A Highly Strained All‐BODIPY‐Based Nanohoop

ABSTRACT

Highly strained π‐conjugated nanohoops present significant synthetic challenges but offer interesting platforms for exploring unique physical properties. Here, we report the synthesis of β‐β directly connected strained cyclic boron‐dipyrromethene (BODIPY) tetramer—[4]CBDP, with its structure unambiguously confirmed by single‐crystal X‐ray diffraction. Importantly, the radially conjugated architecture narrows the HOMO‐LUMO gap, yielding panchromatic absorption spanning the visible spectrum with an edge extending into the NIR‐I window, and resulting in a large Stokes shift (77 nm). Computational results indicate that [4]CBDP exhibits a high strain energy of 155 kcal/mol; yet it remains stable under ambient conditions (air/light) in both solution and the solid state.

We report the synthesis of novel [4]cyclo‐BODIPY nanohoop ([4]CBDP), a highly strained cyclic tetramer featuring direct β‐β linkages between BODIPY units. Single‐crystal X‐ray diffraction analysis confirms its radially conjugated architecture. [4]CBDP demonstrates panchromatic visible absorption extending into the NIR‐I window and its application as a heavy‐atom‐free photosensitizer.

Highly strained bent macrocycles with radially continuous π‐conjugation and highly distorted geometries are expected to exhibit physical and chemical properties not possessed by conventional acyclic motifs [1, 2]. Since the successful synthesis of [n]cycloparaphenylenes ([n]CPPs) by Jasti [3], Itami [4], and Yamago [5], et al., the properties of [n]CPPs have attracted significant attention due to their unique structures and properties [6, 7, 8, 9, 10, 11]. Extensive studies reveal that the structural and electronic characteristics of [n]CPPs and related derivatives are highly dependent on a delicate balance between strain and π‐conjugation [12]. Additionally, incorporating various conjugated systems (such as donors, acceptors, heteroaromatic or polycyclic aromatic hydrocarbon units) into the scaffold of [n]CPPs is an effective approach to modify their optoelectronic and structural characteristics [13, 14, 15]. In the literature, many hybrid carbon nanohoops have been reported by embedding functional groups into CPP‐based nanohoops (Figure 1a) [16, 17, 18]. In addition, another type of conjugated nanohoops can be constructed by directly coupling these functional groups to form different bent nanohoops without phenylene units in the ring backbones (Figure 1b) [19, 20, 21, 22, 23]. The systematic variation in the type, size, and spatial arrangement of conjugated systems enables precise tuning of electronic structures and band gaps.

FIGURE 1.

Design strategies for conjugated systems in nanohoops. (a) Embedded and (b) homocoupling types. (c) This work: all‐BODIPY‐based nanohoop.

BODIPY compounds are characterized by high molar absorptivity, rich photophysical properties, and good stability, making them valuable for many applications such as bioimaging and photodynamic therapy [24, 25, 26]. Interestingly, the advent of cycloparaphenylenes can provide a structural platform for confining electron‐deficient BODIPY units within circular geometries featuring quasi‐infinite conjugation [27, 28, 29]. Recent studies have successfully embedded BODIPY units into carbon nanohoops, endowing these systems with distinct size‐dependent photophysical and host‐guest properties not achievable in linear analogues [30, 31, 32, 33, 34]. Compared with conventional BODIPY monomers and BODIPY‐based carbon nanohoops, cyclic all‐BODIPY architectures represent a more challenging synthetic target [35]. The all‐BODIPY‐based nanohoop formed via a homocoupling strategy features a π‐electron network composed entirely of BODIPY units, enabling continuous π‐delocalization spanning the entire macrocycle. Meanwhile, the high molecular symmetry and substantial ring strain of the cyclic backbone further modulate the electron density distribution. This structure‐electronic property synergy may endow the architectures with novel physicochemical characteristics. Therefore, the synthesis of such a structure is highly desirable and of significant interest.

Herein, we present the first synthesis of [4]cyclo‐BODIPY nanohoop ([4]CBDP, Figure 1c) via a platinum‐mediated assembly of phenyl‐substituted BODIPY building blocks, followed by reductive elimination reaction. The radially conjugated architecture of [4]CBDP narrows its HOMO‐LUMO gap, resulting in broad absorption spanning the entire visible spectrum, with an absorption edge extending into the first near‐infrared window (NIR‐I) and demonstrating a substantial Stokes shift. Notably, computational and experimental studies reveal that [4]CBDP maintains exceptional stability despite a considerable strain energy of 155 kcal/mol.

The key steps in the synthesis of [4]CBDP are shown in Figure 2. Using readily available BODIPY 1 as the starting material [36], treatment with arylstannane as a weak nucleophile in the presence of aluminum chloride directly afforded aryl‐boron‐substituted dibromo BODIPY derivative 2 [37]. The Miyaura borylation reaction was then employed to convert 2 into the 4,4‐diaryl‐substituted diborylated BODIPY 3. Macrocyclization was achieved via platinum‐mediated cyclization [5]. Specifically, in the presence of cesium fluoride, the precursor 3 was combined with an equimolar amount of Pt(COD)Cl₂ (COD = 1, 5‐cyclooctadiene) in anhydrous THF under a nitrogen atmosphere. The mixture was stirred at 55°C for 36 h to afford the platinum complex. Without isolating the macrocyclic Pt complex, subsequent reductive elimination was performed with PPh₃. After extensive purification by flash column chromatography, the target compound [4]CBDP was obtained as a dark blue solid in 21% yield over two steps. In addition, mass spectrometry detected compounds with the same molecular mass, potentially suggesting the presence of the isomers of [4]CBDP, but only in trace yield.

FIGURE 2.

Synthesis procedures for [4]CBDP. Reagents and conditions: i) Tributyl(p‐tolyl)stannane, AlCl₃, Toluene, 80°C, 2 h, 78%; ii) (Bpin)₂, Pd₂(dba)₃, XPhos, KOAc, Dioxane, 100°C, 12 h, 85%; iii) Pt(cod)Cl₂, CsF, THF, 55°C, 36 h; iv) PPh₃, Toluene, 110°C, 12 h, 21% over two steps.

The molecular structure of [4]CBDP was comprehensively characterized by mass spectrometry, NMR spectroscopy, and single‐crystal X‐ray diffraction analysis (Figures 3 and S1–S18). MALDI‐TOF mass spectrometry of [4]CBDP revealed a molecular ion peak at m/z 1697.8452 (calculated for C₁₂₀H₁₀₀B₄N₈ [M]⁺: 1697.8477), which matched well with the calculated data (see Figure S15). Needle‐like single crystals suitable for X‐ray crystallography were obtained by slowly diffusing hexane into a chlorobenzene solution, unambiguously confirming the structure of [4]CBDP through single‐crystal X‐ray diffraction analysis (see Figure 3) [38]. In the solid state, [4]CBDP crystallizes in the orthorhombic space group and adopts a structure featuring an elliptical cavity with dimensions of 11.3 Å along the major axis and 9.7 Å along the minor axis. The crystal structure features a distorted tetrahedral configuration for the boron atom, with an average N₁–B–N₂ angle of 101.3°. The bending angle θ _BDP measures the angle between the two five‐membered rings (shown in green fill) in each dipyrromethene unit of [4]CBDP, which is 130.5°. This result indicates that the structure of each dipyrromethene unit in [4]CBDP is noticeably distorted after macrocycle formation.

FIGURE 3.

X‐ray single crystal structure of [4]CBDP. (a and b) ORTEP drawing with 50% thermal probability. Hydrogen atoms and solvent molecules are omitted for clarity. The diameter was measured as the distance between the two midpoints of the C‐C bonds located at the opposite side of the wall. (c) Definition of the bend angle θ _BDP. (d) The packing structure of [4]CBDP. The lattice parameters a, b, and c represent the repeating periods along the a‐axis, b‐axis, and c‐axis, respectively. a = 14.4751(14) Å, b = 33.332(3) Å, c = 48.299(5) Å. (e) Molecular packing of [4]CBDP in the crystalline state.

A systematic crystallographic analysis of [4]CBDP was performed to understand the molecular interactions and arrangement in the single crystal state. Figures S17a–c illustrate the top view of a single‐layer arrangement, the top view of a multilayer arrangement, and the side view of a two‐layer arrangement, respectively. In the single crystal state, three different types of dimer interactions can be observed: A‐A and A‐B interactions in the monolayer arrangement, and A‐C interactions in the bilayer arrangement. To further investigate the interactions between dimers with different arrangements, we conducted noncovalent interaction (NCI) gradient isosurfaces and reduced density gradient (RDG) analyses [39, 40]. Figure S18 demonstrates the weak interactions within dimers of varying arrangements in the [4]CBDP single crystal state. These results indicate that A‐A arranged dimers have stronger interactions compared to A‐B and A‐C arrangements, mainly due to interactions between C‐C atoms and π‐π between the planes of the phenyl ring substituents. Figures S17d–f illustrate various intramolecular interactions in the three dimer arrangements, including C‐C, C‐H, C‐H‐C, and C‐H‐H‐C interactions. The Hirshfeld surface analysis on the [4]CBDP crystal (Figure S17i) showed that for a single [4]CBDP molecule, it is primarily connected to the surrounding [4]CBDP molecules through 73.7% H‐H, 23.8% C‐H, and 2.6% C‐C interatomic interactions, forming a three‐dimensional skeleton.

To further investigate the relationship between structures, electronic structures, and optoelectronic properties of [4]CBDP, density functional theory calculations were performed with the theoretical level of RB3LYP‐D3BJ/6‐31G(d,p) using Gaussian 09 software (Figures S19–S22)[41]. The calculations of the frontier molecular orbitals (MOs) indicate that the highest occupied molecular orbitals (HOMOs) and the lowest unoccupied molecular orbitals (LUMOs) of [4]CBDP are focused on π‐type MOs, corresponding to the significant electronic transitions of π → π* (Figure 4a). For the BODIPY‐embedded carbon nanohoops ([n]CPP‐BODIPY), their HOMO and LUMO are mainly localized on the oligo‐p‐phenylene units and BODIPY moieties, respectively, resulting in low π‐delocalization efficiency across the entire π‐system. In contrast, the HOMO and LUMO of [4]CBDP are uniformly distributed over the entire π‐conjugated skeleton. The effective π‐conjugation of its macrocyclic framework endows [4]CBDP with a higher HOMO energy level than that of [n]CPP‐BODIPY. Calculations reveal that the HOMO‐LUMO energy gap of [4]CBDP is 2.23 eV, whereas the HOMO‐LUMO energy gap of the BODIPY derivative monomer 5 is 3.10 eV (see Table S2). These results can be attributed to the larger π‐conjugated system within the cyclic structure, reducing the HOMO‐LUMO energy gap. Electrostatic potential (ESP) analysis (Figure S23) reveals that the negative ESP value at approximately ‐25 kcal/mol of [4]CBDP is primarily located in the macrocyclic carbon skeleton. In contrast, the positive ESP value is mainly found near the protons, at about 20 kcal/mol. This indicates the presence of highly polarized C‐H bonds in the [4]CBDP nanohoop.

FIGURE 4.

(a) TDDFT‐calculated molecular orbitals and energy diagrams of [4]CBDP. The f value represents the oscillator strength. (b) UV‐vis absorption (dashed line) and fluorescence (solid line) spectra of monomer 5 (red) and [4]CBDP (blue) in CH₂Cl₂ solutions (1.0 × 10⁻⁶ M) at room temperature. Inset: photographs of the color of monomer 5 (I) and [4]CBDP (II) in CH₂Cl₂ solutions under ambient light.

The photophysical properties of [4]CBDP were studied by UV‐vis absorption spectroscopy, steady‐state fluorescence spectroscopy, and theoretical studies (Figures 4b and S24‐S30). In the UV‐vis absorption spectra, a strong influence of cyclic conjugation and strain is observed in [4]CBDP compared to the unstrained reference monomer 5. At room temperature, the UV‐vis absorption spectrum of [4]CBDP in dichloromethane solution shows broad absorption covering the entire visible light region from 300 nm to 900 nm (Figure 4b), with the absorption edge extending into the first near‐infrared window. Additionally, the maximum absorption peak occurs at 660 nm with a molar extinction coefficient of approximately 2.4 × 10⁵ M⁻¹cm⁻¹, resulting in a deep blue solution. In contrast, monomer 5 exhibits a typical small‐molecule absorption spectrum, featuring narrow and sharp absorption bands. The spectrum is characterized by a maximum absorption peak at 498 nm (≈ 5.1 × 10⁴ M⁻¹cm⁻¹). To better understand the absorption spectra, we conducted time‐dependent density functional theory (TD‐DFT) calculations for [4]CBDP (Tables S3–S8). Due to the molecular asymmetry, the maximum absorption wavelengths of [n]CPP‐BODIPY are primarily governed by the allowed HOMO → LUMO transition, with a molar extinction coefficient of approximately 10⁴ M⁻¹cm⁻¹. In comparison, for the highly molecular symmetric [4]CBDP, DFT calculations reveal that the absorption band at ∼730 nm is significantly suppressed, corresponding to the HOMO → LUMO transition with a low oscillator strength (f = 0.0009). The absorption at 660 nm arises from a combination of HOMO → LUMO+1 and HOMO → LUMO+2 transitions. These transitions possess orthogonal transition dipole moments, which explains the relatively high extinction coefficient observed for [4]CBDP. Notably, the absorption feature of [4]CBDP showed a significant redshift (>160 nm) compared to monomer 5, which matched well with their HOMO‐LUMO gaps based on theoretical calculations.

Upon excitation at this wavelength, the compound exhibits photoluminescence (PL) with a peak maximum at 737 nm, corresponding to a Stokes shift of 77 nm. The significant structural non‐planarity of [4]CBDP facilitates pronounced geometric relaxation in the excited state, shifting the emission bathochromically and resulting in an enlarged Stokes shift. The photoluminescence quantum yield (PLQY) in dichloromethane, measured using the integrating sphere absolute method, was determined to be quite low at <0.01, indicating dominant non‐radiative decay pathways. Compared to monomer 5, the spectrum of [4]CBDP is significantly red‐shifted. The absolute PLQY of monomer 5 was determined to be 0.01 in dichloromethane. In contrast, the extended and distorted π‐conjugated skeleton of [4]CBDP may introduce more non‐radiative decay pathways. Meanwhile, the forbidden character of the unique HOMO‐LUMO transition in the cyclic structure, together with the narrowed electronic energy gap, promotes the dissipation of excited‐state energy through non‐radiative decay and intersystem crossing (ISC), thus leading to the lower fluorescence quantum yield [42].

Using the methodology reported by Itami (see Figure S31 and Table S9) [4, 43], the strain energy of [4]CBDP was estimated to be 155 kcal/mol. Importantly, the high ring strain causes the twist angle to decrease in order to counteract the increase in strain energy. Minimization of the twist angle enhances π‐overlap and effectively strengthens the conjugation between BODIPY units. When compared on a per‐heavy‐atom (C, N, B) basis, its strain energy (∼3.2 kcal/mol per heavy atom) is slightly lower than that of [5]CPP (∼4.0 kcal/mol per heavy atom) [44, 45]. It is noteworthy that high ring strain typically compromises structural stability. Indeed, [5]CPP decomposes into an insoluble bright‐yellow material within approximately 24 h unless stored under an inert atmosphere. To evaluate the stability of [4]CBDP, photostability experiments were conducted in a dichloromethane solution (see Figure S27b). Surprisingly, results indicated that [4]CBDP can remain stable both as a solid and in solution under air and ambient light for at least few weeks. StrainViz analysis (see Figure S32) reveals that the maximum strain in [4]CBDP is concentrated at the C(sp ²)–C(sp ²) single bonds connecting the individual BODIPY chromophores, with a maximum local strain energy of 2.99 kcal/mol. In contrast, the exocyclic aromatic substituents and the BODIPY core moieties exhibit significantly lower strain energies, owing to their greater structural flexibility.

Since the excellent photochemical properties and stability of [4]CBDP, it could be used as a good photosensitizer (PS) for photodynamic therapy (PDT). PDT typically involves irradiating a PS with light of a specific wavelength in the presence of molecular oxygen to generate reactive oxygen species (ROS), which induce the destruction of tumor cells [46, 47]. Upon irradiation, the PS is excited to its singlet state (¹PS*), undergoes ISC to the triplet state (³PS*), and subsequently engages in intermolecular electron transfer (Type I) and/or energy transfer (Type II) with adjacent substrates (Figure 5a) [48]. Recently, Ke group [32] reported that the rigid backbone of [7]CPP‐BODIPY restricts structural relaxation, favoring slow transitions and the formation of the triplet state. Notably, due to the larger steric hindrance, smaller cavity size, and higher ring strain of [4]CBDP, it possesses an even more rigid framework. Simultaneously, the extremely weak fluorescence (Φ _F < 0.01) implies the existence of an efficient non‐radiative decay pathway from the singlet state (S₁). Based on this observation, we hypothesized that [4]CBDP may undergo an efficient ISC process from S₁ to the triplet state (T₁). To verify this, we characterized the triplet excited‐state properties of [4]CBDP using nanosecond transient absorption (ns‐TA) spectroscopy (see Figure 5b). Upon pulsed laser excitation at 400 nm, a distinct negative peak was observed at ca. 660 nm, which matches the steady‐state absorption spectrum, confirming that it corresponds to the ground‐state bleach (GSB) band. Two broad excited‐state absorption (ESA) bands were detected at 500–580 nm and 700–800 nm, typical characteristics of BODIPY triplet states [49]. Single‐exponential decay fitting of the ns‐TA kinetic trace at 725 nm yielded a triplet lifetime of 1.3 µs.

FIGURE 5.

(a) Schematic diagram of the mechanism for reactive oxygen species generation. (b) Nanosecond transient absorption spectra of [4]CBDP in deaerated CHCl₃ after pulsed laser excitation (λ_ex = 400 nm). Inset: decay trace of [4]CBDP at 725 nm. Fluorescence spectra of (c) DCFH and (d) DHR 123 at different time points in the presence of 10 µM [4]CBDP after irradiation by white LED light source (400‐800 nm, 20 mW/cm²).

Based on these triplet‐state properties, we further systematically investigated the ROS generation capability of [4]CBDP. The generation of ROS was assessed using 2′,7′‐dichlorodihydrofluorescein (DCFH) as a fluorescent probe, by monitoring the increase in fluorescence intensity at 522 nm upon irradiation. As shown in Figures 5c and S33, the solution of DCFH in the presence of [4]CBDP exhibited fluorescence enhancement at 522 nm following 6‐min white light irradiation (400‐800 nm white LED light, 20 mW/cm²), confirming efficient ROS production. Dihydrorhodamine 123 (DHR 123) assays further confirmed ROS generation. In the presence of [4]CBDP, significant fluorescence enhancement of DHR 123 was observed under light irradiation, reflecting rapid ROS generation efficiency (see Figures 5d and S34). These findings demonstrate that [4]CBDP can rapidly generate ROS upon light irradiation, making it a promising heavy‐atom‐free PS with potential applications in PDT in the future [50, 51].

Conclusion

In summary, we present the synthesis of highly strained [4]CBDP (a novel β‐β directly connected cyclic BODIPY tetramer), with its structure confirmed by X‐ray crystallography. Its radially conjugated architecture narrows the HOMO‐LUMO gap, yielding panchromatic visible to NIR‐I absorption and a 77 nm Stokes shift. Remarkably, [4]CBDP exhibits exceptional stability despite a high strain of 155 kcal/mol, challenging the established notion that high strain energy is associated with structural instability. This concurrent high strain and stability in [4]CBDP make it a promising platform for exploring the relationship between strain and optoelectronics in π‐systems. ROS generation analysis confirms [4]CBDP as a heavy‐atom‐free PS, while its distinctive photophysical properties and long triplet lifetime position it as highly promising for significant promise in PDT applications.

Author Contributions

Bing Yuan: methodology, writing – original draft, writing – review and editing, investigation, data curation, formal analysis. Fangming Zhao: methodology, data curation, investigation, formal analysis. Jinyi Wang: software, data curation, investigation, validation. Nan Yin: investigation, methodology. Wen Zhang: investigation, methodology. Meng Zhou: investigation, methodology. Xinyu Zhang: investigation, methodology, supervision, data curation, writing – review and editing, funding acquisition, formal analysis. Zheng Zhou: methodology, investigation, funding acquisition, supervision, validation. Pingwu Du: conceptualization, investigation, supervision, project administration, writing – original draft, writing – review and editing, funding acquisition.

Conflicts of Interest

The authors declare no conflicts of interest.

Supporting information

Supporting File 1: anie72838‐sup‐0001‐SuppMat.docx.

Supporting File 2: anie72838‐sup‐0002‐cif.zip.

Data Availability Statement

The data that supports the findings of this study are available in the supplementary material of this article.