# Colorimetric fluoride ion sensors based on dipyrrolic and bipyrrolic compounds: Synthesis and anion recognition

Flávio Figueira, Andreia S.F. Farinha, Adriano Santana, Johannes S.

Vrouwenvelder, Augusto C. Tomé, Dmitry Chernyshov, Filipe A. Almeida

Paz, José A.S. Cavaleiro, João P.C. Tomé

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## ► To cite this version:

Flávio Figueira, Andreia S.F. Farinha, Adriano Santana, Johannes S. Vrouwenvelder, Augusto C. Tomé, et al.. Colorimetric fluoride ion sensors based on dipyrrolic and bipyrrolic compounds: Synthesis and anion recognition. Dyes and Pigments, 2025, 233, pp.112535. 10.1016/j.dyepig.2024.112535. hal-05099683

HAL Id: hal-05099683

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Submitted on 6 Jun 2025

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# Colorimetric fluoride ion sensors based on dipyrrrolic and bipyrrrolic compounds: Synthesis and anion recognition

Flávio Figueira<sup>a,b,*</sup>, Andreia S.F. Farinha<sup>c</sup>, Adriano Santana<sup>c</sup>, Johannes S. Vrouwenvelder<sup>c</sup>, Augusto C. Tomé<sup>b</sup>, Dmitry Chernyshov<sup>d</sup>, Filipe A. Almeida Paz<sup>a</sup>, José A.S. Cavaleiro<sup>b</sup>, João P.C. Tomé<sup>b,e,**</sup>

## ARTICLE INFO

### Keywords:

Colorimetric sensing

Fluoride sensing

Anion binding

Bipyrrole

Dipyrrromethane

Push-pull chromophores

## ABSTRACT

The synthesis and spectroscopic studies of four sensors for fluoride chromogenic sensing are described. The new compounds were prepared by the Knoevenagel condensation of diformyl-substituted bipyrrrolic and dipyrrrolic synthons ([2,2'-bipyrrole]-5,5'-dicarbaldehyde and dipyrrromethane-1,9-dicarbaldehyde moieties) with malononitrile or indane-1,3-dione. They strongly absorb in the visible region and significant color changes occur in the presence of fluoride anions. Acetate and dihydrogenphosphate anions also induce observable colorimetric changes, albeit to a lesser extent. These changes, which are visible to the unaided eye, are associated with NH-bonding interactions that are unique to each anion. Non-linear regression analysis of the ground- and excited-state changes revealed anion recognition in a 2:1 stoichiometry (Host:Guest), where the electronegative character of the substituents (malononitrile or indane-1,3-dione residues) controls the sensitivity of the binding. The proposed systems all feature exceptional anion receptors that display an impressive chromogenic response through NH-bonding. Among these, compound 3 stands out with exceptionally high affinity constants of up to 7.39x10⁹ M⁻², as well as an extremely low limit of detection at 92 ppm. NMR spectroscopy and mass spectrometry confirmed the structures of the synthesized compounds, with increased complexity in the NMR spectra due to the presence of malononitrile and indane-1,3-dione moieties. These findings highlight the potential of incorporating highly conjugated push-pull chromophores into bipyrrrolic and dipyrrrolic synthons for improved fluoride sensing performance in terms of both binding and signaling.

## 1. Introduction

The design of compounds capable of interacting with anions is a significant field of research in organic chemistry, providing cleaner methods for waste treatment, sensors, and the development of compounds that can bind and transport anions across lipid bilayer membranes [1-7]. Anion detection is a critical area of research and is approached through various methods, such as electrochemical and calorimetric methods [8,9]. Also, NMR spectroscopy are excellent

methods for anion detection providing in some cases detailed insights into molecular interactions and thermodynamic binding yet they are expensive, time-consuming, and requires high concentrations of analytes [10]. On the other hand, optical methods such as fluorescence and surface plasmon resonance are powerful for real-time monitoring and offer high sensitivity and selectivity but are costly, and also require sophisticated equipment [11,12].

Colorimetric detection, by contrast, addresses many of these limitations by offering a simple, cost-effective, and rapid approach to anion

<footnote><sup>a</sup> CICECO – Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, 3810-193, Aveiro, Portugal</footnote>

<footnote><sup>b</sup> LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193, Aveiro, Portugal</footnote>

<footnote><sup>c</sup> Water Desalination and Reuse Center (WDRC), Division of Biological and Environmental Sciences (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900, Saudi Arabia</footnote>

<footnote><sup>d</sup> Swiss-Norwegian Beamlines, The European Synchrotron, European Synchrotron Radiation Facility, 6, Rue Jules Horowitz, Grenoble, 38000, France</footnote>

<footnote><sup>e</sup> Centro de Química Estrutural, Institute of Molecular Sciences & Departamento de Engenharia Química, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal</footnote>

<footnote>* Corresponding author. Department of Chemistry, CICECO – Aveiro Institute of Materials, University of Aveiro, 3810-193, Aveiro, Portugal.</footnote>

<footnote>** Corresponding author. CQE, IMS, DEQ, Instituto Superior Técnico, 1049-001, Lisboa, Portugal.
E-mail addresses: ffigueira@ua.pt (F. Figueira), jtome@tecnico.ulisboa.pt (J.P.C. Tomé).</footnote>
detection. It does not require expensive equipment, as the changes can often be observed by the unaided eye, and it is less susceptible to complex sample matrices [12]. Although colorimetry might not provide the same level of sensitivity or detailed information as some of the aforementioned techniques, its ease of use, robustness, and applicability in a wide range of conditions make it a highly valuable tool, particularly in field settings or where quick, qualitative assessments are sufficient [13].

In recent years, extensive research has been conducted on the development of chromogenic anion sensors that exhibit high substrate selectivity and distinct colorimetric response patterns [12,14–16]. In this regard pyrrole-containing anion binding motifs, such as guanidinium-containing amidopyrroles and pyrrole-2, 5-dicarboxamides, are particularly useful in this field because of their NH protons stability, which remain accessible to hydrogen bonding across a broad pH range [17–22]. Understanding the photophysical and thermodynamic processes involved in sensing anions is crucial for the modulation of specific hydrogen bonding interactions and recognition patterns for each anion [23]. For instance, besides being an important micronutrient, an excess consumption of fluoride can lead to various harmful effects. Long-term exposure to fluoride levels exceeding 4 ppm can result in dental and skeletal fluorosis, leading to tooth discoloration and ligament and bone calcification, as well as bone deformities and other physiological issues that can ultimately be life-threatening [24]. Furthermore, fluoride possesses a comparatively high hydration energy when contrasted with other anions (–ΔH° = 100–110 kcal/mol), and its relatively small ionic radius (1.47 Å) makes it difficult to align multiple binding sites [25]. Recently, a few colorimetric sensors have been

reported for fluoride detection with limit of detection down to 2 ppm, which is an order of magnitude lower than WHO guidelines [26]. However, these studies present various detection methods and chromophores centered on metallic elements, which may be environmentally harmful [27–30]. In light with our recent results, we aim to investigate the potential benefits of incorporating highly conjugated push-pull chromophores into bipyrrolic and dipyrrolic synths, specifically [2,2'-bipyrrole]-5,5'-dicarbaldehyde and dipyrromethane-1, 9-dicarbaldehyde moieties, with the expectation of improving the sensing performance in terms of both binding and signaling for fluoride [31–44]. For that, indane-1,3-dione and malononitrile moieties were introduced in both pyrrolic synths [45]. This approach augmented the signal output and dramatic changes in anion selectivity compared to the parent calix [4]pyrrole previously published in literature (Table S1 entries 5–7). In two distinct studies, some of us investigated and documented the colorimetric properties of mono- and di-substituted calixpyrroles [46,47]. Surprisingly, we discovered that disubstituted calix [4]pyrroles altered their stoichiometry from a 1:1 to a 1:2 ratio of Host:Guest (H:G) [47]. Therefore herein, we describe the synthesis, structural characterization, and anion-binding properties of bipyrrolic and dipyrrolic structures functionalized with malononitrile (3 and 5) and indane-1,3-dione (4 and 6). In addition to determining the affinity constants of our chemosensors for a series of common anions, we tried to elucidate the mechanisms of the specific colorimetric recognition of the fluoride species.

<figure><img src="image_3.png" /><figcaption>Fig. 1. Synthesis of compounds 3 to 6. The color of the rings serves as an indicator of the hue they exhibit in a DMSO solution.</figcaption></figure>
## 2. Results and discussion

To access compounds **3–6** (Fig. 1), we employed [2,2'-bipyrrole]-5,5'-dicarbaldehyde (**1**) and 5-methyl-5-phenyldipyrromethane-1,9-dicarbaldehyde (**2**), which were synthesized using previously reported methods [22,48,49]. The NMR characterization of both compounds aligns with the findings reported in the literature (Figs. S1–S4) [48,50,51].

Compound **3** was prepared in 76 % yield by dissolving **1** and six equivalents of malononitrile in DMSO with a catalytic amount of NEt₃ at 100 °C for 12 h. The synthesis of **4**, under the same conditions used for **3** but with 1,3-indanedione was unsuccessful, resulting in complex mixtures with most of the unreacted starting material. However, **4** could be prepared reacting **2** with 1,3-indanedione in low yield (16 %), when piperidine was used as catalyst instead of NEt₃ [52–54]. The activity of piperidine is related to the formation of intermediate imine groups that are more reactive than the formyl groups of the starting material.

The previous achievements leading to bipyrrrolic compounds **3** and **4** motivated us to look for dipyrrrolic systems using similar methods. To this end, derivative **2** was reacted with the same active methylene compounds, resulting in the formation of compounds **5** and **6** with yields of up to 70 %.

NMR spectroscopy and mass spectrometry allowed us to verify the structure of all synthesized compounds (See Figs. S5–S16 in the SI). In particular, the NMR spectra of compounds **3–6** displayed increased complexity in both the ¹H and ¹³C regions owing to the presence of malononitrile and indane-1,3-dione moieties. A notable distinction consistently observed in all compounds is the shift of the signal corresponding to the proton of the CHO group around δ 9.50 ppm in compounds **1** and **2** to δ 7.80 ppm for the Knoevenagel products. High-quality crystals of compound **6** were obtained and the single-crystal X-ray diffraction analysis provided valuable insights into the structure of this compound in the solid state (see Fig. 2).

Compounds **3** and **4** exhibit intense absorption bands with maximum absorbance at 505 and 517 nm, respectively, while compounds **5** and **6** show maximum absorbance at 409 and 465 nm, respectively (see Fig. 3).

The different absorption maxima between bipyrrrolic compounds **3** and **4** (Fig. 3, Arrow A) and the dipyrrromethane compounds can be

<figure><img src="image_4.png" /><figcaption>Fig. 3. Absorption spectra of compounds **3–6**, showing distinct absorption maxima differences between the bipyrrrole and dipyrrromethane derivatives. The plot highlights the enhanced conjugation in bipyrrrole-based compounds (**3** and **4**) when compared to the dipyrrromethane-based ones (**5** and **6**). Arrow A illustrates the dissimilarity in the absorption profiles of bipyrrrole **3** and dipyrrromethane **5** (difference = 96 nm), whereas arrow B highlights the difference in the absorption profiles of dipyrrromethanes **5** and **6** (difference = 56 nm).</figcaption></figure>

attributed to their distinct electronic structures and the degree of conjugation present within these molecules. Bipyrrrolic compounds exhibit a larger conjugation, where the overlap of π-orbitals across adjacent bonds permits electron delocalization over a wide portion of the molecule, thus stabilizing the electronic energy levels. This stabilization results in a red shift of the absorption maxima which is attributed to the diminution in the energy gap between the ground and excited states. The influence of the dipyrrromethane substituents also impacts their UV–Vis absorption maxima, with compound **6** displaying a higher absorption maximum than **5** (Fig. 3, Arrow B). This difference can be attributed to the conjugation profile, which directly affects the energy levels of the molecular orbitals as well as the electron-withdrawing variations between the substituents. The UV–Vis absorption maxima difference between bipyrrrolic and dipyrrromethane compounds not only reflects their structural and electronic differences, but also has implications in their use as chromogenic sensors.

The prepared compounds were tested to sense a series of anions (see Fig. S17). We found that of the NH groups interaction with anions could be significantly modulated by the electron-withdrawing groups at the α-position, leading to significant changes in the absorption profiles. As anticipated, a notable color variation was observed for all compounds where **3** and **5** show variation with three different anions and compounds **5** and **6** show a tremendous colorimetric specificity towards fluoride anions (see Fig. 4).

Interestingly, the longer-wavelength absorption of bipyrrrolic compounds **3** and **4** allows them to be more sensitive to visible color changes upon anion binding, responding with color differences to a wide range of anions than dipyrrromethanes **5** and **6**. Solutions of bipyrrrolic sensors **3** and **4** exhibited color changes to the unaided eye upon the addition of fluoride, acetate and, to a lesser extent, dihydrogenphosphate solutions (as shown in Fig. 4). In contrast, compounds **5** and **6** showed notable differences in color only in the presence of fluoride anions. It is important to emphasize the higher selectivity response of compound **6** to the fluoride anion (F⁻) compared to the other compounds tested (**3**, **4**, and **5**) in terms of colorimetric variation. This exceptional performance is likely attributed to the specific structural features of compound **6**, including its indane-13-dione substituents, which enhance its ability to interact with

<figure><img src="image_5.png" /><figcaption>Fig. 2. Schematic representation of the molecular unit present in compound **6**. Non-hydrogen atoms are depicted as thermal ellipsoids drawn at the 50 % probability level while hydrogen atoms are shown as small spheres with arbitrary radii.</figcaption></figure>
<figure><img src="image_6.png" /><figcaption>**Fig. 4.** Colorimetric responses of di- and bipyrrrolic compounds to anions. There is a notable color change in DMSO solutions of compounds 3–6 (1.0 × 10⁻⁵ M) upon the addition of various tetrabutylammonium anion solutions (concentration of 5.0 × 10⁻⁶ M). The color modifications, observable by the unaided eye, highlight the distinct sensitivities of the compounds to fluoride (F⁻), chloride (Cl⁻), acetate (AcO⁻), and dihydrogenphosphate (H₂PO₄⁻) anions, with the most pronounced change occurring in the presence of F⁻.</figcaption></figure>

fluoride ions more effectively. This response underlines the potential of compound 6 as a highly efficient sensor for detecting fluoride anions, making it particularly suitable for applications where high and selectivity are crucial.

Based on these results the following analysis of the pyrrolic sensors involved titrating DMSO solutions with the active anions as their tetrabutylammonium salts and then fitting the resulting experimental data (see Figs. S18–S21). Interestingly, 6 exhibited a remarkable colorimetric response in the presence of fluoride anions. This property is highly advantageous for the development of visual sensors, allowing for simple detection of fluoride without the need for expensive instrumentation. Fig. 5A and B depict the data from the titration of compounds 5 and 6 with fluoride and the corresponding data fitted with different stoichiometry equations (see Fig. 5C and D), along with the residuals (the equations and methods used to fit the real values are discussed in the

experimental section).

The presence of more than one isobestic point and the shape of the curves pinpoint a more complex stoichiometry than a simple 1:1 host: guest (H:G) complex. Consequently, to better understand the interaction stoichiometry, we decided to apply the possible tree equations for this system, describing the formation of the 2:1, 1:1, and 1:2 H:G complexes (see Fig. 5C and D). The lowest residual values were calculated using a standard nonlinear regression with a 2:1 H:G ratio. This conclusion was realized by trial and error fitting of the data with the corresponding nonlinear regression curves for the 1:1, 1:2, and 2:1 H:G models. Additionally, the Job plots analysis conducted for compounds 3 through 6 in relation to fluoride, using the continuous variations method, reached a maximum value at a mole fraction of $X_F \approx 0.33$, confirming that the molar ratio between ligand and fluoride in the complex is 2:1 [55].

The affinity constants calculated by fitting these values in 2:1 H:G stoichiometry are listed in Table 1.

In general, sensors 3–6 show enhanced detection abilities and have a very high affinity towards fluoride ions, which is significantly higher than that of other anions ($K > 10^8 M^{-2}$ in DMSO). Among these, sensors 3 and 5 stand out for their strong binding to fluoride ($K > 10^9 M^{-2}$ in DMSO), which explains their pronounced color changes upon fluoride detection. However, when comparing their responses to acetate and dihydrogenphosphate ions, sensor 4 displayed a notably higher selectivity towards acetate, as indicated by its selectivity ratio ($KAcO^- / H_2PO_4^-$ of 36.7).

In contrast, while sensor 6 does not interact with dihydrogenphosphate ions, sensors 3 and 4, are not as selective for a single anion type despite their high fluoride affinity. In comparison, dipyrromethane-based sensors, 5 and 6, offer a more distinct color change for fluoride and are more selective for acetate over dihydrogenphosphate, albeit with generally lower binding strengths. Compound 6 especially stands out for its ability to specifically detect fluoride and acetate, ignoring phosphate. This shows a trend in which 5 and 6 lead to better discrimination between different anions, with a particular emphasis on effective fluoride detection and compounds 3 and 4 without showing a chromogenic specificity can show higher selectivity towards acetate when compared with dihydrogenphosphate.

NMR titration experiments were performed on compound 5 by gradual addition of fluoride anions (see Fig. 6). These experiments revealed hydrogen bonding, indicated by a shift in the chemical shift of the NH protons from 9.5 to 15 ppm (see Fig. 6, blue dot).

This shift occurred as a result of the formation of an adduct between compound 5 and the fluoride anion. Essentially, the observed chemical shift represents an average signal from both the free host molecule and the host when it is bound to the guest, assuming that the interaction between them is rapid on the NMR timescale. This process of binding continues effectively until reaching 0.5 equivalents of fluoride anion. Beyond this concentration, a notable broadening of most spectrum peaks is observed, while the chemical shift of the NH protons (see Fig. 6, blue dot) does not change significantly. This behavior at concentrations higher than 0.5 equivalents of fluoride without further changes in the chemical shift of the NH protons, confirms a 2:1 H:G binding stoichiometry. The presence of broadened peaks with the continuous addition of fluoride anion until 2.0 equivalents points to a dynamic equilibrium between compound 5 being bound and unbound to the fluoride anions. Such observations imply that binding introduces dynamic processes in the system, allowing for the exchange between the free and bound states of the host molecule. For concentrations higher than 0.5 equivalents of fluoride anion most of the resonances began to experience severe broadening with no significant changes in the NH chemical shift confirming a 2:1 H:G binding stoichiometry. The observation of broadened peaks upon the addition of fluoride indicates that a dynamic equilibrium exists between bound and unbound states. Binding events can introduce dynamic processes, such as exchange between free and bound states.

The NMR study further reveals modifications in the β-pyrrolic
<figure><img src="image_7.png" /><figcaption>**Fig. 5.** A) and B) Data from the titration of compounds 5 and 6 with fluoride anions. C) and D) Experimental data fit with different stoichiometry equations, along with the residuals of compounds 5 and 6 (the equations and methods used to fit the real values are discussed in the experimental section). The analysis of pyrrolic sensors 5 and 6 involved a titration with fluoride as its tetrabutylammonium salts, and then fitting the resulting experimental data with various stoichiometry equations. The residuals were obtained for each fit.</figcaption></figure>

<table><caption>**Table 1**

Binding constants (K in M⁻²) and limits of detection (LOD) for sensors 3–6 at 22 °C in DMSO. (n.d., not measurable).</caption><thead><tr><th></th><th>3 (M<sup>-2</sup>)</th><th>4 (M<sup>-2</sup>)</th><th>5 (M<sup>-2</sup>)</th><th>6 (M<sup>-2</sup>)</th></tr></thead><tbody><tr><td>F<sup>-</sup></td><td>7.39 &times; 10<sup>9</sup></td><td>3.96 &times; 10<sup>8</sup></td><td>3.19 &times; 10<sup>9</sup></td><td>2.81 &times; 10<sup>8</sup></td></tr><tr><td>AcO<sup>-</sup></td><td>1.42 &times; 10<sup>8</sup></td><td>2.16 &times; 10<sup>8</sup></td><td>6.77 &times; 10<sup>8</sup></td><td>1.43 &times; 10<sup>7</sup></td></tr><tr><td>H<sub>2</sub>PO<sub>4</sub><sup>-</sup></td><td>1.50 &times; 10<sup>7</sup></td><td>5.88 &times; 10<sup>6</sup></td><td>5.21 &times; 10<sup>7</sup></td><td>n.d.</td></tr><tr><td>K<sub>F</sub>/AcO<sup>-</sup></td><td>52.0</td><td>1.8</td><td>4.7</td><td>19.6</td></tr><tr><td>KAcO<sup>-</sup>/H<sub>2</sub>PO<sub>4</sub><sup>-</sup></td><td>9.5</td><td>36.7</td><td>13.0</td><td>n.d.</td></tr><tr><td>LOD (F<sup>-</sup>)</td><td>92.0 ppm</td><td>138 ppm</td><td>117 ppm</td><td>152 ppm</td></tr></tbody></table>

protons (see Fig. 6, red and yellow dots). In spite of the fact that the β-pyrrolic proton signals (depicted in Fig. 6 as a red dot) display a shift (indicated by a yellow dot in Fig. 6), they do not engage in hydrogen bonding with the fluoride ions in a direct manner. Instead, their changes

in chemical shifts are indicative of the broader structural and electronic rearrangements occurring within the sensor molecule because of fluoride binding. This observation of ¹H NMR signal shift upon addition of fluoride anion enriches our understanding of the binding mechanism, illustrating that the entire molecular framework of the sensor responds to the presence of fluoride, not just the immediate binding site.

The optimized geometries and binding energies of compounds 5 and 6 with various anions were determined using Density Functional Theory (DFT) calculations at the M062X/6-311+g (d,p) level. The inclusion of thermal corrections and the electrostatic effects of the solvent (DMSO) using the Polarizable Continuum Model (PCM) provides a comprehensive understanding of the molecular interactions at play. These calculations are instrumental in revealing the molecular architecture and potential anion binding sites, facilitating a deeper understanding of the anion recognition capabilities of each compound.

The findings indicate that compound 6, with its indane-1,3-dione
<figure><img src="image_8.png" /><figcaption>Fig. 6. ¹H NMR titration of compound 5 in CDCl₃ with fluoride anion.</figcaption></figure>

substituents, has a high propensity for self-aggregation, significantly influencing its anion binding efficacy, particularly with larger anions like acetate and dihydrogenphosphate. This tendency towards self-aggregation underscores the complexity of predicting anion binding behavior based solely on structural considerations. Although NMR tritations suggested a 2:1 H:G stoichiometry for fluoride binding, computational limitations necessitated the evaluation of binding energies at a 1:1 ratio. This approach, albeit a simplification, still provides valuable insights that align with experimental observations (see Table 2) [56].

The analysis of binding energies revealed a clear difference in the interaction strengths of compounds 5 and 6 with the studied anions. Compound 5 exhibits significantly negative binding energies with fluoride, acetate, and dihydrogenphosphate (Eb = -8.3, -8.1 and -9.6 kcal/mol, respectively), indicating robust and favorable interactions. These strong interactions are reflected in the higher affinity constants of 5 when compared with those of 6, suggesting a more efficient fluoride recognition process (Table 1). Conversely, compound 6 shows much lower, or even positive, binding energies for acetate and dihydrogenphosphate (Eb = 0 and 4.0 kcal/mol, respectively), highlighting weaker or unfavorable interactions.

The discrepancy between binding energies and colorimetric responses, particularly in the context of chromogenic specificity, suggests

that factors beyond simple binding energy calculations must be considered. Interestingly, with larger acetate or dihydrogenphosphate anions, it is more challenging to stabilize the host–guest complex and, therefore, the binding energies increase, showing no chromogenic change towards these anions. The adaptability of acyclic hosts arises from their inherent flexibility, enabling an adjustable fit with fluoride anions and enhancing the efficiency of binding interactions. The open structure of acyclic compounds may improve accessibility and functionalization of binding sites, diminishing steric hindrances and optimizing interaction dynamics with fluoride anions.

Additionally, a close comparison with similar works already published in the literature despite the relatively high affinity constants for fluoride, most of the compounds prepared in these works (see Table S1) did not display the same colorimetric specificity as compound 5. Only acyclic compounds proved to be as efficient as 5, as evidenced by the results in entries 12 and 18 (see Table S1) [57,58]. Collectively, these traits emphasize the ability of acyclic structures to achieve high efficiency and specificity in anion binding applications, particularly for fluoride chromogenic host sensors.

To create a practical fluoride sensor, several small pieces of standard filter paper were soaked in THF solutions containing compound 6. After drying at room temperature overnight, the filter papers coated with sensors were subjected to different anion solutions, and the subsequent
<table><caption>**Table 2**
Optimized geometries of compounds **5** and **6** for each anion and their corresponding binding energies in DMSO. (Color scheme: C (gray), O (red), N (blue), H (light gray), P (brown), Cl (light blue).</caption><thead><tr><th></th><th>5</th><th>6</th></tr></thead><tbody><tr><td>F<sup>-</sup></td><td><img src="image_0_0.png" alt="Chemical structure of F<sup>-</sup> ion"></td><td><img src="image_0_1.png" alt="Chemical structure of F<sup>-</sup> ion with color annotation"></td></tr><tr><td>AcO<sup>-</sup></td><td><img src="image_0_2.png" alt="Chemical structure of AcO<sup>-</sup> ion"></td><td><img src="image_0_3.png" alt="Chemical structure of AcO<sup>-</sup> ion with color annotation"></td></tr><tr><td>H<sub>2</sub>PO<sub>4</sub><sup>-</sup></td><td><img src="image_0_4.png" alt="Chemical structure of H<sub>2</sub>PO<sub>4</sub><sup>-</sup> ion"></td><td><img src="image_0_5.png" alt="Chemical structure of H<sub>2</sub>PO<sub>4</sub><sup>-</sup> ion with color annotation"></td></tr></tbody></table>

color changes were recorded (see Fig. 7).

The resulting color changes are in accordance with the results discussed above where in this case only fluoride induced stronger color change. As expected, the chemosensors **6** is able to discriminate cyanide and also when adsorbed in paper.

## Ion

In summary, compounds **3–6** exhibit strong light absorption in the spectrum and display significant colorimetric changes when anions are present. Additionally, acetate and dihydrophate induce less pronounced colorimetric changes. The constant ratio $K_{F\text{AcO}}$ for sensor **6** is 19.6. The color variation in the substituted compounds indicates specific color changes in the absence of fluoride, and the smaller side chains increase the binding general. According to molecular modeling studies, the size of the side groups play a crucial role in the binding mode length of the association constants. The proposed systems are an exceptional chromogenic response upon binding fluorine hydrogen bonding, with color changes occurring only in the absence of fluoride anions for sensor **6**. This study emphasizes the of comprehending the photophysical and thermodynamic involved in anion sensing to modulate specific hydrogen interactions with fluoride.

## Total Section

### and reagents

In progress was monitored by thin-layer chromatography on nick precoated silica plates: Merck Fertigplatten Kiesel-gel 60

electra were obtained on a Bruker Avance-300 spectrometer at a frequency of 300.13 MHz for ¹H and 75.47 MHz for ¹³C solvent peak (DMSO-d₆ or CDCl₃) was used as an internal

reference (relative to TMS and given in ppm).

HRMS were recorded on VG AutoSpec-M spectrometer, using chloroform and methanol as solvent, with 3-nitrobenzyl alcohol (NBA) as a matrix. A Shimadzu UV/2501 PC spectrophotometer was used for all UV–Vis titrations and absorption spectra (200–800 nm). Anions were

<figure><img src="image_9.png" /><figcaption>**Fig. 7.** Colorimetric response of paper-based sensors impregnated with compound **6** upon exposure to various anions in aqueous solutions. Small pieces of filter paper were soaked in THF solutions containing compound **6** and dried overnight. The treated papers were then exposed to different anion solutions and the resulting color changes were recorded. Note the distinct color change observed for fluoride (F⁻) compared to other anions tested. For reference, a coated filter paper that only interacted with distilled water was used as a control (labeled as REF).</figcaption></figure>
used as their tetrabutylammonium salts as acquired from sigma Aldrich. Column chromatography was carried out over silica gel (Merck, 230–400 mesh).

Bipyrrroles, dipyrrromethanes, and their formylated counterparts were prepared according to previously published procedures [48,49, 51].

### UV–Visible spectroscopic titrations

The anion-binding tests were followed by UV–Vis spectroscopy at 22 °C using DMSO. Several anions such as fluoride, chloride, bromide, acetate, dihydrogenphosphate, nitrate, and nitrite have been used as tetrabutylammonium salts. Equations (1)–(3) were used to determine the affinity constants [59].

Non-linear regression for the 2:1 (H:G) complex ($K_{2:1}$ units are M⁻²)

$$ \frac{A}{l} = \frac{[H] \cdot K_{11} \cdot \Delta\epsilon_{11} \cdot [G] + K_{11} \cdot K_{21} \cdot \Delta\epsilon_{21} \cdot [G] [H]}{1 + K_{11} \cdot [G] + K_{11} \cdot K_{21} \cdot [G] [H]} \quad (1) $$

Non-linear regression for the 1:1 (H:G) complex ($K_{1:1}$ units are M⁻¹)

$$ \frac{A}{l} = \frac{[H] \cdot K \cdot \Delta\epsilon \cdot [G]}{1 + K \cdot [H]} \quad (2) $$

Non-linear regression for the 1:2 (H:G) complex ($K_{1:2}$ units are M⁻²)

$$ \frac{A}{l} = \frac{[H] \cdot K_{11} \cdot \Delta\epsilon_{11} \cdot [G] + K_{11} \cdot K_{12} \cdot \Delta\epsilon_{12} \cdot [G]^2}{1 + K_{11} \cdot [G] + K_{11} \cdot K_{12} \cdot [G]^2} \quad (3) $$

Where A is the absorbance, l is the path length, K is the affinity constant, Δε is the molar absorptivity coefficient, [H] and [G] the concentration of the sensor and anion, respectively.

### Preparation of compounds 1 to 6

#### Synthesis of compound 1 [48,51]

In a sealed, round-bottomed flask containing 2,2'-bipyrrrole (1.01 g, 7.56 mmol) and purged with nitrogen, dry DMF (4.60 mL, 58.5 mmol) was added with a syringe. POCl₃ (2.17 mL, 23.9 mmol) was then slowly added dropwise over a period of 15 min at a temperature of 0 °C. The mixture was then heated to 60 °C for 1 h. Afterward, a 3 M aqueous solution of sodium acetate was carefully added to the reaction using a syringe. The reaction was allowed to continue for 2 h at a temperature of 80 °C. Following the completion of these steps, the mixture was filtered, and the resulting yellow-green solid was dried under reduced pressure. This product was used without further purification and weighed 1.32 g (7.0 mmol) with a yield of 84 %.

¹H NMR (300 MHz, CDCl₃) δ 11.89 (s, 2H, NH), 9.31 (s, 2H, CHO, Hf), 6.76 (dd, *J* = 3.9, 2.3 Hz, 2H, β-pyrrolic), 6.46 (dd, *J* = 3.9, 2.4 Hz, 2H, β-pyrrolic).

¹³C NMR (75 MHz, CDCl₃) δ 178.1 (CHO), 132.9, 131.2, 121.3, 109.5.

Melting Point: >350 °C

#### Synthesis of compound 2 [49]

POCl₃ (0.46 mL, 5.00 mmol) was slowly dripped into a 100 mL round-bottomed flask containing DMF (6.12 mmol) at 0 °C under an inert nitrogen atmosphere over a period of 15 min. Subsequently, dry dichloromethane (10.0 mL) was added, and the mixture was stirred at room temperature for 15 min. The mixture was cooled back to 0 °C, and 5-methyl-5-phenyldipyrrromethane (0.76 g, 3.25 mmol) dissolved in dry dichloromethane (25.0 mL) was added dropwise over 30 min. The mixture was then allowed to react at room temperature for 1 h before being warmed to 40 °C for 15 min and cooled back to room temperature. Saturated sodium carbonate solution (50.0 mL) was then added, and the mixture was stirred for 12 h at room temperature. The mixture was extracted with ethyl acetate (3 × 100 mL), and the organic layers were combined, dried over Na₂SO₄, filtered, and concentrated. The crude

product was purified using silica gel chromatography and hexane/ethyl acetate (70:30) to yield 0.80 g (84 % yield) of dipyrrromethane-1,9-dicarbaldehyde 2.

¹H NMR (300 MHz, CDCl₃) δ 9.80 (s, 2H, NH), 9.57 (s, 2H, CHO) 7.37–7.23 (m, 3H), 7.14–7.05 (m, 2H), 6.89 (dd, *J* = 3.9, 2.4 Hz, 2H), 6.14 (dd, *J* = 3.9, 2.6 Hz, 2H), 2.12 (s, 3H).

¹³C NMR (75 MHz, CDCl₃) δ 179.0 (CHO), 145.5, 144.4, 132.6, 128.7, 127.6, 127.1, 121.8, 110.4, 45.5, 28.4.

Melting Point: 223.4 °C

#### Synthesis of compound 3

A mixture of [2,2'-bipyrrrole]-5,5'-dicarbaldehyde (1) (50.0 mg, 0.26 mmol), malononitrile (0.10 g, 1.56 mmol) and a catalytic amount of NEt₃ (50.0 µL) in DMSO (3.0 mL) was stirred at 80 °C for 12 h. The reaction progress was monitored by TLC. After cooling the mixture to room temperature, water was added, and the precipitate was filtered to obtain a brown solid. After the powder had been dried, it was suspended in a solution of dichloromethane and agitated for 1 h. Subsequent filtering yielded 55 mg of 3 (η = 76 %) and no additional purification steps were deemed necessary.

¹H NMR (300 MHz, DMSO-d₆) δ 12.76 (s, 2H, NH₃), 7.82 (s, 2H), 7.54–7.45 (d, *J* = 4.5, 2H, β-pyrrolic), 7.06 (d, *J* = 4.4 Hz, 2H, β-pyrrolic).

¹³C NMR (75 MHz, DMSO-d₆) δ 145.5, 131.8, 128.3, 119.4, 115.6, 115.0, 113.3.

HRMS (ESI): *m/z* calculated for C₁₆H₉N₆ = 285.0883 [M+H]⁺, found 285.0872.

Melting Point: >350 °C

#### Synthesis of compound 4

To a mixture of [2,2'-bipyrrrole]-5,5'-dicarbaldehyde (1) (50.0 mg, 0.26 mmol), indane-1,3-dione (227.9 mg, 1.56 mmol) and a catalytic amount of piperidine (50.0 µL) in DMSO (3.0 mL) was added activated 4 Å molecular sieves (80.0 mg). The reaction was heated at 80 °C for 12 h and monitored by TLC. Then, the reaction mixture was allowed to cool to room temperature and water (5.0 mL) was added. The mixture was extracted with ethyl acetate (3 × 20.0 mL) and the organic phase was purified by silica gel chromatography. Compound 4 was obtained in 16 % yield.

¹H NMR (300 MHz, DMSO-d₆): δ 13.41 (d, *J* = 1.5 Hz, 2H, NH), 7.98–7.88 (m, 8H), 7.78 (s, 2H), 7.31 (d, *J* = 2.9 Hz, 2H, β-pyrrolic), 6.93 (d, *J* = 4.1 Hz, 2H, β-pyrrolic).

¹³C NMR (126 MHz, DMSO-d₆): δ 190.2, 189.0, 141.5, 139.7, 139.4, 135.4, 135.2, 123.6, 122.6, 122.5, 116.1, 114.2.

HRMS (ESI): *m/z* calculated for C₂₈H₁₇N₂O₄ = 445.1182 [M+H]⁺, found 445.1178.

Melting Point: >350 °C

#### Synthesis of compounds 5 and 6:

To a solution of dipyrrromethane 2 (30.0 mg, 0.10 mmol), indane-1,3-dione (0.30 mmol) or malononitrile (0.30 mmol) in dichloromethane (3.0 mL), 4 Å molecular sieves (50.0 mg) and a catalytic amount of NEt₃ (30.0 µL) were added. The mixture was left at room temperature until the starting material was completely consumed. After stirring for 6h, the resulting mixture was concentrated under vacuum and purified by flash chromatography (silica gel) using dichloromethane as the eluent. The yellowish/orange fraction was crystallized from a mixture of dichloromethane and hexane to produce 5 (70 % yield) or 6 (58 % yield) as yellow powders.

**Compound 5.** ¹H NMR (300 MHz, CDCl₃): δ 13.26 (s, 1H, NH), 7.87–7.84 (m, 2H), 7.78–7.75 (m, 2H, Hr), 7.72–7.62 (m, 6H, Hn, Hs and Ht), 7.46–7.31 (m, 3H, Hh, Hl, and Hk), 7.24–7.20 (m, 2H, Hl and Hj), 7.07 (dd, *J* = 4.0, 2.1 Hz, 2H, β-pyrrolic Hc), 6.40 (dd, *J* = 4.0, 2.4 Hz, 2H, β-pyrrolic Hb), 2.42 (s, 3H, H).
¹³C NMR (75 MHz, CDCl₃): δ 192.0, 190.7, 148.6, 141.1, 140.1, 134.6, 134.3, 132.7, 130.6, 128.8, 127.7, 127.2, 127.1, 122.6, 122.4, 119.8, 114.2, 46.5, 27.01.

HRMS (ESI): *m/z* calculated for C₃₆H₂₅N₂O₄ = 549.1808 [M+H]⁺, found 549.1803.

Melting Point: 229.8 °C

**Compound 6.** ¹H NMR (300 MHz, CDCl₃): *δ* 9.37 (s, 2H), 7.44–7.37 (m, 5H, phenyl), 7.15–7.07 (m, 2H, *β*-pyrrolic), 7.03–6.97 (m, 2H), 6.44–6.04 (m, 2H, *β*-pyrrolic H), 2.17 (s, 3H, CH₃).

¹³C NMR (75 MHz, CDCl₃): *δ* 147.7, 145.4, 142.2, 129.5–128.6, 126.7 (C₆), 126.6, 125.7, 115.6, 114.3, 112.1, 46.0, 27.3.

HRMS (ESI): *m/z* calculated for C₂₄H₁₇N₆Na = 411.1334 [M+Na]⁺, found 411.1338.

Melting Point: 271.7 °C

### CRediT authorship contribution statement

**Flávio Figueira:** Writing – original draft, Investigation, Formal analysis, Data curation.
**Andreia S.F. Farinha:** Writing – review & editing, Investigation, Formal analysis, Data curation.
**Adriano Santana:** Validation, Software, Resources, Investigation.
**Johannes S. Vrouwenvelder:** Writing – review & editing, Resources, Data curation.
**Augusto C. Tomé:** Writing – review & editing, Supervision, Formal analysis, Data curation.
**Dmitry Chernyshov:** Software, Resources, Data curation.
**Filipe A. Almeida Paz:** Writing – review & editing, Software, Resources, Formal analysis, Data curation.
**José A.S. Cavaleiro:** Writing – review & editing, Supervision.
**JoãoP.C. Tomé:** Writing – review & editing, Supervision, Funding acquisition.

### Declaration of generative AI in scientific writing

During the preparation of this work the authors used [Paperpal/Prime] in order to improve language and readability. After using this tool/service, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication.

### Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

### Acknowledgements

This work was developed within the scope of the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020 (DOI 10.54499/UIDB/50011/2020), & LA/P/0006/2020 (DOI 10.54499/LA/P/0006/2020), LAQV-REQUIMTE (LA/P/0008/2020, UIDP/50006/2020 and UIDB/50006/2020), CQE (UIDB/00100/2020 and UIDP/00100/2020) and IMS (LA/P/0056/2020) research units, financed by national funds through the FCT/MCTES (PIDDAC). The research contract of FF (REF-168-89-ARH/2018) is funded by national funds (OE), through FCT, in the scope of the framework contract foreseen in Nos. 4, 5 and 6 of article 23 of the Decree-Law 57/2016, of August 29, changed by Law 57/2017, of July 19. We thank the European Synchrotron Research Facility (ESRF) for approving the research proposal CH-5240.

This research used the resources of the Supercomputing Laboratory at King Abdullah University of Science and Technology (KAUST) in Thuwal, Saudi Arabia.

## Appendix A. Supplementary data

Supplementary data to this article can be found online at https://doi.org/10.1016/j.dyepig.2024.112535.

## Data availability

Data will be made available on request.

## References

[1] Langton MJ, Serpell CJ, Beer PD. Anion recognition in water: recent advances from a supramolecular and macromolecular perspective. Angew Chem Int Ed 2016;55: 1974–87.

[2] Zhao J, Yang D, Yang X-J, Wu B. Anion coordination chemistry: from recognition to supramolecular assembly. Coord Chem Rev 2019;378:415–44.

[3] Molina P, Zapata F, Caballero A. Anion recognition strategies based on combined noncovalent interactions. Chem Rev 2017;117:9907–72.

[4] Chen L, Berry SN, Wu X, Howe ENW, Gale PA. Advances in anion receptor chemistry. Chem 2020;6:61–141.

[5] Wu X, Howe ENW, Gale PA. Supramolecular transmembrane anion transport: new assays and insights. Acc Chem Res 2018;51:1870–9.

[6] Gale PA, Davis JT, Quesada R. Anion transport and supramolecular medicinal chemistry. Chem Soc Rev 2017;46:2497–519.

[7] Davis JT, Gale PA, Quesada R. Advances in anion transport and supramolecular medicinal chemistry. Chem Soc Rev 2020;49:6056–86.

[8] Hein R, Beer PD, Davis JJ. Electrochemical anion sensing: supramolecular approaches. Chem Rev 2020;120:1888–935.

[9] Falconer RJ. Applications of isothermal titration calorimetry – the research and technical developments from 2011 to 2015. J Mol Recogn 2016;29:504–15.

[10] Xu Z, Liu C, Zhao S, Chen S, Zhao Y. Molecular sensors for NMR-based detection. Chem Rev 2018;119:195–230.

[11] Aletti AB, Gillen DM, Gunnlaugsson T. Luminescent/colorimetric probes and (chemo-) sensors for detecting anions based on transition and lanthanide ion receptor/binding complexes. Coord Chem Rev 2018;354:98–120.

[12] Dhiman S, Ahmad M, Singla N, Kumar G, Singh P, Luxami V, et al. Chemodosimeters for optical detection of fluoride anion. Coord Chem Rev 2020; 405:213138.

[13] Ghosh A, Jose DA, Kaushik R. Anthraquinones as versatile colorimetric reagent for anions. Sens Actuators, B 2016;229:545–60.

[14] Kashyap S, Singh R, Singh UP. Inorganic and organic anion sensing by azole family members. Coord Chem Rev 2020;417:213369.

[15] Gale PA, Caltagirone C. Fluorescent and colorimetric sensors for anionic species. Coord Chem Rev 2018;354:2–27.

[16] Al-Saidi HM, Khan S. Recent advances in thiourea based colorimetric and fluorescent chemosensors for detection of anions and neutral analytes: a review. Crit Rev Anal Chem 2024;54:93–109.

[17] Hein R, Beer PD, Davis JJ. Electrochemical anion sensing: supramolecular approaches. Chem Rev 2020;120:1888–935.

[18] Vargas-Zúñiga GI, Sessler JL. Pyrrole N–H anion complexes. Coord Chem Rev 2017;345:281–96.

[19] He Q, Vargas-Zúñiga GI, Kim SH, Kim SK, Sessler JL. Macrocycles as ion pair receptors. Chem Rev 2019;119:9753–835.

[20] Figueira F, Rodrigues JMM, Farinha AAS, Cavaleiro JAS, Tomé JPC. Synthesis and anion binding properties of porphyrins and related compounds. J Porphyr Phthalocyanines 2016;20:950–65.

[21] Gale Philip A, Howe Ethan NW, Wu X. Anion receptor chemistry. Chem 2016;1: 351–422.

[22] Yu C, Jiao L, Yin H, Zhou J, Pang W, Wu Y, et al. α-/β-Formylated boron–dipyrrin (BODIPY) dyes: regioselective syntheses and photophysical properties. Eur J Org Chem 2011;2011:5460–8.

[23] Kaur N, Kaur G, Fegade UA, Singh A, Sahoo SK, Kuwar AS, et al. Anion sensing with chemosensors having multiple NH recognition units. Trends Anal Chem 2017;95: 86–109.

[24] Dey S, Giri B. Fluoride fact on human health and health problems: a review. Med Clin Rev 2016;2:1–6.

[25] Zhou Y, Zhang JF, Yoon J. Fluorescence and colorimetric chemosensors for fluoride-ion detection. Chem Rev 2014;114:5511–71.

[26] Samanta T, Das N, Shunmugam R. Intramolecular charge transfer-based rapid colorimetric in-field fluoride ion sensors. ACS Sustainable Chem Eng 2021;9: 10176–83.

[27] Mukherjee S, Shah M, Chaudhari K, Jana A, Sudhakar C, Srikrishnarka P, et al. Smartphone-based fluoride-specific sensor for rapid and affordable colorimetric detection and precise quantification at sub-ppm levels for field applications. ACS Omega 2020;5:25253–63.

[28] Kumar A, Bhatt M, Vyas G, Bhatt S, Paul P. Sunlight induced preparation of functionalized gold nanoparticles as recyclable colorimetric dual sensor for aluminum and fluoride in water. ACS Appl Mater Interfaces 2017;9:17359–68.

[29] Dey S, Kumar A, Mondal PK, Chopra D, Roy R, Jindani S, et al. Ultrasensitive colorimetric detection of fluoride and arsenate in water and mammalian cells using recyclable metal oxacalixarene probe: a lateral flow assay. Sci Rep 2022;12:17119.

[30] Das R, Talukdar D, Sarma PJ, Kuilya H, Thakuria R, Choudhury D, et al. Colorimetric detection of fluoride ions in aqueous medium using thiourea derivatives: a transition metal ion assisted approach. Dalton Trans 2021;50: 15287–95.

[31] Figueira F, Farinha ASF, Tomé AC, Cavaleiro JAS, Almeida Paz FA, Tomé JPC. Synthesis of hexaphyrins and N-fused pentaphyrins bearing pyridin-4-ylsulfanyl groups. J Porphyr Phthalocyanines 2014;18:824–31.
[32] Figueira F, Farinha ASF, Muteto PV, Poléto MD, Verli H, Gomes MTSR, et al. [28] Hexaphyrin derivatives for anion recognition in organic and aqueous media. Chem Commun 2016;52:2181–4.

[33] Figueira F, Marques I, Farinha ASF, Tomé AC, Cavaleiro JAS, Silva AMS, et al. Unprecedented double aza-michael addition within a sappyrhin core. Chem Eur J 2016;22:14349–55.

[34] Gale PA. Structural and molecular recognition studies with acyclic anion receptors. Acc Chem Res 2006;39:465–75.

[35] Cametti M, Rissanen K. Highlights on contemporary recognition and sensing of fluoride anion in solution and in the solid state. Chem Soc Rev 2013;42:2016–38.

[36] Kaur N, Kaur G, Fegade UA, Singh A, Sahoo SK, Kuwar AS, et al. Anion sensing with chemosensors having multiple NH recognition units. Trends Anal Chem 2017;95: 86–109.

[37] He Q, Tu P, Sessler JL. Supramolecular chemistry of anionic dimers, trimers, tetramers, and clusters. Chem 2018;4:46–93.

[38] Figueira F, Paz FAA, Tomé JPC. Meso pyridin-4-ylsulfanyl substituted doubly N-confused pentafluorophenyl[26]hexaphyrin. J Porphyr Phthalocyanines 2023;27: 1042–8.

[39] Ramos CIV, Figueira F, Poléto MD, Amado FML, Verli H, Tomé JPC, et al. ESI-MS/MS of expanded porphyrins: a look into their structure and aromaticity. J Mass Spectrom 2016;51:342–9.

[40] Farinha ASF, Tomé AC, Cavaleiro JAS. Synthesis of new calix[4]pyrrole derivatives via 1,3-dipolar cycloadditions. Tetrahedron 2010;66:7595–9.

[41] Farinha ASF, Calvete MJF, Paz FAA, Tomé AC, Cavaleiro JAS, Sessler JL, et al. Octatosylaminophthalocyanine: a reusable chromogenic anion chemosensor. Sens Actuators, B 2014;201:387–94.

[42] Sedghi R, Javadi H, Heidari B, Rostami A, Varma RS. Efficient optical and UV-vis chemosensor based on chromo probes-polymeric nanocomposite hybrid for selective recognition of fluoride ions. ACS Omega 2019;4:16001–8.

[43] Lee JY, Cho EJ, Mukamel S, Nam KC. Efficient fluoride-selective fluorescent host: experiment and theory. J Org Chem 2004;69:943–50.

[44] Boiocchi M, Del Boca L, Gómez DE, Fabbrizzi L, Licchelli M, Monzani E. Nature of Urea–Fluoride interaction: incipient and definitive proton transfer. J Am Chem Soc 2004;126:16507–14.

[45] Nishiyabu R, Anzenbacher P. 1,3-Indane-Based chromogenic calixpyrroles with Push–Pull chromophores: synthesis and anion sensing. Org Lett 2006;8:359–62.

[46] Farinha ASF, Tomé AC, Cavaleiro JAS. (E)-3-(meso-Octamethylcalix[4]pyrrol-2-yl) propenal: a versatile precursor for calix[4]pyrrole-based chromogenic anion sensors. Tetrahedron Lett 2010;51:2184–7.

[47] Farinha ASF, Fernandes MRC, Tomé AC. Chromogenic anion molecular probes based on β,β'-disubstituted calix[4]pyrroles. Sens Actuators, B 2014;200:332–8.

[48] Rapoport H, Castagnoli N. 2,2'-Bipyrrole. J Am Chem Soc 1962;84:2178–81.

[49] Rohand T, Dolusić E, Ngo HT, Maes W, Dehaen W. Efficient synthesis of aryldipyrromethanes in water and their application in the synthesis of corroles and dipyrromethenes. ARKIVOC (Gainesville, FL, U S) 2007;10:307–24.

[50] Rapoport H, Castagnoli N, Holden KG. 2,2'-:5',2'-:Terpyrrole. J Org Chem 1964;29: 883–5.

[51] Rapoport H, Holden KG. The synthesis of prodigiosin. J Am Chem Soc 1962;84: 635–42.

[52] Dalessandro EV, Collin HP, Guimarães LGL, Valle MS, Pliego JR. Mechanism of the piperidine-catalyzed Knoevenagel condensation reaction in methanol: the role of iminium and enolate ions. J Phys Chem B 2017;121:5300–7.

[53] Fioravanti S, Pellacani L, Tardella PA, Vergari MC. Facile and highly stereoselective one-pot synthesis of either (E)- or (Z)-Nitro alkenes. Org Lett 2008; 10:1449–51.

[54] van Beurden K, de Koning S, Molendijk D, van Schijndel J. The Knoevenagel reaction: a review of the unfinished treasure map to forming carbon-carbon bonds. Green Chem Lett Rev 2020;13:349–64.

[55] Savić TD, Saponjić ZV, Comor MI, Nedeljković JM, Dramićanin MD, Nikolić MG, et al. Surface modification of anatase nanoparticles with fused ring salicylate-type ligands (3-hydroxy-2-naphthoic acids): a combined DFT and experimental study of optical properties. Nanoscale 2013;5:7601–12.

[56] Mennucci B, Tomasi J, Cammi R, Cheeseman JR, Frisch MJ, Devlin FJ, et al. Polarizable Continuum model (PCM) calculations of solvent effects on optical rotations of chiral molecules. J Phys Chem A 2002;106:6102–13.

[57] Lv Y, Guo Y, Xu J, Shao S. Simple indole-based colorimetric sensors with electron-withdrawing chromophores: tuning selectivity in anion sensing. J Fluor Chem 2011;132:973–7.

[58] Gowri V, Jalwal S, Dar AH, Gopal A, Muthukrishnan A, Bajaj A, et al. A subtle change in substituent enabled multi-ways fluorine anion signals including paper-strip colorimetric detection using urea-functionalized push-pull chromophore receptor. J Photochem Photobiol, A 2021;410:113163.

[59] Ackermann T, Connors KA. Binding constants — the measurement of molecular complex stability, 91. New York: John Wiley & Sons; 1987. p. 1398.