Introduction

Fluorescent dyes have been intensively studied by the scientific community in multidisciplinary areas, like protein analysis [1], gene expression [2], mark subcellular organelles [3] and sensors [4,5,6]. The technological interest of these dyes has allowed their successful application as active media of tunable lasers, in the development of photoelectronic devices, such as fluorescent probes and chemical sensor, or monitoring the physicochemical characteristics of the surrounding ambiences [7].

Among the available classes of fluorescent dyes, BODIPY (acronym for boron-dipyrromethene, IUPAC name, 4,4-Difluoro-5,7-Dimethyl-4-Bora−3a,4a-Diaza-s-Indacene) have received special attention, due to their potential application in optoelectronics, medicine and biology [8]. Also, core such as 1,3,5-triazines, which has a high electron mobility and structural characteristics such as π conjugation, planarity, thermal and photochemical stability, has recently become a promissory structure for the synthesis of photochemical materials. [9].

The number of units of BODIPY are directly related with the enhancement of molecule fluorescence [10]. Indeed, hybrid compounds with two BODIPY units exhibited a higher fluorescence emission when compared with a hybrid compound linked to a single BODIPY [11]. However, there are not any studies about how the number of BODIPY, the presence of triazine core and an electron donor group in the final structure affect solvatochromism. Thus, we sought to synthesize 1,3,5-triazine derivatives linked to both BODIPY and electron donor groups to compare these with previously described compounds such as 2 and 3 which were synthetized by different synthetic approaches, which have in their structure the 1,3,5-triazine-core linked to BODIPY system with one unit of BODIPY in 2 and two units in 3, nevertheless in both molecules without the presence of electron donating groups.

Experimental

Synthesis

Reagents were obtained from Sigma-Aldrich Brasil Ltd. (São Paulo, SP—Brazil) and were readily used in the synthetic procedures. Solvents were obtained from local suppliers and treated according to established purification protocols. The structures of the BODIPYs synthesized herein were determined by 125 MHz 13C-NMR and 500 MHz 1H-NMR using a Bruker DRX 500-MHz NMR system from Bruker Daltonics® (Billerica, MA, USA), using a Shimadzu IR-Prestige 21 system from Shimadzu (Kyoto, Japan), and a high-resolution electrospray mass spectrometer (HRMS-ESI) using the ultrOTOFQ—ESI-TOF system from Bruker Daltonics ® (Billerica, MA, USA).

Synthesis of 6. This is a cyanuric Chloride derivative used as starting material to obtain 8 in better yield. In this way, to a solution of dichloromethane (15 mL) and cyanuric chloride 4 (368 mg, 2.2 mmol) in a ice bath at 0 °C was added dropwise a solution of valine 5 (289 mg, 1.9 mmol) and triethylamine (TEA) (310 μL, 2.2 mmol) in dichloromethane which was also at 0 °C. Product formation was monitored using thin layer chromatography (TLC), the end of the reaction was noted as soon as the starting material was consumed. The product was recrystallized using ethyl acetate and ether. Product was used in the next step.

Synthesis of 8 To a stirring solution of dimethylpyrrole 7 (273 mg, 0.66 mmol) and 6 (428 mg, ≈4 mmol) in CH2Cl2 at room temperature under inert atmosphere, three drops of trifluoroacetic acid (TFA) were added. After 3 h of stirring under these conditions, a solution of 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) (150 mg, 0.66 mmol) in was added to the reaction, and the mixture was stirred for another 4 h. The mixture was washed 3 times with 0.1 M NaOH(aq), dried under Na2SO4, filtered, and combined TEA (2.4 mL, 15 mmol) and Boron trifluoride ethyl etherate (BF3.OEt2) (2 mL, 15 mmol) at room temperature. The solution was washed with water (3 times) and dried under Na2SO4. The solvent was removed by distillation under reduced pressure and the oily residue was purified by flash column chromatography (230–400 mesh, hexane/ethyl acetate/TEA 75:23:2) to yield 110 mg (0.129 mmol) of 8 (40%). 1H NMR (400 MHz, CDCl3) δ 7.30 (d, J = 7.9 Hz, 1H), 6.97–6.90 (m, 4H), 6.05–5.97 (m, 4H), 3.79 (s, 6H), 2.56 (s, 12H), 1.55 (s, 12H), (125 MHz, CDCl3) δ 173.9, 156.3, 152.6, 143.6, 142.0, 140.8, 134.2, 131.8, 123.7, 121.8, 121.1, 113.4, 77.1, 56.9, 15.0, HRMS-ESI: [M + H]+ calculated for C43H40ClF4N7O4+: 852,3025; found: 852.3036.

Synthesis of 9: To a stirring solution of dimethylpyrrole 7 (200 mg, 0.6 mmol) and valine 5 (300 μL, ≈2 mmol) in CH2Cl2 at room temperature under inert atmosphere, three drops of TFA were added. After 3 h of stirring under these conditions, a solution of DDQ (150 mg, 0.66 mmol) in CH2Cl2 was added to the reaction, and the mixture was stirred for another 4 h. The mixture was washed 3 times with 0.1 M NaOH(aq), dried under Na2SO4, filtered, and combined TEA (2.4 mL, 15 mmol) and BF3.OEt2 (2 mL, 15 mmol) at room temperature. The solution was washed with water (3 times) and dried under Na2SO4. The solvent was removed by distillation under reduced pressure and the oily residue was purified by flash column chromatography (230–400 mesh, hexane/ethyl acetate/TEA 75:23:2) to yield 204 mg (0.39 mmol) (65.0%). 1H NMR (300 MHz, CDCl3) δ 7.04 (d. J = 6.8 Hz. 1H). 6.79 (dd. J = 6.4. 1.7 Hz. 2H). 6.00 (s. 2H). 5.80 (s. 2H). 3.88 (s. 3H). 2.57 (s. 6H). 1.50 (s. 6H) 13CNMR (75 MHz, CDCl3) δ 155.4, 147.4, 146.,2, 143.1, 141.6, 131.8, 126.,6, 121.1, 1152, 110.5, 56.2, 14.5.

Synthesis of 10: To a solution of dichloromethane (15 mL) and cyanuric chloride 4 (40 mg, 2 mmol) in an ice bath at 0 °C was added dropwise a solution of 9 (80 mg, 0.2 mmol) and TEA (70 μL, 0.5 mmol) in dichloromethane. After the addition, the system was left under stirring at 0 °C for 1 h, the formation of the product was monitored using thin layer chromatography. Product was purified using (230–400 mesh, hexane/ethyl acetate/95:5). The product is a solid orange. 30 mg. 29% yield. 1H NMR (300 MHz, CDCl3) δ 7.29 (dd. J = 6.6. 2.1 Hz. 1H). 6.99 (d. J = 2.1 Hz. 2H). 6.04 (s. 2H). 3.79 (s. 3H). 2.58 (s. 6H). 1.55 (s. 6H 13C NMR (75 MHz, CDCl3) δ 173.8, 155.9, 152.1, 143.1, 141.5, 140.6, 133.8, 131.4, 123.3, 121.5, 120.7, 113.0, 77.2, 56.4, 15.4, 14.7. HRMS-ESI: [M + H]+ calculated for C23H20BCl2F2N5O2 518.1128; found: 518.1127.

Photophysical Parameters

Absorption spectra were obtained on an Agilent 8453 UV-Visible spectrophotometer at room temperature in the solvents described above. Steady state fluorescence spectra were obtained on a Shimadzu RF5301PC spectrofluorimeter with a xenon arc lamp as the light source while using an excitation wavelength (λexc) of 470 nm.

The MicroTime 100 Upright Time-resolved Fluorescence Microscope™, was used to obtain the time-resolved fluorescence spectroscopy. One drop of sample was placed in Upright microscope BX43 from Olympus, data acquisition was made based on the method of Time-Correlated Single Photon Counting (TCSPC) in the unique Time-Tagged Time Resolved (TTTR) measurement mode Simultaneous data acquisition of up to two channels. The system software ®SymPhoTime64, was used by fitting an exponential decay curve to the obtained data, Fluorescence Lifetime Correlation Spectroscopy (FLCS).

Quantum yields were obtained by a comparative method [12] using fluorescein in 0.1 M NaOH(aq) as the standard (φ = 0.91, λexc = 470 nm) [13]. The quantum yield of the tested compound (φx) was calculated using Eqs. (1), where φst is the quantum yield of the standard, mx and mst are the slopes for the test compound and standard compound, and ƞx and ƞst are the refractive indexes of the solvents.

(1)

Nonradiative (κnr) and radiative (κr) were calculated from experimentally measured fluorescence quantum yield φ and calculated fluorescence lifetime τ according to Eqs. (2) and (3) [14].

$$ \varphi =\frac{\kappa_{nr}}{\kappa_r+{\kappa}_{nr}} $$
(2)
$$ \tau =\frac{1}{\kappa_r+{\kappa}_{nr}} $$
(3)

The influence of solvent parameters and descriptors over 1,3,5-triazina-BODIPYs’ characteristics was analyzed via a simple linear regression and multilinear regression analyses. Statistical calculations were done using R free software.

Results and Discussion

Synthesis

The synthetic routes used to obtain the three BODIPY derivatives for this work are shown in Figs. 1 and 2. The reaction between 5 and 4 in dichloromethane at room temperature produced the 1.3.5-triazine derivative 6. For obtaining 8, we applied the trifluoroacetic acid method, as described by Lindsey for meso-substituted dipyrromethanes [15]. Thus, reaction between 6 and 7, followed by oxidation with DDQ and complexation with BF3.OEt2 in triethylamine (TEA) produced 8. In addition, this procedure was used to synthesize meso-dihydroxyphenil BODIPY 9. Meanwhile, reaction between 9 and 4, in dichloromethane at 0 °C produced 10 (Fig. 3).

Fig. 1
figure 1

Similar BOPIDY-1,3,5-triazine s structures reported in the literature

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Fig. 2
figure 2

Synthesis of two units of BODIPY linked by 1,3,5-triazine, experimental conditions: a TFA. b DDQ. c BF3·Et2O, TEA

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Fig. 3
figure 3

Synthesis of BODIPY without 1.3.5-triazine (9) and one unit of BODIPY linked to 1,3,5-triazine experimental conditions: a TFA. b DDQ. c BF3·Et2O, TEA

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Photophysical Properties

Photophysical properties of the synthesized BODIPYs were tested in five solvents with different polarities: Methanol (MeOH), acetonitrile (MeCN), tetrahydrofurane (THF) dichloromethane (DCM) and hexane (HEX). To compare with BODIPY without meso substitution we used data reported by Rezende et al. [16], and to compare with meso-1,3,5-triazina-BODIPY we used data reported by zhou et al. [11]. These data are summarized together with our experimental datas in Tables 1, 2 and 3.

Table 1 Parameter of absorption and emission spectra of compound 8, 9 and 10 compared with unsubstituided BODIPY 1
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Table 2 Parameter of absorption and emission spectra of compound 2 and 3
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Table 3 Fluorescence lifetime, quantum yield, coefficient of radiative and non-radiative decay of 8, 9, 10 and 1
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The photophysical properties of compounds 8, 9 and 10 were investigated by UV–Vis spectra and fluorescence spectra as shown in Fig. 4. All of them exhibited the maximum absorption at around 500 nm, due to strong S0-S1 transition [17] and which were similar to that of compound 1, 2 and 3.

Fig. 4
figure 4

UV absorption and Fluorescence emission of 3 BODIPY synthetized a: 8, b:9 and c:10

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We observed that for all solvents, molecules 8 and 10 had a hypsochromic shift for λabs and a bathochromic shift for λem, when compared with 1. Similar effect was found when the λabs of MeOH and λem of DCM in 2 and 3 were compared with 1. This result showed that the presence of 1,3,5-triazine core is responsible for hypsochromic shifts. Which is due to π - π* transition that frequently cause a hypsochromic shift [18].

When hydroxyl-methoxyphenyl group was added (9) on the BODIPY, there was a hypsochromic shift in λabs in all solvents. Just with DCM the λem wavelength had a hypsochromic shift. Blue-shift absorption bands were observed due to the electron-donating character of this type of group, which generally increases the LUMO energy and increases the HOMO−LUMO gap [19,20,21]. Regarding the number of BODIPY units, there was no observed significant shift when 2 and 3 were compared with 1.

Figure 5 shows a comparative intensity of compounds 8, 9 and 10. In polar solvents, intensity of absorption and emission were greater for 8 and 10 than 9. This differences is due to the high electron mobility and π conjugation of 1,3,5-triazine core that increase the intensity of energy emitted causing the intramolecular charge transfer and mesomeric dipole moment thus, increasing the intensity of emission. [9].

Fig. 5
figure 5

Comparative graphs of absorption and fluorescence for 8 (black), 9 (red) and 10(blue)

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Figure 6 showed that the presence of 1,3,5-triazine decreases the quantum yield. Value for 1 is φ = 0.95 and values of molecules 2 and 3 are about φ = 0.1; addition of methoxy group caused two times increase in the φ values for all solvents about φ = 0.3. This showed that 1,3,5-triazine linked by phenyl to the core of BODIPY causes the loss of the ability to dissipate energy by rotational and vibrational relaxation [22]. In addition, values of the non-radiative deactivation constants are in an order of magnitude higher than the radiative ones that confirms the hypothesis; the results leads us to think that the presence of triazine core causes the energy to be dissipated by other pathways [23]. The Stokes shift (Δv), which was calculated from the wavenumber of maximum absorption and emission intensities, was variably increased with the addition of meso-substituent, 9 was two times higher than 1. In spite of the presence of 1,3,5-triazine core and methoxy group in the system to increase the values but we did not find a significant increment.

Fig. 6
figure 6

Comparative values of absortion and emission of BODIPY-1,3,5-triazine synthetized 8,9 and 10 with reported valued of BODIPY and BODIPY-1,3,5-triazine 1, 2 and 3

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Solvatochromic Effects

The Dimroth-Reichardt solvent ionizing power index (ETN) [13], the dielectric constant (εr) and dipolar moment [24], of binary solvent systems were collected to rationalize the obtained results. The solvent polarity measured like ETN affects significantly the photophysical properties, in 8 and 9, in the regression analysis with heightened polarity of solvents the FWHMabs value decreased, except for values obtained with DCM. Already the differences obtained in analysis of solvatochromism in other studies had been reported [16]. The inverse trend was observed in the regression analysis of ETN, DM and εr for 10 had a positive slope which was three times higher than 8 and 9. Emission charts, all the compounds present a slight positive slope, and in the fluorescence, the non-polar solvents present the greatest difference between the analyzed molecules. Our results agree with the literature which said that Polar solvents are commonly related to broader peaks due to the enhanced interaction of the solvent molecules with the transition dipole moment of the fluorophores [25].

When we did the comparison with the values reported by Rezende et al. who did the same lineal regression for BODIPYS meso-subsituited. we found that FMWH values were 2 times higher than values reported for BODIPY 1 [16]. That is, because the electronic excitation that is connected with a reduction in dipole moment in agreement with a considerable charge transfer and the introduction of substituents in the acceptor part, that increased its electron affinity and led to the result obtained [26].

We decided to perform the analysis of solvent parameters and emission maxima (vem), stokes shift (Δv) and wavenumber (cm − 1) of absorption maxima (vabs), through a multilinear regression. This kind of analysis allows the simultaneous study of the effect of several solvent parameters. For the analysis we used the catalán solvents parameter [27], solvent acidity (SA), basicity (SB), dipolarity (SdP) and polarizability (SP) because it was reported for BODIPY that, catalán solvents parameters resulted in a better correlation [16].

The results showed that there is a marked stabilizing effect due to the presence of the 1,3,5-triazine ring, due to the large differences shown between 1 and 8, 10, 2 and 3. When comparing the obtained value for polarizability (SP) we find that the value obtained for 2 and 3 in magnitude is less than 1, the addition of the methoxy group to the system further decreased the value. For dipolarity (SdP) we found that the values of 2 and 3 are close to zero, presenting an average difference of 150 units. However, when introducing the methoxy group into the system, the influence of the dipolarity of the solvent is greater, the values observed for 8 and 10 are 5 times larger than the values of 2 and 3, this result is related to the high dispersions observed in Fig. 7. Values for 8, 9, 10, 2 and 3, are positives, indicating blue shifts with increasing SdP. This positive value of SdP suggests that the excited state dipole moment is smaller than that of the ground state [28].

Fig. 7
figure 7

Linear regression of emission and absorption peak lengths against solvent parameters. 5 (gray), 6 (blue) and 7 (orange)

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The introduction of the 1,3,5-triazine ring decreased the effect of the acidity and the basicity of the solvent on the absorption of the BODIPY-1,3,5-triazine system; however, the differences are smaller when compared with the other variables. The introduction of the methyl group, the differences between the values of 2 and 3 increased with 8 and 10, which showed that in the addition of the methyl group, in more basic pH, the photophysical properties can be maintained almost unaltered. Positive values of SB and SA indicated the existence of a destabilized excited state in polar and basic solvents, which decreased upon excitation. Our results showed that for BODIPY-1,3,5-triazine solvent dipolarity is not the sole factor affecting the position of the absorption maxima and that solvent basicity (SB) and polarizability (SP) are additional, although minor contributors (Tables 4 and 5).

Table 4 Values of solvent polarity parameters used for solvatochromism analyses
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Table 5 Correlation coefficients and regression coefficients analysis of Ʋabs, Ʋem and ΔƲ
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Conclusion

In conclusion, the presence of a single core BODIPY and electron donor in derivatives of 1,3,5-triazine generate a stabilization effect by electronic conjugation doing to molecule be less susceptible to changes due to physicochemical characteristics of solvent however, the addition of more BODIPY units reduce the electronic stability. Here, we reported the first study of salvatochromism phenomena using a novel BODIPY-triazine compound and how its structure do not alter photophysical properties of 1,3,5 traizine derivatives.