[2.2]Paracyclophane (PCP) is a typical cyclophane that was first synthesized and isolated in 1949 as a pyrolysis product of para-xylene [1]. PCP includes two strongly interacting benzene unit “decks” with a distance of ~3.09 Å, which are connected by two ethylene “bridges” (~2.78 Å) (Figure 1) [2]. The two benzene rings stacked at such close proximity can lead to transannular π–π strain in the aromatic rings and cause deviation from the normal molecular structure. The strain, distorted structure and transannular effects alter the photophysical and optoelectronic properties of PCP scaffolds. Therefore, due to the intriguing structure and the unusual photophysical [3] and optoelectronic properties [4] of PCP scaffolds, they have been successfully used as privileged scaffolds in asymmetric synthesis [5], π-stacked polymers [6], energy materials [7], and organic fluorescent dyes [8] and have aroused wide interest in biological and materials science fields [9].

Conventional organic fluorescent dyes include cyanines [10], BODIPYs (4,4-difluoro-4-bora-3a,4a-diazas-indacene) [11], rhodamine analogues [12], squaraines [13], and porphyrins [14]. BODIPY dyes have a large π-conjugated skeleton and exhibit excellent photophysical properties in dilute solution. However, when in high concentration in solution or a state of aggregation, BODIPY dyes tend to adopt a face-to-face stacking mode (H-aggregation) and usually display an aggregation-caused emission quenching (ACQ) effect, which limits their application. Fortunately, the ACQ effect can be effectively overcome using an aggregation-induced emission (AIE) strategy, which was introduced by Tang et al. and has since been widely used [15]. Many AIE skeletons, such as 1,1,2,3,4,5-hexaphenylsilone and tetraphenylethylene, have been developed and applied in organic fluorescent dyes. These skeletons have twisted structures and can effectively inhibit the intermolecular π–π interactions occurring in the aggregation state. Taking advantage of PCP scaffolds, the introduction of a PCP group to BODIPY or BODIPY analogues can also result in elimination of the strong π–π interactions between the intermolecular indacene planes and achieve an AIE effect. Therefore, the introduction of the PCP skeleton to organic fluorescent dyes improves the photophysical properties of fluorescent dyes and has received increasing attention in recent decades.

Circularly polarized luminescence (CPL) has many potential applications in chirality sensing [16], optical displays ^[17][18][19][17,18,19], and chiroptical materials ^[20][21][20,21]. The two key factors to satisfy the requirements of the above applications during the development of CPL materials are high fluorescence quantum yield (Φ_f) and high luminescent dissymmetry factors (|g_lum|) [22]. In recent years, CPL-active small organic molecules (CPL-SOMs) have received wide attention due to their easy derivatization, excellent processability, tunable wavelengths, high fluorescence quantum yields, and low toxicity ^{[23][24][25][26][27]}[23,24,25,26,27]. However, many CPL-SOMs suffer from the disadvantages of small |g_lum| values and aggregation-caused quenching (ACQ). An AIE strategy is also effective for achieving higher Φ_f and larger |g_lum| values, and has been applied to overcome ACQ in CPL-SOMs [28]. It is well known that AIE-active SOMs display no or weak fluorescence in dilute solution but become highly emissive as aggregates or in a solid state, which may increase Φ_f and amplify the |g_lum| values.

2. Application of PCP Skeleton in Modifying Dyes

It is well known that many reported organic fluorescent dyes suffer from small Stokes shifts, which affects their fluorescence emission efficiency. Therefore, it is necessary to develop a fluorescent dye with large Stokes shifts, superior optical properties, and good stability ^[29][31]. Due to the special electronic structure, [2.2]paracyclophanyl fluorescent dyes exhibit intrinsic fluorescence and can be applied to access new fluorescent dyes ^[30][32]. In 2019, Delcourt’s group reported a series of [2.2]paracyclophane-fused coumarin systems (Scheme 1) ^[31][33], which are compact heteroaromatic PCP dyes with unique three-dimensional (3D) structures. The introduction of the PCP skeleton allows the synthesis of 3D coumarin systems and improvement of the photophysical properties through large Stokes shifts and red-shifted absorption and emission bands. Furthermore, when planar chiral 4-formyl [2.2]paracyclophane was introduced to these [2.2]paracyclophane-fused coumarins, the resulting product exhibited promising chiroptical properties with |g_lum| up to 5 × 10⁻³. In order to investigate the influence of the PCP motif and its “phane” interaction on the spectroscopic properties of fluorophores 1−5, the authors compared the different photophysical properties of these emitters (Table 1). Compared with [2.2]paracyclophane (Table 1, entry 1), the 3D coumarins (Table 1, entries 2−6) exhibited red-shifted absorption and emission bands. Moreover, when compared with the absorption and emission maxima of 4-amino [2.2]paracyclophane (Table 1, entry 7) and paracyclophane-deprived model compound 5a (Table 1, entry 9), the 3D coumarins also showed red-shifted absorption and emission bands. These results indicate that larger π-conjugation systems form between the PCP skeleton and the coumarin skeleton. Importantly, compared with commercially available coumarin 4, the wavelength absorption in the UV−vis spectra of fluorophores 1−3 was lower, and a remarkably large Stokes shift (230 nm) was obtained for coumarin 2d. In addition, in comparison with the behaviors of their unsubstituted analogues (±)-1b and (±)-1d, the 3D coumarins (±)-2a and (±)-2b with bromine atoms showed observed hypsochromic shifts of the emission bands, which indicated that the through-space interactions in the PCP skeleton could influence the photophysical properties of these 3D coumarins. Therefore, these results demonstrate that PCP can be introduced into coumarin fluorophores as a stable electron donor group and regulate the photophysical properties of these dyes. BODIPY dyes tend to assemble into H-aggregates because of the large π-conjugated frameworks, and most BODIPY dyes usually show ACQ in the aggregation state. In order to solve this problem, BODIPY dyes can be employed as J-aggregation scaffolds. However, finding suitable building blocks for BODIPY J-aggregates remains a great challenge. In 2009, Meállet-Renault et al. ^[32][34] reported on a new type of hindered BODIPY dye prepared by modification of its pyrrole substituents. They introduced a PCP skeleton into the core of BODIPY to increase steric hindrance and prevent π–π stacking, which improved the photophysical properties of the BODIPY; these PCP-BODIPY dyes 6a−d showed red-shifted absorption and emission bands compared with Ph-BODIPY dye 7 (Table 1, entries 10,11, Scheme 2). Accordingly, the Stokes shifts of these PCP-BODIPY dyes 6a−d ranged between 881 and 1290 cm⁻¹, which were higher values than for the Ph-BODIPY dye 7. These results may be due to the electron-donating nature and the steric hindrance of PCP, which enhance the conjugation effect and limit the possibilities for reorientation of the PCP group in the excited state. In particular, when their films were prepared by drop-casting, their emission bands were narrower than those in solution, and their fluorescence quantum yields increased dramatically and solid-state fluorescence were obtained, which may be attributed to the J-like aggregates in the film. In 2021, Liu and co-workers reported a new PCP-BODIPY dye 8 (Scheme 2) ^[33][35] as an example of a BODIPY dye with J-aggregation, which can induce second near-infrared fluorescence. First, the authors revealed that when the meso-position of BODIPY was changed from phenyl to [2.2]paracyclophane, compound PCP-BODIPY dye 8 showed red-shifted absorption and emission bands centered at 722 and 795 nm in comparison with its analog compound Ph-BODIPY 9 (λ_abs = 700 nm and λ_em = 750 nm) (Table 1, entries 12,13). This phenomenon can be attributed to the stronger electron-conjugation effect of the PCP group. In addition, they explored the J-aggregation behavior of PCP-BODIPY dye 8 by investigating the emission changes in tetrahydrofuran (THF)–water binary solvents with variations in water volumetric fraction. The results indicated that PCP-BODIPY dye 8 can exhibit J-aggregation and showed a weak NIR-II emission band around 1000 nm when the water volumetric fractions reached 80% and 90%. Moreover, the authors found that the photophysical properties of Ph-BODIPY 9 indicated H-aggregation-induced emission quenching in the aggregation state, which demonstrated that the introduction of the PCP group played a key role in the J-aggregation behavior of PCP-BODIPY dye 8. Because of the NIR-II emission capability of PCP-BODIPY dye 8 in both THF–water and solid state, the authors also investigated the stability of the NIR-II emissive J-aggregates in NPs (Figure 2). The results indicated that the NIR-II emissive J-aggregates could be efficiently stabilized in a pluronic F-127 matrix. To verify the biological imaging capability of PCP-BODIPY 8, these authors prepared the PCP-BODIPY NPs by encapsulating the PCP- PCP-BODIPY 8 aggregates into a pluronic F-127 matrix and performed both in vitro and in vivo NIR-II imaging. The results of in vitro imaging revealed that the PCP-BODIPY 8 NPs had good NIR-II imaging penetration depth up to 8 mm, which was higher than the 6 mm of the clinically approved NIR-I dye indocyanine green (ICG). Moreover, the results of the in vivo imaging experiment showed that the brightness and clarity of PCP-BODIPY 8 NPs were higher than that of ICG under the same imaging conditions. Accordingly, the fluorescence of PCP-BODIPY 8 NPs decreased gradually with increase in time from 5 min to 24 h, in contrast to the undetectable fluorescence of ICG when the time was increased to 8 h. These results demonstrate that the PCP-BODIPY 8 NPs have higher resolution and longer-term NIR-II imaging ability than ICG. Furthermore, the potential application of PCP-BODIPY 8 NPs in mapping lymph nodes and image-guided cancer surgery was also investigated in nude mice. All the above results indicate that the steric and conjugation effect of the PCP skeleton plays a key role in manipulating the photophysical properties of BODIPY dyes and promoting their application in biological sensing and imaging.