A High‐Affinity “Synthavidin” Receptor for Squaraine Dyes

Abstract

Strong‐binding host‐guest pairings in aqueous media have potential as “supramolecular glues” in biomedical techniques, complementing the widely‐used (strept)avidin‐biotin combination. We have previously found that squaraine dyes are bound very strongly by tetralactam macrocycles possessing anthracenyl units as cavity walls. Here we show that replacing the anthracenes with pentacyclic 5,7,12,14–tetrahydro–5,7,12,14–tetraoxapentacene (TOP) units generates receptors which bind squaraines with increased affinities (around Ka = 1010m‑1) and improved selectivities. Binding can be followed through changes to squaraine fluorescence and absorbance. The TOP units are easy to prepare and potentially variable, while the TOP‐based receptor shows improved photostability, both in itself and in complex with squaraines. The results suggest that this system could prove valuable in the further development of practical “synthavidin” chemistry.

Expanding the Hydrophobic Cavity Surface of Azocalix[4]arene to Enable Biotin/Avidin Affinity with Controlled Release

“…Their findings indicated that increasing the buried hydrophobic surface area of recognition pairs is important for improving binding affinities in aqueous solution. Established examples of ultrahigh‐affinity receptors, such as cucurbiturils, [18c] tetralactam macrocycle, [17d] Xcage, [17e] corralarenes, [17f,g] further highlighted the substantial impact of reinforcing the hydrophobic effect within the cavity on augmenting aqueous recognition affinity. However, merely increasing hydrophobic interacting surface area may not consistently ensure an enhancement in binding strength.…”

Adaptive and Ultrahigh‐Affinity Recognition in Water by Sulfated Conjugated Corral[5]arene

“…Despite of these endeavor, most synthetic receptors known today struggle [15][16][17][18] to achieve biomolecular range affinities (K a > 10 6 M À 1 ) in aqueous solution because of the enthalpy-entropy compensation effect. [19,20] Synthetic receptors with ultrahigh affinities (i.e., K a > 10 9 M À 1 ) in water are still scarce and mainly limited to cucurbiturils, [7,21,22] with a few examples scattered among tetralactam macrocycles, [13,23,24] molecular cages, [25] calix [4]pyrrole, [26,27] and pillararenes. [12] Nevertheless, these limited instances of ultrahigh-affinity recognition pairs have already demonstrated significant potential across diverse applications, including protein purification, [6,28] noncovalent molecular conjugation, [29] drug sequestration, [12,30] bioimaging, [25,31] drug delivery, [32][33][34][35] and soft materials.…”