An efficient method for the synthesis of π-expanded phosphonium salts

Abstract

A new straightforward methodology for the synthesis of phosphonium salts integrated with a π-conjugated scaffold has been developed using phosphine oxides. It is now possible to obtain cyclic phosphonium salts possessing up to eight conjugated rings and bearing e.g. pyrrole, thiophene, indole or benzofuran scaffolds from abundant and commercially available materials in high yields. An enticing feature of this general strategy is that this one-step procedure typically does not require chromatographic purification. Still greater synthetic possibilities are related to the fact that even demanding scaffolds such as azulene, pyrene or fluorene can be bridged with the phospholium subunit. Starting from 1,4-dihydropyrrolo[3,2-b]pyrrole, heretofore rarely observed ladder-type bis-phosphonium salts were effectively prepared. This strategy was also extended into the preparation of cyclic arsonium salt. The ability to form phosphonium salts possessing such manifold scaffolds translated into diverse photophysical properties ranging from non-fluorescent dyes to thiophene-derivatives emitting quantitatively in the blue region. Geometry change induced by light absorption has a predominant influence on the fate of the molecules’ excited state. It was shown, in analogy to previous results, that cyclic tetraarylphosphonium salts migrate through the membrane of living cells to localize in the mitochondria similarly to the well-known triarylphosphonium salts.

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Introduction

Heterocyclic analogs of polycyclic aromatic hydrocarbons possessing phosphorus atom(s) have received considerably less systematic attention than architectures possessing oxygen, nitrogen and sulfur.^1,2 Extensive efforts have been devoted to advancing such classes as phosphines,^3,4 phosphine oxides,^5,6 phosholes^7–12 and phosphonium salts.^13–35 In the most recent years, new possibilities were discovered also for phosphorines,^36–38 azaphospholes^39,40 and phosphaquinolin-2-ones.^41,42 As far as electronegativity, valence and coordination number are concerned, phosphorus is quite specific compared to other heteroatoms. For these reasons, studies of the impact of its insertion on the optical/redox properties of PAHs are intense and have led to the discovery of materials with promising optoelectronic properties.³ Among various architectures, phosphonium salts possessing one or two σ⁴,λ⁴-P⁺ are relatively less explored.^13–34 Most employed routes towards phosphonium salts is S_N2 quaternization of σ³,λ³-P cyclic chromophores. This, however, requires pre-synthesized cyclic phosphines.^{17–19,21,23,28,30–34} Several annulation methods of ortho-alkynyl arylphosphines have directly led to the formation of benzo[b]phospholium salts, in gold⁴³ or acid-catalyzed processes²⁵ (Scheme 1A). π-Expanded phosphonium salts have also been prepared through Cu-catalyzed C–H functionalization^13,24 or electrolysis⁴⁴ of appropriately substituted arylphosphines (Scheme 1B). In 2010 Manabe and Ishikawa described the cyclization of [1,1′-biphenyl]-2-yldicyclohexylphosphane in the presence of Tf₂O (Scheme 1C).⁴⁵ Later on, Miura et al. reported that diarylphosphine oxides undergo Tf₂O-catalyzed cyclization to form phosphine oxides (Scheme 1D).⁴⁶ An analogous idea has also been reported for reaction with alkynes.^47,48 Inspired by these reports, we decided to develop a straightforward synthetic protocol for the conversion of triarylphosphine oxides into cyclic phosphonium salts, which would be one of the most concise routes toward these valuable compounds (Scheme 1E).

Scheme 1 Selected synthetic methods for cyclic diarylphosphonium salts.

Results and discussion

Synthesis

To our delight, the reaction of phosphine oxide 1a with trifluoromethanesulfonic anhydride in the presence of diisopropylethylamine (DIPEA) yielded the formation of phospholium salt 2a in a quantitative yield after just 1 hour (Scheme 2). A quick evaluation revealed that a similar result is observed when the reaction is conducted without the addition of a base. Furthermore, under these conditions, the purification of the products was greatly simplified. We thus synthesized a series of phosphine oxides (1b–x), to evaluate the method's scope and limitations and subsequently subjected these compounds to the optimized reaction conditions (Scheme 2). Intramolecular electrophilic attack on 5-membered heteroaromatic rings of thiophene, benzothiophene, benzofuran and indoles resulted in the formation of new five-membered phospholium rings in good yields and without the need for chromatographic purification of the products 2a–f,h–i,p,t–v,x and 4a–b. Most salts can be easily isolated from the reaction mixture by suspending them in 10% methanol or isopropanol in diethyl ether, followed by filtration.

Scheme 2 Scope and limitations of the transformation of phosphine oxides into phosphonium salts. Ar = 4-nBu-C₆H₄- isolated yields, conditions: ^a DCM, rt, ^b toluene 90 °C, ^c reaction was conducted in the presence of 1.5 equiv. of DIPEA.

Based on earlier precedence and especially on Miura's papers,^46–48 a plausible reaction mechanism was proposed (Scheme S1†). Initially, after the attack of triflic anhydride on phosphorus atom, the intermediate phosphonium salt forms. Subsequently the attack of this salt as an electrophile on aromatic ring leads to the formation of P–C bond and formation of five-membered ring (phosphacyclic intermediate). Finally, an elimination of triflic acid affords the final product.

Surprisingly, furan derivative 1c required an alternative set of conditions, which included employing toluene as the solvent and increasing the temperature to achieve a full conversion of the substrate and yield 68% of dye 2c. For phosphine oxide 1f, containing an indolic N–H bond, only C3 substitution product 2f was observed. Moreover, for indole derivatives 2h and 2i successful formation of corresponding 6- and 7-membered rings was observed, showcasing the broad versatility of the method. The latter product's structure was confirmed with the aid of X-ray crystallography (CCDC 2405937, Fig. S251†). The positive outcome of the transformation observed on electron-rich aromatic rings encouraged us to try the method for π-expansion of more sophisticated systems – namely 1,4-dihydropyrrolo[3,2-b]pyrroles (DHPP).^49,50 Specially designed substrates 1j–n were synthesized and subjected to the optimized reaction conditions. DHPPs are known to be unstable under acidic conditions.^49,50 In order to prevent acid-induced decomposition of both products and substrates, the transformation was conducted in the presence of DIPEA. The same base was used for other substrates possessing very electron-rich scaffolds which are prone to acid-induced decomposition i.e. 2h and 2q. Centrosymmetric dyes 2j–l bearing a DHPP scaffold were formed in good yields, despite lowered nucleophilicity of the aromatic system after the first electrophilic attack (Scheme 2).

Unsymmetrical derivative 2m was formed in a slightly diminished yield and a similar outcome was observed for the consecutive formation of two 6-membered rings in compound 2n. Moreover, the C–P bond formation at the benzene ring decorated with electron-donating substituents was tested. Despite bearing only one electron-donating group, 5-oxatruxene derivative 2o was formed under the milder set of conditions, however, in diminished yields (Scheme 2).

Though efficient transformation of other monosubstituted phosphine oxides 1r,s required more vigorous conditions, corresponding products were formed in very good yields. On the other hand, 1,3-dimethoxydibenzo[b,d]phospholium 2t was efficiently formed at room temperature. The discovered methodology's usefulness toward the modification of electron-rich systems prompted us to test it for the synthesis of PAHs-derived phosphonium salts. Guaiazulene derivative 2u was obtained under the milder set of conditions in a decent yield. On the other hand, phosphonium indeno[2,1-a]pyrene, dibenzo[f,ij]tetraphene and benzo[a]aceanthrylene analogues 2v–x were efficiently formed upon treating phosphine oxides 1v–x with Tf₂O in toluene at 90 °C (Scheme 2).

Intrigued by the broad scope of the developed strategy, we inspected whether the described reaction could also be utilized in an intermolecular process. Subjecting electron-rich arene to the phosphine oxide resulted in the formation of tetraarylphosphonium salt in good yields (with 46% for 4a, Scheme 3A). Encouraged by this result, we attempted to widen the scope to include arsenic derivatives (as it is an element from the same periodic table row). Experiments revealed that arsine oxides also undergo this reaction, leading to, among others, the corresponding tetraarylarsonium derivative 4b (58%). The results prompted us to examine an intramolecular variant of arsine oxide cyclization. We thus discovered that the presence of an indole subunit increases the instability of the obtained arsine, however, fast workup enables its isolation. Further oxidation furnishes arsine oxide, which turned out to be unstable and decomposed to a yellow substance. Hence, alternative conditions were developed allowing one-step oxidation and cyclization. Utilization of di-t-butylperoxide, which is commonly used as a radical initiator,⁵¹ in the presence of Tf₂O, turned out to be an inert oxygen source, allowing arsolium ring incorporation with a 58% reaction yield for 6 (Scheme 3B).

Scheme 3 A – Intermolecular variant of the transformation, B – one-pot synthesis of arsolium salt.

Electrochemistry

The electrochemical properties of the synthesized compounds were studied using cyclic voltammetry. For most of them, irreversible reduction events were detected, with the onset potential values ranging between −1.40 V (vs. Fc/Fc⁺ couple) for guaiazulene derivative 2u and −2.32 V for acyclic salt 4a. Replacing MeCN with DMF and 1,2-dichloroethane has not altered the irreversibility of reduction (Fig. S226 and S227†). However, for PAH analogues 2v and 2w, a reversible reduction process could be observed (Table S1, Fig. S219–S243†). Despite being cationic, the products could also be electrochemically oxidized, as observed on the cyclic voltammograms in the form of irreversible events at onset potentials ranging from 0.95 V (vs. Fc/Fc⁺ couple) for 2u to 1.61 V for dimethoxybenzene derived product 2t. An even lower-lying reversible oxidation event was observed at E^ox_1/2 = 0.33 V vs. Fc/Fc⁺ for the unsymmetrical DHPP derivative 2m. Measured onset oxidation and reduction potentials were utilized to evaluate the HOMO and LUMO energies of the phosphonium salts (vide infra).

Experimental and computational analysis of photophysical properties

Photophysical properties of phosphonium salts were measured in dichloromethane, tetrahydrofuran, acetonitrile and solid state (Table 1, Table S1, Fig. S162–S210†). Similarly to other organic dyes, the optical properties can be modulated by π-electron system expansion,⁵² heteroatom exchange⁵³ or introduction of electron-donating or electron-withdrawing substituents.^54,55 Thus, absorption spectra cover a wide range of the UV-Vis spectrum, starting from λ_abs = 288 nm for 4a up to 602 nm for 2x and are affected by solvent polarity, changing molar extinction coefficient (ε), shape and absorption maxima (λ_abs) for most studied dyes.⁵⁶ According to Table 1, most salts containing 5-membered phospholium subunit (2a–e,g,o,s), possess ε ≤ 5000 M⁻¹ cm⁻¹ for the most red-shifted bands, which stand in line with rather low oscillator strengths (Tables S3, S5, S7, S9, S11 and S15†) for the S₀ → S₁ electron transitions (f = 0.1–0.2). The S₀ → S₁ transition for the simple phospholium salts is described by the HOMO–LUMO configuration. As presented in e.g. Table S3,† the Highest Occupied Molecular Orbital (HOMO) electron density is located at molecule's periphery, while Lowest Molecular Unoccupied Orbital (LUMO) it is mostly concentrated within the distinctly acceptor phosphacycle. Therefore, photon absorption initiates an electron density shift from the molecule's periphery toward the P⁺ center. On the other hand, ring expansion to a 6-membered phosphorinium doesn't change the first excitation orbital configuration. However, electron density distribution over LUMO becomes less affected by the P⁺ center, while at HOMO it is mostly maintained, which results in rising oscillator strength, f = 0.313 (Tables S16 and S17†), and ε up to 11 000 M⁻¹ cm⁻¹ for 2h (Table 1).

Table 1 Spectroscopic data in dichloromethane (red), tetrahydrofuran (orange), and acetonitrile (blue) for phosphonium salts

λ_abs/λ_em – absorption/emission wavelength, ε – molar absorption coefficient, Δν – Stokes shift, Φ_FL – fluorescence quantum yield, # – determined for transition between S₀ and S₁ states, * – determined for two emission bands, ^a – measured after addition of 100 μl of DBU.

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Positively charged phosphacycles share another feature, namely, large Stokes shifts (Δν), starting from ≈2000 cm⁻¹ for 2q,r up to 10 000 cm⁻¹ for 2i,s (Table 1). Moreover, comparing emission spectra vs. solvent polarity reveals a solvatofluorochromic response, which becomes more pronounced as the π-electron system expands, like for 2m (Fig. 1). Nevertheless, a lack of strict correlation with solvent polarity (Table S2, Fig. S209 and S210†) suggests that the solvatochromic response must be related to complex solvation processes.

Fig. 1 Absorption (solid) and emission (dot) spectra of 2m in toluene (black), dichloromethane (red), tetrahydrofuran (orange) and acetonitrile (blue).

In typical donor–acceptor compounds, an immense Δν and solvatofluorochromism are related to excitation-driven changes in electric dipole moment,^57,58 which is not the case in the discussed charged phosphacycles. More in-depth analysis performed on model systems 2b, 2g, 2k and 2m in a broader range of solvents and utilizing E_T (30) parameter,⁵⁹ as well as a more detailed solvation model⁶⁰ didn't provide an appropriate correlation (Table S2, Fig. S209–S218†). However indicates that the solvatofluorochromism primarily depends on two solvent parameters: basicity and dipolarity. Thus, the origin of the observed phenomena must be related to differences in cation solvation in both the ground (¹GS) and excited states (¹LE), as well as the geometrical changes arising upon excitation (Fig. 2).

Fig. 2 Angles and bond lengths for 2f in ground state (¹GS), local excited state (¹LE) and so-called charge transfer state (¹CT), visualizing the excitation-driven geometrical changes within the phospholium subunit.

Photon absorption-driven changes in molecular geometry also significantly impact the fate of the molecule in the excited state. A computational study of a few selected molecules (see ESI†) reveals that, disregarding the triplet states population, the photophysics of cations is primarily a competition between the local excited state (¹LE) and the so-called charge transfer state (¹CT). The electron density at ¹CT indicates that electron transfer occurs from the π-system to the P⁺ or As⁺ centres, leading to distinct geometrical changes. The consequence of formal charge separation is vanishingly small oscillator strength for the ¹CT → ¹GS electronic transition, which, combined with a remarkable decrease in the ¹CT state energy, makes the deactivation of the excited state through ¹CT the main nonradiative channel.

Influence of heteroatoms and geometry

The significant number of phosphonium salts synthesized possessing various five-membered heterocyclic rings provides the material for investigating the influence of heteroatoms on their photophysical properties. In-depth analysis however reveals that there is no clear correlation especially as far as fluorescence quantum yield is concerned. The comparison of salts 2d, 2e and 2f based on benzothiophene, benzofuran and indole reveals almost no differences in emission intensity and only moderate bathochromic shift of emission for indole-based dye 2f. Typically oxygen-to-sulfur swap leads to small HOMO destabilization.⁶¹ However, in the case of 2d,e the impact of the sulfur atom is barely distinguishable (Fig. 3, Table 1, Fig. S167 and S169†), suggesting that the PPh₂⁺ moiety⁶² strongly affects the electronic structure than the O to S displacement. There is however significant impact of geometry within for example phosphonium salts bearing indole scaffold (Table 1). Depending on the linkage position between indole moiety and quaternary phosphonium salt, the fluorescence quantum yield varies from almost quantitative to 2%. Interestingly the influence of heteroatom is visible for DHPPs 2j–2n. Fluorescence quantum yield of benzothiophene-based dye 2j is more than 20 times higher than for benzofuran-based 2k, whereas the strongest fluorescence is in the case of salt 2l possessing benzenes as flanking units. Again the change of geometry so that P-atom bridges positions 3 and 6 of DHPP core with N-phenyl (rather than C-phenyl) substituent causes large changes in photophysics including e.g. ≈60 nm hypsochromic shift of emission. The largest change however is caused by replacing quadrupolar centrosymmetric dyes 2j, 2k, 2l with non-symmetrical salt 2m. The latter one has weak but strongly bathochromically shifted emission (Table 1). On the other hand, replacing P with As leads to a distinct stabilization of LUMO, indicating a stronger acceptor character of the arsolium compared to the phospholium subunit. Moreover, a heavier pnictogen atom distinctly affects fluorescence, making 6 a non-emissive salt. According to calculations, 6 after excitation to the ¹LE, which proves to be unstable, immediately rearranges to the ¹CT, located at the As⁺ center (Fig. S242 and S245†). Then the intersection between ¹CT and ¹GS leads to intense internal conversion being responsible for the nonradiative deactivation of the excited state.

Fig. 3 Energy diagram representing changes in energy of frontier orbitals vs. the change of heteroatom. HOMO and LUMO levels are determined via cyclic voltammetry.

Impact of phosphacycle ring size

To investigate the influence of phosphacycle size on photophysics, salts 2g,h,i were chosen due to their highest structural similarity. It has to be pointed out that the differences in substitution pattern (2-phenyl (2g) substitution vs. 4-phenyl substitution (2h)) slightly affect the electron density distribution within HOMO and its energy. Thus, observed changes can be correlated to phosphacycle size. Absorption spectra comparison indicates that the ring expansion, leads to a hypsochromic shift accompanied by the appearance of a distinct vibronic progression as well as a gradual rise of ε (Table 1, Fig. S174, S176 and S178†), from 371 nm (ε = 3800 M⁻¹ cm⁻¹) for 2g to 300 nm (ε = 15 800 M⁻¹ cm⁻¹) for 2i in dichloromethane.

These trends imply that upon phosphacycle expansion, distinct changes in electronic structure take place. While the energy of HOMO remains virtually unaffected, with the electron density distribution confined within the indole part (Tables S15, S16 and S18), the LUMO energy significantly rises passing from a five- to a seven-membered ring (Fig. 4) and causing blue-shift of the absorption spectrum. This results from a weaker impact of the P⁺ center on orbital stabilization, due to a reduction of π*–σ* coupling contributions to LUMO (Tables S15, S16 and S18†). Moreover, ring expansion entails a significant drop in fluorescence quantum yield from ≈100% for 2g to 2% for 2i, as a result of intense deactivation of the excited state through the ¹CT nonradiative channel.

Fig. 4 Energy diagram representing changes in energy of frontier orbitals vs. ring size. HOMO and LUMO levels are determined via cyclic voltammetry.

Photophysics of zwitterions

Among synthesized compounds, 2f and 2x possess an acidic hydrogen atom. Thus, in the presence of a base like 1,8-diazabicyclo(5.4.0)undec-7-ene (DBU), 2f,x can be transformed into zwitterions. This process is notably reversible, meaning that upon TfOH addition, the uncharged species reverts to their cationic form. Interestingly, 2x undergoes deprotonation even in the absence of a base, enabling estimation of its acidic dissociation constant (pK_a) in dichloromethane to be around 7.05 (eqn (S1)†). More than 10 orders of magnitude increase of the pK_a, compared to 9-phenylfluorene in dimethylsulfoxide (pK_a = 17.9),⁶³ reveals a strong influence of PPh₂⁺ moiety on acidic properties enhancement. Moreover, the absorption spectra (Fig. S204†) of 2x indicate a significant equilibrium shift (Scheme 4) to the right with increasing solvent polarity. As a result of the presence of two forms in the solution, double fluorescence can be observed in acetonitrile, with λ_em = 355 nm and 652 nm. Spectroscopic changes arising upon deprotonation are nicely illustrated in the case of 2f, where a distinct absorption band at ≈355 nm (ε = 4500 M⁻¹ cm⁻¹) becomes flattened (ε < 2500 M⁻¹ cm⁻¹) after proton abstraction, thus determining λ_abs becomes challenging for 2f′ (Fig. S191†). The decrease of the molar extinction coefficient stands in line with the calculated oscillator strengths for the S₀ → S₁ transition (for 2f: f = 0.133 and 2f′: f = 0.025). Passing from 2f to the 2f′ also noticeably impacts the emissive properties, causing a bathochromic shift of the fluorescence spectrum of about 3000 cm⁻¹ (Table 1, Fig. S171 and S173†), accompanied by a 26-times drop of Φ_FL. The ADC(2) method calculations performed for 2f and 2f′ give deeper insight into the excited molecule deactivation process. According to the energy diagram (Fig. 5), deprotonation of 2f significantly lowers the energy, not only of ¹LE, but also of the ¹CT state in 2f′. Moreover, excited molecule relaxation causes the inversion of both the ¹LE and ¹CT states, leading to an intersection between ¹CT and ¹GS. Making ¹CT an intense nonradiative deactivation channel, resulting in residual fluorescence with Φ_FL ≈ 2% for 2f′.

Scheme 4 Deprotonation of 2f (a) and 2x (b).

Fig. 5 A qualitative scheme of the excitation energies and radiative transitions of 2f (left) and 2f* (right) was obtained with the ADC(2) method. Solid lines denote the energies of the lowest excited singlet states (¹LE – blue and ¹CT – red) computed at their optimized equilibrium geometries. Dashed lines denote the respective state's energy calculated at the complementary state's equilibrium geometry. Vertical arrows represent fluorescence from the respective excited singlet state, with the energy of the vertical transition and the oscillator strength indicated. Molecular orbitals singly occupied in the relevant electronic state, LE-blue, and CT-red, are shown.

Fluorescence imaging

It is well-known that triarylphosphonium salts are anchors enabling the selective localization of fluorophores in mitochondria.^64–68 In 2019, the groups of Koshevoy, Romero-Nieto and Chou reported that a cyclic tetraarylphosphonium salt possessing an anthracene core also localizes in mitochondria.²⁴ Inspired by these observations,²⁸ we became curious whether our new cyclic tetraarylphosphonium salts could display analogous behavior. Salt 2g was selected as a model system due to its strong green fluorescence (Table 1). We performed studies of the localization of dye 2g in the U-87 cell line. The conducted fluorescence confocal microscopy experiments revealed that the subcellular distribution of salt 2g produces a staining pattern consistent with selective mitochondrial localization after only a short incubation period (15–30 min) (Fig. 6A, Fig. S248–S250†). The selective intracellular localization of dye 2g in U-87 cells was confirmed by co-localization with MitoTracker Red, a mitochondria-selective fluorescent label commonly used in confocal microscopy (Fig. 6B). The co-localization of salt 2g with MitoTracker Red was confirmed by Fluorescence Resonance Energy Transfer (FRET) microscopy between the two compounds. Irradiation at 405 nm, the wavelength appropriate for salt 2g, also excites the MitoTracker Red (Fig. 6A–C). The Pearson's coefficient (r = 0.676 ± 0.017) and Manders’ coefficients (M1 = 0.894 ± 0.054 and M2 = 0.738 ± 0.091) of colocalization of salt 2g and MitoTracker Red were calculated.

Fig. 6 Intracellular localization of 2g compound and MitoTracker Red as detected using confocal fluorescence microscopy. (A) fluorescence of 2g compound, excitation wavelength 405 nm, emission wavelength 500 ± 50 nm, (B) fluorescence of Mito Red compound, excitation wavelength 405 nm, emission wavelength 594 ± 50 nm. (C) overlay picture recorded sequentially as at (A) and (B) parameters for two fluorophores in living cells U-87. Scale bar 20 μm.

Conclusions

Phosphine oxides derived from heterocycles and polycyclic aromatic hydrocarbons can be activated with Tf₂O to form cyclic phosphonium salts integrated with the π-conjugated scaffold. Our strategy exhibits versatility concerning substrate scope, as both electron-rich and electron-neutral aromatics are compatible with this reaction. A broad range of π-conjugated phosphonium salts based on diverse aromatic scaffolds can be synthesized easily, in good yield, and without chromatographic purification. The method's versatility has been showcased by incorporating such demanding moieties as azulene, 1,4-dihydropyrrolo[3,2-b]pyrrole and 5-oxatruxene. Importantly, arsonium salts could also be assessed, suggesting that this route could be easily adapted for the preparation of further derivatives. Critically, the photophysical properties of quaternary salts are affected by the type of fused heterocycle, the size of the phosphacycle, and π-expansion. Our strategy allowed rapid access to new cationic dyes, which often possessed both strong fluorescence as well as an emission wavelength strongly dependent on the phosphacycle size. Ab initio calculations revealed that competition between ¹LE and ¹CT is the key factor influencing the photophysical characteristics and determines the fate of the molecule's excited state. This discovery will provide the impetus for future explorations that use cyclic tetraarylphosphonium salts.

Author contributions

K.G. conceived the idea. K.G. and Ł.W.C. performed all synthetic experiments. A.W. performed imaging studies and A.S. supervised them. A.L.S. performed computational studies, analyzed data, wrote and reviewed the manuscript. D.T.G. supervised the project, performed formal analysis, and wrote and reviewed the manuscript. All the authors discussed the results and commented on the manuscript. All authors have approved the final version of the manuscript.

Data availability

The data supporting the article has been included as part of the ESI.†

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

This project has received funding from the European Union's Horizon 2020 Research and Innovation Program under the Marie Skłodowska-Curie grant agreement no. 101007804 and from European Research Council (ARCHIMEDES, 101097337). Views and opinions expressed are, however, those of the authors only and do not necessarily reflect those of the European Union or the European Research Council Executive Agency. Neither the European Union nor the granting authority can be held responsible for them. The work was also financially supported by the Polish National Science Centre, Poland (OPUS 2020/37/B/ST4/00017). We thank Joseph Milton and Natalia D. Gryko for English proofreading.

References

1. A. Borissov, Y. K. Maurya, L. Moshniaha, W.-S. Wong, M. Żyła-Karwowska and M. Stępień, Recent Advances in Heterocyclic Nanographenes and Other Polycyclic Heteroaromatic Compounds, Chem. Rev., 2022, 122, 565–788.
2. M. Stępień, E. Gońka, M. Żyła and N. Sprutta, Heterocyclic Nanographenes and Other Polycyclic Heteroaromatic Compounds: Synthetic Routes, Properties, and Applications, Chem. Rev., 2017, 117, 3479–3716.
3. T. Baumgartner, Insights on the Design and Electron-Acceptor Properties of Conjugated Organophosphorus Materials, Acc. Chem. Res., 2014, 47, 1613–1622.
4. M. Stolar and T. Baumgartner, Phosphorus–Containing Materials for Organic Electronics, Chem. – Asian J., 2014, 9, 1212–1225.
5. E. Regulska, P. Hindenberg, A. Espineira-Gutierrez and C. Romero-Nieto, Synthesis, Post–Functionalization and Properties of Diphosphapentaarenes, Chem. – Eur. J., 2023, 29, e202202769.
6. N. König, Y. Godínez-Loyola, H. Weiske, S. Naumov, P. Lönnecke, R. Tonner-Zech, C. A. Strassert and E. Hey-Hawkins, Access to Strong Thieno[3,2-b]phosphole-Based Solid-State Emitters via Manganese(III)-Mediated Oxidative Annulation, Chem. Mater., 2023, 35, 8218–8228.
7. J. Fidelius, K. Schwedtmann, S. Schellhammer, J. Haberstroh, S. Schulz, R. Huang, M. C. Klotzsche, A. Bauzá, A. Frontera, S. Reineke and J. J. Weigand, Convenient access to π-conjugated 1,3-azaphospholes from alkynes via [3 + 2]-cycloaddition and reductive aromatization, Chem, 2024, 10, 644–659.
8. K. Nishimura, K. Hirano and M. Miura, Direct Synthesis of Dibenzophospholes from Biaryls by Double C–P Bond Formation via Phosphenium Dication Equivalents, Org. Lett., 2020, 22, 3185–3189.
9. P. Hibner-Kulicka, J. A. Joule, J. Skalik and P. Bałczewski, Recent studies of the synthesis, functionalization, optoelectronic properties and applications of dibenzophospholes, RSC Adv., 2017, 7, 9194–9236.
10. H. Hattori, K. Ishida and N. Sakai, Synthetic Strategies for Accessing Dibenzophosphole Scaffolds, Synthesis, 2024, 193–219.
11. M. P. Duffy, W. Delaunay, P.-A. Bouit and M. Hissler, π-Conjugated phospholes and their incorporation into devices: components with a great deal of potential, Chem. Soc. Rev., 2016, 45, 5296–5310.
12. Z. Wang, B. S. Gelfand and T. Baumgartner, Dithienophosphole–Based Phosphinamides with Intriguing Self–Assembly Behavior, Angew. Chem., Int. Ed., 2016, 55, 3481–3485.
13. S. Nieto, P. Metola, V. M. Lynch and E. V. Anslyn, Synthesis of a Novel Bisphosphonium Salt Based on 2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl (Binap), Organometallics, 2008, 27, 3608–3610.
14. A. Fukazawa, E. Yamaguchi, E. Ito, H. Yamada, J. Wang, S. Irle and S. Yamaguchi, Zwitterionic Ladder Stilbenes with Phosphonium and Borate Bridges: Intramolecular Cascade Cyclization and Structure–Photophysical Properties Relationship, Organometallics, 2011, 30, 3870–3879.
15. L. Qiu, W. Hu, D. Wu, Z. Duan and F. Mathey, Regioselective Synthesis of 2- or 2,7-Functionalized Pyrenes via Migration, Org. Lett., 2018, 20, 7821–7824.
16. X. Zhao, Z. Gan, C. Hu, Z. Duan and F. Mathey, Planar Polycyclic Oxaphosphoranes Incorporating a Benzophosphole Unit, Org. Lett., 2017, 19, 5814–5817.
17. P.-A. Bouit, A. Escande, R. Szűcs, D. Szieberth, C. Lescop, L. Nyulászi, M. Hissler and R. Réau, Dibenzophosphapentaphenes: Exploiting P Chemistry for Gap Fine-Tuning and Coordination-Driven Assembly of Planar Polycyclic Aromatic Hydrocarbons, J. Am. Chem. Soc., 2012, 134, 6524–6527.
18. Y. Ren, W. H. Kan, M. A. Henderson, P. G. Bomben, C. P. Berlinguette, V. Thangadurai and T. Baumgartner, External-Stimuli Responsive Photophysics and Liquid Crystal Properties of Self-Assembled “Phosphole-Lipids”, J. Am. Chem. Soc., 2011, 133, 17014–17026.
19. Y. Koyanagi, S. Kawaguchi, K. Fujii, Y. Kimura, T. Sasamori, N. Tokitoh and Y. Matano, Effects of counter anions, P-substituents, and solvents on optical and photophysical properties of 2-phenylbenzo[b]phospholium salts, Dalton Trans., 2017, 46, 9517–9527.
20. T. Delouche, A. Vacher, E. Caytan, T. Roisnel, B. Le Guennic, D. Jacquemin, M. Hissler and P. Bouit, Multi–Stage Redox Systems Based on Dicationic P–Containing Polycyclic Aromatic Hydrocarbons, Chem. – Eur. J., 2020, 26, 8226–8229.
21. P. Hindenberg, F. Rominger and C. Romero-Nieto, Phosphorus Post–Functionalization of Diphosphahexaarenes, Chem. – Eur. J., 2019, 25, 13146–13151.
22. P. Hindenberg, A. López-Andarias, F. Rominger, A. de Cózar and C. Romero-Nieto, A Guide for the Design of Functional Polyaromatic Organophosphorus Materials, Chem. – Eur. J., 2017, 23, 13919–13928.
23. T. A. Schaub, S. M. Brülls, P. O. Dral, F. Hampel, H. Maid and M. Kivala, Organic Electron Acceptors Comprising a Dicyanomethylene–Bridged Acridophosphine Scaffold: The Impact of the Heteroatom, Chem. – Eur. J., 2017, 23, 6988–6992.
24. A. Belyaev, Y. Chen, Z. Liu, P. Hindenberg, C. Wu, P. Chou, C. Romero-Nieto and I. O. Koshevoy, Intramolecular Phosphacyclization: Polyaromatic Phosphonium P–Heterocycles with Wide–Tuning Optical Properties, Chem. – Eur. J., 2019, 25, 6332–6341.
25. S. Arndt, M. M. Hansmann, F. Rominger, M. Rudolph and A. S. K. Hashmi, Direct Access to π–Extended Phosphindolium Salts by Simple Proton–Induced Cyclization of (o –Alkynylphenyl)phosphanes, Chem. – Eur. J., 2017, 23, 5429–5433.
26. B. Yang, S. Yan, C. Li, H. Ma, F. Feng, Y. Zhang and W. Huang, Mn(iii)-mediated C–P bond activation of diphosphines: toward a highly emissive phosphahelicene cation scaffold and modulated circularly polarized luminescence, Chem. Sci., 2023, 14, 10446–10457.
27. A. Belyaev, Y.-T. Chen, S.-H. Su, Y.-J. Tseng, A. J. Karttunen, S. P. Tunik, P.-T. Chou and I. O. Koshevoy, Copper-mediated phospha-annulation to attain water-soluble polycyclic luminophores, Chem. Commun., 2017, 53, 10954–10957.
28. K. Andoh, M. Murai, P. Bouit, M. Hissler and S. Yamaguchi, Dithieno[3,2– b; 2′,3′– f ]phosphepinium–Based Near–Infrared Fluorophores: p x –π* Conjugation Inherent to Seven–Membered Phosphacycles, Angew. Chem., Int. Ed., 2024, 63, e202410204.
29. A. Fukazawa, H. Yamada and S. Yamaguchi, Phosphonium– and Borate–Bridged Zwitterionic Ladder Stilbene and Its Extended Analogues, Angew. Chem., Int. Ed., 2008, 47, 5582–5585.
30. X. He, J. Lin, W. H. Kan and T. Baumgartner, Phosphinine Lipids: A Successful Marriage between Electron–Acceptor and Self–Assembly Features, Angew. Chem., Int. Ed., 2013, 52, 8990–8994.
31. J. C. Chan, W. H. Lam, H. Wong, W. Wong and V. W. Yam, Tunable Photochromism in Air–Stable, Robust Dithienylethene–Containing Phospholes through Modifications at the Phosphorus Center, Angew. Chem., Int. Ed., 2013, 52, 11504–11508.
32. E. Yamaguchi, C. Wang, A. Fukazawa, M. Taki, Y. Sato, T. Sasaki, M. Ueda, N. Sasaki, T. Higashiyama and S. Yamaguchi, Environment–Sensitive Fluorescent Probe: A Benzophosphole Oxide with an Electron–Donating Substituent, Angew. Chem., Int. Ed., 2015, 54, 4539–4543.
33. Y. Ren, W. H. Kan, V. Thangadurai and T. Baumgartner, Bio–Inspired Phosphole–Lipids: From Highly Fluorescent Organogels to Mechanically Responsive FRET, Angew. Chem., Int. Ed., 2012, 51, 3964–3968.
34. (a) Y. Matano, A. Saito, T. Fukushima, Y. Tokudome, F. Suzuki, D. Sakamaki, H. Kaji, A. Ito, K. Tanaka and H. Imahori, Fusion of Phosphole and 1,1′–Biacenaphthene: Phosphorus(V)–Containing Extended π–Systems with High Electron Affinity and Electron Mobility, Angew. Chem., 2011, 123, 8166–8170; (b) P. Federmann, H. K. Wagner, P. W. Antoni, J.-M. Mörsdorf, J. L. Pérez Lustres, H. Wadepohl, M. Motzkus and J. Ballmann, A 2,2′-diphosphinotolane as a versatile precursor for the synthesis of P-ylidic mesoionic carbenes via reversible C–P bond formation, Org. Lett., 2019, 21, 2033–2038.
35. Y. Wang, G. Su, M. Li, L. Yao, W. A. Chalifoux and W. Yang, Synthesis of P-Containing Polycyclic Aromatic Hydrocarbons from Alkynyl-phosphonium Salts, Org. Lett., 2024, 26, 5280–5284.
36. K. Yasuda and S. Ito, A π–Extension Process from 9–Phosphaanthracene Leading to Phosphatetraphenes and Phosphatetracenes, ChemPlusChem, 2023, 88, e202300277.
37. P. de Koe and F. Bickelhaupt, 10–Phenyldibenzo[b,e]phosphorin, Angew. Chem., Int. Ed. Engl., 1968, 7, 889–890.
38. T. Baumgartner and R. Réau, Organophosphorus π-Conjugated Materials (Chem. Rev. 2006, 106, 4681–4727. Published on the Web November 8, 2006.), Chem. Rev., 2007, 107, 303–303.
39. J. W. Heinicke, Electron–Rich Aromatic 1,3–Heterophospholes – Recent Syntheses and Impact of High Electron Density at σ 2 P on the Reactivity, Eur. J. Inorg. Chem., 2016, 2016, 575–594.
40. S. Wu, A. L. Rheingold, J. A. Golen, A. B. Grimm and J. D. Protasiewicz, Synthesis of a Luminescent Azaphosphole, Eur. J. Inorg. Chem., 2016, 2016, 768–773.
41. J. P. Bard, S. G. Bolton, H. J. Howard, J. N. McNeill, T. P. de Faria, L. N. Zakharov, D. W. Johnson, M. D. Pluth and M. M. Haley, 2-λ 5 -Phosphaquinolin-2-ones as Non-cytotoxic, Targetable, and pH-Stable Fluorophores, J. Org. Chem., 2023, 88, 15516–15522.
42. J. P. Bard, H. J. Bates, C.-L. Deng, L. N. Zakharov, D. W. Johnson and M. M. Haley, Amplification of the Quantum Yields of 2-λ 5 -Phosphaquinolin-2-ones through Phosphorus Center Modification, J. Org. Chem., 2020, 85, 85–91.
43. S. Arndt, M. M. Hansmann, P. Motloch, M. Rudolph, F. Rominger and A. S. K. Hashmi, Intramolecular anti –Phosphinoauration of Alkynes: An FLP–Motivated Approach to Stable Aurated Phosphindolium Complexes, Chem. – Eur. J., 2017, 23, 2542–2547.
44. T. Zhang, M. Cai, W. Zhao, M. Liu, N. Jiang, Q. Ge and H. Cong, Electrochemical oxidative intramolecular annulation of aryl phosphine compounds: an efficient approach for synthesizing π-conjugated phosphonium salts, Green Chem., 2023, 25, 1351–1355.
45. S. Ishikawa and K. Manabe, Synthesis of hydroxylated oligoarene-type phosphines by a repetitive two-step method, Tetrahedron, 2010, 66, 297–303.
46. K. Nishimura, K. Hirano and M. Miura, Synthesis of Dibenzophospholes by Tf 2 O-Mediated Intramolecular Phospha-Friedel–Crafts-Type Reaction, Org. Lett., 2019, 21, 1467–1470.
47. Y. Unoh, K. Hirano and M. Miura, Metal-Free Electrophilic Phosphination/Cyclization of Alkynes, J. Am. Chem. Soc., 2017, 139, 6106–6109.
48. K. Nishimura, Y. Unoh, K. Hirano and M. Miura, Phosphenium–Cation–Mediated Formal Cycloaddition Approach to Benzophospholes, Chem. – Eur. J., 2018, 24, 13089–13092.
49. A. Janiga, E. Glodkowska-Mrowka, T. Stoklosa and D. T. Gryko, Synthesis and Optical Properties of Tetraaryl–1,4–dihydropyrrolo[3,2–b]pyrroles, Asian J. Org. Chem., 2013, 2, 411–415.
50. M. Krzeszewski, Ł. Dobrzycki, A. L. Sobolewski, M. K. Cyrański and D. T. Gryko, Saddle-shaped aza-nanographene with multiple odd-membered rings, Chem. Sci., 2023, 14, 2353–2360.
51. T. V. RajanBabu, N. S. Simpkins and T. V. RajanBabu, in Encyclopedia of Reagents for Organic Synthesis, John Wiley & Sons, Ltd, Chichester, UK, 2005.
52. V. Brega, S. N. Kanari, C. T. Doherty, D. Che, S. A. Sharber and S. W. Thomas, Spectroscopy and Reactivity of Dialkoxy Acenes, Chem. – Eur. J., 2019, 25, 10400–10407.
53. K. Górski, J. Mech-Piskorz and M. Pietraszkiewicz, From truxenes to heterotruxenes: playing with heteroatoms and the symmetry of molecules, New J. Chem., 2022, 46, 8939–8966.
54. K. Górski, D. Kusy, S. Ozaki, M. Banasiewicz, R. Valiev, S. R. Sahoo, K. Kamada, G. Baryshnikov and D. T. Gryko, The interplay of intersystem crossing and internal conversion in quadrupolar tetraarylpyrrolo[3,2-b]pyrroles, J. Mater. Chem. C, 2024, 12, 1980–1987.
55. T. Ma, J. Dong and D.-T. Yang, Heteroatom-boron-heteroatom-doped π-conjugated systems: structures, synthesis and photofunctional properties, Chem. Commun., 2023, 59, 13679–13689.
56. H. A. Frank, J. A. Bautista, J. Josue, Z. Pendon, R. G. Hiller, F. P. Sharples, D. Gosztola and M. R. Wasielewski, Effect of the Solvent Environment on the Spectroscopic Properties and Dynamics of the Lowest Excited States of Carotenoids, J. Phys. Chem. B, 2000, 104, 4569–4577.
57. A. Marini, A. Muñoz-Losa, A. Biancardi and B. Mennucci, What is Solvatochromism?, J. Phys. Chem. B, 2010, 114, 17128–17135.
58. K. Górski, I. Deperasińska, G. V. Baryshnikov, S. Ozaki, K. Kamada, H. Ågren and D. T. Gryko, Quadrupolar Dyes Based on Highly Polarized Coumarins, Org. Lett., 2021, 23, 6770–6774.
59. J. P. Cerón-Carrasco, D. Jacquemin, C. Laurence, A. Planchat, C. Reichardt and K. Sraïdi, Solvent polarity scales: determination of new E T (30) values for 84 organic solvents, J. Phys. Org. Chem., 2014, 27, 512–518.
60. J. Catalán, Toward a Generalized Treatment of the Solvent Effect Based on Four Empirical Scales: Dipolarity (SdP, a New Scale), Polarizability (SP), Acidity (SA), and Basicity (SB) of the Medium, J. Phys. Chem. B, 2009, 113, 5951–5960.
61. K. Górski, K. Noworyta and J. Mech-Piskorz, Influence of the heteroatom introduction on the physicochemical properties of 5-heterotruxenes containing nitrogen, oxygen and sulfur atom, RSC Adv., 2020, 10, 42363–42377.
62. C. Fave, M. Hissler, T. Kárpáti, J. Rault-Berthelot, V. Deborde, L. Toupet, L. Nyulászi and R. Réau, Connecting π-Chromophores by σ-P–P Bonds: New Type of Assemblies Exhibiting σ–π-Conjugation, J. Am. Chem. Soc., 2004, 126, 6058–6063.
63. W. S. Matthews, J. E. Bares, J. E. Bartmess, F. G. Bordwell, F. J. Cornforth, G. E. Drucker, Z. Margolin, R. J. McCallum, G. J. McCollum and N. R. Vanier, Equilibrium acidities of carbon acids. VI. Establishment of an absolute scale of acidities in dimethyl sulfoxide solution, J. Am. Chem. Soc., 1975, 97, 7006–7014.
64. Q. Hu, M. Gao, G. Feng and B. Liu, Mitochondria–Targeted Cancer Therapy Using a Light–Up Probe with Aggregation–Induced–Emission Characteristics, Angew. Chem., Int. Ed., 2014, 53, 14225–14229.
65. C. W. T. Leung, Y. Hong, S. Chen, E. Zhao, J. W. Y. Lam and B. Z. Tang, A Photostable AIE Luminogen for Specific Mitochondrial Imaging and Tracking, J. Am. Chem. Soc., 2013, 135, 62–65.
66. R. Roopa, N. Kumar, V. Bhalla and M. Kumar, Development and sensing applications of fluorescent motifs within the mitochondrial environment, Chem. Commun., 2015, 51, 15614–15628.
67. H. Ogasawara, Y. Tanaka, M. Taki and S. Yamaguchi, Late-stage functionalisation of alkyne-modified phospha-xanthene dyes: lysosomal imaging using an off–on–off type of pH probe, Chem. Sci., 2021, 12, 7902–7907.
68. G. D. Kumar, M. Banasiewicz, A. Wrzosek, R. P. Kampa, M. H. E. Bousquet, D. Kusy, D. Jacquemin, A. Szewczyk and D. T. Gryko, Probing the flux of mitochondrial potassium using an azacrown-diketopyrrolopyrrole based highly sensitive probe, Chem. Commun., 2022, 58, 4500–4503.

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Footnote

† Electronic supplementary information (ESI) available: Synthetic procedures, NMR spectra, UV-Vis spectra, cyclic voltammograms, and characteristics, computational details, Cartesian coordinates of ground and excited states, and X-ray structure details. CCDC 2405937 (2i). For ESI and crystallographic data in CIF or other electronic format see DOI: https://doi.org/10.1039/d5qo00708a

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