Highly selective and sensitive macrocycle-based dinuclear foldamer for fluorometric and colorimetric sensing of citrate in water

Abstract

The selective detection of citrate anions is essential for various biological functions in living systems. A quantitative assessment of citrate is required for the diagnosis of various diseases in the human body; however, it is extremely challenging to develop efficient fluorescence and color-detecting molecular probes for sensing citrate in water. Herein, we report a macrocycle-based dinuclear foldamer (1) assembled with eosin Y (EY) that has been studied for anion binding by fluorescence and colorimetric techniques in water at neutral pH. Results from the fluorescence titrations reveal that the 1·EY ensemble strongly binds citrate anions, showing remarkable selectivity over a wide range of inorganic and carboxylate anions. The addition of citrate anions to the 1·EY adduct led to a large fluorescence enhancement, displaying a detectable color change under both visible and UV light in water up to 2 μmol. The biocompatibility of 1·EY as an intracellular carrier in a biological system was evaluated on primary human foreskin fibroblast (HF) cells, showing an excellent cell viability. The strong binding properties of the ensemble allow it to be used as a highly sensitive, detective probe for biologically relevant citrate anions in various applications.

A Copper(II) Macrocycle Complex for Sensing Biologically Relevant Organic Anions in a Competitive Fluorescence Assay: Oxalate Sensor or Urate Sensor?

“…This structure showed significant resemblance to the structure reported by Rhaman et al ( Figure 1 e). 23 One exception is the absence of an internal binding pocket in the structure by Rhaman et al. due to the near complete masking by methyl groups.…”

“…Citrate is larger than oxalate and has been proposed to bind to the external face of the related copper(II) macrocycle that contains thiophene groups in lieu of the phenyl groups in the present study ( Figure 1 e). 23 Due to the prominence of ethylenediamine tetraacetic acid (EDTA) used as an anticoagulant in blood collection, it was necessary to determine its potential for interference with the assay. We observed 82% recovery of fluorescence with ethylenediamine tetraacetic acid (EDTA) in the assay at 500 μM ( Figure 4 ).…”

“… 22 (e) Copper(II)-based macrocycle showing 1:1 citrate–sensor interaction. 23 Coordinated water molecules were removed from all structures for visibility. All 3D structures (other than panel e middle) were viewed and exported from Mercury 4.0.0 ( ) with space fill atomic radii set to 1× van der Waals radii.…”

“…Panels b, c, and e show two different perspectives in space fill. The middle panel of e was reproduced from ref ( 23 ) (Copyright 2018 Springer Nature Limited) and is licensed under a Creative Commons License permitting reproduction ( )).…”

High performance intensiometric direct- and inverse-response genetically encoded biosensors for citrate

“…A variety of synthetic fluorescent indicators for citrate have been reported, including ones based on indicator displacement assays [11][12][13] , turn-on fluorescence complexation 14 , competitive binding of metal ions such as Eu 3+ and Pb 2+ (Refs. 15,16 ), and aggregation induced emission 17 .…”