Low-Entropy-Penalty Synthesis of Giant Macrocycles for Good Self-Assembly and Emission Enhancement

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However, traditionally prevalent macrocyclic compounds exhibit specific cavities with diameters usually less than 1 nm, limiting their range of applications in supramolecular chemistry. The efficient synthesis of giant macrocycles remains a significant challenge because an increase in the monomer number results in cyclization-entropy loss. In this study, we developed a low-entropy-penalty synthesis strategy for producing giant macrocycles in high yields. In this process, long and rigid monomers possessing two reaction modules were condensed with paraformaldehyde via Friedel–Crafts reaction. A series of giant macrocycles with cavities of sizes ranging from 2.0 nm to 4.7 nm were successfully synthesized with cyclization yields of up to 72%. Experimental results and theoretical calculations revealed that extending the monomer length rather than increasing the monomer numbers could notably reduce the cyclization-entropy penalty and avoid configuration twists, thereby favoring the formation of giant macrocycles with large cavities. Significantly, the excellent self-assembly capacity of these giant macrocycles promoted their assembly into organogels in various solvents. The obtained xerogels exhibited enhanced photoluminescence quantum efficiencies of up to 83.1%. Mechanism investigation revealed that the excellent assembly capacity originated from the abundant π–π interactions sites of the giant macrocycles. The outstanding emission enhancement resulted from the restricted nonradiative decay processes of rotation/vibration and improved radiative decay process of fluorescence. This study provides an effective and general method for achieving giant macrocycles, thereby expanding the supramolecular toolbox for host–guest chemistry and assembly applications. Moreover, the intriguingly assembly and photophysical properties demonstrate the feasibility of developing novel and unique properties by expanding the macrocycle size. Physical sciences/Chemistry/Organic chemistry Physical sciences/Chemistry/Supramolecular chemistry giant macrocycles entropy penalty photoluminescence self-assembly supramolecular chemistry Figures Figure 1 Figure 2 Figure 3 Introduction Macrocyclic compounds are key tools for theoretical and practical investigations in supramolecular chemistry. 1–9 Considerable effort has been made in designing and synthesizing macrocycles 10–17 , studying their recognition 3,4,6,11,17,18 and self-assembly properties, 19–23 and exploring their applications in various fields such as biomedicine, 24–26 optoelectronics, 27–30 sensing, 31–34 and adsorption and separation 35–37 . The cavities of traditional macrocycles such as cyclodextrins, calix[ n ]arenes, cucurbit[ n ]urils, and pillar[ n ]arenes, are usually less than 1 nm in diameter, which severely limits their scope of application. Efficient synthesis of macrocycles with large cavities is a formidable challenge. The conventional approach to enlarge the cavity size involves increasing the number of monomer units; however, this method usually does not yield giant macrocycles. First, increasing the monomer numbers usually results in a twisted configuration with small cavities owing to the directivity of covalent bonds. For example, ε-/ι-cyclodextrins, 38 calix[ 8 , 10 ]arenes, 39–41 cucurbit[ 13 – 15 ]urils, 42,43 and pillar[ 8 – 10 ]arenes 44 possess twisted small cavities rather than the expected single large cavity. Moreover, the sizes of these macrocyclic cavities are even smaller than those of their homologues with less monomer numbers (Figure S1 ). Second, cyclization itself leads to a loss of conformational freedom, and an increase in the number of monomer units results in a larger entropy penalty and a sharp decrease in cyclization yields (Figure S1 ). Calix[ 6 , 8 ]arenes exhibit cyclization yields of 64% and 74%, while that of calix[ 10 ]arene is only 3% 45,46 . The cyclization yields of cucurbit[ 13 – 15 ]urils are only 0.2–3% 42,43,47 and pillar[ 8 – 10 ]arenes are only 1–2% 44,48 (Figure S1 ). Although there are a few pioneering studies that have proposed excellent methods for constructing giant macrocycles, the approaches are limited by tedious synthesis and low yields. 49–52 In this study, we report a low-entropy-penalty synthesis of giant covalent organic macrocycles, p -oligophen[ n ]arenes, by the condensation of long and rigid monomer possessing two reaction modules with paraformaldehyde via Friedel–Crafts reaction. The reversibility of the Friedel–Crafts reaction facilitates macrocyclization with a self-correcting ability and results in a thermodynamically stable product in high yield. The inertness of methylene after removal of the catalysts ensured the high stability of the macrocycles. More importantly, extending the monomer length rather than increasing the monomer numbers could significantly reduce the cyclization-entropy loss, avoid configuration twists, and facilitate the formation of giant macrocycles with large cavities, excellent self-assembly capacities, and outstanding luminescence performances. Results and Discussion We first calculated the entropy penalty (-ΔS) 53 resulting from extending the monomer length of p -oligophen[ n ]arenes (our strategy), and compared it to that of increasing monomer numbers of pillar[ n ]arenes and calix[ n ]arenes (conventional strategy) (Figs. 1 and S2). From pillar[ 5 ]arene to pillar[ 10 ]arene, the number of phenyl units in macrocycle increased from 5 to 10, the -ΔS increased 7.9-fold, and the cyclization yields reduced from 71–2% (Fig. 1 a). 44,48 Conversely, from terphen[ 3 ]arene to octaphen[ 3 ]arene, the number of phenyl units in macrocycle increased from 9 to 24, and the -ΔS only increased 0.9-fold, indicating the great advantages of the proposed strategy (Fig. 1 b). We then verify the effectiveness of our strategy experimentally. By coupling 4,4''-dibromoterphenyl with two 2,4-dimethoxyphenylboronic acid reaction modules, a rigid quinquephenyl monomer ( M1 ) was synthesized in 81% yield (Scheme S2, and Figures S3 -5). Monomer M1 was further condensed with paraformaldehyde ((CH 2 O) n ) using a Lewis acid catalyst to form cyclic products quinquephen[ 3 – 6 ]arenes ( QP [ 3 – 6 ]). This cyclization reaction can be performed in various solvents, such as 1,2-dichloroethane (DCE), tetrachloroethane (TCE), dichloromethane (DCM), and CHCl 3 , and catalysts, such as BF 3 ·Et 2 O, FeCl 3 , AlCl 3 , and trifluoromethanesulfonic acid (TfOH)) (Table S1 ). Under optimized conditions of using DCE as the solvent and BF 3 ·Et 2 O as the catalyst (8%), and at 25 °C for 2 h, QP [ 3 – 6 ] can be obtained with an overall yield of 72% (44% for QP [ 3 ], 23% for QP [ 4 ], 5% for QP [ 5 ], and trace amounts for QP [ 6 ]) (Schemes 1a , S1, S3, and Figures S6 –15). This relatively high cyclization yield indicates that our strategy is significant in producing giant macrocycles. 54 We further expanded the monomer size and synthesized a dihexylheptaphenyl monomer ( M2 ) (Schemes S4–6, and Figures S16–24). It should be noted that two n -hexyl groups were introduced to the monomer to increase its solubility. Utilizing similar cyclization conditions, heptaphen[ 3 – 6 ]arenes ( HP [ 3 – 6 ]) were synthesized in 45% yield for HP [ 3 ]; trace amounts for HP [ 4 – 6 ] were detected using high-resolution mass spectrometry (HR-MS) (Schemes 1b , S7, and Figures S25–30). Although the cyclic trimer is the dominant product, HP [ 3 ] has a skeleton consisting of 21 phenyls, much larger than traditional macrocyclic arenes. Single-crystal structures provided clear insights into the conformations and atomic-level structures (Scheme 1 , and Table S2 ). QP [ 3 ] exhibited a side length of 2.0 nm, and the macrocycle had a relatively electronegative cavity (Figure S31). However, we did not obtain single crystals of QP [ 4 – 6 ] and HP [ 3 – 6 ]; therefore, the calculated structures were obtained using the Mopac2016 program method. From QP [ 4 ] to QP [ 5 ] and QP [ 6 ], the macrocyclic sizes increased from 2.0 nm to 3.2 nm and 3.8 nm, respectively (Figures S32–34). In the case of larger macrocycles HP [ 3 – 6 ], their macrocyclic sizes increased from 2.8 nm for HP [ 3 ] to 3.3 nm for HP [ 4 ], 4.6 nm for HP [ 5 ], and 4.7 nm for HP [ 6 ] (Scheme 1b , and Figures S35–38). Giant cavity sizes demonstrate the advantages of the proposed strategy. Furthermore, the surface electrostatic potential maps proved that all the macrocycles possessed a relatively electronegative cavity (Figures S31b–38b). In addition to the 2,4-dimethoxyphenyl reaction module, the 2,5-dimethoxyphenyl reaction module was evaluated. Since linear monomer cannot give any cyclic products, we then used a V-shaped 2,5-dimethoxyquinquephenyl monomer ( M3 ) with an angle of 120°. It produced a hexagonal macrocycle ( 2,5-QP [ 3 ], 17% yield) and a saddle-shaped macrocycle ( 2,5-QP [ 4 ], 5% yield) (Schemes 2a , S8–12 and Figures S39–51). Single-crystal structures confirmed that even the cyclic trimer ( 2,5-QP [ 3 ]) possessed a giant cavity size of 2.0 nm, proved the good universality of our strategy for constructing giant macrocycles (Scheme 2a ). By constructing 2,5-dimethoxyheptaphenyl monomers ( M4 and M5 ), the monomer sizes could be expanded and larger giant macrocycles of 2,5-dimethoxyheptaphen[ n ]arenes ( CN-HP [ 3 – 5 ] and CHO-HP [ 3 – 4 ]) could be produced under similar conditions (Schemes 2b , S13–18, and Figures S52–73). For CN-HP [ 3 – 5 ], the cyclic trimer CN-HP [ 3 ], tetramer CN-HP [ 4 ], and pentamer CN-HP [ 5 ] were obtained in 15%, 8%, and 4% yields, respectively (Scheme S16, and Figures S59–64). For CHO-HP [ 3 – 4 ], the cyclic trimer CHO-HP [ 3 ] and tetramer CHO-HP [ 4 ] were obtained in yields of 12%, and 6%, respectively (Scheme S18, and Figures S68–73). Furthermore, all the macrocycles possessed relatively electronegative cavities (Figures S74–78). Modifiability is crucial for the further development of host–guest recognition, assembly, and functional applications; the preset CN and CHO groups in these macrocycles make it convenient to construct assembly and functional materials. We also examined the feasibility of modifying the giant macrocycles through post-modification. As a typical example, BBr 3 was gradually added to a solution of 2,5-QP [ 3 ] in DCM and stirred at 0 °C for 3 days under a nitrogen atmosphere. The per-hydroxylated macrocycle 2,5-QP [ 3 ] -OH was obtained in 97% yield after quenching and drying (Scheme S19 and Figures S79–81). This result verified the good modifiability of the synthesized giant macrocycles because further modification could be easily performed via reactive OH groups. During the purification of QP [ 3 ] and cultivation of its single-crystal structure, a supramolecular gel was formed in DCM/hexane and THF/hexane. This intriguing phenomenon suggests that QP [ 3 ] probably has a good assembly capacity. Under typical conditions, 0.5 mL of DCM solution dissolving 5 mg of QP [ 3 ] was dropped 0.4 mL of hexane, resulting in the immediate formation of a gel. Conversely, monomer M1 was unable to form such a gel (Figure S82). HP [ 3 ] also formed an organogel under similar conditions (1:1 DCM/hexane) (Figs. 2 c–d, and g–h). Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used for morphology characterization. Both xerogels of QP [ 3 ] and HP [ 3 ] were fibrous with length and width of 10–100 µm and 20–300 nm, respectively (Figs. 2 a–d). Monomers M1 and M2 exhibited disordered structures (Figs. 2 e–h). Powder X-ray diffraction (PXRD) experiments demonstrated the non-crystalline state of the xerogels, and a broad peak at approximately 2θ = 20° indicated the existence of π-π interactions (Figure S83). 55 To elucidate the assembly mechanism, we evaluated two additional cyclic trimers: quaterphen[ 3 ]arenes ( QT [ 3 ]) and terphen[ 3 ]arenes ( TP [ 3 ]). The monomer units of QT [ 3 ] and TP [ 3 ] possessed one and two fewer phenyls than that of QP [ 3 ], respectively (Figs. 2 j). Under the same gelation conditions, TP [ 3 ] remained a clear solution, QT [ 3 ] produced some precipitates, and QP [ 3 ] formed a non-flowing white gel even when the bottle was inverted. This indicated that with an increased in the macrocycle size, the assembly capacity increased. The single-crystal structures of TP [ 3 ], QT [ 3 ], and QP [ 3 ] provided more information about the assembly at the atomic level (Figures S84–87, and Table S4 ). In the solid state, every QP [ 3 ] molecule (cyan) was tightly stacked with the other five molecules (red, purple, orange, and gray) via thirteen phenyls and provided multiple π-π interactions sites (2.7, 2.8, 2.9, 3.1, 3.1, 3.1, 3.1, 3.2, 3.2, 3.2, 3.3, 3.4, 3.6, and 3.8 Å) (Fig. 2 k). One edge of the triangular QP [ 3 ] (cyan) completely overlapped with that of another (orange). Conversely, the remaining two edges were stacked with two other parallel molecules (red and purple) and complemented by additional molecules (gray) (Figures S84a and S85). For smaller macrocycle QT [ 3 ], every molecule (orange) was stacked with three other molecules (gray) via six phenyls and provided limited number of π–π interactions sites (3.1, 3.1, 3.5, 3.5, 3.9, and 3.9 Å) (Figures S84b, and 86). The smallest molecule TP [ 3 ] interacts with other molecules (gray) via only four phenyls and provides the least number of π–π interactions sites (2.9, 3.2, 3.2, 3.8, and 3.8 Å) (Figures S84c, and S87). These results clearly revealed that larger macrocycles could provide more π–π interaction sites and therefore better assembly capacity. Accordingly, the largest macrocycle QP [ 3 ] facilely formed organogel, moderate macrocycle QT [ 3 ] produced precipitates, and the smallest macrocycle TP [ 3 ] remained a clear solution. These macrocycles also exhibit intriguingly photophysical properties. QP [ 3 ] had a strong blue emission peak at 408 nm and a slight red shift compared to the monomer M1 in the DCM solution (Figs. 3 a and S88a). The UV-Vis spectra showed similar peaks at 316 nm for QP [ 3 ] and 319 nm for M1 (Figure S88b). These results proved that the methylene bridging had a limited effect on the ground state but a significant effect on the excited states of the quinquephenyl units. After assembly into the xerogel, the emission of QP [ 3 ] exhibited a red shift to 414 nm, whereas monomer M1 in the solid state had an emission identical to that in the solution (400 nm) (Figs. 3 a and S88c). This result indicates that the assembly of the xerogel is a J-aggregate which was consistent with the packing mode of single-crystal structures. 56,57 The delay-time photoluminescence spectra showed a dual emission with peaks at 414 nm and 508 nm. As the delay time increased from 0.2 ms to 5 ms, the peak at 414 nm sharply disappeared and the peak at 508 nm remained. This observation hints a phosphorescent nature of the QP [ 3 ] xerogel, further proved by the millisecond lifetime (0.35 ms) (Figs. 3 b and S88d). Time-resolved PL decay spectra proved the fluorescence lifetimes of QP [ 3 ] (peak at 414 nm, τ = 1.1 ns) and M1 (peak at 400 nm, τ = 0.86 ns) (Figure S89a-b). HP [ 3 ] xerogel exhibited similar emission with a dual emission of intense fluorescence (peak at 388 nm, τ = 1.1 ns) and phosphorescence (peak at 534 nm, τ = 0.37 ms), which was further supported by the delay-time photoluminescence spectra (Figs. 3 b, S89d and S90a). In a DCM solution, HP [ 3 ] exhibited an absorption peak similar to that of monomer M2 and an intense blue emission (Figure S90b–c). Notably, the photoluminescence efficiencies were 72.8% for QP [ 3 ] and 83.1% for HP [ 3 ] in the xerogels, far higher than those of their monomers (43.1% for M1 and 33.5% for M2 ) (Figs. 3 c and S91–92). This remarkable emission enhancement inspired us to determine the origin. According to Kasha’s rule, an excited molecule generally decays fast and highly efficiently to the lowest excited singlet S 1 . Subsequently, S 1 undergoes three competing decay processes: radiative decay to the S 0 by emitting fluorescence with a rate constant \({\text{k}}_{r}^{F}\) , decay to the ground state S 0 via nonradiative process with a rate constant \({\text{k}}_{nr}^{F}\) , and conversion to the triplet state (T n , n ≥ 1) with an intersystem crossing rate constant k 𝑖𝑠𝑐 . T 1 further decays to S 0 via a radiative process of phosphorescence with a rate constant \({\text{k}}_{r}^{P}\) or a nonradiative process with a rate constant of \({\text{k}}_{nr}^{P}\) . 58 For these giant macrocycles, the radiative decay rate constant of the singlet state was enhanced to \({\text{k}}_{r}^{F}\) = 6.7 × 10 8 s −1 for macrocyclic xerogels QP [ 3 ], which is larger than that of the monomers powder of M1 ( \({\text{k}}_{r}^{F}\) = 5.0 × 10 8 s −1 ) (Table S5 ). Such improvements were also found in macrocyclic xerogels HP [ 3 ] ( \({\text{k}}_{r}^{F}\) = 7.6 × 10 8 s − 1 ) and M2 ( \({\text{k}}_{r}^{F}\) = 1.5 × 10 8 s −1 ). Moreover, the nonradiative decay rate constants of the macrocyclic xerogels ( \({\text{k}}_{nr}^{F}\) = 2.5 × 10 8 s −1 for QP [ 3 ], and \({\text{k}}_{nr}^{F}\) = 1.5 × 10 8 s −1 for HP [ 3 ]) smaller than that of the monomers powder ( \({\text{k}}_{nr}^{F}\) = 6.6 × 10 8 s −1 for M1 , \({\text{k}}_{nr}^{F}\) = 2.9 × 10 8 s − 1 for M2 ) (Table S5 ). The larger \({\text{k}}_{r}^{F}\) and smaller \({\text{k}}_{nr}^{F}\) of the macrocyclic xerogels indicated that the macrocyclic assembly significantly suppressed the nonradiative decay and promoted the radiative decay of QP [ 3 ] and HP [ 3 ]. Because τ p = 1/( \({k}_{r}^{P}\) + \({k}_{nr}^{P}\) ), the similar phosphorescence lifetimes between macrocyclic xerogels and monomers powder indicated that their \({k}_{r}^{P}\) + \({k}_{nr}^{P}\) were near identical in a disordered monomer and macrocyclic assembly. This reveals that the assembly has negligible effects on their triplet state radiative and nonradiative decay processes. Based on these photophysical properties and aforementioned assembly investigation, a possible mechanism for the emission enhancement of macrocyclic assembly was proposed. Macrocycles QP [ 3 ] and HP [ 3 ] were strictly confined in the xerogels assembly via multiple intermolecular π-π interactions. Accordingly, their nonradiative decay processes of rotation/vibration were restricted, the radiative decay process of fluorescence was boosted, and eventually their photoluminescent quantum efficiencies were promoted (Figs. 3 d). Conclusion In summary, we reported a novel strategy of low-entropy-penalty synthesis for the concise and efficient preparation of giant covalent organic macrocycles. This strategy was realized by coupling multiple phenyl units with two 2,4-dimethoxyphenyl or 2,5-dimethoxyphenyl reaction modules to form long and rigid monomers and further condensing them with paraformaldehyde using BF 3 ·Et 2 O as the catalyst. As the macrocycles size was increased by extending the monomers length, the cyclization-entropy penalties were significantly lower than those of increasing the monomer numbers. Giant macrocycles QP [ 3 – 6 ], HP [ 3 – 6 ], 2,5-QP [ 3 – 4 ]), CN-HP [ 3 – 5 ] and CHO-HP [ 3 – 4 ] were facilely synthesized, and the total cyclization yield reached 72%. These giant electron-rich macrocycles possessed cavity sizes in the range 2.0–4.7 nm and are among the largest macrocycles. Significantly, the giant macrocycles spawned excellent assembly properties and facilitated the formation of organogels in various solvents. Mechanism investigation revealed that this self-assembly capacity originated from abundant π–π interaction sites provided by giant macrocycles. Moreover, these multiple intermolecular π–π interactions in the organogel assembly enormously restricted the nonradiative decay processes of rotation/vibration, boosted the radiative decay process of fluorescence, and eventually remarkably promoted the quantum efficiencies to 72.8% and 83.1%. This study provides an effective and general method for producing giant macrocycles with specific properties. Further research on the synthesis, host–guest recognition, and chiral assembly of giant macrocycles is currently underway in our laboratory. Declarations AUTHOR INFORMATION Corresponding Authors *Email: [email protected] ; [email protected] Notes The authors declare no competing financial interests. ACKNOWLEDGMENT The authors gratefully acknowledge the National Natural Science Foundation of China (21971192, 21772118, and 22201211), the Natural Science Foundation of Tianjin City (20JCZDJC00200), and Open Research Fund of School of Chemistry and Chemical Engineering, Henan Normal University. The authors also gratefully acknowledge Professors Dong-Sheng Guo and Kang Cai for their helpful discussions. References Cram DJ, Kaneda T, Helgeson RC, Lein GM (1979) Spherands - ligands whose binding of cations relieves enforced electron-electron repulsions. J Am Chem Soc 101:6752–6754 Lehn JM, Sauvage JP (1975) Cryptates. XVI. [2]-Cryptates. Stability and selectivity of alkali and alkaline-earth macrobicyclic complexes. J Am Chem Soc 97:6700–6707 Pedersen CJ (1967) Cyclic polyethers and their complexes with metal salts. J Am Chem Soc 89:2495–2496 Szejtli J (1982) Cyclodextrins and Their Inclusion Complexes. Akad Kiado Budapest Hungary 34 Crini G, Review (2014) A History of Cyclodextrins. 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Angew Chem Int Ed 42:1210–1250 Würthner F, Kaiser TE, Saha-Möller CR (2011) J-Aggregates: From Serendipitous Discovery to Supramolecular Engineering of Functional Dye Materials. Angew Chem Int Ed 50:3376–3410 Ma S et al (2021) Organic molecular aggregates: From aggregation structure to emission property. Aggregate 2:e96 Baroncini M, Bergamini G, Ceroni P (2017) Rigidification or interaction-induced phosphorescence of organic molecules. Chem Commun 53:2081–2093 Schemes Schemes 1 and 2 are available in the Supplementary Files section Additional Declarations There is NO Competing Interest. Supplementary Files 24QP3checkcif.pdf 24QP3.cif 25QP3checkcif.pdf 25QP3.cif TP3checkcif.pdf TP3.cif SupportingInformation.docx Schemes.docx GA.png Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3846672","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":267567744,"identity":"c37067b9-8f4a-4e9a-a4cf-d7438cf100cd","order_by":0,"name":"Chunju Li","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAr0lEQVRIiWNgGAWjYFCCww0HPjAcALEMiNVysOHgDBK1MDYw85Ckhb/xYONhmz93EhvYm7dJMNTcIaxF4sDBhsO5bc8SG3iOlUkwHHtGWIsBA0hLw+HEBokcMwnGhsNEarH4A9Qi/4YULQxsIFt4iNQC8svB3rbDxm08acUWCceI0MI/4/DhDz/+HJbtZz+88caHGiK0AK2B0GwgIoEIDUBrGohSNgpGwSgYBSMZAACuAEMgz9HNCQAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0001-7450-4867","institution":"Tianjin Normal University","correspondingAuthor":true,"prefix":"","firstName":"Chunju","middleName":"","lastName":"Li","suffix":""},{"id":267567745,"identity":"4da31f99-26de-4f20-9c53-2c70c5143d90","order_by":1,"name":"Xiao-Na Sun","email":"","orcid":"","institution":"Tianjin Normal University","correspondingAuthor":false,"prefix":"","firstName":"Xiao-Na","middleName":"","lastName":"Sun","suffix":""},{"id":267567746,"identity":"70f35c39-4f15-4802-bbf5-56ba05baa7e9","order_by":2,"name":"Ao Liu","email":"","orcid":"","institution":"Tianjin Normal University","correspondingAuthor":false,"prefix":"","firstName":"Ao","middleName":"","lastName":"Liu","suffix":""},{"id":267567747,"identity":"ce7efb97-066b-46bf-ab02-e941de78815d","order_by":3,"name":"Kaidi Xu","email":"","orcid":"","institution":"Shanghai University","correspondingAuthor":false,"prefix":"","firstName":"Kaidi","middleName":"","lastName":"Xu","suffix":""},{"id":267567748,"identity":"83e665a7-1bbc-48be-98e8-56e806a8c719","order_by":4,"name":"Zhe Zheng","email":"","orcid":"","institution":"Tianjin Normal University","correspondingAuthor":false,"prefix":"","firstName":"Zhe","middleName":"","lastName":"Zheng","suffix":""},{"id":267567749,"identity":"9b2c5295-39ae-4b6e-a3e5-f7396757ad68","order_by":5,"name":"Kai Xu","email":"","orcid":"","institution":"Tianjin Normal University","correspondingAuthor":false,"prefix":"","firstName":"Kai","middleName":"","lastName":"Xu","suffix":""},{"id":267567750,"identity":"35498301-3d62-4b8a-9e20-98ad3d3ac50a","order_by":6,"name":"Ming Dong","email":"","orcid":"","institution":"Tianjin Normal University","correspondingAuthor":false,"prefix":"","firstName":"Ming","middleName":"","lastName":"Dong","suffix":""},{"id":267567751,"identity":"43f4fbf0-b32d-4ab4-b8dd-046badd8673d","order_by":7,"name":"Jian Li","email":"","orcid":"","institution":"Shanghai University","correspondingAuthor":false,"prefix":"","firstName":"Jian","middleName":"","lastName":"Li","suffix":""},{"id":267567752,"identity":"0437196d-c4b3-4cee-b169-7b359f73b20b","order_by":8,"name":"Zhi-Yuan Zhang","email":"","orcid":"","institution":"Tianjin Normal University","correspondingAuthor":false,"prefix":"","firstName":"Zhi-Yuan","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2024-01-09 00:05:39","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3846672/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3846672/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":49837773,"identity":"f23bc785-7c99-48d0-917b-b5a4ecfb4653","added_by":"auto","created_at":"2024-01-18 19:44:54","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":156623,"visible":true,"origin":"","legend":"\u003cp\u003eRelation between the calculated cyclization-entropy penalty (-ΔS) and the number of phenyl units in macrocycles in (a) conventional strategy and (b) our strategy.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-3846672/v1/6df2be0f3b5c255340415555.png"},{"id":49837778,"identity":"f61ef0bb-947c-487d-9b7b-0342f9f22834","added_by":"auto","created_at":"2024-01-18 19:44:54","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":758699,"visible":true,"origin":"","legend":"\u003cp\u003e(a–h) Morphology characterization of (a–b) \u003cstrong\u003eQP[3] \u003c/strong\u003exerogel, (c–d) \u003cstrong\u003eHP[3]\u003c/strong\u003e xerogel, (e–f) monomer \u003cstrong\u003eM1 \u003c/strong\u003epowder, and (g–h) monomer \u003cstrong\u003eM2\u003c/strong\u003e powder using (a, c, e, g) SEM and (b, d, f, h) TEM. (i) Schematic of the increased assembly capacity from monomers (\u003cstrong\u003eM1\u003c/strong\u003e and \u003cstrong\u003eM2\u003c/strong\u003e) to macrocycles (\u003cstrong\u003eQP[3]\u003c/strong\u003e and \u003cstrong\u003eHP[3]\u003c/strong\u003e). (j) Schematic of the increased assembly capacity with increasing size of macrocycles from terphen[3]arenes (\u003cstrong\u003eTP[3]\u003c/strong\u003e) to quaterphen[3]arenes (\u003cstrong\u003eQT[3]\u003c/strong\u003e) and quinquephen[3]arenes (\u003cstrong\u003eQP[3]\u003c/strong\u003e). (k) Single-crystal structures of \u003cstrong\u003eQP[3]\u003c/strong\u003e. The hydrogen atoms are omitted for the sake of clarity.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-3846672/v1/62b9766033905be476904e1f.png"},{"id":49837775,"identity":"79cd8066-3076-475f-9dda-fc2366055851","added_by":"auto","created_at":"2024-01-18 19:44:54","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":253074,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-3846672/v1/da1e42aafde07992c017876e.png"},{"id":52497157,"identity":"84fe7fe4-00d8-47ce-84da-11df2f30122b","added_by":"auto","created_at":"2024-03-12 08:53:25","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1346768,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3846672/v1/f1534ab6-6a1a-4923-af1b-e3201e3eb16d.pdf"},{"id":49837774,"identity":"fd175551-08ed-4817-8414-7666fbacd298","added_by":"auto","created_at":"2024-01-18 19:44:54","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":111324,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"24QP3checkcif.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3846672/v1/25c672e3d5116ad66e4f5e1d.pdf"},{"id":49837779,"identity":"66d856a4-7c53-47b5-850a-f876369476f3","added_by":"auto","created_at":"2024-01-18 19:44:55","extension":"cif","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":4776810,"visible":true,"origin":"","legend":"","description":"","filename":"24QP3.cif","url":"https://assets-eu.researchsquare.com/files/rs-3846672/v1/c910b1c851512b6988d9c23b.cif"},{"id":49837777,"identity":"d911ba03-6609-4611-99e9-dc579216c1c7","added_by":"auto","created_at":"2024-01-18 19:44:54","extension":"pdf","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":94712,"visible":true,"origin":"","legend":"","description":"","filename":"25QP3checkcif.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3846672/v1/d66b77fdc8b4fdc84d6441b7.pdf"},{"id":49837781,"identity":"de157a44-7f03-4ccb-bb46-93b71ae0bf25","added_by":"auto","created_at":"2024-01-18 19:44:55","extension":"cif","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":1095610,"visible":true,"origin":"","legend":"","description":"","filename":"25QP3.cif","url":"https://assets-eu.researchsquare.com/files/rs-3846672/v1/253a7922d682338fed5b51dd.cif"},{"id":49837782,"identity":"344651c5-621e-4951-8ef8-68d58c91c8cc","added_by":"auto","created_at":"2024-01-18 19:44:55","extension":"pdf","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":177263,"visible":true,"origin":"","legend":"","description":"","filename":"TP3checkcif.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3846672/v1/f75ade7352b1fe46c03d231c.pdf"},{"id":49837883,"identity":"6ec8fdad-3148-451e-908f-090cffdf2c9f","added_by":"auto","created_at":"2024-01-18 19:52:54","extension":"cif","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":32620,"visible":true,"origin":"","legend":"","description":"","filename":"TP3.cif","url":"https://assets-eu.researchsquare.com/files/rs-3846672/v1/cdf2ad7fb69b7ca1fc97e63b.cif"},{"id":49837785,"identity":"7d0e7a7d-9977-44e3-a83b-ef30bf133ae5","added_by":"auto","created_at":"2024-01-18 19:44:57","extension":"docx","order_by":7,"title":"","display":"","copyAsset":false,"role":"supplement","size":47375816,"visible":true,"origin":"","legend":"","description":"","filename":"SupportingInformation.docx","url":"https://assets-eu.researchsquare.com/files/rs-3846672/v1/ae7b1a44292157188274d844.docx"},{"id":49837783,"identity":"695250f9-68ed-4826-9a8a-0abd2d7280f3","added_by":"auto","created_at":"2024-01-18 19:44:55","extension":"docx","order_by":8,"title":"","display":"","copyAsset":false,"role":"supplement","size":9037287,"visible":true,"origin":"","legend":"","description":"","filename":"Schemes.docx","url":"https://assets-eu.researchsquare.com/files/rs-3846672/v1/cb30d7fce08adabf376e6dc5.docx"},{"id":49837780,"identity":"7aa4b866-f6d9-48f0-bde8-fc9ddb5c1229","added_by":"auto","created_at":"2024-01-18 19:44:55","extension":"png","order_by":9,"title":"","display":"","copyAsset":false,"role":"supplement","size":118332,"visible":true,"origin":"","legend":"","description":"","filename":"GA.png","url":"https://assets-eu.researchsquare.com/files/rs-3846672/v1/1b279c1a941d0bc35e953ca3.png"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Low-Entropy-Penalty Synthesis of Giant Macrocycles for Good Self-Assembly and Emission Enhancement","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMacrocyclic compounds are key tools for theoretical and practical investigations in supramolecular chemistry.\u003csup\u003e1\u0026ndash;9\u003c/sup\u003e Considerable effort has been made in designing and synthesizing macrocycles\u003csup\u003e10\u0026ndash;17\u003c/sup\u003e, studying their recognition\u003csup\u003e3,4,6,11,17,18\u003c/sup\u003e and self-assembly properties,\u003csup\u003e19\u0026ndash;23\u003c/sup\u003e and exploring their applications in various fields such as biomedicine,\u003csup\u003e24\u0026ndash;26\u003c/sup\u003e optoelectronics,\u003csup\u003e27\u0026ndash;30\u003c/sup\u003e sensing,\u003csup\u003e31\u0026ndash;34\u003c/sup\u003e and adsorption and separation\u003csup\u003e35\u0026ndash;37\u003c/sup\u003e. The cavities of traditional macrocycles such as cyclodextrins, calix[\u003cem\u003en\u003c/em\u003e]arenes, cucurbit[\u003cem\u003en\u003c/em\u003e]urils, and pillar[\u003cem\u003en\u003c/em\u003e]arenes, are usually less than 1 nm in diameter, which severely limits their scope of application. Efficient synthesis of macrocycles with large cavities is a formidable challenge. The conventional approach to enlarge the cavity size involves increasing the number of monomer units; however, this method usually does not yield giant macrocycles. First, increasing the monomer numbers usually results in a twisted configuration with small cavities owing to the directivity of covalent bonds. For example, ε-/ι-cyclodextrins,\u003csup\u003e38\u003c/sup\u003e calix[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]arenes,\u003csup\u003e39\u0026ndash;41\u003c/sup\u003e cucurbit[\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]urils,\u003csup\u003e42,43\u003c/sup\u003e and pillar[\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]arenes\u003csup\u003e44\u003c/sup\u003e possess twisted small cavities rather than the expected single large cavity. Moreover, the sizes of these macrocyclic cavities are even smaller than those of their homologues with less monomer numbers (Figure \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e). Second, cyclization itself leads to a loss of conformational freedom, and an increase in the number of monomer units results in a larger entropy penalty and a sharp decrease in cyclization yields (Figure \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e). Calix[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]arenes exhibit cyclization yields of 64% and 74%, while that of calix[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]arene is only 3%\u003csup\u003e45,46\u003c/sup\u003e. The cyclization yields of cucurbit[\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]urils are only 0.2\u0026ndash;3%\u003csup\u003e42,43,47\u003c/sup\u003e and pillar[\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]arenes are only 1\u0026ndash;2% \u003csup\u003e44,48\u003c/sup\u003e (Figure \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e). Although there are a few pioneering studies that have proposed excellent methods for constructing giant macrocycles, the approaches are limited by tedious synthesis and low yields.\u003csup\u003e49\u0026ndash;52\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIn this study, we report a low-entropy-penalty synthesis of giant covalent organic macrocycles, \u003cem\u003ep\u003c/em\u003e-oligophen[\u003cem\u003en\u003c/em\u003e]arenes, by the condensation of long and rigid monomer possessing two reaction modules with paraformaldehyde via Friedel\u0026ndash;Crafts reaction. The reversibility of the Friedel\u0026ndash;Crafts reaction facilitates macrocyclization with a self-correcting ability and results in a thermodynamically stable product in high yield. The inertness of methylene after removal of the catalysts ensured the high stability of the macrocycles. More importantly, extending the monomer length rather than increasing the monomer numbers could significantly reduce the cyclization-entropy loss, avoid configuration twists, and facilitate the formation of giant macrocycles with large cavities, excellent self-assembly capacities, and outstanding luminescence performances.\u003c/p\u003e"},{"header":"Results and Discussion","content":"\u003cp\u003eWe first calculated the entropy penalty (-\u0026Delta;S)\u003csup\u003e53\u003c/sup\u003e resulting from extending the monomer length of \u003cem\u003ep\u003c/em\u003e-oligophen[\u003cem\u003en\u003c/em\u003e]arenes (our strategy), and compared it to that of increasing monomer numbers of pillar[\u003cem\u003en\u003c/em\u003e]arenes and calix[\u003cem\u003en\u003c/em\u003e]arenes (conventional strategy) (Figs. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e and S2). From pillar[\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e]arene to pillar[\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e]arene, the number of phenyl units in macrocycle increased from 5 to 10, the -\u0026Delta;S increased 7.9-fold, and the cyclization yields reduced from 71\u0026ndash;2% (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003ea).\u003csup\u003e44,48\u003c/sup\u003e Conversely, from terphen[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e]arene to octaphen[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e]arene, the number of phenyl units in macrocycle increased from 9 to 24, and the -\u0026Delta;S only increased 0.9-fold, indicating the great advantages of the proposed strategy (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eb).\u003c/p\u003e\n\u003cp\u003eWe then verify the effectiveness of our strategy experimentally. By coupling 4,4\u0026apos;\u0026apos;-dibromoterphenyl with two 2,4-dimethoxyphenylboronic acid reaction modules, a rigid quinquephenyl monomer (\u003cstrong\u003eM1\u003c/strong\u003e) was synthesized in 81% yield (Scheme S2, and Figures \u003cspan class=\"InternalRef\"\u003eS3\u003c/span\u003e-5). Monomer \u003cstrong\u003eM1\u003c/strong\u003e was further condensed with paraformaldehyde ((CH\u003csub\u003e2\u003c/sub\u003eO)\u003csub\u003en\u003c/sub\u003e) using a Lewis acid catalyst to form cyclic products quinquephen[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e]arenes (\u003cstrong\u003eQP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e]). This cyclization reaction can be performed in various solvents, such as 1,2-dichloroethane (DCE), tetrachloroethane (TCE), dichloromethane (DCM), and CHCl\u003csub\u003e3\u003c/sub\u003e, and catalysts, such as BF\u003csub\u003e3\u003c/sub\u003e\u0026middot;Et\u003csub\u003e2\u003c/sub\u003eO, FeCl\u003csub\u003e3\u003c/sub\u003e, AlCl\u003csub\u003e3\u003c/sub\u003e, and trifluoromethanesulfonic acid (TfOH)) (Table \u003cspan class=\"InternalRef\"\u003eS1\u003c/span\u003e). Under optimized conditions of using DCE as the solvent and BF\u003csub\u003e3\u003c/sub\u003e\u0026middot;Et\u003csub\u003e2\u003c/sub\u003eO as the catalyst (8%), and at 25 \u0026deg;C for 2 h, \u003cstrong\u003eQP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e] can be obtained with an overall yield of 72% (44% for \u003cstrong\u003eQP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e], 23% for \u003cstrong\u003eQP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e], 5% for \u003cstrong\u003eQP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e], and trace amounts for \u003cstrong\u003eQP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e]) (Schemes \u003cspan class=\"InternalRef\"\u003e1a\u003c/span\u003e, S1, S3, and Figures \u003cspan class=\"InternalRef\"\u003eS6\u003c/span\u003e\u0026ndash;15). This relatively high cyclization yield indicates that our strategy is significant in producing giant macrocycles.\u003csup\u003e54\u003c/sup\u003e We further expanded the monomer size and synthesized a dihexylheptaphenyl monomer (\u003cstrong\u003eM2\u003c/strong\u003e) (Schemes S4\u0026ndash;6, and Figures S16\u0026ndash;24). It should be noted that two \u003cem\u003en\u003c/em\u003e-hexyl groups were introduced to the monomer to increase its solubility. Utilizing similar cyclization conditions, heptaphen[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e]arenes (\u003cstrong\u003eHP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e]) were synthesized in 45% yield for \u003cstrong\u003eHP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e]; trace amounts for \u003cstrong\u003eHP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e] were detected using high-resolution mass spectrometry (HR-MS) (Schemes \u003cspan class=\"InternalRef\"\u003e1b\u003c/span\u003e, S7, and Figures S25\u0026ndash;30). Although the cyclic trimer is the dominant product, \u003cstrong\u003eHP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e] has a skeleton consisting of 21 phenyls, much larger than traditional macrocyclic arenes.\u003c/p\u003e\n\u003cp\u003eSingle-crystal structures provided clear insights into the conformations and atomic-level structures (Scheme \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e, and Table \u003cspan class=\"InternalRef\"\u003eS2\u003c/span\u003e). \u003cstrong\u003eQP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e] exhibited a side length of 2.0 nm, and the macrocycle had a relatively electronegative cavity (Figure S31). However, we did not obtain single crystals of \u003cstrong\u003eQP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e] and \u003cstrong\u003eHP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e]; therefore, the calculated structures were obtained using the Mopac2016 program method. From \u003cstrong\u003eQP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e] to \u003cstrong\u003eQP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e] and \u003cstrong\u003eQP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e], the macrocyclic sizes increased from 2.0 nm to 3.2 nm and 3.8 nm, respectively (Figures S32\u0026ndash;34). In the case of larger macrocycles \u003cstrong\u003eHP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e], their macrocyclic sizes increased from 2.8 nm for \u003cstrong\u003eHP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e] to 3.3 nm for \u003cstrong\u003eHP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e], 4.6 nm for \u003cstrong\u003eHP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e], and 4.7 nm for \u003cstrong\u003eHP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e] (Scheme \u003cspan class=\"InternalRef\"\u003e1b\u003c/span\u003e, and Figures S35\u0026ndash;38). Giant cavity sizes demonstrate the advantages of the proposed strategy. Furthermore, the surface electrostatic potential maps proved that all the macrocycles possessed a relatively electronegative cavity (Figures S31b\u0026ndash;38b).\u003c/p\u003e\n\u003cp\u003eIn addition to the 2,4-dimethoxyphenyl reaction module, the 2,5-dimethoxyphenyl reaction module was evaluated. Since linear monomer cannot give any cyclic products, we then used a V-shaped 2,5-dimethoxyquinquephenyl monomer (\u003cstrong\u003eM3\u003c/strong\u003e) with an angle of 120\u0026deg;. It produced a hexagonal macrocycle (\u003cstrong\u003e2,5-QP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e], 17% yield) and a saddle-shaped macrocycle (\u003cstrong\u003e2,5-QP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e], 5% yield) (Schemes \u003cspan class=\"InternalRef\"\u003e2a\u003c/span\u003e, S8\u0026ndash;12 and Figures S39\u0026ndash;51). Single-crystal structures confirmed that even the cyclic trimer (\u003cstrong\u003e2,5-QP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e]) possessed a giant cavity size of 2.0 nm, proved the good universality of our strategy for constructing giant macrocycles (Scheme \u003cspan class=\"InternalRef\"\u003e2a\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eBy constructing 2,5-dimethoxyheptaphenyl monomers (\u003cstrong\u003eM4\u003c/strong\u003e and \u003cstrong\u003eM5\u003c/strong\u003e), the monomer sizes could be expanded and larger giant macrocycles of 2,5-dimethoxyheptaphen[\u003cem\u003en\u003c/em\u003e]arenes (\u003cstrong\u003eCN-HP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e] and \u003cstrong\u003eCHO-HP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e]) could be produced under similar conditions (Schemes \u003cspan class=\"InternalRef\"\u003e2b\u003c/span\u003e, S13\u0026ndash;18, and Figures S52\u0026ndash;73). For \u003cstrong\u003eCN-HP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e], the cyclic trimer \u003cstrong\u003eCN-HP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e], tetramer \u003cstrong\u003eCN-HP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e], and pentamer \u003cstrong\u003eCN-HP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e] were obtained in 15%, 8%, and 4% yields, respectively (Scheme S16, and Figures S59\u0026ndash;64). For \u003cstrong\u003eCHO-HP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e], the cyclic trimer \u003cstrong\u003eCHO-HP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e] and tetramer \u003cstrong\u003eCHO-HP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e] were obtained in yields of 12%, and 6%, respectively (Scheme S18, and Figures S68\u0026ndash;73). Furthermore, all the macrocycles possessed relatively electronegative cavities (Figures S74\u0026ndash;78). Modifiability is crucial for the further development of host\u0026ndash;guest recognition, assembly, and functional applications; the preset CN and CHO groups in these macrocycles make it convenient to construct assembly and functional materials. We also examined the feasibility of modifying the giant macrocycles through post-modification. As a typical example, BBr\u003csub\u003e3\u003c/sub\u003e was gradually added to a solution of \u003cstrong\u003e2,5-QP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e] in DCM and stirred at 0 \u0026deg;C for 3 days under a nitrogen atmosphere. The per-hydroxylated macrocycle \u003cstrong\u003e2,5-QP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003cstrong\u003e-OH\u003c/strong\u003e was obtained in 97% yield after quenching and drying (Scheme S19 and Figures S79\u0026ndash;81). This result verified the good modifiability of the synthesized giant macrocycles because further modification could be easily performed via reactive OH groups.\u003c/p\u003e\n\u003cp\u003eDuring the purification of \u003cstrong\u003eQP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e] and cultivation of its single-crystal structure, a supramolecular gel was formed in DCM/hexane and THF/hexane. This intriguing phenomenon suggests that \u003cstrong\u003eQP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e] probably has a good assembly capacity. Under typical conditions, 0.5 mL of DCM solution dissolving 5 mg of \u003cstrong\u003eQP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e] was dropped 0.4 mL of hexane, resulting in the immediate formation of a gel. Conversely, monomer \u003cstrong\u003eM1\u003c/strong\u003e was unable to form such a gel (Figure S82). \u003cstrong\u003eHP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e] also formed an organogel under similar conditions (1:1 DCM/hexane) (Figs. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003ec\u0026ndash;d, and g\u0026ndash;h). Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used for morphology characterization. Both xerogels of \u003cstrong\u003eQP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e] and \u003cstrong\u003eHP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e] were fibrous with length and width of 10\u0026ndash;100 \u0026micro;m and 20\u0026ndash;300 nm, respectively (Figs. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003ea\u0026ndash;d). Monomers \u003cstrong\u003eM1\u003c/strong\u003e and \u003cstrong\u003eM2\u003c/strong\u003e exhibited disordered structures (Figs. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003ee\u0026ndash;h). Powder X-ray diffraction (PXRD) experiments demonstrated the non-crystalline state of the xerogels, and a broad peak at approximately 2\u0026theta;\u0026thinsp;=\u0026thinsp;20\u0026deg; indicated the existence of \u0026pi;-\u0026pi; interactions (Figure S83).\u003csup\u003e55\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eTo elucidate the assembly mechanism, we evaluated two additional cyclic trimers: quaterphen[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e]arenes (\u003cstrong\u003eQT\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e]) and terphen[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e]arenes (\u003cstrong\u003eTP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e]). The monomer units of \u003cstrong\u003eQT\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e] and \u003cstrong\u003eTP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e] possessed one and two fewer phenyls than that of \u003cstrong\u003eQP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e], respectively (Figs. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003ej). Under the same gelation conditions, \u003cstrong\u003eTP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e] remained a clear solution, \u003cstrong\u003eQT\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e] produced some precipitates, and \u003cstrong\u003eQP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e] formed a non-flowing white gel even when the bottle was inverted. This indicated that with an increased in the macrocycle size, the assembly capacity increased. The single-crystal structures of \u003cstrong\u003eTP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e], \u003cstrong\u003eQT\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e], and \u003cstrong\u003eQP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e] provided more information about the assembly at the atomic level (Figures S84\u0026ndash;87, and Table \u003cspan class=\"InternalRef\"\u003eS4\u003c/span\u003e). In the solid state, every \u003cstrong\u003eQP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e] molecule (cyan) was tightly stacked with the other five molecules (red, purple, orange, and gray) via thirteen phenyls and provided multiple \u0026pi;-\u0026pi; interactions sites (2.7, 2.8, 2.9, 3.1, 3.1, 3.1, 3.1, 3.2, 3.2, 3.2, 3.3, 3.4, 3.6, and 3.8 \u0026Aring;) (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003ek). One edge of the triangular \u003cstrong\u003eQP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e] (cyan) completely overlapped with that of another (orange). Conversely, the remaining two edges were stacked with two other parallel molecules (red and purple) and complemented by additional molecules (gray) (Figures S84a and S85). For smaller macrocycle \u003cstrong\u003eQT\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e], every molecule (orange) was stacked with three other molecules (gray) via six phenyls and provided limited number of \u0026pi;\u0026ndash;\u0026pi; interactions sites (3.1, 3.1, 3.5, 3.5, 3.9, and 3.9 \u0026Aring;) (Figures S84b, and 86). The smallest molecule \u003cstrong\u003eTP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e] interacts with other molecules (gray) via only four phenyls and provides the least number of \u0026pi;\u0026ndash;\u0026pi; interactions sites (2.9, 3.2, 3.2, 3.8, and 3.8 \u0026Aring;) (Figures S84c, and S87). These results clearly revealed that larger macrocycles could provide more \u0026pi;\u0026ndash;\u0026pi; interaction sites and therefore better assembly capacity. Accordingly, the largest macrocycle \u003cstrong\u003eQP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e] facilely formed organogel, moderate macrocycle \u003cstrong\u003eQT\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e] produced precipitates, and the smallest macrocycle \u003cstrong\u003eTP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e] remained a clear solution.\u003c/p\u003e\n\u003cp\u003eThese macrocycles also exhibit intriguingly photophysical properties. \u003cstrong\u003eQP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e] had a strong blue emission peak at 408 nm and a slight red shift compared to the monomer \u003cstrong\u003eM1\u003c/strong\u003e in the DCM solution (Figs. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003ea and S88a). The UV-Vis spectra showed similar peaks at 316 nm for \u003cstrong\u003eQP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e] and 319 nm for \u003cstrong\u003eM1\u003c/strong\u003e (Figure S88b). These results proved that the methylene bridging had a limited effect on the ground state but a significant effect on the excited states of the quinquephenyl units. After assembly into the xerogel, the emission of \u003cstrong\u003eQP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e] exhibited a red shift to 414 nm, whereas monomer \u003cstrong\u003eM1\u003c/strong\u003e in the solid state had an emission identical to that in the solution (400 nm) (Figs. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003ea and S88c). This result indicates that the assembly of the xerogel is a J-aggregate which was consistent with the packing mode of single-crystal structures.\u003csup\u003e56,57\u003c/sup\u003e The delay-time photoluminescence spectra showed a dual emission with peaks at 414 nm and 508 nm. As the delay time increased from 0.2 ms to 5 ms, the peak at 414 nm sharply disappeared and the peak at 508 nm remained. This observation hints a phosphorescent nature of the \u003cstrong\u003eQP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e] xerogel, further proved by the millisecond lifetime (0.35 ms) (Figs. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eb and S88d). Time-resolved PL decay spectra proved the fluorescence lifetimes of \u003cstrong\u003eQP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e] (peak at 414 nm, \u0026tau;\u0026thinsp;=\u0026thinsp;1.1 ns) and \u003cstrong\u003eM1\u003c/strong\u003e (peak at 400 nm, \u0026tau;\u0026thinsp;=\u0026thinsp;0.86 ns) (Figure S89a-b). \u003cstrong\u003eHP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e] xerogel exhibited similar emission with a dual emission of intense fluorescence (peak at 388 nm, \u0026tau;\u0026thinsp;=\u0026thinsp;1.1 ns) and phosphorescence (peak at 534 nm, \u0026tau;\u0026thinsp;=\u0026thinsp;0.37 ms), which was further supported by the delay-time photoluminescence spectra (Figs. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eb, S89d and S90a). In a DCM solution, \u003cstrong\u003eHP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e] exhibited an absorption peak similar to that of monomer \u003cstrong\u003eM2\u003c/strong\u003e and an intense blue emission (Figure S90b\u0026ndash;c). Notably, the photoluminescence efficiencies were 72.8% for \u003cstrong\u003eQP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e] and 83.1% for \u003cstrong\u003eHP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e] in the xerogels, far higher than those of their monomers (43.1% for \u003cstrong\u003eM1\u003c/strong\u003e and 33.5% for \u003cstrong\u003eM2\u003c/strong\u003e) (Figs. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003ec and S91\u0026ndash;92).\u003c/p\u003e\n\u003cp\u003eThis remarkable emission enhancement inspired us to determine the origin. According to Kasha\u0026rsquo;s rule, an excited molecule generally decays fast and highly efficiently to the lowest excited singlet S\u003csub\u003e1\u003c/sub\u003e. Subsequently, S\u003csub\u003e1\u003c/sub\u003e undergoes three competing decay processes: radiative decay to the S\u003csub\u003e0\u003c/sub\u003e by emitting fluorescence with a rate constant \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({\\text{k}}_{r}^{F}\\)\u003c/span\u003e\u003c/span\u003e, decay to the ground state S\u003csub\u003e0\u003c/sub\u003e via nonradiative process with a rate constant \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({\\text{k}}_{nr}^{F}\\)\u003c/span\u003e\u003c/span\u003e, and conversion to the triplet state (T\u003csub\u003en\u003c/sub\u003e, n\u0026thinsp;\u0026ge;\u0026thinsp;1) with an intersystem crossing rate constant k\u003csub\u003e𝑖𝑠𝑐\u003c/sub\u003e. T\u003csub\u003e1\u003c/sub\u003e further decays to S\u003csub\u003e0\u003c/sub\u003e via a radiative process of phosphorescence with a rate constant \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({\\text{k}}_{r}^{P}\\)\u003c/span\u003e\u003c/span\u003eor a nonradiative process with a rate constant of \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({\\text{k}}_{nr}^{P}\\)\u003c/span\u003e\u003c/span\u003e.\u003csup\u003e58\u003c/sup\u003e For these giant macrocycles, the radiative decay rate constant of the singlet state was enhanced to \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({\\text{k}}_{r}^{F}\\)\u003c/span\u003e\u003c/span\u003e = 6.7 \u0026times; 10\u003csup\u003e8\u003c/sup\u003e s\u003csup\u003e\u0026minus;1\u003c/sup\u003e for macrocyclic xerogels \u003cstrong\u003eQP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e], which is larger than that of the monomers powder of \u003cstrong\u003eM1\u003c/strong\u003e (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({\\text{k}}_{r}^{F}\\)\u003c/span\u003e\u003c/span\u003e = 5.0 \u0026times; 10\u003csup\u003e8\u003c/sup\u003e s\u003csup\u003e\u0026minus;1\u003c/sup\u003e) (Table \u003cspan class=\"InternalRef\"\u003eS5\u003c/span\u003e). Such improvements were also found in macrocyclic xerogels \u003cstrong\u003eHP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e] ( \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({\\text{k}}_{r}^{F}\\)\u003c/span\u003e\u003c/span\u003e = 7.6 \u0026times; 10\u003csup\u003e8\u003c/sup\u003e s\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e ) and \u003cstrong\u003eM2\u003c/strong\u003e ( \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({\\text{k}}_{r}^{F}\\)\u003c/span\u003e\u003c/span\u003e = 1.5 \u0026times; 10\u003csup\u003e8\u003c/sup\u003e s\u003csup\u003e\u0026minus;1\u003c/sup\u003e ). Moreover, the nonradiative decay rate constants of the macrocyclic xerogels (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({\\text{k}}_{nr}^{F}\\)\u003c/span\u003e\u003c/span\u003e= 2.5 \u0026times; 10\u003csup\u003e8\u003c/sup\u003e s\u003csup\u003e\u0026minus;1\u003c/sup\u003e for \u003cstrong\u003eQP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e], and \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({\\text{k}}_{nr}^{F}\\)\u003c/span\u003e\u003c/span\u003e= 1.5 \u0026times; 10\u003csup\u003e8\u003c/sup\u003e s\u003csup\u003e\u0026minus;1\u003c/sup\u003e for \u003cstrong\u003eHP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e]) smaller than that of the monomers powder (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({\\text{k}}_{nr}^{F}\\)\u003c/span\u003e\u003c/span\u003e= 6.6 \u0026times; 10\u003csup\u003e8\u003c/sup\u003e s\u003csup\u003e\u0026minus;1\u003c/sup\u003e for \u003cstrong\u003eM1\u003c/strong\u003e, \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({\\text{k}}_{nr}^{F}\\)\u003c/span\u003e\u003c/span\u003e= 2.9 \u0026times; 10\u003csup\u003e8\u003c/sup\u003e s\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e for \u003cstrong\u003eM2\u003c/strong\u003e) (Table \u003cspan class=\"InternalRef\"\u003eS5\u003c/span\u003e). The larger \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({\\text{k}}_{r}^{F}\\)\u003c/span\u003e\u003c/span\u003e and smaller \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({\\text{k}}_{nr}^{F}\\)\u003c/span\u003e\u003c/span\u003e of the macrocyclic xerogels indicated that the macrocyclic assembly significantly suppressed the nonradiative decay and promoted the radiative decay of \u003cstrong\u003eQP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e] and \u003cstrong\u003eHP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e]. Because \u0026tau;\u003csub\u003ep\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;1/(\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({k}_{r}^{P}\\)\u003c/span\u003e\u003c/span\u003e+ \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({k}_{nr}^{P}\\)\u003c/span\u003e\u003c/span\u003e), the similar phosphorescence lifetimes between macrocyclic xerogels and monomers powder indicated that their \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({k}_{r}^{P}\\)\u003c/span\u003e\u003c/span\u003e+ \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({k}_{nr}^{P}\\)\u003c/span\u003e\u003c/span\u003e were near identical in a disordered monomer and macrocyclic assembly. This reveals that the assembly has negligible effects on their triplet state radiative and nonradiative decay processes. Based on these photophysical properties and aforementioned assembly investigation, a possible mechanism for the emission enhancement of macrocyclic assembly was proposed. Macrocycles \u003cstrong\u003eQP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e] and \u003cstrong\u003eHP\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e] were strictly confined in the xerogels assembly via multiple intermolecular \u0026pi;-\u0026pi; interactions. Accordingly, their nonradiative decay processes of rotation/vibration were restricted, the radiative decay process of fluorescence was boosted, and eventually their photoluminescent quantum efficiencies were promoted (Figs.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003ed).\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn summary, we reported a novel strategy of low-entropy-penalty synthesis for the concise and efficient preparation of giant covalent organic macrocycles. This strategy was realized by coupling multiple phenyl units with two 2,4-dimethoxyphenyl or 2,5-dimethoxyphenyl reaction modules to form long and rigid monomers and further condensing them with paraformaldehyde using BF\u003csub\u003e3\u003c/sub\u003e\u0026middot;Et\u003csub\u003e2\u003c/sub\u003eO as the catalyst. As the macrocycles size was increased by extending the monomers length, the cyclization-entropy penalties were significantly lower than those of increasing the monomer numbers. Giant macrocycles \u003cb\u003eQP\u003c/b\u003e[\u003cspan additionalcitationids=\"CR4 CR5\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], \u003cb\u003eHP\u003c/b\u003e[\u003cspan additionalcitationids=\"CR4 CR5\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], \u003cb\u003e2,5-QP\u003c/b\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]), \u003cb\u003eCN-HP\u003c/b\u003e[\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] and \u003cb\u003eCHO-HP\u003c/b\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] were facilely synthesized, and the total cyclization yield reached 72%. These giant electron-rich macrocycles possessed cavity sizes in the range 2.0\u0026ndash;4.7 nm and are among the largest macrocycles. Significantly, the giant macrocycles spawned excellent assembly properties and facilitated the formation of organogels in various solvents. Mechanism investigation revealed that this self-assembly capacity originated from abundant π\u0026ndash;π interaction sites provided by giant macrocycles. Moreover, these multiple intermolecular π\u0026ndash;π interactions in the organogel assembly enormously restricted the nonradiative decay processes of rotation/vibration, boosted the radiative decay process of fluorescence, and eventually remarkably promoted the quantum efficiencies to 72.8% and 83.1%. This study provides an effective and general method for producing giant macrocycles with specific properties. Further research on the synthesis, host\u0026ndash;guest recognition, and chiral assembly of giant macrocycles is currently underway in our laboratory.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAUTHOR INFORMATION\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCorresponding Authors\u003c/p\u003e\n\u003cp\u003e*Email: [email protected]; [email protected]\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNotes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing financial interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eACKNOWLEDGMENT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors gratefully acknowledge the National Natural Science Foundation of China (21971192, 21772118, and 22201211), the Natural Science Foundation of Tianjin City (20JCZDJC00200), and Open Research Fund of School of Chemistry and Chemical Engineering, Henan Normal University. The authors also gratefully acknowledge Professors Dong-Sheng Guo and Kang Cai for their helpful discussions.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCram DJ, Kaneda T, Helgeson RC, Lein GM (1979) Spherands - ligands whose binding of cations relieves enforced electron-electron repulsions. J Am Chem Soc 101:6752\u0026ndash;6754\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLehn JM, Sauvage JP (1975) Cryptates. XVI. [2]-Cryptates. Stability and selectivity of alkali and alkaline-earth macrobicyclic complexes. J Am Chem Soc 97:6700\u0026ndash;6707\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePedersen CJ (1967) Cyclic polyethers and their complexes with metal salts. J Am Chem Soc 89:2495\u0026ndash;2496\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSzejtli J (1982) Cyclodextrins and Their Inclusion Complexes. 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Angew Chem Int Ed 42:1210\u0026ndash;1250\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eW\u0026uuml;rthner F, Kaiser TE, Saha-M\u0026ouml;ller CR (2011) J-Aggregates: From Serendipitous Discovery to Supramolecular Engineering of Functional Dye Materials. Angew Chem Int Ed 50:3376\u0026ndash;3410\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMa S et al (2021) Organic molecular aggregates: From aggregation structure to emission property. Aggregate 2:e96\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBaroncini M, Bergamini G, Ceroni P (2017) Rigidification or interaction-induced phosphorescence of organic molecules. Chem Commun 53:2081\u0026ndash;2093\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Schemes","content":"\u003cp\u003eSchemes 1 and 2 are available in the Supplementary Files section\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"giant macrocycles, entropy penalty, photoluminescence, self-assembly, supramolecular chemistry","lastPublishedDoi":"10.21203/rs.3.rs-3846672/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3846672/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eMacrocycles are key tools for molecular recognition and self-assembly. However, traditionally prevalent macrocyclic compounds exhibit specific cavities with diameters usually less than 1 nm, limiting their range of applications in supramolecular chemistry. The efficient synthesis of giant macrocycles remains a significant challenge because an increase in the monomer number results in cyclization-entropy loss. In this study, we developed a low-entropy-penalty synthesis strategy for producing giant macrocycles in high yields. In this process, long and rigid monomers possessing two reaction modules were condensed with paraformaldehyde via Friedel–Crafts reaction. A series of giant macrocycles with cavities of sizes ranging from 2.0 nm to 4.7 nm were successfully synthesized with cyclization yields of up to 72%. Experimental results and theoretical calculations revealed that extending the monomer length rather than increasing the monomer numbers could notably reduce the cyclization-entropy penalty and avoid configuration twists, thereby favoring the formation of giant macrocycles with large cavities. Significantly, the excellent self-assembly capacity of these giant macrocycles promoted their assembly into organogels in various solvents. The obtained xerogels exhibited enhanced photoluminescence quantum efficiencies of up to 83.1%. Mechanism investigation revealed that the excellent assembly capacity originated from the abundant π–π interactions sites of the giant macrocycles. The outstanding emission enhancement resulted from the restricted nonradiative decay processes of rotation/vibration and improved radiative decay process of fluorescence. This study provides an effective and general method for achieving giant macrocycles, thereby expanding the supramolecular toolbox for host–guest chemistry and assembly applications. Moreover, the intriguingly assembly and photophysical properties demonstrate the feasibility of developing novel and unique properties by expanding the macrocycle size.\u003c/p\u003e","manuscriptTitle":"Low-Entropy-Penalty Synthesis of Giant Macrocycles for Good Self-Assembly and Emission Enhancement","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-18 19:44:49","doi":"10.21203/rs.3.rs-3846672/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"94732f90-4931-4a78-bd2e-9ee9cbff9e4d","owner":[],"postedDate":"January 18th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":28189378,"name":"Physical sciences/Chemistry/Organic chemistry"},{"id":28189379,"name":"Physical sciences/Chemistry/Supramolecular chemistry"}],"tags":[],"updatedAt":"2024-03-12T08:45:17+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-18 19:44:49","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3846672","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3846672","identity":"rs-3846672","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}