Synthesis, characterization and self-assembly of novel fluorescent alkoxy-substituted 1, 4-diarylated 1, 2, 3-triazoles organogelators

2.1 Materials and methods

Differential Scan Calorimetry (DSC; TA 2920) was used to measure the melting points. The ¹H/¹³C NMR spectral analysis was performed on Bruker Avance 400 MHz. Perkin-Elmer 2400 (Norwalk, USA) was used to determine the elemental analysis. An Ultraviolet-Agilent from Cary Series was used to conduct the UV/Vis absorption spectra. The fluorescence quantum yields (Ф) and fluorescence spectral analysis were investigated by VARIAN CARY ECLIPSE. The fluorescence quantum yields (Ф) were determined using solutions of rhodamine 6G (Ф_r = 0.95) and rhodamine 101 (Ф_r = 0.96) in absolute ethanol as quantum yield standards. FT-IR Bruker Vectra 33 was used to get infrared spectra. A Quanta FEG 250 apparatus was used for the scanning electron microscopy (SEM) examination. In this experiment, we prepared an organogel in n-octanol, which was then air-dried on a clean glass slide. The gold-coated xerogel was exposed to annealing overnight at 45 °C. Unless otherwise stated, all materials used in the experiments were from Sigma-Aldrich and Merck (Egypt). Compounds 1 (1,3‑dialkoxy‑4,6‑diethynylbenzene) and 2 (5‑azido‑1,3‑dialkoxybenzene) were synthesized in accordance with previous procedures (Afzali et al., 2021; Fakhrutdinov et al., 2021). Thin layer chromatography was utilized to observe the progress of reactions using aluminium-backed plate loaded with a coating of silica gel 60 under an ultraviolet lamp (UV₂₅₄). Silica gel 60 was applied to purify the synthesized compounds by flash column chromatography.

2.2 Gelation procedure

Compounds 3a-c were dissolved in the specified solvents and heated at boiling point in a closed glass vial to generate a transparent solution, and subjected to cooling to ambient temperature to create gels. In 15–25 min, the gels formed relying on the organogelator concentration and the length of the aliphatic chain. The gel formation was confirmed by the “stable-to-inversion” approach as indicated by the solvent disappearance in the inverted vial. The reversibility was examined by heating (2 °C/min) the organogel-containing glass vial placed topsy-turvy in an oil bath. The temperature at which the gel collapses is reported as the gel melting point. The above procedures were repeated to designate a good reversibility.

2.3 Cytotoxicity assay

BJ1 skin fibroblast cells were used to conduct the cytotoxicity experiment in vitro following the previously established MTT proliferation technique (Abumelha et al., 2020).

2.4 Antibacterial activity

The antibacterial properties of the synthesized triazoles were explored against S. aureus and E. coli under AATCC (100:1999) (Aldalbahi et al., 2021).

2.5 Synthesis procedures

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2.6 General synthesis of triazoles 3a-c

A mixture of diethynyl 1 (1 mmol), azido compound 2 (2 mmol), TBTA (tris((1-benzyl-4-triazolyl)methyl)amine; 0.1 mmol), sodium ascorbate (0.2 mmol) was dissolved in a mixture of distilled water:t-BuOH:CH₂Cl₂ (1:2:8) under argon atmosphere. Copper(II) sulfate (CuSO₄·5H₂O; 0.1 mmol) was then added to the mixture, followed with stirring under ambient conditions for 22 h. The reaction system was covered with aluminum foil to ensure that the reaction occurs in the dark. After complete consumption of alkyne, the mixture was diluted with dichloromethane. The organic layer was then subjected to extraction with dichloromethane, three times washing with aqueous brine. The dichloromethane solution was dried on magnesium sulfate (anhydrous), filtered off under vacuum, and finally dichloromethane was evaporated using a rotary evaporator. The solid product was subjected to column chromatography (ethyl acetate/ether 2/7).

Tetrahexyl-5, 5′-(4, 4′-(4, 6-bis(hexyloxy)-1, 3-phenylene)-bis(1H-1,2,3-triazole-4, 1-diyl))diiso-phthalate 3a.

Prepared from 1 (326 mg, 1 mmol), azido compound 2a (750 mg, 2 mmol), TBTA (tris((1-benzyl-4-triazolyl)methyl)amine; 53 mg, 0.1 mmol), sodium ascorbate (40 mg, 0.2 mmol) and copper(II) sulfate (16 mg, 0.1 mmol). Prepared as a white powder with 88% (947 mg) yield; mp 191–192 °C; ¹H NMR (400 MHz; CDCl₃): 9.46 (s, 1H), 8.84 (s, 2H), 8.78 (s, 4H), 8.63 (s, 2H), 6.72 (s, 1H), 4.43 (t, J = 6.02 Hz, 8H), 4.20 (t, J = 6.11 Hz, 4H), 1.89 (m, 4H), 1.83 (m, 8H), 1.28–1.59 (m, 36H), 0.91 (t, J = 4.77 Hz, 18H); ¹³C NMR (400 MHz; CDCl₃): 165.85, 157.59, 145.73, 138.80, 133.86, 129.93, 128.64, 125.85, 119.72, 112.80, 97.47, 79.75, 66.20, 32.94, 31.567, 29.72, 29.36, 28.80, 26.10, 22.54, 14.20; IR (ν/cm⁻¹): 3065 (C-H aryl stretch), 2917 (CH alkyl asymmetric stretching), 2847 (CH alkyl stretch), 1731 (C = O stretch), 1589 (C = N), 1503 (C = C aryl bend), 1330 (C-O), 1188 (CH₂ alkyl bending), 1122 (CH₃ alkyl bending), 862 (C-H aryl bending), 723 (CH₂ alkyl bending rocking); Elemental analysis of C₆₂H₈₈N₆O₁₀ (1076.66): C 69.12, H 8.23, N 7.80; Found: 68.96, H 8.15, N 7.71.

Tetranonyl-5, 5′-(4, 4′-(4, 6-bis(hexyloxy)-1, 3-phenylene)-bis(1H-1,2,3-triazole-4, 1-diyl))diiso-phthalate 3b.

Prepared from 1 (326 mg, 1 mmol), azido compound 2b (918 mg, 2 mmol), TBTA (tris((1-benzyl-4-triazolyl)methyl)amine; 53 mg, 0.1 mmol), sodium ascorbate (40 mg, 0.2 mmol) and copper(II) sulfate (16 mg, 0.1 mmol). Prepared as a white powder with 81% (1.05 g) yield; mp 165–167 °C; ¹H NMR (400 MHz; CDCl₃): 9.41 (s, 1H), 8.80 (s, 2H), 8.76 (s, 4H), 8.58 (s, 2H), 6.70 (s, 1H), 4.39 (t, J = 6.18 Hz, 8H), 4.22 (t, J = 6.25 Hz, 4H), 1.88 (m, 4H), 1.85 (m, 8H), 1.25–1.67 (m, 60H), 0.92 (t, J = 4.81 Hz, 18H); ¹³C NMR (400 MHz; CDCl₃): 165.76, 157.64, 146.68, 139.79, 133.83, 129.78, 126.39, 123.72, 119.45, 110.74, 96.18, 69.73, 66.02, 31.91, 30.38, 29.77, 29.31, 29.21, 28.77, 25.87, 23.65, 22.28, 14.27; IR (ν/cm⁻¹): 3069 (C-H aryl stretch), 2918 (CH alkyl asymmetric stretch), 2850 (CH alkyl symmetric stretching), 1729 (C = O stretch), 1582 (C = N), 1508 (C = C aryl bend), 1337 (C-O), 1191 (CH₂ alkyl bend), 1125 (CH₃ alkyl bend), 867 (CH aryl bend), 728 (CH₂ alkyl bending rocking); Elemental analysis of C₇₄H₁₁₂N₆O₁₀ (1244.84): C 71.35, H 9.06, N 6.75; Found: C 71.48, H 9.15, N 6.83.

Tetradodecyl-5, 5′-(4, 4′-(4, 6-bis(hexyloxy)-1, 3-phenylene)-bis(1H-1,2,3-triazole-4, 1-diyl)) diiso-phthalate 3c.

Prepared from 1 (326 mg, 1 mmol), azido compound 2c (1.09 g, 2 mmol), TBTA (tris((1-benzyl-4-triazolyl)methyl)amine; 53 mg, 0.1 mmol), sodium ascorbate (40 mg, 0.2 mmol) and copper(II) sulfate (16 mg, 0.1 mmol). Prepared as a white powder with 78% (1.10 g) yield; mp 128–130 °C; ¹HNMR (400 MHz; CDCl₃): 9.45 (s, 1H), 8.80 (s, 2H), 8.79 (s, 4H), 8.62 (s, 2H), 6.71 (s, 1H), 4.37 (t, J = 6.28 Hz, 8H), 4.19 (t, J = 6.35 Hz, 4H), 1.86 (m, 4H), 1.84 (m, 8 H), 1.31–1.57 (m, 84H), 0.90 (t, J = 4.88 Hz,18H); ¹³C NMR (400 MHz; CDCl₃): 165.26, 157.58, 145.84, 138.51, 133.45, 129.70, 127.61, 124.40, 119.60, 111.74, 96.38, 68.66, 66.81, 31.72, 31.20, 29.80, 29.68, 29.41, 29.26, 28.60, 26.77, 26.26, 22.64, 22.35, 14.11, 13.75; IR (ν/cm⁻¹): 3070 (CH aryl stretch), 2919 (CH alkyl stretch), 2851 (CH alkyl stretch), 1733 (C = O stretch), 1586 (C = N), 1501 (C = C aryl bend), 1328 (C-O), 1182 (CH₂ alkyl bending), 1116 (CH₃ alkyl bending), 858 (C-H aryl bending), 725 (CH₂ alkyl bending rocking); Elemental analysis of C₈₆H₁₃₆N₆O₁₀ (1413.03): C 73.05, H 9.69, N 5.94; Found: C 72.91, H 9.78, N 6.07.

3.1 Synthesis and characterization

The major aim of the present research work was to prepare new fluorescent alkoxy-substituted 1, 4-diarylated 1, 2, 3-triazole gelators. The diethynyl compound 1 (1,3‑dialkoxy‑4,6‑diethynylbenzene) and azido compound 2 (5‑azido‑1,3‑dialkoxybenzene) compounds were synthesized in accordance with previous procedures (Afzali et al., 2021; Fakhrutdinov et al., 2021). As depicted in Scheme 1, alkoxy-substituted 1, 4-diarylated 1, 2, 3-triazoles (3a, 3b and 3c) were synthesized in relatively high yields using Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC) of compound 1 comprising two terminal alkyne groups and two terminal alkoxy substitutents with 5‑azido‑1,3‑dialkoxybenzene 2 with different alkoxy chain lengths. ¹H/¹³C NMR, FTIR, and elemental analysis were used to prove the molecular structures of the novel compounds 3a-c. ¹H NMR spectra of compound 3a-c exhibited distinct signals for the alkoxy chain substituents ranging from ∼ 0.90 to ∼ 4.43 ppm. The symmetrical CH peaks of the 1, 2, 3-triazole heterocyclic rings were monitored to downfield shift at ∼ 8.50 ppm. The ¹³C NMR spectra of 3a-c displayed 1, 2, 3-triazole C-H signal at ∼ 145 ppm. The infrared spectra of 3a-c showed strong absorbance peaks of the alkoxy groups at ∼ 2920 and ∼ 2850 cm⁻¹.

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Scheme 1

Synthesis of triazolo-based organogelators 3a-c.

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3.2 Photophysical properties

A stimuli-responsive chemical or product has the ability to vary its absorbance or emission spectra responding to external stimuli, like heat and/or light (Mellerup and Wang, 2019; Moulin et al., 2020; Rastogi and Kandasubramanian, 2019). Some selected solvents were used to study the UV–Vis absorption and fluorescence properties of the current alkoxy-substituted 1, 4-diarylated 1, 2, 3-triazole compounds as shown in Table 1. Both absorbance and fluorescence maxima of the alkoxy-substituted 1, 4-diarylated 1, 2, 3-triazole derivatives were reported in a range of solvents, including n-propanol, ethanol, n-octanol, DMSO, THF, toluene, benzene, acetonitrile, DMF, CH₂Cl₂ and hexane. It was revealed that all of the triazole derivatives absorb light in the UV–Vis region. The current alkoxy-substituted 1, 4-diarylated 1, 2, 3-triazole derivatives demonstrated an emission wavelength lower than that for previously reported conjugate triazole molecular systems (Ahmed and Xiong, 2021; Torres et al., 2021; Zhang et al., 2017). The π-π* transition is responsible for those absorption bands (Wang et al., 2010). The absorption wavelengths of the symmetric series were monitored to increase with raising the alkoxy chain length. This indicates that the excited state of the shorter alkoxy chain substituted triazole is lower than the excited state of the longer alkoxy chain substituted diarylated triazole. An increase in the UV–Vis absorption wavelength (Bathochromic shift) associated with a drop in fluorescence emission maxima was monitored when the length of the aliphatic tail was increased. Solvatochromic and solvatofluorochromic characteristics were shown in the UV–Vis absorption and fluorescence wavelengths in various solvents of different polarities. As the polarity of the solvent increases, a rise in the maximum wavelength was monitored in the absorption (positive solvatochromism) and fluorescence (positive solvatofluorochromism) spectra. In addition, it was found that the fluorescence quantum yield decreases when the length of the aliphatic alkoxy chain increases.

3.3 Gelation properties

The nanofibrous architectures of self-assembled π-conjugated molecular systems have been reported with various characteristics in comparison to these π-conjugate building blocks themselves. Emission has been a critical character with the ability to display a key responsiveness to the surrounding environment. For example, emissive structures have a significant modulation effects on wavelength and intensity of emission as a result of forming supramolecular systems. Therefore, emissive assemblies are priceless materials for detecting a variety of analytes (Lin et al., 2019; Lin et al., 2017; Sasaki et al., 2020). In the current study, no gelation was monitored for the synthesized tetrahexyl-substituted triazole adduct 3a. The prepared alkoxy-substituted 1, 4-diarylated 1, 2, 3-triazole gelators composed of four terminal alkoxy groups of high flexibility separated with the rigid bis(triazole)aryl core responsible for π-stacking. Aggregation of these alkoxy-substituted 1, 4-diarylated 1, 2, 3-triazole molecular gelators provide three dimensional entanglements of nanofibrous network that can be controlled by crystal formation and degree of solubility. Gelators 3a-c are soluble in some solvents upon heating. Upon dissolution of compounds 3a-c in solvents by heating, and then cooling to ambient temperature, a solid-like organogel was formed and monitored by the ‘‘stable to inversion’’ method as illustrated in Fig. 1. The gel formation of adducts 3a-c was studied in several organic solvents. The values of critical gel concentration for gelator 3b were monitored to be solvent-dependent ranging between 1.84 and 9.28 mM. Compound 3b shows a considerable capacity to gelate various organic solvents such as ethylacetate, chloroform, acetonitrile and n-octanol. However, adduct 3b was partially gelated in other solvents such as n-propanol and toluene, hexane and displayed no gelation in other solvents such as dichloromethane, THF, ethanol, 1,2-dichloroethane, DMF, DMSO and benzene. The gelation study of adducts 3a-c in various solvents is presented in Table 2. Compound 3a demonstrated low solubility in organic solvents. Thus, it precipitates in many solvents. On the other hand, compound 3c demonstrated a very high solubility in organic solvents. Thus, it is displayed formation of solutions in many solvents. All organogels formed in organic solvents are either colorless or white non-flowing oganogels. The sol–gel switchable course was thermally reversible. The synthesized organogelators demonstrated similar photophysical properties similar to those monitored in their respective solution-based photophysical properties. The alkyl chains are non-polar moieties comprising only single bonds with carbon and hydrogen atoms. Therefore, the interactions among alkyl chains are comparatively weak London/Dispersion van der Waals forces, which usually increase as the length of the alkyl chain increases as a result of increasing the molecule surface area. Thus, compounds 3b-c with longer alkyl chains demonstrated an improved organogel formation as compared to compound 3a with the shorter length of alkyl chains.

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Fig. 1

Thermal and emission reversibility of gel 3b (n-octanol) monitored by the stable to inversion approach under ultraviolet (UV) and visible (Vis) lights.

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As shown in Fig. 2, the blue shifting of the fluorescence maxima for the gel state of 3b in comparison to that in an ethyl alcohol solution (diluted) indicates the presence of H-aggregates in the supramolecular organogel (Lin et al., 2019). It has been shown that H-aggregate systems have a propensity to form two-dimensional nanofibers due to the intermolecular van der Waals interactions of tetraalkoxyls as well as intermolecular π-stacks of rigid bis(triazole)aryl core.

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Fig. 2

Normalized emission spectra of 3b in solution (n-octanol; 1.09 × 10^-5 mol L^-1) and organogel states.

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Table 3 shows both fluorescence wavelength and quantum yield of 3a-c in solution and organogel (or partial organogel) states. The gel demonstrated different fluorescence wavelengths in comparison to the respective sol states of the same gelator. In n-octanol, the fluorescence of 3b at 315 nm for the sol state shifts to 293 nm for the organogel state. The partial gel demonstrated lower shifting in the fluorescence wavelength in comparison to the completely gel formation case. For 3a and 3b, the quantum efficiency was observed to improve in the oranogel state in comparison to the solution state (Altoom 2021; Radwan and Makhlouf, 2021).

The thermal stability of the synthesized triazole 3b in n-octanol was explored by investigating the critical gel concentration reliant gel → sol conversion as illustrated in Fig. 3. The organogel melting point was recorded to rise between 41 and 55 °C with raising the gelator concentration between 1.84 and 14.00 mmol/L. This improved thermostability can be ascribed to the high crowd of the gelator molecules in the fiber bulk. However, the organogel melting point decreased when the gelator concentration increased to a value above 14.00 mmol/L. These increments monitored for the gel → sol transition temperature could be attributed to increasing the 1D fiber aggregation imparting this fiber higher flexibility to result in nanofibrous entanglement, and accordingly rising the transition temperature.

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Fig. 3

Gel → sol transition temperature against the organogelator (3b) quantity in n-octanol.

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To investigate the gel → sol reversibility, the temperature-dependent transition was explored (Fig. 4). The non-flowing solid-like gel was heated to boiling (∼195 °C for n-octanol) until a transparent solution formed. The collapsing temperature of the gel was reported. The solution was then placed on a flat surface to settle for a few minutes at room temperature (∼25 °C) to allow the organogel to regenerate as confirmed by the “stable to inversion” approach. This procedure was repeated to designate no change occurred in the gel → sol switching temperature proving good reversibility.

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Fig. 4

Temperature-dependent sol-to-gel-to-sol reversibility without fatigue for 3b.

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3.4 Morphological properties

Using SEM analysis, the surface morphologies of the triazole gelators 3a-c were examined to analyze the roles of π-stacks and van der Waals forces in guiding their formation. The self-assembled intertwined nanofibers were found to be well-ordered and homogeneous. SEM images were used to study the aggregation morphology of gelator 3b dried xerogel (Fig. 5). Sample of dried xerogel from gelator 3b was transferred to a glass slide and examined using SEM to demonstrate three dimensional entangled assemblies accounting for the immobilization of solvent molecules. Examination of SEM images displayed higher order of nanofibrous assemblies with the ability to bundle and generate strong and highly porous entanglements indicating highly directed intermolecular attraction forces. Nanofibers with diameters of 250–320 nm and few micrometres long were monitored in the SEM micrographs of 3b from n-octanol. The self-assembly of 3b creates nanofibers via immobilization of organic solvents. When it comes to gelators, the presence of lengthy alkoxy groups has been observed as a key component in improving their stability.

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Fig. 5

SEM micrographs of dried xerogel generated from gelator 3b in n-octanol.

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3.5 Cytotoxicity measurements

Compounds 3a-c were tested for cytotoxicity in vitro to determine the viability of certain BJ1 skin fibroblast cells exposed to these triazoles. Compounds 3a and 3b did not seem to affect on the cell proliferation. However, compound 3c begins to lose its viability to result in 91.33 % viable cells. Because organic chemicals tend to precipitate out of solution, there is less room for cell growth, resulting in a drop in cell numbers. The current alkoxy-substituted 1, 4-diarylated 1, 2, 3-triazoles, as a consequence of these findings, are clearly harmless compounds. Thus, they can be potentially used for drug delivery applications. The antibacterial properties were also examined against S. aureus and E. coli to show acceptable antibacterial activity as shown in Table 4. However, the antibacterial activity decreased with raising the alkoxy chain length. Thus, the best antibacterial performance was monitored for compound 3a.

Antimicrobial activity of nitrogen-containing heterocyclic compounds has been observed (Heravi and Zadsirjan, 2020; Zhang et al., 2010). The class of nitrogen-containing heterocyclic triazoles is especially intriguing because of its intrinsic biological activity (Gondru et al., 2021) and considerable utility as molecular building blocks in synthetic transformations (Patil et al., 2020; Phatak et al., 2020). Thus, scientists are now working to create novel functionalized triazole derivatives and investigate their biological effects. However, a little research studies have been reported on the synthesis of antibacterial triazoles (Nalawade et al., 2019; Yadav et al., 2018). Moreover, the development of triazole-based fluorescent organogels has not been described yet. The synthesis of innovative compounds with biological has been significant (Aragón-Muriel et al., 2021; Hernández-Romero et al., 2021; Ríos-Malváez et al., 2021; Rufino-Felipe et al., 2021). Several low molecular mass organogels have recently been reported to be effective antibacterial and drug delivery materials that are not cytotoxic (Esposito et al., 2018; Rowley et al., 2020). Bioimaging, antimicrobials, and drug delivery systems all benefit from the newly synthesized triazole-based fluorescent low molecular mass organogels.