A supramolecular five-component relay switch that exposes the mechanistic competition of dissociativeversusassociative binding to cucurbiturils by ratiometric fluorescence monitoring

Abstract

A putrescine derivative of aminomethyladamantane is established as a ditopic guest with two mutually exclusive binding sites for cucurbit[6]uril and cucurbit[7]uril.

Teaching indicators to unravel the kinetic features of host–guest inclusion complexes

“…30 The concept is transferable to protein-ligand interactions, as exemplified for human serum albumin (HSA) as a biological important carrier protein 31,32 that is commercially available. 35,36 Fig. 3c demonstrates the determination of the kinetic rate constants for the binding of the anti-inflammatory drug phenylbutazone 34,35 (PBZ) to HSA by kinGDA.…”

“…The second competitive kinetic method, the pseudo-first order kinGDA (kinGDA PFO ), has a close analogy to some literature reports, 18,36 and allows for measuring k HG out values without explicit knowledge of the kinetic rate constants of the indicator dye. Firstly, host and guest are equilibrated, followed by the spiked addition of excess of a high-affinity dye.…”

“…The kinetic methods introduced herein provide meaningful rate constants if the host-guest and host-dye displacement mechanism follow a strict dissociative and not an additional, occasionally observed, 36 associative mechanism. Several tests can be adopted to validate a dissociative mechanism.…”

Simultaneous analyte indicator binding assay (SBA) for the monitoring of reversible host–guest complexation kinetics

“…[1][2][3][4][5][6][7][8] The understanding of the major factors influencing the rate constants of association and dissociation is crucial also for the application of cavitands in the biomedical field, 9 catalysis, 10,11 and self-sorting multicomponent systems. 12,13 Time-resolved measurements provide insights into the subtle mechanistic details of the inclusion of simple 14,15 and ditopic guests [16][17][18] as well as those of the cationinduced release of encapsulated molecules. 19 Moreover, the importance of ligand-receptor reversible binding kinetics is increasingly recognized as selection criterion in the search for potent pharmaceutical ingredients.…”

Supramolecular Chemistry in the Biomembrane

“…Nowadays, indicator displacement assays are very popular, in which a dye noncovalently binds to a molecular receptor and thereby changes its optical properties; subsequent addition of an analyte displaces the dye from the receptor, which restores the optical properties of the dye in solution. [23] The commonly fast and reversible response in displacement-based chemosensors has allowed advanced versions of indicator displacement assays for the detection of enzyme activity, [24] membrane transport, [18c, 25] screening, [26] reaction monitoring, [27] and quantification of surface groups. [28] An alternative approach to self-assembled chemosensors is the use of monolayer and bilayer membranes, with membrane-bound amphiphilic receptor and reporter groups.…”