Can we beat the biotin–avidin pair?: cucurbit[7]uril-based ultrahigh affinity host–guest complexes and their applications

Abstract

The design of synthetic, monovalent host-guest molecular recognition pairs is still challenging and of particular interest to inquire into the limits of the affinity that can be achieved with designed systems. In this regard, cucurbit[7]uril (CB[7]), an important member of the host family cucurbit[n]uril (CB[n], n = 5-8, 10, 14), has attracted much attention because of its ability to form ultra-stable complexes with multiple guests. The strong hydrophobic effect between the host cavity and guests, ion-dipole and dipole-dipole interactions of guests with CB portals helps in cooperative and multiple noncovalent interactions that are essential for realizing such strong complexations. These highly selective, strong yet dynamic interactions can be exploited in many applications including affinity chromatography, biomolecule immobilization, protein isolation, biological catalysis, and sensor technologies. In this review, we summarize the progress in the development of high affinity guests for CB[7], factors affecting the stability of complexes, theoretical insights, and the utility of these high affinity pairs in different challenging applications.

High Affinity Macrocycle Threading by a Near-Infrared Croconaine Dye with Flanking Polymer Chains

“…To date, the highest binding constants have been achieved using macrocyclic cucurbituril molecules as host systems. 6–8 Alternative approaches based on synthetic cyclophane systems have the potential advantage that the binding partners can be optically or redox active, 9-12 but they are presently limited by relatively weak association constants in water. 13,14 Recently, we discovered an unusually effective supramolecular process that threaded a tetralactam macrocycle onto a fluorescent squaraine dye (Scheme 1) that was flanked by two long polyethylene glycol (PEG) chains.…”

Influence of supramolecular encapsulation of camptothecin by cucurbit[7]uril: reduced toxicity and preserved anti-cancer activity

“…12,13 In comparison with CDs, CB[n]s typically have much higher binding affinities and higher selectivity towards a variety of guest molecules. 14,15 Within the CB [n] family, CB [7] has attracted the most attention as a potent drug delivery carrier owing to its superior solubility in water and appropriate size that can form complexes with numerous organic and organometallic guest molecules of biomedical interest. [16][17][18] In addition, it has been demonstrated that CB [7] exhibited little toxicity at sub-mM concentrations or even up to 1 mM concentration in in vitro cellular models.…”

The Cucurbit[7]Uril‐Based Supramolecular Chemistry for Reversible B/Z‐DNA Transition

“…Previous studies suggest that the AM molecule can form very stable host–guest complex with CB7 20. Therefore, this event is expected to drive the release of free spm and reinduce the transition from B‐ to Z‐DNA.…”