Chiral recognition of naproxen enantiomers based on fluorescence quenching of bovine serum albumin–stabilized gold nanoclusters

https://doi.org/10.1016/j.saa.2017.05.029Get rights and content

Highlights

  • A simple, fast and green method for chiral recognition of S- and R-naproxen has been introduced.

  • The fluorescence intensity of bovine serum albumin–stabilized gold nanoclusters was quenched.

  • The chiral recognition occurred due to steric effect between bovine serum albumin and naproxen.

Abstract

A simple, fast and green method for chiral recognition of S- and R-naproxen has been introduced. The method was based on quenching of the fluorescence intensity of bovine serum albumin–stabilized gold nanoclusters in the presence of naproxen enantiomers. The quenching intensity in the presence of S-naproxen was higher than R-naproxen when phosphate buffer solution at pH 7.0 was used. The chiral recognition occurred due to steric effect between bovine serum albumin conformation and naproxen enantiomers. Two linear determination range were established as 7.4 × 10−7–9.1 × 10−6 and 9.1 × 10−6–3.1 × 10−5 mol L−1 for both enantiomers and detection limits of 7.4 × 10−8 mol L 1 and 9.5 × 10−8 mol L−1 were obtained for S- and R-naproxen, respectively. The developed method showed good repeatability and reproducibility for the analysis of a synthetic sample. To make the procedure applicable to biological samples, the removal of heavy metals from the sample is suggested before any analytical attempt.

Introduction

All enzymes, carbohydrates, amino acids, proteins, nucleosides and some alkaloids and hormones are known to be chiral in character [1], [2]. In pharmaceutical industries, 56% of the synthesized drugs are chiral and 88% of them are racemates as reported in literature [1], [3]. Depending of the type of application, one enantiomer is active while the other may produce harmful side-effects and toxicity [4]. Since individual enantiomers of pharmaceuticals are often differ in their pharmacological bioactivity, and may undergo different pharmacokinetic and metabolic fates in the biological systems, chiral recognition is of great concern in medical science and pharmaceutics.

Naproxen (naprosyn) [(+)6-methoxy-α-methyl-2-naphthaleneacetic acid], as a chiral compound (Scheme 1), is often used as a nonsteroidal anti-inflammatory analgesic drug [5]. It is used in the treatment of many diseases such as rheumatoid arthritis, osteoarthritis, juvenile rheumatoid arthritis, ankylosing spondylitis, acute gout and primary dysmenorrhea [6]. Only the S, (+) isomer of naproxen, exhibits dose-related anti-inflammatory, analgesic and antipyretic activity in animals, thus, only this isomer is included in the naproxen formulations [5]. As reported, the pharmacological activity of S-naproxen is 28 times higher than R-naproxen [7].

Different analytical methods have been developed for the chiral recognition of biomolecules and drugs including high performance liquid chromatography [7], [8], [9], gas chromatography [10], [11], [12], electrophoresis [13], spectrophotometry [14], [15], electrochemistry [16], [17], spectrofluorimetry [18], [19]. Some of these methods are time-consuming, expensive and require expertise operator; thus, it is desirable to develop a simple, sensitive, and efficient assay for chiral recognition to overcome the above mentions problems in recognition of chiral compounds.

Based on new technologies provided for development of biosensors [17], [20], particularly by discovery of fluorescent nanomaterials such as gold nanoclusters (AuNCs), new opportunities have been generated for targeting applications [21], [22], [23]. AuNCs, with small size regime, are comparable to Fermi wavelength of the conduction electrons [24] and exhibit molecule-like properties in the experiments based on probing the absorption and fluorescence spectra [25]. On the other hand, metal nanoclusters can be passivated by a monolayer of organic ligands, which results in a high fluorescence intensity. In this regard, protein-stabilized gold nanoclusters have attracted special usage due to their facile synthesis, strong fluorescence emission, high photostability, non-toxicity and high biocompatibility [26]. For instance, cystatin C [27], biothiols [28], glucose [29], cysteine [30], acetylcholinesterase activity [31] as well as cyanide [32] and mercury [33] have been successfully determined based on quenching of the fluorescence of bovine serum albumin–stabilized gold nanoclusters (BSA-AuNCs).

A preliminary test showed that S-naproxen had higher affinity in quenching the fluorescence intensity of BSA-AuNCs than R-naproxen. Considering this, a simple and reliable fluorometric method for the chiral recognition of naproxen enantiomers has been developed. Factors affecting quenching intensity such as pH, buffer type and concentration in the sample matrix as well as the effect of temperature have been investigated.

Section snippets

Reagents

Naproxen enantiomers were purchased from Merck. To prepare the stock solutions of both R- and S-naproxen (1.0 × 10−2 mol L−1), 11.5 mg of each enantiomer was dissolved in individual 5-mL volumetric flask and was diluted with deionized water. The working solutions of each enantiomer with a concentration of 1.0 × 10−4 mol L−1 was prepared from their stock solutions. Bovine serum albumin and gold (III) tetrachloride trihydrate (HAuCl4·3H2O) were obtained from Sigma-Aldrich and their individual solutions

Characterization of BSA-AuNCs

The FT-IR spectra of both BSA and BSA-AuNCs were recorded as shown in Fig. 1. The IR peaks of pure BSA at 3420, 3055, 1650, and 1539 cm−1 are assigned to the stretching vibration of single bondOH, amide A (mainly single bondNH stretching vibration), amide I (mainly Cdouble bondO stretching vibrations), and amide II (the coupling of bending vibrate of Nsingle bondH and stretching vibrate of Csingle bondN) bands, respectively [37], [38]. The difference between the IR spectrum of pure BSA and BSA-AuNCs revealed that the characteristic peak of single bondNH groups

Conclusion

Bovine serum albumin–stabilized gold nanoclusters (BSA-AuNCs) have been used for chiral recognition of naproxen enantiomers based on fluorescence quenching of BSA-AuNCs. The method was very simple, fast and did not require any expensive or hazardous reagents. A dynamic quenching mechanism was detected for BSA-AuNCs and naproxen enantiomers interaction. It was supposed that the chiral discrimination was possible due to the steric hindrances when either S- or R-naproxen interacted with bovine

Acknowledgments

The authors wish to express their gratitude to Shiraz University (91GCU3M172254) Research Council for the financial support of this work.

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