Dinuclear Zinc(II) Macrocyclic Complex as Receptor for Selective Fluorescence Sensing of Pyrophosphate

Abstract

A new diethylenetriamine-derived macrocycle known as L, bearing 2-methylquinoline arms and containing m-xylyl spacers, was prepared in good yield by a one-pot [2 + 2] Schiff base condensation procedure, followed by reduction with sodium borohydride. Up to now this is the first hexaazamacrocycle with appended fluorophore units. Single-crystal X-ray diffraction determination of the dinuclear zinc(II) complex of L showed that metal centers are located at about 7.20(2) Å from one another. This complex exhibits only weak fluorescence in aqueous solution, but the addition of 1 equiv of pyrophosphate (PPi) caused a 21-fold enhancement of the fluorescence intensity. The sensor response is linear up to a value of 10 μM HPPi(3-) and has a detection limit of 300 nM. The receptor behaves as a highly selective sensor for pyrophosphate as other anions, including phosphate, phenylphosphate (PhP), adenosine monophosphate (AMP), adenosine diphosphate (ADP), and adenosine triphosphate (ATP), failed to induce any fluorescence change and practically do not affect the fluorescence intensity of the sensor in the presence of HPPi(3-). Competition titrations carried out in aqueous solution at pH 7.4 [in 20 mM 3-(N-morpholino)propanesulfonic acid (MOPS) buffer] by spectrofluorometry revealed a high association constant value of 6.22 log units for binding of PPi by the dinuclear zinc(II) receptor, one of the highest reported values for colorimetric/fluorometric sensors able to work under real aqueous physiological conditions, while association constant values for binding of the other phosphorylated substrates are in the 5.51-4.03 log unit range.

Recent Advances in Macrocyclic Fluorescent Probes for Ion Sensing

“…Mesquita et al recently reported PPi sensing with the zinc complex of methylquinoline-substituted azamacrocycle 43 ( Figure 18 ) [ 119 ]. This system demonstrated exceptional selectivity and sensitivity for PPi over a variety of competing anions including other phosphorous-based anions, with a 21-fold fluorescence increase and small (10 nm) blue shift to 370 nm upon the addition of one equivalent of PPi.…”

“…A solution containing TPE/imidazolium macrocycle 42 and one equivalent of Zn(OAc) 2 reports PPi binding via an AIE mechanism, which gives rise to a significant fluorescence enhancement at 472 nm [ 118 ]. In a similar vein, the Zn 2+ complex of methylquinoline-substituted azamacrocycle 43 has shown exceptional selectivity and sensitivity for PPi over other phosphorous-based anions, returning a 21-fold fluorescence increase in the presence of PPi (1 equivalent) via an ICT mechanism [ 119 ].…”

Pyrophosphate Prompted Aggregation‐Induced Emission: Chemosensor Studies, Cell Imaging, Cytotoxicity, and Hydrolysis of the Phosphoester Bond with Alkaline Phosphatase

“…The detection and quantification of inorganic phosphates are crucial because of their role in many environmental and biological processes . Pyrophosphate is a dimeric form of inorganic phosphate which has a decisive role in the cellular metabolic process, real‐time DNA sequencing, energy storage, signal transduction, ATP hydrolysis, and calcium pyrophosphate deposition etc . Moreover, pyrophosphate has become an indispensable biomarker for diagnosis of numerous diseases like chondrocalcinosis, arthritis, and cancer .…”

Design and Synthesis of a Dinuclear Copper(II) Probe for Selective Fluorescence Sensing of Pyrophosphate

“…Recently, intracellular PPi in low concentration has become an important indicator for early cancer research [14,15]. Therefore, the development of high-efficient probes for the detection and discrimination of PPi has become an attractive and challenging task in recent years [16][17][18][19][20].…”