Mechanosynthesis of Diaminobiphenyls-Based Schiff’s Bases as Simple Probes for the Naked-Eye Detection of Cyanide Ion

Abstract

Cyanide ions are known to be lethal for insects and mammals and harmful for the environment, and new methods for their selective detection are in high demand. Herein, the mechanosynthesis of simple Schiff’s bases-based probes S1–S3 for visual detection of CN⁻ anion is reported. These probes were obtained by means of a reaction between isomeric 4,4-, 3,3- and 2,2-diaminobiphenyls and 4-nitrobenzaldehyde under ball milling conditions. The probes showed high selectivity and sensitivity toward CN⁻ anion via a dramatic “yellow-to-dark purple” color change with a detection limit of 26 × 10³, 8.7 × 10³ and 14 × 10³ ppm for S1–S3, respectively. The proposed mechanism of the detection suggests the deprotonation of a proton from an imine moiety, followed by the formation of charge transfer complexes (CTC).

1. Introduction

CN⁻ ion donors are heavily involved in a wide variety of industrial processes, for instance, for the manufacturing of synthetic fibers, resins, and herbicides in mining and metallurgical branches such as gold extraction and in galvanic processes, accompanied by potential environmental contamination [1,2]. In nature, cyanides are produced by cyanobacteria, certain fungi, and algae [3]. In the form of cyanogenic glycosides cyanides are presented as antifeedants in a number of plants and plant seeds, such as cassava, seeds of bitter almonds, apples, and apricots [4,5]. According to the World Health Organization (WHO, Geneva, Switzerland), the allowed level of cyanide in drinking water should not exceed 2 µg/L [6]. The high toxicity of cyanide is associated with its ability to inhibit the enzyme cytochrome-c oxidase, which prevents the transport of electrons from cytochrome-c to oxygen and interrupts the generation of aerobically produced ATP to cause histotoxic hypoxia [7].

Based on all of the above, there is a demand for analytical systems for CN⁻ detection and/or monitoring at potential pollution sources for early warning of seepage of hazardous wastes. Nowadays, numerous methods and equipment have found an application in the purpose of analyzing soil, water, and air [8]. The instrumental methods have several drawbacks; for instance, they are bulky, expensive, require specific qualification, and are inappropriate for prompt analysis. However, colorimetric chemosensor tests are the most widespread because of their fast response, high sensitivity and selectivity, visual/naked-eye detection, ease of use, high selectivity, cheapness, and wide range of target analytes [9]. In addition to a large number of reports on chemical sensors that are able to detect cyanide by means of reversible binding to a receptor site to cause the generation of a visual signal via fluorescence or color change [10], many reports are published on the rational design of various probes that are able to detect cyanide via nucleophilic addition to a receptor site. Recently, many molecular probes for the visual cyanide detection were reported [11], including indoles [12] or bisindoles [13], 2-(trifluoroacetylamino)anthraquinone [14], cyanine dyes and related indoliminium NIR dyes [15], acyltriazene [16], squarane [17], acridinium salt [18], benzils [19], (het)aryl-substituted dienes [20,21], etc. Even though some of these chemosensors/probes could be very efficient and selective, their preparation requires multistep synthesis, which sometimes involves expensive metal catalysts or reagents and/or tedious methods for the purification.

(Aza) Schiff’s bases [22,23] provide different mechanisms for the cyanide detection. In the most common scenario, the deprotonation of (aza) Schiff’s base molecules [24,25,26] takes place to cause a dramatic color change. The mechanism involved hydrogen bonding formation followed by hydrogen abstraction by CN⁻. To ensure efficient hydrogen abstraction in most cases the strong hydrogen bond donors, such as hydroxy- or NH-moieties, as well as strong acceptors, such nitro-group(s) need to be introduced into the structure of Schiff’s bases [27,28,29,30,31]. In most cases, the above-mentioned Schiff’s bases could be prepared via multi-step synthesis by using organic solvents and column chromatography. In addition, the most probes exhibited an almost identical colorimetric response towards both CN⁻ and F⁻ ions.

In this manuscript, we wish to report a method for the preparation of Schiff’s bases, such as bis(4-nitrobenzylidene)-[1,1′-biphenyl]-4,4′-diamine S1, bis(4-nitrobenzylidene)-[1,1′-biphenyl]-3,3′-diamine S2, and bis(4-nitrobenzylidene)-[1,1′-biphenyl]-2,2′-diamine S3 (also available from several vendors) as simple highly selective colorimetric probes for the CN⁻ anion, by using both traditional solvent-based and mechanochemical (under ball milling conditions) synthesis.

2. Materials and Methods

Unless otherwise indicated, all common reagents and solvents were used from commercial suppliers without further purification. Benzidine, 2-nitroaniline, 3-nitroaniline, Pd(OAc)₂, Pd/C, 4-nitrobenzaldehyde were purchased from Sigma-Aldrich, Merck. Iodo-2-nitrobenzene (m.p. 48–49 °C [32]), and iodo-3-nitrobenzene [32], 3,3′-dinitro-1,1′-biphenyl [33], m.p. 178–180 °C, and corresponding [1,1′-biphenyl]-diamines B2 and B3 [34] were synthesized according to the reported procedures. Mechanochemical reactions were performed in the ball mill Retsch PM100 by using a 25 mL stainless steel jar with 4 stainless steel 10 mm-diameter milling balls at 500 rpm. TLC and column chromatography were carried out on SiO₂. ¹H NMR and ¹³C NMR spectra were recorded at room temperature at 400 and 100 MHz, respectively, on a Bruker DRX-400 spectrometer using CDCl₃ or DMSO-d₆ as the solvents. Hydrogen chemical shifts were referenced to the hydrogen resonance of the corresponding solvent (DMSO-d₆, δ = 2.50 ppm, or CDCl₃, δ = 7.26 ppm). Carbon chemical shifts were referenced to the carbon resonances of the solvent (CDCl₃, δ = 77.16 ppm). Peaks were labeled as singlet (s), doublet (d), triplet (t), and multiplet (m). Melting points were measured by the Stuart SMP10 melting point apparatus. Mass spectra were recorded on a SHIMADZU GCMS-QP2010 Ultra with electronic ionization (EI). UV–Vis absorption spectra were recorded on a Shimadzu UV-1800 spectrophotometer by using quartz cells with a 1 cm path length at room temperature. For UV/Vis titration experiments, tetrabutylammonium cyanide (TBACN) and tetrabutylammonium hydroxide (TBAOH) purchased from Sigma-Aldrich were used.

2.1. General Methods for the Synthesis of Probes S1–S3

2.1.1. Method A

A mixture of corresponding diamino-biphenylene (450 mg, 1 mmol, 1 eq), 4-nitrobenzaldehyde (302 mg, 2 mmol, 2 eq), and 3 drops of acetic acid in methanol (10 mL) was stirred at 68 °C for 8 h. Then ethyl acetate (10 mL) and water (20 mL) were added to the reaction mixture, and the product was extracted. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. Product yields for S1, S2, and S3 were 70.0%, 65.4%, and 60.3%, respectively.

2.1.2. Method B

The mixture of the corresponding diamino-biphenylene (225 mg, 0.5 mmol, 1 eq) and 4-nitrobenzaldehyde (151 mg, 1 mmol, 2 eq) and 3 drops of acetic acid was ball milled at 500 rpm for 1 h at room temperature. The reaction mixture was dissolved in ethyl acetate (20 mL) and washed with water (3 × 10 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. Product yields for S1, S2, and S3 were 94.8%, 87.5%, and 76.7%, respectively.

N⁴,N⁴′-bis(4-nitrobenzylidene)biphenyl-4,4′-diamine S1: ¹H NMR (DMSO-d6, 400 MHz) δ: 8.92 (s, 2 H, N=CH), 8.38–8.24 (m, 8 H, Ph-NO₂), 7.85–7.50 (m, 8 H, biphenyl). IR (KBr, cm⁻¹) ν: 1342 (-NO₂), 1531 (C=C), 1683 (C=N). ¹³C NMR (DMSO-d6, 100 MHz) δ 158.72, 149.73, 148.86, 141.56, 137.97, 129.65, 127.38, 124.01, 122.05. MS (m/z, %): 450 (M⁺, 100), 434 (7.36), 433 (22.92), 402 (7.90), 356 (7.98), 317 (6.78), 254 (11.37), 241 (11.56), 225 (13.49), 178 (14.39), 152 (37.65), 127 (17.09), 113 (6.00), 77 (12.34), 65 (7.10), 51 (7.31), 39 (2.71). m.p. 246–248 °C. Yellow powder.

N³,N³′-bis(4-nitrobenzylidene)biphenyl-3,3′-diamine S2: ¹H NMR (DMSO-d6, 400 MHz) δ: 8.95 (s, 2 H, N=CH), 8.39 (d, ³J = 8.0 Hz, 4 H, Ph-NO₂), 8.24–8.20 (d, ³J = 8.0 Hz, 8 H, Ph-NO₂), 7.73–7.69 (d, 4 H, biphenyl), 7.57 (m, 2 H, biphenyl), 7.39–7.37 (m, 2 H, biphenyl). ¹³C NMR (DMSO-d6, 100 MHz) δ 159.50, 151.26, 148.87, 141.49, 140.83, 129.85, 125.25, 123.99, 121.00, 119.19. MS (m/z, %): 450 (M⁺, 100), 434 (7.36), 433 (22.92), 402 (7.90), 356 (7.98), 317 (6.78), 254 (11.37), 241 (11.56), 225 (13.49), 178 (14.39), 152 (37.65), 127 (17.09), 113 (6.00), 77 (12.34), 65 (7.10), 51 (7.31), 39 (2.71). m.p. > 250 °C. Yellow powder.

N²,N²′-bis(4-nitrobenzylidene)biphenyl-2,2′-diamine S3: ¹H NMR (DMSO-d6, 400 MHz) δ: 8.41(s, 2 H, N=CH), 8.21 (d, ³J = 8.0 Hz, 4 H, Ph-NO₂), 7.64 (d, ³J = 8.0 Hz, 4 H, Ph-NO₂), 7.51–7.37 (m, 6 H, biphenyl), 7.19 (d, ³J = 8.0 Hz, 2 H, biphenyl). ¹³C NMR (DMSO-d6, 100 MHz) δ 158.17, 149.79,148.60, 141.33, 134.35, 130.97, 129.09, 128.83, 126.24, 123.88, 118.08. MS (m/z, %): 450 (M⁺, 100), 434 (7.36), 433 (22.92), 402 (7.90), 356 (7.98), 317 (6.78), 254 (11.37), 241 (11.56), 225 (13.49), 178 (14.39), 152 (37.65), 127 (17.09), 113 (6.00), 77 (12.34), 65 (7.10), 51 (7.31), 39 (2.71). m.p. 227–229 °C. Yellow powder.

Limits of detection (LOD) for the CN⁻ by the probes S1–S3 were calculated according to Equation (1) [35]:

$$LOD=\frac{3\times \sigma }{k}$$

(1)

Equation (1): The calculation of LOD, where σ is the standard deviation of the chromophore intensity in the absence of an analyte (TBACN) and k is the slope of the linear calibration curve.

3. Results and Discussion

Since the first report of H. Schiff [36], the most common way (a conventional method) for their preparation [37] is the acid-catalyzed reaction of nucleophilic addition of aliphatic or aromatic amines to carbonyl compounds in solution upon heating to result in hemiaminals, followed by dehydration. Compared to the conventional methods, the ball milling under solvent-free conditions for the Schiff’s base preparation looks more attractive due to the shorter reaction times [38,39].

It should be noted that the synthesis of N⁴,N⁴′-bis(4-nitrobenzylidene)biphenyl-4,4′-diamine S1 was reported previously [40,41], however, with much prolonged reaction time (48 h) or in absolute ethanol with comparable reaction yields.

Based on the above, to prepare the probes S1–S3, we used solvent-free conditions under ball milling as the most preferable method. The probes S1–S3 were synthesized by means of the reaction between the corresponding isomeric 4,4- (B1), 3,3- (B2), and 2,2- (B3) diamino-biphenyls and 4-nitrobenzaldehyde (Scheme 1).

For comparison, we carried out the same reaction in methanol under reflux. As we expected, the ball milling conditions proved to be more efficient in many respects, such as reaction time (1 h), reaction yield (up to 95%), reduced solvent consumption (only for purification), and room temperature conditions, while for the solvent-based reaction (in our case) a more prolonged reaction time (8 h) was required and much lower reaction yields (70%) were observed.

The structures of the products S1–S3 were confirmed by ¹H, ¹³C NMR, and IR-spectroscopy (see Supporting Information for details).

As a next step, the visual response of the probes S1–S3 to CN⁻ in solution was studied. Thus, in a DMSO solution of S1–S3 (1.1 × 10⁻³ M) upon the addition of tetrabutylammonium cyanide (TBACN, 1.4 × 10⁻² M) a dramatic color change from yellow to orange-purple was observed (Figure 1). Depending on the structure of S1–S3, the colors varied from dark orange (S1) to dark purple (S3). The plausible mechanism for this interaction is presented below (Figure 2). Thus, the interaction involves the initial partial deprotonation of the CH=N moiety of the probes S1–S3 by the CN⁻ ion. This deprotonation was observed by means of a ¹H NMR experiment in the case of S3 (Figure S30 ESI†). Thus, in DMSO-d6, the addition of 3.0 eq. of TBACN results in the complete disappearance of the proton signal of CH=N moiety at 8.45 ppm, which confirms the deprotonation of this moiety. Most probably, the presence of strong electron-withdrawing NO₂ group in the para-position of an aromatic moiety in the structure of S1–S3 polarizes strongly the imine bond, which makes this imine proton more acidic. After that, the formation of deeply colored charge-transfer complexes with another molecule of S1–S3 takes place. This concept was confirmed by a similar color change after the addition of 0–1.35 μM of tetrabutylammonium hydroxide (TBAOH) as a strong base in DMSO as well as UV-titration studies (Figures S31–S34 ESI†).

To gain more evidence, the photophysical studies of S1–S3 were carried out. Thus, in UV spectra of DMSO solution, probe S1 (22µM) exhibits an absorption band with a maximum at 295 nm, and the addition of TBACN in concentrations 0–1.35 mM results in the appearance of a new absorption band at 575 nm, which can be attributed to the formation of the charge-transfer complex (Figure S35 ESI†). In the case of probe S2, one absorption peak at 275 nm was observed, and a new growing peak at 475 nm was detected upon the addition of TBACN (Figure S36 ESI†). For the probe S3, one absorption peak at 295 nm was observed, and a new peak at 555 nm was observed upon the addition of TBACN (Figure 3a). For the most representative probe, S3, we attempted to carry out Job plot experiment in order to determine the stoichiometry of the complex and the binding mode between S3 and the CN^- ion. However, the increasing hypochromic shift with the increasing concentration of the TBACN never reached a steady state, and the mathematical representation (A = e^x) where A—absorbance; X—concentration (see Figure S37 ESI†) can be seen as an exponential dependence. The observed result corresponds to the literature data [42,43,44,45,46] according to which the job plot method could not be fully validated in the case of supramolecular assemblies with low to moderate association constants. In addition, for the probes S1–S3, the CN^- detection limit (LOD) was calculated according to Equation (1), which was found to be 26 × 10³, 8.7 × 10³ and 14 × 10³ ppm, respectively.

It is worth mentioning that the addition of other anions, such as Cl⁻, HPO₄⁻, I⁻, ClO₄⁻, CH₃CO₂⁻, and even F⁻, to the solution of the most representative probe S3 in DMSO results in no color change or only subtle color changes (Figure 3b), while the presence of CN⁻ can be easily distinguished by the naked eye due to the dramatic color change, which is detectable in the UV/Vis scale. All of the above-mentioned confirms the high selectivity of S3 toward the CN⁻ anion among other anions.

As a final step, to explore the potential application of the herein reported probes for environmental monitoring, the test strips for the CN⁻ ion detection were prepared by means of impregnation of filter paper with the solution of the most representative probe S3 in DMSO (0.014 M) with the following air-drying. As a result, the S3-impregnated test strips demonstrated the selectivity and sensitivity to CN⁻ (14 mM) ions via a dramatic color change (Figure 3c).

4. Conclusions

In summary, simple Schiff’s base probes S1–S3 for the detection of cyanide ions were prepared by using a reaction between isomeric 4,4-, 3,3-, and 2,2-diaminobiphenyls and 4-nitrobenzaldehyde under ball milling conditions. The obtained probes demonstrated a selective visual response to the CN^- ion over other anions in a solution of DMSO via a dramatic color change with a detection limit of 26 × 10³, 8.7 × 10³ and 14 × 10³ ppm for S1–S3, respectively. The plausible mechanism of the reaction suggests a deprotonation of CH=N moieties of S1–S3 with the following formation of a deeply colored charge transfer complex with another molecule of S1–S3, which is detectable by means of ¹H NMR and UV/vis-methods. To confirm the practical application of the obtained probes for the detection of CN⁻, S3-impregnated test strips were prepared, which demonstrated the selective detection of CN⁻ via a dramatic color change.