The World of Cucurbiturils — From Peculiarity to Commodity

Abstract

More than a century ago, while Robert Behrend ( Figure 1) and his coworkers were investigating acid-catalyzed condensation reactions between glycoluril and formaldehyde, [1] a mysterious white material was the result. The German chemist had unknowingly synthesized the parent cucurbituril, yet recognized that this as-yet-unnamed material could be dissolved in water in the presence of either protons or alkali ions, and easily formed complexes with metal salts and organic dyes.[2] This peculiarity has now matured into an internationally well-recognized area of supramolecular chemistry that is intensively being pursued. While the first synthesis of cucurbituril is, unarguably but in retrospect, Behrends biggest achievement, he was known during his lifetime for the first synthesis of uric acid, [3] for carrying out the first potentiometric titration, [4] and even for an organic name reaction, the Behrend rearrangement. [5] After 75 years of dormancy, investigations by Mock and coworkers in the 1980 s led to the structural elucidation of the white solid as being a discrete macrocyclic pumpkin-shaped hexamer [8] as opposed to an open-chain ladder polymer. They coined the name "cucurbituril" in reflection of the botanical name for pumpkin. Recognition of the structure immediately led to comprehensive investigations of its host-guest inclusion behavior, which also revealed a particularly high affinity towards organic ammonium cations.[9] At present, unique applications of cucurbiturils in diverse areas are rapidly unfolding that will soon render these macrocycles a commodity.Homologues of different sizes, ranging from cucurbit[5]uril to cucurbit[10]uril (Figure 2), as well as equatorially alkylated and hydroxylated derivatives, were isolated and characterized, [10][11][12] showing marked differences in water solubility, guest affinity as well as guest size selectivity, and binding stoichiometry. In particular, the possibility to study these fascinating macrocycles in neutral aqueous solution has attracted much attention since applications in many areas, including biology, are now in sight. Moreover, it has become possible to contrast the inclusion properties and binding strengths of this new class of synthetic host molecules with established macrocyclic receptors, such as cyclodextrins and water-soluble calixarenes. In fact, cucurbiturils are competitive in several respects, such as their low toxicity, [13,14] and far superior in many others, particularly their high chemical stability, large complexation-induced pK a shifts, as well as their tight, selective binding (see articles in this special issue).Initial investigations on cucurbit[6]uril focused on its binding preferences and the determination of the binding constants of its host-guest complexes. [15][16][17] These studies have continued to attract attention also for the larger homologues, driven, among other things, by the exceptional kinetics and thermodynamics of binding. It was Mock and coworkers who also laid the foundation for many lines of applications of cu...

Chaperone-Assisted Formation of Cucurbit[8]uril-Based Molecular Porous Materials with One-Dimensional Channel Structure

“…In recent years, CB[8] has been extensively studied on account of its scope in the fields of molecular recognition and supramolecular self-assembly. , Nevertheless, a major drawback that has limited its broad application is its difficult isolation and purification from a synthesized complex mixture. In our work, owing to the chaperoning effect, a new, facile and efficient strategy to recycle and purify CB[8] in complex solution was developed.…”

Radical-radical rotaxanes with tetracationic cyclophane ring, and quaternary azaaromatic rotaxanes with cage macrocycles

“…In 35 the cucurbituril CB7 serves as a ring. It should be noted that cucurbiturils have good host properties, 72 they form highly stable complexes with aromatic amines and quatemary pyridinium compounds 73 and serve for construction of molecular switches and machines.…”

William L. Mock and Cucurbituril: The Resurrection of the Behrend Paper of 1905

“…Using the hindsight of history, they suggest that the production of the uncharacterized product of the condensation of glycouril with formaldehyde dwarfs Behrend's synthesis of uric acid and the organic reaction that bears his name. 18 For over a decade after the resurrection of the Behrend 1905 paper, the entire corpus of work on cucurbituril available in the literature emerged from Mock's laboratory at the University of Illinois at Chicago. The remarkable ability of cucurbituril to encapsulate guests and the use of the molecular cavity to perform the cycloaddition reaction were forerunners of click ■ REFERENCES…”