Amino Acid Derivative of Calix[4]Arene as Schiff Base for Sensing of Copper(II)

Introduction

Calixarenes are cyclic oligomer which have been applied as ionic and molecular recognition in the past years [1].

The Calixarene chemists have highly noticed selective proteins, anionic or cationic sensing by changing in quenching effect on fluorescence as a result of its relative ease in addition to high sensitivity and selectivity [2,3].

The development of chemosensors for recognizing copper ions has attracted a great deal of interest thanks to its vital role in chemical and biological systems [4,5]. Disproportionate amounts of copper ions could possibly result in neurodegenerative diseases and amyotro- phiclateral sclerosis [6]. Different Methods such as UV, near infrared and emission spectroscopies were developed for sensing of copper ions using and sensing mechanisms engaging photoinduced electron transfer,
fluorescence resonance energy transfer, internal charge transfer, nanotechnology and other photophysical properties which are compatible with the analysis of Cu²⁺ in biological systems [7].

It is extremely popular that calixarens can convert to other conformations very fast [8]. If the desired function is protein or cationic and anionic recognition, the molecular receptor which has been synthesized, have a prudent balance between flexibility and rigidity. So that it can interact with the different guests. Due to the rigid Calix [4] arene platform and its small cavity, it is not able to accommodating different guest. Calixarenes macrocycle could be modified by functionalization at their upper or the lower rim [9].

Most reported chemosensors for copper ions contain the attachment of fluorophore units to the macrocyclic or chelating scaffolds. Among famous macrocyclic frameworks, calix [4] arenes are known to be highly useful building for achieving ionic and  molecular  recognition [10], possibly because of their preorganized cavity and facile modifiability.

Schiff bases (imines) are also known to serve as good chelating sites for metal ions [11]. Hence, a molecular probe that has a calixarene scaffold, fluorescence moiety and a Schiff base substructure seems to be worth examining for recognizing metal ions [12].

Here we explain the synthesis of new Schiff-base calix[4]arene receptor with various functional units for the identification of copper ion in acetonitrile solution.

Materials and Methods

We have used commercial quality solvents and reagents. All cation solutions were prepared from their perchlorate salts and solution of Cu⁺ was also provided from CuI salt.

¹H, ¹³C NMR spectra were recorded on a Bruker Avance spectrometer at 500 and 125 MHz using CDCl₃ with TMS reference. In order to record infrared spectra¸ a Galaxy series FT-IR 5000 spectrophotometer was applied. The melting points were measured by using of a Buchi B-545 apparatus (uncorrected). A Qstare ERSI-q- TOF was used to recording of High resolution mass spectra (HRMS). Florescence spectra were recorded on JASCO FP-6500.

Synthesis Compounds (1- 3) were prepared based on the literature methods [13, 14]. The synthesis of other compounds (4-5) was done by adjusting known synthetic procedures.

Figure S1: 1H NMR (400 MHz, CDCl3) spectrum of 4   Click here to View figure

 

25,26,27-Tripropoxy-28-[(3-(4-formylphenoxy)­propoxy)]­-5,11,17,23­tetra (tertbutyl)calix[4]arene (4, C₆₃H₈₄O₆)

p-hydroxybenzaldehyde 0.23 g (1.92 mmol) and a mixture of 3, 0.9 g (1 mmol) and K₂CO₃, 0.43 g (3.11mmol) dissolved  in acetonitrile (50 mL), and the solution was stirred for 60 hours were refluxed. After cooling, the solvent evaporated under vacuum. The residue solid was extracted with CH₂Cl₂ (100 mL) and rinsed off with water (50 mL) and 1 M HCl (2 × 50 mL). Then the organic layer was dried over MgSO₄ and crystallized from CH₂Cl₂: methanol (1:1). Yield 0.84g (85%) 4. T_mp.: 211–213^ºC;IR, ν, cm⁻¹: 1667 (C=O) ; ¹H NMR, δ, ppm: δ= 0.93t (6H, CH₃), 1.02 s (18H, -C(CH₃)₃), 1.05 s (9H, -C(CH₃)₃), 1.2 s (9H, -C(CH₃)₃), 1.3 t(3H, CH₃), 2.01-2.07m (6H, -OCH₂-CH₂-CH₃-), 2.67 m(2H, -OCH₂-CH₂-CH₂O-), 3.18 d (4H, J = 12.5 Hz, ArCH₂Ar), 3.82 t (4H, -OCH₂-CH₂-CH₂-),3.93 t(2H, -OCH₂), 4.15 t (2H, -OCH₂), 4.31t (2H, -OCH₂), 4.35 d (4H, 2J = 12.5 Hz, ArCH₂Ar), 6.74 d (4H, J = 2.0 Hz, ArH), 6.92 s (4H, ArH), 7.08 d (2H, J = 2.0 Hz, ArH), 7.89 d(2J = 11.9 Hz, 2H, ArH), 9.94 s (H, CHO); ¹³C NMR (125 MHz) δ= 10.71, 10.85, 23.69, 23.82, 30.37, 31.47, 31.50, 31.80, 31.95, 31.98, 34.17, 34.30, 66.61, 72.08, 72.21, 77.72, 115.14, 125.15, 125.32, 125.47, 125.59, 132.43, 133.55, 133.76, 134.71, 144.63, 144.75, 145.19, 153.70, 164.71, 191.21; HRMS m/z= (951.47) [M]⁺

Figure S2: 13C NMR (100 MHz, CDCl3) spectrum of 4   Click here to View figure

 

25,26,27-Tripropoxy-28-[(3-[(methyl 2-(benzyliden amino) propanoate)]propoxy)]-5,11,17,23 tetra(tertbutyl)calix[4]arene (5, C₆₇H₉₁NO₇)

A solution of L-Alanine methyl ester hydrochloride 0.04 g (0.37 mmol) and triethylamine (1 mL, excess) in MeOH (10 mL) were added to solution of compound 4 0.2 g (0.37 mmol) in CHCl₃ (50 mL) and the reaction mixture was refluxed for 2 days. After cooling the crude material was crystallized from CHCl₃: MeOH (1:3). Yield 0.7g ( 71%) 5. T_mp.:110–114^oC IR, ν, cm⁻¹: 1750 (C=O); ¹H NMR, δ, ppm: δ= 1.02 s (9H, -C(CH₃)₃), δ= 1.04s (18H, -C(CH₃)₃), 1.05-1.12 m (18H, -C(CH₃)₃ and CH₃) ), 1.22 d (3H, CH₃), 1.55 m (6H, -OCH₂-CH₂-CH₃-), 2.07 m(2H, -OCH₂-CH₂-CH₂O-), 3.14 d (4H, J = 12.3 Hz, ArCH₂Ar), 3.72-4.05 m (14H, -OCH₂-CH₂-CH₂-, OCH₃, CH-CH₃), 4.40 d (4H, 2J = 12.3 Hz, ArCH₂Ar), 6.68-6.94 m (13H, ArH and CH); HRMS m/z= (1055.6644) [M]⁺

Figure S3: FT-IR spectrum of 4   Click here to View figure

 

Results and Discussion

In this work we synthesized new chiral Schiff base calix[4]arene and also investigated identification properties of it towards different metal ions. The synthesis of 5 is depicted in Figure 1.

To prepare the 4¸ p-hydroxybenzaldehyde was added to 3 in CH₃CN in presence of K₂CO₃ as a base. Compound 4 was characterized by a combination of FT-IR, ¹H NMR and HRMS. The spectral data of 5 could be found in the experimental section. Compound 5 is asymmetric because of the connection of amino acid as a chiral subunits in the calix[4]arene.

Figure 1: Synthetic route of 5 Click here to View figure

Figure S4: High-resolution mass spectrum (HRMS) of 4 Click here to View figure

 

Selectivity and sensitivity of the synthesized receptor 5 were studied by using fluorescence titration experiments in CH₃CN solution. The Data analysis and K_a values were determined by Sigmaplot-software. Our results show that receptor 5can be served as a selective metal sensors. Figure 3 illustrates how adding a number of metal ions can change the fluorescence intensity of molecular receptor 5 relatively. From this data, it can be observed that whereas no remarkable change occurs by adding number of metal ions, Cu²⁺ generates a significant quenching on its emission band. This could be applied as a fluorescence sensor which needed a complete investigation of 5 through fluorescence spectroscopy when different ions are present. fluorescence emission spectrum of 5 was recorded from 300 to 550 nm by exciting it at 290 nm when the emission maximum was recorded at 330 nm.

Binding constants (K_a) were calculated by equation based on literature [15].

The fluorescence intensity of 5 in the presence increasing concentration of Cu²⁺ is shown in Figure2. According to our fluorescence spectral studies the association constant between 5 and Cu²⁺ was 1.2 × 10⁵ M⁻¹.

Figure 2: Changes in fluorescence intensity of 5 (40 µM) in ACN in presence of Cu2+ (0-16.7 µM) and resulting titration curve Click here to View figure

Figure S5: 1H NMR (400 MHz, CDCl3) spectrum of 5 Click here to View figure

 

More over¸ In order to understand the selectivity Cu²⁺ by the receptor¸ comparative cations fluorescence measurements were done with different cations. It has been found that Cu²⁺ does confer significant change in the fluorescence measurements. (Figure 3)

Figure 3: Fluorescence selectivity of 5 toward Cu2+ over various competitve ions Click here to View figure

 

The Job’s plot studies show a 1:1 stoichiometry between (5) and Cu²⁺ion.

In order to examine the interaction between Schiff base moiety 6 (Figure 4) and different ions metal, this compound was prepared based on the literature methods [16]. Our results show that only the Schiff base moiety has no interaction with the metal ions.

Figure 4: The structure of Schiff base moiety, 6   Click here to View figure

Figure S6: High-resolution mass spectrum (HRMS) of 5 Click here to View figure

 

Acknowledgements

Partial financial support by Chemistry and Chemical Engineering Research Center of Iran is greatly appreciated.

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