Calixarene 1960070 221176680 2008-06-23T11:04:21Z DOI bot 6652755 Citation maintenance. Initiated by [[User:Fconaway|Fconaway]]. You can [[WP:DOI|use this bot]] yourself! Please [[User:DOI_bot/bugs|report any bugs]]. A '''calixarene''' is a [[macrocycle]] or [[Cyclic compound|cyclic]] [[oligomer]] based on a [[hydroxyalkylation]] product of a [[phenol]] and an [[aldehyde]] <sup>[1]</sup>. The word calixarene is derived from calix or [[Chalice (cup)|chalice]] because this type of molecule resembles a vase and from the word [[arene]] that refers to the aromatic building block. Calixarenes have [[hydrophobic]] cavities that can hold smaller molecules or ions and belong to the class of [[cavitand]]s known in [[Host-guest chemistry]]. Calixarene [[IUPAC nomenclature|nomenclature]] is straightforward and involves counting the number of [[repeating unit]]s in the ring and include it in the name. A calix[4]arene has 4 units in the ring and a calix[6]arene has 6. A [[substituent]] in the [[meso position]] '''R<sub>b</sub>''' is added to the name with a prefix C- as in C-methylcalix[6]arene. ==Synthesis== The aromatic components are derived from [[phenol]], [[resorcinol]] or [[pyrogallol]], For phenol, the aldehyde most often used is simply [[formaldehyde]], while larger aldehydes ([[acetaldehyde]], or larger) are generally required in condensation reactions with resorcinol and pyrogallol. The [[chemical reaction]] ranks under [[electrophilic aromatic substitution]]s followed by an [[elimination]] of water and then a second aromatic substitution. The reaction is [[acid]] catalysed or [[base (chemistry)|base]] [[catalysis|catalysed]]. Calixarenes are difficult to produce because it is all too easy to end up with complex mixtures of linear and cyclic oligomers with different numbers of repeating units. With finely tuned starting materials and reaction conditions synthesis can also be surprisingly easy. In 2005, research produced a pyrogallol[4]arene by simply mixing a [[solvent-free]] dispersion of [[isovaleraldehyde]] with pyrogallol and a catalytic amount of [[P-Toluenesulfonic acid|''p''-toluenesulfonic acid]] in a [[mortar and pestle]] <sup>[2]</sup>. Calixarenes as parent compounds are sparingly soluble and are high melting crystalline solids <sup>[3]</sup>. [[image:Calixarene-schema.png|700px|center|from left to right with n = 4 calix[4]arene, resorcinol[4]arene, pyrogallol[4]arene. Ra is an alkyl substituent, Rb is hydrogen with formaldehyde or phenyl with benzaldehyde, Rc is hydrogen in the parent compounds]] ==Structure== Calixarenes are characterised by a three-dimensional basket, cup or bucket shape. In calix[4]arenes the internal [[volume]] is around 10 cubic [[nanometer]]s. Calixarenes are characterised by a wide '''upper rim''' and a narrow '''lower rim''' and a central '''annulus'''. With phenol as a starting material the 4 [[hydroxyl]] groups are '''intrannular''' on the lower rim. In a resorcin[4]arene 8 hydroxyl groups are placed '''extraannular''' on the upper ring. Calixarenes exist in different [[chemical conformation]]s because rotation around the methylene bridge is not difficult. In calix[4]arene 4 up-down conformations exist: '''cone''' ( [[point group]] C<sub>2v</sub>,C<sub>4v</sub>), '''partial cone''' C<sub>s</sub>, '''1,2 alternate''' C<sub>2h</sub> and '''1,3 alternate''' D<sub>2d</sub>. The 4 hydroxyl groups interact by [[hydrogen bond]]ing and stabilize the cone conformation. This conformation is in dymamic equilibrium with the other conformations. Conformations can be locked in place with proper substituents replacing the hydroxyl groups which increase the [[rotational barrier]]. Alternatively placing a bulky substituent on the upper rim also locks a conformation. The calixarene based on [[p-tert-butyl phenol]] is also a cone [http://www.iupac.org/publications/pac/1993/pdf/6503x0387.pdf]. {| align="center" border="1" |[[image:P-tert-butylcalix-4-arene.png|300px]] |[[image:Calixarene.png|300px]] |- |Calix[4]arene with para-tert-butyl substituents |3D representation of a cone conformation |} ==History== [[Adolf von Baeyer]] pioneered the chemistry of calixarenes although he was unable to determine its structure and did not realise its potential (he was pursuing dyes). In 1872 he mixed [[benzaldehyde]] with [[pyrogallol]] and a strong [[acid]] and noted a red-brown [[resin]] with a marked [[viscosity]] increase. He also used [[resorcinol]] and [[formaldehyde]] which he had to prepare from [[iodoform]] himself because a commercial grade of formaldehyde at that time had not been realised yet. In 1894 the [[Lederer-Manasse hydroxyalkylation]] was invented as a synthetic tool for the preparation of hydroxylmethyl phenols, bringing calixarenes one step closer. In 1902 [[Leo Baekeland]] made [[phenol formaldehyde resin]]s a commercial success under the trade name [[Bakelite]]. In these resins phenol and formaldehyde are exhaustively condensed with each other to form heavily [[cross-link]]ed [[polymers]]. The first attempt to control the reaction was made by Alois Zinke and Erich Ziegler in 1942. They employed [[aromatic para substituent|para substituted]] phenols which inhibits crosslinking and should result in a linear polymer with formaldehyde. So in 1944 [[p-tert-butyl phenol]] with formaldehyde and [[sodium hydroxide]] in [[linseed oil]] as a solvent produced for the first time a crystalline solid with a high melting point rather than a resin. In the same year another duo by the names of Niederl and Vogel did something similar with a para substituted [[resorcinol]] and they were the first to postulate a cyclic tetramer. In these days structure elucidation was limited to determination of [[molar mass]] by [[freezing-point depression]] and [[functional group]] analysis. [[John Cornforth]] was in 1955 the first to realize the potential of calixarenes as a basket analogue to [[enzyme]]s and repeated the work done by Zinke. he obtained a mixture of products and elicited the services of [[Dorothy Crowfoot Hodgkin]] for structure elucidation by [[X-ray crystallography]] but with limited success. First commercial success came to calixarenes in the nineteen fifties when the company [[Petrolite]] started a range of calixarene products as [[demulsifier]]s user in the [[oil industry]]. The word calixarene was coined by David Gutsche [http://www.chm.tcu.edu/gutsche.htm] in 1975 who was also interested in this type of compound as [[biomimetic]], since the molecule resembled the ''[[calyx krater]]'' vases of ancient Greece. It was by then established that unmodified calixarenes exhibit extensive conformational mobility so that the basket was not much of a basket after all. [[Donald J. Cram]] fixed this shortcoming by inventing a way of immobilizing calixarenes. He was able to freeze in a conformation by so called lower rim functionalization, replacing the [[hydroxyl]] groups by larger [[substituent]]s. The [[acetate]] calixarene fixates the molecule as a partial cone, whereas the [[carbonate ester]] yields the full cone. ==Host guest interactions== Calixarenes are efficient [[sodium]] [[ionophore]]s and are applied as such in chemical [[sensor]]s. With the right chemistry these molecules exhibit great selectivity towards other cations. Calixarenes are used in commercial applications as sodium selective [[electrode]]s for the measurement of sodium levels in blood. Calixarenes also form complexes with [[cadmium]], [[lead]], [[lanthanide]]s and [[actinide]]s. [http://www.chem.ox.ac.uk/icl/beergroup/calixarene.htm] Calix[5]arene and the C<sub>70</sub> [[fullerene]] in [[p-xylene]] form a ball-and-socket supramolecular complex. [http://www.rsc.org/publishing/journals/CC/article.asp?doi=b306411p] calixarenes also form exo-calix ammonium salts with aliphatic amines such as [[piperidine]]. <sup>[4]</sup> See [[Host-guest chemistry]]. ==Molecular self-assembly== [[Molecular self-assembly]] of resorcinarenes and pyrogallolarenes lead to larger [[supramolecular assemblies]] [http://www.chem.missouri.edu/faculty/Atwood/research.html]. Both in the crystalline state and in solution, they are known to form hexamers that are akin to certain [[Archimedean solid]]s with an internal volume of around one cubic [[nanometer]] (nanocapsules). (Isobutylpyrogallol[4]arene)<sub>6</sub> is held together by 48 [[intermolecular]] hydrogen bonds. The remaining 24 hydrogen bonds are [[intramolecular]]. The cavity is filled by a number of solvent molecules. <sup>[5]</sup> ==Applications== Calixarenes are applied in enzyme mimetics, ion sensitive electrodes or sensors, selective membrames, non-linear optics [http://www.rsc.org/publishing/journals/CC/article.asp?doi=b502045j] and in [[HPLC]] stationary phase [http://www.chromtech.net.au/grom-calixarene.cfm]. In addition, in [[nanotechnology]] calixarenes are used as [[negative resist]] for high-resolution [[electron beam lithography]] [http://dx.doi.org/10.1063/1.115958]. A tetrathia[4]arene is found to mimic [[aquaporin]] proteins <sup>[6]</sup>. This calixarene adopts a 1,3-alternate conformation (methoxy groups populate the lower ring) and water is not contained in the basket but grabbed by two opposing [[tert-butyl]] groups on the outer rim in a pincer. The nonporous and [[hydrophobic]] crystals are soaked in water for 8 hours in which time the calixarene:water ratio nevertheless acquires the value of one. Calixarenes are able to accelerate reactions taking place inside the concavity by a combination of local concentration effect and polar stabilization of the [[transition state]]. An extended resorcin[4]arene [[cavitand]] is found to accelerate the [[reaction rate]] of a [[Menshutkin reaction]] between [[quinuclidine]] and butylbromide by a factor of 1600 <sup>[7]</sup>. In '''heterocalixarenes''' the phenolic units are replaced by [[heterocycle]]s <sup>[8]</sup>, for instance by [[furan]]s in calix[n]furanes and by [[pyridine]]s in calix[n]pyridines. Calixarenes have been used as the [[macrocycle]] portion of a [[rotaxane]] and two calixarene molecules covalently joined together by the lower rims form [[carcerand]]s. ==Esthetics== Building esthetic molecules with calixarenes include thus far a molecular [[Football World Cup]] [http://www.rsc.org/publishing/journals/NJ/article.asp?doi=a805959d]. == References == * <sup>[1]</sup> a) {{cite book | author=Gutsche, C. David | title=Calixarenes | location=Cambridge | publisher=Royal Society of Chemistry | year=1989 | id=ISBN 0-85186-385-X}}; b) {{GoldBookRef | title=Calixarenes | file=C00783 | year=1995}} * <sup>[2]</sup> {{cite journal | author=Antesberger J, Cave GW, Ferrarelli MC, Heaven MW, Raston CL, Atwood JL | title=Solvent-free, direct synthesis of supramolecular nano-capsules | journal=Chemical communications (Cambridge, England) | volume=. | issue=7 | year=2005 | pages=892–4 | pmid=15700072 | doi=10.1039/b412251h}} * <sup>[3]</sup> {{cite journal | author=McMahon G, O’Malley S, Nolan K and Diamond D | title=Important Calixarene Derivatives – their Synthesis and Applications | journal=[[Arkivoc]] | volume=Part | issue=vii | year=2003 | pages=}} [http://www.arkat-usa.org/ark/journal/2003/I07_McKervey/AM-720R/720R.asp Article] * <sup>[4]</sup> {{cite journal | author=Nachtigall FF, Lazzarotto M and Braz FNJ | title=Interaction of Calix[4]arene and Aliphatic Amines: A Combined NMR, Spectrophotometric and Conductimetric Investigation | journal=Journal of the Brazilian Chemical Society | volume=13 | issue=3 | year=2002 | pages= | doi=10.1590/S0103-50532002000300002}} [http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532002000300002 Article] * <sup>[5]</sup> {{cite journal | author=Atwood JL, Barbour LJ, Jerga A | title=Organization of the interior of molecular capsules by hydrogen bonding | journal=[[Proceedings of the National Academy of Sciences]] | volume=99 | issue=8 | year=2002 | pages=4837–41 | pmid=11943875 | doi=10.1073/pnas.082659799}} * <sup>[6]</sup> {{cite journal | author=Thallapally PK, Lloyd GO, Atwood JL, Barbour LJ | title=Diffusion of water in a nonporous hydrophobic crystal | journal=Angewandte Chemie (International ed. in English) | volume=44 | issue=25 | year=2005 | pages=3848–51 | pmid=15892031 | doi=10.1002/anie.200500749}} * <sup>[7]</sup> {{cite journal | author=Purse BW, Gissot A, Rebek J Jr | title=A deep cavitand provides a structured environment for the menschutkin reaction | journal=[[Journal of the American Chemical Society]] | volume=127| issue=32 | year=2005 | pages=11222–3 | pmid=16089433 | doi=10.1021/ja052877}} * <sup>[8]</sup> {{cite journal | author=Subodh Kumar, Dharam Paul, Harjit Singh| title=Syntheses, structures and interactions of heterocalixarenes | journal=[[Arkivoc]] | volume=05-1699LU| issue= | year=2006 | pages=17–25 | pmid=}} [http://www.arkat-usa.org/ark/journal/2006/I09_General/1699/05-1699LU%20as%20published%20mainmanuscript.pdf Article] [[Category:supramolecular chemistry]] [[de:Calixaren]] [[fr:Calixarène]] [[ja:カリックスアレーン]] [[ru:Каликсарены]]