Amidofluorene-appended lower rim 1,3-diconjugate of calix[4]arene: synthesis, characterization and highly selective sensor for Cu2+

Amidofluorene-appended lower rim 1,3-diconjugate of calix[4]arene: synthesis, characterization and highly selective sensor for Cu2+ Rahman Hosseinzadeh*1, Mohammad Nemati1, Reza Zadmard2 and Maryam Mohadjerani3 Full Research Paper Open Access Address: 1Department of Organic Chemistry, Faculty of Chemistry, University of Mazandaran, Babolsar, Iran, 2Chemistry and Chemical Engineering Research Center of Iran (CCERCI), Tehran, Iran and 3Department of Molecular and Cell Biology, Faculty of Basic Science, University of Mazandaran, Babolsar, Iran Beilstein J. Org. Chem. 2016, 12, 1749–1757. doi:10.3762/bjoc.12.163 Email: Rahman Hosseinzadeh* - Associate Editor: N. Sewald * Corresponding author Received: 03 May 2016 Accepted: 14 July 2016 Published: 04 August 2016 © 2016 Hosseinzadeh et al.; licensee Beilstein-Institut. License and terms: see end of document. Keywords: calix[4]arene; chemosensor; copper ions; fluorene; fluorescence Abstract Functionalization of calix[4]arene with amidofluorene moieties at the lower rim led to formation of the 1,3-diconjugate of calix[4]arene L as a novel fluorescent chemosensor for Cu2+. The receptor molecule L exhibited a pronounced selectivity towards Cu2+ over other mono and divalent ions. The formation of the complex between L and Cu2+ was evaluated by absorption, fluorescence and 1H NMR spectroscopy. The sensor L showed a remarkable color change from colorless to purple and a fluorescence quenching only upon interaction with Cu2+. The 1:1 stoichiometry of the obtained complex has been determined by Job’s plot. The association constant determined by fluorescence titration was found to be 1.8 × 106 M−1. The sensor showed a linear response toward Cu2+ in the concentration range from 1 to 10 µM with a detection limit of 9.6 × 10−8 M. Introduction Owing to the substantial role of fluorescent chemosensors in biological, environmental, and chemical processes, their design and synthesis, especially for detection of metal ions has attracted great attention in supramolecular chemistry [1-4]. Copper is one of the crucial biological elements, which presents as catalytic cofactor for a variety of metallo-enzymes such as superoxide dismutase, cytochrome c oxidase, lysyl oxidase and tyrosinase, etc. [5-9]. However, excess amounts of Cu2+ are hazardous, due to generate reactive oxygen species (ROS) that disturbs cellular metabolism [10,11]. On the other hand, its deficiency may cause haematological and neurological diseases [12]. Therefore, the selective and sensitive measurement of Cu2+ ions – either as significant environmental pollutant or an essential trace element in human body – is a great challenge and 1749 Beilstein J. Org. Chem. 2016, 12, 1749–1757. the development of synthetic receptors based on organic ligands for the detection of Cu2+ seems to be necessary [13]. Accordingly, during the last decades, synthesis and modification of chemosensors based on supramolecular structures, especially calixarene derivatives, has been an appealing field for research [14]. Calixarene has been considered as an effective molecular scaffold in the improvement of fluorescent and chromogenic sensors, especially for metal-ion recognition [14,15]. Calix[4]arene derivatives having different binding centers such as nitrogen, oxygen and sulfur sites for recognition of metal ions can be readily synthesized [14,16,17]. A number of calix[4]arene-based fluorescence sensors for copper ions have been reported in the literature [18-27], including calix[4]arene bearing anthraceneisoxazolymethyl [3], quinolone [28], 5-nitrosalicylaldehyde [29], 3-alkoxy-2-naphthoic acid [30], coumarine [31] and benzothiazole [10,15] groups. In continuation of our studies on developing novel chemosensors containing fluorenyl moieties as fluorogenic group [32-34], we report here the design and synthesis of a new fluoreneappended 1,3-diconjugate of calix[4]arene (L), which possess distal amide groups on the lower rim of the conical framework to recognize Cu 2+ with high sensitivity and specificity (Scheme 1). Scheme 1: Fluorene appended 1,3-diconjugate of calix[4]arene. Results and Discussion 2 with 9H-fluoren-2-amine (4, obtained from nitration of fluorene and reduction of the resulting 2-nitrofluorene, (3)) in the presence of N,N-dicyclohexylcarbodiimide (DCC) in dichloromethane at room temperature gave the desired receptor L in 81% yield (Scheme 2). All the compounds including receptor L has been characterized by various spectral techniques such as 1H, 13C NMR and high resolution mass spectrometry (HRMS) (see Supporting Information File 1, Figures S1–S11). General procedure for UV–vis experiments The evaluation of cation-ligand interaction was performed with UV–vis spectroscopy. The UV–vis measurement of receptor L in CH3CN exhibited three absorption peaks at 282, 290, and 314 nm. Furthermore, the variation of UV–vis spectra was monitored by adding 10 equivalents of different metal ions as perchlorate salts (Cu2+, Hg2+, Pb2+, Zn2+,Co2+, Ni2+, Cd2+, Ag+, Ba2+, K+, Na+ and Li+). Unlike Cu2+ ions, the addition of 10 equiv of other metal ions to the 1.0 × 10 −5 M solutions of L resulted in no significant changes in the absorption spectra of ligand L. However, addition of Cu2+ to L resulted in a blue shift of the absorption band in the area of 280–290 nm (see Supporting Information File 1, Figure S12). Furthermore, a weak and broad absorption band from 600–800 nm was also observed (Figure 1). As shown in Figure 2, there was an evident color change from colorless to purple, which could be observed by the naked eye. The selectivity of receptor L towards Cu 2+ was precisely assessed by UV–vis spectroscopy during titration with different concentrations of Cu2+ from 0 to 100 equivalents in CH3CN. In the absence of Cu2+ ions, the ligand L exhibited three absorption bands at ≈282, ≈290 and ≈314 nm (Figure 3). Upon addition of Cu2+, the absorption band at 282 nm showed a blue shift along with an increase in peak intensity. The two observed isosbestic points at 295 and 318 nm upon addition of Cu2+ revealed formation of a stable complex between L and the copper ion. Moreover, upon addition of Cu2+, at higher concentrations of L a broad signal appeared at the area of 600–800 nm which can be related to a d→d transition (see Supporting Information File 1, Figure S13). This result is in accordance with those reported in literature [10] and indicates that the L binds copper as Cu2+. Synthesis The synthesis of 5,11,17,23-tetra-tert-butyl-25,27-di[(9Hfluoren-2-yl)aminocarbonylmethoxy]-26,28-dihydroxycalix[4]arene (L) is depicted in Scheme 1. The synthesis began with the reaction of p-tert-butylcalix[4]arene and ethyl bromoacetate in the presence of potassium carbonate in acetonitrile. Ester hydrolysis of compound 1 afforded the 5,11,17,23-tetratert-butyl-25,27-di(hydroxycarbonylmethoxy)-26-28-dihydroxy calix[4]arene (2) in high yield. Coupling of this diacid Fluorescence titrations of L wi (...truncated)