Hg²⁺ mediated quinazoline ensemble for highly selective recognition of Cysteine

Highlights

• A quinazoline A1 derived was synthesized and used to recognize Hg²⁺.

• The Hg²⁺ detection limit (3.5 × 10⁻⁷ mol L⁻¹) is reported.

• This fluorescence change was further supported by DFT/TD-DFT calculations.

• The probe A1 + Hg²⁺ ensemble is also further successfully utilized for detection of the Cysteine.

• This system can also be applied in real samples.

Abstract

A fluorimetric sensor for Hg²⁺ ion and Cysteine based on quinazoline platform was designed and synthesized by one step reaction and characterized by using common spectroscopic methods. Time Dependent Density Functional Theory calculations shows that probe behaves as “ON–OFF” fluorescent quenching sensor via electron transfer/heavy atom effect. Receptor was found to exhibit selective fluorescence quenching behavior over the other competitive metal ions, and also the receptor-Hg²⁺ ensemble act as an efficient “OFF–ON” sensor for Cysteine. Moreover this sensor has also been successfully applied to detection of Hg²⁺ in natural water samples with good recovery.

Introduction

In recent years the recognition and monitoring of the heavy metal ions such as Hg²⁺, Pb²⁺, Cd²⁺ and Cu²⁺ is one of the most challenging field [1], [2], [3], [4]. Design and synthesis of selective sensor for Hg²⁺ is particularly important, since Hg²⁺ is hazardous metal and can cause detrimental effects on the environment even at very low concentration [5]. Mercury can easily penetrate through the skin and respiratory cell membranes and create difficulty in thyroid and adrenal hormone system [6]. Methyl mercury [7] derived from ionic/elemental mercury by bacteria affects a pregnant woman that reflects development delays in child [8], [9]. The US Environmental Protection Agency (EPA) recommended a limit of 2 ppb of Hg²⁺ in potable water [10]. Due to these harmful effects, designing new chromophore for analysis of Hg²⁺ becomes significant. Various techniques such as atomic absorption spectroscopy [11], atomic emission spectroscopy [12], electro chemical methods [13], [14] and photophysical methods have been used to detect the transition/heavy metal ions. Among these, photophysical methods are widely used due to its high selectivity, sensitivity and simple way of sample preparation. On the other hand intracellular thiol containing amino acids play vital role in biosynthesis and they are functional compounds of many proteins and enzymes [15], [16], [17]. Cysteine (Cys) and Homo Cysteine (Hcy) are biologically essential molecules required for the growth of cells and tissues in living systems. Especially the Cysteine levels are linked to many diseases such as Alzheimer, AIDS and cancer. Deficiency of Cysteine can cause delayed growth, liver damage, oedema, lethargy, fat loss, skin lesions and Psoriasis etc., [18], [19].

Numerous fluorescent chemosensors designed for sensing Hg²⁺ based on coumarin derivatives [20], [21], Hydroxyquinoline [22], Podants [23], [24], Rhodamines [25], Pyrene derivatives [26], quinazoline [27] and heterocyclic based moieties [28] culminated in either large fluorescence enhancement or quenching phenomena. Huang et al. [29] reported anthraquinone containing thiourea subunit as a colorimetric sensor for Hg²⁺. 2-Aminopyridine unit has been utilized for the fluorescent detection of Hg²⁺ by Ghosh et al. [30]. However most of the reported sensors have difficulty in distinguishing Hg²⁺ from Ag⁺ or Fe³⁺, which compete with Hg²⁺ for the binding sites of the sensor molecule. Mechanisms such as photo induced electron transfer (PET) [31], intramolecular charge transfer (ICT) [32], twisted intramolecular charge transfer (TICT) [33], metal–ligand charge transfer (MLCT) [34] and fluorescence resonance energy transfer (FRET) [35] have been invoked to explain the observed enhancement or quenching of fluorescence. In many of the fluorescent chemosensors for Hg²⁺ there may be a large fluorescence quenching because of PET property and heavy atom effect [36], [37]. Hitherto reported Hg²⁺ recognizing target compounds experienced multistep synthesis and tedious work-up. Therefore the design of sensors that can be easily synthesized for Hg²⁺ binding is of particular interest. The receptor containing nitrogen/oxygen and sulfur atom prefers the coordination of Hg²⁺ [38] over the competing transition metal ions. Besides Hg²⁺ various fluorescent chemosensors has been designed for the recognition of biological thiols based on different mechanism [39], [40], [41], [42], [43]. Due to the strong affinity of thiols towards Hg²⁺, the thiol containing amino acids easily binds with the Hg²⁺ ions. Recently, Fu et al. [44] and Li et al. [45] proposed a squarine and thiacalixarene-Hg²⁺ ensemble fluorescence assay for thiol containing amino acids, which involves enervating synthetic procedures.

In the present study, we have synthesized the probe A1 from 2-aminobenzohydrazide with CS₂ in single step process according to a literature procedure [46], [47]. Recently, Thar et al. reported the same probe as an electrochemical sensor for silver by employing stripping voltammetry method [48]. A1 is highly selective and sensitive turn-off fluorescent sensor for Hg²⁺ which could be utilized to quantify Hg²⁺ levels for health care and environmental monitoring. Further we applied the A1 + Hg²⁺ ensemble as a turn-on fluorescence sensor for Cysteine.