Arylisoquinoline-derived organoboron dyes with a triaryl skeleton show dual fluorescence

Four new dyes that derive from borylated arylisoquinolines were prepared, containing a third aryl residue (naphthyl, 4-methoxynaphthyl, pyrenyl or anthryl) that is linked via an additional stereogenic axis. The triaryl cores were synthesized by Suzuki couplings and then transformed into boronic acid esters by employing an Ir(I)-catalyzed reaction. The chromophores show dual emission behavior, where the long-wavelength emission band can reach maxima close to 600 nm in polar solvents. The fluorescence quantum yields of the dyes are generally in the range of 0.2–0.4, reaching in some cases values as high as 0.5–0.6. Laser-flash photolysis provided evidence for the existence of excited triplet states. The dyes form fluoroboronate complexes with fluoride anions, leading to the observation of the quenching of the long-wavelength emission band and ratiometric response by the build-up of a hypsochromically shifted emission signal.


Introduction
Boron-containing tri-and tetra-coordinated chromophores have attracted considerable interest due to their often peculiar and highly advantageous photophysical properties that include spec-trally tunable and highly intense fluorescence [1,2]. On the one hand, those compounds that contain the boron atom in a valence-saturated situation corresponding to sp 3 hybridization Scheme 1: Synthesis of the precursors 2, 3, and 5.
As part of our research program we have developed arylisoquinolines that integrate a boronic acid ester [37][38][39] or a BMes 2 unit [6,40]. The presence of the boron-substituent confers interesting photophysical properties to these dyes such as intramolecular charge-transfer processes and tunable redshifted emission bands. Generally, the so far investigated borylated arylisoquinoline dyes show principally fluorescence quenching (on-off switching) on the formation of the corresponding fluoroboronate complexes [37].
Herein, we extended our previously reported arylisoquinolinederived organoboron dye platform with an additional axially linked aryl residue (see structures 16-19 in Figure 1) in the expectation to modulate the fluorescence properties and fluoride response of these dyes. The additional aryl residues allow the verification of the effect of aromatic conjugation (naphthyl, anthryl, pyrenyl) and electron-donor strength (naphthyl versus 4-methoxynaphthyl) on the photophysical properties. Beside the observation of interesting dual emission properties for these dyes, some showed a pronounced ratiometric fluorescence response on fluoride ion addition.
With the triflates 8-11 at hand, these were transformed into the triaryl systems 12-15 following a similar Pd-catalyzed one-pot borylation-Suzuki coupling strategy as mentioned above, using 1-chloroisoquinoline as the coupling partner (Scheme 3). The desired compounds 12-15 were obtained in 44-70% yield. The 1 H NMR spectra, recorded at 25 °C, showed the coexistence of the syn and anti atropisomers because of the slow rotation around the chiral axis at this temperature. Free rotation around the C-C bond was observed at 80 °C and hence, variable-temperature 1 H NMR studies showed coalescence of the signals to give an average spectrum (see Supporting Information File 1).
The synthesis of the borylated dyes 16-19 was carried out following a methodology that was previously reported by some of us [42] and that is based on the Ir-catalyzed nitrogen-directed ortho-borylation of arylisoquinolines [37,38]. Despite of the presence of many aromatic C-H bonds which could be borylated, the choice of a suitable pyridine-hydrazone ligand [42] allowed to perform the borylation reactions at 55 °C, showing complete regioselectivity in the C-H borylation. This procedure afforded the dyes 16-19 in good to very good yields of 51-83% (Scheme 3). The introduction of the Bpin moiety hinders the free rotation around axis A (Scheme 3) of the compounds 16-19; therefore, complex mixtures of the syn/anti atropoisomers (0.45:0.55; syn:anti) were observed in NMR spectroscopy. To facilitate the C-C bond rotation around axis B (Scheme 3) and simplify the NMR spectra, the measurements were undertaken at 80 °C in C 6 D 6 using a screw-cap NMR tube. Although significant changes were registered, a complete coalescence of the signals was not observed. The chiral HPLC analysis (see HPLC traces in Supporting Information File 1) demonstrated the high purity of compounds 16-19. The sharp peaks and separation times higher than 2 minutes are in accordance with a high rotation barrier. All compounds were identified by their 1 H and 13 C NMR spectra. The sp 2 character of the boron was confirmed by 11 B NMR spectroscopy, revealing a typical resonance signal at 31-32 ppm [43]. Hence, the iso- quinoline nitrogen does not engage in the formation of an intramolecular Lewis pair, akin to related borylated arylisoquinolines [37,38].

UV-vis absorption and fluorescence properties
The absorption and fluorescence properties of the herein investigated dyes 16-19 in air-equilibrated solutions, using three solvents (dichloromethane, acetonitrile, dimethyl sulfoxide), are summarized in Table 1. A first inspection of these data showed that the UV-vis absorption spectra feature the typical bands corresponding to their aromatic moieties (see Figure 2 for the spectra in acetonitrile). For example, for the dyes 18 and 19 π-π* transition bands in the wavelength range of 330-400 nm with characteristic vibronic fine structure were observed. Further, the dyes have a sharp peak at 322 nm that is assigned to the isoquinoline chromophore. The only exception is dye 18 where this peak is hidden under a strong absorption band corresponding to the pyrenyl moiety.
Most interesting are the fluorescence properties of the dyes (see spectra in Figure 2), which revealed a dual emission phenomenon (see ratio I LW /I SW of the intensities I of the long-wavelength (LW) and short-wavelength (SW) emission band; Table 1). The monitoring of the emission corresponding to both bands yields identical excitation spectra which also coincide with the absorption spectra of the dyes. This underpins the authenticity of the emission signals. The appearance of the LW emission for all investigated dyes can be clearly linked to the presence of the boron-containing substituent. This follows from the observation that the corresponding arylisoquinolines without boron substitution feature only one blue-shifted emission band that is very similar to the SW band of the borylated dye, e.g., the non-borylated analogues of the dyes 17, 18, and 19 fea-  ture a single emission band with a maximum at 401, 442, and 420 nm, in acetonitrile, respectively. These are tentatively assigned to π-π* transitions of the variable aryl moiety. Interestingly, in tetrahydrofuran, containing oxygen as donor atom, only the SW emission band is seen, i.e., λ fluo,max = 409 nm (16), 402 nm (17), 426 nm (18), 425 nm (19). This points to the interpretation that the SW emission has its origin in a Lewis adduct between the boron center as acceptor and the solvent as donor. The maxima of the rather broad LW bands of the dyes are observed between 510 and 590 nm in acetonitrile, corresponding to maximal apparent Stokes shifts of ca. 190-270 nm. As demonstrated previously for other borylated arylisoquinoline dyes [37,38], the emission energy of the LW band is tightly linked with the redox potential of the aryl residue. Having in mind that the borylated naphthyl is present in all four dyes it is instructive to compare the oxidation potentials (E ox ) of the additional aryl residues. This leads to the following order: naph- [44]. On the one hand, the dye with the easiest oxidizable aromatic residue (dye 19) has the most red-shifted emission maximum, being at 582 nm in acetonitrile. On the other hand, dye 17 with a naphthyl, that is harder to oxidize, shows the most blue-shifted LW emission (maximum at 514 nm in acetonitrile). The LW emission maxima of other dyes (16 and 18) are situated in between. These trends support that for the herein investigated dyes intramolecular charge-transfer (ICT) phenomena might play a role in the observation of the LW emission features. According to our previous observations the electron-acceptor moiety is likely constituted by the isoquinolinyl moiety [37,38], while the donor is related to the electronically variable aryl residue. Comparing the emission maxima of the dyes in the less polar dichloromethane with those in the highly polar dimethyl sulfoxide, additional trends can be seen.   β-carotene triplet sensitization experiments the signals at 410 nm (dye 18) and 430 nm (dye 19) were assigned to excited triplet states as well. An additional signal at 470 nm for dye 18 is insensitive to oxygen and was tentatively attributed to the formation of a pyrene-based radical cation, resulting from photoionization [46].

Interaction with fluoride anions
The presence of the boronic acid ester moiety does not only contribute to significant changes in the fluorescence properties but constitutes also a potential binding motif for Lewis bases. In this context it is well established that the electron-deficient trivalent boron can bind anions, such as fluoride or cyanide, through interaction with the vacant 2p π orbital [30]. In  19)), which are very comparable to the constants that were obtained for related borylated arylisoquinoline dyes [37].

Conclusion
The family of borylated arylisoquinoline dyes was extended by members that contain additional aryl substituents, leading to compounds with two stereogenic axes. The dyes show pronounced dual emission patterns with long-wavelength maxima close to 600 nm in polar solvents such as acetonitrile or dimethyl sulfoxide. The emission maxima of the long-wavelength band vary systematically with the electron-donor strength of the additional aryl residue (naphthyl, 4-methoxynaphthyl, pyrenyl, anthryl). This provides some hint that intramolecular charge-transfer phenomena are likely involved.
Laser-flash photolysis studies provided insights into the existence of excited triplet states. The addition of fluoride anions led to pronounced fluorescence quenching effects, as the result of the formation of fluoroboronate complexes. In the case of the pyrenyl-and anthryl-substituted dyes a clear ratiometric behavior was noted. No quenching was seen for the addition of cyanide ions or bromide and chloride. This makes the new dyes selective fluorescent receptors for fluoride anions.

Experimental
General methods and materials 1 H NMR spectra were recorded at 400 MHz or 500 MHz and 13 C NMR spectra were recorded at 100 MHz or 125 MHz.
Chloroform-d (CDCl 3 ), acetone-d 6 ((CD 3 ) 2 CO) and benzene-d 6 (C 6 D 6 ) were used as solvents and the solvent peak was employed as reference. 11 B NMR spectra were recorded with complete proton decoupling at 160 MHz, using BF 3 ·Et 2 O (0.00 ppm for 11 B NMR) as standard.
UV-vis absorption and corrected fluorescence spectra were measured with standard equipment (Shimadzu UV-1603 and Varian Cary Eclipse), using quartz cuvettes of 1 cm optical path length. The fluorescence quantum yields were determined with quinine sulfate as standard reference (Φ fluo = 0.55 in 0.05 M H 2 SO 4 ) [50,51]. The lifetimes were measured by time-correlated single-photon counting (Edinburgh instruments FLS 920).
Laser-flash photolysis experiments were performed using a XeCl excimer laser (λ exc = 308 nm; 17 ns fwhm; 20 mJ/pulse). Alternatively, a Q-switched Nd:YAG laser (Quantel Brilliant, 355 nm, 5 ns fwhm, 15 mJ/pulse) was coupled to a mLFP-111 Luzchem miniaturized equipment. The concentration of 16-19 was kept in the range of 20-30 μM in acetonitrile. The solutions were air-equilibrated or bubbled for 30 min with N 2 or O 2 before acquisition. All the experiments were carried out at room temperature.
The detailed procedures for the synthesis of the precursors can be found in Supporting Information File 1. Below the borylation of the precursors 12-15 to yield the dyes 16-19 is described and the NMR characterization data of the dyes are given.
General procedure for the Ir-catalyzed borylation -synthesis of the dyes 16-19 Following the described procedure [42], a dried Schlenk tube was loaded with the substrate (12-15) and B 2 Pin 2 (1 equiv). After three vacuum-argon cycles, 1 mL catalyst stock solution per 0.5 mmol substrate and pinacolborane (HBPin, 5 mol %) was added. The reaction mixture was stirred at 55 °C until quantitative consumption of the starting material. The mixture was cooled to room temperature, concentrated to dryness, and the crude product was purified by column chromatography (n-hexane/EtOAc mixtures).