Cucurbit[7]uril as a Supramolecular Artificial Enzyme for Diels–Alder Reactions

Abstract

The ability to mimic the activity of natural enzymes using supramolecular constructs (artificial enzymes) is a vibrant scientific research field. Herein, we demonstrate that cucurbit[7]uril (CB[7]) can catalyse Diels-Alder reactions for a number of substituted and unreactive N-allyl-2-furfurylamines under biomimetic conditions, without the need for protecting groups, yielding powerful synthons in previously unreported mild conditions. CB[7] rearranges the substrate in a highly reactive conformation and shields it from the aqueous environment, thereby mimicking the mode of action of a natural Diels-Alderase. These findings can be directly applied to the phenomenon of product inhibition observed in natural Diels-Alderase enzymes, and pave the way toward the development of novel, supramolecular-based green catalysts.

Kinetics Inside, Outside and Through Cucurbiturils

“…Endo preference increases also in the presence of the macrocycle (endo/exo ratio 90 : 10 to 96 : 4 and 97 : 3 for CB [8]-bound tryptophane 92 a and abrine 92 b, respectively). [137] We [138,139] and Scherman [139] showed that CB [7] and CB [8] catalyze the intramolecular Diels-Alder cycloaddition of Nallyl-2-furfurylamines 93 (see Scheme 14) with rate enhancements greater than 10 3 for guests 93 b-93 e and CB [7]. The authors show convincing evidence that a ternary complex between the amino acid, the pyridine moiety of guest 90 and CB [8] is formed, with copper bound to both units, and the dienophile portion of guest 90 left outside the macrocycle near the rim and available for reaction with cyclopentadiene (see Figure 11).…”

Cucurbituril As A Versatile Tool to Tune the Functions of Proteins

“…Cucurbiturils are a series of supramolecular macrocyclic hosts with n glycoluril bridged by 2n methylenes, yielding cucurbituril series (CB [5,6,7,8,10,13,14,15]). CB [5][6][7][8][9][10] (except for CB [13][14][15]) share a common pumpkin-shaped structure with a large hydrophobic cavity and two negatively charged portals.…”

“…Cucurbiturils are a series of supramolecular macrocyclic hosts with n glycoluril bridged by 2n methylenes, yielding cucurbituril series (CB [5,6,7,8,10,13,14,15]). CB [5][6][7][8][9][10] (except for CB [13][14][15]) share a common pumpkin-shaped structure with a large hydrophobic cavity and two negatively charged portals. [26][27][28][29] Crystal structures indicates that the four biocompatible CB[n]s, such CB, [5] CB, [6] CB [7] and CB [8] have the same height of 9.1 Å and diverse outer diameters ranging from 13.1 Å -17.5 Å .According to the sizes of the cavities, the smaller cucurbituril of CB [5] can complex with some metal cations and gas molecules.…”

“…[14][15][16][17][18][19] For example, activity changes could be found both in CB [8]induced FGG-cap-9 dimer [18] (compared with FGG-cap-9 monomer) and CB [8]-induced split-luciferase complementation [19] (compared with split fragments). [14][15][16][17][18][19] For example, activity changes could be found both in CB [8]induced FGG-cap-9 dimer [18] (compared with FGG-cap-9 monomer) and CB [8]-induced split-luciferase complementation [19] (compared with split fragments).…”

“…Recently, CB[n]s-based supramolecular assembly has been widely used to tune the functions of proteins. [14][15][16][17][18][19] For example, activity changes could be found both in CB [8]induced FGG-cap-9 dimer [18] (compared with FGG-cap-9 monomer) and CB [8]-induced split-luciferase complementation [19] (compared with split fragments). Other properties could be tuned by CB[n]s-induced protein assembly.…”