencedirect.com/science/article/pii/B978012409547212582X |chapter=6.04 - Deep-Cavity Cavitands in Self-Assembly}}</ref>

===Calixarenes=== Calixarenes and related formaldehyde-arene condensates (resorcinarenes and pyrogallolarenes) form a class of hosts that form inclusion compounds.<ref name=":05"/><ref>{{cite book |last1=Wishard |first1=A. |last2=Gibb |first2=B.C. |title=Calixarenes and beyond |publisher=Springer |isbn=978-3-319-31867-7 |pages=195–234 |chapter=A chronology of cavitands|doi=10.1007/978-3-319-31867-7_9 |year=2016 }}</ref> Pillararenes (pillered arenes) 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.<ref name="Cram2003">{{cite journal|title=''The Taming of Cyclobutadiene'' Donald J. Cram, Martin E. Tanner, Robert Thomas|journal=Angewandte Chemie International Edition in English|volume=30|issue=8|pages=1024–1027|year=1991|doi=10.1002/anie.199110241|last1=Cram|first1=Donald J.|last2=Tanner|first2=Martin E.|last3=Thomas|first3=Robert}}</ref>

===Cyclodextrins and cucurbiturils=== [[File:Pillar5arene Feb2013.png|thumb|Chemical structure of pillar[5]arene]] Cyclodextrins (CDs) are tubular molecules composed of several glucose units connected by ether bonds. The three kinds of CDs--α-CD (six units), β-CD (seven units), and γ-CD (eight 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 two PEG chains. β-CD can bind with thiophene-based molecules.<ref name=":05"/> Cyclodextrins are well established hosts for the formation of inclusion compounds.{{ref|1}}{{ref|2}}{{ref|3}} An example is when ferrocene is inserted into the cyclodextrin at 100°C under hydrothermal conditions.<ref>{{cite journal|title=A unique tetramer of 4:5-cyclodextrin–ferrocene in the solid state|author1=Yu Liu |author2=Rui-Qin Zhong |author3=Heng-Yi Zhang |author4=Hai-Bin Song |journal=Chemical Communications|issue=17|year=2010|pages=2211–2213|doi=10.1039/B418220K|pmid=15856099}}</ref>

Cucurbiturils are macrocyclic molecules made of glycoluril ({{chem2|\dC4H2N4O2\d}}) monomers, linked by methylene bridges ({{chem2|\sCH2\s}}). The oxygen atoms are located along the edges of the band and are tilted inwards, forming a partly enclosed cavity (cavitand). Cucurbit[n]urils have similar size of γ-CD, which also behave similarly (''e.g.'', one cucurbit[n]uril can thread onto two PEG chains).<ref name=":05" />

=== Cryptophanes === [[File:Fig_2_Sample_of_some_macrocyclic_rings.png|thumb|359x359px|a) Structure of Cryptophanes. b) Structure of Resorcinarenes and Pyrogallolarenes. c) Structure of cucurbit[n]urils. Redrawn from source material.<ref name=":05"/>]] 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.<ref name=":05"/>

===Crown ethers and cryptands=== thumb|386x386px|a) Structure of 18-crown-6. b) Threading of crown ether and 1,2,3-triazole (rotaxane). Redrawn from source material. c) Inclusion of a-CD and polyethylene glycol (PEG) d) Threading of b-cyclodextrin and thiophene-based molecule. Redrawn from source material.<ref name=":05"/> Crown ethers 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.<ref name=":05"/> 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.<ref name=":12"/> Crown ether complexes of metal cations (and the corresponding complexes of cryptands) are not considered to be inclusion complexes, since the guest is bound by forces stronger than van der Waals bonding.

===Chiral capsules=== thumb|100px|left|The "egg shell" molecular capsulethumb|500px|'''Figure 7.''' Interlacing salt bridges that connect the two halves of the molecular capsule Molecular capsules have been developed with a chiral interiors.<ref name=capsule>{{cite journal | vauthors = Kuberski B, Szumna A | title = A self-assembled chiral capsule with polar interior | journal = Chemical Communications | issue = 15 | pages = 1959–61 | date = April 2009 | pmid = 19333456 | doi = 10.1039/b820990a }}</ref> This capsule is made of two halves, like a plastic easter egg (Figure 6). Salt bridge interactions between the two halves cause them to self-assemble in solution (Figure 7). They are stable even when heated to 60&nbsp;°C.

==Polymeric hosts== Zeolites 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.<ref name=Ullmann/>

Silica clathrasil are compounds that are structurally similar to clathrate hydrates with a SiO<sub>2</sub> framework and can be found in a range of marine sediments.<ref>{{Cite journal |last1=Momma |first1=Koichi |last2=Ikeda |first2=Takuji |last3=Nishikubo |first3=Katsumi |last4=Takahashi |first4=Naoki |last5=Honma |first5=Chibune |last6=Takada |first6=Masayuki |last7=Furukawa |first7=Yoshihiro |last8=Nagase |first8=Toshiro |last9=Kudoh |first9=Yasuhiro |date=September 2011 |title=New silica clathrate minerals that are isostructural with natural gas hydrates |journal=Nature Communications |language=en |volume=2 |issue=1 |page=196 |doi=10.1038/ncomms1196 |pmid=21326228 |bibcode=2011NatCo...2..196M |issn=2041-1723|doi-access=free }}</ref>

Clathrate compounds, with formula ''A''<sub>8</sub>''B''<sub>16</sub>''X''<sub>30</sub>, 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.<ref>{{Cite journal |last1=Nolas |first1=G. S. |last2=Cohn |first2=J. L. |last3=Slack |first3=G. A. |last4=Schujman |first4=S. B. |date=1998-07-13 |title=Semiconducting Ge clathrates: Promising candidates for thermoelectric applications |journal=Applied Physics Letters |language=en |volume=73 |issue=2 |pages=178–180 |doi=10.1063/1.121747 |bibcode=1998ApPhL..73..178N |issn=0003-6951|doi-access=free }}</ref><ref>{{cite journal | vauthors=((Beekman, M.)), ((Morelli, D. T.)), ((Nolas, G. S.)) | journal=Nature Materials | title=Better thermoelectrics through glass-like crystals | volume=14 | issue=12 | pages=1182–1185 | date=2015 | issn=1476-4660 | doi=10.1038/nmat4461| pmid=26585077 | bibcode=2015NatMa..14.1182B }}</ref> 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 Ni(CN)<sub>4</sub>·Ni(NH<sub>3</sub>)<sub>2</sub>(arene). These materials crystallize with small aromatic guests (benzene, certain xylenes), and this selectivity has been commercially exploited for the separation of these hydrocarbons.<ref name=Ullmann/> Metal organic frameworks (MOFs) form clathrates.

Urea, a small molecule with the formula {{chem2|O\dC(NH2)2}}, 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.<ref name="Worsch 2002">{{cite book | date=2002 | last1=Worsch | first1=Detlev | last2=Vögtle | first2=Fritz | title=Topics in Current Chemistry | chapter=Separation of enantiomers by clathrate formation | publisher=Springer-Verlag | isbn=3-540-17307-2 | doi=10.1007/bfb0003835 | pages=21–41}}</ref> Several other organic molecules form clathrates: thiourea, hydroquinone, and Dianin's compound.<ref name=Ullmann/>

==Thermodynamics of host–guest interactions== {{main| Determination of equilibrium constants}}

When the host and guest molecules combine to form a single complex, the equilibrium is represented as <math display="block">H + G \leftrightharpoons HG</math> and the equilibrium constant, <math>K</math>, is defined as <math display="block">K=\frac{[HG]}{[H] [G]}</math> where <math>[X]</math> denotes the concentration of a chemical species <math>X</math> (all activity coefficients are assumed to have a numerical values of 1). The mass-balance equations, at any data point, <math display="block">T_H = [H] + K [H] [G]</math> <math display="block">T_G = [G] + K [H] [G]</math> where <math>T_G</math> and <math>T_H</math> represent the total concentrations, of host and guest, can be reduced to a single quadratic equation in, say, <math>[G]</math> and so can be solved analytically for any given value of <math>K</math>. The concentrations <math>[H]</math> and <math>[HG]</math> can then derived. <math display="block">[H] = T_H - T_G + [G]</math> <math display="block">[HG] = K [H] [G]</math> The next step in the calculation is to calculate the value, <math>X^{calc}_i</math>, of a quantity corresponding to the quantity observed <math>X^{obs}_i</math>. Then, a sum of squares, <math>U</math>, over all data points, <math>np</math>, can be defined as <math display=block>U=\sum_{i=1,np} (X^{obs}_i -X^{calc}_i)^2</math> and this can be minimized with respect to the stability constant value, <math>K</math>, and a parameter such as the chemical shift of the species <math>HG</math> (nmr data) or its molar absorbency (uv/vis data). This procedure is applicable to 1:1 adducts.

===Experimental techniques=== thumb|right|300px|Set of NMR spectra from a host–guest titration thumb|240px|right|Typical ultraviolet–visible spectra for a host–guest system With nuclear magnetic resonance (NMR) spectra, the observed chemical shift value, {{mvar|{{overbar|δ}}}}, 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.

<math display="block">A_\lambda = \ell\sum_{i = 1}^N \varepsilon_{i,\lambda} c_i</math>

Where <math>\lambda</math> is a wavelength, <math>\ell</math> is the optical path length of the cuvette which contains the solution of the ''N'' compounds (chromophores), <math>\varepsilon_{i,\lambda} </math> is the molar absorbance (also known as the extinction coefficient) of the ''i''th chemical species at the wavelength <math>\lambda</math>, and <math>c_i</math> 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.<ref>{{Cite journal |last1=Dai |first1=Wenbo |last2=Niu |first2=Xiaowei |last3=Wu |first3=Xinghui |last4=Ren |first4=Yue |last5=Zhang |first5=Yongfeng |last6=Li |first6=Gengchen |last7=Su |first7=Han |last8=Lei |first8=Yunxiang |last9=Xiao |first9=Jiawen |last10=Shi |first10=Jianbing |last11=Tong |first11=Bin |last12=Cai |first12=Zhengxu |last13=Dong |first13=Yuping |date=2022-03-21 |title=Halogen Bonding: A New Platform for Achieving Multi-Stimuli-Responsive Persistent Phosphorescence |url=https://onlinelibrary.wiley.com/doi/10.1002/anie.202200236 |journal=Angewandte Chemie International Edition |language=en |volume=61 |issue=13 |article-number=e202200236 |doi=10.1002/anie.202200236 |pmid=35102661 |s2cid=246443916 |issn=1433-7851|url-access=subscription }}</ref> In this circumstance, α-CD and CB can be used,<ref>{{Cite journal |last1=Yan |first1=Xi |last2=Peng |first2=Hao |last3=Xiang |first3=Yuan |last4=Wang |first4=Juan |last5=Yu |first5=Lan |last6=Tao |first6=Ye |last7=Li |first7=Huanhuan |last8=Huang |first8=Wei |last9=Chen |first9=Runfeng |date=January 2022 |title=Recent Advances on Host–Guest Material Systems toward Organic Room Temperature Phosphorescence |url=https://onlinelibrary.wiley.com/doi/10.1002/smll.202104073 |journal=Small |language=en |volume=18 |issue=1 |article-number=2104073 |doi=10.1002/smll.202104073 |pmid=34725921 |s2cid=240421091 |issn=1613-6810|url-access=subscription }}</ref><ref>{{Cite journal |last1=Xu |first1=Wen-Wen |last2=Chen |first2=Yong |last3=Lu |first3=Yi-Lin |last4=Qin |first4=Yue-Xiu |last5=Zhang |first5=Hui |last6=Xu |first6=Xiufang |last7=Liu |first7=Yu |date=February 2022 |title=Tunable Second-Level Room-Temperature Phosphorescence of Solid Supramolecules between Acrylamide–Phenylpyridium Copolymers and Cucurbit[7]uril |url=https://onlinelibrary.wiley.com/doi/10.1002/anie.202115265 |journal=Angewandte Chemie International Edition |language=en |volume=61 |issue=6 |article-number=e202115265 |doi=10.1002/anie.202115265 |pmid=34874598 |s2cid=244922727 |issn=1433-7851|url-access=subscription }}</ref> 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.<ref>{{Cite journal |last1=Zhu |first1=Weijie |last2=Xing |first2=Hao |last3=Li |first3=Errui |last4=Zhu |first4=Huangtianzhi |last5=Huang |first5=Feihe |date=2022-11-08 |title=Room-Temperature Phosphorescence in the Amorphous State Enhanced by Copolymerization and Host–Guest Complexation |url=https://pubs.acs.org/doi/10.1021/acs.macromol.2c00680 |journal=Macromolecules |language=en |volume=55 |issue=21 |pages=9802–9809 |doi=10.1021/acs.macromol.2c00680 |bibcode=2022MaMol..55.9802Z |s2cid=253051272 |issn=0024-9297|url-access=subscription }}</ref>

Another technique for evaluating host–guest interactions is calorimetry.

==Aspiration applications== Host guest complexation is pervasive in biochemistry. Many protein hosts recognize and hence selectively bind other biomolecules. When the protein host is an enzyme, the guests are called substrates.

=== Self-healing === thumb|308x308px|Self-healing mechanism of host–guest interaction by a) using host–small-guest molecule and b) host–polymer. Redrawn from source material.<ref name=":3">{{Cite journal |last1=Ikura |first1=Ryohei |last2=Park |first2=Junsu |last3=Osaki |first3=Motofumi |last4=Yamaguchi |first4=Hiroyasu |last5=Harada |first5=Akira |last6=Takashima |first6=Yoshinori |date=December 2022 |title=Design of self-healing and self-restoring materials utilizing reversible and movable crosslinks |journal=NPG Asia Materials |language=en |volume=14 |issue=1 |page=10 |doi=10.1038/s41427-021-00349-1 |bibcode=2022npjAM..14...10I |issn=1884-4049|doi-access=free }}</ref><ref name=":4">{{Cite journal |last1=Xie |first1=Jing |last2=Yu |first2=Peng |last3=Wang |first3=Zhanhua |last4=Li |first4=Jianshu |date=2022-03-14 |title=Recent Advances of Self-Healing Polymer Materials via Supramolecular Forces for Biomedical Applications |url=https://pubs.acs.org/doi/10.1021/acs.biomac.1c01647 |journal=Biomacromolecules |language=en |volume=23 |issue=3 |pages=641–660 |doi=10.1021/acs.biomac.1c01647 |pmid=35199999 |s2cid=247082155 |issn=1525-7797|url-access=subscription }}</ref> A self-healing hydrogel can be constructed from modified cyclodextrin and adamantane.<ref name=":3" /><ref name="Park 2002008">{{Cite journal |last1=Park |first1=Junsu |last2=Murayama |first2=Shunsuke |last3=Osaki |first3=Motofumi |last4=Yamaguchi |first4=Hiroyasu |last5=Harada |first5=Akira |last6=Matsuba |first6=Go |last7=Takashima |first7=Yoshinori |date=October 2020 |title=Extremely Rapid Self-Healable and Recyclable Supramolecular Materials through Planetary Ball Milling and Host–Guest Interactions |url=https://onlinelibrary.wiley.com/doi/10.1002/adma.202002008 |journal=Advanced Materials |language=en |volume=32 |issue=39 |article-number=2002008 |doi=10.1002/adma.202002008 |pmid=32844527 |bibcode=2020AdM....3202008P |s2cid=221326154 |issn=0935-9648|url-access=subscription }}</ref> 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.<ref name=":4" />

===Encapsulation and release: fragrances and drugs=== Cyclodextrin forms inclusion compounds with fragrances which are more stable towards exposure to light and air. When incorporated into textiles, the fragrance lasts much longer due to the slow-release action.<ref>{{cite journal|title=Fragrance-release Property of β-Cyclodextrin Inclusion Compounds and their Application in Aromatherapy |first1=C. X. |last1=Wang |first2=Sh. L. |last2=Chen |journal=Journal of Industrial Textiles|volume=34|pages=157–166|year=2005|issue=3 |doi=10.1177/1528083705049050|s2cid=95538902 }}</ref>

Photolytically sensitive caged compounds have been examined as containers for releasing drugs or reagents.<ref>{{cite journal|last=Ellis-Davies|first=Graham C. R.|title=Caged compounds: Photorelease technology for control of cellular chemistry and physiology|journal=Nature Methods|year=2007|doi=10.1038/nmeth1072|pmid=17664946|volume=4|issue=8|pages=619–628|pmc=4207253}}</ref><ref>{{Cite journal |last1=Blanco-Gómez |first1=Arturo |last2=Cortón |first2=Pablo |last3=Barravecchia |first3=Liliana |last4=Neira |first4=Iago |last5=Pazos |first5=Elena |last6=Peinador |first6=Carlos |last7=García |first7=Marcos D. |date=2020 |title=Controlled binding of organic guests by stimuli-responsive macrocycles |url=http://xlink.rsc.org/?DOI=D0CS00109K |journal=Chemical Society Reviews |language=en |volume=49 |issue=12 |pages=3834–3862 |doi=10.1039/D0CS00109K |pmid=32395726 |issn=0306-0012|hdl=2183/31671 |s2cid=218599759 |hdl-access=free }}</ref>

=== Encryption === An encryption system constructed by pillar[5]arene, spiropyran and pentanenitrile (free state and grafted to polymer) was created by Wang ''et al.''. After UV irradiation, spiropyran transforms into merocyanine. When 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.<ref>{{Cite journal |last1=Ju |first1=Huaqiang |last2=Zhu |first2=Chao Nan |last3=Wang |first3=Hu |last4=Page |first4=Zachariah A. |last5=Wu |first5=Zi Liang |last6=Sessler |first6=Jonathan L. |last7=Huang |first7=Feihe |date=February 2022 |title=Paper without a Trail: Time-Dependent Encryption using Pillar[5]arene-Based Host–Guest Invisible Ink |url=https://onlinelibrary.wiley.com/doi/10.1002/adma.202108163 |journal=Advanced Materials |language=en |volume=34 |issue=6 |article-number=2108163 |doi=10.1002/adma.202108163 |pmid=34802162 |bibcode=2022AdM....3408163J |s2cid=244482426 |issn=0935-9648|url-access=subscription }}</ref> Another strategy is based on the metallacages and polycyclic aromatic hydrocarbons.<ref>{{Cite journal |last1=Hou |first1=Yali |last2=Zhang |first2=Zeyuan |last3=Lu |first3=Shuai |last4=Yuan |first4=Jun |last5=Zhu |first5=Qiangyu |last6=Chen |first6=Wei-Peng |last7=Ling |first7=Sanliang |last8=Li |first8=Xiaopeng |last9=Zheng |first9=Yan-Zhen |last10=Zhu |first10=Kelong |last11=Zhang |first11=Mingming |date=2020-11-04 |title=Highly Emissive Perylene Diimide-Based Metallacages and Their Host–Guest Chemistry for Information Encryption |url=https://pubs.acs.org/doi/10.1021/jacs.0c09904 |journal=Journal of the American Chemical Society |language=en |volume=142 |issue=44 |pages=18763–18768 |doi=10.1021/jacs.0c09904 |pmid=33085462 |bibcode=2020JAChS.14218763H |s2cid=224824066 |issn=0002-7863}}</ref> Because of the fluorescence emission differences between the complex and the cages, the information could be encrypted.

=== Mechanical properties === 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.<ref name="Park 2002008"/><ref>{{Cite journal |last1=Jin |first1=Jia-Ni |last2=Yang |first2=Xi-Ran |last3=Wang |first3=Yan-Fang |last4=Zhao |first4=Lei-Min |last5=Yang |first5=Liu-Pan |last6=Huang |first6=Liping |last7=Jiang |first7=Wei |date=2023-01-18 |title=Mechanical Training Enabled Reinforcement of Polyrotaxane-Containing Hydrogel |journal=Angewandte Chemie |volume=135 |issue=8 |doi=10.1002/ange.202218313 |bibcode=2023AngCh.135E8313J |issn=0044-8249}}</ref><ref>{{Cite journal |last1=Wang |first1=Shuaipeng |last2=Chen |first2=Yong |last3=Sun |first3=Yonghui |last4=Qin |first4=Yuexiu |last5=Zhang |first5=Hui |last6=Yu |first6=Xiaoyong |last7=Liu |first7=Yu |date=2022-01-20 |title=Stretchable slide-ring supramolecular hydrogel for flexible electronic devices |journal=Communications Materials |language=en |volume=3 |issue=1 |page=2 |doi=10.1038/s43246-022-00225-7 |bibcode=2022CoMat...3....2W |issn=2662-4443|doi-access=free }}</ref> 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.<ref>{{Cite journal |last1=Huang |first1=Zehuan |last2=Chen |first2=Xiaoyi |last3=O'Neill |first3=Stephen J. K. |last4=Wu |first4=Guanglu |last5=Whitaker |first5=Daniel J. |last6=Li |first6=Jiaxuan |last7=McCune |first7=Jade A. |last8=Scherman |first8=Oren A. |date=January 2022 |title=Highly compressible glass-like supramolecular polymer networks |url=https://www.nature.com/articles/s41563-021-01124-x |journal=Nature Materials |language=en |volume=21 |issue=1 |pages=103–109 |doi=10.1038/s41563-021-01124-x |pmid=34819661 |bibcode=2022NatMa..21..103H |s2cid=244532641 |issn=1476-1122|url-access=subscription }}</ref>

===Sensing=== Silicon surfaces functionalized with tetraphosphonate cavitands have been used to singularly detect sarcosine in water and urine solutions.<ref>{{Cite journal|last=Biavardi|first=Elisa|date=February 14, 2011|title=Exclusive recognition of sarcosine in water and urine by a cavitand-functionalized silicon surface|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=109|issue=7|doi=10.1073/pnas.1112264109|pmid=22308349|pages=2263–2268|pmc=3289311|bibcode=2012PNAS..109.2263B|doi-access=free}}</ref>

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).<ref>{{cite journal | title = Newer optical-based molecular devices from older coordination chemistry | journal = Dalton Transactions | year = 2003| volume = 10 | pages = 1902–1913 | doi = 10.1039/b212447p | author1 = de Silva, A.P. | author2 = McCaughan, B | author3 = McKinney, B.O. F. | author4 = Querol, M. | issue = 10}}</ref> 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).<ref>{{cite journal | title = Supramolecular Analytical Chemistry | journal = Journal of Organic Chemistry | year = 2007| volume = 72 | pages = 687–699 | doi = 10.1021/jo0617971 | author1 = Anslyn, E. | pmid=17253783 | issue = 3}}</ref> thumb|300px|right|Types of chemosensors: (1) indicator–spacer–receptor (ISR), (2) indicator-displacement assay (IDA)

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.<ref>{{cite journal | title = Indicator-displacement assays | journal = Coord. Chem. Rev. | year = 2006 | volume = 250 | pages = 3118–3127 | doi = 10.1016/j.ccr.2006.04.009 | author1 = Nguyen, B. | author2 = Anslyn, E. | issue = 23–24}}</ref>

thumb|175px|left|Indicator-displacement assay indicators: (1) azure A, (2) thiazole orange Chemical sensing techniques such as C-IDA have biological implications. For example, protamine is a coagulant that is routinely administered after cardiopulmonary surgery that counteracts the anti-coagulant activity of heparin. 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 heparin 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.<ref>{{cite journal | doi = 10.1016/0049-3848(94)90158-9 | title = A method for the quantitation of protamine in plasma | journal = Thrombosis Research | year = 1994 | volume = 74 | issue = 4 | pages = 427–434 | pmid = 7521974 | author1 = Yang, V. | author2 = Fu, Y. | author3 = Teng, C. | author4 = Ma, S. | author5 = Shanberge, J.| hdl = 2027.42/31577 | url = https://deepblue.lib.umich.edu/bitstream/2027.42/31577/1/0000505.pdf| hdl-access = free }}</ref>

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 is higher when it is bound to dsDNA than when it is unbound.<ref>{{cite journal | title = A method for the quantitation of protamine in plasma | journal = Nucleic Acids Research | year = 1996 | volume = 24 | pages = 1179–1186 | doi = 10.1093/nar/24.7.1179 | author1 = Eggleston, A. | author2 = Rahim, N. | author3 = Kowalczykowski, S | author4 = Ma, S. | author5 = Shanberge, J. | issue = 7| pmc = 145774 | pmid=8614617}}</ref><ref>{{cite journal |last1=Biancardi|first1=Alessandro |last2=Tarita|first2=Biver |last3=Alberto |first3=Marini |last4=Benedetta |first4=Mennucci |last5=Fernando |first5=Secco |title=Thiazole orange (TO) as a light-switch probe: a combined quantum-mechanical and spectroscopic study |journal=Physical Chemistry Chemical Physics |date=2011 |volume=13 |issue=27 |pages=12595–12602 |doi=10.1039/C1CP20812H |pmid=21660321 |bibcode=2011PCCP...1312595B }}</ref>

===Conformational switching=== 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.<ref>{{cite journal | title = Guest Transport in a nonporous Organic Solid via Dynamic van der Waals Cooperativity | journal = Science | year = 2002 | volume = 298 | pages = 1000–1002 | doi = 10.1126/science.1077591 | author1 = Atwood, J | author2 = Barbour, L | author3 = Jerga, A | author4 = Schottel, L | pmid=12411698 | issue = 5595|bibcode = 2002Sci...298.1000A| s2cid = 17584598 }}</ref><ref>{{cite journal | title = Dynamic porous properties of coordination polymers inspired by hydrogen bonds| journal = Chemical Society Reviews | year = 2005 | volume = 34 | pages = 109–119 | doi = 10.1039/b313997m | author1 = Kitagawa, S | author2 = Uemura, K | issue = 2 | pmid = 15672175}}</ref> Most of these studies have been focused in studying an organic or metal-organic framework.<ref>{{cite journal | title = Methane and Carbon Dioxide Storage in a Porous van der Waals Crystal | journal = Angewandte Chemie | year = 2005 | volume = 44 | pages = 1816–1820 | doi = 10.1002/anie.200461704 | author1 = Sozzani, P | author2 = Bracco, S | author3 = Commoti, A | author4 = Ferretti, R | author5 = Simonutti, R | pmid=15662674 | issue = 12}}</ref><ref>{{cite journal | title = A Contrivance for a Dynamic Porous Framework: Cooperative Guest Adsorption Based on Square Grids Connected by Amide−Amide Hydrogen Bonds | journal = J. Am. Chem. Soc. | year = 2004 | volume = 126 | pages = 3817–3828 | doi = 10.1021/ja039914m | author1 = Uemura, K | author2 = Kitagawa, S | author3 = Fukui, K | author4 = Saito, K | pmid=15038736 | issue = 12| bibcode = 2004JAChS.126.3817U }}</ref> 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.<ref>{{cite journal | title = Guest-Induced Conformational Switching in a Single Crystal | journal = Angewandte Chemie | year = 2006 | volume = 45 | pages = 5856–5859 | doi = 10.1002/anie.200602057 | author1 = Dobrzanska, L | author2 = Lloyd, G | author3 = Esterhuysen, C | author4 = Barbour, L | pmid=16871642 | issue = 35}}</ref>

===Environmental applications=== Host guest systems have been proposed to remove hazardous materials. Certain calix[4]arenes bind cesium-137 ions, which could in principle be applied to clean up radioactive wastes. Some receptors bind carcinogens.<ref>{{cite journal | title = Structural Characterization of the [Cs(p-tert-butylcalix[4]arene -H) (MeCN)] Guest–Host System by 13C-133Cs REDOR NMR | journal = Journal of Physical Chemistry B | year = 2001 | volume = 105 | pages = 5887–5891| doi = 10.1021/jp004559x | author1 = Eric Hughes | author2 = Jason Jordan | author3 = Terry Gullion | issue = 25}}</ref><ref>{{cite journal | title = Extraction of Carcinogenic Aromatic Amines from Aqueous Solution Using Calix[n]arene Derivatives as Carriers | journal = Journal of Hazardous Materials | year = 2009 | volume = 168 | pages = 1170–1176 | doi = 10.1016/j.jhazmat.2009.02.150 | author1 = Serkan Erdemir | author2 = Mufit Bahadir | author3 = Mustafa Yilmaz | pmid=19345489 | issue = 2–3| bibcode = 2009JHzM..168.1170E }}</ref>

===Alcohol=== According to food chemist Udo Pollmer of the European Institute of Food and Nutrition Sciences in Munich, alcohol can be molecularly encapsulated in cyclodextrines, a sugar derivate. In this way, encapsuled in small capsules, the fluid can be handled as a powder. The cyclodextrines can absorb an estimated 60 percent of their own weight in alcohol.<ref>[http://www.wz-newsline.de/sro.php?redid=67450 Alcohol powder: Alcopops from a bag] {{webarchive|url=https://web.archive.org/web/20070927000016/http://www.wz-newsline.de/sro.php?redid=67450 |date=2007-09-27 }}, Westdeutsche Zeitung, 28 October 2004 (German)</ref> A US patent has been registered for the process as early as 1974.<ref>[https://patents.google.com/patent/US3795747 Preparation of an Alcohol Containing Powder], General Foods Corporation March 31, 1972</ref>

== See also == *Cryptophane

==Further reading== *{{cite journal |doi=10.1021/cr200213s |title=Fluorescent Dyes and Their Supramolecular Host/Guest Complexes with Macrocycles in Aqueous Solution |date=2011 |last1=Dsouza |first1=Roy N. |last2=Pischel |first2=Uwe |last3=Nau |first3=Werner M. |journal=Chemical Reviews |volume=111 |issue=12 |pages=7941–7980 |pmid=21981343 }} *{{cite journal |doi=10.1021/cr5005315 |title=Supramolecular Amphiphiles Based on Host–Guest Molecular Recognition Motifs |date=2015 |last1=Yu |first1=Guocan |last2=Jie |first2=Kecheng |last3=Huang |first3=Feihe |journal=Chemical Reviews |volume=115 |issue=15 |pages=7240–7303 |pmid=25716119 }} *{{cite journal |doi=10.1021/cr200333h |title=NMR Insights into Dendrimer-Based Host–Guest Systems |date=2012 |last1=Hu |first1=Jingjing |last2=Xu |first2=Tongwen |last3=Cheng |first3=Yiyun |journal=Chemical Reviews |volume=112 |issue=7 |pages=3856–3891 |pmid=22486250 }} *{{cite journal |doi=10.1021/acs.chemrev.9b00839 |title=Functional Supramolecular Polymeric Networks: The Marriage of Covalent Polymers and Macrocycle-Based Host–Guest Interactions |date=2020 |last1=Xia |first1=Danyu |last2=Wang |first2=Pi |last3=Ji |first3=Xiaofan |last4=Khashab |first4=Niveen M. |last5=Sessler |first5=Jonathan L. |last6=Huang |first6=Feihe |journal=Chemical Reviews |volume=120 |issue=13 |pages=6070–6123 |pmid=32426970 }} *{{cite journal |doi=10.1021/cr5006342 |title=Photoresponsive Host–Guest Functional Systems |date=2015 |last1=Qu |first1=Da-Hui |last2=Wang |first2=Qiao-Chun |last3=Zhang |first3=Qi-Wei |last4=Ma |first4=Xiang |last5=Tian |first5=He |journal=Chemical Reviews |volume=115 |issue=15 |pages=7543–7588 |pmid=25697681 }}

==References== {{reflist}}

{{Branches of chemistry}}

{{DEFAULTSORT:Host–guest chemistry}} Category:Supramolecular chemistry Category:Equilibrium chemistry