Dynamically Analyte-Responsive Macrocyclic Host–Fluorophore Systems

Abstract

CONSPECTUS: Host-guest chemistry commenced to a large degree with the work of Pedersen, who in 1967 first reported the synthesis of crown ethers. The past 45 years have witnessed a substantial progress in the field, from the design of highly selective host molecules as receptors to their application in drug delivery and, particularly, analyte sensing. Much effort has been expended on designing receptors and signaling mechanism for detecting compounds of biological and environmental relevance. Traditionally, the design of a chemosensor comprises one component for molecular recognition, frequently macrocycles of the cyclodextrin, cucurbituril, cyclophane, or calixarene type. The second component, used for signaling, is typically an indicator dye which changes its photophysical properties, preferably its fluorescence, upon analyte binding. A variety of signal transduction mechanisms are available, of which displacement of the dye from the macrocyclic binding site is one of the simplest and most popular ones. This constitutes the working principle of indicator displacement assays. However, indicator displacement assays have been predominantly exploited in a static fashion, namely, to determine absolute analyte concentrations, or, by using combinations of several reporter pairs, to achieve a differential sensing and, thus, identification of specific food products or brands. In contrast, their use in biological systems, for example, with membranes, cells, or with enzymes has been comparably less explored, which led us to the design of the so-called tandem assays, that is, dynamically analyte-responsive host-dye systems, in which the change in analyte concentrations is induced by a biological reaction or process. This methodological variation has practical application potential, because the ability to monitor these biochemical pathways or to follow specific molecules in real time is of paramount interest for both biochemical laboratories and the pharmaceutical industry. We will begin by describing the underlying principles that govern the use of macrocycle-fluorescent dye complexes to monitor time-dependent changes in analyte concentrations. Suitable chemosensing ensembles are introduced, along with their fluorescence responses (switch-on or switch-off). This includes supramolecular tandem assays in their product- and substrate-selective variants, and in their domino and enzyme-coupled modifications, with assays for amino acid decarboxylases, diamine, and choline oxidase, proteases, methyl transferases, acetylcholineesterase (including an unpublished direct tandem assay), choline oxidase, and potato apyrase as examples. It also includes the very recently introduced tandem membrane assays in their published influx and unpublished efflux variants, with the outer membrane protein F as channel protein and protamine as bidirectionally translocated analyte. As proof-of-principle for environmental monitoring applications, we describe sensing ensembles for volatile hydrocarbons.

Interactions of cucurbit[7]uril and β-cyclodextrin with some nucleobases

“…In this respect, the binding properties of cucurbiturils towards different organic, inorganic or biological species through a combination of ion-dipole, dipole-dipol, hydrogen bonding, and hydrophobic interactions lead to the formation of inclusion or exclusion complexes [12][13][14][15]. The synthesis of cucurbit [6]uril by condensation reaction of glycoluril and formaldehyde during an acid-catalyzed reaction was reported by Behrend et al way back in 1905 [16].…”

pH-responsive molecular assemblies of pyridylbutadiene derivative with cucurbit[7]uril

“…Owing to the unique structural characteristics, CBs function as remarkable hosts for binding several organic uorophores (guests) with greater affinity and selectivity through hydrophobic interactions involving the rigid cavities or ion-dipole interactions with the carbonyl groups. 8,9 The inertness of the cavity and the absence of absorption or uorescence in the visible region also impart CBs as a great host for supramolecular interaction studies. 8,9 In particular, CBs are known to interact strongly with cationic uorophores.…”

“…8,9 The inertness of the cavity and the absence of absorption or uorescence in the visible region also impart CBs as a great host for supramolecular interaction studies. 8,9 In particular, CBs are known to interact strongly with cationic uorophores. 10,11 Encapsulation of the guest in the CB cavity causes the guest to experience rigid or a lower polar environment and results in distinct photophysical and photochemical behavior.…”

“…10,11 Encapsulation of the guest in the CB cavity causes the guest to experience rigid or a lower polar environment and results in distinct photophysical and photochemical behavior. 7,12 Among all the known CBs, cucurbit [7]uril (CB7) and cucurbit [8]uril (CB8) were extensively used for these investigations because of their water solubility and suitability of their cavity size for encapsulating different guest molecules. 6,[13][14][15][16][17] Cucurbiturils have been utilized as a template for stereoselective photodimerization, 18 supramolecular catalysis, 19 inhibition and disintegration of amyloid brils for therapeutics, 20 radionuclide separation, 21 construction of supramolecular assemblies, 22,23 and to modulate photophysical properties 10,24 for several cationic pyridinium or viologen derivatives.…”

Label-Free Fluorescent Determination of Sunset Yellow in Soft Drinks Based on an Indicator-Displacement Assay

“…IDA has become a popular approach for electrochemical/optical sensing by utilizing noncovalent interactions between a receptor (the host), indicator (the guest), and an analyte (the competitive guest) [1]. The sensing principle of IDA relies on the competition between a test substance and an indicator for the same binding site on the host [8][9][10]. When an analyte is added to a solution containing a hostindicator complex, the analyte displaces the indicator from the binding site.…”