AbstractThe 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.

AbstractThe 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.

The impact of remote substituents on the affinity of cucurbit[n]urils (CB[n]) towards a homologous series of guests, which differ from one another only by a single substituent, and adopt the same geometry within the cavity of the macrocycle, is presented for the first time, and is used to decipher the competition between water and the carbonylated portal of CB[7] for the stabilization of positively charged guests. Binding affinities of CB[7] towards substituted N-benzyl-trimethylsilylmethylammonium cations relative to the unsubstituted member (X = H) range from 0.9 (X = CH3) to 3.1 (X = SO2CF3), and correlate very precisely with a linear combination of Swain–Lupton field/inductive (F; 67%) and resonance (R; 33%) parameters tabulated for each substituent. We show that this subtle sensitivity results exclusively from the balance between two competing mechanisms, on which the substituents exert an approximately 11 times greater impact: (1) the solvation of the ammonium unit and its immediate surroundings by water in the free guests, and (2) the coulombic attraction between the ammonium unit and the rim of CB[7] in the complexes.

Cucurbit[n]urils (CB[n], n = 6–8) interact strongly with metal-bound 4′-substituted terpyridine ligands (M = Fe(II) and Ir(III)) via CH···O hydrogen bonding, despite significant separation between the positive metallic cation and the carbonylated rim of CB[n], and the location of the latter in the second coordination sphere of the metal ion. While water has been shown to mediate interactions between cations and CB[n]s in some assemblies, mediation by organic ligands is unprecedented. The recognition process is driven by the contrasted combination of extremely favorable binding enthalpies (up to 20.2 kcal/mol) and very unfavorable entropic components (as low as −10.2 kcal/mol). Dynamic oligomers were prepared in the presence of CB[8], which acts as a “soft”, noncovalent linker between metal/terpyridine complexes, and interconnects two 4′-substituents inside its cavity. Social self-sorting between CB[8] and metal/terpyridine complexes bearing 4′-(2-naphthyl) and 4′-(2,3,5,6-tetrafluorophenyl) substituents was also observed, and could afford well-organized oligomers with alternating Fe(II) and Ir(III) cations.

Biphenyl derivatives bearing a dimethylsulfonium group at position 3 and three different substituents at position 4 (H, F and CH3) have been prepared as probes to test the validity of the “supramolecular buttressing” concept. We define the latter as the alteration, by a neighboring unit, of a substituent effect on intermolecular recognition. In this case, the 4-substituents exert some pressure on the 3-dimethylsulfonium groups and control the ratio of their syn and anti conformations. As free species, biphenyls bearing 4-H and 4-F substituents are present as approximately equimolar mixtures of syn and anti-conformers, while the biphenyl scaffold with a 4-CH3 group adopts the anti-conformation exclusively. The 3-dimethylsulfonium substituents then interact with one of the carbonylated portals of Cucurbit[7]uril (CB[7]), and their conformations affect the position of the guests inside the cavity of the macrocycle, thereby validating our “supramolecular buttressing” model. Surprisingly however, binding affinities towards CB[7] are barely affected by the nature of the 4-substituents and the conformations of the neighboring sulfonium groups, despite very different electronic densities presented to the CB[7] portal in their syn or anti conformations. Solvation was found to dramatically smoothen host–guest Columbic interactions, although the latter remain important in the recognition process. Replacing the positively charged 3-dimethylsulfonium unit with an isopropyl substituent decreases the affinity of the biphenyl guest by 1000-fold.

The dethreading rate of a polyaminated axle flanked by two benzo-15-crown-5 stoppers from the cavity of Cucurbit[7]uril (CB[7]) was enhanced by up to 500 times in the presence of aqueous metallic and organic cations. Cations likely stabilize the highest energy transition state of the dethreading process by interacting with both crown ether and CB[7] units.

This review highlights the past six year advances in the blossoming field of cucurbit[n]uril chemistry. Because of their exceptional recognition properties in aqueous medium, these pumpkin-shaped macrocycles have been generating some tremendous interest in the supramolecular community. They have also become key units in various self-organizing and stimulus-controlled assemblies, as well as in advanced materials and drug carriers. The scope of this review is limited to the main family of cucurbit[n]urils (n = 5, 6, 7, 8, 10). The reader will find an overview of their preparation, their physicochemical and biological properties, as well as their recognition abilities towards various organic and inorganic guests. Detailed thermodynamic and kinetic considerations, as well as multiple applications including supramolecular catalysis are also discussed.

A series of silver/cucurbituril nanoparticles and aggregates have been prepared upon reduction of silver nitrate with sodium borohydride in the presence of different cucurbit[n]uril (CB[n]) macrocycles; CB[7] and CB[8] allow the formation of stable solutions of monocrystalline, narrowly dispersed nanoparticles (5.3 and 3.7 nm, respectively), while CB[5] and CB[6] induce rapid aggregation and sedimentation. The rigidity of CB[5] and CB[6], and their possible lack of suitable arrangement at the silver surface, may explain the poor stabilization of these silver assemblies, while the more flexible CB[7] and CB[8] may undergo some minor distortions and better adapt to the requirements of the metallic surface; computer modeling supports the existence of interactions between the silver nanoparticles and the oxygen atoms of the CB[n] carbonylated rim. The optimal silver nitrate/CB[7] ratio for the formation of stable nanoparticles is 1:1−2:1, while large excesses of silver or CB[7] trigger aggregation. Masking the portals of CB[7] by adding a bulky, positively charged guest into its cavity has a surprisingly minor effect on the stability of the silver/CB[7] assemblies; in such a case, the CB[7] rim is still expected to interact with the NPs, albeit via a fraction of its carbonyl oxygen atoms.

Cucurbit[6]-, [7]-, and [8]uril can catalyze the silver(I)-promoted desilylation of trimethylsilylalkynyl-containing pseudorotaxanes by stabilizing a key π-alkynyl silver intermediate through favorable interactions between the metallic cation and the cavitand carbonylated portal.

The kinetics of cucurbit[6]uril slippage along a polyaminated axle are highly dependent on even minor sterical alterations of the guest. According to in silico experiments, a plausible threading mechanism includes the deprotonation of the ammoniums prior to slippage, their tunneling through the cavitand as neutral amines, and their reprotonation upon exiting cucurbit[6]uril.

Cucurbit[6]-, cucurbit[7]-, and cucurbit[6]uril cavitands can be aligned along a spermine derivative axle in a well-defined, kinetically favored sequence at room temperature, and can undergo a reorganization toward a more stable [4]pseudorotaxane bearing three cucurbit[6]uril units upon thermally induced scrambling.

Biphenyl derivatives bearing a dimethylsulfonium group at position 3 and three different substituents at position 4 (H, F and CH3) have been prepared as probes to test the validity of the “supramolecular buttressing” concept. We define the latter as the alteration, by a neighboring unit, of a substituent effect on intermolecular recognition. In this case, the 4-substituents exert some pressure on the 3-dimethylsulfonium groups and control the ratio of their syn and anti conformations. As free species, biphenyls bearing 4-H and 4-F substituents are present as approximately equimolar mixtures of syn and anti-conformers, while the biphenyl scaffold with a 4-CH3 group adopts the anti-conformation exclusively. The 3-dimethylsulfonium substituents then interact with one of the carbonylated portals of Cucurbit[7]uril (CB[7]), and their conformations affect the position of the guests inside the cavity of the macrocycle, thereby validating our “supramolecular buttressing” model. Surprisingly however, binding affinities towards CB[7] are barely affected by the nature of the 4-substituents and the conformations of the neighboring sulfonium groups, despite very different electronic densities presented to the CB[7] portal in their syn or anti conformations. Solvation was found to dramatically smoothen host–guest Columbic interactions, although the latter remain important in the recognition process. Replacing the positively charged 3-dimethylsulfonium unit with an isopropyl substituent decreases the affinity of the biphenyl guest by 1000-fold.