A rhodamine-nitronaphthalimide Hg(II) complex for the simultaneous detection of oxidised and reduced glutathione

https://doi.org/10.1016/j.snb.2019.126825Get rights and content

Highlights

  • The unique crystal structure of 1 shows coplanar chromophores—energy transfer processes such as FRET can readily occur.

  • The 1:Hg complex gives a unique fluorescent response for both forms of the biologically relevant glutathione (GSH and GSSG).

  • Cellular imaging shows that 1 readily crosses cell membranes and has potential use in evaluating biochemical redox processes.

Abstract

Dual-fluorophore systems have attracted attention as they offer versatile photophysical properties and multiple mechanisms for sensing. Here we report that the Hg2+ complex of rhodamine-nitronaphthalimide conjugate 1 functions as a switch-on sensor for the simultaneous detection of reduced (GSH) and oxidised (GSSG) glutathione via a resonance Rayleigh scattering process, with detection limits of 4.3 μM and 11.9 μM, respectively. Hydroxide anion regenerates nitronanphthalimide 1 causing the fluorescence to “switch-off”, and the system is recyclable. This photophysical behaviour towards Hg2+, GSH and HO‾ forms the basis of a molecular level INHIBIT and AND logic gate.

Graphical abstract

The Hg(II) complex of rhodamine-nitronaphthalimide 1 can sense and discriminate both the oxidised and reduced forms of glutathione (GSSG and GSH).

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Introduction

Optical and fluorescent chemosensors are attractive cost effective alternatives to sophisticated analytical instrumentation as they can be designed for highly selective and real-time sensing with low detection limits [[1], [2], [3], [4], [5], [6]]. Such chemosensors have found use in both cellular imaging and environmental monitoring applications [[7], [8], [9]]. The majority of fluorescent sensors and probes are based on only a handful of fluorophores (such as rhodamines, fluoresceins, BODIPYs, coumarins, cyanines and aminonaphthalimides) [[10], [11], [12], [13], [14], [15], [16], [17], [18]] with analyte response elicited by means of photo-induced electron transfer (PET) [19,20] or modulation of an intramolecular charge transfer (ICT) process [21].

One approach for accessing new fluorophores, and in turn new sensing systems, is to develop hybrids or conjugates of existing fluorophores, and a number of such moieties have recently been developed that measure analytes through aggregation-induced emission, [22,23] Förster resonance energy transfer (FRET) [[24], [25], [26]], PET [27,28], and through-bond energy transfer (TBET) [29].

Amongst these, a number of rhodamine-naphthalimide conjugates have been prepared for the detection of Hg2+ and other species [22,[30], [31], [32], [33], [34], [35]], but the utility of the resultant metal complexes is relatively unexplored. Only a small number of Hg2+ complexes have been reported as sensors or probes in their own right [36,37], including for small anionic species such as iodide and cyanide [38,39]. Given the well-known affinity of Hg2+ for sulfur containing species [[40], [41], [42]], such as glutathione, there is considerable scope for further development. Glutathione (GSH) plays a key physiological role in regulating cellular redox homeostasis [43,44] and is the most abundant water soluble non-protein cellular thiol (1–10 mM) [45] protecting against oxidative stress by capturing free radicals [46]. Under oxidative stress, it continuously converts into glutathione disulfide (GSSG). Changes in cellular GSH and GSSG concentrations are linked with various serious diseases such as cancer, AIDS, liver damage, neurodegenerative diseases and heart problems [[47], [48], [49]] and as such rapid means for the detection of these species is of importance in clinical diagnostics. Most reported glutathione sensors can only detect the reduced form and suffer from auto-oxidation of glutathione, leading to inaccuracy in measurement [[50], [51], [52], [53], [54], [55]].

Here we report that the Hg2+ complex of the novel rhodamine-nitronaphthalimide conjugate 1 can indicate both the oxidised and reduced forms of glutathione by resonance Rayleigh scattering. Furthermore, because of the distinct responses of 1 to Hg2+, GSH and HOˉ, the system can be used as a molecular level INHIBIT and AND logic gate.

Section snippets

Synthesis and characterisation of 1 and its Hg2+ complex

The conjugate 1 was synthesised in two steps. First, rhodamine B and ethylene diamine (EDA) were reacted to form the known monoamine (RBN) (see ESI Fig. S1) [56]. Next, RBN was heated with 4-nitro-1,8-naphthalic anhydride to give the desired conjugate 1 (Scheme 1). The new compound was characterised by 1H NMR, 13C NMR, mass spectrometry (see ESI Fig. S2, S3 and S4) and X-ray crystallography.

The X-ray diffraction study revealed that conjugate 1 crystallised in monoclinic form with space group

Conclusions

In conclusion, rhodamine-naphthalimide conjugate 1 has been constructed and Hg2+ ion forms a 1:1 complex with 1 in which the rhodamine spirolactam ring opens to initiate the FRET process (λem = 583 nm). The 1:Hg2+ complex could be employed as a selective resonance Rayleigh scattering based sensor for both the reduced and oxidised form of glutathione (detection limit GSH 4.3 μM and GSSG 11.9 μM). Addition of the hydroxide anion efficiently quenched the fluorescence of the 1:Hg2+ complex and the

General experimental

Rhodamine B, 4-nitro-1,8-naphthalic anhydride (Sigma Aldrich) and ethylene diamine (Oakwood Chemical) were purchased from commercial sources. All metal nitrate salts were purchased from Alfa Aesar. All anions were used as their tetrabutyl ammonium salts except tetramethyl ammonium hydroxide and were purchased from Sigma Aldrich. All biomolecules (carboxylic acids, dicarboxylic acids and sulfur containing species) were obtained from Sigma Aldrich and used as supplied.

Melting points were measured

Conflicts of interest

There are no conflicts to declare

Acknowledgements

The authors would like to thank Deakin University for an Alfred Deakin Fellowship for H.S., the Australian government for a Research Training Program Scholarship (JL), and the Westpac Scholars Trust for a Research Fellowship (EJN), and are also immensely grateful to Prof. A.P. De Silva (Belfast) for helpful discussions.

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