Quinazoline copper(II) ensemble as turn-on fluorescence sensor for cysteine and chemodosimeter for NO

Highlights

• Quinazoline based fluorescence chemosensor is an ON–Off fluorescent sensor for Cu(II), the Cu(II) complex is an Off–ON sensor for Cys and an Off–ON chemodosimeter for NO.

• QHYN displays simple method of synthesis and high stability.

• TD-DFT calculations and cyclic voltammetric studies were performed for the recognition behaviour of QHYN upon addition of Cu²⁺.

Abstract

A fluorescent quinazoline based chemosensor QHYN had been designed and synthesized. It exhibits high sensitivity and selectivity towards Cu²⁺ over other metal ions in DMSO:H₂O (1:9, v/v) at pH = 7.4 [HEPES buffer] by fluorescence quenching. Addition of nitric oxide to a solution of this QHYN·Cu(II) restores the fluorescence. This is attributed to the reduction of the Cu(II) centre by nitric oxide to diamagnetic Cu(I). The fluorescence response of QHYN·Cu(II) to NO is direct and specific, which is a significant improvement over commercially available small molecule-based chemodosimeter probe that are capable of detecting NO. The QHYN·Cu(II) also acts as an efficient “off–on” fluorescent sensor for cysteine with high sensitivity.

Introduction

The development of fluorescent molecules for the photophysical detection of cations [1], [2], anions [3], sugars and proteins [4], [5] has attracted considerable attention due to their prime importance for biological and environmental applications [6]. After zinc and iron, copper is the significant metal pollutant and also the third most abundant essential trace element in the human biology. Nevertheless copper(II) metabolically requires homeostasis for its inadequacy results in anaemia, and irregularity in glucose and cholesterol metabolism [7] while its surplus in the body leads to Menkes disease, Wilson disease [8], [9] and so on. So it is necessary to observe copper levels in biological systems and in the environment.

Various analytical methods such as photometric methods, atomic absorption spectroscopy (AAS), inductively coupled plasma emission or mass spectrometry (ICP-ES, ICP-MS), total reflection X-ray fluorimetry (TXRF) and anodic stripping voltammetry [10], [11], [12] (ASV), though provide good detection limit for detection of copper ions, involve high cost instrumentation and tedious procedure. Among these methods photophysical methods are widely used due to its high selectivity, simplicity and sensitivity. In addition the photophysical methods make feasible bio-imaging of analytes. Many fluorescent probes for copper revealing either fluorescence On–Off or Off–On types have been developed [13], [14], [15].

In recent years, metal analyte bound fluorescent receptor are being developed as sensors for detection of small molecules like NO, cysteine [16], [17]. Nitric oxide is a neutral molecule with one unpaired electron, and it is a signal transduction molecule in the physiological and biological systems. It plays major role in the cardiovascular system as well as in the central and peripheral nervous systems [18]. Elevated levels of NO production are implicated with various diseases, while minimum level of NO is necessary for protecting liver from ischaemia disease [19]. In earlier days, small-molecule fluorescent probes reported for NO detection such as o-diaminonaphthalene and o-diaminofluorescein respond only to NO₂⁻, N₂O₃, the oxidized products of NO, rather than NO directly [20], [21]. Transition-metal complexes had been investigated as platforms for NO detection. Number of iron complexes, which can act as sensors for NO in aqueous medium, exhibit only modest turn-on emission with NO and these are air sensitive [22]. Nowadays the reduction of Cu(II) to Cu(I) by nitric oxide can offer a good methodology for nitric oxide detection but many of the reported fluorescence probes for NO involves complicated procedures. Besides they display a decrease in fluorescence after reaction with NO [23] and are pH-sensitive. In our case the QHYN preparation is very easy and the method offers excellent yield. The molecule QHYN is not pH/air sensitive in nature. Of the twenty amino acids cysteine (Cys), an important and essential amino acid, plays crucial role in the biological systems because of its thiol group [24], [25]. In addition Cys is a building block of proteins and key factor in enzyme reaction. It can also be used as radio-protective agent, cancer indicator and connected to Alzheimer, Parkinson and autoimmune syndrome, etc. [26], [27]. Hence the quantitative detection of NO/cysteine is of immense value.

In continuation of our ongoing research for the development of fluorescent chemosensors [28], [29], [30] here in we report simple rapid and easily synthesizable QHYN Schiff base derivative [31] as a fluorescent probe for Cu²⁺ ions. Subsequent investigation of Cu²⁺ bound QHYN reveals its capability to sense NO as well as cysteine independently. To the best of our knowledge this is the simple molecule based fluorescent sensor that allows the detection of both nitric oxide (NO) and cysteine (Cys) independently.