Fluorescence Response and Self‐Assembly of a Tweezer‐Type Synthetic Receptor Triggered by Complexation with Heme and Its Catabolites

Abstract

There is increasing interest in the development and applications of synthetic receptors that recognize target biomolecules in aqueous media. We have developed a new tweezer‐type synthetic receptor that gives a significant fluorescence response upon complexation with heme in aqueous solution at pH 7.4. The synthetic receptor consists of a tweezer‐type heme recognition site and sulfo‐Cy5 as a hydrophilic fluorophore. The receptor–heme complex exhibits a supramolecular amphiphilic character that facilitates the formation of self‐assembled aggregates, and both the tweezer moiety and the sulfo‐Cy5 moiety are important for this property. The synthetic receptor also exhibits significant fluorescence responses to biliverdin and bilirubin, but shows very weak fluorescence responses to flavin mononucleotide, folic acid, and nicotinamide adenine dinucleotide, which contain smaller π‐scaffolds.

Control of the stepwise self-assembly process of a pH-responsive amphiphilic 4-aminoquinoline-tetraphenylethene conjugate

“…S1†). 25 In that study, we found that a synthetic receptor bearing sulfo-Cy5 (Fig. S1b†) exhibits a change in the fluorescence intensity between pH 6 and 8 probably due to the self-assembly through the protonation and deprotonation of the 4-AQ moiety, 25 b although precise details were not determined.…”

“…The pH-dependent change in the UV-Vis absorption spectra (Fig. S3b†) suggests that 1 mostly exists in its diprotonated form at pH 5.5, 25,32 and that electrostatic repulsion was alleviated by the electrostatic screening effect imparted by 0.10 M NaCl. 12,13 The absorbance of 1 at 330 nm continuously decreased when increasing the pH from 5.5 to 7.8.…”

“…This interpretation was supported by the pH-dependent change in the UV-Vis absorption spectra through the protonation of the 4-AQ moiety of chloroquine 32 and our previous results. 25 The shift in the apparent p K a value of the protonated 4-AQ 28,29,32 of 1 (Fig. S3a†) is probably due to the self-assembly effects.…”

“…Previously, we have addressed the development of tweezer-type synthetic receptors for heme in aqueous media. 25 Based on the knowledge that 4-AQ antimalarial agents, 26 such as chloroquine (Fig. 1), exhibit the heme-binding ability, 27 the synthetic receptors consist of two 4-AQ moieties bearing tertiary aliphatic amines at the terminal of their side chains (Fig.…”

“…The TPE and 4-AQ moieties were anticipated to contribute to self-assembly through non-covalent interactions including π–π stacking and hydrophobic interactions. 25 Since 1 can exist in its neutral, monoprotonated, and diprotonated forms (Scheme 1), the pH-dependent self-assembly behavior of 1 was expected.…”