Bismacrocycle: Structures and Applications

In the past half-century, macrocycles with different structures and functions, have played a critical role in supramolecular chemistry. Two macrocyclic moieties can be linked to form bismacrocycle molecules. Compared with monomacrocycle, the unique structures of bismacrocycles led to their specific recognition and assembly properties, also a wide range of applications, including molecular recognition, supramolecular self-assembly, advanced optical material construction, etc. In this review, we focus on the structure of bismacrocycle and their applications. Our goal is to summarize and outline the possible future development directions of bismacrocycle research.


Introduction
In the past six decades, macrocycles with different structures and properties have emerged. These macrocycles include crown ethers [1][2][3], cyclodextrins [4][5][6], calixarenes [7,8], cucurbiturates [9,10], and carbon-rich macrocycles [11][12][13], etc. They have continuously promoted the development of supramolecular chemistry. As important hosts, macrocycles have been widely used in molecular recognition [14][15][16], assembly [17][18][19], molecular machine construction [20][21][22][23], novel material development [24][25][26][27][28], drug exploration [29][30][31], etc. To date, the design and synthesis of macrocycles with special structures and properties is one of the core driving forces of supramolecular chemistry. The combination of multiple cavities and active sites is a promising strategy. Herein, one macrocycle with two cavities is defined as a bismacrocycle. Currently, macrocycle-related studies have been extensive, and their supramolecular chemical properties have also been widely investigated. As the combination result of two macrocycles, a bismacrocycle can effectively expand their properties with high reliability and predictability on the basis of the reports involving its macrocyclic moieties (Scheme 1). However, even some review papers explore related study of specific bismacrocycles [32,33], the summary of bismacrocycles as the subject is lacking [34]. Herein, recent progress of bismacrocycles study is reviewed. It provides an important reference for bismacrocycle-related research (e.g., supramolecular assembly, supramolecular polymer construction, etc.). Specifically, the latest developments in bicyclic compounds since 2017 were summarized for further driving their research development in different fields.

Bis(crown ether)
Smid group synthesized the first bis(crown ether) in 1975 [35], which exhibited stronger interactions with cations (e.g., K + , NH 4 + ) than the corresponding mono(crown ether). It initiated the research on the host with double macrocyclic moieties (i.e., bismacrocycle) in the following decades. To date, a large number of bismacrocycles were generated and widely used in molecular recognition [36] and supramolecular polymer studies [37,38].
In 2017, Liu group synthesized a bis(crown ether) 1 ( Figure 1) [39]. The 1 contained photosensitive 9,10-diphenylanthracene block and terminal pyridinyl groups. It can coordinate with lanthanide metal ions to construct assembly 2. Under ultraviolet light, 2 can undergo photocatalytic oxidation to form 3 with excellent luminescence performance. Heating induced 3 returning to 2. The light/thermal regulation between 2 and 3 indicates its good potential to achieve molecular machines and logic gate systems.

Bis(crown ether)
Smid group synthesized the first bis(crown ether) in 1975 [35], which exhibited stronger interactions with cations (e.g., K + , NH4 + ) than the corresponding mono(crown ether). It initiated the research on the host with double macrocyclic moieties (i.e., bismacrocycle) in the following decades. To date, a large number of bismacrocycles were generated and widely used in molecular recognition [36] and supramolecular polymer studies [37,38].
In 2017, Liu group synthesized a bis(crown ether) 1 ( Figure 1) [39]. The 1 contained photosensitive 9,10-diphenylanthracene block and terminal pyridinyl groups. It can coordinate with lanthanide metal ions to construct assembly 2. Under ultraviolet light, 2 can undergo photocatalytic oxidation to form 3 with excellent luminescence performance. Heating induced 3 returning to 2. The light/thermal regulation between 2 and 3 indicates its good potential to achieve molecular machines and logic gate systems. Figure 1. The 1 forms 2 with lanthanide cations, and 1 after UV illumination can further generate 3 with lanthanide cations, and 2 transforms to 3 after UV illumination, and then changes to 2 after heating. Reprinted with permission from ref. [39], copyright 2017 American Chemical Society.
Meanwhile, an anthracene-bridged bis(crown ether) 12 ( Figure 4) [42] was reported by the Liu group. A novel photochromic pseudo [3]rotaxane 13 was formed between 12 and (R/S)-2,2′-binaphthyl secondary ammonium salt guest (R/S)-14. The intrinsic chiral transfer from (R/S)-14 to 12 is accompanied by fluorescence resonance energy transfer (FRET). Photo-oxidation of anthracene on 12 can further modulate circular dichroism (ICD) and FRET of (R/S)-13 treated with 365 nm UV light or heating. The multi-stimuli reactive chiral transfer materials can be used to developing chiral functional materials.  In the same year, Stang and colleagues synthesized a bis(crown ether) 15 ( Figure 5) [43] containing a pyridine linking unit. The 15 and platinum formed the complex 16 ( Figure 5a). Hydrogen bonding interactions between 16 and water induced supramolecular polymer 17 with excellent adhesion to hydrophilic surfaces (e.g., glass). Reprinted with permission from ref. [43], copyright 2019 American Chemical Society.
In 2020, Yan and colleagues obtained bis(crown ether) 18 containing two dialkylammonium salt units. Its self-cross-linking supramolecular polymer network (SPN) formed on the basis of the interaction between its crown ether and dialkylammonium units ( Figure 6) [44]. The gel-sol transition of SPN can be modulated with temperature or pH. This study is instructive for developing gel materials with non-covalent interactions. In 2020, Yan and colleagues obtained bis(crown ether) 18 containing two dialkylammonium salt units. Its self-cross-linking supramolecular polymer network (SPN) formed on the basis of the interaction between its crown ether and dialkylammonium units ( Figure 6) [44]. The gel-sol transition of SPN can be modulated with temperature or pH. This study is instructive for developing gel materials with non-covalent interactions. with permission from ref. [43], copyright 2019 American Chemical Society.
In 2020, Yan and colleagues obtained bis(crown ether) 18 containing two dialkylammonium salt units. Its self-cross-linking supramolecular polymer network (SPN) formed on the basis of the interaction between its crown ether and dialkylammonium units ( Figure 6) [44]. The gel-sol transition of SPN can be modulated with temperature or pH. This study is instructive for developing gel materials with non-covalent interactions. Figure 6. Schematic representation of self-cross-linking supramolecular polymer network formation with 18. Reprinted with permission from ref. [44], copyright 2020 American Chemical Society.
In 2017, Liu group synthesized a biscyclodextrin 19 ( Figure 7a) [49] bridged with dithiophene. The 19 is converted to 20 under UV light, and 20 returned to 19 after visible light irradiation. The 19 form 22 with the porphyrin tricarboxylate guest 21, then 22 further self-assembles to form 23. The 23 aggregation generated the binary supermolecular nanoassembly 24. The 23 co-assembles with amphipathic near-infrared (NIR) cyanine fluorochrome 25 to construct 26, and then further aggregated to obtain a larger ternary supermolecular nanoassembly 27. The 25 significantly induced 27 fluorescence enhancement ( Figure 7b). Nanoparticles 24 or 27 emitted red light at a maximum wavelength at 647 nm or 680 nm under 417 nm excitation, respectively. Both were fluorescence quenched after treating with 254 nm UV light. Subsequently, the luminescence can be restored under >450 nm light (Figure 7c,d). The light-modifiable multivariate nano-assembled structures provides a new strategy to design and develop photoconvertible photoluminescent materials.
ther self-assembles to form 23. The 23 aggregation generated the binary supermolecular nanoassembly 24. The 23 co-assembles with amphipathic near-infrared (NIR) cyanine fluorochrome 25 to construct 26, and then further aggregated to obtain a larger ternary supermolecular nanoassembly 27. The 25 significantly induced 27 fluorescence enhancement ( Figure 7b). Nanoparticles 24 or 27 emitted red light at a maximum wavelength at 647 nm or 680 nm under 417 nm excitation, respectively. Both were fluorescence quenched after treating with 254 nm UV light. Subsequently, the luminescence can be restored under >450 nm light (Figure 7c,d). The light-modifiable multivariate nano-assembled structures provides a new strategy to design and develop photoconvertible photoluminescent materials.
The azobenzene unit was used as a bridging unit to generate bis(β-cyclodextrin) 28 ( Figure 8) [50]. Trans-28 and adamantanyl-modified diphenylalanine (30) form bilayer 2D nanosheets 29. Differently, cis-28 and 30 forms 1D nanotubes 31. The 29 and 31 can be converted to each other via UV/visible illumination or heating. This study provides a new way to achieve light control assembly morphology. The azobenzene unit was used as a bridging unit to generate bis(β-cyclodextrin) 28 ( Figure 8) [50]. Trans-28 and adamantanyl-modified diphenylalanine (30) form bilayer 2D nanosheets 29. Differently, cis-28 and 30 forms 1D nanotubes 31. The 29 and 31 can be converted to each other via UV/visible illumination or heating. This study provides a new way to achieve light control assembly morphology. The bipyridinyl unit was used as linker to obtain bis(β-cyclodextrin) 32 ( Figure 9) [51]. The 32 formed a 3:1 complex with Ru(II), which can bind with adamantane-modified anthracene (33) in aqueous solution to form 34. The 34 can accumulate in the nucleus of cancer cells and induce reactive oxygen species production under visible light irradiation. The net result was effective anticancer activity. This work provided a new strategy for light-driven bright agents for cancer treatment. The bipyridinyl unit was used as linker to obtain bis(β-cyclodextrin) 32 ( Figure 9) [51]. The 32 formed a 3:1 complex with Ru(II), which can bind with adamantane-modified anthracene (33) in aqueous solution to form 34. The 34 can accumulate in the nucleus of cancer cells and induce reactive oxygen species production under visible light irradiation. The net result was effective anticancer activity. This work provided a new strategy for light-driven bright agents for cancer treatment.

Biscalixarene
Calixarene is a class of artificial macrocycles with high application value in chemical, biological, material, environmental, and other multidisciplinary fields due to their low cost, efficient synthesis, and unique properties [7,8]. From the end of the last century, biscalixarenes have been developed for supramolecular assembly and supramolecular polymer construction [52].
In 2018, Ma and colleagues reported a novel water-soluble vibration-induced emission (VIE) molecule 35 ( Figure 10) [53]. Two quaternary ammonium groups on 35 can insert into the cavity of 36. Then supramolecular aggregates 37 was created. Free 35 emits orange-red light, while fixed 35 emits blue light. Fluorescence emission from orange-red to white to blue is achieved via controlling the ratio between 36 and 35. Acetylcholine (ACH) was added in 37 solutions to displace 35 and thus restore orange fluorescence. Such strategies using reversible supramolecular self-assembly to control the emission of VIE molecules provide new ideas to develop tunable luminescent materials.

Biscalixarene
Calixarene is a class of artificial macrocycles with high application value in chemical, biological, material, environmental, and other multidisciplinary fields due to their low cost, efficient synthesis, and unique properties [7,8]. From the end of the last century, biscalixarenes have been developed for supramolecular assembly and supramolecular polymer construction [52].
In 2018, Ma and colleagues reported a novel water-soluble vibration-induced emission (VIE) molecule 35 ( Figure 10) [53]. Two quaternary ammonium groups on 35 can insert into the cavity of 36. Then supramolecular aggregates 37 was created. Free 35 emits orange-red light, while fixed 35 emits blue light. Fluorescence emission from orange-red to white to blue is achieved via controlling the ratio between 36 and 35. Acetylcholine (ACH) was added in 37 solutions to displace 35 and thus restore orange fluorescence. Such strategies using reversible supramolecular self-assembly to control the emission of VIE molecules provide new ideas to develop tunable luminescent materials.
Linking two calix [5]arene with chiral binaphthalene provides chiral biscalix [5]arene 38 and 39. Both interact with C 60 on C 60 -appended poly-(phenylacetylene) 40 to affect the helix of the polymer ( Figure 11) [54]. It is a new approach to control the helical conformation of polyacetylene via host-guest interactions. Linking two calix [5]arene with chiral binaphthalene provides chiral biscalix [5]arene 38 and 39. Both interact with C60 on C60-appended poly-(phenylacetylene) 40 to affect the helix of the polymer ( Figure 11) [54]. It is a new approach to control the helical conformation of polyacetylene via host-guest interactions.

Bispillararene
In 2020, Cong group introduced tetraphenylethylene as linker to obtain novel fluorescent bispillararene 45 ( Figure 13) [56]. The fluorescence of crystalline 45 changes from light blue to yellow after grinding, and then it can be returned to blue treated with pxylene vapor. Further information encryption patterns can be prepared.

Bispillararene
In 2020, Cong group introduced tetraphenylethylene as linker to obtain novel fluorescent bispillararene 45 ( Figure 13) [56]. The fluorescence of crystalline 45 changes from light blue to yellow after grinding, and then it can be returned to blue treated with p-xylene vapor. Further information encryption patterns can be prepared.

Bispillararene
In 2020, Cong group introduced tetraphenylethylene as linker to obtain novel fl rescent bispillararene 45 ( Figure 13) [56]. The fluorescence of crystalline 45 changes f light blue to yellow after grinding, and then it can be returned to blue treated wit xylene vapor. Further information encryption patterns can be prepared.    In 2023, Hu group linked two pillar [5]arenes through C-C double-bonds to obtain bispillar [5]arene 50 containing a tetraphenylethylene (TPE) unit ( Figure 15) [58]. Hostguest studies showed that 50 can form a ring-piercing structure with adiponitrile 51 or sebaconitrile 52 in a 1:2 ratio, and then 50 and 52 formed a linear supramolecular polyme. Furthermore, 50 forms a supramolecular layered polymer 54 with 53, and 54 can be used as a photocatalyst to catalyse the dehalogenation reaction. In 2023, Hu group linked two pillar [5]arenes through C-C double-bonds to obtain bispillar [5]arene 50 containing a tetraphenylethylene (TPE) unit ( Figure 15) [58]. Hostguest studies showed that 50 can form a ring-piercing structure with adiponitrile 51 or sebaconitrile 52 in a 1:2 ratio, and then 50 and 52 formed a linear supramolecular polyme. Furthermore, 50 forms a supramolecular layered polymer 54 with 53, and 54 can be used as a photocatalyst to catalyse the dehalogenation reaction.  In 2023, Hu group linked two pillar [5]arenes through C-C double-bonds to obtain bispillar [5]arene 50 containing a tetraphenylethylene (TPE) unit ( Figure 15) [58]. Hostguest studies showed that 50 can form a ring-piercing structure with adiponitrile 51 or sebaconitrile 52 in a 1:2 ratio, and then 50 and 52 formed a linear supramolecular polyme. Furthermore, 50 forms a supramolecular layered polymer 54 with 53, and 54 can be used as a photocatalyst to catalyse the dehalogenation reaction.

Bishelicarene
Chen and colleagues reported a pair of enantiomer bishelic [6]arenes P/M-55 ( Figure 16) [59] in 2022. It contained two chiral helic [6]arene units. P/M-55 self-assembles with guest 56, a tetraphenylethylene derivative containing two quaternary ammonium units. Finally, a chiral supramolecular polymer 57 formed. The anthracene contained guest 58 combined with 57 to further obtain emission-enhanced supramolecular gel 59. The circular polarization luminescence (CPL) performance of 59 is induced by the chiral transfer from P/M-55 to the non-chiral guest 58. Furthermore, regulating the ratio of guests 56 and 58 in 59 can emit white light. This work provides a new strategy to construct CPL active supramolecular gel through chiral bismacrocycles.
Molecules 2023, 28, x FOR PEER REVIEW 13 of 29 Figure 15. Schematic representation of the controlled assembly and photocatalytic process between 50 and guest 51-53. Reprinted with permission from ref. [58], copyright 2023 Wiley-VCH.

Bishelicarene
Chen and colleagues reported a pair of enantiomer bishelic [6]arenes P/M-55 ( Figure  16) [59] in 2022. It contained two chiral helic [6]arene units. P/M-55 self-assembles with guest 56, a tetraphenylethylene derivative containing two quaternary ammonium units. Finally, a chiral supramolecular polymer 57 formed. The anthracene contained guest 58 combined with 57 to further obtain emission-enhanced supramolecular gel 59. The circular polarization luminescence (CPL) performance of 59 is induced by the chiral transfer from P/M-55 to the non-chiral guest 58. Furthermore, regulating the ratio of guests 56 and 58 in 59 can emit white light. This work provides a new strategy to construct CPL active supramolecular gel through chiral bismacrocycles. Reprinted with permission from ref. [59], copyright 2022 American Chemical Society.

Biscucurbituril
Zhang group synthesized the biscucurbit [7]uril 60 in rotaxane in 2017 ( Figure 17) [60]. Guest 61 containing N,N-dimethyladamantylammonium (DMAD) on both end groups was added to bind 60. Supramolecular polymer 62 was rapidly formed with a high polymerization degree. To control the polymerization degree, dicarboxylate guest 63 was used to interact with 60 to form complex 64. Then 61 was subsequently added in the system to replace 63 due to its stronger affinity with 60. However, the slow dissociation rate of 63 induced the polymerization degree of 62 can be controlled. When the environment pH was changed, the supramolecular polymerization process was suspended when the pD value increased from 9.7 to 10.8, while the supramolecular polymer remained stable Reprinted with permission from ref. [59], copyright 2022 American Chemical Society.

Biscucurbituril
Zhang group synthesized the biscucurbit [7]uril 60 in rotaxane in 2017 ( Figure 17) [60]. Guest 61 containing N,N-dimethyladamantylammonium (DMAD) on both end groups was added to bind 60. Supramolecular polymer 62 was rapidly formed with a high polymerization degree. To control the polymerization degree, dicarboxylate guest 63 was used to interact with 60 to form complex 64. Then 61 was subsequently added in the system to replace 63 due to its stronger affinity with 60. However, the slow dissociation rate of 63 induced the polymerization degree of 62 can be controlled. When the environment pH was changed, the supramolecular polymerization process was suspended when the pD value increased from 9.7 to 10.8, while the supramolecular polymer remained stable for several days. In this work, pH modulated the dissociation rate of the pre-saturated complex 64, and further regulated the polymerization degree of 62. for several days. In this work, pH modulated the dissociation rate of the pre-saturated complex 64, and further regulated the polymerization degree of 62.

Bisheteracalixarenes
Wang and colleagues used bridging units with different angles and stiffnesses to connect two oxacalix [2]arene [2]triazines to obtain bisheteracalixarenes (65-69) (Figure 18a) [61]. The crystal structure of 65-67 and 69 proved that the rigid bridged units can control the orientation of the two large ring cavities, and further modified the stoichiometry of the complexation between each bismacrocycle and chloride aion. Further supramolecular oligomers between 67 and binary naphthalene-1,5-disulfonate anion (70) was generated ( Figure 18b). The coherent self-assembled particles formed via mixing 67 and 1 molar equiv. of 70. This study was carried out by rational design of electron-deficient bismacrocycle building units to produce the challenging anion-π interaction-directed self-assembly.

Bisheteracalixarenes
Wang and colleagues used bridging units with different angles and stiffnesses to connect two oxacalix [2]arene [2]triazines to obtain bisheteracalixarenes (65-69) (Figure 18a) [61]. The crystal structure of 65-67 and 69 proved that the rigid bridged units can control the orientation of the two large ring cavities, and further modified the stoichiometry of the complexation between each bismacrocycle and chloride aion. Further supramolecular oligomers between 67 and binary naphthalene-1,5-disulfonate anion (70) was generated ( Figure 18b). The coherent self-assembled particles formed via mixing 67 and 1 molar equiv. of 70. This study was carried out by rational design of electron-deficient bismacrocycle building units to produce the challenging anion-π interaction-directed self-assembly.

Pyridinium Bismacrocycle
Pyridinium macrocycles (e.g., "blue box" and its derivatives) have been used for a wide range of applications in supramolecular structures, host, and guest chemistry, catalysis, extraction and sequestration, and molecular electronics due to their unique structures and properties [63]. In addition, pyridinium bismacrocycles have also shown promising applications in supramolecular self-assembly, anion recognition, and bioimaging. In

Pyridinium Bismacrocycle
Pyridinium macrocycles (e.g., "blue box" and its derivatives) have been used for a wide range of applications in supramolecular structures, host, and guest chemistry, catalysis, extraction and sequestration, and molecular electronics due to their unique structures and properties [63]. In addition, pyridinium bismacrocycles have also shown promising applications in supramolecular self-assembly, anion recognition, and bioimaging.
In 2019, Cao group synthesized the aggregation-induced emission (AIE) pyridinium bismacrocycles 73 containing three tetraphenylethene (TPE) units. (Figure 20a) [64] 73 emits orange light (cantered at 595 nm) in acetonitrile with Φ F as 19.7%, while it emits strong yellow light (cantered at 580 nm) in water with a Φ F as 97.7%. The fluorescence intensity of 73 changed very little with the percentage of water in acetonitrile lower than 80%, and increased rapidly with the percentage above 80%. The 73 forms nanosphere supramolecular assemblies 74 with diameters ranging from 25 to 77 nm in water, with a maximum emission wavelength of 580 nm (excitation wavelength 410 nm). The addition of NiR to the aqueous solution of 74 leads to the formation of further spherical supramolecular assemblies 75 with an increasing diameter as 35 to 83 nm through highly ordered coassembly. Due to FRET (Φ ET = 77.5%) between 73 and NiR with a high antenna effect (14.3), the maximum emission wavelength of 75 is redshifted to 650 nm (excitation wavelength as 410 nm). This AIE fluorescent nanomaterial has potential applications in cancer cell imaging and diagnosis/photodynamic therapy. In 2021, this group further introduced four different substituents (i.e., NO 2 , Br, OCH 3 , or OH) on 73 (Figure 20b) [65], resulting in bismacrocycle 76-79 with AIE properties. Electron-absorbing groups on 76 or 77 can prohibit the intramolecular PET process between TPE donor and acceptor so that induced enhanced fluorescence. Conversely, 78 and 79 containing electron-donating groups cannot prohibit intramolecular PET process and then cause fluorescence bursts. The 76-79 can also self-assemble into nanospheres in MeCN or H 2 O (1% MeCN). ATP can be encapsulated in the cavities or gaps of the nanospheres formed with 73, 76-79. ATP binding leads to a significant fluorescence reduction in 76, which can be used to detect ATP. cell imaging and diagnosis/photodynamic therapy. In 2021, this group further introduced four different substituents (i.e., NO2, Br, OCH3, or OH) on 73 (Figure 20b) [65], resulting in bismacrocycle 76-79 with AIE properties. Electron-absorbing groups on 76 or 77 can prohibit the intramolecular PET process between TPE donor and acceptor so that induced enhanced fluorescence. Conversely, 78 and 79 containing electron-donating groups cannot prohibit intramolecular PET process and then cause fluorescence bursts. The 76-79 can also self-assemble into nanospheres in MeCN or H2O (1% MeCN). ATP can be encapsulated in the cavities or gaps of the nanospheres formed with 73, 76-79. ATP binding leads to a significant fluorescence reduction in 76, which can be used to detect ATP.  Reprinted with permission from ref. [66], copyright 2022 Elsevier.
In 2022, Zhao and colleagues synthesized 82 (Figure 22a) [67], a water-soluble pyridinium bismacrocycles containing a perylene diimides (PDIs) core. The 82 was encapsulated by double cationic molecular straps on both sides of PDI so that prevents PDI aggregation induced fluorescence quench even at high concentration (e.g., 2 mM) (Figure 22a). Cell fluorescence imaging studies showed that 82 co-localized with the lysosomal labelling dye LysoTracker Red in RAW 264.7 cells with an overlay coefficient as 0.98 and cell viability greater than 95% at all concentration tests (1-200 µM) (Figure 22b). PDI radical species from 82 reduction remained stable at room temperature and heat (60 °C), exhibited photothermal performance without significant decay for 20 cycles under 808 nm radiation. PDI in 82 can be converted in situ to PDI radicals with hydrogenases on the surface of the anaerobic bacterium E. coli, and can rise from 25 °C to 68 °C in 15 min under 808 nm laser radiation (Figure 22c). This work provides a new strategy to design and synthesis In 2022, Zhao and colleagues synthesized 82 (Figure 22a) [67], a water-soluble pyridinium bismacrocycles containing a perylene diimides (PDIs) core. The 82 was encapsulated by double cationic molecular straps on both sides of PDI so that prevents PDI aggregation induced fluorescence quench even at high concentration (e.g., 2 mM) (Figure 22a). Cell fluorescence imaging studies showed that 82 co-localized with the lysosomal labelling dye LysoTracker Red in RAW 264.7 cells with an overlay coefficient as 0.98 and cell viability greater than 95% at all concentration tests (1-200 µM) (Figure 22b). PDI radical species from 82 reduction remained stable at room temperature and heat (60 • C), exhibited photothermal performance without significant decay for 20 cycles under 808 nm radiation. PDI in 82 can be converted in situ to PDI radicals with hydrogenases on the surface of the anaerobic bacterium E. coli, and can rise from 25 • C to 68 • C in 15 min under 808 nm laser radiation (Figure 22c). This work provides a new strategy to design and synthesis water-soluble non-aggregated organic dyes. lated by double cationic molecular straps on both sides of PDI so that prevents PDI aggregation induced fluorescence quench even at high concentration (e.g., 2 mM) (Figure 22a). Cell fluorescence imaging studies showed that 82 co-localized with the lysosomal labelling dye LysoTracker Red in RAW 264.7 cells with an overlay coefficient as 0.98 and cell viability greater than 95% at all concentration tests (1-200 µM) (Figure 22b). PDI radical species from 82 reduction remained stable at room temperature and heat (60 °C), exhibited photothermal performance without significant decay for 20 cycles under 808 nm radiation. PDI in 82 can be converted in situ to PDI radicals with hydrogenases on the surface of the anaerobic bacterium E. coli, and can rise from 25 °C to 68 °C in 15 min under 808 nm laser radiation (Figure 22c). This work provides a new strategy to design and synthesis water-soluble non-aggregated organic dyes. A similar strategy can be applied to design more bismacrocycle. In 2023, Wei and colleagues generated a water-soluble pyridinium bismacrocycles 83 ( Figure 23) [68] containing a naphthalene diimide core. The 83 acts as an electron-deficient host that binds strongly to electron-rich guests such as water-insoluble 2,7-diaminofluorene (84), fluorene (85), 2-aminofluorene (86), tetrathiafulvalene (87), and water-soluble oligoethylene glycol redshifts. Upon 1064 nm laser irradiation, aqueous solutions of 842 ⊂ 83, 872 ⊂ 83, or 882 ⊂ 83 exhibited significant warming with thermal conversion efficiency value as 37.6%, 39.9%, and 47.4%, respectively. Upon 1064 nm laser irradiation, the non-toxic 882 ⊂ 83 completely killed HeLa cells, and E. coli and S. aureus, achieving efficient NIR-II photothermal conversion for cancer cell and bacterial ablation (Figure 20 top left). This study provides new avenues to design and apply biocompatible NIR-II light absorbers with well-defined structures.

Imidazolium Bismacrocycle
In 2020, Cao group synthesized imidazolium bismacrocycles 97 and 98 ( Figure 26) [76] with TPE core induced AIE properties. The 97 and 98 show good emission in a wide range of solvents. The 97 changed its emission colour from blue to green (Δλ = 12 nm) after grinding, and returned to blue after fumigation with water vapor. Due to the complete flattening of the benzene ring in the bicyclic structure at high pressure, a large red shift in the emission wavelength (Δλ = ~72 nm) of 97 was observed. Due to the restricted rotation of the anthracene group in 98, its emission peak does not vary with pressure. An acetonitrile solution of 98 underwent an oxidation reaction under 365 nm light and the fluorescence gradually changed from green to blue within a few minutes. The synthesis of such novel molecules for mechanochromic and photochromic luminescence can provide novel smart luminescent materials.

Imidazolium Bismacrocycle
In 2020, Cao group synthesized imidazolium bismacrocycles 97 and 98 ( Figure 26) [76] with TPE core induced AIE properties. The 97 and 98 show good emission in a wide range of solvents. The 97 changed its emission colour from blue to green (∆λ = 12 nm) after grinding, and returned to blue after fumigation with water vapor. Due to the complete flattening of the benzene ring in the bicyclic structure at high pressure, a large red shift in the emission wavelength (∆λ =~72 nm) of 97 was observed. Due to the restricted rotation of the anthracene group in 98, its emission peak does not vary with pressure. An acetonitrile solution of 98 underwent an oxidation reaction under 365 nm light and the fluorescence gradually changed from green to blue within a few minutes. The synthesis of such novel molecules for mechanochromic and photochromic luminescence can provide novel smart luminescent materials.

Imidazolium Bismacrocycle
In 2020, Cao group synthesized imidazolium bismacrocycles 97 and 98 ( Figure 26) [76] with TPE core induced AIE properties. The 97 and 98 show good emission in a wide range of solvents. The 97 changed its emission colour from blue to green (Δλ = 12 nm) after grinding, and returned to blue after fumigation with water vapor. Due to the complete flattening of the benzene ring in the bicyclic structure at high pressure, a large red shift in the emission wavelength (Δλ = ~72 nm) of 97 was observed. Due to the restricted rotation of the anthracene group in 98, its emission peak does not vary with pressure. An acetonitrile solution of 98 underwent an oxidation reaction under 365 nm light and the fluorescence gradually changed from green to blue within a few minutes. The synthesis of such novel molecules for mechanochromic and photochromic luminescence can provide novel smart luminescent materials.

Azabiscycloparaphenylene
Stępień and colleagues obtained the radially conjugated azabiscycloparaphenylene (azabis-CPP) 99 in 2019 ( Figure 27) [77]. The 9,9 -bicarbazole core of 99 acts as a stereospecific element giving the entire molecule an "8" twisted structure. The electronic circular dichroism (ECD) spectra of each pure 99 enantiomer contains two major Cotton effects with opposite signs. The curvature control method proposed in this work can reduce the electronic band gap while maintaining a large conjugate length in the nano-hoop system.

Azabiscycloparaphenylene
Stępień and colleagues obtained the radially conjugated azabiscycloparaphenylene (azabis-CPP) 99 in 2019 ( Figure 27) [77]. The 9,9′-bicarbazole core of 99 acts as a stereospecific element giving the entire molecule an "8" twisted structure. The electronic circular dichroism (ECD) spectra of each pure 99 enantiomer contains two major Cotton effects with opposite signs. The curvature control method proposed in this work can reduce the electronic band gap while maintaining a large conjugate length in the nano-hoop system. Figure 27. The structure of the 99 and a schematic diagram of its π-electronic system. Reprinted with permission from ref. [77], copyright 2019 American Chemical Society.
In 2021, Sun group obtained the azabis-CPP 100-102 ( Figure 28) [78] with the cyclocondensation between two o-diamine-substituted CPP derivative moieties and a 4,5,9,10-tetraketopyrene. The structure of 100-102 rapidly interconverts between cis-and trans-conformations. Analysis of the NMR hydrogen spectra of the well-solubilized 102 at different temperatures revealed >99% trans structure at temperatures below 183 K. The maximum emission wavelength of 102 in dichloromethane was 616 nm, the brightest fluorophore of the CPP derivatives with λem > 600 nm, and its high quantum yield of 80% was one of the highest values for CPP derivatives. The 102 can bind C60 with a 1:2 ratio in solution.

Biscycloparaphenylene (bis-CPP)
In 2019, Cong group synthesized bis-CPP 103 (Figure 29) [79] bridged by benzene rings [80]. The main steps involve the inversion of the dianthracene retro- [4 + 4] cycloreversion, and the ring expansion in the 64-membered macrocycle by transannular aryne [4 + 2] cycloaddition. The crystal structure shows that the two CPPs in 103 linked by the pentiptycene core are ellipsoidal in shape. The 103 precursor was treated with HPLC chiral seperation and further reduction to obtain its enantiomer with an average luminescence dissymmetry factor (glum) as 3.4 × 10 −3 . Figure 27. The structure of the 99 and a schematic diagram of its π-electronic system. Reprinted with permission from ref. [77], copyright 2019 American Chemical Society.
In 2021, Sun group obtained the azabis-CPP 100-102 ( Figure 28) [78] with the cyclocondensation between two o-diamine-substituted CPP derivative moieties and a 4,5,9,10tetraketopyrene. The structure of 100-102 rapidly interconverts between cisand transconformations. Analysis of the NMR hydrogen spectra of the well-solubilized 102 at different temperatures revealed >99% trans structure at temperatures below 183 K. The maximum emission wavelength of 102 in dichloromethane was 616 nm, the brightest fluorophore of the CPP derivatives with λ em > 600 nm, and its high quantum yield of 80% was one of the highest values for CPP derivatives. The 102 can bind C 60 with a 1:2 ratio in solution.

Azabiscycloparaphenylene
Stępień and colleagues obtained the radially conjugated azabiscycloparaphenylene (azabis-CPP) 99 in 2019 ( Figure 27) [77]. The 9,9′-bicarbazole core of 99 acts as a stereospecific element giving the entire molecule an "8" twisted structure. The electronic circular dichroism (ECD) spectra of each pure 99 enantiomer contains two major Cotton effects with opposite signs. The curvature control method proposed in this work can reduce the electronic band gap while maintaining a large conjugate length in the nano-hoop system. Figure 27. The structure of the 99 and a schematic diagram of its π-electronic system. Reprinted with permission from ref. [77], copyright 2019 American Chemical Society.
In 2021, Sun group obtained the azabis-CPP 100-102 ( Figure 28) [78] with the cyclocondensation between two o-diamine-substituted CPP derivative moieties and a 4,5,9,10-tetraketopyrene. The structure of 100-102 rapidly interconverts between cis-and trans-conformations. Analysis of the NMR hydrogen spectra of the well-solubilized 102 at different temperatures revealed >99% trans structure at temperatures below 183 K. The maximum emission wavelength of 102 in dichloromethane was 616 nm, the brightest fluorophore of the CPP derivatives with λem > 600 nm, and its high quantum yield of 80% was one of the highest values for CPP derivatives. The 102 can bind C60 with a 1:2 ratio in solution.

Biscycloparaphenylene (bis-CPP)
In 2019, Cong group synthesized bis-CPP 103 (Figure 29) [79] bridged by benzene rings [80]. The main steps involve the inversion of the dianthracene retro- [4 + 4] cycloreversion, and the ring expansion in the 64-membered macrocycle by transannular aryne [4 + 2] cycloaddition. The crystal structure shows that the two CPPs in 103 linked by the pentiptycene core are ellipsoidal in shape. The 103 precursor was treated with HPLC chiral seperation and further reduction to obtain its enantiomer with an average luminescence dissymmetry factor (glum) as 3.4 × 10 −3 .

Biscycloparaphenylene (bis-CPP)
In 2019, Cong group synthesized bis-CPP 103 (Figure 29) [79] bridged by benzene rings [80]. The main steps involve the inversion of the dianthracene retro- [4 + 4] cycloreversion, and the ring expansion in the 64-membered macrocycle by transannular aryne [4 + 2] cycloaddition. The crystal structure shows that the two CPPs in 103 linked by the pentiptycene core are ellipsoidal in shape. The 103 precursor was treated with HPLC chiral seperation and further reduction to obtain its enantiomer with an average luminescence dissymmetry factor (glum) as 3.4 × 10 −3 .
110 containing a distorted benzene core similar as 108 (Figure 31(b1)) [83]. The 110 fluoresces displayed a maximum emission wavelength at 475 nm under an excitation wavelength as 380 nm in THF, with. The fluorescence quantum yield was ~3% and a fluorescence lifetime was 4.23 ns. Increasing water proportion in THF beyond 60%, 110 showed a new emission band at ~577 nm with gradually decreasing emission at 475 nm ( Figure  31(b2)). The results indicate that 110 is characterized by both the aggregation-caused quenching (ACQ) and AIE effects, and can induce tunable emission from cyan to red, including near-white light emission (Figure31(b3,b4)). The temperature-dependent CD spectra demonstrate the strong stability of both 110 enantiomeric isomers. Moreover, the AIE effect of 110 enhances its CPL properties. This molecule has potential applications as white light emitters, AIE sensors, and chiral luminescent materials. In 2021, Juríček group synthesized two fluorescent bis-CPPs, 111 [84]and 112 [85] (Figure 32a), containing peropyrene cores. The X-ray diffraction (XRD) analysis of single crystals of 111 and 112 demonstrated that they are fully conjugated framework structures with C2 symmetry. The 111 cannot interact with C60 or C70 due to spatial resistance. In contrast, 112 can form a 1:1 complex with C60 ( Figure 32b). In 2021, Juríček group synthesized two fluorescent bis-CPPs, 111 [84] and 112 [85] (Figure 32a), containing peropyrene cores. The X-ray diffraction (XRD) analysis of single crystals of 111 and 112 demonstrated that they are fully conjugated framework structures with C 2 symmetry. The 111 cannot interact with C 60 or C 70 due to spatial resistance. In contrast, 112 can form a 1:1 complex with C 60 (Figure 32b). In 2022, Cong and colleagues synthesized 113 ( Figure 33) [86], a fully conjugated bis-CPP containing a flexible cyclooctathiophene core. The crystals of 113 and C60 or C70 were obtained by slow volatilization of o-dichlorobenzene in excess of C60 or C70, respectively. The assembly structure of 113 with C60 or C70 in a 1:2 ratio to form a peanut-like topology was isolated and verified. In 2022, Cong and colleagues synthesized 113 ( Figure 33) [86], a fully conjugated bis-CPP containing a flexible cyclooctathiophene core. The crystals of 113 and C 60 or C 70 were obtained by slow volatilization of o-dichlorobenzene in excess of C 60 or C 70 , respectively. The assembly structure of 113 with C 60 or C 70 in a 1:2 ratio to form a peanut-like topology was isolated and verified.
In 2022, Cong and colleagues synthesized 113 (Figure 33) [86], a fully conjugated bis CPP containing a flexible cyclooctathiophene core. The crystals of 113 and C60 or C70 wer obtained by slow volatilization of o-dichlorobenzene in excess of C60 or C70, respectively The assembly structure of 113 with C60 or C70 in a 1:2 ratio to form a peanut-like topolog was isolated and verified.

Conclusions
In summary, we highlighted recent progress of the bismacrocycle study. The comb nation of double cavities brings unique properties. To date, bismacrocycles were used i the construction of luminescent materials, supramolecular self-assembly, and supramo lecular functional polymers (e.g., gels). The current strategies to generated bismacrocycle included using functionalized linking unit to join two macrocycles (e.g., crown ethers, cy clodextrins, calixarene, cucurbiturates, etc.). In these cases, since both cavities are known their guest recognition properties are easily accessible for subsequent functionalisatio studies. Especially, the simple introduction of functionalized bridging units (e.g., anthra cene, azobenzene, dithiophene, etc.) facilitates the property modification of the resulte bismacrocycles and further supramolecular structures. Its simple synthesis steps and low cost are more conducive to pushing the relevant research results to practical application Bismacrocycles also can be generated as a whole. This strategy focuses on the introductio Figure 33. Crystal structure of a complex of 113 formed in a 1:2 ratio with C 60 or C 70 . Reprinted with permission from ref. [86], copyright 2022 Wiley-VCH.

Conclusions
In summary, we highlighted recent progress of the bismacrocycle study. The combination of double cavities brings unique properties. To date, bismacrocycles were used in the construction of luminescent materials, supramolecular self-assembly, and supramolecular functional polymers (e.g., gels). The current strategies to generated bismacrocycles included using functionalized linking unit to join two macrocycles (e.g., crown ethers, cyclodextrins, calixarene, cucurbiturates, etc.). In these cases, since both cavities are known, their guest recognition properties are easily accessible for subsequent functionalisation studies. Especially, the simple introduction of functionalized bridging units (e.g., anthracene, azobenzene, dithiophene, etc.) facilitates the property modification of the resulted bismacrocycles and further supramolecular structures. Its simple synthesis steps and low cost are more conducive to pushing the relevant research results to practical applications. Bismacrocycles also can be generated as a whole. This strategy focuses on the introduction of functional structures (e.g., TPE, PDI, etc.) into the bismacrocycles ( Table 1). The advantage corresponding to the strategy is some properties (e.g., AIE) can be expected shown in the final product, and mainly used to further supramolecular chemistry exploration.
The design and synthesis of bismacrocycle compounds with outstanding structural novelty and performance is a major challenge in related research. The combination between the art of current bismacrocyclic research and computational methods [87][88][89][90] lead the design and study of specific functionally oriented bismacrocycles. As one of the fastdeveloping research frontiers, it is expected that bismacrocycle-related chemistry will be further penetrated many fields, including advanced optical materials, disease treatment, and molecular machines, etc. Bismacrocycle study will provide more excellent solutions to achieve the precise construction and properties of complex systems. of functional structures (e.g., TPE, PDI, etc.) into the bismacrocycles ( Table 1). The advantage corresponding to the strategy is some properties (e.g., AIE) can be expected shown in the final product, and mainly used to further supramolecular chemistry exploration. of functional structures (e.g., TPE, PDI, etc.) into the bismacrocycles ( Table 1). The advantage corresponding to the strategy is some properties (e.g., AIE) can be expected shown in the final product, and mainly used to further supramolecular chemistry exploration. Self-assembly, Supramolecular polymer, Luminescent material, chiral luminescent material, anticancer active materials.
Biscalixarene of functional structures (e.g., TPE, PDI, etc.) into the bismacrocycles ( Table 1). The advantage corresponding to the strategy is some properties (e.g., AIE) can be expected shown in the final product, and mainly used to further supramolecular chemistry exploration. Bispillararene of functional structures (e.g., TPE, PDI, etc.) into the bismacrocycles ( Table 1). The advantage corresponding to the strategy is some properties (e.g., AIE) can be expected shown in the final product, and mainly used to further supramolecular chemistry exploration. Bishelicarene of functional structures (e.g., TPE, PDI, etc.) into the bismacrocycles ( Table 1). The advantage corresponding to the strategy is some properties (e.g., AIE) can be expected shown in the final product, and mainly used to further supramolecular chemistry exploration. Biscucurbituril of functional structures (e.g., TPE, PDI, etc.) into the bismacrocycles ( Table 1). The advantage corresponding to the strategy is some properties (e.g., AIE) can be expected shown in the final product, and mainly used to further supramolecular chemistry exploration. of functional structures (e.g., TPE, PDI, etc.) into the bismacrocycles ( Table 1). The advantage corresponding to the strategy is some properties (e.g., AIE) can be expected shown in the final product, and mainly used to further supramolecular chemistry exploration. of functional structures (e.g., TPE, PDI, etc.) into the bismacrocycles ( Table 1). The advantage corresponding to the strategy is some properties (e.g., AIE) can be expected shown in the final product, and mainly used to further supramolecular chemistry exploration. Biscalix [4]pyrroles Two/multi-component self-assembly, anion recognition.

Biscycloparaphenylene Biscycloparaphenylene
Complex chiral (luminescent) compounds, VOC adsorbent materials, self-assembly, The design and synthesis of bismacrocycle compounds with outstanding structural novelty and performance is a major challenge in related research. The combination between the art of current bismacrocyclic research and computational methods [87][88][89][90] lead the design and study of specific functionally oriented bismacrocycles. As one of the fastdeveloping research frontiers, it is expected that bismacrocycle-related chemistry will be further penetrated many fields, including advanced optical materials, disease treatment, and molecular machines, etc. Bismacrocycle study will provide more excellent solutions to achieve the precise construction and properties of complex systems. Biscalix [4]pyrroles Two/multi-component self-assembly, anion recognition.

Biscycloparaphenylene Biscycloparaphenylene
Complex chiral (luminescent) compounds, VOC adsorbent materials, self-assembly, The design and synthesis of bismacrocycle compounds with outstanding structural novelty and performance is a major challenge in related research. The combination between the art of current bismacrocyclic research and computational methods [87][88][89][90] lead the design and study of specific functionally oriented bismacrocycles. As one of the fastdeveloping research frontiers, it is expected that bismacrocycle-related chemistry will be further penetrated many fields, including advanced optical materials, disease treatment, and molecular machines, etc. Bismacrocycle study will provide more excellent solutions to achieve the precise construction and properties of complex systems.   Biscalix [4]pyrroles Two/multi-component self-assembly, anion recognition.

Biscycloparaphenylene Biscycloparaphenylene
Complex chiral (luminescent) compounds, VOC adsorbent materials, self-assembly, The design and synthesis of bismacrocycle compounds with outstanding structural novelty and performance is a major challenge in related research. The combination between the art of current bismacrocyclic research and computational methods [87][88][89][90] lead the design and study of specific functionally oriented bismacrocycles. As one of the fastdeveloping research frontiers, it is expected that bismacrocycle-related chemistry will be further penetrated many fields, including advanced optical materials, disease treatment, and molecular machines, etc. Bismacrocycle study will provide more excellent solutions to achieve the precise construction and properties of complex systems.   Biscalix [4]pyrroles Two/multi-component self-assembly, anion recognition.

Biscycloparaphenylene Biscycloparaphenylene
Complex chiral (luminescent) compounds, VOC adsorbent materials, self-assembly, The design and synthesis of bismacrocycle compounds with outstanding structural novelty and performance is a major challenge in related research. The combination between the art of current bismacrocyclic research and computational methods [87][88][89][90] lead the design and study of specific functionally oriented bismacrocycles. As one of the fastdeveloping research frontiers, it is expected that bismacrocycle-related chemistry will be further penetrated many fields, including advanced optical materials, disease treatment, and molecular machines, etc. Bismacrocycle study will provide more excellent solutions to achieve the precise construction and properties of complex systems.